Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer.

Resistance to mitochondrial apoptosis is a major driver of chemoresistance in pancreatic ductal adenocarcinoma (PDAC). However, pharmacological manipulation of the mitochondrial apoptosis threshold in PDAC cells remains an unmet therapeutic goal. We hypothesized that fatty acid synthase inhibitors (FASNis), a family of targeted metabolic therapeutics recently entering the clinic, could lower the apoptotic threshold in chemoresistant PDAC cells and be synergistic with BH3 mimetics that neutralize anti-apoptotic proteins.

The TB27 Transcriptomic Model for Predicting Culture Conversion.

Rationale: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of . Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.

Objective: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.

Role of drug induced nuclear CTSL (nCTSL) in DNA damage response in cancer- therapeutic implications.

In our efforts to enhance sensitivity to PARP inhibitors, we identified clofarabine (CLF) as a potential therapy for drug-resistant ovarian cancer and nuclear trafficking of Cathepsin L (CTSL) as a treatment- responsive biomarker. Using PARP inhibitor-sensitive and -resistant OC cell lines, ex vivo cultures of patient-derived ovarian ascites (OVA), primary ovarian tumors, and xenografts (PDX), we found that CLF monotherapy induces nuclear CTSL (nCTSL) in CLF-responsive cells (CLF-r) and sensitizes them to PARP inhibitors olaparib and rucaparib. In CLF non-responsive cells (CLF-nr), a combination of CLF with olaparib is necessary for nCTSL trafficking and synergy.

Evaluation of the current status, significance, and availability of prostate MRI und MRI guided biopsy in Germany.

Evaluation of the current status, significance and availability of multiparametric prostate MRI and MRI-guided biopsy in Germany.A voluntary web-based questionnaire with 26 distinct items was emailed to members of the German Radiological Society (DRG) and the Professional Association of German Radiologists (BDR). The questions referred to personal qualification, acquisition, quality, and management of prostate MRI, and assessment of the importance of the method.

Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.

The ADP-ribosyl hydrolases PARG and ARH3 counteract PARP enzymatic activity by removing ADP-ribosylation. PARG and ARH3 activities have a synthetic lethal effect; however, the specific molecular mechanisms underlying this response remain unknown. Here, we show that the PARG and ARH3 synthetic lethality is enhanced further in the presence of DNA alkylating agents, suggesting that the inability to revert ADP-ribosylation primarily affects the repair of alkylated DNA bases.