PAF1-mediated transcriptional reprogramming confers docetaxel resistance in advanced prostate cancer.

Advanced prostate cancer (PCa) remains a significant clinical challenge, and docetaxel plays a significant role in disease management. Despite the efficacy of docetaxel as a first-line chemotherapy, resistance often develops. We developed three clinically relevant in vitro PCa cell models and transcriptomic analysis identified that the Paf1/RNA polymerase II complex component (PAF1)-associated pluripotent-transcription factor (TF), SOX2, plays a crucial role in docetaxel resistance.

Sugar symphony: glycosylation in cancer metabolism and stemness.

Glycosylation is a complex co-translational and post-translational modification (PTM) in eukaryotes that utilizes glycosyltransferases to generate a vast array of glycoconjugate structures. Recent studies have highlighted the role of glycans in regulating essential molecular, cellular, tissue, organ, and systemic biological processes with significant implications for human diseases, particularly cancer. The metabolic reliance of cancer, spanning tumor initiation, disease progression, and resistance to therapy, necessitates a range of uniquely altered cellular metabolic pathways.

Pathological Variables and Laboratory Values in Infants with Neonatal Cholestasis Showing Nonexcretion on Tc-99m Mebrofenin Hepatobiliary Scans: A Descriptive Study.

Introduction: Cholescintigraphy using Tc-99m Mebrofenin is routinely performed as an initial diagnostic test in infants with neonatal cholestasis suspected of having biliary atresia. Demonstration of drainage of bile into the small intestine indicates patency of the biliary tract and thus rules out biliary atresia. Non-excretion of tracer into the small intestine, however, can be caused by obstructive as well as non-obstructive conditions, and it is known that false-positive findings are found with the use of Tc-99m Mebrofenin scintigraphy.

Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.

Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic and -extrinsic mechanisms. The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion.

PAF1/HIF1α axis rewires the glycolytic metabolism to fuel aggressiveness of pancreatic cancer.

Background: PAF1/PD2 deregulation contributes to tumorigenesis, drug resistance, and cancer stem cell maintenance in Pancreatic Cancer (PC). Recent studies demonstrate that metabolic reprogramming plays a role in PC progression, but the mechanism is poorly understood. Here, we focused on examining the role of PAF1/PD2 in the metabolic rewiring of PC.