@article {pmid32617838,
year = {2021},
author = {Hashinokuchi, A and Akamine, T and Kometani, T and Shikada, Y and Nozoe, T and Kato, S},
title = {Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.},
journal = {General thoracic and cardiovascular surgery},
volume = {69},
number = {1},
pages = {137-141},
pmid = {32617838},
issn = {1863-6713},
mesh = {Aged ; *Breast Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local ; Pleurodesis ; *Pneumothorax/etiology/therapy ; Quality of Life ; Recurrence ; Thoracic Surgery, Video-Assisted ; },
abstract = {We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.},
}

Aged
*Breast Neoplasms
Female
Humans
Neoplasm Recurrence, Local
Pleurodesis
*Pneumothorax/etiology/therapy
Quality of Life
Recurrence
Thoracic Surgery, Video-Assisted

@article {pmid32050826,
year = {2020},
author = {Mostyka, M and Jessurun, J and Matrai, C},
title = {Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.},
journal = {International journal of surgical pathology},
volume = {28},
number = {6},
pages = {668-671},
doi = {10.1177/1066896920905887},
pmid = {32050826},
issn = {1940-2465},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Granuloma, Respiratory Tract/chemically induced/*pathology ; Humans ; Lung/pathology ; Pulmonary Fibrosis/chemically induced/pathology ; },
abstract = {Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.},
}

Adult
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Breast Neoplasms/drug therapy/*pathology
Carcinoma, Ductal, Breast/drug therapy/*pathology
Female
Granuloma, Respiratory Tract/chemically induced/*pathology
Humans
Lung/pathology
Pulmonary Fibrosis/chemically induced/pathology

@article {pmid33824828,
year = {2021},
author = {Khanam, R and Fanous, IS and Fadhel, EN and Hyder, T and Brufsky, A},
title = {Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.},
journal = {Cureus},
volume = {13},
number = {3},
pages = {e13677},
pmid = {33824828},
issn = {2168-8184},
abstract = {Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.},
}

@article {pmid33824344,
year = {2021},
author = {Kricheli-Katz, T and Regev, T},
title = {The effect of language on performance: do gendered languages fail women in maths?.},
journal = {NPJ science of learning},
volume = {6},
number = {1},
pages = {9},
pmid = {33824344},
issn = {2056-7936},
abstract = {Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.},
}

@article {pmid33818021,
year = {2021},
author = {Alyami, H and Yoo, TK and Cheun, JH and Lee, HB and Jung, SM and Ryu, JM and Bae, SJ and Jeong, J and Yoon, CI and Ahn, J and Paik, PS and Cho, MK and Park, WC},
title = {Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.},
journal = {Journal of breast cancer},
volume = {},
number = {},
pages = {},
doi = {10.4048/jbc.2021.24.e16},
pmid = {33818021},
issn = {1738-6756},
abstract = {PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.

METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.

RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.

CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.},
}

@article {pmid33402291,
year = {2021},
author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I},
title = {[Ductal carcinomas of the parotid gland].},
journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique},
volume = {25},
number = {2},
pages = {155-160},
doi = {10.1016/j.canrad.2020.06.034},
pmid = {33402291},
issn = {1769-6658},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics & numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; },
abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.

MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.

RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.

CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/pathology
Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery
Carcinoma, Ductal, Breast/pathology/secondary
Facial Nerve/surgery
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neck Dissection/statistics & numerical data
Neoplasm Invasiveness
Parotid Gland/diagnostic imaging/surgery
Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery
Prognosis
Retrospective Studies
Skin Neoplasms/pathology

@article {pmid33140128,
year = {2021},
author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH},
title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {478},
number = {4},
pages = {679-686},
pmid = {33140128},
issn = {1432-2307},
support = {SHF/FG668S/2015//SingHealth Foundation/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention & control ; Prognosis ; Proportional Hazards Models ; },
abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.},
}

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*immunology/metabolism/*pathology/therapy
Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy
Disease-Free Survival
Female
Follow-Up Studies
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention & control
Prognosis
Proportional Hazards Models

@article {pmid32636849,
year = {2020},
author = {Siegers, GM and Dutta, I and Kang, EY and Huang, J and Köbel, M and Postovit, LM},
title = {Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity.},
journal = {Frontiers in immunology},
volume = {11},
number = {},
pages = {1287},
pmid = {32636849},
issn = {1664-3224},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Intraepithelial Lymphocytes/*immunology ; Middle Aged ; Nodal Protein/*immunology/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Triple Negative Breast Neoplasms/*immunology/metabolism ; Tumor Escape/*immunology ; Tumor Microenvironment/*immunology ; },
abstract = {Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.},
}

Aged
Aged, 80 and over
Female
Humans
Intraepithelial Lymphocytes/*immunology
Middle Aged
Nodal Protein/*immunology/metabolism
Receptors, Antigen, T-Cell, gamma-delta/*immunology
Triple Negative Breast Neoplasms/*immunology/metabolism
Tumor Escape/*immunology
Tumor Microenvironment/*immunology

@article {pmid32338774,
year = {2020},
author = {Kumar, V and Agrawal, R and Pandey, A and Kopf, S and Hoeffgen, M and Kaymak, S and Bandapalli, OR and Gorbunova, V and Seluanov, A and Mall, MA and Herzig, S and Nawroth, PP},
title = {Compromised DNA repair is responsible for diabetes-associated fibrosis.},
journal = {The EMBO journal},
volume = {39},
number = {11},
pages = {e103477},
pmid = {32338774},
issn = {1460-2075},
support = {R37 AG046320/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; //Helmholtz Cross Program Topic Metabolic Dysfunction/ ; //Foundation for Diabetes Research/ ; GRK 1874-DIAMICOM//Deutsche Forschungsgemeinschaft (DFG)/ ; R01 AG027237/AG/NIA NIH HHS/United States ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/ ; },
mesh = {A549 Cells ; *DNA End-Joining Repair ; Diabetes Mellitus, Type 1/genetics/*metabolism/pathology ; Diabetes Mellitus, Type 2/genetics/*metabolism/pathology ; Fibrosis ; HEK293 Cells ; Humans ; },
abstract = {Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD+ /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.},
}

A549 Cells
*DNA End-Joining Repair
Diabetes Mellitus, Type 1/genetics/*metabolism/pathology
Diabetes Mellitus, Type 2/genetics/*metabolism/pathology
Fibrosis
HEK293 Cells
Humans

@article {pmid33776732,
year = {2021},
author = {Sugimoto, H and Oda, G and Yokoyama, M and Hayashi, K and Yoshino, M and Ogawa, A and Hosoya, T and Nakagawa, T and Uetake, H},
title = {Hydronephrosis Caused by Metastatic Breast Cancer.},
journal = {Case reports in oncology},
volume = {14},
number = {1},
pages = {378-385},
doi = {10.1159/000513903},
pmid = {33776732},
issn = {1662-6575},
abstract = {Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.},
}

@article {pmid32758491,
year = {2020},
author = {Sechrist, H and Glasgow, A and Bomeisl, P and Gilmore, H and Harbhajanka, A},
title = {Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.},
journal = {Human pathology},
volume = {104},
number = {},
pages = {54-65},
doi = {10.1016/j.humpath.2020.07.022},
pmid = {32758491},
issn = {1532-8392},
mesh = {Aged ; *Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology/therapy ; Clinical Decision-Making ; Female ; *Gene Expression Profiling ; Humans ; *Immunohistochemistry ; *In Situ Hybridization ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Receptor, ErbB-2/analysis/genetics ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Retrospective Studies ; *Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Transcriptome ; Treatment Outcome ; },
abstract = {Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.},
}

Aged
*Biomarkers, Tumor/analysis/genetics
Breast Neoplasms/*chemistry/*genetics/pathology/therapy
Clinical Decision-Making
Female
*Gene Expression Profiling
Humans
*Immunohistochemistry
*In Situ Hybridization
Middle Aged
Neoplasm Grading
Predictive Value of Tests
Receptor, ErbB-2/analysis/genetics
Receptors, Estrogen/analysis/genetics
Receptors, Progesterone/analysis/genetics
Retrospective Studies
*Reverse Transcriptase Polymerase Chain Reaction
Risk Assessment
Risk Factors
Transcriptome
Treatment Outcome

@article {pmid33725931,
year = {2021},
author = {Oh, BH and Woo, CG and Lee, YJ and Park, YS},
title = {Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.},
journal = {Medicine},
volume = {100},
number = {11},
pages = {e24373},
doi = {10.1097/MD.0000000000024373},
pmid = {33725931},
issn = {1536-5964},
support = {NRF-2019R1A2C1085809//Chungbuk National University Korea National University Development Project (2020)/ ; },
mesh = {Brain Neoplasms/metabolism/*secondary ; Breast Neoplasms, Male/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.

PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).

DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).

INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).

OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.

LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.},
}

Brain Neoplasms/metabolism/*secondary
Breast Neoplasms, Male/metabolism/*pathology
Carcinoma, Ductal, Breast/metabolism/*secondary
Humans
Male
Middle Aged
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism

@article {pmid32580398,
year = {2020},
author = {Kim, HM and Koo, JS},
title = {Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes.},
journal = {International journal of molecular sciences},
volume = {21},
number = {12},
pages = {},
pmid = {32580398},
issn = {1422-0067},
support = {2016 (6-2016-0163)//faculty research grant from Yonsei University College of Medicine/ ; },
mesh = {Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/metabolism/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/*classification/*immunology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; STAT6 Transcription Factor/metabolism ; Survival Rate ; },
abstract = {The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.},
}

Antigens, CD/metabolism
Antigens, Differentiation, Myelomonocytic/metabolism
Biomarkers, Tumor/*metabolism
Breast Neoplasms/immunology/metabolism/*pathology
Carcinoma, Ductal, Breast/immunology/metabolism/*pathology
Case-Control Studies
Female
Follow-Up Studies
Forkhead Transcription Factors/metabolism
Humans
Lymphocytes, Tumor-Infiltrating/*classification/*immunology
Prognosis
Receptor, ErbB-2/metabolism
Receptors, Cell Surface/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies
STAT6 Transcription Factor/metabolism
Survival Rate

@article {pmid33730716,
year = {2021},
author = {Bar-Or, RL and Kor, A and Jaljuli, I and Lev-Ran, S},
title = {The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.},
journal = {European addiction research},
volume = {},
number = {},
pages = {1-9},
doi = {10.1159/000513776},
pmid = {33730716},
issn = {1421-9891},
abstract = {INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.

METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.

RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).

CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.},
}

@article {pmid33204409,
year = {2020},
author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R},
title = {Case Report: Metastatic breast cancer to the gallbladder.},
journal = {F1000Research},
volume = {9},
number = {},
pages = {343},
pmid = {33204409},
issn = {2046-1402},
mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; },
abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.},
}

Aged, 80 and over
Breast Neoplasms/*pathology/therapy
*Cholecystitis, Acute/etiology/surgery
Female
*Gallbladder Neoplasms/secondary/surgery
Humans

@article {pmid33710293,
year = {2021},
author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY},
title = {Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.},
journal = {JAMA network open},
volume = {4},
number = {3},
pages = {e211785},
doi = {10.1001/jamanetworkopen.2021.1785},
pmid = {33710293},
issn = {2574-3805},
abstract = {Importance: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.

Objective: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.

This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.

Exposures: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.

Main Outcomes and Measures: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.

Results: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001).

Conclusions and Relevance: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.},
}

@article {pmid33645934,
year = {2021},
author = {Da Costa, I and Belnou, P and Soulier, A and Lapidus, N and Tsai, ES and Bourcier, E and Moisi, L and Sautet, A and Bonnet, F and Lescot, T and Verdonk, F},
title = {Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.},
journal = {European journal of anaesthesiology},
volume = {38 Suppl 1},
number = {},
pages = {S67-S68},
doi = {10.1097/EJA.0000000000001271},
pmid = {33645934},
issn = {1365-2346},
mesh = {Aged ; Aged, 80 and over ; Female ; France/epidemiology ; Hemorrhage/*epidemiology/etiology ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Postoperative Complications/epidemiology ; Recovery of Function/*physiology ; Time Factors ; Time-to-Treatment/*statistics & numerical data ; Treatment Outcome ; },
}

Aged
Aged, 80 and over
Female
France/epidemiology
Hemorrhage/*epidemiology/etiology
Hip Fractures/complications/*surgery
Humans
Male
Middle Aged
Outcome Assessment, Health Care
Postoperative Complications/epidemiology
Recovery of Function/*physiology
Time Factors
Time-to-Treatment/*statistics & numerical data
Treatment Outcome

@article {pmid32019280,
year = {2020},
author = {Wu, J and Ding, S and Lin, L and Fei, X and Lin, C and Andriani, L and Goh, C and Huang, J and Hong, J and Gao, W and Zhu, S and Wang, H and Huang, O and Chen, X and He, J and Li, Y and Shen, K and Chen, W and Zhu, L},
title = {Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.},
journal = {Cancer research and treatment},
volume = {52},
number = {3},
pages = {671-679},
pmid = {32019280},
issn = {2005-9256},
support = {81572581//National Natural Science Foundation of China/ ; 81772797//National Natural Science Foundation of China/ ; 14411950200//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 14411950201//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 16411966- 900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 201840323//Grant of Shanghai municipal commission of health and family planning/ ; },
mesh = {Adenocarcinoma, Mucinous/metabolism/pathology/*therapy ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/metabolism/pathology/*therapy ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; China/epidemiology ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; *Transcriptome ; },
abstract = {PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).

Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.

RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).

CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.},
}

Adenocarcinoma, Mucinous/metabolism/pathology/*therapy
Biomarkers, Tumor/*genetics
Breast Neoplasms/metabolism/pathology/*therapy
Carcinoma, Ductal, Breast/metabolism/pathology/*therapy
China/epidemiology
Combined Modality Therapy
Female
Follow-Up Studies
Humans
Middle Aged
Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics
Prognosis
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies
Survival Rate
*Transcriptome

@article {pmid32043593,
year = {2020},
author = {Shahir, M and Mahmoud Hashemi, S and Asadirad, A and Varahram, M and Kazempour-Dizaji, M and Folkerts, G and Garssen, J and Adcock, I and Mortaz, E},
title = {Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.},
journal = {Journal of cellular physiology},
volume = {235},
number = {10},
pages = {7043-7055},
pmid = {32043593},
issn = {1097-4652},
mesh = {Animals ; Biomarkers/metabolism ; Cell Communication/immunology ; Cell Proliferation/physiology ; Cells, Cultured ; Cytokines/immunology/metabolism ; Dendritic Cells/*immunology/metabolism ; Exosomes/*immunology/metabolism ; Female ; Immune Tolerance/*immunology ; Immunity/immunology ; Inflammation/immunology/metabolism ; Lymphocytes/immunology/metabolism ; Mesenchymal Stem Cells/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; },
abstract = {Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.},
}

Animals
Biomarkers/metabolism
Cell Communication/immunology
Cell Proliferation/physiology
Cells, Cultured
Cytokines/immunology/metabolism
Dendritic Cells/*immunology/metabolism
Exosomes/*immunology/metabolism
Female
Immune Tolerance/*immunology
Immunity/immunology
Inflammation/immunology/metabolism
Lymphocytes/immunology/metabolism
Mesenchymal Stem Cells/*immunology/metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL

@article {pmid33628571,
year = {2021},
author = {Sarawagi, A and Maxwell, J},
title = {Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.},
journal = {Case reports in surgery},
volume = {2021},
number = {},
pages = {8812315},
doi = {10.1155/2021/8812315},
pmid = {33628571},
issn = {2090-6900},
abstract = {Background: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.

Conclusion: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.},
}

@article {pmid33581714,
year = {2021},
author = {Saeed, U and Uppal, SR and Piracha, ZZ and Rasheed, A and Aftab, Z and Zaheer, H and Uppal, R},
title = {Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy.},
journal = {Virology journal},
volume = {18},
number = {1},
pages = {34},
pmid = {33581714},
issn = {1743-422X},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology/*isolation & purification ; COVID-19/*diagnosis/epidemiology/immunology/virology ; COVID-19 Serological Testing/*methods ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; SARS-CoV-2/genetics/immunology/*isolation & purification ; Young Adult ; },
abstract = {Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Antigens, Viral/immunology/*isolation & purification
COVID-19/*diagnosis/epidemiology/immunology/virology
COVID-19 Serological Testing/*methods
Child
Cross-Sectional Studies
Female
Humans
Male
Middle Aged
Pakistan/epidemiology
Reagent Kits, Diagnostic
Real-Time Polymerase Chain Reaction
Reproducibility of Results
SARS-CoV-2/genetics/immunology/*isolation & purification
Young Adult

@article {pmid33621744,
year = {2021},
author = {Gupta, V and Agarwal, P and Deshpande, P},
title = {Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.},
journal = {Annals of diagnostic pathology},
volume = {52},
number = {},
pages = {151722},
doi = {10.1016/j.anndiagpath.2021.151722},
pmid = {33621744},
issn = {1532-8198},
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.

MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.

RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.

CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.

MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.},
}

@article {pmid33611829,
year = {2021},
author = {Huang, D and Zhou, B and Luo, ZZ and Yu, SC and Tang, B},
title = {Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.},
journal = {The Kaohsiung journal of medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1002/kjm2.12367},
pmid = {33611829},
issn = {2410-8650},
support = {//The Science and Technology Plan of Jiangxi Province Health Committee, Grant/Award Number: 20204366/ ; //The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee, Grant/Award Number: 20181001/ ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4+ T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.},
}

@article {pmid31980982,
year = {2020},
author = {Zhao, Y and Wang, Y and Zhu, F and Zhang, J and Ma, X and Zhang, D},
title = {Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients.},
journal = {Clinical and experimental medicine},
volume = {20},
number = {2},
pages = {249-259},
pmid = {31980982},
issn = {1591-9528},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/therapy ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*genetics ; Middle Aged ; Minichromosome Maintenance Complex Component 3/*genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; },
abstract = {Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.},
}

Adult
Aged
Biomarkers, Tumor/*genetics
Breast Neoplasms/*genetics/pathology/therapy
Carcinoma, Ductal, Breast/*genetics/pathology/therapy
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Kaplan-Meier Estimate
Ki-67 Antigen/*genetics
Middle Aged
Minichromosome Maintenance Complex Component 3/*genetics
Oligonucleotide Array Sequence Analysis
Prognosis
Real-Time Polymerase Chain Reaction
Retrospective Studies

@article {pmid32424149,
year = {2020},
author = {Cheung, SM and Husain, E and Masannat, Y and Miller, ID and Wahle, K and Heys, SD and He, J},
title = {Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.},
journal = {British journal of cancer},
volume = {123},
number = {2},
pages = {261-267},
pmid = {32424149},
issn = {1532-1827},
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Female ; Glycolysis/genetics ; Humans ; Lactate Dehydrogenase 5/genetics/metabolism ; Lactic Acid/isolation & purification/*metabolism ; Magnetic Resonance Spectroscopy ; Middle Aged ; *Prognosis ; Receptors, Estrogen/genetics/*metabolism ; },
abstract = {BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.

METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.

RESULTS: There was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = -0.3734, p = 0.0421).

CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.},
}

Adult
Aged
Biomarkers, Tumor/genetics/metabolism
Breast Neoplasms/*diagnosis/metabolism/pathology
Female
Glycolysis/genetics
Humans
Lactate Dehydrogenase 5/genetics/metabolism
Lactic Acid/isolation & purification/*metabolism
Magnetic Resonance Spectroscopy
Middle Aged
*Prognosis
Receptors, Estrogen/genetics/*metabolism

@article {pmid32599083,
year = {2020},
author = {Grabenstetter, A and Mohanty, AS and Rana, S and Zehir, A and Brannon, AR and D'Alfonso, TM and DeLair, DF and Tan, LK and Ross, DS},
title = {E-cadherin immunohistochemical expression in invasive lobular carcinoma of the breast: correlation with morphology and CDH1 somatic alterations.},
journal = {Human pathology},
volume = {102},
number = {},
pages = {44-53},
pmid = {32599083},
issn = {1532-8392},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Antigens, CD/biosynthesis/*genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cadherins/biosynthesis/*genetics ; Carcinoma, Lobular/diagnosis/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Mutation ; },
abstract = {E-cadherin (ECAD) immunohistochemical (IHC) expression is lost in ∼90% of invasive lobular carcinomas (ILCs) owing to genomic alterations of CDH1. We examined morphologic features and ECAD IHC expression in invasive breast carcinomas (BCs) with known CDH1 alterations. Between January 2014 and May 2018, 202 cases of BC with a CDH1 somatic alteration were identified. ECAD expression was lost in 77% (155/202) of cases and was retained in 23% (47/202) cases. Most (90%, 139/155) ECAD-negative cases were morphologically classified as ILC, while the remaining (10%, 16/155) were invasive mammary carcinoma with mixed ductal and lobular features (IMC). Of 47 cases with ECAD staining, 62% (29/47) were classified as ILC, 23% (11/47) were classified as IMC, and 15% (7/47) were classified as invasive ductal carcinoma (IDC). Of note, 51% (24/47) of ECAD-positive cases were initially diagnosed as IDC or IMC based on ECAD expression alone. For ECAD-negative BCs, 98% (152/155) of CDH1 alterations were truncating, and 2% (3/155) were variants of unknown significance (VUS). Truncating CDH1 alterations were identified in the majority of ECAD-positive BCs (72%, 34/47); however, VUS-type CDH1 alterations were more prevalent (28%, 13/47) in ECAD-positive BCs than in ECAD-negative BCs. Although 90% of ECAD-negative tumors were compatible with ILC in this study, 17% (29/168) of ILC cases were ECAD positive. In addition, CDH1 truncating alterations were seen in ECAD-positive ILC, supporting the notion of aberrant ECAD staining. Therefore, ECAD IHC expression must be interpreted in conjunction with morphology, and BC with classic histologic features of ILC should not be reclassified as IDC/IMC based solely on the status of ECAD IHC expression.},
}

Antigens, CD/biosynthesis/*genetics
Biomarkers, Tumor/*analysis
Breast Neoplasms/diagnosis/genetics/*pathology
Cadherins/biosynthesis/*genetics
Carcinoma, Lobular/diagnosis/genetics/*pathology
Female
Gene Expression Regulation, Neoplastic/physiology
Humans
Immunohistochemistry
Mutation

@article {pmid32354932,
year = {2020},
author = {Fujii, T and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Shirabe, K},
title = {Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.},
journal = {In vivo (Athens, Greece)},
volume = {34},
number = {3},
pages = {1365-1369},
pmid = {32354932},
issn = {1791-7549},
mesh = {Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/etiology/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Leukocyte Count ; *Lymphocyte Count ; Middle Aged ; Neutrophils ; *Platelet Count ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tumor Microenvironment ; },
abstract = {BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation.

PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (≥2.5) and based on their PLRs: low (<130) and high (≥130). We determined the relationships between the SUVmax or PLR and clinicopathological features.

RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax.

CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.},
}

Aged
Biomarkers, Tumor
Breast Neoplasms/*diagnostic imaging/etiology/*pathology
Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology
Female
*Fluorodeoxyglucose F18
Humans
Leukocyte Count
*Lymphocyte Count
Middle Aged
Neutrophils
*Platelet Count
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
Tumor Microenvironment

@article {pmid32438745,
year = {2020},
author = {Moran Lauter, AN and Rutter, L and Cook, D and O'Rourke, JA and Graham, MA},
title = {Examining Short-Term Responses to a Long-Term Problem: RNA-Seq Analyses of Iron Deficiency Chlorosis Tolerant Soybean.},
journal = {International journal of molecular sciences},
volume = {21},
number = {10},
pages = {},
pmid = {32438745},
issn = {1422-0067},
support = {Project 5030-21220-006-00D//Agricultural Research Service/ ; },
mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; Iron/*deficiency ; Plant Leaves/genetics ; Plant Necrosis and Chlorosis/*genetics ; Plant Roots/genetics ; *RNA-Seq ; Signal Transduction ; Soybeans/*genetics ; Stress, Physiological/genetics ; Transcription Factors/metabolism ; },
abstract = {Iron deficiency chlorosis (IDC) is a global crop production problem, significantly impacting yield. However, most IDC studies have focused on model species, not agronomically important crops. Soybean is the second largest crop grown in the United States, yet the calcareous soils across most of the upper U.S. Midwest limit soybean growth and profitability. To understand early soybean iron stress responses, we conducted whole genome expression analyses (RNA-sequencing) of leaf and root tissue from the iron efficient soybean (Glycine max) cultivar Clark, at 30, 60 and 120 min after transfer to iron stress conditions. We identified over 10,000 differentially expressed genes (DEGs), with the number of DEGs increasing over time in leaves, but decreasing over time in roots. To investigate these responses, we clustered our expression data across time to identify suites of genes, their biological functions, and the transcription factors (TFs) that regulate their expression. These analyses reveal the hallmarks of the soybean iron stress response (iron uptake and homeostasis, defense, and DNA replication and methylation) can be detected within 30 min. Furthermore, they suggest root to shoot signaling initiates early iron stress responses representing a novel paradigm for crop stress adaptations.},
}

Gene Expression Profiling
Gene Expression Regulation, Plant
Gene Ontology
Iron/*deficiency
Plant Leaves/genetics
Plant Necrosis and Chlorosis/*genetics
Plant Roots/genetics
*RNA-Seq
Signal Transduction
Soybeans/*genetics
Stress, Physiological/genetics
Transcription Factors/metabolism

@article {pmid33530236,
year = {2021},
author = {Liu, N and Li, S and Jia, J and Qiao, Y and Li, Y},
title = {Advanced breast cancer with cachexia: A case report.},
journal = {Medicine},
volume = {100},
number = {4},
pages = {e24397},
pmid = {33530236},
issn = {1536-5964},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*complications/therapy ; Cachexia/etiology/*therapy ; Fatal Outcome ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; },
abstract = {RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients.

PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache.

DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area.

INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions.

OUTCOMES: She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.

LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.},
}

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Breast Neoplasms/*complications/therapy
Cachexia/etiology/*therapy
Fatal Outcome
Female
Humans
Mastectomy/*methods
Middle Aged

@article {pmid33484951,
year = {2021},
author = {Lemmer, IL and Willemsen, N and Hilal, N and Bartelt, A},
title = {A guide to understanding endoplasmic reticulum stress in metabolic disorders.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {101169},
doi = {10.1016/j.molmet.2021.101169},
pmid = {33484951},
issn = {2212-8778},
abstract = {BACKGROUND: The global rise of metabolic disorders, such as obesity, type 2 diabetes, and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore disturbed ER function, known as "ER stress," is a key feature of metabolic disorders.

SCOPE OF REVIEW: As ER stress remains a poorly defined phenomenon, this review provides a general guide to understanding the nature, etiology, and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction.

MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell type-specific metabolic control by hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.},
}

@article {pmid32853021,
year = {2021},
author = {Bakhtari, N and Mozdarani, H and Salimi, M and Omranipour, R},
title = {Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.},
journal = {Neoplasma},
volume = {68},
number = {1},
pages = {190-199},
doi = {10.4149/neo_2020_200225N185},
pmid = {32853021},
issn = {0028-2685},
mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/blood/genetics/radiotherapy ; Female ; Humans ; Leukocytes, Mononuclear/metabolism ; *MicroRNAs/biosynthesis/blood ; Middle Aged ; ROC Curve ; Radiation Tolerance ; },
abstract = {Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47±9.93) and 30 healthy women (mean age: 44.43±6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p<0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mirR-22 might be a potential biomarker for the prediction of CR in BC patients.},
}

Adult
Biomarkers, Tumor/blood/genetics
*Breast Neoplasms/blood/genetics/radiotherapy
*Carcinoma, Ductal, Breast/blood/genetics/radiotherapy
Female
Humans
Leukocytes, Mononuclear/metabolism
*MicroRNAs/biosynthesis/blood
Middle Aged
ROC Curve
Radiation Tolerance

@article {pmid32439746,
year = {2020},
author = {Bacorn, C and Kim, E and Borowsky, AD and Lin, LK},
title = {Previously undiagnosed neuroendocrine tumour mimicking breast cancer metastasis to the orbit.},
journal = {BMJ case reports},
volume = {13},
number = {5},
pages = {},
doi = {10.1136/bcr-2020-234629},
pmid = {32439746},
issn = {1757-790X},
mesh = {Adenocarcinoma/*pathology/therapy ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*secondary/therapy ; Diplopia ; Female ; Humans ; Intestinal Neoplasms/*pathology/therapy ; Neuroendocrine Tumors/*pathology/therapy ; Octreotide/therapeutic use ; Orbit ; Orbital Neoplasms/*secondary/therapy ; Pancreatic Neoplasms/*pathology/therapy ; Stomach Neoplasms/*pathology/therapy ; },
abstract = {Metastatic neuroendocrine neoplasms to the breast are rare and histopathologic overlap with mammary carcinomas has led to misdiagnosis. We present a case of a middle-aged woman with diplopia and a right medial rectus mass. Metastatic breast cancer was initially suspected based on a history of invasive ductal carcinoma. Detailed immunohistochemistry of the orbital biopsy, gallium-68 dotatate positron emission tomography-CT, and reevaluation of her prior breast specimen, demonstrated that her initial breast carcinoma diagnosis was in error and she was ultimately diagnosed with a previously unknown gastrointestinal neuroendocrine tumour metastatic to both the orbit and breast. This case highlights the challenges of differentiating between metastatic neuroendocrine tumours and invasive mammary carcinomas with neuroendocrine differentiation both in the breast and in the orbit. It is important to recognise the overlap so that a primary neuroendocrine neoplasm is not missed, or treatment significantly delayed.},
}

Adenocarcinoma/*pathology/therapy
Aged
Antineoplastic Agents, Hormonal/therapeutic use
Breast Neoplasms/*secondary/therapy
Diplopia
Female
Humans
Intestinal Neoplasms/*pathology/therapy
Neuroendocrine Tumors/*pathology/therapy
Octreotide/therapeutic use
Orbit
Orbital Neoplasms/*secondary/therapy
Pancreatic Neoplasms/*pathology/therapy
Stomach Neoplasms/*pathology/therapy

@article {pmid31748977,
year = {2020},
author = {Petry, V and Bonadio, RC and Cagnacci, AQC and Senna, LAL and Campos, RDNG and Cotti, GC and Hoff, PM and Fragoso, MCBV and Estevez-Diz, MDP},
title = {Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).},
journal = {Familial cancer},
volume = {19},
number = {1},
pages = {47-53},
pmid = {31748977},
issn = {1573-7292},
mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/genetics/*radiotherapy ; Female ; Fibrosarcoma/epidemiology ; Follow-Up Studies ; *Genes, p53 ; *Germ-Line Mutation ; Humans ; Leiomyosarcoma/epidemiology ; Li-Fraumeni Syndrome/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Young Adult ; },
abstract = {The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.},
}

Adult
Brazil/epidemiology
Breast Neoplasms/genetics/*radiotherapy
Female
Fibrosarcoma/epidemiology
Follow-Up Studies
*Genes, p53
*Germ-Line Mutation
Humans
Leiomyosarcoma/epidemiology
Li-Fraumeni Syndrome/*genetics
Middle Aged
Neoplasm Recurrence, Local
Neoplasms, Radiation-Induced/*epidemiology
Radiotherapy, Adjuvant/adverse effects
Retrospective Studies
Young Adult

@article {pmid32423910,
year = {2020},
author = {O'Connor, P and Bhadbhade, P and Khan, Q and Williamson, S},
title = {Acral vascular syndrome during an immune checkpoint inhibitor.},
journal = {BMJ case reports},
volume = {13},
number = {5},
pages = {},
doi = {10.1136/bcr-2019-233463},
pmid = {32423910},
issn = {1757-790X},
mesh = {African Americans ; Diagnosis, Differential ; Female ; Fingers/blood supply/pathology ; Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Middle Aged ; Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery ; Thrombosis ; Vasculitis ; },
abstract = {Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.},
}

African Americans
Diagnosis, Differential
Female
Fingers/blood supply/pathology
Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery
Humans
Immune Checkpoint Inhibitors/*adverse effects
Middle Aged
Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery
Thrombosis
Vasculitis

@article {pmid31902119,
year = {2020},
author = {Acun, T and Senses, KM},
title = {Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {27},
number = {3},
pages = {483-489},
doi = {10.1007/s12282-019-01042-6},
pmid = {31902119},
issn = {1880-4233},
support = {2017-50737594-02//Bülent Ecevit Üniversitesi/ ; 217S251//Türkiye Bilimsel ve Teknolojik Araştirma Kurumu/ ; },
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology ; DNA Copy Number Variations ; *DNA Methylation ; Down-Regulation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; Humans ; *Mutation ; Prognosis ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Survival Rate ; },
abstract = {BACKGROUND: DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer.

METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively.

RESULTS: DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n = 121) compared with adjacent normal breast tissues (n = 32) (p < 0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n = 626) (p = 0.0096) and relapse-free survival (n = 1764) (p = 5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines.

CONCLUSIONS: In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.},
}

Biomarkers, Tumor/genetics/*metabolism
Breast Neoplasms/genetics/metabolism/*mortality/pathology
Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology
DNA Copy Number Variations
*DNA Methylation
Down-Regulation
Female
Follow-Up Studies
*Gene Expression Regulation, Neoplastic
HSP40 Heat-Shock Proteins/genetics/*metabolism
Humans
*Mutation
Prognosis
Promoter Regions, Genetic
RNA, Messenger/genetics/metabolism
Survival Rate

@article {pmid33462216,
year = {2021},
author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P},
title = {Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {426},
pmid = {33462216},
issn = {2041-1723},
mesh = {Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus, Experimental/chemically induced/*complications ; Diabetic Neuropathies/etiology/*pathology ; Female ; Ganglia, Spinal/cytology/pathology ; Humans ; Lysosomes ; Male ; Mice ; Mice, Knockout ; Nociception/*physiology ; Pro-Opiomelanocortin/*deficiency/genetics ; Proteolysis ; Receptors, Opioid, mu/genetics/metabolism ; Sensory Receptor Cells/*pathology ; Streptozocin/toxicity ; },
abstract = {Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.},
}

Aged
Aged, 80 and over
Animals
Diabetes Mellitus, Experimental/chemically induced/*complications
Diabetic Neuropathies/etiology/*pathology
Female
Ganglia, Spinal/cytology/pathology
Humans
Lysosomes
Male
Mice
Mice, Knockout
Nociception/*physiology
Pro-Opiomelanocortin/*deficiency/genetics
Proteolysis
Receptors, Opioid, mu/genetics/metabolism
Sensory Receptor Cells/*pathology
Streptozocin/toxicity

@article {pmid33429799,
year = {2021},
author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A},
title = {Clinicopathologic features of single bone metastasis in breast cancer.},
journal = {Medicine},
volume = {100},
number = {1},
pages = {e24164},
pmid = {33429799},
issn = {1536-5964},
mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; },
abstract = {ABSTRACT: The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.},
}

Adult
Aged
Bone Neoplasms/*classification/pathology
Bone and Bones/*pathology/physiopathology
Breast Neoplasms/*complications
Female
Humans
Middle Aged
Neoplasm Metastasis/*physiopathology

@article {pmid33371069,
year = {2020},
author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L},
title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.},
journal = {Medicine},
volume = {99},
number = {51},
pages = {e23406},
doi = {10.1097/MD.0000000000023406},
pmid = {33371069},
issn = {1536-5964},
mesh = {Acrylamides/administration & dosage/*therapeutic use ; Adult ; Aminoquinolines/administration & dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2/antagonists & inhibitors/metabolism ; },
abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.

PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.

DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.

INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.

OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.

CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.},
}

Acrylamides/administration & dosage/*therapeutic use
Adult
Aminoquinolines/administration & dosage/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Breast Neoplasms/*pathology
Carcinoma, Ductal, Breast
Chemotherapy, Adjuvant
ErbB Receptors/*genetics/*metabolism
Female
Humans
Mastectomy
Neoplasm Metastasis
Neoplasm Staging
Receptor, ErbB-2/antagonists & inhibitors/metabolism

@article {pmid33468810,
year = {2020},
author = {Ishihara, S and Kashiwagi, S and Asano, Y and Kawano, Y and Kouhashi, R and Yabumoto, A and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M},
title = {[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {13},
pages = {2089-2091},
pmid = {33468810},
issn = {0385-0684},
abstract = {Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.},
}

@article {pmid33247280,
year = {2020},
author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D},
title = {Increased cyber-biosecurity for DNA synthesis.},
journal = {Nature biotechnology},
volume = {38},
number = {12},
pages = {1379-1381},
pmid = {33247280},
issn = {1546-1696},
mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; },
}

*Computer Security
DNA/*biosynthesis
Genetic Engineering
Plasmids/genetics

@article {pmid31789065,
year = {2020},
author = {Tijani, S and Sharma, K and Yuen, H and Shaaban, A},
title = {Metastatic "Ductal Carcinoma In Situ-Like" Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature.},
journal = {International journal of surgical pathology},
volume = {28},
number = {4},
pages = {436-439},
doi = {10.1177/1066896919888744},
pmid = {31789065},
issn = {1940-2465},
mesh = {Axilla ; Biomarkers, Tumor/analysis/metabolism ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Diagnosis, Differential ; Diagnostic Errors/prevention & control ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy ; Middle Aged ; },
abstract = {Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.},
}

Axilla
Biomarkers, Tumor/analysis/metabolism
Breast/diagnostic imaging/pathology/surgery
Breast Neoplasms/*pathology
Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery
Carcinoma, Lobular/*diagnosis/secondary/surgery
Diagnosis, Differential
Diagnostic Errors/prevention & control
Female
Humans
Lymph Node Excision
Lymph Nodes/*pathology
Lymphatic Metastasis/*diagnosis/pathology
Mammography
Mastectomy
Middle Aged

@article {pmid33445940,
year = {2020},
author = {Bartovská, Z and Andrle, F and Beran, O and Zlámal, M and Řezáč, D and Murinova, I and Holub, M},
title = {Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.},
journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne},
volume = {69},
number = {4},
pages = {164-171},
pmid = {33445940},
issn = {1210-7913},
abstract = {AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature.

PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results. These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software.

RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc).

CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.},
}

@article {pmid32063604,
year = {2020},
author = {Granados, K and Hüser, L and Federico, A and Sachindra, S and Wolff, G and Hielscher, T and Novak, D and Madrigal-Gamboa, V and Sun, Q and Vierthaler, M and Larribère, L and Umansky, V and Utikal, J},
title = {T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.},
journal = {British journal of cancer},
volume = {122},
number = {7},
pages = {1023-1036},
pmid = {32063604},
issn = {1532-1827},
support = {OAICE-CAB-09-133-2015//Universidad de Costa Rica (University of Costa Rica)/International ; PED-054-2015-2//Ministerio de Ciencia Tecnología y Telecomunicaciones (Ministerio de Ciencia Tecnología y Telecomunicaciones de Costa Rica)/International ; 259332240 / RTG 2099//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; },
mesh = {Animals ; Calcium Channels, T-Type/*genetics ; Disease Models, Animal ; Female ; Humans ; Melanoma/*drug therapy/pathology ; Mice ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; },
abstract = {BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).

METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.

RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.

CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.},
}

Animals
Calcium Channels, T-Type/*genetics
Disease Models, Animal
Female
Humans
Melanoma/*drug therapy/pathology
Mice
Protein Kinase Inhibitors/pharmacology/*therapeutic use

@article {pmid31388122,
year = {2020},
author = {Goodes, LM and King, GK and Rea, A and Murray, K and Boan, P and Watts, A and Bardsley, J and Hartshorn, C and Thavaseelan, J and Rawlins, M and Brock, JA and Dunlop, SA},
title = {Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.},
journal = {Spinal cord},
volume = {58},
number = {1},
pages = {25-34},
pmid = {31388122},
issn = {1476-5624},
mesh = {Adult ; Catheters, Indwelling/statistics & numerical data ; Humans ; Incidence ; Inpatients/statistics & numerical data ; Length of Stay/*statistics & numerical data ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications/*epidemiology ; Time Factors ; Urinary Catheterization/adverse effects/*statistics & numerical data ; Urinary Tract Infections/*epidemiology/etiology ; Western Australia/epidemiology ; },
abstract = {STUDY DESIGN: Retrospective audit.

OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).

SETTING: Western Australian Hospitals managing SCI patients.

METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.

RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively).

CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.

SPONSORSHIP: None.},
}

Adult
Catheters, Indwelling/statistics & numerical data
Humans
Incidence
Inpatients/statistics & numerical data
Length of Stay/*statistics & numerical data
Middle Aged
Retrospective Studies
Spinal Cord Injuries/complications/*epidemiology
Time Factors
Urinary Catheterization/adverse effects/*statistics & numerical data
Urinary Tract Infections/*epidemiology/etiology
Western Australia/epidemiology

@article {pmid32748295,
year = {2020},
author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T},
title = {Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.},
journal = {International journal of clinical oncology},
volume = {25},
number = {12},
pages = {2130-2137},
doi = {10.1007/s10147-020-01756-0},
pmid = {32748295},
issn = {1437-7772},
mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Bone Neoplasms/secondary ; Carcinoma, Ductal/mortality/*pathology ; Hormones ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/mortality/*pathology ; Retrospective Studies ; },
abstract = {BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).

METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.

RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively).

CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.},
}

Aged
Aged, 80 and over
Biopsy, Large-Core Needle/*methods
Bone Neoplasms/secondary
Carcinoma, Ductal/mortality/*pathology
Hormones
Humans
Male
Middle Aged
Prognosis
Prostatic Neoplasms/mortality/*pathology
Retrospective Studies

@article {pmid31871301,
year = {2020},
author = {Chen, G and Ding, XF and Pressley, K and Bouamar, H and Wang, B and Zheng, G and Broome, LE and Nazarullah, A and Brenner, AJ and Kaklamani, V and Jatoi, I and Sun, LZ},
title = {Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {6},
pages = {1486-1496},
doi = {10.1158/1078-0432.CCR-19-2478},
pmid = {31871301},
issn = {1557-3265},
support = {R01 CA192564/CA/NCI NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Down-Regulation ; Everolimus/*pharmacology ; Female ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Nude ; Mice, Transgenic ; Receptor, ErbB-2/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Xenograft Model Antitumor Assays ; },
abstract = {PURPOSE: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.

EXPERIMENTAL DESIGN: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.

RESULTS: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell-formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.

CONCLUSIONS: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.},
}

Animals
Antineoplastic Agents/*pharmacology
Biomarkers, Tumor/metabolism
Breast Neoplasms/*drug therapy/metabolism/pathology
Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology
Cell Line, Tumor
Cell Movement
Disease Progression
Down-Regulation
Everolimus/*pharmacology
Female
Humans
Matrix Metalloproteinase 9/chemistry/*metabolism
Mice
Mice, Nude
Mice, Transgenic
Receptor, ErbB-2/genetics/metabolism
Spheroids, Cellular/drug effects/metabolism/pathology
Xenograft Model Antitumor Assays

@article {pmid32811533,
year = {2020},
author = {Chao, X and Liu, L and Sun, P and Yang, X and Li, M and Luo, R and Huang, Y and He, J and Yun, J},
title = {Immune parameters associated with survival in metaplastic breast cancer.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {92},
pmid = {32811533},
issn = {1465-542X},
mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*immunology/metabolism ; Biomarkers, Tumor/*immunology/metabolism ; Breast Neoplasms/*immunology/*mortality/pathology/therapy ; CD8-Positive T-Lymphocytes/*immunology ; Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor/*immunology/metabolism ; Survival Rate ; Tumor Microenvironment/*immunology ; },
abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.

METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.

RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.

CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.},
}

Adult
Aged
Aged, 80 and over
B7-H1 Antigen/*immunology/metabolism
Biomarkers, Tumor/*immunology/metabolism
Breast Neoplasms/*immunology/*mortality/pathology/therapy
CD8-Positive T-Lymphocytes/*immunology
Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy
Female
Humans
Lymphocytes, Tumor-Infiltrating/immunology
Middle Aged
Neoplasm Metastasis
Prognosis
Programmed Cell Death 1 Receptor/*immunology/metabolism
Survival Rate
Tumor Microenvironment/*immunology

@article {pmid32782013,
year = {2020},
author = {Kurozumi, S and Alsaleem, M and Monteiro, CJ and Bhardwaj, K and Joosten, SEP and Fujii, T and Shirabe, K and Green, AR and Ellis, IO and Rakha, EA and Mongan, NP and Heery, DM and Zwart, W and Oesterreich, S and Johnston, SJ},
title = {Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {85},
pmid = {32782013},
issn = {1465-542X},
support = {AAM127669/WT_/Wellcome Trust/United Kingdom ; SAC160073/KOMEN/Susan G. Komen/United States ; },
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Computer Simulation ; Databases, Genetic/statistics & numerical data ; Female ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.

METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.

RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2-11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04-5.05; p = 0.040).

CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.},
}

Biomarkers, Tumor/*genetics
Breast Neoplasms/genetics/metabolism/*pathology
Carcinoma, Ductal, Breast/genetics/metabolism/*pathology
Carcinoma, Lobular/genetics/metabolism/*pathology
Computer Simulation
Databases, Genetic/statistics & numerical data
Female
Humans
Middle Aged
*Mutation
Prognosis
Receptor, ErbB-2/*genetics
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies
Survival Rate

@article {pmid32279596,
year = {2020},
author = {Duman, B and Kuşman, A and Çolak, B and Şenler, FÇ and Kumbasar, H},
title = {Tamoxifen-induced acute mania: A case report.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {26},
number = {8},
pages = {2025-2027},
doi = {10.1177/1078155220915959},
pmid = {32279596},
issn = {1477-092X},
mesh = {Acute Disease ; Antineoplastic Agents, Hormonal/*adverse effects ; Breast Neoplasms/*drug therapy ; Female ; Humans ; Mania/*chemically induced ; Middle Aged ; Tamoxifen/*adverse effects ; },
abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.

CASE REPORT: A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21 days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.

MANAGEMENT AND OUTCOME: The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24 h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.

DISCUSSION: To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.},
}

Acute Disease
Antineoplastic Agents, Hormonal/*adverse effects
Breast Neoplasms/*drug therapy
Female
Humans
Mania/*chemically induced
Middle Aged
Tamoxifen/*adverse effects

@article {pmid33391657,
year = {2020},
author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J},
title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.},
journal = {Journal of surgical case reports},
volume = {2020},
number = {12},
pages = {rjaa535},
doi = {10.1093/jscr/rjaa535},
pmid = {33391657},
issn = {2042-8812},
abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.},
}

@article {pmid32609836,
year = {2020},
author = {Sreekumar, S and Levine, KM and Sikora, MJ and Chen, J and Tasdemir, N and Carter, D and Dabbs, DJ and Meier, C and Basudan, A and Boone, D and McAuliffe, PF and Jankowitz, RC and Lee, AV and Atkinson, JM and Oesterreich, S},
title = {Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.},
journal = {Endocrinology},
volume = {161},
number = {9},
pages = {},
pmid = {32609836},
issn = {1945-7170},
support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Line, Tumor ; Estradiol/pharmacology ; Estrogen Receptor alpha/*genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Invasiveness ; Protein Processing, Post-Translational/drug effects ; Proteolysis/drug effects ; Ubiquitination/drug effects ; },
abstract = {Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.},
}

*Breast Neoplasms/genetics/metabolism/pathology
Carcinoma, Ductal, Breast/genetics/metabolism/pathology
*Carcinoma, Lobular/genetics/metabolism/pathology
Cell Line, Tumor
Estradiol/pharmacology
Estrogen Receptor alpha/*genetics/*metabolism
Female
Gene Expression Regulation, Neoplastic/drug effects
Humans
MCF-7 Cells
Neoplasm Invasiveness
Protein Processing, Post-Translational/drug effects
Proteolysis/drug effects
Ubiquitination/drug effects

@article {pmid32694843,
year = {2019},
author = {Seitz, S and Kwon, Y and Hartleben, G and Jülg, J and Sekar, R and Krahmer, N and Najafi, B and Loft, A and Gancheva, S and Stemmer, K and Feuchtinger, A and Hrabe de Angelis, M and Müller, TD and Mann, M and Blüher, M and Roden, M and Berriel Diaz, M and Behrends, C and Gilleron, J and Herzig, S and Zeigerer, A},
title = {Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.},
journal = {Nature metabolism},
volume = {1},
number = {10},
pages = {1009-1026},
doi = {10.1038/s42255-019-0124-x},
pmid = {32694843},
issn = {2522-5812},
abstract = {Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.},
}

@article {pmid31538688,
year = {2020},
author = {Haynes, HR and Rose, DSC},
title = {Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.},
journal = {The breast journal},
volume = {26},
number = {2},
pages = {245-246},
doi = {10.1111/tbj.13538},
pmid = {31538688},
issn = {1524-4741},
mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasms, Multiple Primary/*pathology ; },
abstract = {We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.},
}

Aged
Axilla
Breast Neoplasms/*pathology
Carcinoma, Ductal, Breast/*secondary
Female
Humans
Immunohistochemistry
Leukemia, Lymphocytic, Chronic, B-Cell/*pathology
Lymph Nodes/*pathology
Lymphatic Metastasis
Neoplasms, Multiple Primary/*pathology

@article {pmid33356097,
year = {2020},
author = {Zhong, S and Wong, HC and Low, HY and Zhao, R},
title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.0c18795},
pmid = {33356097},
issn = {1944-8252},
abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.},
}

@article {pmid33342987,
year = {2020},
author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M},
title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {12},
pages = {1703-1705},
pmid = {33342987},
issn = {0385-0684},
mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; },
abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.},
}

Axilla
*Breast Diseases
*Breast Neoplasms/surgery
*Carcinoma, Ductal, Breast/complications/surgery
Female
Humans
Lymph Node Excision
Lymph Nodes
Lymphatic Metastasis
Mastectomy
Middle Aged
Sentinel Lymph Node Biopsy

@article {pmid33106505,
year = {2020},
author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC},
title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {18276},
pmid = {33106505},
issn = {2045-2322},
mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Whole Exome Sequencing ; },
abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.},
}

Bayes Theorem
Biomarkers, Tumor/*genetics
Breast Neoplasms/*diagnosis/genetics
Calcinosis/*diagnosis/genetics
Early Detection of Cancer
Female
Gene Expression Profiling/*methods
Gene Expression Regulation, Neoplastic
Humans
Oligonucleotide Array Sequence Analysis
Prognosis
Taiwan
Whole Exome Sequencing

@article {pmid33331427,
year = {2020},
author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF},
title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.},
journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery},
volume = {33},
number = {3},
pages = {e1525},
doi = {10.1590/0102-672020200003e1525},
pmid = {33331427},
issn = {2317-6326},
abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.

AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.

METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.

RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.

CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.},
}

@article {pmid32661241,
year = {2020},
author = {Tasdemir, N and Ding, K and Savariau, L and Levine, KM and Du, T and Elangovan, A and Bossart, EA and Lee, AV and Davidson, NE and Oesterreich, S},
title = {Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {11487},
pmid = {32661241},
issn = {2045-2322},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; 5F30CA203154/NH/NIH HHS/United States ; K99CA237736/NH/NIH HHS/United States ; 1F31CA203055-01/NH/NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA203055/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; },
mesh = {Autoantigens/genetics ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Proteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/genetics ; Phosphatidylinositol 3-Kinases/genetics ; *Proteomics ; Proto-Oncogene Proteins c-akt/genetics ; Ribosomal Protein S6 Kinases, 90-kDa/genetics ; Signal Transduction/genetics ; Transcriptome/*genetics ; },
abstract = {Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.},
}

Autoantigens/genetics
Breast Neoplasms/*genetics/pathology
Cadherins/genetics
Carcinoma, Lobular/*genetics/pathology
Cell Differentiation/genetics
Female
Gene Expression Regulation, Neoplastic/genetics
Humans
Inhibitor of Differentiation Protein 1/genetics
Inhibitor of Differentiation Proteins/genetics
Intracellular Signaling Peptides and Proteins/genetics
Membrane Proteins/genetics
Middle Aged
Neoplasm Invasiveness/genetics/pathology
Neoplasm Proteins/genetics
Phosphatidylinositol 3-Kinases/genetics
*Proteomics
Proto-Oncogene Proteins c-akt/genetics
Ribosomal Protein S6 Kinases, 90-kDa/genetics
Signal Transduction/genetics
Transcriptome/*genetics

@article {pmid33316685,
year = {2020},
author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.},
journal = {Surgical oncology},
volume = {36},
number = {},
pages = {91-98},
doi = {10.1016/j.suronc.2020.11.015},
pmid = {33316685},
issn = {1879-3320},
abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.

PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.

RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.

CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.},
}

@article {pmid33243732,
year = {2020},
author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J},
title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {40},
number = {11},
pages = {1593-1600},
pmid = {33243732},
issn = {1673-4254},
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; },
abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.

METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.

RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.

CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.},
}

*Breast Neoplasms/genetics
*Carcinoma, Ductal, Breast/genetics
Humans
Jumonji Domain-Containing Histone Demethylases
Lymphatic Metastasis
Matrix Metalloproteinase 2
Prognosis
Vascular Endothelial Growth Factor A

@article {pmid33027370,
year = {2020},
author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI},
title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.},
journal = {Arquivos brasileiros de cardiologia},
volume = {115},
number = {3},
pages = {480-490},
doi = {10.36660/abc.20190306},
pmid = {33027370},
issn = {1678-4170},
mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; },
abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.

OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.

METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.

RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).

CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).},
}

Animals
Humans
*Hypertension, Pulmonary/chemically induced
Hypertrophy, Right Ventricular/chemically induced
Male
Monocrotaline/toxicity
*Pulmonary Arterial Hypertension
Rats
Rats, Wistar

@article {pmid32868877,
year = {2020},
author = {Murray, AS and Hyland, TE and Sala-Hamrick, KE and Mackinder, JR and Martin, CE and Tanabe, LM and Varela, FA and List, K},
title = {The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.},
journal = {Oncogene},
volume = {39},
number = {41},
pages = {6421-6436},
doi = {10.1038/s41388-020-01436-3},
pmid = {32868877},
issn = {1476-5594},
support = {R01 CA160565/CA/NCI NIH HHS/United States ; R01 CA222359/CA/NCI NIH HHS/United States ; F31 CA217148/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use ; Apoptosis/drug effects/genetics ; Breast/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Cell Line, Tumor ; Cell Survival/genetics ; Datasets as Topic ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology ; },
abstract = {Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.},
}

Animals
Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use
Apoptosis/drug effects/genetics
Breast/pathology
Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology
Cell Line, Tumor
Cell Survival/genetics
Datasets as Topic
Disease Progression
Drug Resistance, Neoplasm/genetics
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mammary Glands, Animal/pathology
Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology
Membrane Proteins/genetics/*metabolism
Mice
Mice, Knockout
Serine Endopeptidases/genetics/*metabolism
Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology

@article {pmid32480118,
year = {2020},
author = {Chan, SJ and Ein-Dor, T and Mayopoulos, PA and Mesa, MM and Sunda, RM and McCarthy, BF and Kaimal, AJ and Dekel, S},
title = {Risk factors for developing posttraumatic stress disorder following childbirth.},
journal = {Psychiatry research},
volume = {290},
number = {},
pages = {113090},
doi = {10.1016/j.psychres.2020.113090},
pmid = {32480118},
issn = {1872-7123},
mesh = {Adult ; Delivery, Obstetric/*psychology/statistics & numerical data ; Female ; Humans ; Labor, Obstetric/*psychology ; Mental Health ; Parturition/*psychology ; Postpartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Pregnancy Outcome/epidemiology/psychology ; Prevalence ; Risk Factors ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; },
abstract = {Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.},
}

Adult
Delivery, Obstetric/*psychology/statistics & numerical data
Female
Humans
Labor, Obstetric/*psychology
Mental Health
Parturition/*psychology
Postpartum Period/*psychology
Pregnancy
Pregnancy Complications/*epidemiology
Pregnancy Outcome/epidemiology/psychology
Prevalence
Risk Factors
Stress Disorders, Post-Traumatic/*epidemiology
Surveys and Questionnaires

@article {pmid32202536,
year = {2020},
author = {Szentirmai, E and Giannico, GA},
title = {Intraductal carcinoma of the prostate.},
journal = {Pathologica},
volume = {112},
number = {1},
pages = {17-24},
doi = {10.32074/1591-951X-5-20},
pmid = {32202536},
issn = {1591-951X},
mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Prostatectomy/trends ; Prostatic Neoplasms/*diagnosis/*genetics/therapy ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.},
}

Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy
Diagnosis, Differential
Humans
Male
Prostatectomy/trends
Prostatic Neoplasms/*diagnosis/*genetics/therapy

@article {pmid31992119,
year = {2020},
author = {Billena, C and Padia, S and O'Brien, B and Knoble, J and Gokhale, A and Rajagopalan, M},
title = {Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.},
journal = {Immunotherapy},
volume = {12},
number = {2},
pages = {123-130},
doi = {10.2217/imt-2019-0020},
pmid = {31992119},
issn = {1750-7448},
mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy ; Female ; Humans ; Nivolumab/*therapeutic use ; Radiodermatitis/complications/*etiology ; Radiotherapy, Adjuvant ; },
abstract = {Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.},
}

Aged
Antineoplastic Agents, Immunological/*therapeutic use
Breast Neoplasms/complications/*drug therapy/*radiotherapy
Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy
Female
Humans
Nivolumab/*therapeutic use
Radiodermatitis/complications/*etiology
Radiotherapy, Adjuvant

@article {pmid31486035,
year = {2020},
author = {Delaunay, T and Achard, C and Grégoire, M and Tangy, F and Boisgerault, N and Fonteneau, JF},
title = {A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2058},
number = {},
pages = {127-132},
doi = {10.1007/978-1-4939-9794-7_8},
pmid = {31486035},
issn = {1940-6029},
mesh = {Animals ; Antigen-Presenting Cells/immunology/metabolism ; Cell Death/immunology ; Dendritic Cells/immunology/metabolism ; Genetic Therapy/methods ; Genetic Vectors/*genetics ; Humans ; *Immunomodulation ; Immunophenotyping ; Monocytes/immunology/metabolism ; Neoplasms/*immunology/metabolism/pathology/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/*genetics/immunology ; },
abstract = {Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).},
}

Animals
Antigen-Presenting Cells/immunology/metabolism
Cell Death/immunology
Dendritic Cells/immunology/metabolism
Genetic Therapy/methods
Genetic Vectors/*genetics
Humans
*Immunomodulation
Immunophenotyping
Monocytes/immunology/metabolism
Neoplasms/*immunology/metabolism/pathology/therapy
Oncolytic Virotherapy
Oncolytic Viruses/*genetics/immunology

@article {pmid33302909,
year = {2020},
author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB},
title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1217},
pmid = {33302909},
issn = {1471-2407},
support = {W81XWH-17-1-0011//U.S. Department of Defense/ ; W81XWH-15-1-0040//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; },
abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.

METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX®, or S-ODX) for each patient and evaluated their combined prognostic ability.

RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX < 26) and high risk (S-ODX ≥26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.

CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.},
}

@article {pmid33278619,
year = {2020},
author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H},
title = {Reduction of 30-day death rates from Staphylococcus aureus bacteraemia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijid.2020.11.199},
pmid = {33278619},
issn = {1878-3511},
abstract = {OBJECTIVES: Most Japanese hospitals need to keep higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximise the effect of these QCIs in a small number of infectious diseases specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious diseases consultations (IDCs).

METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalised structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.

RESULTS: A total of 114 patients with SAB were analysed. The 30-day all-cause mortality was significant between the two periods (17.3% vs. 4.8%, p = 0.02). Age, 3 QCI point ≥1, and Pitt bacteraemia score ≥3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.

CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence of QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.},
}

@article {pmid33251496,
year = {2020},
author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J},
title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.},
journal = {iScience},
volume = {23},
number = {12},
pages = {101763},
doi = {10.1016/j.isci.2020.101763},
pmid = {33251496},
issn = {2589-0042},
abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b-/- mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b-/- embryos. Akr1a1b-/- mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b-/- mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.},
}

@article {pmid32371885,
year = {2020},
author = {Schwarz, D and Hidmark, AS and Sturm, V and Fischer, M and Milford, D and Hausser, I and Sahm, F and Breckwoldt, MO and Agarwal, N and Kuner, R and Bendszus, M and Nawroth, PP and Heiland, S and Fleming, T},
title = {Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {7593},
pmid = {32371885},
issn = {2045-2322},
mesh = {Animals ; Biopsy ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology ; Disease Models, Animal ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging/methods/standards ; Mice ; Microscopy ; Microscopy, Electron ; },
abstract = {In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.},
}

Animals
Biopsy
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1/complications
Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology
Disease Models, Animal
Humans
Image Processing, Computer-Assisted
*Magnetic Resonance Imaging/methods/standards
Mice
Microscopy
Microscopy, Electron

@article {pmid33239449,
year = {2020},
author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J},
title = {CaM Kinase II-δ is Required for Diabetic Hyperglycemia and Retinopathy but not Nephropathy.},
journal = {Diabetes},
volume = {},
number = {},
pages = {},
doi = {10.2337/db19-0659},
pmid = {33239449},
issn = {1939-327X},
abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications, Instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM Kinase II δ (CaMKIIδ) that is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle but also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.},
}

@article {pmid33238981,
year = {2020},
author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C},
title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1145},
doi = {10.1186/s12885-020-07635-1},
pmid = {33238981},
issn = {1471-2407},
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.

METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.

RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.

CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.},
}

@article {pmid32139710,
year = {2020},
author = {Roy, S and Kumar, R and Mittal, V and Gupta, D},
title = {Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {4113},
pmid = {32139710},
issn = {2045-2322},
support = {SRF//Council of Scientific and Industrial Research (CSIR)/International ; SRF//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/PR6963/BID/7/427/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/BI/25/066/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; },
mesh = {Algorithms ; Breast Neoplasms/*classification/genetics ; Carcinoma, Ductal, Breast/*classification/genetics ; Databases, Genetic ; Datasets as Topic ; Early Detection of Cancer ; Female ; Gene Ontology ; Humans ; Machine Learning ; Microarray Analysis ; Models, Biological ; Neoplasm Staging ; Protein Interaction Maps ; RNA, Neoplasm ; RNA-Seq ; Reproducibility of Results ; *Supervised Machine Learning ; *Transcriptome ; },
abstract = {Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.},
}

Algorithms
Breast Neoplasms/*classification/genetics
Carcinoma, Ductal, Breast/*classification/genetics
Databases, Genetic
Datasets as Topic
Early Detection of Cancer
Female
Gene Ontology
Humans
Machine Learning
Microarray Analysis
Models, Biological
Neoplasm Staging
Protein Interaction Maps
RNA, Neoplasm
RNA-Seq
Reproducibility of Results
*Supervised Machine Learning
*Transcriptome

@article {pmid32269189,
year = {2020},
author = {Lee, YH and Kwon, MJ and Park, JH and Jeong, SJ and Kim, TH and Jeong, HW and Lee, SH},
title = {Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {59},
number = {13},
pages = {1665-1669},
pmid = {32269189},
issn = {1349-7235},
mesh = {Adrenal Gland Neoplasms/*complications/surgery ; Adrenalectomy ; Adult ; Biopsy ; Breast Neoplasms/*complications/therapy ; Cafe-au-Lait Spots/pathology ; Female ; Humans ; Incidental Findings ; Neurofibromatosis 1/*complications ; Pheochromocytoma/*complications ; Skin Neoplasms/pathology ; },
abstract = {A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.},
}

Adrenal Gland Neoplasms/*complications/surgery
Adrenalectomy
Adult
Biopsy
Breast Neoplasms/*complications/therapy
Cafe-au-Lait Spots/pathology
Female
Humans
Incidental Findings
Neurofibromatosis 1/*complications
Pheochromocytoma/*complications
Skin Neoplasms/pathology

@article {pmid33130707,
year = {2020},
author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T},
title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {9},
pages = {1387-1389},
pmid = {33130707},
issn = {0385-0684},
mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; },
abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.},
}

*Breast Neoplasms/genetics/surgery
*Carcinoma, Ductal
*Carcinoma, Ductal, Breast/surgery
*Carcinoma, Intraductal, Noninfiltrating
Child
Female
*Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery
Humans
Mastectomy

@article {pmid33209168,
year = {2020},
author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A},
title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].},
journal = {The Pan African medical journal},
volume = {37},
number = {},
pages = {41},
doi = {10.11604/pamj.2020.37.41.21336},
pmid = {33209168},
issn = {1937-8688},
abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.},
}

@article {pmid33126344,
year = {2020},
author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z},
title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.},
journal = {Medicine},
volume = {99},
number = {44},
pages = {e22904},
pmid = {33126344},
issn = {1536-5964},
mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; },
abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.},
}

Age Factors
Anticarcinogenic Agents/therapeutic use
*Breast Neoplasms/drug therapy/pathology
China/epidemiology
Female
Humans
Imatinib Mesylate/*therapeutic use
Incidence
*Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology
Male
Middle Aged
*Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology
Prognosis
Retrospective Studies
Risk Factors
Sex Factors
Survival Analysis
Time Factors

@article {pmid32051475,
year = {2020},
author = {Beetch, M and Harandi-Zadeh, S and Yang, T and Boycott, C and Chen, Y and Stefanska, B and Mohammed, SI},
title = {DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {2415},
doi = {10.1038/s41598-020-59260-4},
pmid = {32051475},
issn = {2045-2322},
mesh = {Animals ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary ; *DNA Methylation ; Disease Progression ; Dog Diseases/*genetics/pathology ; Dogs/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/*veterinary ; },
abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.},
}

Animals
Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary
*DNA Methylation
Disease Progression
Dog Diseases/*genetics/pathology
Dogs/*genetics
Female
Gene Expression Regulation, Neoplastic
Triple Negative Breast Neoplasms/genetics/pathology/*veterinary

@article {pmid33163280,
year = {2020},
author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.},
journal = {American journal of cancer research},
volume = {10},
number = {10},
pages = {3415-3427},
pmid = {33163280},
issn = {2156-6976},
abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.},
}

@article {pmid31941968,
year = {2020},
author = {Elmetwali, T and Salman, A and Wei, W and Hussain, SA and Young, LS and Palmer, DH},
title = {CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {342},
pmid = {31941968},
issn = {2045-2322},
mesh = {Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Apoptosis/drug effects ; CD40 Antigens/metabolism ; CD40 Ligand/genetics/*metabolism/pharmacology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Cell Proliferation ; Dendritic Cells/cytology/immunology/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Vectors/genetics/metabolism ; Humans ; Immunoglobulins/metabolism ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Membrane Glycoproteins/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Urinary Bladder Neoplasms/immunology/metabolism/pathology ; },
abstract = {In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.},
}

Antigens, CD/metabolism
Antigens, Neoplasm/metabolism
Apoptosis/drug effects
CD40 Antigens/metabolism
CD40 Ligand/genetics/*metabolism/pharmacology
CD8-Positive T-Lymphocytes/cytology/immunology/metabolism
Cell Line, Tumor
Cell Membrane/*metabolism
Cell Proliferation
Dendritic Cells/cytology/immunology/metabolism
Gene Expression Regulation, Neoplastic/drug effects
Genetic Vectors/genetics/metabolism
Humans
Immunoglobulins/metabolism
Interferon-gamma/metabolism
Interleukin-10/metabolism
Leukocytes, Mononuclear/cytology/metabolism
Membrane Glycoproteins/metabolism
T-Lymphocytes/cytology/*immunology/metabolism
Urinary Bladder Neoplasms/immunology/metabolism/pathology

@article {pmid31849934,
year = {2019},
author = {Alexia, C and Cren, M and Louis-Plence, P and Vo, DN and El Ahmadi, Y and Dufourcq-Lopez, E and Lu, ZY and Hernandez, J and Shamilov, F and Chernysheva, O and Vasilieva, M and Vorotnikov, I and Vishnevskay, Y and Tupitsyn, N and Rossi, JF and Villalba, M},
title = {Polyoxidonium® Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer.},
journal = {Frontiers in immunology},
volume = {10},
number = {},
pages = {2693},
pmid = {31849934},
issn = {1664-3224},
mesh = {Adenocarcinoma/*drug therapy/immunology ; Adjuvants, Immunologic/*therapeutic use ; Adult ; Aged ; Breast Neoplasms/*drug therapy/immunology ; Cell Differentiation/drug effects/immunology ; Chemotherapy, Adjuvant/methods ; Dendritic Cells/*drug effects/immunology ; Female ; Humans ; Killer Cells, Natural/drug effects/immunology ; Lymphocyte Activation/drug effects/immunology ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Middle Aged ; Neoadjuvant Therapy/methods ; Piperazines/*therapeutic use ; Polymers/*therapeutic use ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; },
abstract = {Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.},
}

Adenocarcinoma/*drug therapy/immunology
Adjuvants, Immunologic/*therapeutic use
Adult
Aged
Breast Neoplasms/*drug therapy/immunology
Cell Differentiation/drug effects/immunology
Chemotherapy, Adjuvant/methods
Dendritic Cells/*drug effects/immunology
Female
Humans
Killer Cells, Natural/drug effects/immunology
Lymphocyte Activation/drug effects/immunology
Lymphocytes, Tumor-Infiltrating/drug effects/immunology
Middle Aged
Neoadjuvant Therapy/methods
Piperazines/*therapeutic use
Polymers/*therapeutic use
T-Lymphocytes, Cytotoxic/drug effects/immunology

@article {pmid33148662,
year = {2020},
author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV},
title = {Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-20-0696},
pmid = {33148662},
issn = {1538-7445},
abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique features compared to the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell-RNA-sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knock out (KO). Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a pre-adaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFN-γ mediated growth inhibition via activation of IRF1. This study reveals single cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance.},
}

@article {pmid32586354,
year = {2020},
author = {Blohmer, M and Zhu, L and Atkinson, JM and Beriwal, S and Rodríguez-López, JL and Rosenzweig, M and Brufsky, AM and Tseng, G and Lucas, PC and Lee, AV and Oesterreich, S and Jankowitz, RC},
title = {Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {70},
pmid = {32586354},
issn = {1465-542X},
support = {SAC160073/KOMEN/Susan G. Komen/United States ; CCR14300865/KOMEN/Susan G. Komen/United States ; SAC150021/KOMEN/Susan G. Komen/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; U24 CA180921/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy ; Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Orbital Neoplasms/metabolism/radiotherapy/*secondary ; Prognosis ; Radiotherapy, Intensity-Modulated ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.

METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.

RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.

CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.},
}

Adult
Aged
Breast Neoplasms/metabolism/*pathology/*radiotherapy
Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy
Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy
Female
Follow-Up Studies
Humans
Lymphatic Metastasis
Middle Aged
Orbital Neoplasms/metabolism/radiotherapy/*secondary
Prognosis
Radiotherapy, Intensity-Modulated
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies
Survival Rate
Treatment Outcome

@article {pmid30712460,
year = {2020},
author = {Song, G and He, L and Yang, X and Yang, Y and Cai, X and Liu, K and Feng, G},
title = {Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.},
journal = {The Journal of international medical research},
volume = {48},
number = {1},
pages = {300060518815364},
pmid = {30712460},
issn = {1473-2300},
mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cluster Analysis ; Databases, Genetic ; *Disease Progression ; Down-Regulation/genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Reproducibility of Results ; Signal Transduction/genetics ; Up-Regulation/genetics ; },
}

Breast Neoplasms/*genetics/*pathology
Carcinoma in Situ/*genetics/*pathology
Carcinoma, Ductal, Breast/*genetics/*pathology
Cluster Analysis
Databases, Genetic
*Disease Progression
Down-Regulation/genetics
Female
Gene Expression Profiling
*Gene Expression Regulation, Neoplastic
Humans
Neoplasm Proteins/genetics/metabolism
Reproducibility of Results
Signal Transduction/genetics
Up-Regulation/genetics

@article {pmid31673038,
year = {2019},
author = {Golberg, A and Sheviryov, J and Solomon, O and Anavy, L and Yakhini, Z},
title = {Molecular harvesting with electroporation for tissue profiling.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {15750},
doi = {10.1038/s41598-019-51634-7},
pmid = {31673038},
issn = {2045-2322},
mesh = {Animals ; Electroporation/*methods ; Female ; Gene Ontology ; Genomics ; Hep G2 Cells ; Humans ; Kidney/*metabolism/pathology ; Liver/*metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/metabolism/pathology ; Proteomics ; RNA, Neoplasm/metabolism ; Transplantation, Heterologous ; },
abstract = {Recent developments in personalized medicine are based on molecular measurement steps that guide personally adjusted medical decisions. A central approach to molecular profiling consists of measuring DNA, RNA, and/or proteins in tissue samples, most notably in and around tumors. This measurement yields molecular biomarkers that are potentially predictive of response and of tumor type. Current methods in cancer therapy mostly use tissue biopsy as the starting point of molecular profiling. Tissue biopsies involve a physical resection of a small tissue sample, leading to localized tissue injury, bleeding, inflammation and stress, as well as to an increased risk of metastasis. Here we developed a technology for harvesting biomolecules from tissues using electroporation. We show that tissue electroporation, achieved using a combination of high-voltage short pulses, 50 pulses 500 V cm-1, 30 µs, 1 Hz, with low-voltage long pulses 50 pulses 50 V cm-1, 10 ms, delivered at 1 Hz, allows for tissue-specific extraction of RNA and proteins. We specifically tested RNA and protein extraction from excised kidney and liver samples and from excised HepG2 tumors in mice. Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumors and of tumor environment and to related diagnosis practices.},
}

Animals
Electroporation/*methods
Female
Gene Ontology
Genomics
Hep G2 Cells
Humans
Kidney/*metabolism/pathology
Liver/*metabolism/pathology
Mice
Mice, Nude
Neoplasm Proteins/metabolism
Neoplasms/genetics/metabolism/pathology
Proteomics
RNA, Neoplasm/metabolism
Transplantation, Heterologous

@article {pmid31578784,
year = {2020},
author = {Patel, DP and Herrick, JS and Stoffel, JT and Elliott, SP and Lenherr, SM and Presson, AP and Welk, B and Jha, A and Myers, JB and , },
title = {Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.},
journal = {Neurourology and urodynamics},
volume = {39},
number = {1},
pages = {211-219},
doi = {10.1002/nau.24172},
pmid = {31578784},
issn = {1520-6777},
mesh = {Adult ; Female ; Health Behavior ; Humans ; Intermittent Urethral Catheterization/*adverse effects ; Male ; Middle Aged ; Patient Compliance ; Patient Satisfaction ; *Quality of Life ; Registries ; Spinal Cord Injuries/*complications ; Urinary Bladder, Neurogenic/*etiology ; Urinary Tract Infections/*etiology ; },
abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.

METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.

RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).

CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.},
}

Adult
Female
Health Behavior
Humans
Intermittent Urethral Catheterization/*adverse effects
Male
Middle Aged
Patient Compliance
Patient Satisfaction
*Quality of Life
Registries
Spinal Cord Injuries/*complications
Urinary Bladder, Neurogenic/*etiology
Urinary Tract Infections/*etiology

@article {pmid31171819,
year = {2019},
author = {Chavez, DE and Gronau, I and Hains, T and Kliver, S and Koepfli, KP and Wayne, RK},
title = {Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {8329},
doi = {10.1038/s41598-019-44772-5},
pmid = {31171819},
issn = {2045-2322},
mesh = {*Adaptation, Physiological ; Animals ; Animals, Wild/genetics ; *Biological Evolution ; Body Patterning ; Canidae/*genetics ; Computational Biology ; DNA/analysis ; Diet ; Female ; *Genomics ; Genotype ; Hedgehog Proteins/genetics ; Molar ; Monte Carlo Method ; Pigmentation ; Predatory Behavior ; },
abstract = {Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.},
}

*Adaptation, Physiological
Animals
Animals, Wild/genetics
*Biological Evolution
Body Patterning
Canidae/*genetics
Computational Biology
DNA/analysis
Diet
Female
*Genomics
Genotype
Hedgehog Proteins/genetics
Molar
Monte Carlo Method
Pigmentation
Predatory Behavior

@article {pmid32719289,
year = {2020},
author = {Dhia, SB and Belaid, I and Stita, W and Hochlaf, M and Ezzairi, F and Ahmed, SB},
title = {Bilateral parotid gland metastasis from a breast invasive ductal carcinoma.},
journal = {Journal of cancer research and therapeutics},
volume = {16},
number = {3},
pages = {672-674},
doi = {10.4103/jcrt.JCRT_1047_17},
pmid = {32719289},
issn = {1998-4138},
mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/therapy ; Palliative Care ; Parotid Neoplasms/*secondary/therapy ; },
abstract = {Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.},
}

Breast Neoplasms/*pathology/therapy
Carcinoma, Ductal, Breast/*pathology/therapy
Combined Modality Therapy
Fatal Outcome
Female
Humans
Middle Aged
Neoplasm Recurrence, Local/*pathology/therapy
Palliative Care
Parotid Neoplasms/*secondary/therapy

@article {pmid32088208,
year = {2020},
author = {Guillet, C and Rechsteiner, M and Bellini, E and Choschzick, M and Moskovszky, L and Dedes, K and Papassotiropoulos, B and Varga, Z},
title = {Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.},
journal = {Human pathology},
volume = {98},
number = {},
pages = {64-73},
doi = {10.1016/j.humpath.2020.02.002},
pmid = {32088208},
issn = {1532-8392},
mesh = {Adult ; Age of Onset ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Heredity ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; *Mutation ; Papilloma/*genetics/pathology/surgery ; Pedigree ; Phenotype ; Proto-Oncogene Proteins c-akt/*genetics ; },
abstract = {Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.},
}

Adult
Age of Onset
Biomarkers, Tumor/*genetics
Breast Neoplasms/*genetics/pathology/surgery
Class I Phosphatidylinositol 3-Kinases/*genetics
DNA Mutational Analysis
Female
Genetic Predisposition to Disease
Heredity
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
*Mutation
Papilloma/*genetics/pathology/surgery
Pedigree
Phenotype
Proto-Oncogene Proteins c-akt/*genetics

@article {pmid32050925,
year = {2020},
author = {Dettogni, RS and Stur, E and Laus, AC and da Costa Vieira, RA and Marques, MMC and Santana, IVV and Pulido, JZ and Ribeiro, LF and de Jesus Parmanhani, N and Agostini, LP and Dos Reis, RS and de Vargas Wolfgramm Dos Santos, E and Alves, LNR and Garcia, FM and Santos, JA and do Prado Ventorim, D and Reis, RM and Louro, ID},
title = {Potential biomarkers of ductal carcinoma in situ progression.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {119},
pmid = {32050925},
issn = {1471-2407},
support = {0468/2015//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66141494/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66271126/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 0698/2015//Fundação de Amparo à Pesquisa do Espirito Santo-Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (FAPES-CAPES)/ ; },
mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism ; Computational Biology ; Disease Progression ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome ; },
abstract = {BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.

METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.

RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.

CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.},
}

Aged
Aged, 80 and over
*Biomarkers, Tumor
Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism
Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism
Computational Biology
Disease Progression
Disease Susceptibility
Female
Gene Expression Profiling
Humans
Middle Aged
Neoplasm Grading
Neoplasm Staging
Protein Interaction Mapping
Protein Interaction Maps
Transcriptome

@article {pmid33097605,
year = {2020},
author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB},
title = {A Requirement for p120-catenin in the metastasis of invasive ductal breast cancer.},
journal = {Journal of cell science},
volume = {},
number = {},
pages = {},
doi = {10.1242/jcs.250639},
pmid = {33097605},
issn = {1477-9137},
abstract = {We have examined the effects of targeted p120 KO in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment leading ultimately to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo. The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.},
}

@article {pmid32619221,
year = {2020},
author = {Escoter-Torres, L and Greulich, F and Quagliarini, F and Wierer, M and Uhlenhaut, NH},
title = {Anti-inflammatory functions of the glucocorticoid receptor require DNA binding.},
journal = {Nucleic acids research},
volume = {48},
number = {15},
pages = {8393-8407},
pmid = {32619221},
issn = {1362-4962},
mesh = {Animals ; DNA/*genetics/metabolism ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation/genetics ; Glucocorticoids/genetics/metabolism ; Humans ; Inflammation/*genetics/pathology ; Mice ; Protein Interaction Domains and Motifs/genetics ; RNA-Seq ; Receptors, Glucocorticoid/*genetics ; Transcriptional Activation/genetics ; },
abstract = {The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR's anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR's zinc finger, that still tether via protein-protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.},
}

Animals
DNA/*genetics/metabolism
DNA-Binding Proteins/*genetics
Gene Expression Regulation/genetics
Glucocorticoids/genetics/metabolism
Humans
Inflammation/*genetics/pathology
Mice
Protein Interaction Domains and Motifs/genetics
RNA-Seq
Receptors, Glucocorticoid/*genetics
Transcriptional Activation/genetics

@article {pmid32031117,
year = {2020},
author = {Söyleyici, NA and Aslan, F and Avcýkurt, AS and Akgün, GA},
title = {Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.},
journal = {Indian journal of pathology & microbiology},
volume = {63},
number = {1},
pages = {19-24},
doi = {10.4103/IJPM.IJPM_658_19},
pmid = {32031117},
issn = {0974-5130},
mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/surgery ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Trans-Activators/*genetics ; Vascular Endothelial Growth Factor A/genetics ; },
abstract = {Background: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.

Methods: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.

Results: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.

Conclusion: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.},
}

Adult
Biomarkers, Tumor
Breast Neoplasms/*genetics/*pathology
Carcinoma, Ductal, Breast/*genetics/surgery
Case-Control Studies
Female
Humans
Immunohistochemistry
Mastectomy
Middle Aged
Prognosis
Trans-Activators/*genetics
Vascular Endothelial Growth Factor A/genetics

@article {pmid32031116,
year = {2020},
author = {Varma, K and Chauhan, A and Bhargava, M and Misra, V and Srivastava, S},
title = {Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.},
journal = {Indian journal of pathology & microbiology},
volume = {63},
number = {1},
pages = {13-18},
doi = {10.4103/IJPM.IJPM_419_19},
pmid = {32031116},
issn = {0974-5130},
mesh = {Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; beta Catenin/*genetics ; },
abstract = {Background: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.

Materials and Methods: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.

Results: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.

Conclusion: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.},
}

Breast Neoplasms/classification/*genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology
Cyclin D1/*genetics
Female
Genetic Association Studies
Humans
Immunohistochemistry
Middle Aged
Prognosis
beta Catenin/*genetics