@article {pmid34225099,
year = {2021},
author = {Pariyar, M and Johns, A and Thorne, RF and Scott, RJ and Avery-Kiejda, KA},
title = {Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.},
journal = {Neoplasia (New York, N.Y.)},
volume = {23},
number = {8},
pages = {743-753},
doi = {10.1016/j.neo.2021.05.016},
pmid = {34225099},
issn = {1476-5586},
mesh = {*Biomarkers, Tumor ; Chromosome Mapping ; Computational Biology/methods ; *DNA Copy Number Variations ; DNA Methylation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Ontology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Molecular Sequence Annotation ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*etiology/mortality/*pathology ; },
abstract = {Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.},
}

*Biomarkers, Tumor
Chromosome Mapping
Computational Biology/methods
*DNA Copy Number Variations
DNA Methylation
Disease Progression
Female
Gene Expression Profiling
Gene Ontology
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Lymph Nodes/*pathology
Lymphatic Metastasis
Molecular Sequence Annotation
Neoplasm Staging
Prognosis
Triple Negative Breast Neoplasms/*etiology/mortality/*pathology

@article {pmid34062284,
year = {2021},
author = {Salles, DC and Vidotto, T and Faisal, FA and Tosoian, JJ and Guedes, LB and Muranyi, A and Bai, I and Singh, S and Yan, D and Shanmugam, K and Lotan, TL},
title = {Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.},
journal = {The Journal of molecular diagnostics : JMD},
volume = {23},
number = {8},
pages = {1030-1041},
pmid = {34062284},
issn = {1943-7811},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Molecular Diagnostic Techniques/methods/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics/*metabolism ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Reproducibility of Results ; },
abstract = {This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.},
}

Adult
Aged
*Biomarkers, Tumor
Humans
Immunohistochemistry/methods
Kaplan-Meier Estimate
Male
Middle Aged
*Molecular Diagnostic Techniques/methods/standards
Neoplasm Grading
Neoplasm Staging
PTEN Phosphohydrolase/genetics/*metabolism
Prognosis
Prostate/metabolism/*pathology
Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality
Protein Binding
Proto-Oncogene Proteins c-myc/genetics/*metabolism
Reproducibility of Results

@article {pmid33567280,
year = {2021},
author = {Greulich, F and Wierer, M and Mechtidou, A and Gonzalez-Garcia, O and Uhlenhaut, NH},
title = {The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.},
journal = {Cell reports},
volume = {34},
number = {6},
pages = {108742},
pmid = {33567280},
issn = {2211-1247},
mesh = {Animals ; Enhancer Elements, Genetic/*immunology ; Inflammation/genetics/immunology ; Macrophages/*immunology ; Mice ; *Multiprotein Complexes/genetics/immunology ; *RNA-Seq ; *Receptors, Glucocorticoid/genetics/immunology ; Transcription, Genetic/*immunology ; },
abstract = {Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.},
}

Animals
Enhancer Elements, Genetic/*immunology
Inflammation/genetics/immunology
Macrophages/*immunology
Mice
*Multiprotein Complexes/genetics/immunology
*RNA-Seq
*Receptors, Glucocorticoid/genetics/immunology
Transcription, Genetic/*immunology

@article {pmid33148628,
year = {2022},
author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.},
journal = {Journal of clinical pathology},
volume = {75},
number = {1},
pages = {10-17},
pmid = {33148628},
issn = {1472-4146},
support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Whole Exome Sequencing ; },
abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.

METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).

RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.

CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.},
}

Adenocarcinoma, Mucinous/*genetics/pathology
Breast/pathology
Breast Neoplasms/*genetics/pathology
Chromosome Aberrations
Female
Genomics
Humans
Lung Neoplasms/*genetics/pathology
Mutation
Neuroendocrine Tumors/*genetics/pathology
Pancreatic Neoplasms/*genetics/pathology
Receptors, Estrogen/genetics
Transcription Factors/genetics
*Transcriptome
Whole Exome Sequencing

@article {pmid34969739,
year = {2022},
author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Shibutani, M and Tanaka, H and Hirakawa, K and Ohira, M},
title = {The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.},
journal = {Anticancer research},
volume = {42},
number = {1},
pages = {311-320},
doi = {10.21873/anticanres.15487},
pmid = {34969739},
issn = {1791-7530},
mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy/methods ; Smoking/*adverse effects ; },
abstract = {BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy.

PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.

RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).

CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.},
}

Adult
Aged
Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology
Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology
Disease Progression
Female
Humans
Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology
Middle Aged
Neoplasm Invasiveness/diagnostic imaging/pathology
Retrospective Studies
Sentinel Lymph Node Biopsy/methods
Smoking/*adverse effects

@article {pmid34396426,
year = {2021},
author = {Kobayashi, H and Nakai, T and Nakanishi, Y and Esumi, M and Masuda, S},
title = {Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.},
journal = {Molecular medicine reports},
volume = {24},
number = {4},
pages = {},
pmid = {34396426},
issn = {1791-3004},
mesh = {Adult ; Breast ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Carcinoma, Lobular/*classification/genetics/pathology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; *Phylogeny ; Polymorphism, Single Nucleotide ; },
abstract = {Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.},
}

Adult
Breast
Breast Neoplasms/*classification/genetics/pathology
Carcinoma, Ductal, Breast/*classification/genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
Carcinoma, Lobular/*classification/genetics/pathology
Female
Genotype
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
*Phylogeny
Polymorphism, Single Nucleotide

@article {pmid34009452,
year = {2021},
author = {Kusafuka, K and Ito, I and Hirata, K and Miyamoto, K and Shimizu, T and Satomi, H and Inagaki, H and Suzuki, M},
title = {A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.},
journal = {Medical molecular morphology},
volume = {54},
number = {3},
pages = {281-288},
pmid = {34009452},
issn = {1860-1499},
mesh = {Asians ; Biomarkers, Tumor/analysis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery ; ErbB Receptors/analysis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Japan ; Keratin-19/analysis/genetics ; Keratin-5/analysis/genetics ; Keratin-6/analysis/genetics ; Lip/surgery ; Lip Neoplasms/*diagnosis/metabolism/surgery ; Middle Aged ; Receptors, Androgen/analysis/genetics ; SOXE Transcription Factors/analysis/genetics ; },
abstract = {Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.},
}

Asians
Biomarkers, Tumor/analysis
Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery
ErbB Receptors/analysis/genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Japan
Keratin-19/analysis/genetics
Keratin-5/analysis/genetics
Keratin-6/analysis/genetics
Lip/surgery
Lip Neoplasms/*diagnosis/metabolism/surgery
Middle Aged
Receptors, Androgen/analysis/genetics
SOXE Transcription Factors/analysis/genetics

@article {pmid33443130,
year = {2021},
author = {Trinh, A and Gil Del Alcazar, CR and Shukla, SA and Chin, K and Chang, YH and Thibault, G and Eng, J and Jovanović, B and Aldaz, CM and Park, SY and Jeong, J and Wu, C and Gray, J and Polyak, K},
title = {Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.},
journal = {Molecular cancer research : MCR},
volume = {19},
number = {4},
pages = {623-635},
doi = {10.1158/1541-7786.MCR-20-0949},
pmid = {33443130},
issn = {1557-3125},
support = {R35 CA197623/CA/NCI NIH HHS/United States ; U01 CA195469/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; U24 CA224331/CA/NCI NIH HHS/United States ; R50 CA211482/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/*immunology ; Carcinoma, Ductal, Breast/*genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology ; Female ; Genomics ; Humans ; Immune System ; },
abstract = {The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.},
}

Breast Neoplasms/*genetics/*immunology
Carcinoma, Ductal, Breast/*genetics/*immunology
Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology
Female
Genomics
Humans
Immune System

@article {pmid34884926,
year = {2021},
author = {Kang, M and Lee, H and Byeon, SJ and Kwon, GY and Jeon, SS},
title = {Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.},
journal = {International journal of molecular sciences},
volume = {22},
number = {23},
pages = {},
pmid = {34884926},
issn = {1422-0067},
support = {NRF-2020R1A2C2007662//National Research Foundation of Korea/ ; NRF-2020R1C1C1005054//National Research Foundation of Korea/ ; },
mesh = {Animals ; DNA Repair/genetics ; Genomic Instability ; Humans ; Male ; *Mutation ; Precision Medicine ; Prostatic Neoplasms/*genetics/*pathology/therapy ; Xenograft Model Antitumor Assays ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.},
}

Animals
DNA Repair/genetics
Genomic Instability
Humans
Male
*Mutation
Precision Medicine
Prostatic Neoplasms/*genetics/*pathology/therapy
Xenograft Model Antitumor Assays

@article {pmid34185678,
year = {2021},
author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, S and Aerts, HJWL and Homeyer, A and Lewis, R and Akbarzadeh, A and Bontempi, D and Clifford, W and Herrmann, MD and Höfener, H and Octaviano, I and Osborne, C and Paquette, S and Petts, J and Punzo, D and Reyes, M and Schacherer, DP and Tian, M and White, G and Ziegler, E and Shmulevich, I and Pihl, T and Wagner, U and Farahani, K and Kikinis, R},
title = {NCI Imaging Data Commons.},
journal = {Cancer research},
volume = {81},
number = {16},
pages = {4188-4193},
pmid = {34185678},
issn = {1538-7445},
support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; HHSN261201500001G/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; HHSN261201500001W/CA/NCI NIH HHS/United States ; },
mesh = {Biomedical Research/trends ; Cloud Computing ; Computational Biology/methods ; Computer Graphics ; Computer Security ; Data Interpretation, Statistical ; Databases, Factual ; Diagnostic Imaging/*methods/standards ; Humans ; Image Processing, Computer-Assisted ; *National Cancer Institute (U.S.) ; Neoplasms/*diagnostic imaging/*genetics ; Pilot Projects ; Programming Languages ; Radiology/methods/standards ; Reproducibility of Results ; Software ; United States ; User-Computer Interface ; },
abstract = {The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. SIGNIFICANCE: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.},
}

Biomedical Research/trends
Cloud Computing
Computational Biology/methods
Computer Graphics
Computer Security
Data Interpretation, Statistical
Databases, Factual
Diagnostic Imaging/*methods/standards
Humans
Image Processing, Computer-Assisted
*National Cancer Institute (U.S.)
Neoplasms/*diagnostic imaging/*genetics
Pilot Projects
Programming Languages
Radiology/methods/standards
Reproducibility of Results
Software
United States
User-Computer Interface

@article {pmid34769077,
year = {2021},
author = {Kohlhase, DR and McCabe, CE and Singh, AK and O'Rourke, JA and Graham, MA},
title = {Comparing Early Transcriptomic Responses of 18 Soybean (Glycine max) Genotypes to Iron Stress.},
journal = {International journal of molecular sciences},
volume = {22},
number = {21},
pages = {},
pmid = {34769077},
issn = {1422-0067},
support = {3625-21220-006-00D//USDA-ARS/ ; IOW04714//USDA/ ; FAR0024859//North Central Soybean Research Program/ ; },
mesh = {*Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Iron/*metabolism ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; Transcriptome ; },
abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress that negatively affects soybean (Glycine max [L.] Merr.) production. Much of our knowledge of IDC stress responses is derived from model plant species. Gene expression, quantitative trait loci (QTL) mapping, and genome-wide association studies (GWAS) performed in soybean suggest that stress response differences exist between model and crop species. Our current understanding of the molecular response to IDC in soybeans is largely derived from gene expression studies using near-isogenic lines differing in iron efficiency. To improve iron efficiency in soybeans and other crops, we need to expand gene expression studies to include the diversity present in germplasm collections. Therefore, we collected 216 purified RNA samples (18 genotypes, two tissue types [leaves and roots], two iron treatments [sufficient and deficient], three replicates) and used RNA sequencing to examine the expression differences of 18 diverse soybean genotypes in response to iron deficiency. We found a rapid response to iron deficiency across genotypes, most responding within 60 min of stress. There was little evidence of an overlap of specific differentially expressed genes, and comparisons of gene ontology terms and transcription factor families suggest the utilization of different pathways in the stress response. These initial findings suggest an untapped genetic potential within the soybean germplasm collection that could be used for the continued improvement of iron efficiency in soybean.},
}

*Gene Expression Regulation, Plant
Genome-Wide Association Study
Iron/*metabolism
Quantitative Trait Loci
Soybeans/*genetics/metabolism
Stress, Physiological
Transcriptome

@article {pmid34340541,
year = {2021},
author = {Pickford, AK and Michel-Todó, L and Dupuy, F and Mayor, A and Alonso, PL and Lavazec, C and Cortés, A},
title = {Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.},
journal = {mBio},
volume = {12},
number = {4},
pages = {e0163621},
pmid = {34340541},
issn = {2150-7511},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Antigens, Protozoan/immunology ; *Gene Expression Profiling ; *Genetic Variation ; Host-Parasite Interactions/*genetics/immunology ; Humans ; Malaria, Falciparum/immunology/*parasitology ; Plasmodium falciparum/*genetics/immunology ; Protozoan Proteins/*genetics/immunology ; Transcriptome ; },
abstract = {Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.},
}

Antigens, Protozoan/immunology
*Gene Expression Profiling
*Genetic Variation
Host-Parasite Interactions/*genetics/immunology
Humans
Malaria, Falciparum/immunology/*parasitology
Plasmodium falciparum/*genetics/immunology
Protozoan Proteins/*genetics/immunology
Transcriptome

@article {pmid34315379,
year = {2021},
author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Chaudhary, FA and Khan, MI},
title = {Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.},
journal = {Current rheumatology reviews},
volume = {17},
number = {4},
pages = {421-427},
doi = {10.2174/1573397117666210727095552},
pmid = {34315379},
issn = {1875-6360},
mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Feasibility Studies ; Humans ; *Obesity/complications ; *Osteoarthritis, Knee/drug therapy/therapy ; *Overweight/complications ; Pain ; *Self Care/methods ; Treatment Outcome ; },
abstract = {INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese.

MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.

RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.

CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.},
}

Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
Feasibility Studies
Humans
*Obesity/complications
*Osteoarthritis, Knee/drug therapy/therapy
*Overweight/complications
Pain
*Self Care/methods
Treatment Outcome

@article {pmid34972731,
year = {2022},
author = {Salih, MM and Higgo, AA and Eed, EM},
title = {Prognostic Significance of p16 Protein Expression in Breast Cancer.},
journal = {In vivo (Athens, Greece)},
volume = {36},
number = {1},
pages = {336-340},
doi = {10.21873/invivo.12707},
pmid = {34972731},
issn = {1791-7549},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Female ; Humans ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Progesterone/genetics ; },
abstract = {BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.

PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.

RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.

CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.},
}

Biomarkers, Tumor/genetics
*Breast Neoplasms/genetics
*Carcinoma, Ductal, Breast/genetics
Female
Humans
Prognosis
Receptor, ErbB-2/genetics
Receptors, Progesterone/genetics

@article {pmid34011405,
year = {2021},
author = {Dinca, SC and Greiner, D and Weidenfeld, K and Bond, L and Barkan, D and Jorcyk, CL},
title = {Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.},
journal = {Breast cancer research : BCR},
volume = {23},
number = {1},
pages = {56},
pmid = {34011405},
issn = {1465-542X},
support = {R25 GM123927/GM/NIGMS NIH HHS/United States ; 1C06RR020533/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; 0619737//National Science Foundation/ ; 0923535//National Science Foundation/ ; AR298//Smylie Family Cancer Fund (US)/ ; 2017237//United States - Israel Binational Science Foundation/ ; },
mesh = {Amino Acid Oxidoreductases/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Matrix/*metabolism ; Female ; Glycosylation ; Humans ; Inflammation ; Neoplasm Metastasis ; Oncostatin M/genetics/*metabolism/pharmacology ; Oncostatin M Receptor beta Subunit/genetics/metabolism ; Prognosis ; Signal Transduction ; Tumor Microenvironment ; Up-Regulation/genetics ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a serious problem for patients as it metastasizes, decreasing 5-year patient survival from > 95 to ~ 27%. The breast tumor microenvironment (TME) is often saturated with proinflammatory cytokines, such as oncostatin M (OSM), which promote epithelial-to-mesenchymal transitions (EMT) in IDC and increased metastasis. The extracellular matrix (ECM) also plays an important role in promoting invasive and metastatic potential of IDC. Specifically, the reorganization and alignment of collagen fibers in stromal ECM leads to directed tumor cell motility, which promotes metastasis. Lysyl oxidase like-2 (LOXL2) catalyzes ECM remodeling by crosslinking of collagen I in the ECM. We propose a novel mechanism whereby OSM induces LOXL2 expression, mediating stromal ECM remodeling of the breast TME.

METHODS: Bioinformatics was utilized to determine survival and gene correlation in patients. IDC cell lines were treated with OSM (also IL-6, LIF, and IL-1β) and analyzed for LOXL2 expression by qRT-PCR and immunolabelling techniques. Collagen I contraction assays, 3D invasion assays, and confocal microscopy were performed with and without LOXL2 inhibition to determine the impact of OSM-induced LOXL2 on the ECM.

RESULTS: Our studies demonstrate that IDC patients with high LOXL2 and OSM co-expression had worse rates of metastasis-free survival than those with high levels of either, individually, and LOXL2 expression is positively correlated to OSM/OSM receptor (OSMR) expression in IDC patients. Furthermore, human IDC cells treated with OSM resulted in a significant increase in LOXL2 mRNA, which led to upregulated protein expression of secreted, glycosylated, and enzymatically active LOXL2. The expression of LOXL2 in IDC cells did not affect OSM-promoted EMT, and LOXL2 was localized to the cytoplasm and/or secreted. OSM-induced LOXL2 promoted an increase in ECM collagen I fiber crosslinking, which led to significant fiber alignment between cells and increased IDC cell invasion.

CONCLUSIONS: Aligned collagen fibers in the ECM provide pathways for tumor cells to migrate more easily through the stroma to nearby vasculature and tissue. These results provide a new paradigm through which proinflammatory cytokine OSM promotes tumor progression. Understanding the nuances in IDC metastasis will lead to better potential therapeutics to combat against the possibility.},
}

Amino Acid Oxidoreductases/genetics/*metabolism
Breast Neoplasms/genetics/*metabolism/pathology
Carcinoma, Ductal, Breast/genetics/metabolism/pathology
Cell Line, Tumor
Collagen Type I/metabolism
Epithelial-Mesenchymal Transition/genetics
Extracellular Matrix/*metabolism
Female
Glycosylation
Humans
Inflammation
Neoplasm Metastasis
Oncostatin M/genetics/*metabolism/pharmacology
Oncostatin M Receptor beta Subunit/genetics/metabolism
Prognosis
Signal Transduction
Tumor Microenvironment
Up-Regulation/genetics

@article {pmid33421821,
year = {2021},
author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z},
title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.},
journal = {Cancer treatment and research communications},
volume = {26},
number = {},
pages = {100300},
doi = {10.1016/j.ctarc.2020.100300},
pmid = {33421821},
issn = {2468-2942},
mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; },
abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.

CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.

CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.},
}

Axilla
Biopsy, Large-Core Needle
Breast/diagnostic imaging/pathology/surgery
Breast Neoplasms/*diagnosis/pathology/therapy
CDX2 Transcription Factor/analysis/*metabolism
Carcinoma, Ductal, Breast/*diagnosis/secondary
Chemoradiotherapy, Adjuvant
Female
Humans
Lymph Nodes/pathology
Lymphatic Metastasis/*diagnosis/pathology
Mammography
Mastectomy, Segmental
Middle Aged
Neoplasm Staging
Ultrasonography

@article {pmid34689837,
year = {2021},
author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E},
title = {The effect of rehabilitation protocol using mobile health in overweight and obese patients with knee osteoarthritis: a clinical trial.},
journal = {Advances in rheumatology (London, England)},
volume = {61},
number = {1},
pages = {63},
pmid = {34689837},
issn = {2523-3106},
mesh = {Clinical Protocols ; Humans ; Middle Aged ; *Obesity/complications ; *Osteoarthritis, Knee/rehabilitation ; *Overweight/complications ; *Telemedicine ; Treatment Outcome ; },
abstract = {OBJECTIVE: The objective of this randomized controlled trial (RCT) was to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) combined with mobile health (mHealth) applications on knee pain, mobility, functional activity and activities of daily living (ADL) among knee osteoarthritis (OA) patients who were overweight and obese.

METHODS: This study was a single-blind, RCT conducted at Teaching Bay of Rehmatul-Lil-Alameen Post Graduate Institute of Cardiology between February and November 2020. 114 knee OA patients who were overweight and obese were randomly divided by a computer-generated number into the rehabilitation group with mHealth (RGw-mHealth) to receive LLRP + instructions of daily care (IDC) combined with mHealth intervention, rehabilitation group without mHealth (RGwo-mHealth) to receive LLRP + IDC intervention and control group (CG) to receive IDC intervention. All three groups were also provided leaflets explaining about their intervention. The primary outcome measure was knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index score. The secondary outcome measures were mobility measured by the Timed up and go (TUG) test, functional activity measured by the patient-specific functional scale (PSFS), and ADL measured by the Katz Index of independence in ADL scores.

RESULTS: Among the 114 patients who were randomized (mean age, 53 years), 96 (84%) completed the trial. After 3-months of intervention, patients in all three groups had statistically significant knee pain reduction (RGw-mHealth: 2.54; RGwo-mHealth: 1.47; and CG: 0.37) within groups (P < 0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in mobility, functional activity, and ADL within groups (P < 0.05), but no improvement was noted in the CG (p > 0.05). As indicated in the overall analysis of covariance, there were statistically significant differences in the mean knee pain, mobility, functional activity, and ADL changes between groups after 3-months (p < 0.001). The pairwise between-group comparisons (Bonferroni post hoc analysis) of the knee pain, mobility, functional activity, and ADL scores at 3-months revealed that patients in the RGw-mHealth had significantly higher mean change in the knee pain, TUG test, functional activity, and ADL scores compared to patients in the RGwo-mHealth or CG.

CONCLUSION: Reduction in knee pain, improvement in mobility, functional activity, and ADL were more among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Trial registration National Medical Research Registry: NMRR-20-1094-52911. Date of registration: 05-05-2020. URL: https://www.nmrr.gov.my .},
}

Clinical Protocols
Humans
Middle Aged
*Obesity/complications
*Osteoarthritis, Knee/rehabilitation
*Overweight/complications
*Telemedicine
Treatment Outcome

@article {pmid34949235,
year = {2021},
author = {Mavhungu, R and Bhuiyan, M and Ooko, F},
title = {Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.},
journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde},
volume = {111},
number = {11b},
pages = {1129-1131},
doi = {10.7196/SAMJ.2021.v111i11b.16108},
pmid = {34949235},
issn = {2078-5135},
abstract = {BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.

OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.

METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.

RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The most common histological type was invasive ductal cell carcinoma (IDC) (87%).

CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or IV). We recommend provision of mammography services in regional hospitals.},
}

@article {pmid34945830,
year = {2021},
author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY},
title = {Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.},
journal = {Journal of personalized medicine},
volume = {11},
number = {12},
pages = {},
doi = {10.3390/jpm11121358},
pmid = {34945830},
issn = {2075-4426},
abstract = {BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).

RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.

CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.},
}

@article {pmid34672684,
year = {2021},
author = {Yadav, S and Hu, C and Nathanson, KL and Weitzel, JN and Goldgar, DE and Kraft, P and Gnanaolivu, RD and Na, J and Huang, H and Boddicker, NJ and Larson, N and Gao, C and Yao, S and Weinberg, C and Vachon, CM and Trentham-Dietz, A and Taylor, JA and Sandler, DR and Patel, A and Palmer, JR and Olson, JE and Neuhausen, S and Martinez, E and Lindstrom, S and Lacey, JV and Kurian, AW and John, EM and Haiman, C and Bernstein, L and Auer, PW and Anton-Culver, H and Ambrosone, CB and Karam, R and Chao, E and Yussuf, A and Pesaran, T and Dolinsky, JS and Hart, SN and LaDuca, H and Polley, EC and Domchek, SM and Couch, FJ},
title = {Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {39},
number = {35},
pages = {3918-3926},
pmid = {34672684},
issn = {1527-7755},
support = {P01 CA087969/CA/NCI NIH HHS/United States ; R01 CA097396/CA/NCI NIH HHS/United States ; K07 CA092044/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; R01 CA225662/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 CA204819/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; R01 CA067264/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; R01 CA047147/CA/NCI NIH HHS/United States ; U01 CA082004/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genetic Testing/*methods ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Young Adult ; },
abstract = {PURPOSE: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.

MATERIALS AND METHODS: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).

RESULTS: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.

CONCLUSION: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/*genetics
Breast Neoplasms/genetics/*pathology
Carcinoma, Ductal, Breast/genetics/*pathology
Carcinoma, Lobular/genetics/*pathology
Case-Control Studies
Female
Follow-Up Studies
*Genetic Predisposition to Disease
Genetic Testing/*methods
*Germ-Line Mutation
Humans
Middle Aged
Prognosis
Young Adult

@article {pmid34423517,
year = {2021},
author = {Yun, NK and Slostad, JA and Naqib, A and Frankenberger, C and Perez, CB and Ghai, R and Usha, L},
title = {Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.},
journal = {The oncologist},
volume = {26},
number = {12},
pages = {1000-1005},
pmid = {34423517},
issn = {1549-490X},
mesh = {*Breast Neoplasms/genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Precision Medicine ; Sequence Analysis, DNA ; },
abstract = {Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.},
}

*Breast Neoplasms/genetics
Female
Genomics
High-Throughput Nucleotide Sequencing
Humans
Precision Medicine
Sequence Analysis, DNA

@article {pmid34884498,
year = {2021},
author = {Betz, IR and Qaiyumi, SJ and Goeritzer, M and Thiele, A and Brix, S and Beyhoff, N and Grune, J and Klopfleisch, R and Greulich, F and Uhlenhaut, NH and Kintscher, U and Foryst-Ludwig, A},
title = {Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.},
journal = {International journal of molecular sciences},
volume = {22},
number = {23},
pages = {},
pmid = {34884498},
issn = {1422-0067},
mesh = {Animals ; Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects/metabolism/pathology ; PPAR alpha/genetics/*metabolism ; PPAR delta/genetics/*metabolism ; },
abstract = {Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.},
}

Animals
Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology
Cardiotonic Agents/*pharmacology
Catecholamines/*toxicity
Fatty Acids, Monounsaturated/*pharmacology
Gene Expression Regulation/*drug effects
Male
Mice
Mice, Inbred C57BL
Myocytes, Cardiac/drug effects/metabolism/pathology
PPAR alpha/genetics/*metabolism
PPAR delta/genetics/*metabolism

@article {pmid34645713,
year = {2021},
author = {Teodorescu, K and Plonsky, O and Ayal, S and Barkan, R},
title = {Frequency of enforcement is more important than the severity of punishment in reducing violation behaviors.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {42},
pages = {},
pmid = {34645713},
issn = {1091-6490},
mesh = {COVID-19/*prevention & control/virology ; Decision Making ; Humans ; Probability ; *Punishment ; SARS-CoV-2/isolation & purification ; },
abstract = {External enforcement policies aimed to reduce violations differ on two key components: the probability of inspection and the severity of the punishment. Different lines of research offer different insights regarding the relative importance of each component. In four studies, students and Prolific crowdsourcing participants (Ntotal = 816) repeatedly faced temptations to commit violations under two enforcement policies. Controlling for expected value, we found that a policy combining a high probability of inspection with a low severity of fines (HILS) was more effective than an economically equivalent policy that combined a low probability of inspection with a high severity of fines (LIHS). The advantage of prioritizing inspection frequency over punishment severity (HILS over LIHS) was greater for participants who, in the absence of enforcement, started out with a higher violation rate. Consistent with studies of decisions from experience, frequent enforcement with small fines was more effective than rare severe fines even when we announced the severity of the fine in advance to boost deterrence. In addition, in line with the phenomenon of underweighting of rare events, the effect was stronger when the probability of inspection was rarer (as in most real-life inspection probabilities) and was eliminated under moderate inspection probabilities. We thus recommend that policymakers looking to effectively reduce recurring violations among noncriminal populations should consider increasing inspection rates rather than punishment severity.},
}

COVID-19/*prevention & control/virology
Decision Making
Humans
Probability
*Punishment
SARS-CoV-2/isolation & purification

@article {pmid33692758,
year = {2021},
author = {Togashi, K and Nishitsuka, K and Hayashi, S and Namba, H and Goto, S and Takeda, Y and Suzuki, S and Kato, T and Yamada, Y and Konno, E and Yoshioka, T and Yamakawa, M and Sonoda, Y and Suzuki, T and Yamashita, H},
title = {Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {625663},
pmid = {33692758},
issn = {1664-2392},
mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary ; Exophthalmos/diagnostic imaging/*etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Orbital Neoplasms/complications/diagnostic imaging/*secondary ; },
abstract = {Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.

Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.

Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.},
}

Breast Neoplasms/complications/diagnostic imaging/*pathology
Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary
Exophthalmos/diagnostic imaging/*etiology
Female
Humans
Magnetic Resonance Imaging
Middle Aged
Orbital Neoplasms/complications/diagnostic imaging/*secondary

@article {pmid33135196,
year = {2021},
author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T},
title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.},
journal = {Histopathology},
volume = {79},
number = {3},
pages = {338-346},
pmid = {33135196},
issn = {1365-2559},
support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; },
abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.

METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.

CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.},
}

Adult
Aged
Biomarkers, Tumor/analysis/genetics
Carcinoma, Ductal/diagnosis/genetics/pathology
*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology
Diagnosis, Differential
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Middle Aged
Mutation
Oncogene Fusion
Oxyphil Cells/pathology
Proto-Oncogene Proteins B-raf/*genetics
Proto-Oncogene Proteins c-ret/*genetics
*Salivary Gland Neoplasms/diagnosis/genetics/pathology
Salivary Glands/pathology
Sequence Analysis, RNA
Transcription Factors/*genetics

@article {pmid33191115,
year = {2021},
author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV},
title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.},
journal = {Clinical breast cancer},
volume = {21},
number = {3},
pages = {210-217},
doi = {10.1016/j.clbc.2020.08.009},
pmid = {33191115},
issn = {1938-0666},
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; },
abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.

MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.

RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.

CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeqTM. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.},
}

Breast Neoplasms/*genetics/pathology
Carcinoma, Ductal, Breast/genetics
Carcinoma, Lobular/genetics
*DNA Copy Number Variations
Female
Gene Expression Regulation, Neoplastic/*genetics
High-Throughput Nucleotide Sequencing/*methods
Humans
Neoplasm Invasiveness
Neoplasm Staging

@article {pmid32943456,
year = {2020},
author = {Richard, F and Majjaj, S and Venet, D and Rothé, F and Pingitore, J and Boeckx, B and Marchio, C and Clatot, F and Bertucci, F and Mariani, O and Galant, C and Eynden, GVD and Salgado, R and Biganzoli, E and Lambrechts, D and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C and Desmedt, C},
title = {Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {23},
pages = {6254-6265},
doi = {10.1158/1078-0432.CCR-20-2268},
pmid = {32943456},
issn = {1557-3265},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary ; Carcinoma, Lobular/genetics/immunology/metabolism/*secondary ; Female ; Follow-Up Studies ; Genomics/*methods ; Humans ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Stromal Cells/*immunology ; Survival Rate ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.

EXPERIMENTAL DESIGN: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.

RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.

CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.},
}

Biomarkers, Tumor/*genetics
Breast Neoplasms/genetics/immunology/metabolism/*pathology
Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary
Carcinoma, Lobular/genetics/immunology/metabolism/*secondary
Female
Follow-Up Studies
Genomics/*methods
Humans
Lymphatic Metastasis
Lymphocytes, Tumor-Infiltrating/*immunology
Middle Aged
*Mutation
Prognosis
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies
Stromal Cells/*immunology
Survival Rate

@article {pmid34899603,
year = {2021},
author = {Kopf, S and Kumar, V and Kender, Z and Han, Z and Fleming, T and Herzig, S and Nawroth, PP},
title = {Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {765201},
doi = {10.3389/fendo.2021.765201},
pmid = {34899603},
issn = {1664-2392},
abstract = {Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.},
}

@article {pmid33534078,
year = {2021},
author = {Oses, G and Cases, C and Valduvieco, I and Farrús, B and Alonso, I and Caparrós, X and Mases, J and Muñoz-Guglielmetti, D and Biete, A and Castro, C and Escudero, E and Molina, M and Herreros, A and Saez, J and Mollà, M},
title = {Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.},
journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {23},
number = {8},
pages = {1593-1600},
pmid = {33534078},
issn = {1699-3055},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*radiation effects ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery ; Electrons/*therapeutic use ; Female ; Fibrosis/pathology ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; Postoperative Complications ; Prospective Studies ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Treatment Outcome ; },
abstract = {PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost.

MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0.

RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema.

CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.},
}

Adult
Aged
Aged, 80 and over
Breast/*radiation effects
Breast Neoplasms/mortality/*radiotherapy/surgery
Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery
Electrons/*therapeutic use
Female
Fibrosis/pathology
Humans
Intraoperative Period
Mastectomy, Segmental
Middle Aged
Neoplasm Recurrence, Local/prevention & control
Postoperative Complications
Prospective Studies
Radiation Injuries/pathology
Radiotherapy Dosage
Treatment Outcome

@article {pmid34829743,
year = {2021},
author = {Liu, PF and Shu, CW and Yang, HC and Lee, CH and Liou, HH and Ger, LP and Tzeng, YT and Wang, WC},
title = {Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.},
journal = {Biomedicines},
volume = {9},
number = {11},
pages = {},
doi = {10.3390/biomedicines9111514},
pmid = {34829743},
issn = {2227-9059},
support = {MOST 108-2320-B-037-038, MOST 109-2320-B-037-015-MY3//The Ministry of Science and Technology/ ; KMU-Q109008; KMU-Q110002//Kaohsiung Medical University Research Foundation/ ; NSYSUKMU 109-I007; NSYSUKMU-110-I006//The National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC108A04//Kaohsiung Medical University Research Center Grant/ ; VGHKS106-015; VGHKS107-014//Kaohsiung Veterans General Hospital/ ; },
abstract = {Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.},
}

@article {pmid34427055,
year = {2021},
author = {Morigny, P and Kaltenecker, D and Zuber, J and Machado, J and Mehr, L and Tsokanos, FF and Kuzi, H and Hermann, CD and Voelkl, M and Monogarov, G and Springfeld, C and Laurent, V and Engelmann, B and Friess, H and Zörnig, I and Krüger, A and Krijgsveld, J and Prokopchuk, O and Fisker Schmidt, S and Rohm, M and Herzig, S and Berriel Diaz, M},
title = {Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {12},
number = {5},
pages = {1333-1351},
pmid = {34427055},
issn = {2190-6009},
support = {J4224-B34/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Benzaldehydes ; Biomarkers ; *Cachexia/drug therapy/etiology ; Humans ; Mice ; Oximes ; *Pancreatic Neoplasms ; Prospective Studies ; },
abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.

METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.

RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.

CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.},
}

1-Alkyl-2-acetylglycerophosphocholine Esterase
Animals
Benzaldehydes
Biomarkers
*Cachexia/drug therapy/etiology
Humans
Mice
Oximes
*Pancreatic Neoplasms
Prospective Studies

@article {pmid32561662,
year = {2020},
author = {Sestak, I and Filipits, M and Buus, R and Rudas, M and Balic, M and Knauer, M and Kronenwett, R and Fitzal, F and Cuzick, J and Gnant, M and Greil, R and Dowsett, M and Dubsky, P},
title = {Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {17},
pages = {4682-4687},
doi = {10.1158/1078-0432.CCR-20-0260},
pmid = {32561662},
issn = {1557-3265},
support = {5032/CRUK_/Cancer Research UK/United Kingdom ; C569/A16891/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast/*pathology/surgery ; Breast Neoplasms/genetics/*mortality/pathology/therapy ; Carcinoma, Lobular/genetics/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials, Phase III as Topic ; Datasets as Topic ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/genetics/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Risk Assessment/methods ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC).

EXPERIMENTAL DESIGN: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR.

RESULTS: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)].

CONCLUSIONS: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.},
}

Aged
Antineoplastic Agents, Hormonal/therapeutic use
Breast/*pathology/surgery
Breast Neoplasms/genetics/*mortality/pathology/therapy
Carcinoma, Lobular/genetics/*mortality/pathology/therapy
Chemotherapy, Adjuvant/methods
Clinical Trials, Phase III as Topic
Datasets as Topic
Disease-Free Survival
Female
Follow-Up Studies
Gene Expression Profiling
Humans
Kaplan-Meier Estimate
Mastectomy
Middle Aged
Neoplasm Recurrence, Local/*epidemiology/genetics/pathology
Prognosis
Randomized Controlled Trials as Topic
Receptor, ErbB-2/analysis/metabolism
Receptors, Estrogen/analysis/metabolism
Receptors, Progesterone/analysis/metabolism
Risk Assessment/methods

@article {pmid34610495,
year = {2021},
author = {Rousseau, S and Katz, D and Shlomi-Polachek, I and Frenkel, TI},
title = {Prospective risk from prenatal anxiety to post traumatic stress following childbirth: The mediating effects of acute stress assessed during the postnatal hospital stay and preliminary evidence for moderating effects of doula care.},
journal = {Midwifery},
volume = {103},
number = {},
pages = {103143},
doi = {10.1016/j.midw.2021.103143},
pmid = {34610495},
issn = {1532-3099},
mesh = {Anxiety/etiology ; *Doulas ; Female ; Humans ; Length of Stay ; Parturition ; Postpartum Period ; Pregnancy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/etiology ; },
abstract = {OBJECTIVE: Growing literature has identified childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth. The current study is the first to prospectively examine a pathway of risk from mothers' prenatal trait-anxiety, to Acute-Stress-Immediately-Following-Childbirth, and later symptoms of Post-Traumatic-Stress-Following-Childbirth, in a low-risk community sample. Auxiliary analyses explored whether doula care during childbirth moderated risk.

METHOD: 149 pregnant women were randomly selected. Prenatal trait-anxiety was assessed toward the end of pregnancy, Acute-Stress-Immediately-Following-Childbirth at two-days post-partum, and symptoms of Post-Traumatic-Stress-Following-Childbirth at one-month post-partum.

RESULTS: Results indicated a significant indirect pathway from prenatal trait-anxiety to Post-Traumatic-Stress-Following-Childbirth, through Acute-Stress-Immediately-Following-Childbirth. Two groups were generated ad hoc for auxiliary analyses: participants who opted to receive doula care during childbirth (n=21; 14%) versus participants who received care as usual (n=128; 86%). Analyses provided preliminary support for doula care as a potential moderator of risk.

CONCLUSIONS: Results point toward prenatal trait-anxiety and Acute-Stress-Immediately-Following-Childbirth as significant risk factors for Post-Traumatic-Stress-Following-Childbirth. Findings inform preventive screening implicating the prenatal period as well as the postnatal hospital stay as important time windows for preventive screening. Finally, preliminary support for moderating effects of doula care suggest that preventive interventions administered during the perinatal period may effectively reduce anxiety-related risk for Post-Traumatic-Stress-Following-Childbirth.},
}

Anxiety/etiology
*Doulas
Female
Humans
Length of Stay
Parturition
Postpartum Period
Pregnancy
Prospective Studies
*Stress Disorders, Post-Traumatic/etiology

@article {pmid32532588,
year = {2020},
author = {Brings, S and Fleming, T and Herzig, S and Nawroth, PP and Kopf, S},
title = {Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study.},
journal = {Journal of diabetes and its complications},
volume = {34},
number = {9},
pages = {107648},
doi = {10.1016/j.jdiacomp.2020.107648},
pmid = {32532588},
issn = {1873-460X},
mesh = {*Albuminuria/diagnosis/etiology ; Cathepsin D/urine ; Cathepsin L/*urine ; Cohort Studies ; *Diabetes Mellitus, Type 2/complications/diagnosis ; *Glycation End Products, Advanced/urine ; Humans ; Tandem Mass Spectrometry ; },
abstract = {AIMS: Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study.

METHODS: We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients.

RESULTS: The detection limit of CTSD and CTSL in urine was 2.4 ng/l and 19.1 ng/l, respectively. CTSD (p < 0.0001, r = 0.555) and CTSL (p < 0.0001, r = 0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p = 0.012, r = 0.225; CTSL: p < 0.001, r = 0.376). A strong non-linear association between CTSD (r = 0.568), CTSL (r = 0.588) and change in albuminuria over four years was present. High levels of CTSL (p = 0.007, beta = -0.366) were associated with an improvement of albuminuria after four years.

CONCLUSIONS: A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.},
}

*Albuminuria/diagnosis/etiology
Cathepsin D/urine
Cathepsin L/*urine
Cohort Studies
*Diabetes Mellitus, Type 2/complications/diagnosis
*Glycation End Products, Advanced/urine
Humans
Tandem Mass Spectrometry

@article {pmid33863935,
year = {2021},
author = {Nobili, S and Mannini, A and Parenti, A and Raggi, C and Lapucci, A and Chiorino, G and Paccosi, S and Di Gennaro, P and Vezzosi, V and Romagnoli, P and Susini, T and Coronnello, M},
title = {Establishment and characterization of a new spontaneously immortalized ER-/PR-/HER2+ human breast cancer cell line, DHSF-BR16.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {8340},
pmid = {33863935},
issn = {2045-2322},
mesh = {Aged ; Breast Neoplasms/drug therapy/*genetics/*pathology/surgery ; CD24 Antigen/genetics/metabolism ; Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Movement ; Chemotherapy, Adjuvant ; Epithelial Cell Adhesion Molecule/genetics/metabolism ; Female ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Intracellular Membranes/metabolism ; Keratin-7/genetics/metabolism ; Keratin-8/genetics/metabolism ; Neoadjuvant Therapy ; *Receptor, ErbB-2 ; *Receptors, Estrogen ; *Receptors, Progesterone ; Spheroids, Cellular/pathology ; },
abstract = {Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER-/PR-/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24-/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.},
}

Aged
Breast Neoplasms/drug therapy/*genetics/*pathology/surgery
CD24 Antigen/genetics/metabolism
Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery
Cell Line, Tumor
Cell Movement
Chemotherapy, Adjuvant
Epithelial Cell Adhesion Molecule/genetics/metabolism
Female
Humans
Hyaluronan Receptors/genetics/metabolism
Intracellular Membranes/metabolism
Keratin-7/genetics/metabolism
Keratin-8/genetics/metabolism
Neoadjuvant Therapy
*Receptor, ErbB-2
*Receptors, Estrogen
*Receptors, Progesterone
Spheroids, Cellular/pathology

@article {pmid34556291,
year = {2021},
author = {Mangiardi-Veltin, M and Chamming's, F and Jaffre, A and Rousvoal, A and Tunon de Lara, C and Brouste, V and Hoppe, S and Sénéchal, C},
title = {[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].},
journal = {Bulletin du cancer},
volume = {108},
number = {11},
pages = {999-1009},
doi = {10.1016/j.bulcan.2021.05.007},
pmid = {34556291},
issn = {1769-6917},
mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/genetics ; Cancer Care Facilities ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics ; Postoperative Complications/*epidemiology ; Prevalence ; Prophylactic Mastectomy/*adverse effects/methods ; Reoperation ; Retrospective Studies ; Time Factors ; },
abstract = {INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.

METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.

RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).

DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.},
}

Adult
Aged
Breast Neoplasms/diagnostic imaging/*epidemiology/genetics
Cancer Care Facilities
Female
Genes, BRCA1
Genes, BRCA2
Humans
Middle Aged
Mutation
Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics
Postoperative Complications/*epidemiology
Prevalence
Prophylactic Mastectomy/*adverse effects/methods
Reoperation
Retrospective Studies
Time Factors

@article {pmid34781971,
year = {2021},
author = {Kostoglou, A and Vlastos, D and Bakalis, A and Ghosh, D},
title = {Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.},
journal = {World journal of surgical oncology},
volume = {19},
number = {1},
pages = {328},
pmid = {34781971},
issn = {1477-7819},
mesh = {Adult ; *Breast Neoplasms/complications ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Opsoclonus-Myoclonus Syndrome/etiology ; Positron Emission Tomography Computed Tomography ; Prognosis ; },
abstract = {BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.

CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.

CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.},
}

Adult
*Breast Neoplasms/complications
Female
Humans
Mastectomy
Neoplasm Recurrence, Local
*Opsoclonus-Myoclonus Syndrome/etiology
Positron Emission Tomography Computed Tomography
Prognosis

@article {pmid33229203,
year = {2021},
author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M},
title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual & rare site of metastasis from the common cancer.},
journal = {Oral oncology},
volume = {115},
number = {},
pages = {105098},
doi = {10.1016/j.oraloncology.2020.105098},
pmid = {33229203},
issn = {1879-0593},
mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; },
abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual & exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck & non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.},
}

Aged
Bone Neoplasms/secondary
Breast Neoplasms/*diagnosis
Female
Humans
Maxilla/*pathology
Maxillary Neoplasms/*secondary
Neoplasm Metastasis

@article {pmid34765304,
year = {2021},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study.},
journal = {American journal of cancer research},
volume = {11},
number = {10},
pages = {4966-4980},
pmid = {34765304},
issn = {2156-6976},
abstract = {To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.},
}

@article {pmid33416185,
year = {2021},
author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD},
title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.},
journal = {Oncology reports},
volume = {45},
number = {2},
pages = {706-716},
doi = {10.3892/or.2020.7880},
pmid = {33416185},
issn = {1791-2431},
mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; },
abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.},
}

Animals
Breast/pathology/surgery
Breast Neoplasms/*genetics/mortality/pathology/surgery
Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery
Cell Line, Tumor
DNA-Binding Proteins/*genetics
Disease Progression
Disease-Free Survival
Epithelial-Mesenchymal Transition/genetics
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mastectomy
Mice
MicroRNAs/genetics/*metabolism
Neoplasm Recurrence, Local/*epidemiology/genetics
RNA-Binding Proteins/*genetics
Xenograft Model Antitumor Assays

@article {pmid33263939,
year = {2021},
author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.},
journal = {The journal of pathology. Clinical research},
volume = {7},
number = {2},
pages = {113-120},
pmid = {33263939},
issn = {2056-4538},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Whole Exome Sequencing ; },
abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.},
}

Adult
Breast Neoplasms/complications/diagnosis/*genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology
Class I Phosphatidylinositol 3-Kinases/*genetics
*DNA Copy Number Variations
DNA Mutational Analysis
Female
Humans
Mutation
Papilloma/complications/diagnosis/*genetics/pathology
Whole Exome Sequencing

@article {pmid32686908,
year = {2020},
author = {Ma, L and Qi, L and Li, S and Yin, Q and Liu, J and Wang, J and She, C and Li, P and Liu, Q and Wang, X and Li, W},
title = {Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.},
journal = {Thoracic cancer},
volume = {11},
number = {9},
pages = {2493-2505},
pmid = {32686908},
issn = {1759-7714},
support = {81702481//National Natural Science Foundation of China/ ; 15JCQNJC44800//Natural Science Foundation of Tianjin City/ ; 18JCYBJC27600//Natural Science Foundation of Tianjin City/ ; },
mesh = {Brain Neoplasms/*enzymology/*secondary ; Breast Neoplasms/*complications/*enzymology/pathology ; Female ; Histone Deacetylases/*metabolism ; Humans ; Middle Aged ; },
abstract = {BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.

METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.

RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.

CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.

KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.},
}

Brain Neoplasms/*enzymology/*secondary
Breast Neoplasms/*complications/*enzymology/pathology
Female
Histone Deacetylases/*metabolism
Humans
Middle Aged

@article {pmid32661669,
year = {2021},
author = {Rooper, LM and Thompson, LDR and Gagan, J and Oliai, BR and Weinreb, I and Bishop, JA},
title = {Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.},
journal = {Head and neck pathology},
volume = {15},
number = {1},
pages = {179-185},
pmid = {32661669},
issn = {1936-0568},
mesh = {Aged ; Aged, 80 and over ; Carcinoma, Ductal/genetics/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Parotid Neoplasms/genetics/*pathology ; },
abstract = {Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.},
}

Aged
Aged, 80 and over
Carcinoma, Ductal/genetics/*pathology
Female
Humans
Lymph Nodes/*pathology
Male
Middle Aged
Oncogene Proteins, Fusion/genetics
Parotid Neoplasms/genetics/*pathology

@article {pmid33428505,
year = {2021},
author = {Nevagi, RJ and Good, MF and Stanisic, DI},
title = {Plasmodium infection and drug cure for malaria vaccine development.},
journal = {Expert review of vaccines},
volume = {20},
number = {2},
pages = {163-183},
doi = {10.1080/14760584.2021.1874923},
pmid = {33428505},
issn = {1744-8395},
mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration & dosage ; Humans ; Malaria/immunology/parasitology/*prevention & control ; Malaria Vaccines/*administration & dosage/immunology ; Plasmodium/*immunology/parasitology ; },
abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.},
}

Animals
Antigens, Protozoan/immunology
Antimalarials/administration & dosage
Humans
Malaria/immunology/parasitology/*prevention & control
Malaria Vaccines/*administration & dosage/immunology
Plasmodium/*immunology/parasitology

@article {pmid33073677,
year = {2020},
author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY},
title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.},
journal = {Technology in cancer research & treatment},
volume = {19},
number = {},
pages = {1533033820960760},
pmid = {33073677},
issn = {1533-0338},
mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; },
abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.},
}

Breast Neoplasms/*genetics/pathology
Female
Gene Expression Regulation, Neoplastic/genetics
Humans
Ki-67 Antigen/genetics
Middle Aged
Neoplasm Recurrence, Local/*genetics/pathology
Paraffin Embedding
Real-Time Polymerase Chain Reaction/*methods
Receptor, ErbB-2/genetics
Receptors, Estrogen/genetics
Transcriptome/*genetics

@article {pmid34708717,
year = {2021},
author = {Wang, YY and Liu, C and Chen, X and Ji, J and Zhu, SL and Sun, Q and Zhang, K and Zhu, J and Zhao, S and Wang, YW and Ma, R and Wang, JL},
title = {Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.},
journal = {The Chinese journal of physiology},
volume = {64},
number = {5},
pages = {251-256},
doi = {10.4103/cjp.cjp_72_21},
pmid = {34708717},
issn = {0304-4920},
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; Female ; HSP90 Heat-Shock Proteins/*genetics ; Humans ; *Nipple Discharge ; },
abstract = {Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.},
}

Biomarkers, Tumor
*Breast Neoplasms/diagnosis
Female
HSP90 Heat-Shock Proteins/*genetics
Humans
*Nipple Discharge

@article {pmid34238275,
year = {2021},
author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K},
title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.},
journal = {BMC cancer},
volume = {21},
number = {1},
pages = {790},
pmid = {34238275},
issn = {1471-2407},
mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; },
abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.

METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.

RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.

CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.},
}

Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology
Cell Line, Tumor
Cell Proliferation
Female
Humans

@article {pmid32220886,
year = {2020},
author = {Pareja, F and Brown, DN and Lee, JY and Da Cruz Paula, A and Selenica, P and Bi, R and Geyer, FC and Gazzo, A and da Silva, EM and Vahdatinia, M and Stylianou, AA and Ferrando, L and Wen, HY and Hicks, JB and Weigelt, B and Reis-Filho, JS},
title = {Whole-Exome Sequencing Analysis of the Progression from Non-Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {14},
pages = {3682-3693},
pmid = {32220886},
issn = {1557-3265},
support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA Copy Number Variations ; DNA Mutational Analysis ; Disease Progression ; Female ; *Genetic Heterogeneity ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/diagnosis/*genetics/pathology ; Whole Exome Sequencing ; },
abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level of intralesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.

EXPERIMENTAL DESIGN: Synchronous DCIS (n = 27) and invasive ductal carcinomas of no special type (IDC-NSTs; n = 26) from 25 patients, and pure DCIS (n = 7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n = 56) or massively parallel sequencing targeting ≥410 key cancer-related genes (n = 4). Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic analyses were defined using validated computational methods.

RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intralesion genetic heterogeneity than DCIS where no clonal selection was observed.

CONCLUSIONS: Intralesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a nonobligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.},
}

Adult
Aged
Biomarkers, Tumor/genetics
Breast/pathology
Breast Neoplasms/diagnosis/*genetics/pathology
Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology
Class I Phosphatidylinositol 3-Kinases/genetics
DNA Copy Number Variations
DNA Mutational Analysis
Disease Progression
Female
*Genetic Heterogeneity
Humans
Middle Aged
Neoplasm Grading
Neoplasms, Multiple Primary/diagnosis/*genetics/pathology
Whole Exome Sequencing

@article {pmid34716548,
year = {2021},
author = {Cattaneo, C and Rieg, S and Schwarzer, G and Müller, MC and Blümel, B and Kern, WV},
title = {Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {34716548},
issn = {1439-0973},
abstract = {PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes.

METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression.

RESULTS: A total of 151 patients with a median age of 68 years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76).

CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.},
}

@article {pmid34707969,
year = {2021},
author = {Blum, K and Bowirrat, A and Gondre Lewis, MC and Simpatico, TA and Ceccanti, M and Steinberg, B and Modestino, EJ and Thanos, PK and Baron, D and McLaughlin, T and Brewer, R and Badgaiyan, RD and Ponce, JV and Lott, L and Gold, MS},
title = {Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.},
journal = {Current psychopharmacology},
volume = {10},
number = {},
pages = {},
doi = {10.2174/2211556010666210215155509},
pmid = {34707969},
issn = {2211-5560},
abstract = {Background: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.

Objective: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.

Method: Genetic Addiction Risk Score (GARS®) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.

Results: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).

Conclusion: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.},
}

@article {pmid34048471,
year = {2021},
author = {Brock, EJ and Jackson, RM and Boerner, JL and Li, Q and Tennis, MA and Sloane, BF and Mattingly, RR},
title = {Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.},
journal = {PloS one},
volume = {16},
number = {5},
pages = {e0252314},
pmid = {34048471},
issn = {1932-6203},
support = {F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; },
abstract = {Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.},
}

Breast Neoplasms/genetics/*metabolism
Carcinoma, Ductal, Breast/genetics/*metabolism
Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism
Cell Line, Tumor
Cells, Cultured
Female
Humans
Immunoblotting
Immunohistochemistry
Intracellular Signaling Peptides and Proteins/genetics/*metabolism
Mitogen-Activated Protein Kinase 1/genetics/*metabolism
Mitogen-Activated Protein Kinase 3/genetics/*metabolism
Nerve Tissue Proteins/genetics/*metabolism

@article {pmid34698916,
year = {2021},
author = {Deshpande, SS and Malik, SC and Conforti, P and Lin, JD and Chu, YH and Nath, S and Greulich, F and Dumbach, MA and Uhlenhaut, NH and Schachtrup, C},
title = {P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.},
journal = {Cell and tissue research},
volume = {},
number = {},
pages = {},
pmid = {34698916},
issn = {1432-0878},
support = {1442/8-1//Deutsche Forschungsgemeinschaft/ ; 1442/9-1//Deutsche Forschungsgemeinschaft/ ; },
abstract = {Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75NTR-/-) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75NTR-/- NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75NTR-/- NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75NTR-/- NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.},
}

@article {pmid34133406,
year = {2021},
author = {Akhavan, AA and Wirtz, EC and Ollila, DW and Bhatt, N},
title = {An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.},
journal = {Plastic and reconstructive surgery},
volume = {148},
number = {2},
pages = {299-303},
doi = {10.1097/PRS.0000000000008155},
pmid = {34133406},
issn = {1529-4242},
mesh = {Adalimumab/*adverse effects ; Breast Implantation/*adverse effects/instrumentation ; Breast Implants/*adverse effects ; Breast Neoplasms/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant/adverse effects/methods ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery ; Mastectomy/adverse effects ; Middle Aged ; Surface Properties ; Tissue Expansion Devices/*adverse effects ; },
abstract = {SUMMARY: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.},
}

Adalimumab/*adverse effects
Breast Implantation/*adverse effects/instrumentation
Breast Implants/*adverse effects
Breast Neoplasms/diagnosis/pathology/therapy
Carcinoma, Ductal, Breast/diagnosis/pathology/therapy
Chemotherapy, Adjuvant/adverse effects/methods
Female
Humans
Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery
Mastectomy/adverse effects
Middle Aged
Surface Properties
Tissue Expansion Devices/*adverse effects

@article {pmid34349234,
year = {2021},
author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL},
title = {Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.},
journal = {Spinal cord},
volume = {59},
number = {9},
pages = {948-958},
pmid = {34349234},
issn = {1476-5624},
support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; 90IF0121/ACL/ACL HHS/United States ; 90IF0121/ACL/ACL HHS/United States ; },
mesh = {Catheters, Indwelling ; Humans ; Psychometrics ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; },
abstract = {STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).

SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.

METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".

RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.

CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.},
}

Catheters, Indwelling
Humans
Psychometrics
*Spinal Cord Injuries/complications/diagnosis
Surveys and Questionnaires
*Urinary Bladder, Neurogenic/diagnosis/etiology

@article {pmid34345005,
year = {2021},
author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL},
title = {Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.},
journal = {Spinal cord},
volume = {59},
number = {9},
pages = {939-947},
pmid = {34345005},
issn = {1476-5624},
support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; },
mesh = {Bayes Theorem ; Catheters, Indwelling ; Humans ; Reproducibility of Results ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; United States ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; },
abstract = {STUDY DESIGN: This is a descriptive psychometrics study.

OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.

SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n = 306), or by voiding (SCI, n = 103; MS, n = 383).

METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement > 10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.

RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.

CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.},
}

Bayes Theorem
Catheters, Indwelling
Humans
Reproducibility of Results
*Spinal Cord Injuries/complications/diagnosis
Surveys and Questionnaires
United States
*Urinary Bladder, Neurogenic/diagnosis/etiology

@article {pmid33090732,
year = {2020},
author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M},
title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {11},
number = {6},
pages = {1459-1475},
pmid = {33090732},
issn = {2190-6009},
mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; },
abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.

METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, ApcMin/+ mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer™ platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.

RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.

CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.},
}

Animals
*Cachexia/etiology
*Ceramides/metabolism
Humans
Mice
Muscular Atrophy
*Neoplasms/complications
Quality of Life

@article {pmid32467291,
year = {2020},
author = {Shan, NL and Minden, A and Furmanski, P and Bak, MJ and Cai, L and Wernyj, R and Sargsyan, D and Cheng, D and Wu, R and Kuo, HD and Li, SN and Fang, M and Maehr, H and Kong, AN and Suh, N},
title = {Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal Carcinoma In Situ by Vitamin D Compounds.},
journal = {Cancer prevention research (Philadelphia, Pa.)},
volume = {13},
number = {8},
pages = {673-686},
pmid = {32467291},
issn = {1940-6215},
support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AT007036/AT/NCCIH NIH HHS/United States ; R01 AT009152/AT/NCCIH NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology/*prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Methylation/drug effects ; Datasets as Topic ; Disease Progression ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness/pathology/prevention & control ; Neoplastic Stem Cells/*drug effects/pathology ; RNA-Seq ; Signal Transduction/drug effects/genetics ; Up-Regulation/drug effects ; Vitamin D/*administration & dosage/analogs & derivatives ; },
abstract = {Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA-sequencing, we found that vitamin D compounds downregulated genes involved in maintenance of breast cancer stem-like cells (e.g., GDF15), epithelial-mesenchymal transition, invasion, and metastasis (e.g., LCN2 and S100A4), and chemoresistance (e.g., NGFR, PPP1R1B, and AGR2), while upregulating genes associated with a basal-like phenotype (e.g., KRT6A and KRT5) and negative regulators of breast tumorigenesis (e.g., EMP1). Gene methylation status was analyzed to determine whether the changes in expression induced by vitamin D compounds occurred via this mechanism. Ingenuity pathway analysis was performed to identify upstream regulators and downstream signaling pathway genes differentially regulated by vitamin D, including TP63 and vitamin D receptor -mediated canonical pathways in particular. This study provides a global profiling of changes in the gene signature of DCIS regulated by vitamin D compounds and possible targets for chemoprevention of DCIS progression to IDC in patients.},
}

Breast Neoplasms/*drug therapy/genetics/pathology
Carcinoma, Ductal, Breast/genetics/pathology/*prevention & control
Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology
Cell Line, Tumor
Cell Proliferation/drug effects
DNA Methylation/drug effects
Datasets as Topic
Disease Progression
Down-Regulation/drug effects
Epithelial-Mesenchymal Transition/drug effects/genetics
Female
Gene Expression Regulation, Neoplastic/drug effects
Humans
Neoplasm Invasiveness/pathology/prevention & control
Neoplastic Stem Cells/*drug effects/pathology
RNA-Seq
Signal Transduction/drug effects/genetics
Up-Regulation/drug effects
Vitamin D/*administration & dosage/analogs & derivatives

@article {pmid34461516,
year = {2022},
author = {Meng, J and Yang, Q and Wan, W and Zhu, Q and Zeng, X},
title = {Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).},
journal = {Food chemistry},
volume = {369},
number = {},
pages = {130885},
doi = {10.1016/j.foodchem.2021.130885},
pmid = {34461516},
issn = {1873-7072},
mesh = {Animals ; *Biogenic Amines ; China ; Enterobacter ; *Enterobacteriaceae/genetics ; Fermentation ; },
abstract = {The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.},
}

Animals
*Biogenic Amines
China
Enterobacter
*Enterobacteriaceae/genetics
Fermentation

@article {pmid34659834,
year = {2021},
author = {Ntirenganya, F and Twagirumukiza, JD and Bucyibaruta, G and Rugwizangoga, B and Rulisa, S},
title = {Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.},
journal = {International journal of breast cancer},
volume = {2021},
number = {},
pages = {5560559},
doi = {10.1155/2021/5560559},
pmid = {34659834},
issn = {2090-3170},
abstract = {Background: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women.

Objectives: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda.

Methods: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis.

Results: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI 2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI 4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI 3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI 1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI 1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype.

Conclusion: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.},
}

@article {pmid34657058,
year = {2021},
author = {Takagi, H and Fukai, H and Misawa, S and Kurogochi, A and Kirii, Y},
title = {[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {48},
number = {10},
pages = {1255-1257},
pmid = {34657058},
issn = {0385-0684},
mesh = {*Anemia/drug therapy/etiology ; Aromatase Inhibitors ; Bone Marrow ; *Breast Neoplasms/complications/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Peritoneal Neoplasms ; *Thrombocytopenia/drug therapy/etiology ; },
abstract = {The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.},
}

*Anemia/drug therapy/etiology
Aromatase Inhibitors
Bone Marrow
*Breast Neoplasms/complications/drug therapy/surgery
Female
Humans
Mastectomy
Middle Aged
*Peritoneal Neoplasms
*Thrombocytopenia/drug therapy/etiology

@article {pmid34392891,
year = {2021},
author = {Roberts, WC and Jeong, M},
title = {Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {157},
number = {},
pages = {101-106},
doi = {10.1016/j.amjcard.2021.07.023},
pmid = {34392891},
issn = {1879-1913},
mesh = {Adult ; Aged ; Cardiomyopathies/complications/epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Female ; Follow-Up Studies ; *Forecasting ; Heart Failure/epidemiology/etiology/surgery ; Heart Transplantation ; Humans ; Incidence ; Middle Aged ; Peripartum Period ; Pregnancy ; *Pregnancy Complications, Cardiovascular ; Retrospective Studies ; Texas/epidemiology ; Young Adult ; },
abstract = {Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.},
}

Adult
Aged
Cardiomyopathies/complications/epidemiology
Cardiomyopathy, Dilated/*complications/epidemiology
Female
Follow-Up Studies
*Forecasting
Heart Failure/epidemiology/etiology/surgery
Heart Transplantation
Humans
Incidence
Middle Aged
Peripartum Period
Pregnancy
*Pregnancy Complications, Cardiovascular
Retrospective Studies
Texas/epidemiology
Young Adult

@article {pmid34103599,
year = {2021},
author = {Bin Kanner, Y and Ganoth, A and Tsfadia, Y},
title = {Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {12024},
pmid = {34103599},
issn = {2045-2322},
mesh = {Allosteric Regulation ; Amino Acid Substitution ; Humans ; Multidrug Resistance-Associated Proteins/*chemistry/*genetics ; *Mutation, Missense ; Protein Domains ; Protein Structure, Secondary ; },
abstract = {Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.},
}

Allosteric Regulation
Amino Acid Substitution
Humans
Multidrug Resistance-Associated Proteins/*chemistry/*genetics
*Mutation, Missense
Protein Domains
Protein Structure, Secondary

@article {pmid32343605,
year = {2021},
author = {Liu, CR and Meng, FH},
title = {DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.},
journal = {Cancer biotherapy & radiopharmaceuticals},
volume = {36},
number = {2},
pages = {180-188},
doi = {10.1089/cbr.2019.3504},
pmid = {32343605},
issn = {1557-8852},
mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Proliferation/physiology ; Deoxyribonuclease I/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Middle Aged ; Phenotype ; Prognosis ; Transfection ; },
abstract = {Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.},
}

Biomarkers, Tumor/metabolism
Breast Neoplasms/genetics/*metabolism/pathology
Cell Proliferation/physiology
Deoxyribonuclease I/*metabolism
Epithelial-Mesenchymal Transition
Female
Humans
Middle Aged
Phenotype
Prognosis
Transfection

@article {pmid33667422,
year = {2021},
author = {Schwartz, CJ and Boroujeni, AM and Khodadadi-Jamayran, A and Heguy, A and Snuderl, M and Jour, G and Cotzia, P and Darvishian, F},
title = {Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.},
journal = {Human pathology},
volume = {111},
number = {},
pages = {67-74},
doi = {10.1016/j.humpath.2021.02.005},
pmid = {33667422},
issn = {1532-8392},
support = {P30 CA016087/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; },
abstract = {Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.},
}

Aged
Aged, 80 and over
Biomarkers, Tumor/genetics
Breast Neoplasms/*genetics/*pathology
Carcinoma, Ductal, Breast/*genetics/*pathology
Carcinoma, Papillary/*genetics/*pathology
Class I Phosphatidylinositol 3-Kinases/genetics
Female
Humans
Male
Middle Aged
Mutation
Retrospective Studies

@article {pmid32457515,
year = {2020},
author = {Goodes, LM and King, GK and Goodwin, DM and Watts, A and Bardsley, J and Middleton, J and Bragge, P and Dunlop, SA},
title = {Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.},
journal = {Spinal cord},
volume = {58},
number = {12},
pages = {1291-1300},
pmid = {32457515},
issn = {1476-5624},
mesh = {Humans ; Inpatients ; Longitudinal Studies ; *Spinal Cord Injuries/therapy ; *Urinary Bladder, Neurogenic/etiology/therapy ; },
abstract = {STUDY DESIGN: Qualitative survey.

OBJECTIVES: Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.

SETTING: Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).

METHODS: Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.

RESULTS: Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6 hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.

CONCLUSIONS: Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.},
}

Humans
Inpatients
Longitudinal Studies
*Spinal Cord Injuries/therapy
*Urinary Bladder, Neurogenic/etiology/therapy

@article {pmid32239352,
year = {2020},
author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G},
title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {127},
number = {6},
pages = {893-898},
doi = {10.1007/s00702-020-02179-x},
pmid = {32239352},
issn = {1435-1463},
mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; },
abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.},
}

Anxiety/etiology
*Cognitive Dysfunction/etiology
*Gait Disorders, Neurologic
Humans
Neuropsychological Tests
*Parkinson Disease/complications

@article {pmid34016957,
year = {2021},
author = {Egea, V and Kessenbrock, K and Lawson, D and Bartelt, A and Weber, C and Ries, C},
title = {Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.},
journal = {Cell death & disease},
volume = {12},
number = {6},
pages = {516},
pmid = {34016957},
issn = {2041-4889},
mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Chemokine CXCL12/*metabolism ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics/*metabolism/pathology ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/biosynthesis/*genetics ; Transfection ; Tumor Hypoxia/*physiology ; },
abstract = {Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.},
}

Animals
Cell Communication/physiology
Cell Differentiation/physiology
Cell Proliferation/physiology
Chemokine CXCL12/*metabolism
Disease Models, Animal
Female
Humans
Mammary Neoplasms, Experimental/genetics/*metabolism/pathology
Mesenchymal Stem Cells/*metabolism/pathology
Mice
Mice, Inbred BALB C
MicroRNAs/biosynthesis/*genetics
Transfection
Tumor Hypoxia/*physiology

@article {pmid33238073,
year = {2021},
author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S},
title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.},
journal = {Pathology international},
volume = {71},
number = {1},
pages = {24-32},
doi = {10.1111/pin.13044},
pmid = {33238073},
issn = {1440-1827},
mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; },
abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.},
}

Adolescent
Adult
Aged
B7-H1 Antigen/*metabolism
Biomarkers, Tumor/analysis
*Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology
Dendritic Cells/metabolism/pathology
Female
Histiocytes/metabolism/pathology
*Histiocytic Sarcoma/immunology/metabolism/pathology
Humans
Immunohistochemistry
Immunophenotyping
In Situ Hybridization, Fluorescence
Japan
Langerhans Cell Sarcoma/immunology/metabolism/pathology
Lymphoma, Follicular/immunology/metabolism/pathology
Male
Middle Aged
Retrospective Studies
T-Lymphocytes/metabolism

@article {pmid32511899,
year = {2020},
author = {Yamaguchi, T and Akahane, T and Harada, O and Kato, Y and Aimono, E and Takei, H and Tasaki, T and Noguchi, H and Nishihara, H and Kamata, H and Tanimoto, A},
title = {Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis.},
journal = {Diagnostic cytopathology},
volume = {48},
number = {11},
pages = {965-971},
doi = {10.1002/dc.24511},
pmid = {32511899},
issn = {1097-0339},
mesh = {Carcinoma/*genetics ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Gene Frequency/genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lymph Nodes/pathology ; Mutation/genetics ; Neoplasms/*genetics ; Sequence Analysis, DNA/methods ; Thyroid Gland/pathology ; },
abstract = {BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.

METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.

RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.

CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.},
}

Carcinoma/*genetics
Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods
Gene Frequency/genetics
Genome/*genetics
High-Throughput Nucleotide Sequencing/methods
Humans
Lymph Nodes/pathology
Mutation/genetics
Neoplasms/*genetics
Sequence Analysis, DNA/methods
Thyroid Gland/pathology

@article {pmid34634714,
year = {2021},
author = {Kufel, WD and Mastro, KA and Steele, JM and Wang, D and Riddell, SW and Paolino, KM and Thomas, SJ},
title = {Impact of a pharmacist-facilitated, evidence-based bundle initiative on Staphylococcus aureus bacteremia management.},
journal = {Diagnostic microbiology and infectious disease},
volume = {101},
number = {4},
pages = {115535},
doi = {10.1016/j.diagmicrobio.2021.115535},
pmid = {34634714},
issn = {1879-0070},
abstract = {OBJECTIVE: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).

METHODS: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.

RESULTS: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.

CONCLUSIONS: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.},
}

@article {pmid33662042,
year = {2021},
author = {Mohamed, RI and Bargal, SA and Mekawy, AS and El-Shiekh, I and Tuncbag, N and Ahmed, AS and Badr, E and Elserafy, M},
title = {The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.},
journal = {PloS one},
volume = {16},
number = {3},
pages = {e0247837},
pmid = {33662042},
issn = {1932-6203},
mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Precision Medicine ; Transcriptome ; Up-Regulation ; },
abstract = {In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.},
}

Breast Neoplasms/*genetics
Carcinoma, Ductal, Breast/*genetics
Carcinoma, Lobular/*genetics
*DNA Repair
Female
*Gene Expression Regulation, Neoplastic
Humans
MicroRNAs/genetics
Precision Medicine
Transcriptome
Up-Regulation

@article {pmid32871469,
year = {2020},
author = {Molocea, CE and Tsokanos, FF and Herzig, S},
title = {Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.},
journal = {Current opinion in pharmacology},
volume = {53},
number = {},
pages = {101-116},
doi = {10.1016/j.coph.2020.07.006},
pmid = {32871469},
issn = {1471-4973},
mesh = {Animals ; Appetite Regulation ; *Cachexia/etiology/immunology/metabolism/therapy ; Humans ; Inflammation Mediators/immunology ; Macrophages/immunology ; *Neoplasms/complications/immunology/metabolism/therapy ; *Obesity/immunology/metabolism/therapy ; },
abstract = {Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.},
}

Animals
Appetite Regulation
*Cachexia/etiology/immunology/metabolism/therapy
Humans
Inflammation Mediators/immunology
Macrophages/immunology
*Neoplasms/complications/immunology/metabolism/therapy
*Obesity/immunology/metabolism/therapy

@article {pmid32650989,
year = {2020},
author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Patocskai, E and Nouraie, M},
title = {Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients.},
journal = {Clinical breast cancer},
volume = {20},
number = {6},
pages = {511-519},
doi = {10.1016/j.clbc.2020.05.016},
pmid = {32650989},
issn = {1938-0666},
mesh = {Adult ; Breast/pathology/surgery ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/statistics & numerical data ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Iran/epidemiology ; Mammaplasty/*adverse effects/methods/statistics & numerical data ; Margins of Excision ; Mastectomy, Segmental/*adverse effects/statistics & numerical data ; Middle Aged ; Neoadjuvant Therapy/methods/statistics & numerical data ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Reoperation/statistics & numerical data ; Retrospective Studies ; },
abstract = {BACKGROUND: Breast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients.

PATIENTS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented.

RESULTS: Nine hundred thirty-seven patients with a mean ± standard deviation age of 48.1 ± 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence.

CONCLUSION: OBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.},
}

Adult
Breast/pathology/surgery
Breast Neoplasms/diagnosis/mortality/pathology/*therapy
Chemotherapy, Adjuvant/statistics & numerical data
Disease-Free Survival
Female
Follow-Up Studies
Humans
Iran/epidemiology
Mammaplasty/*adverse effects/methods/statistics & numerical data
Margins of Excision
Mastectomy, Segmental/*adverse effects/statistics & numerical data
Middle Aged
Neoadjuvant Therapy/methods/statistics & numerical data
Neoplasm Recurrence, Local/*epidemiology
Neoplasm Staging
Postoperative Complications/*epidemiology/etiology
Prospective Studies
Reoperation/statistics & numerical data
Retrospective Studies

@article {pmid32416533,
year = {2020},
author = {Syed, AP and Greulich, F and Ansari, SA and Uhlenhaut, NH},
title = {Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.},
journal = {Current opinion in pharmacology},
volume = {53},
number = {},
pages = {35-44},
doi = {10.1016/j.coph.2020.03.003},
pmid = {32416533},
issn = {1471-4973},
mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Genomics ; Glucocorticoids/*pharmacology ; Humans ; RNA, Untranslated ; Receptors, Glucocorticoid/genetics ; Transcription, Genetic ; },
abstract = {Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis.},
}

Animals
Anti-Inflammatory Agents/*pharmacology
Genomics
Glucocorticoids/*pharmacology
Humans
RNA, Untranslated
Receptors, Glucocorticoid/genetics
Transcription, Genetic

@article {pmid34587404,
year = {2021},
author = {Yang, L and Xiong, Y and Sun, Z and Lin, X and Ni, H},
title = {Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.},
journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer},
volume = {40},
number = {3},
pages = {51-61},
doi = {10.1615/JEnvironPatholToxicolOncol.2021038118},
pmid = {34587404},
issn = {2162-6537},
mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects/physiology ; Benzylisoquinolines/*pharmacology ; Body Weight/drug effects ; Carcinogens/toxicity ; Cell Proliferation/drug effects/physiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Lipid Peroxidation/drug effects ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/drug effects ; },
abstract = {AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.

METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.

RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.

CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.},
}

9,10-Dimethyl-1,2-benzanthracene/toxicity
Animals
Antineoplastic Agents, Phytogenic/*pharmacology
Apoptosis/*drug effects/physiology
Benzylisoquinolines/*pharmacology
Body Weight/drug effects
Carcinogens/toxicity
Cell Proliferation/drug effects/physiology
Female
Gene Expression Regulation, Neoplastic/drug effects
Lipid Peroxidation/drug effects
Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology
NF-kappa B/metabolism
Phosphatidylinositol 3-Kinases/metabolism
Proto-Oncogene Proteins c-akt/metabolism
Rats
Signal Transduction/drug effects

@article {pmid32362500,
year = {2020},
author = {Dianatinasab, M and Rezaian, M and HaghighatNezad, E and Bagheri-Hosseinabadi, Z and Amanat, S and Rezaeian, S and Masoudi, A and Ghiasvand, R},
title = {Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.},
journal = {Clinical breast cancer},
volume = {20},
number = {4},
pages = {e516-e528},
doi = {10.1016/j.clbc.2020.03.007},
pmid = {32362500},
issn = {1938-0666},
mesh = {Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diet Surveys/*statistics & numerical data ; *Feeding Behavior ; Female ; Humans ; Risk Assessment/statistics & numerical data ; Risk Factors ; },
abstract = {The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I2 = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I2 = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I2 = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I2 = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I2 = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.},
}

Breast Neoplasms/*epidemiology/etiology
Carcinoma, Ductal, Breast/*epidemiology/etiology
Carcinoma, Lobular/*epidemiology/etiology
Case-Control Studies
Diet Surveys/*statistics & numerical data
*Feeding Behavior
Female
Humans
Risk Assessment/statistics & numerical data
Risk Factors

@article {pmid32299754,
year = {2020},
author = {El Abbass, KA and Abdellateif, MS and Gawish, AM and Zekri, AN and Malash, I and Bahnassy, AA},
title = {The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.},
journal = {Clinical breast cancer},
volume = {20},
number = {4},
pages = {e373-e384},
doi = {10.1016/j.clbc.2019.11.008},
pmid = {32299754},
issn = {1938-0666},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy ; Case-Control Studies ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Healthy Volunteers ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; Primary Cell Culture ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Cells, Cultured ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).

METHODS: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.

RESULTS: The number of CD44+CD24-/low cells associated significantly at the end of culture with the expression level of Wnt, β-catenin, and distant metastasis (P < .001, P = .015 and P = .003, respectively). There was significant association between the mammosphere number and CD44+CD24-/low cells as well as AKT expression (P = .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P < .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P = .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P < .001, P = .001, P = .014, respectively).

CONCLUSION: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.},
}

Adult
Aged
Biomarkers, Tumor/*genetics
Breast/*pathology/surgery
Breast Neoplasms/diagnosis/*genetics/pathology/therapy
Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy
Case-Control Studies
Cell Proliferation/genetics
Female
Gene Expression Regulation, Neoplastic
Healthy Volunteers
Humans
Middle Aged
Neoplasm Staging
Neoplastic Stem Cells/*pathology
Primary Cell Culture
Retrospective Studies
Signal Transduction/genetics
Tumor Cells, Cultured
Young Adult

@article {pmid34557972,
year = {2021},
author = {Han, J and Harrison, L and Patzelt, L and Wu, M and Junker, D and Herzig, S and Berriel Diaz, M and Karampinos, DC},
title = {Imaging modalities for diagnosis and monitoring of cancer cachexia.},
journal = {EJNMMI research},
volume = {11},
number = {1},
pages = {94},
pmid = {34557972},
issn = {2191-219X},
support = {SFB824/A9//deutsche forschungsgemeinschaft/ ; },
abstract = {Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-D-glucose (18FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.},
}

@article {pmid34555180,
year = {2021},
author = {Giroud, M and Jodeleit, H and Prentice, KJ and Bartelt, A},
title = {Adipocyte function and the development of cardiometabolic disease.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP281979},
pmid = {34555180},
issn = {1469-7793},
abstract = {KEY POINTS: Obesity and the associated adipocyte pathology are risk factors for cardiovascular disease Translational research is possible but strongly depends on the mouse model used White adipose tissue inflammation contributes to metabolic and vascular dysfunction Brown adipose tissue thermogenesis supports metabolic and vascular function ABSTRACT: Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications, and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance, and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology, and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which makes temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators, and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease. Abstract figure legend While cardiometabolic health is associated with adipose tissue browning and beneficial adipokine profiles, obesity leads to adipose tissue whitening, inflammation, and atherosclerosis. This article is protected by copyright. All rights reserved.},
}

@article {pmid34528573,
year = {2021},
author = {Trontzas, IP and Syrigos, NK and Kotteas, EA},
title = {A case of trastuzumab-induced dermatomyositis.},
journal = {Journal of cancer research and therapeutics},
volume = {17},
number = {4},
pages = {1112-1114},
doi = {10.4103/jcrt.JCRT_209_19},
pmid = {34528573},
issn = {1998-4138},
abstract = {Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.},
}

@article {pmid34466203,
year = {2021},
author = {Zingue, S and Atenguena, EO and Zingue, LL and Tueche, AB and Njamen, D and Nkoum, AB and Ndom, P},
title = {Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.},
journal = {The Pan African medical journal},
volume = {39},
number = {},
pages = {182},
pmid = {34466203},
issn = {1937-8688},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Cameroon/epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology ; Early Detection of Cancer/methods ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult ; },
abstract = {Introduction: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).

Methods: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaoundé General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.

Results: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 ± 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 ± 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).

Conclusion: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Breast Neoplasms/diagnosis/*epidemiology/pathology
Breast Neoplasms, Male/diagnosis/*epidemiology/pathology
Cameroon/epidemiology
Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology
Early Detection of Cancer/methods
Female
Hospitals, General
Humans
Male
Middle Aged
Neoplasm Grading
Retrospective Studies
Risk Factors
Survival Rate
Young Adult

@article {pmid34452576,
year = {2021},
author = {Ameli, F and Ghafourina Nassab, F and Masir, N and Kahtib, F},
title = {Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {22},
number = {8},
pages = {2603-2609},
doi = {10.31557/APJCP.2021.22.8.2603},
pmid = {34452576},
issn = {2476-762X},
abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.},
}

@article {pmid34449311,
year = {2021},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {142},
number = {},
pages = {111991},
doi = {10.1016/j.biopha.2021.111991},
pmid = {34449311},
issn = {1950-6007},
abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.

CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.},
}

@article {pmid34448091,
year = {2021},
author = {Jimbo, H and Horimoto, Y and Okazaki, M and Ishizuka, Y and Kido, H and Saito, M},
title = {Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.},
journal = {Surgical case reports},
volume = {7},
number = {1},
pages = {197},
pmid = {34448091},
issn = {2198-7793},
abstract = {BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.

CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.

CONCLUSIONS: The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.},
}

@article {pmid34437555,
year = {2021},
author = {Shulman, D and Shnitzer-Akuka, M and Reifen-Tagar, M},
title = {The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.},
journal = {PloS one},
volume = {16},
number = {8},
pages = {e0254375},
pmid = {34437555},
issn = {1932-6203},
abstract = {Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.},
}

@article {pmid34417460,
year = {2021},
author = {Gonzalez-Rellan, MJ and Fondevila, MF and Fernandez, U and Rodríguez, A and Varela-Rey, M and Veyrat-Durebex, C and Seoane, S and Bernardo, G and Lopitz-Otsoa, F and Fernández-Ramos, D and Bilbao, J and Iglesias, C and Novoa, E and Ameneiro, C and Senra, A and Beiroa, D and Cuñarro, J and Dp Chantada-Vazquez, M and Garcia-Vence, M and Bravo, SB and Da Silva Lima, N and Porteiro, B and Carneiro, C and Vidal, A and Tovar, S and Müller, TD and Ferno, J and Guallar, D and Fidalgo, M and Sabio, G and Herzig, S and Yang, WH and Cho, JW and Martinez-Chantar, ML and Perez-Fernandez, R and López, M and Dieguez, C and Mato, JM and Millet, O and Coppari, R and Woodhoo, A and Fruhbeck, G and Nogueiras, R},
title = {O-GlcNAcylated p53 in the liver modulates hepatic glucose production.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {5068},
pmid = {34417460},
issn = {2041-1723},
mesh = {Acetylglucosamine/*metabolism ; Animals ; Base Sequence ; Caloric Restriction ; Cell Line ; Colforsin/pharmacology ; Diabetes Mellitus, Type 2/complications/metabolism ; Epinephrine/metabolism ; Glucagon/metabolism ; Glucocorticoids/metabolism ; Gluconeogenesis/drug effects ; Glucose/*metabolism ; Glycosylation ; Hepatocytes/drug effects/metabolism ; Humans ; Hydrocortisone/metabolism ; Hyperglycemia/complications/metabolism ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/metabolism ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein Stability/drug effects ; Pyruvic Acid/metabolism ; RNA, Messenger/genetics/metabolism ; Transcription, Genetic/drug effects ; Tumor Suppressor Protein p53/genetics/*metabolism ; },
abstract = {p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.},
}

Acetylglucosamine/*metabolism
Animals
Base Sequence
Caloric Restriction
Cell Line
Colforsin/pharmacology
Diabetes Mellitus, Type 2/complications/metabolism
Epinephrine/metabolism
Glucagon/metabolism
Glucocorticoids/metabolism
Gluconeogenesis/drug effects
Glucose/*metabolism
Glycosylation
Hepatocytes/drug effects/metabolism
Humans
Hydrocortisone/metabolism
Hyperglycemia/complications/metabolism
Insulin Resistance
Intracellular Signaling Peptides and Proteins/metabolism
Liver/drug effects/*metabolism
Mice, Inbred C57BL
Mice, Knockout
Obesity/complications/metabolism
Phosphoenolpyruvate Carboxykinase (GTP)/metabolism
Promoter Regions, Genetic/genetics
Protein Binding/drug effects
Protein Stability/drug effects
Pyruvic Acid/metabolism
RNA, Messenger/genetics/metabolism
Transcription, Genetic/drug effects
Tumor Suppressor Protein p53/genetics/*metabolism

@article {pmid34413744,
year = {2021},
author = {Moghimi, M and Khodadadi, K},
title = {Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.},
journal = {Case reports in oncology},
volume = {14},
number = {2},
pages = {1134-1138},
pmid = {34413744},
issn = {1662-6575},
abstract = {Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.},
}

@article {pmid34409828,
year = {2021},
author = {Shabanov, GA and Rybchenko, AA and Lugovaya, EA and Vdovenko, SI},
title = {[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {34},
number = {3},
pages = {466-471},
pmid = {34409828},
issn = {1561-9125},
mesh = {*Aging ; *Brain ; Cell Differentiation ; Humans ; Risk Factors ; },
abstract = {For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.},
}

*Aging
*Brain
Cell Differentiation
Humans
Risk Factors

@article {pmid34379693,
year = {2021},
author = {He, X and Anthony, DC and Catoni, Z and Cao, W},
title = {Pulmonary tumor embolism: A retrospective study over a 30-year period.},
journal = {PloS one},
volume = {16},
number = {8},
pages = {e0255917},
pmid = {34379693},
issn = {1932-6203},
abstract = {BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.

RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).

CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.},
}

@article {pmid34359556,
year = {2021},
author = {Zhang, JQ and Cheng, TM and Lin, WC and Chiu, KC and Wu, SY},
title = {Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.},
journal = {Cancers},
volume = {13},
number = {15},
pages = {},
pmid = {34359556},
issn = {2072-6694},
abstract = {PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.

METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).

RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.

CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.},
}

@article {pmid34330920,
year = {2021},
author = {Thomson-Luque, R and Votborg-Novél, L and Ndovie, W and Andrade, CM and Niangaly, M and Attipa, C and Lima, NF and Coulibaly, D and Doumtabe, D and Guindo, B and Tangara, B and Maiga, F and Kone, AK and Traore, K and Kayentao, K and Ongoiba, A and Doumbo, S and Thera, MA and Traoré, B and Seydel, K and Osório, NS and Portugal, S},
title = {Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {4711},
pmid = {34330920},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI099628/AI/NIAID NIH HHS/United States ; },
mesh = {Blood Circulation Time ; Erythrocytes/parasitology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Bacterial ; Gene Ontology ; Genes, Bacterial/genetics ; Humans ; Malaria, Falciparum/*blood/parasitology/physiopathology ; Parasitemia/*blood/parasitology/physiopathology ; Plasmodium falciparum/*genetics/physiology ; },
abstract = {Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.},
}

Blood Circulation Time
Erythrocytes/parasitology
Gene Expression Profiling/*methods
*Gene Expression Regulation, Bacterial
Gene Ontology
Genes, Bacterial/genetics
Humans
Malaria, Falciparum/*blood/parasitology/physiopathology
Parasitemia/*blood/parasitology/physiopathology
Plasmodium falciparum/*genetics/physiology

@article {pmid34320711,
year = {2021},
author = {Fan, T and Wang, CQ and Li, XT and Yang, H and Zhou, J and Song, YJ},
title = {MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {31},
number = {8},
pages = {937-940},
doi = {10.29271/jcpsp.2021.08.937},
pmid = {34320711},
issn = {1681-7168},
mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *MicroRNAs/genetics ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; },
abstract = {OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.

STUDY DESIGN: An experimental study.

PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.

METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT⁃PCR.

RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para⁃carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2) is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.

CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.},
}

*Breast Neoplasms/genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
China
DNA-Binding Proteins/genetics/metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
*MicroRNAs/genetics
RNA-Binding Proteins/genetics
Transcription Factors/genetics

@article {pmid34297787,
year = {2021},
author = {Ahmed, F and Adnan, M and Malik, A and Tariq, S and Kamal, F and Ijaz, B},
title = {Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.},
journal = {PloS one},
volume = {16},
number = {7},
pages = {e0255243},
pmid = {34297787},
issn = {1932-6203},
abstract = {Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.},
}

@article {pmid34293926,
year = {2021},
author = {Chen, X and Li, X and Wang, J and Zhao, L and Peng, X and Zhang, C and Liu, K and Huang, G and Lai, Y},
title = {Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.},
journal = {Biomarkers in medicine},
volume = {15},
number = {12},
pages = {951-963},
doi = {10.2217/bmm-2020-0785},
pmid = {34293926},
issn = {1752-0371},
support = {SZLY2018023//Clinical Research Project of Shenzhen Health Commission,/ ; JCYJ20180507183102747//Science and Technology Development Fund Project of Shenzhen,/ ; //Shenzhen High-level Hospital Construction Fund/ ; JCYJ2017001, JCYJ2017004, JCYJ2017005, JCYJ2017006//Basic Research Project of Peking University Shenzhen Hospital,/ ; LCYJ2017001//Clinical Research Project of Peking University Shenzhen Hospital,/ ; },
abstract = {Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.},
}