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Platinum-resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. As survival is strongly influenced by immunological parameters, immunotherapeutic strategies appear promising. Therefore a better understanding of the interaction between ovarian tumour cells and cells of the immune system is a necessary prerequisite. In the present study we aimed to enlighten the interactions between platinum resistant and platinum sensitive ovarian cancer cells and natural-killer (NK)-cells. Modified FATAL assay was used for determining the killing efficiency of NK-cells for the parental A2780 cells and the cis-platinum resistant A2780cis human ovarian cancer cells. Expression of pro- and anti-apoptotic genes as well as ligands involved in NK-cell receptor recognition were analysed by RT-PCR and flow cytometric analysis. The efficiency of NK mediated cell lysis differs between A2780 cells and the cis-platinum-resistant A2780cis cells. A2780cis cells are less accessible for NK-cell mediated killing. Based on this observation we characterized the molecular basis for resistance mechanisms. Besides an increase in anti-apoptotic genes (especially CIAP-1 and -2) that probably render A2780cis cells more resistant against apoptosis an increased amount of soluble MICA/B seems to be responsible for the lower killing rate of platinum-resistant A2780cis cells compared to their parental A2780 cells.
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http://dx.doi.org/10.3892/ijo.2013.1846 | DOI Listing |
J Cell Mol Med
December 2024
Biosciences Institute, Newcastle University Cancer Centre, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA.
View Article and Find Full Text PDFThe advent of poly(ADP-ribose) polymerase (PARP) inhibitors has resulted in a significant paradigm shift in ovarian cancer treatment. Niraparib, a potent PARP inhibitor, has demonstrated substantial efficacy in both first-line and recurrent disease settings. By targeting homologous recombination DNA repair, a pathway frequently disrupted in ovarian cancer, particularly in the context of BRCA mutations, niraparib induces synthetic lethality.
View Article and Find Full Text PDFExp Ther Med
February 2025
Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China.
The aim of the present study was to explore the role of ovarian cancer G protein-coupled receptor 1 (OGR1) in osteoclast differentiation and activity induced by extracellular acid. The impact of extracellular acidification on osteoclasts was investigated. Briefly, osteoclasts were generated from RAW 264.
View Article and Find Full Text PDFWorld J Clin Oncol
December 2024
Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon.
Background: The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.
Aim: To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.
Methods: We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.
EClinicalMedicine
January 2025
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynaecological Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes.
Methods: This study analyzed incidence patterns (2013-2017) and trends (1988-1992 to 2013-2017) of OC and its subtypes across 65 and 40 countries, respectively.
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