Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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    Reclassification of Clinical Exome Data Leads To Significant Clinical Assessment Changes in Almost Half of the Patients
    (2023) Bayraktar, Umut Arda; Sahin, Feride Iffet; Polat, Mert; Terzi, Yunus Kastm
    Purpose: With the global accumulation of genetic/clinical data, we are understanding the clinical significance of the reclassification of pathogenicity for gene variants. We hypothesized that this evolution in classification(s) may cause clinically-relevant discrepancies in the genetic risk assessment of subjects. In this study, we sought to reclassify the clinical exome sequence (CES) data of our patients to assess whether these changes would have clinical significance.Materials and Methods: The study included CES data of 23 cases diagnosed with cancer or familial cancer predisposition. The variants were first classified in 2020 and then reclassified a year after based on the ACMG database. Chart reviews were performed to record clinical history and interventions.Results: In the first classification of CES data, a total of 80 variants were identified as being not benign (26 likely pathogenic/pathogenic and 54 variants of undetermined significance (VUS)). The clinical significance of fifteen variants (19%) changed after reclassification in 10 patients (43%). The only upgraded variant was the c.9097 dup in exon 23 of BRCA2 gene (likely pathogenic to pathogenic). Fourteen variants were downgraded at reanalysis in 9 patients: from pathogenic to likely pathogenic (2 variants), pathogenic to VUS (2), likely pathogenic to VUS (4), and VUS to benign (6).Conclusion: Considering that the clinical significance of CES data changed due to reclassification in almost half of the studied patients, we believe genetic variant-related data should be assessed at regular intervals, regardless of follow-up status in the clinic.
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    Morphine: Patient Knowledge and Attitudes in the Central Anatolia Part of Turkey
    (2014) Colak, Dilsen; Oguz, Arzu; Yazilitas, Dogan; Immamoglu, Inanc Goksen; Altinbas, Mustafa; 24998575
    Background: In Muslim majority countries (MMC) opioid use for pain management is extremely low. The underlying factors contributing to this are not well defined. Aim: The aim of this study was to survey the attitudes of cancer patients towards morphine use for pain management in a MMC and identify the factors that influence patient decisions to accept or refuse morphine as treatment for cancer pain. Settings/participants: Patients were questioned whether they had pain or not, the severity and the medications for pain management. Questions included what type of medication they thought morphine was, whether or not they would be willing to take morphine if recommended for pain management and the basis for their decision if they were against morphine use. Results: Four hundred and eighty-eight patients participated in the study. Some 50% of the patients who refused morphine use and 36.8% of the patients who would prefer another drug, if possible, identified fear of addiction as the basis for their decision. Reservation of morphine for later in their disease was the case for 22.4% of the patients who refused morphine use. Only 13.7 % of the patients refusing morphine and 9.7% of the patients who preferred another drug, if possible, cited religious reasons as the basis for this decision. Conclusions: Identifying the underlying factors contributing to low opioid use for pain management in MMC is important. Once the underlying factors were identified, all efforts should be taken to overcome them as they are barriers to improving patient pain management.
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    Metformin: Hype or Hope for Cancer
    (2017) Nar, Asli; 0000-0003-0998-8388; AAA-2743-2021
    Current studies show that especially pancreatic, liver, endometrial, colorectal, bladder and breast cancer incidences are increased by the presence of type 2 diabetes mellitus (T2DM). Possible links between T2DM and cancer include hyperinsulinemia, dysregulation of adipocytokines and hyperglycemia as well as shared confounding risk factors. There is evidence emerging from experimental and clinical studies that metformin can play a crucial anti-cancereous role. Since 2005, multiple studies showed the association between metformin and the reduction of risk in cancers of pancreas, colorectal, stomach, liver, breast and esophagus in diabetes cases. It was also claimed to improve survival in some cancers. Metformin is an insulin sensitizer and mainly acts through inhibiting hepatic gluconeogenesis by activating LKB1/AMP-activated protein kinase (AMPK). Metformin was found to have anti-cancerous and anti-metastatic effects mainly through activating AMPK dependent and independent signaling; inhibiting mTOR, MAPK, HER2, NF-kappa B, IGF signaling pathways and with its possible immuno-modulatory effects. Further studies are needed to evaluate the potential of metformin as adjuvant therapy for cancer especially in non-diabetic patients.
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    Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance
    (2018) Kutuk, Ozgur; Kale, Justin; Brito, Glauber Costa; Andrews, Talluhan S.; Leber, Brian; Letai, Anthony; Andrews, David W.; 0000-0001-9854-7220; AAH-1671-2019
    Akt is a pro-survival kinase frequently activated in human cancers and is associated with more aggressive tumors that resist therapy. Here, we connect Akt pathway activation to reduced sensitivity to chemotherapy via Akt phosphorylation of Bax at residue S184, one of the pro-apoptotic Bcl-2 family proteins required for cells to undergo apoptosis. We show that phosphorylation by Akt converts the pro-apoptotic protein Bax into an anti-apoptotic protein. Mechanistically, we show that phosphorylation (i) enables Bax binding to pro-apoptotic BH3 proteins in solution, and (ii) prevents Bax inserting into mitochondria. Together, these alterations promote resistance to apoptotic stimuli by sequestering pro-apoptotic activator BH3 proteins. Bax phosphorylation correlates with cellular resistance to BH3 mimetics in primary ovarian cancer cells. Further, analysis of the TCGA database reveals that 98% of cancer patients with increased BAX levels also have an upregulated Akt pathway, compared to 47% of patients with unchanged or decreased BAX levels. These results suggest that in patients, increased phosphorylated anti-apoptotic Bax promotes resistance of cancer cells to inherent and drug-induced apoptosis.