conclusions pmf-dependent efflux mechanism appears to play an important role in the mdr phenotype of a. baumannii clinical strains. background multidrug-resistant (mdr) strains of acinetobacter baumannii have been increasingly reported as a major cause of nosocomial infections, and have created major therapeutic problems worldwide. objectives the aim of the present study was to evaluate the rol...

tuberculosis is a serious global public health problem and its high prevalence is stron gly associated with the enhancement of drug resistance. in this study we demonstrate a multiplex allele-specific polymerase chain reaction (mas)-pcr assay to simultaneously detect mutations in the first and third bases of the embb gene codon 306 atg in ethambutol (emb) resistant isolates of mycobacterium tub...

Primary resistance to vincristine (VCR) has been selected in rhabdomyosarcoma xenograft HxRh12 by sequential administration of VCR at 1.5 and subsequently 3 mg/kg/passage. The resistant tumor (HxRh12/VCR-3) was approximately 4-fold resistant to VCR and resistance was stable in the absence of selecting pressure (greater than 2 yr). HxRh12/VCR-3 was 2- to 3-fold cross-resistant to L-phenylalanine...

PURPOSE To determine the potential of crenolanib, a potent inhibitor of PDGFRA, to treat malignancies driven by mutant PDGFRA. EXPERIMENTAL DESIGN The biochemical activity of crenolanib was compared with imatinib using a panel of PDGFRA-mutant kinases expressed in several different cell line models, including primary gastrointestinal stromal tumors (GIST) cells. The antiproliferative activity...

Sorafenib has substantial clinical activity as thirdor fourth-line treatment of imatiniband sunitinibresistant gastrointestinal stromal tumors (GIST). Because sorafenib targets both angiogenesis-related kinases (VEGFR) and the pathogenetic kinases found in GIST (KIT or PDGFRA), the molecular basis for sorafenib efficacy in this setting remains unknown. We sought to determine the spectrum of act...

Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed ...

Abstract INTRODUCTION Glioblastoma (GBM) contains cell populations with distinct metabolic requirements, fast-cycling cells harnessing aerobic glycolysis, and treatment-resistant slow-cycling (SCCs) preferentially engaging lipid metabolism. The interaction between immune tumor cells, how their heterogeneity shapes the landscape in GBM has yet to be understood. Objectives: primary objective of t...

PURPOSE Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy. MATERIALS AND METHODS To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gas...

AIM To analyze the correlation between the elevated sensitivity of drug resistant breast cancer cells to the action of lymphokine-activated lymphocytes (LAK) and expression of E-cadherin and other marker proteins by cancer cells and lymphocytes. METHODS Breast tumor explants were cultured with autologous lymphocytes in double diffusion chambers. The results were evaluated by morphological cri...

Despite initial high response rate to tyrosine kinase inhibitor (TKI) treatment, non-small cell lung cancer (NSCLC) patients whose tumors harbour activating mutation in their epidermal growth factor receptors (EGFR) gene invariably develop TKI resistance. Secondary mutation T790M in EGFR and MET amplification were found in over 50% tumors. However, there are up to 30% of cases, whose mechanisms...