Wos Açık Erişimli Yayınlar

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

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    The Distribution and Antimicrobial Susceptibility Profiles of Etiologic Agents Isolated From Bacteremia Episodes Among Immunocompromised Patients
    (2017) Demirkaya, Melike Hamiyet; Yesilkaya, Aysegul; Akcil-Ok, Mehtap; Kurt-Azap, Ozlem; 0000-0002-3171-8926; AAK-4089-2021
    Objective: Bacteremia is the leading cause of morbidity and mortality among immunocompromised patients. The aim of this study is to evaluate the etiology of bacteremia and the antibiotic susceptibilities of etiologic agents among immunocompromised patients followed up from January 1, 2012 to July 30, 2013. Methods: Immunocompromised patients, both inpatient and outpatient treated in our hospital, were followed prospectively. The definition of "immunocompromised patients" consisted of solid organ (kidney, liver) transplantation recipients and hemato-oncologic malignancy patients with a history of chemotherapy in the previous month before bacteremia. Results: This prospective study comprised of 167 bacteremia episodes of 130 consecutive immunocompromised patients. The most isolated group of bacteria was Gram-negative bacteria. Escherichia coli was the most commonly (30.8%) isolated bacteria and the second was coagulase-negative staphylococci (15.1%). Fifty one percent of the E. coli isolates were extended-spectrum beta-lactamasepositive. Acinetobacter baumannii was the second most common bacteria of Gram-negative agents and the ratio of multiple drug-resistant (MDR) isolates among Acinetobacter isolates was 73%. Conclusions: Gram-negative bacteria are the most common causative agents of bacteremia in immunocompromised patients in our hospital. The rising ratio of MDR A. baumannii is a striking problem which causes difficult-to-treat infections.
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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.