Browsing by Subject "phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase"

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    Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells
    (John Wiley and Sons Inc, 2020) Ozdemir Kutbay N.; Biray Avci C.; Sarer Yurekli B.; Caliskan Kurt C.; Shademan B.; Gunduz C.; Erdogan M.
    Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes: AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, and RICTOR genes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets. © 2020 Wiley Periodicals LLC
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    Does Pten have an impact on oogenesis of PCOS mouse models?
    (Cambridge University Press, 2023) Onal T.; Tulay P.; Vatansever H.S.
    Polycystic ovary syndrome (PCOS) is a complex disorder in which the aetiology is still not explained very well. The PI3K/PTEN (phosphatidylinositol 3-kinase/phosphatase and tensin homolog deleted on chromosome 10) pathway is an important pathway that is involved in many mechanisms, including proliferation, growth and motility. PTEN plays a role in granulosa cell proliferation and regulates the differentiation process. The aim of this study was to investigate the expression levels of Pten and Pik3ca in PCOS mouse models with and without any treatment procedures. Three groups of mouse models, PCOS, a PCOS group with clomiphene citrate treatment, and a PCOS group with the combination of clomiphene citrate, metformin and pioglitazone treatment, were established. Ovarian tissues, which were obtained from these groups and a control group with no PCOS, were embedded in paraffin and RNA was extracted. cDNA was synthesized and real-time PCR was conducted to evaluate the expression levels of Pten and Pik3ca. The results of this study showed that both Pten and Pik3ca genes were expressed in the ovarian tissues from the mouse models. Although one-way analysis of variance results showed that Pten was expressed significantly differently in the samples, individual Student's t-tests did not show any significantly different expression levels in each group. This study is important as it shows the expression patterns of two genes in PCOS mouse models with different treatment strategies, including clomiphene citrate, metformin and pioglitazone. The results of this study formed the basis of research studies and investigations into different genes within the PTEN pathway, as well as other pathways that are under investigation. © The Author(s), 2022. Published by Cambridge University Press.
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    P53 and PTEN expression evaluation with molecular evident recent criteria in laryngeal carcinoma
    (Lippincott Williams and Wilkins, 2023) Tan A.; Eskiizmir G.; Kamiloglu U.; Sarioglu S.
    The prognosis of laryngeal cancer is affected by clinicopathological factors. Because of that, an effective prognostic marker is very valuable in managing the clinical process. The p53 evaluation method, used in the literature recently, was used for the first time in laryngeal cancer. We evaluated PTEN with 2 methods with the highest significance in the literature on laryngeal cancer. All demographic and histopathological data from 140 laryngeal cancers were compared with p53 and PTEN expressions and survival. p53 staining patterns were classified as wild and mutant. PTEN expression was evaluated according to the staining intensity named PTEN1 and according to the proportion of stained cells named PTEN2. In the series, 93.6% were males, and the mean survival was 38 months. 69.3% of cases were p53 mutants. PTEN loss was found to be 85.7% and 57.9%, respectively. Tumor size and thyroid cartilage invasion for PTEN1 and age for p53 were identified as independent predictive factors (P <.01). Advanced age, total laryngectomy, and extranodal spread were independent poor prognostic factors for overall survival and the presence of subglottic involvement, perineural invasion, and extranodal spread were for disease-free survival (P <.01). This is the first study in which the new p53 classification was used in laryngeal cancer, and will contribute significantly to the literature with differences from the previous evaluation patterns. Evaluation of PTEN based on staining intensity is more appropriate compared to the percentage of stained cells. © Copyright 2023 the Author(s). Published by Wolters Kluwer Health, Inc.