RPL35A drives ovarian cancer progression by promoting the binding of YY1 to CTCF promoter.

Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.

Analysis of prognostic value of lactate metabolism-related genes in ovarian cancer based on bioinformatics.

BACKGROUND: Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis. RESULTS: Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples. CONCLUSION: A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy.

The immunologic aspects in advanced ovarian cancer patients treated with paclitaxel and carboplatin chemotherapy.

Till now, little is known about the effects of chemotherapy on the immunity of cancer patients and the ideal timing ("window" period) for immunotherapy combined with chemotherapy. In this study, we addressed the immunogenicity of apoptotic ovarian cancer cells induced by paclitaxel and carboplatin, the immunologic aspects in ovarian cancer patients under chemotherapy, and the CTL response when CD8(+) T cells were stimulated with tumor antigen in the "window" period. The immunogenicity of apoptotic ovarian cancer cells was detected first. Then, blood samples from each ovarian cancer patient were obtained before (S(0)) and at days 5-7 (S(1)), days 12-14 (S(2)) and days 25-28 (S(3)) after chemotherapy. The proportions of immunocyte subsets and the function of NK cells were studied. We found that apoptotic ovarian cancer cells elicited a powerful CTL response with antitumor activity in vitro. The proportions of CD3(+) T cells, CD4(+) T cells and the ratio of CD4(+) to CD8(+) cells did not change significantly on S(1), S(2) and S(3), compared to S(0), whereas the percentage of Treg cells decreased remarkably on S(2). The proportions of Th1, Tc1, CD45RO memory T, NKT cells and the ratio of Tc1 to Tc2 cells increased significantly on S(2). IFN-gamma secreting CD8(+) T cells also increased remarkably on S(2), especially when CD8(+) T cells were stimulated with autologous tumor antigen. From our point of view, chemotherapy induces temporary immune reconstitution and augments anti-tumor immune response. It is probable that the "window" period of days 12-14 after chemotherapy provides the best opportunity for immunotherapy.

1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function.

BACKGROUND: The indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) is currently being used in clinical trials in patients with relapsed or refractory solid tumors by inhibiting tumor immune escape. A greater understanding of IDO activity is required to begin to understand the molecular mechanism by which drugs work. This study was conducted to investigate of the clinical significance of 1-methyl-tryptophan (1-MT) in treating carboplatin-resistant (CBP-resistant) ovarian cancer and its mechanism of action. METHODS: Using a medium dose, intermittent treatment method, a clinically relevant CBP-resistant human ovarian cancer cell line (SKOV3/CBP) was established. SKOV3/CBP cells were treated with normal serum (control) or 1-MT (0.25 ng/mL) for 4 h (SKOV3/CBP + 1-MT). Cell proliferation, invasion and IDO expression in SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by MTT assays, Matrigel invasion chambers assays and ELISAs, respectively. The half-maximal inhibitory concentration (IC50) and resistance index (RI) were also calculated. The killing ability of the NK cells and CD8+ T cells co-cultured with SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by LDH activity assays and the INF-γcounting method. RESULTS: The SKOV3/CBP cell line displayed an increased IC50 compared to the SKOV3 cell line (P < 0.05) under CBP treatment. Treatment with 1-MT significantly decreased the IC50 and RI of SKOV3/CBP cells. Furthermore, 1-MT treatment not only reduced the invasion ability, but also suppressed IDO expression in the drug-resistant SKOV3/CBP + 1-MT cell line as compared to the SKOV3/CBP cell line. Furthermore, 1-MT enhanced the killing ability of NK cells and the amount of INF-γsecreted from CD8+ T cells which were co-cultured with the SKOV3/CBP cell line. CONCLUSION: Our data suggested that 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulation of IDO expression which leads to re-activation of immune cell function. We provide a conceptual foundation for the clinical development of 1-MT as an anti-tumor immunomodulator for chemotherapy resistant ovarian cancer patients.

Human papillomavirus vaccination behaviors among gynecological outpatients based on extended unified theory of acceptance and use of technology / 预防医学

Objective@#To investigate the factors affecting human papillomavirus (HPV) vaccination behaviors among gynecological outpatients based on extended unified theory of acceptance and use of technology (UTAUT2), so as to provide insights into the development of HPV vaccination behavioral interventions.@*Methods@# Patients at ages of 45 years and younger that were admitted to the outpatient department of gynecological of Shanxi Provincial People's Hospital from October 2021 to August 2022 were recruited, and the factors affecting HPV vaccination behaviors were identified using UTAUT2.@*Results@#A total of 431 female outpatients were enrolled, including 163 patients at ages of 36 to 45 years (37.82%), 272 cases with an educational level of college degree and above (63.11%) and 253 patients with per capita monthly household income of more than 3 000 Yuan (58.70%). The coverage of HPV vaccination was 24.36%, and the main cause of non-vaccination was difficulty in high-valent HPV vaccine appointment. Price value, social impact and efficacy expectation posed a positive impact on HPV vaccination behaviors via intention of vaccination (β=0.11, 0.08, 0.07, all P<0.05) and intention of vaccination and effort expectancy (β=0.10, 0.07, 0.06, all P<0.05), and effort expectancy played a mediating effect between intention of vaccination and vaccination behaviors (β=0.28, P<0.05).@*Conclusion@#Efficacy expectation, social impact, price value, intention of vaccination and effort expectancy may positively affect HPV vaccination behaviors.

[Immune reconstitution in advanced ovarian cancer patients undergoing first line chemotherapy].

AIM: We investigated the numbers and proportions of lymphocyte subsets in advanced ovarian cancer patients undergoing chemotherapy, so as to identify whether there is immune reconstitution after chemotherapy, and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. METHODS: Blood samples from each ovarian cancer patient were obtained before (S(0)) and at day 5-7 (S(1)), day 12-14 (S(2)) and day 25-28 (S(3)) after chemotherapy in 13 patients. Flow cytometry technique was employed to analyse the numbers, proportions of CD3(+), CD4(+), CD8(+), CD4(+) CD25(+) Treg and memory-like phenotype lymphocyte subsets. RESULTS: Lymphopenia was observed at S1 after chemotherapy, but lymphocytes were found gradually recovered after S1. The numbers of CD3(+), CD4(+), CD8(+) T cells and CD4(+) CD25(+) Treg cells reduced to the lowest on S(1). The proportions of CD8(+) T cells and CD4(+) CD25(+) Treg cells reduced to the lowest on S(1) and S(2) respectively. The proportions of CD45RO(+) memory T cells increased significantly on S(2) while the proportion of CD8(+) CD45RA(+) T cells decreased remarkably on S(2). CONCLUSION: Paclitaxel and carboplatin induce lymphopenia at day 5-7 after chemotherapy, then comes the temporary immune reconstitution. It probably turns out that the "window period" during immune reconstitution offers a best opportunity for cancer immunotherapy.

[Effect of apoptotic ovarian cancer cells induced by paclitaxel-cisplatin on antigen presentation function of DC].

AIM: To explore wheather apoptotic ovarian cancer cells induced by paclitaxel-cisplatin could be cross-presented by antigen presenting cells and promote immune responses. METHODS: DCs were generated from peripheral blood monocytes in RPMI1640 supplemented with GM-CSF and IL-4. After 6 days' incubation, DCs were further co-cultured with either apoptotic HO8910 cell lines induced by paclitaxel-cisplatin or control cells for four hours. Maturation of DCs was compared among different groups according to their surface markers through flow cytometry assay and their phagocytosis ability was evaluated by confocal microscopy scanning assay. RESULTS: Apoptotic ovarian cancer cells induced by paclitaxel-cisplatincan were phagocytized more efficiently by DCs.Resulting is more cellularity and maturation of DCs in apoptotic cell-induced groups than control group (P<0.05). CONCLUSION: Apoptotic ovarian cancer cells induced by paclitaxel-cisplatin exhibit strong immunogenicity, which in turn promote the maturation and antigen presentation of DCs.