Discover. Oncology最新文献

Background: A thorough investigation into the clinicopathologic features and long-term prognosis of early-onset gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is lacking. This study leverages the Surveillance, Epidemiology, and End Results (SEER) database to comprehensively analyze these aspects, addressing this critical knowledge gap.

Methods: Patients diagnosed with GEP-NETs between 2010 and 2020 were categorized into early-onset (≤ 50 years) and late-onset (> 50 years) groups. Clinicopathological features were compared, and propensity score matching (PSM) was applied to mitigate confounding. Kaplan-Meier curves and Cox regression analysis were utilized to evaluate overall survival (OS) and cancer-specific survival (CSS).

Results: Among 35,342 patients (9,968 early-onset; 25,374 late-onset), both groups exhibited rising annual incidence. Early-onset GEP-NETs were more frequently located in the colorectum (66.8% vs. 40.0%) and had higher surgical rates (86.1% vs. 76.1%). They demonstrated superior OS and CSS compared to late-onset counterparts (P < 0.001), confirmed by 1:1 PSM. Lymph node metastasis was lower in early-onset GEP-NETs overall (11.9% vs. 19.7%), but paradoxically higher in small intestine subsets (53.1% vs. 46.9%). Distant metastasis rates were lower in early-onset tumors (5.5% vs. 9.9%), particularly in colorectum (1.2% vs. 3.2%). Predictors of lymph node metastasis in early-onset cases included race, marital status, tumor grade, primary site, T stage, and M stage; predictors of distant metastasis encompassed tumor grade, primary site, T stage, and N stage. Five-year OS and CSS rates for early-onset GEP-NETs were 95.0% and 97.4%, respectively. Multivariate analysis identified marital status, tumor grade, primary site, NM stage, surgery, and chemotherapy as independent OS predictors; tumor grade, primary site, NM stage, surgery, and chemotherapy independently predicted CSS.

Conclusions: Early-onset GEP-NETs exhibit favorable survival and reduced metastasis rates relative to late-onset tumors, underscoring distinct clinical outcomes and warranting tailored management strategies.

Alterations in the vaginal microbiota contribute to the pathogenesis of cervical neoplasia. However, the distinctions in microbiota changes related to different human papillomavirus (HPV) subtypes, as well as the variation in gut microbiota, have not been fully explored. In this research, we endeavored to explore the shifts in the vaginal and intestinal microbiota in correlation with the advancement of cervical neoplasia and HPV infection. A total of 578 vaginal and intestinal cross-sectional specimens were collected from 348 subjects and subjected to 16 S rRNA sequencing. Statistical analyses were performed using R language, and Student's t-test was employed to assess the significance of differences. Both within and between, sample diversity of the vaginal and intestinal microbiota exhibited substantial alterations across cervical intraepithelial neoplasia (CIN) stages and cervical carcinoma. The vaginal genera Lactobacillus, Enterococcus, Peptoniphilus, Atobium, Anerococcus, and Veillonella were associated with different CIN stages and cervical cancer type, whereas Allisonella, Lachnospiracae, Lactobacillus, Staphylococcus, and Sellimonas were associated with varying HPV types. A Random Forest-driven classifier highlighted the predictive potential of differential bacteria in cervical neoplasia and HPV infection, with intestinal bacteria showing higher predictive accuracy in certain instances. Specifically, the accuracy of differentiating CIN I from CIN III was superior for the intestinal bacterial model compared to the vaginal bacterial model (85.52% vs. 83.33%). The model also demonstrated high accuracy in predicting HPV infection, particularly in distinguishing HPV-16 from HPV-18 and HPV-58, with AUC values of 81.61% and 83.07%, respectively, compared to less than 70% for vaginal bacteria. Our findings reveal the intricate interplay among cervical neoplasia, HPV infection, and microbiota, with potential diagnostic and therapeutic implications.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synthesizes current preclinical and clinical advancements in targeting CSCs via DDR inhibitors, including PARP, ATR, ATM, and DNA-PKcs inhibitors, as well as emerging SL targets. Furthermore, advanced therapeutic modalities such as small molecule inhibitors, antibody-drug conjugates, CAR cell therapies, glycan-based approaches, and nanoparticle delivery systems tailored for CSC elimination are discussed. Finally, persistent challenges, including CSC heterogeneity, the immunosuppressive tumor microenvironment, on-target/off-tumor toxicities, and translational hurdles, are addressed, emphasizing the transformative potential of integrated diagnostic platforms leveraging AI, liquid biopsy, multi-omics, and single-cell profiling to usher in a new era of precision oncology for durable cancer control.