The effect of cuproptosis-relevant genes on the immune infiltration and metabolism of gynecological oncology by multiply analysis and experiments validation.

Gynecological cancers are a leading cause of mortality for women, including ovarian cancer (OC), cervical squamous cell carcinoma (CESC), and uterine corpus endometrial carcinoma (UCEC). Nevertheless, these gynecological cancer types have not elucidated the role of cuproptosis and the correlated tumor microenvironment (TME) infiltration features. CRGs had important potential molecular functions and prognostic significance in gynecological cancers, especially in UCEC. Hub CRG, FDX1, was correlated with the CD8+ T cell immune infiltration in UCEC and CESC. FDX1 OE could significantly repress the proliferation ability in UCEC cells by MTT, EdU, and clone formation. High levels of FDX1 could repress ATP and lactic acid but enhance ROS and glucose levels by metabolism assay. The xenograft tumor model indicated that FDX1 OE significantly inhibited the growth of UCEC and attenuated the PCNA, HK2, PKM2, and Ki-67 expression. These CRGs are significant roles that could be potential markers and treatment targets to optimize the TME immune cell infiltration features for gynecological cancer types. FDX1 is a hub CRGs in UCEC to promote immune infiltration and attenuate proliferation and metabolism.

Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and survival of in vitro cultured epithelial ovarian cancer cells.

BACKGROUND: Preclinical evaluation of the anti-neoplastic activity of antisense oligonucleotide (AS) suppression of human insulin-like growth factor I receptor (IGF-IR) in human epithelial ovarian cancer (EOC). METHODS: Ovarian cancer cells from 36 patients with EOC were investigated under serum-free tissue culture conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were evaluated by immunohistochemistry and Western blotting. Cancer cell growth and proliferation assays were performed in triplicates using MTT assay. Apoptosis was evaluated by TUNNEL assay. RESULTS: All ovarian cancer tissue samples tested produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited growth and proliferation and decreased clonogenicity in soft agar assay. AS treatment was demonstrated to inhibit the expression of IGF-1R and decrease the concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer cell lines to cisplatin in vitro through the PI3K pathway. CONCLUSIONS: IGF-IR enhances the proliferation and tumorigenicity of human ovarian cancer cells and inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian cancer.

Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma.

PURPOSE: The optimal treatment of women with advanced adenocarcinoma of uterine cervix is still undefined. We compared concurrent chemoradiation (CCRT) and adjuvant cisplatin-based chemotherapy with CCRT alone for advanced cervical adenocarcinoma in a randomized trial at the Hunan Provincial Tumor Hospital in China. METHODS: From 1998 to 2007, 880 patients with clinical FIGO stages IIB-IVA cervical adenocarcinoma were randomized to receive either CCRT or chemoradiation with one cycle of neo-adjuvant chemotherapy with Paclitaxel (135 mg/m(2))+Cisplatin (75 mg/m(2)) before receiving radiation and two cycles of consolidation chemotherapy with the same drugs after radiotherapy in 3-week intervals. The disease control and survival rates were calculated using the Kaplan-Meier method. RESULTS: All patients completed the treatment plan. 340 patients have relapsed, with a median follow-up duration of 60 months. Patients who received chemoradiation with adjuvant chemotherapy showed a significantly longer disease-free (P<.05), cumulative survival (P<.05) and long-term local tumor control (P<.05). Patients who received CCRT alone had significantly more distant metastasis and pelvic failure than those who received chemoradiation with adjuvant chemotherapy (P<.05). CONCLUSION: Incorporating neo-adjuvant and consolidation chemotherapy with Paclitaxel and Cisplatin into concomitant chemoradiation is highly effective, safe and may be a very promising treatment protocol for advanced cervical adenocarcinoma.