Sex differences in the development of the normal heart and the prevalence of cardiomyopathies have been reported. The molecular basis of these differences remains unclear. Sex differences in the human heart might be related to patterns of gene expression. Recent studies have shown that sex specific differences in gene expression in tissues including the brain, kidney, skeletal muscle, and liver. Similar data is limited for the heart. Herein we address this issue by analyzing donor and post-mortem adult human heart samples originating from 46 control individuals to study whole-genome gene expression in the human left ventricle. Using data from the genotype tissue expression (GTEx) project, we compared the transcriptome expression profiles of male and female hearts. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. The majority of differentially expressed autosomal genes were those involved in the regulation of inflammation, which has been found to be an important contributor to left ventricular remodeling. Specifically, genes on autosomal chromosomes encoding chemokines with inflammatory functions (e.g. CCL4, CX3CL1, TNFAIP3) and a gene that regulates adhesion of immune cells to the endothelium (e.g., VCAM1) were identified with sex-specific expression levels. This study underlines the relevance of sex as an important modifier of cardiac gene expression. These results have important implications in the understanding of the differences in the physiology of the male and female heart transcriptome and how they may lead to different sex specific difference in human cardiac health and its control.
Stem cell therapy holds great promise for the repair and regeneration of damaged myocardium. Disappointing results from recent large-scale randomized trials using adult stem cells, however, have led some to question the efficacy of this new therapeutic. Because most clinical stem cell trials have not incorporated molecular imaging to track cell fate, it may be premature to abandon this approach. Herein, we will review how multimodality imaging can be incorporated into cardiac regenerative therapy to facilitate the translation of stem cell therapy.
Introduction/Objective Adnexal carcinosarcomas (MMMTs) are rare tumors (1–4% ovarian carcinomas) with worse prognosis than high grade serous carcinomas (HGS) at similar stage. They typically present at age 64–66, often with peritoneal involvement. They are biphasic tumors with stem cells undergoing divergent epithelial and sarcomatous differentiation. The epithelial component is usually HGS and drives progression of the tumor. The mesenchymal component can be homologous with high-grade spindled cells or heterologous with malignant cartilage, bone, muscle or fat. Metastases are mostly epithelial; metastatic sarcomatous components are unusual. We reviewed our single- institutional experience of adnexal MMMTs. Methods We reviewed our pathology database (2001–2019) to find all cases of adnexal MMMTs. We reviewed their histological features, histology of metastases and clinical outcomes. Results Our series consisted of 12 cases. Patients aged 41–82 years. The primary tumor sites were ovary (6 cases, 50%), fallopian tube (4, 33%), 1 each (8%) in paratubal region and infundibular ligament. Fallopian tube was involved in 8/12 cases (4 cases as primary MMMT, 4 cases with STIC or HGS). Epithelial component was serous (75%), endometrioid (17%) and mucinous (8%). Sarcomatous component was homologous in 5 cases (41%), heterologous in 7 cases: cartilage (33%), cartilage/muscle (8%), muscle (8%), cartilage/muscle/fat (8%). 3 cases were FIGO stage I, 9 had peritoneal metastases (8 stage III, 1 stage IV). Six cases had metastatic HGS; 3 had metastatic HGS with sarcomatous component, 2 with heterologous elements. Aberrant p53 pattern was seen in 7/12 and TP53 mutation was noted in 6/12. Ten patients received cytoreductive surgery and chemotherapy. 7 patients are alive with progression free survival ranging 6–59 months, 2 survived for 25 and 29 months, 3 are lost to follow-up. Conclusion Metastatic sarcomatous heterologous elements are rare in uterine carcinosarcomas and may suggest adnexal origin. They may correlate with worse outcome; in our series, 1/2 died after 29 months, the other was lost to follow-up. Fallopian tube involvement (75% of our cases) is of significance as identical TP53 mutation has been identified in a case report of ovarian carcinosarcoma with fallopian tube STIC. Also, our 2 cases of infundibular ligament and paratubal region may indicate seeding from fallopian tube. Further studies are needed to confirm the correlation.
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