Min Luo

microRNA-671-5p reduces tumorigenicity of ovarian cancer via suppressing HDAC5 and HIF-1α expression

microRNA (miR)-based therapeutic reference has been established and expanded in the treatment of cancers. For this reason, we explored how miR-671-5p regulated tumorigenicity of ovarian cancer (OC) through regulating histone deacetylase 5 (HDAC5) and hypoxia-inducible factor-1α (HIF-1α). miR-671-5p, HDAC5 and HIF-1α expression levels were determined in OC clinical tissues. The OC cell line H8910 was screened and transfected with the vectors that altered miR-671-5p, HDAC5 and HIF-1α levels. Finally, the proliferation, migration, invasion and apoptosis of the transfected H8910 cells were determined and the role of miR-671-5p and HDAC5 in vivo tumor growth was further discussed. Low expression miR-671-5p and high expression HDAC5 and HIF-1α levels were tested in OC tissues. Up-regulating miR-671-5p or down-regulating HDAC5 or HIF-1α suppressed proliferation, migration, invasion and augmented apoptosis of H8910 cells while silenced miR-671-5p or enhanced HDAC5 caused the opposite consequences. Overexpression of HDAC5 reduced while depletion of HDAC5 enhanced the influence of up-regulated miR-671-5p on OC cell growth. In animal models, suppressing miR-671-5p or promoting HDAC5 encouraged OC tumor growth. A summary delineates that miR-671-5p reduces tumorigenicity of OC via suppressing HDAC5 and HIF-1α expression levels.

Clinical efficacy analysis of chemotherapy of isolated neck lymphatic metastasis in advanced epithelial ovarian cancer

The aim of this study was to retrospectively investigate the efficacy of chemotherapy for neck lymph node metastasis (NLNM) by determining the characteristics and survival of patients with isolated NLNMs metastases from epithelial ovarian carcinoma (EOC) at stage IV of the Federation of Gynecology and Obstetrics (FIGO). The clinicopathological characteristics and survival outcome of 24 cases with stage IV FIGO EOC with isolated NLNM were retrospectively analyzed between December 1, 2014, and November 30, 2021. Among the 24 patients, 2 (8.3%) underwent primary debulking surgery (PDS), 21 (87.5%) received neoadjuvant chemotherapy(NACT) followed by interval debulking surgery (IDS), and 1 (4.2%) received chemotherapy alone. Additionally, 13 (54.2%) cases achieved abdominal R0 debulking, while 11(45.8%) cases achieved R1/R2 debulking. The chemotherapy response of NLNMs included complete response (8/24, 33.3%), partial response (15/24,62.5%), or stable disease (1/24,41.7%). None of the patients received resection or radiotherapy of NLNMs. Recurrence was observed in 15 (62.5%) patients, with only 2 experiencing recurrence of NLNMs. The median progression-free survival (PFS) and overall survival (OS) were 35 months and 48 months, respectively. R0 debulking led to a significantly longer PFS (not reached) and OS (57 months) compared to non-R0 debulking (PFS: 10 months, P = 0.001; OS: 22 months, P = 0.001). Interestingly, patients with EOC with lymphatic recurrence had better OS ( 57 months) than did those with abdominal or distant recurrence (OS: 29 months; P = 0.012). Chemotherapy is an effective treatment for neck lymph nodes metastasis, and a favorable response to chemotherapy could eliminate the necessity for NLNM resection or radiotherapy. Effective control of abdominal disease with surgery may be a critical factor in managing FIGO stage IV EOC patients with isolated NLMNs.

SB225002 Enhances Radiosensitivity in Cervical Cancer via Direct Neutrophil Inhibition and Tumor Cell Suppression.

Radiotherapy resistance is a major contributor to therapeutic failure in cervical cancer, largely due to the immunosuppressive tumor microenvironment (TME). Increasing clinical and experimental evidence underscores the role of neutrophils infiltration in reducing the efficacy of radiation therapy. Additionally, the CXCR2/CXCL signaling axis has been identified as a key regulator of neutrophils recruitment. Our study demonstrates that radiotherapy significantly enhances neutrophils infiltration by activating CXCR2-CXCL signaling and drives their polarization toward a pro-tumor N2-like phenotype through TGF-β signaling in cervical cancer. Further investigation revealed that CXCR2 antagonist SB225002 exerts a synergistic effect with radiotherapy and concurrent chemoradiotherapy in cervical cancer, primarily via inhibiting neutrophils infiltration and alleviating the immunosuppressive TME. Meanwhile, SB225002 exerts direct antitumor activity and enhances the radiosensitivity of cervical cancer cells by facilitating DNA double-strand breaks, promoting G2/M phase cell cycle arrest, and inducing apoptosis. In summary, our findings highlight neutrophils inhibition via CXCR2 antagonist as a promising therapeutic strategy to enhance cervical cancer responsiveness to radiotherapy.