Wos Açık Erişimli Yayınlar

Permanent URI for this collectionhttps://hdl.handle.net/11727/10754

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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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    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.