Fang Ren

CUDC-907 exhibits potent antitumor effects against ovarian cancer through multiple in vivo and in vitro mechanisms

CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo. Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo. Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest. Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.

Single-cell transcriptome profiles the heterogeneity of tumor cells and microenvironments for different pathological endometrial cancer and identifies specific sensitive drugs

AbstractEndometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8+ Tcyto and NK cells were prominent in normal endometrium, whereas CD4+ Treg, CD4+ Tex, and CD8+ Tex cells dominated the tumors. CXCL3+ macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2+ inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2+ iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.

The Global, Regional, and National Burdens of Cervical Cancer Attributable to Smoking From 1990 to 2019: Population-Based Study

Background Cervical cancer is the fourth most common cause of cancer death in women worldwide. Smoking is one of the risk factors for cervical cancer. Understanding the global distribution of the disease burden of cervical cancer attributable to smoking and related changes is of clear significance for the prevention and control of cervical cancer in key populations and for tobacco control. As far as we know, research on the burden of cervical cancer attributable to smoking is lacking. Objective We estimated the disease burden and mortality of cervical cancer attributable to smoking and related trends over time at the global, regional, and national levels. Methods Data were obtained from the Global Burden of Disease study website. Age-standardized rates were used to facilitate comparisons of mortality and disability-adjusted life years (DALYs) at different levels. The estimated annual percentage change (EAPC) was used to assess trends in the age-standardized mortality rate (ASMR) and the age-standardized DALY rate (ASDR). A Pearson correlation analysis was used to evaluate correlations between the sociodemographic index and the age-standardized rates. Results In 2019, there were 30,136.65 (95% uncertainty interval [UI]: 14,945.09-49,639.87) cervical cancer–related deaths and 893,735.25 (95% UI 469,201.51-1,440,050.85) cervical cancer–related DALYs attributable to smoking. From 1990 to 2019, the global burden of cervical cancer attributable to smoking showed a decreasing trend around the world; the EAPCs for ASMR and ASDR were –2.11 (95% CI –2.16 to –2.06) and –2.22 (95% CI –2.26 to –2.18), respectively. In terms of age characteristics, in 2019, an upward trend was observed for age in the mortality of cervical cancer attributable to smoking. Analysis of the trend in DALYs with age revealed an initially increasing and then decreasing trend. From 1990 to 2019, the burden of disease in different age groups showed a downward trend. Among 204 countries, 180 countries showed downward trends, 10 countries showed upward trends, and the burden was stable in 14 countries. The Pearson correlation analysis revealed a significant negative correlation between sociodemographic index and the age-standardized rates of cervical cancer attributable to smoking (ρ=–0.228, P<.001 for ASMR and ρ=–0.223, P<.001 for ASDR). Conclusions An increase over time in the absolute number of cervical cancer deaths and DALYs attributable to smoking and a decrease over time in the ASMR and ASDR for cervical cancer attributable to smoking were observed in the overall population, and differences in these variables were also observed between countries and regions. More attention should be paid to cervical cancer prevention and screening in women who smoke, especially in low- and middle-income countries.