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30 Mar 2023 at 01:47
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Bibliography on: Invasive Ductal Carcinoma (causes)


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RJR: Recommended Bibliography 30 Mar 2023 at 01:47 Created: 

Invasive Ductal Carcinoma (causes)

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

The causes of invasive ductal carcinoma have not been conclusively established. Researchers have determined that cancer can form when the cells in a milk-producing duct undergo changes that cause them to grow uncontrollably, divide very rapidly or remain viable longer than they should. The result is an accumulation of excess cells that can form a mass, or tumor, and potentially spread to nearby lymph nodes and distant areas of the body. The underlying reason for those cellular changes, however, remains unclear.

By evaluating the results of extensive studies, scientists have identified certain hormonal, environmental and lifestyle factors that are believed to influence a person's breast cancer risk, such as smoking, poor nutrition and prior radiation therapy administered to the chest area. Even so, it's important to keep in mind that some individuals who have no risk factors develop cancer, while others with one or more risk factors do not. Most likely, the precise cause is a complex interaction of many factors.

In rare cases, the causes of invasive ductal carcinoma have been traced to inherited attributes, such as mutations of the: (a) Breast cancer gene 1 (BRCA1), a tumor suppressor gene, (b) Breast cancer gene 2 (BRCA2), a tumor suppressor gene, or (c) ErbB2 gene, which produces the HER2 protein that promotes cellular proliferation.

Created with PubMed® Query: ( ("invasive ductal carcinoma" OR IDC) AND (cause OR caused OR etiology) ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2023-03-29
CmpDate: 2023-03-29

Tong S, Jiang N, Wan JH, et al (2023)

The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.

BMC cancer, 23(1):275.

BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.

METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.

RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.

CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.

RevDate: 2023-03-17

Cardona Barberán A, Bonte D, Boel A, et al (2023)

Assisted oocyte activation does not overcome recurrent embryo developmental problems.

Human reproduction (Oxford, England) pii:7080095 [Epub ahead of print].

STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?

SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.

WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.

STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (≥60%) but impaired embryonic development (≤15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.

Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.

We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value = 0.06); 9.35% (30/321, P-value = 0.18), 25.00% (11/44, P-value = 0.75), and 15.91% (7/44, P-value = 0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.

Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.

Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.

This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.


RevDate: 2023-03-28
CmpDate: 2023-03-28

Göransson S, Chen S, Olofsson H, et al (2023)

An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).

Biochemical and biophysical research communications, 654:73-79.

Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.

RevDate: 2023-03-21
CmpDate: 2023-03-21

Egea V, Megens RTA, Santovito D, et al (2023)

Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques.

Cardiovascular research, 119(1):155-166.

AIMS: Atherosclerosis is a chronic inflammatory disease of the arteries leading to the formation of atheromatous plaques. Human mesenchymal stem cells (hMSCs) are recruited from the circulation into plaques where in response to their environment they adopt a phenotype with immunomodulatory properties. However, the mechanisms underlying hMSC function in these processes are unclear. Recently, we described that miRNA let-7f controls hMSC invasion guided by inflammatory cytokines and chemokines. Here, we investigated the role of let-7f in hMSC tropism to human atheromas and the effects of the plaque microenvironment on cell fate and release of soluble factors.

METHODS AND RESULTS: Incubation of hMSCs with LL-37, an antimicrobial peptide abundantly found in plaques, increased biosynthesis of let-7f and N-formyl peptide receptor 2 (FPR2), enabling chemotactic invasion of the cells towards LL-37, as determined by qRT-PCR, flow cytometry, and cell invasion assay analysis. In an Apoe-/- mouse model of atherosclerosis, circulating hMSCs preferentially adhered to athero-prone endothelium. This property was facilitated by elevated levels of let-7f in the hMSCs, as assayed by ex vivo artery perfusion and two-photon laser scanning microscopy. Exposure of hMSCs to homogenized human atheromatous plaque material considerably induced the production of various cytokines, chemokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinases, as studied by PCR array and western blot analysis. Moreover, exposure to human plaque extracts elicited differentiation of hMSCs into cells of the myogenic lineage, suggesting a potentially plaque-stabilizing effect.

CONCLUSIONS: Our findings indicate that let-7f promotes hMSC tropism towards atheromas through the LL-37/FPR2 axis and demonstrate that hMSCs upon contact with human plaque environment develop a potentially athero-protective signature impacting the pathophysiology of atherosclerosis.

RevDate: 2023-03-17

Mitsuyoshi A, Yanagawa T, Kikumori K, et al (2023)

[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].

Gan to kagaku ryoho. Cancer & chemotherapy, 50(3):366-368.

The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.

RevDate: 2023-03-15
CmpDate: 2023-03-10

Ali Khadem Z, S Abdul Wadood Al-Shammaree (2022)

Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.

Archives of Razi Institute, 77(4):1341-1348.

Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.

RevDate: 2023-02-22
CmpDate: 2023-02-22

Arias Ramos D, Alzate JA, Moreno Gómez GA, et al (2023)

Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.

Annals of clinical microbiology and antimicrobials, 22(1):13.

BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.

METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum β-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.

RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58 years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score > 3 points, and not having an infectious disease consultation (IDC).

CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.

RevDate: 2023-03-07
CmpDate: 2023-03-07

Wu Y, Sun S, Huang Y, et al (2023)

Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.

Journal of cancer research and clinical oncology, 149(3):1175-1184.

PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value.

METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC).

RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P = 0.037) and pathological N stage (P = 0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P = 0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P = 0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P = 0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P = 0.029).

CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.

RevDate: 2023-02-24
CmpDate: 2023-02-24

Eum SY, Schurhoff N, Teglas T, et al (2023)

Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.

Molecular and cellular biochemistry, 478(3):581-595.

We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.

RevDate: 2023-02-24
CmpDate: 2023-02-24

Zhang J, Lin H, Hou L, et al (2023)

Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.

Cancer medicine, 12(3):3758-3772.

Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.

RevDate: 2023-02-15
CmpDate: 2023-02-15

Sekido N, Matsuoka M, Takahashi R, et al (2023)

Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.

Spinal cord series and cases, 9(1):3.

STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.

OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.

SETTING: An internet survey.

METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).

RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.

CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.

RevDate: 2023-02-14
CmpDate: 2023-02-14

Górnicki T, Lambrinow J, Mrozowska M, et al (2023)

Expression of RBMS3 in Breast Cancer Progression.

International journal of molecular sciences, 24(3):.

The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.

RevDate: 2023-02-14
CmpDate: 2023-02-14

Sui Y, Li S, Fu XQ, et al (2023)

Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.

Journal of translational medicine, 21(1):109.

BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.

RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.

CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.

RevDate: 2023-02-14
CmpDate: 2023-02-14

Langley RG, Sofen H, Dei-Cas I, et al (2023)

Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

The British journal of dermatology, 188(2):198-207.

BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.

OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.

METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.

RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.

CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.

RevDate: 2023-02-13
CmpDate: 2023-02-13

Thompson LDR, JA Bishop (2023)

Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.

Advances in anatomic pathology, 30(2):112-129.

Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.

RevDate: 2023-01-28

Maggi G, Vitale C, Cerciello F, et al (2023)

Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.

Sleep medicine reviews, 68:101759 pii:S1087-0792(23)00015-1 [Epub ahead of print].

Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.

RevDate: 2023-02-06
CmpDate: 2023-02-06

Chang YS, Tu SJ, Chen HD, et al (2023)

Integrated genomic analyses of hepatocellular carcinoma.

Hepatology international, 17(1):97-111.

BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.

METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.

RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+ Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+ memory T cells, CD8+ Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.

CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.

RevDate: 2023-02-03
CmpDate: 2023-02-03

Maalmi H, Strom A, Petrera A, et al (2023)

Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.

Diabetologia, 66(3):579-589.

AIMS/HYPOTHESIS: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

METHODS: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.

RESULTS: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.

CONCLUSIONS/INTERPRETATION: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.

RevDate: 2023-01-26

Feredj E, Audureau E, Boueilh A, et al (2023)

Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.

Pathogens (Basel, Switzerland), 12(1):.

BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.

METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.

RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.

RevDate: 2023-01-24
CmpDate: 2023-01-24

Yang Y, Luo D, Gao W, et al (2023)

Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.

Biomolecules, 13(1):.

Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.

RevDate: 2023-01-17
CmpDate: 2023-01-17

Manginstar C, Oley MH, Oley MC, et al (2022)

Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.

Breast disease, 41(1):481-487.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.

METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).

RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019).

CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.

RevDate: 2023-01-17
CmpDate: 2023-01-17

Kridis WB, Feki A, Khmiri S, et al (2022)

Prognostic factors in inflammatory breast cancer: A single-center study.

Breast disease, 41(1):461-469.

BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.

METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.

RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.

CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.

RevDate: 2023-01-17
CmpDate: 2023-01-17

Ying Z, van Eenige R, Beerepoot R, et al (2023)

Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.

Pharmacological research, 187:106634.

Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.

RevDate: 2023-01-06
CmpDate: 2023-01-06

Serrano-Quintero A, Sequeda-Juárez A, Pérez-Hernández CA, et al (2022)

Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.

Photodiagnosis and photodynamic therapy, 40:103174.

BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231).

METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm[2]. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry.

RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF.

CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.

RevDate: 2023-01-10
CmpDate: 2023-01-10

Shapiro-Kulnane L, Selengut M, HK Salz (2022)

Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.

PLoS genetics, 18(12):e1010568.

H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.

RevDate: 2023-01-10
CmpDate: 2023-01-10

Mamtani A, Grabenstetter A, Sevilimedu V, et al (2023)

Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.

Breast cancer research and treatment, 197(2):417-423.

PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.

METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.

RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.

CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.

RevDate: 2023-01-03
CmpDate: 2023-01-03

Levy-Jurgenson A, Tekpli X, Kristensen VN, et al (2023)

Analysis of Spatial Molecular Data.

Methods in molecular biology (Clifton, N.J.), 2614:349-356.

Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.

RevDate: 2022-12-21
CmpDate: 2022-12-21

Lu X, Ying Y, Zhang W, et al (2023)

High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.

Cell biology international, 47(1):201-215.

Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.

RevDate: 2022-12-20
CmpDate: 2022-12-20

Ansari N, Nisar MI, Khalid F, et al (2022)

Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.

Journal of global health, 12:05055.

BACKGROUND: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan.

METHODS: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys®. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis.

RESULTS: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI) = 42.6-47.9) and 82.3% (95% CI = 79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI = 16.1-20.7) and 57.4% (95% CI = 54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR) = 0.8, 95% CI = 0.7-0.9 and RR = 1.2, 95% CI = 1.1-1.4, respectively) and children (RR = 0.7, 95% CI = 0.5-1.0 and RR = 1.4, 95% CI = 1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR = 0.4, 95% CI = 0.3-0.7 and RR = 0.7, 95% CI = 0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR = 0.6, 95% CI = 0.4-0.9 and RR = 0.7, 95% CI = 0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR = 0.7, 95% CI = 0.6-0.9 and RR = 0.8, 95% CI = 0.7-1.0, respectively).

CONCLUSION: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.

RevDate: 2022-12-20
CmpDate: 2022-12-20

Davis AA, Gerratana L, Clifton K, et al (2022)

Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.

EBioMedicine, 86:104316.

BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.

METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.

FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05).

INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.

FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.

RevDate: 2022-12-15

Yuce E, Karakullukcu S, Bulbul H, et al (2023)

The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.

Bratislavske lekarske listy, 124(1):59-63.

INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses.

MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively.

RESULTS: The mean - age was 50.3±12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were ≤ T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was ≤ 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to ≤ 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged.

CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.

RevDate: 2022-12-14
CmpDate: 2022-12-14

Azmat H, Faridi J, Habib HM, et al (2022)

Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.

Journal of cancer research and therapeutics, 18(Supplement):S313-S319.

BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.

OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.

MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.

RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.

CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.

RevDate: 2022-12-13
CmpDate: 2022-12-13

Leikin-Frenkel A, Schnaider Beeri M, I Cooper (2022)

How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.

Nutrients, 14(23):.

Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.

RevDate: 2022-12-12

Gupta NK, Gaur S, DK Pal (2022)

Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.

Urology annals, 14(4):332-335.

INTRODUCTION: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men.

MATERIALS AND METHODS: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P ≤ 0.05 was considered statistically significant.

RESULTS: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients.

CONCLUSION: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.

RevDate: 2022-12-12
CmpDate: 2022-12-12

Lone Z, Benidir T, Rainey M, et al (2022)

Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.

European urology focus, 8(6):1575-1582.

BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.

OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.

We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).

Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.

RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).

CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.

PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

RevDate: 2022-12-07
CmpDate: 2022-12-07

Ortiz-Rey JA, Bellas-Pereira A, San Miguel-Fraile P, et al (2022)

Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.

Archivos espanoles de urologia, 75(9):738-745.

OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.

MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.

RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.

CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.

RevDate: 2022-11-30
CmpDate: 2022-11-30

Shahi V, Agarwal P, Qayoom S, et al (2022)

Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.

Asian Pacific journal of cancer prevention : APJCP, 23(11):3717-3723 pii:90363.

INTRODUCTION: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India.

METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC.

RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection.

CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.

RevDate: 2022-11-29
CmpDate: 2022-11-29

Gupta RB, Dang H, Albreiki D, et al (2022)

Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.

BMC ophthalmology, 22(1):452.

BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma.

CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3 weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation.

CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.

RevDate: 2022-11-23
CmpDate: 2022-11-23

Abbas Z, Nouroz F, S Ejaz (2022)

Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.

Journal of cancer research and therapeutics, 18(6):1743-1753.

BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.

AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.

MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.

RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.

CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.

RevDate: 2022-11-30
CmpDate: 2022-11-23

Kalyan VSRK, Meena S, Karthikeyan S, et al (2022)

Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.

Archives of microbiology, 204(12):721.

The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.

RevDate: 2022-12-06
CmpDate: 2022-12-06

Lin Z, He Y, Qiu C, et al (2022)

A multi-omics signature to predict the prognosis of invasive ductal carcinoma of the breast.

Computers in biology and medicine, 151(Pt A):106291.

BACKGROUND: Precisely evaluating the prognosis of invasive ductal carcinoma (IDC) of the breast is challenging as most prognostic signatures use single-omics data based on gene or clinical information.

METHODS: Whole-slide images (WSIs), transcriptome, and clinical data of breast IDC were collected from the Cancer Genome Atlas Database. The cancer-associated fibroblast (CAF) gene sets were downloaded from the Molecular Signatures Database. The WSI feature was extracted by artificial feature engineering. The CAF prognostic genes were determined by the Gene Set Enrichment Analysis, the Wilcoxon test, and univariate Cox regression. The IDC patients were divided into the training and test sets. The prognostic signatures based on WSIs, IDC-CAFs, bi-omics, and tri-omics were constructed using multivariate Cox regression. The samples were divided into low- and high-risk groups according to the median risk score. The Kaplan-Meier survival and receiver operating characteristic curves were applied to validate the prediction performance of the four signatures.

RESULTS: In total, 508 IDC patients with complete data were included. The area under the curve (AUC) of single-omics signature based on WSI characteristics and CAFs was 0.765 and 0.775, whereas the AUC of bi-omics was 0.823. The tri-omics signature based on WSIs, CAFs, and lymph node status demonstrated the best predictive value with an AUC of 0.897.

CONCLUSION: The multi-omics signature based on WSIs, CAFs, and clinical characteristics showed excellent prediction ability in breast IDC patients, whose risk factors can also provide a valuable diagnostic reference for the clinical course.

RevDate: 2022-11-18
CmpDate: 2022-11-16

Haythorne E, Lloyd M, Walsby-Tickle J, et al (2022)

Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.

Nature communications, 13(1):6754.

Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.

RevDate: 2022-11-17
CmpDate: 2022-11-14

Willemsen N, Kotschi S, A Bartelt (2022)

Fire up the pyre: inosine thermogenic signaling for obesity therapy.

Signal transduction and targeted therapy, 7(1):375.

RevDate: 2022-11-10

Vos DY, Wijers M, Smit M, et al (2022)

Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins.

Arteriosclerosis, thrombosis, and vascular biology [Epub ahead of print].

BACKGROUND: The coiled-coil domain containing 22/coiled-coil domain containing 93/copper metabolism MURR1 domains (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to the cell surface of hepatocytes. Impaired functioning of hepatocytic CCC causes hypercholesterolemia in mice, dogs, and humans. Retriever, a protein complex consisting of subunits VPS26C, VPS35L, and VPS29, is associated with CCC, but its role in endosomal lipoprotein receptor transport is unclear. We here investigated the contribution of retriever to hepatocytic lipoprotein receptor recycling and plasma lipids regulation.

METHODS: Using somatic CRISPR/Cas9 gene editing, we generated liver-specific VPS35L or VPS26C-deficient mice. We determined total and surface levels of LDLR and LRP1 and plasma lipids. In addition, we studied the protein levels and composition of CCC and retriever.

RESULTS: Hepatocyte VPS35L deficiency reduced VPS26C levels but had minimal impact on CCC composition. VPS35L deletion decreased hepatocytic surface expression of LDLR and LRP1, accompanied by a 21% increase in plasma cholesterol levels. Hepatic VPS26C ablation affected neither levels of VPS35L and CCC subunits, nor plasma lipid concentrations. However, VPS26C deficiency increased hepatic LDLR protein levels by 2-fold, probably compensating for reduced LRP1 functioning, as we showed in VPS26C-deficient hepatoma cells. Upon PCSK9 (proprotein convertase subtilisin/kexin type 9)-mediated LDLR elimination, VPS26C ablation delayed postprandial triglyceride clearance and increased plasma TG levels by 26%.

CONCLUSIONS: Our study suggests that VPS35L is shared between retriever and CCC to facilitate LDLR and LRP1 transport from endosomes to the cell surface. Conversely, retriever subunit VPS26C selectively transports LRP1, but not LDLR, and thereby may control hepatic uptake of postprandial TG-rich lipoprotein remnants.

RevDate: 2022-11-12
CmpDate: 2022-11-10

Chen W, Wang G, G Zhang (2022)

Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.

Cancer biology & medicine, 19(10):1487-1495.

RevDate: 2022-11-17
CmpDate: 2022-11-08

Mekheal E, Kania BE, Kumari P, et al (2022)

Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.

The American journal of case reports, 23:e937370.

BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.

RevDate: 2022-10-30

Chen K, Chen X, Y Su (2022)

Is conservative treatment a good choice for pediatric intervertebral disc calcification in children?.

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society [Epub ahead of print].

PURPOSE: Paediatric intervertebral disc calcification (PIDC) is a rare disease, and its aetiology remains unknown. This study aimed to analyse the characteristics and clinical outcomes of patients with PIDC.

METHODS: After applying the exclusion and inclusion criteria, 159 children diagnosed with PIDC were analysed at our hospital between January 2010 and November 2020. Patients' demographic and clinical data were collected, such as sex, pain, duration time, physical examination, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and radiography, computed tomography, and magnetic resonance imaging findings. Patients were followed up for at least 6 months, and radiography or symptoms were evaluated. Fisher's exact test or χ[2]-test was used for statistical analyses.

RESULTS: One hundred and fifty-nine patients were ultimately followed up with for about 12.5 ± 5.8 months. There were 103 male and 56 female, with an average age of 6.08 ± 2.62 years (2 months to 12 years). A total of 109 patients had only one PIDC, 29 patients had two PIDCs, and 21 patients had multiple PIDCs. Thirty patients were found incidentally and were asymptomatic. A total of 106 patients had neck torticollis. Sixteen patients had IDC herniations, fifteen patients had posterior longitudinal ligament calcification, two patients had anterior longitudinal ligament calcification, and 17 patients had herniation of the vertebral canal. All patients underwent conservative treatment, and none underwent surgery. All patients' symptoms resolved after either collar fixation or neck traction.

CONCLUSION: PIDC can be treated conservatively, even when accompanied by herniation, longitudinal ligament calcification, or clinical neck symptoms.


RevDate: 2022-11-02
CmpDate: 2022-11-02

Gautam P, Feroz Z, Tiwari S, et al (2022)

Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.

Asian Pacific journal of cancer prevention : APJCP, 23(10):3481-3490 pii:90330.

BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.

RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.

CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.

RevDate: 2022-10-31
CmpDate: 2022-10-31

Al-Saoudi E, Christensen MMB, Nawroth P, et al (2022)

Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.

Frontiers in endocrinology, 13:891442.

AIMS/HYPOTHESIS: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).

METHODS: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity".

RESULTS: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing.

CONCLUSIONS/INTERPRETATIONS: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.

RevDate: 2022-10-28

Zhang H, Yuan J, Xiang Y, et al (2022)

Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma.

Journal of oncology, 2022:2099327.

The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.

RevDate: 2022-11-08
CmpDate: 2022-10-18

Blawski R, E Toska (2022)

A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.

Cancer research, 82(20):3668-3670.

Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.

RevDate: 2022-11-07
CmpDate: 2022-11-07

Sekar R, Motzler K, Kwon Y, et al (2022)

Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.

Cell metabolism, 34(11):1824-1842.e9.

During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.

RevDate: 2022-10-17
CmpDate: 2022-10-17

Zhao W, Wu T, Zhan J, et al (2022)

Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

Computational and mathematical methods in medicine, 2022:7153491.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.

METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.

RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.

CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.

RevDate: 2022-10-17

Chang YS, Chou YP, Chung CC, et al (2022)

Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes.

Cancers, 14(19):.

In Taiwan, a combination of hepatitis B and C infection, economic boom-related food and alcohol overconsumption, and Chinese medicine prescriptions has led to a high rate of hepatocellular carcinoma (HCC). However, the causative factors and underlying tumor biology for this unique HCC environment have not been identified. Wnt and Hippo signaling pathways play an important regulatory role in HCC development, and their functions are generally considered as positive and negative regulators of cell proliferation, respectively. In this study, we characterized the molecular features of HCC using a newly developed classification system based on the expression of the Wnt-Hippo signaling pathway-related genes. RNA sequencing (RNA-Seq) was performed on liver tumor tissues from 100 patients with liver cancer. RNA-Seq data for 272 previously characterized Wnt-Hippo signaling pathway-related genes were used for hierarchical clustering. We analyzed the data in terms of prognostic value, transcriptome features, immune infiltration, and clinical characteristics, and compared the resulting subclasses with previously published classifications. Four subclasses of HCC (HCCW1-4) were identified. Subclass HCCW1 displayed the highest PCDHB4 expression. Subclass HCCW2 displayed lower Edmondson-Steiner grades (I and II) and CTNNB1 mutation frequencies. Subclass HCCW3 was associated with a good prognosis, the highest PCDHGB7 expression, high CD8+ naïve T cells abundance, and relatively low TP53 mutation rates. Subclass HCCW4 was associated with a poor prognosis, the highest PCDHB2 and PCDHB6 expression, a relatively high abundance of Th1 cells, NKT and class-switched memory B cells, relatively low enrichment of cDC, iDC, and CD4+ memory T cells, and high Edmondson-Steiner grades (III and IV). We also identified Wnt-Hippo signaling pathway-related genes that may influence immune cell infiltration. We developed a panel of 272 Wnt-Hippo signaling pathway-related genes to classify HCC into four groups based on Taiwanese HCC and The Cancer Genome Atlas Liver Hepatocellular Carcinoma datasets. This novel molecular classification system may aid the treatment of HCC.

RevDate: 2022-12-06
CmpDate: 2022-10-17

Wong HY, Sheng Q, Hesterberg AB, et al (2022)

Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.

Nature communications, 13(1):6036.

Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.

RevDate: 2022-10-16
CmpDate: 2022-10-14

Singh N, Singh R, Decker B, et al (2022)

Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.

BMJ case reports, 15(10):.

A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.

RevDate: 2022-11-09
CmpDate: 2022-11-04

Maggi G, Di Meglio D, Vitale C, et al (2022)

The impact of executive dysfunctions on Theory of Mind abilities in Parkinson's disease.

Neuropsychologia, 176:108389.

Theory of Mind (ToM) is the ability to infer and reason about others' mental states, a process impaired by Parkinson's disease (PD). ToM performance in PD seems to be strongly related to executive functioning but the exact nature of this relationship is still unclear. We aim to investigate the direct impact of several executive dysfunctions on ToM deficits (Affective and Cognitive ToM) in PD patients. Sixty-eight PD patients underwent neuropsychological tests evaluating executive control such as inhibition, cognitive flexibility, processing speed or working memory and Cognitive and Affective ToM. We divided participants into two groups based on their performance on executive tests: PD patients with poor executive functioning (PD-EF-) and those with preserved executive functioning (PD-EF+). To explore the direct impact of executive subdomains on ToM abilities, two mediation models were executed in the whole sample. We found that PD patients with poor executive functioning reported poorer scores on Affective and Cognitive ToM tasks than PD patients with preserved executive functions, controlling for age and education. Moreover, parallel mediation models, conducted in the whole sample, indicated that performance on phonological fluency mediated the relationships between educational level and both Affective and Cognitive ToM, controlling the effect of other executive tests. These findings further support the idea that executive functions are crucial in ToM processes. Particularly, phonological fluency, whose execution requires both verbal abilities and cognitive flexibility, mediated ToM performance controlling the effect of other executive functions. The identification of neuropsychological processes underpinning ToM abilities might represent a plausible target for cognitive training to strengthen ToM abilities in PD.

RevDate: 2022-10-05
CmpDate: 2022-10-04

Saeed U, Piracha ZZ, Uppal SR, et al (2022)

SARS-CoV-2 induced hepatic injuries and liver complications.

Frontiers in cellular and infection microbiology, 12:726263.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.

DISCUSSION: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.

CONCLUSION: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.

RevDate: 2022-10-07
CmpDate: 2022-10-04

Mussa FM, Massawe HP, Bhalloo H, et al (2022)

Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.

PloS one, 17(9):e0275420.

INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression.

OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam.

METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant.

RESULTS: 333 participants were recruited. The overall good adherence (≥95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%).

In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.

RevDate: 2022-11-01
CmpDate: 2022-10-03

Silva FHS, Underwood A, Almeida CP, et al (2022)

Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.

Medical oncology (Northwood, London, England), 39(12):212.

BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.

RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.

CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.

RevDate: 2022-09-30
CmpDate: 2022-09-30

Alinezhadi M, Makvandi M, Kaydani GA, et al (2022)

Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.

Asian Pacific journal of cancer prevention : APJCP, 23(9):3201-3207 pii:90303.

BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.

MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.

RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54±16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.

CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.

RevDate: 2022-09-29

Wenger D, Kurumety S, ZB Aydi (2022)

A case report: invasive ductal carcinoma in mosaic Li-Fraumeni syndrome.

Journal of surgical case reports, 2022(9):rjac408.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant condition caused by pathogenic variants in the TP53 tumor suppressor gene and characterized by a high lifetime risk of various cancers with a very early age of onset. We are presenting a 41-year-old woman with right invasive ductal cancer and no family history of cancers, diagnosed with mosaic LFS confirmed with blood and skin punch biopsy samples. She was treated with neoadjuvant chemotherapy, mastectomy and sentinel node biopsy with completion axillary dissection. Adjuvant radiation was not recommended due to increased risk of secondary cancers. She also elected to undergo risk reducing contralateral mastectomy. Further research is warranted to determine the appropriate clinical management and surveillance strategies in patients with mosaic LFS as whether individuals with mosaic LFS have differing cancer risks in comparison to classic germline LFS is unknown.

RevDate: 2022-09-19
CmpDate: 2022-09-19

Walth-Hummel AA, Herzig S, M Rohm (2022)

Nuclear Receptors in Energy Metabolism.

Advances in experimental medicine and biology, 1390:61-82.

Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.

RevDate: 2022-09-09

Ryder JH, Van Schooneveld TC, Lyden E, et al (2022)

The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.

Infection control and hospital epidemiology pii:S0899823X22002094 [Epub ahead of print].

OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance.

DESIGN: Retrospective cohort study from January 2016 to December 2019.

SETTING: Academic quaternary-care referral center.

PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours.

METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score.

RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81).

CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.

RevDate: 2022-09-29
CmpDate: 2022-09-15

Pellegata NS, Berriel Diaz M, Rohm M, et al (2022)

Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.

Cancer metastasis reviews, 41(3):517-547.

Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.

RevDate: 2022-11-08

Malakzai HA, Haidary AM, Gulzar S, et al (2022)

Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.

Cancer management and research, 14:2569-2582.

PURPOSE: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development.

PATIENTS AND METHODS: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan.

RESULTS: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II.

CONCLUSION: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.

RevDate: 2022-08-30
CmpDate: 2022-08-29

Kmiecik A, Ratajczak-Wielgomas K, Grzegrzółka J, et al (2022)

Expression of NUCB2/NESF-1 in Breast Cancer Cells.

International journal of molecular sciences, 23(16):.

Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

RevDate: 2022-08-28

Molinaro J, DeVries P, Ha J, et al (2022)

New-onset hallucinations with amiodarone: a case report.

Annals of general psychiatry, 21(1):34.

BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.

CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12 years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11 years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3 days after the discontinuation of amiodarone.

CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.

RevDate: 2022-09-10
CmpDate: 2022-08-22

Kovalenko I, Roy P, Soni B, et al (2022)

Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.

The American journal of case reports, 23:e936665.

BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.

RevDate: 2022-08-31
CmpDate: 2022-08-31

Brecklinghaus T, Albrecht W, Duda J, et al (2022)

In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay.

Toxicology letters, 368:33-46.

The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.

RevDate: 2022-08-13

Fujita K, Okamura M, Imakita T, et al (2022)

Natural course of pulmonary hyalinizing granuloma over a decade.

Respiratory medicine case reports, 39:101715.

BACKGROUND: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.

CASE PRESENTATION: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.

CONCLUSIONS: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.

RevDate: 2022-11-08
CmpDate: 2022-10-18

Nardone A, Qiu X, Spisak S, et al (2022)

A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.

Cancer research, 82(20):3673-3686.

UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.

RevDate: 2022-08-13
CmpDate: 2022-08-11

Xu A, Chu X, Zhang S, et al (2022)

Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.

BMC cancer, 22(1):872.

BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.

METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).

RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram.

CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.

RevDate: 2022-10-11
CmpDate: 2022-09-30

Sorotos M, Paolini G, D'Orsi G, et al (2022)

Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.

Plastic and reconstructive surgery, 150:4S-12S.

BACKGROUND: Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences.

METHODS: From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant.

RESULTS: After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1).

CONCLUSIONS: Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements.

Risk, II.

RevDate: 2022-08-09
CmpDate: 2022-08-09

Yaltirik Bilgin E, Unal O, N Ciledag (2022)

Vasogenic Edema Pattern in Brain Metastasis.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 32(8):1020-1025.

OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.

STUDY DESIGN: Cross-sectional study.

PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.

METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.

RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC→1.95±0.66 vs. Other→2.48±0.52, Z=-2.301, p=0.021).

CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.

KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.

RevDate: 2022-08-01

Yang ZJ, Liu YX, Huang Y, et al (2022)

The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.

Cancer medicine [Epub ahead of print].

BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.

METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index ≥20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank χ[2] value.

RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease-free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.

RevDate: 2022-08-04
CmpDate: 2022-08-02

Oehler D, Spychala A, Gödecke A, et al (2022)

Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.

BMC biology, 20(1):169.

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.

RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.

CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.

RevDate: 2022-08-08
CmpDate: 2022-08-02

Lee S, HU Osmanbeyoglu (2022)

Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.

Breast cancer research : BCR, 24(1):54.

BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.

METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.

RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.

CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.

RevDate: 2022-07-29

Suzuki Y, Hoshi K, Tominaga K, et al (2023)

A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.

DEN open, 3(1):e144.

A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.

RevDate: 2022-11-07
CmpDate: 2022-10-11

Billeter AT, Scheurlen KM, Israel B, et al (2022)

Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients: A Prospective Cohort Study.

Annals of surgery, 276(5):814-821.

OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.

METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.

RESULTS: MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.

CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

RevDate: 2022-10-09
CmpDate: 2022-07-25

Khanam R, Islam S, Rahman S, et al (2022)

Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.

Journal of global health, 12:05030.

BACKGROUND: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.

METHODS: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.

RESULTS: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16,  95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years.

CONCLUSIONS: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.

RevDate: 2022-07-26
CmpDate: 2022-07-25

Zhu S, Zhao J, Nie L, et al (2022)

Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).

BMC medicine, 20(1):237.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.

METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.

RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.

CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.

RevDate: 2022-07-21

Bhatia JK, Chaudhary T, Boruah D, et al (2022)

Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.

Medical journal, Armed Forces India, 78(3):345-354.

BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.

METHODS: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated.

RESULTS: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels.

CONCLUSIONS: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.

RevDate: 2022-07-21

Somashekhar SP, Jaiswal R, Kumar R, et al (2022)

An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.

European journal of breast health, 18(3):271-278.

OBJECTIVE: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.

MATERIALS AND METHODS: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category.

RESULTS: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.

CONCLUSION: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.

RevDate: 2022-11-08
CmpDate: 2022-09-19

Tokura M, Nakayama J, Prieto-Vila M, et al (2022)

Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.

Cancer research, 82(18):3236-3248.

UNLABELLED: Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC.

SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.

RevDate: 2022-07-19
CmpDate: 2022-07-19

Zhang WT, Zhu GL, Xu WQ, et al (2022)

Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.

Diagnostic pathology, 17(1):61.

PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.

METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.

RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.

CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.

RevDate: 2022-08-27

Syamsu SA, Setiady R, Smaradania N, et al (2022)

Synchronous breast cancer and non-Hodgkin lymphoma: A case report.

International journal of surgery case reports, 97:107398 [Epub ahead of print].

INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.

PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.

CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.

CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.

RevDate: 2022-09-08
CmpDate: 2022-09-08

Ciudad P, Escandón JM, Manrique OJ, et al (2022)

Lymphedema prevention and immediate breast reconstruction with simultaneous gastroepiploic vascularized lymph node transfer and deep inferior epigastric perforator flap: A case report.

Microsurgery, 42(6):617-621.

Breast cancer-related lymphedema following axillary lymph node dissection (ALND) has been documented in 6%-55% of patients, mostly occurring within the next 3 years after radiation or surgery. We present a case of a 53-year-old patient with hormone positive, stage IB, left breast invasive ductal carcinoma treated with immediate lymphatic and microvascular breast reconstruction (MBR) using vascularized lymph node transfer (VLNT) for lymphedema prevention. A deep inferior epigastric perforator (DIEP) flap (18.3 × 11.2-cm) and simultaneous prophylactic gastroepiploic-VLNT (7 × 3-cm), orthotopically inset in the axilla, were used for reconstruction following mastectomy and radical ALND. The procedure was uneventful. The patient did not display increased postoperative arm circumferences. ICG lymphography did not show any changes at 2- and 3-years after surgery. Preventive lymphatic reconstruction with GE-VLNT and immediate MBR using the DIEP flap offers a new possibility for the primary prevention of lymphedema and simultaneous immediate autologous breast reconstruction without the risk of iatrogenic lymphedema. Further studies will be directed to unveil the external validity of these findings and the risk reduction rate of this approach.

RevDate: 2022-08-01
CmpDate: 2022-07-12

Chang C, Zhu J, Li H, et al (2022)

Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.

BMC pediatrics, 22(1):400.

BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).

CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.

CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.

RevDate: 2022-10-25
CmpDate: 2022-10-25

Rakshit S, Sunny JS, George M, et al (2022)

T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.

Journal of cancer research and clinical oncology, 148(12):3421-3436.

PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.

METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.

RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.

CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.

RevDate: 2022-07-16
CmpDate: 2022-06-28

Hardeman AA, Han YJ, Grushko TA, et al (2022)

Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.

PloS one, 17(6):e0268693.

Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.

RevDate: 2022-07-17
CmpDate: 2022-06-28

Weis S, Hagel S, Palm J, et al (2022)

Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.

JAMA network open, 5(6):e2218515.

IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.

OBJECTIVES: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.

This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).

INTERVENTIONS: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.

MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality.

RESULTS: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).

CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.

TRIAL REGISTRATION: drks.de Identifier: DRKS00010135.

RevDate: 2022-07-16
CmpDate: 2022-06-27

Ortega MA, Fraile-Martinez O, García-Montero C, et al (2022)

Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.

Medicina (Kaunas, Lithuania), 58(6):.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

RevDate: 2022-11-15
CmpDate: 2022-11-08

Clawson A, Zahir SF, Stewart S, et al (2022)

Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in Queensland.

Infection, disease & health, 27(4):219-226.

BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI).

AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI.

METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection.

RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p = 0.03). Age, gender, and catheter reinsertion were not associated with UTI development.

CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.

RevDate: 2022-11-15
CmpDate: 2022-09-28

Icht M, Bergerzon-Bitton O, BM Ben-David (2022)

Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.

International journal of language & communication disorders, 57(5):1023-1049.

'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.

RevDate: 2022-07-16
CmpDate: 2022-06-20

Choi JDW, Hughes TMD, Marx G, et al (2022)

The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.

The breast journal, 2022:1199245.

INTRODUCTION: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.

METHODS: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).

CONCLUSION: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

RevDate: 2022-07-29
CmpDate: 2022-06-15

Rebbeck CA, Xian J, Bornelöv S, et al (2022)

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.

Nature communications, 13(1):3399.

Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

RevDate: 2022-07-06
CmpDate: 2022-07-06

Agostinetto E, Nader-Marta G, Paesmans M, et al (2022)

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.

Future oncology (London, England), 18(22):2383-2392.

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

RevDate: 2022-07-16
CmpDate: 2022-06-14

Silva DJ, Miranda G, A Mesquita (2022)

Clinical relevance of receptor conversion in metastatic breast cancer: Case report.

Medicine, 101(23):e29136.

INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.

PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.

DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.

INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated.

OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.

CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.

RevDate: 2022-06-30
CmpDate: 2022-06-30

Zhang Y, Luo X, Chen M, et al (2022)

Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.

Breast cancer research and treatment, 194(2):279-295.

PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.

METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.

RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67 > 20% tumors (P < 0.05). P-ILCs were subdivided into ER+ (63.1%), HER2+ (21.1%) and TN (15.8%). ER+ P-ILCs were mainly showed trabecular and solid growth patterns. Apocrine and solid features were more strongly associated with HER2+ P-ILCs and TN-P-ILCs, respectively. The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had worse prognosis than the same subtypes in the IDC group, while there was no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC had the worst prognosis. Bone was the most common metastatic site in ER+ P-ILCs and TN-P-ILCs. HER2+ P-ILCs tended to metastasize to the brain and liver. DFS of HER2+ P-ILCs and TN-P-ILCs were worse than that of ER+ P-ILCs. Lacking lobular carcinoma in situ and sTILs ≤ 10% were associated with worse survival of ER+ P-ILCs and TN-P-ILCs, respectively. For HER2+ P-ILCs, Ki-67 > 20% and sTILs ≤ 10% were significant factors for lower DFS.

CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

RJR Picks from Around the Web (updated 11 MAY 2018 )