ETS transcription factor ELK3 in human cancers: An emerging therapeutic target.

Cancer is a genetic and complex disorder, resulting from several events associated with onset, development, and metastasis. Tumor suppressors and oncogenes are among the main regulators of tumor progression, contributing to various cancer-related behaviors like cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis. Transcription factors (TFs) could act as tumor suppressors or oncogenes in cancer progression. E-twenty-six/E26 (ETS) family of TFs have a winged helix-turn-helix (HLH) motif, which interacted with specific DNA regions with high levels of purines and GGA core. ETS proteins act as transcriptional repressors or activators to modulate the expression of target genes. ETS transcription factor ELK3 (ELK3), as a type of ETS protein, was shown to enhance in various cancers, suggesting that it may have an oncogenic role. These studies indicated that ELK3 promoted invasion, migration, cell cycle, proliferation, and EMT, and suppressed cell apoptosis. In addition, these studies demonstrated that ELK3 could be a promising diagnostic and prognostic biomarker in human cancer. Moreover, accumulating data proved that ELK3 could be a novel chemoresistance mediator in human cancer. Here, we aimed to explore the overall change of ELK3 and its underlying molecular mechanism in human cancers. Moreover, we aimed to investigate the potential role of ELK3 as a prognostic and diagnostic biomarker as well as its capability as a chemoresistance mediator in cancer.

Prevalence of Multi-Drug Resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa - A High Tuberculosis Endemic Area of Pakistan.

Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.

Molecular detection of rifampicin resistance by GeneXpert® assay among treated and untreated pulmonary tuberculosis patients from Khyber Pakhtunkhwa, Pakistan.

OBJECTIVES: Drug-resistant tuberculosis (TB) is an emerging health problem. Rifampicin (RIF) is the major first-line drug against TB. RIF resistance can be used as a marker for the detection of multidrug-resistant TB (MDR-TB). The purpose of this study was to determine the RIF resistance pattern of Mycobacterium tuberculosis complex isolates among treated and untreated patients in Khyber Pakhtunkhwa, Pakistan. METHODS: A total of 349 drug-treated and untreated TB-diagnosed patients were enrolled in this study. RIF resistance was detected using a GeneXpert® assay for amplification of the RIF resistance-determining region (RRDR) region of the rpoB gene. RESULTS: The overall prevalence of RIF resistance was 5.2% (18/349). Among 49 untreated TB patients, 3 samples (6.1%) were found resistant to RIF. Among 235 patients with a category 1 treatment regimen, 10 samples (4.3%) were resistant to RIF, whilst among 65 patients with a category 2 (Cat-2) treatment regimen, 5 samples (7.7%) were resistant to RIF. A comparison based on patient sex revealed high RIF resistance among male compared with female patients. RIF resistance was highest (4/21; 19.0%) in the 21-40 years age group among Cat-2 patients. CONCLUSIONS: The overall prevalence of RIF resistance was high among treated and untreated TB patients. These findings will be helpful for better monitoring and management of RIF resistance in TB patients from Khyber Pakhtunkhwa, Pakistan.