Inhibition of PI3K/AKT/mTOR and MAPK signaling pathways decreases progranulin expression in ovarian clear cell carcinoma (OCCC) cell line: a potential biomarker for therapy response to signaling pathway inhibitors

AbstractPatients with advanced stage ovarian clear cell carcinoma (OCCC) have a poor prognosis due to resistance to conventional platinum chemotherapy. Recent studies have demonstrated that PI3K/AKT/mTOR and ERK1/2 signaling pathways are involved in this chemoresistance. Progranulin (PGRN) overexpression contributes to cisplatin resistance of epithelial ovarian cancer cell lines. Also, PGRN expression is regulated by AKT/mTOR and ERK1/2 signaling pathways in different cell types. Thus, the present study was designed to identify if PGRN expression is regulated by AKT, mTOR, and ERK1/2 signaling pathways in the OCCC cell line TOV-21G. Cultured TOV-21G cells were incubated with different concentrations of pharmacological cell signaling inhibitors. PGRN expression and phosphorylation of ERK1/2, AKT, and mTOR were assessed by Western blotting. Inhibition of AKT, mTOR, and ERK1/2 significantly reduced PGRN expression. Cell viability was not affected, while cell proliferation significantly decreased with all inhibitors used in this study. These observations demonstrated that inhibition of PI3K/AKT/mTOR and ERK1/2 signaling pathways reduces PGRN expression in TOV-21G cells. Thus, PGRN could be considered as a candidate for explaining the high resistance to platinum-based treatment and a potential biomarker for therapy response to cell signaling inhibitors in patients with OCCC.
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research

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This study protocol was approved by the Institutional Review Board of the hospital. Data Collection Demographic and clinical data were retrieved from medical records in the hospital’s centralized database. These data included the age at diagnosis, International Federation of Obstetrics and Gynecologic (FIGO) stage, tumor histology and grade, type of surgery, and types and cycles of chemotherapy. Disease staging was based on the 2014 FIGO staging system. Optimal debulking surgery was defined as residual tumors with maximal diameters less than 1 cm; the others were defined as suboptimal debulking surgery. Disease rec...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy. Introduction Ovarian cancer is one of the most common malignances in females. The American Cancer Society estimated that there were 22,240 cases of ovarian cancer, and 14,070 deaths, in the United States in 2018 (1). During its early stages, ovarian cancer can be asymptomatic; hence, ~70% of patients have advanced disease when diagnosed and ultimately develop chemotherapeutic drug resistance an...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Rationale: Epithelial ovarian carcinoma (EOC) is the most common type of ovarian carcinoma, and the leading cause of female genital tract cancer-related deaths. However, brain metastasis (BM) of EOC is rare, with an incidence of only 1% to 2%. Ovarian clear cell carcinoma (OCCC), accounting for 5% to 25% of all EOC cases, has a poor prognosis compared with other epithelial cell type carcinomas. Patient concerns: We retrospectively analyzed the clinical data of a 62-year-old female, who was hospitalized with the main complaint of BM detection for 1 month. She was first diagnosed with ovarian cancer in 2004, and underwe...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionsCombining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Authors: Morikawa A, Hayashi T, Kobayashi M, Kato Y, Shirahige K, Itoh T, Urashima M, Okamoto A, Akiyama T Abstract Ovarian clear cell carcinoma (OCCC) is a chemotherapy‑resistant epithelial ovarian cancer with poor prognosis. To identify genomic alterations involved in the development of OCCC, we analyzed somatic copy number alterations in OCCC using comparative genomic hybridization (CGH). Here we showed that the chromosomal regions 8p11.21, 8p11.22, 12p13.31 and 20q13.2 were amplified in OCCC. We also demonstrated that small segments in the chromosomal regions 3q26.1, 4q13.2 and 22q11.23 were deleted...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
This retrospective analysis aimed to clarify the clinical and pathologic features of ovarian clear cell carcinoma (OCCC), and to determine the factors predictive of survival. Data waereextracted from OCCC patients who underwent primary surgery followed by adjuvant chemotherapy in Obstetrics &Gynecology Hospital of Fudan University between January2007 and December 2014. Kaplan-Meier survival estimates and Cox proportional hazards model were used for survival analyses. Of 130 patients (mean age = 56.2 years), 66.2% had stage I disease when the 5-year overall survival and 5-year disease-free survival were 89.2% and 88.1...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
CONCLUSIONS: We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy. PMID: 28822556 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
Abstract Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced c...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
Objectives: Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. Methods: We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before star...
Source: International Journal of Gynecological Cancer - Category: Cancer & Oncology Tags: Ovarian Cancer Source Type: research
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