Purpose of review Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic–pituitary–gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility. Recent findings Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic–pituitary–adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology. Summary Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure. Epigenetic changes include DNA methylation, histone modifications, and microRNA (miRNA) regulation. It is through the study of epigenetics that diagnostic methods for early detection and novel therapeutic strategies may be established for testicular cancer. We performed a comprehensive review of the English medical literature in PubMed by combining search terms including DNA methylation, histone modifications, microRNA (miRNA) regulation, epigenetics, and testicular cancer. DNA methylation is the most extensively studied epigenetic modification. It consists of the addition of a methyl group to nucleotide bases. It has been reported that SGCT contain reduced levels of DNA methylation compared to NSGCT. MiRNAs are small non-coding RNAs that regulate posttranscriptional gene expression. It has been suggested that miRNAs may play a role in the pathogenesis of GCT. Specific expression patterns have been displayed by various miRNAs in patients with GCT. Histones are proteins intertwined with coiled, double-stranded genomic DNA that form a structure known as a nucleosome. The most widely studied histone modifications include acetylation, methylation, and phosphorylation. Methylation of histone proteins has been found in all types of NSGCT. Epigenetics may offer an additional and effective tool in establishing a diagnosis of GCT of the testes, including prognostic information and perhaps enabling targeted treatment in patients with testicular GCT.
4588 Background: Sarcomatoid urothelial carcinoma (SUC), a rare bladder cancer variant, has both epithelial and mesenchymal differentiation along with frequent TERT C228T promoter mutations and has poorer prognosis. In this study, we compared survival outcomes of SUC with classic urothelial carcinoma (CUC) in patients with T2-T4, N0-N1 bladder cancer after definitive therapy. Methods: All cases meeting our inclusion criteria for SUC and CUC during 2004-2019 were identified from National Cancer Database. Sociodemographic and clinicopathological characteristics were analyzed via descriptive and comparative statistics. Propensity-score matching was performed to adjust for baseline differences between SUC and CUC. Overall survival (OS) was compared using Cox proportional-hazards modelling and visualized through Kaplan-Meier curves. Results: 30072 cases of CUC and 480 of SUC were identified. Propensity-score matching resulted in N = 478 patients in both groups. Matched cohorts had no baseline differences in age, sex, race, comorbidities, insurance status, income, distance to hospital, hospital location, rural versus urban residence, histological grade, and proportion getting regional lymph node surgery. Overall, there were 675 males and 281 females, 435 underwent surgery (Sx), and 521 surgery plus chemotherapy (Sx+Cx). For SUC, median survival with Sx vs Sx+Cx was 29.5 months (95%CI 20.0-50.6) vs 43.1 months (95%CI 25.3-64.4) respectively. For CUC, median survival was 56.1 (95%CI 53.7-58.6) vs 78.0 (95%CI 75.1-81.1) months with Sx vs Sx+Cx respectively. Conclusions: SUC has poorer prognosis than CUC. Perioperative chemotherapy along with surgery was associated with improved survival outcomes compared to surgery alone in patients with SUC. Further studies investigating novel immunotherapy agents are warranted to improve oncologic outcomes. [Table: see text]
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