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Assessing the Impacts of Drug Loading and Polymer Type on Dissolution Behavior and Diffusive Flux of GDC-6893 Amorphous Solid Dispersions.
J Pharm Sci
January 2025
Department of Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address:
It is desirable but remains challenging to develop high drug load amorphous solid dispersions (ASDs) without compromising their quality attributes and bio-performance. In this work, we investigated the impacts of formulation variables, such as drug loading (DL) and polymer type, on dissolution behavior, diffusive flux, and in vitro drug absorption of ASDs of a high T compound, GDC-6893. ASDs with two polymers (HPMCAS and PVPVA) and various DLs (20 - 80%) were produced by spray drying and their drug-polymer miscibility was evaluated using solid-state nuclear magnetic resonance (ssNMR).
View Article and Find Full Text PDFAtezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.
ESMO Open
January 2025
Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, (Milan), Italy. Electronic address:
Background: The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC.
View Article and Find Full Text PDFConfocal Endomicroscopy Intestinal Epithelial Barrier Abnormalities in Individuals Without Documented Gastro-Intestinal Disease.
United European Gastroenterol J
January 2025
Department of Gastroenterology, CHU Liège, Liège, Belgium.
Background And Aims: Probe-based confocal endomicroscopy (pCLE) allows real-time microscopic visualization of the intestinal mucosa surface layers. Despite remission achieved through anti-tumor necrosis factor or vedolizumab therapy, anomalies in the intestinal epithelial barrier are observed in inflammatory bowel disease (IBD) patients. Our study aimed to assess these abnormalities in non-IBD individuals and compare them with IBD patients in endoscopic remission to identify the associated factors.
View Article and Find Full Text PDFGut Microbiota Secondary Metabolites: Key Roles in GI Tract Cancers and Infectious Diseases.
Biomedicines
January 2025
Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt.
The gut microbiota, a dynamic ecosystem of trillions of microorganisms, produces secondary metabolites that profoundly influence host health. Recent research has highlighted the significant role of these metabolites, particularly short-chain fatty acids, indoles, and bile acids, in modulating immune responses, impacting epigenetic mechanisms, and contributing to disease processes. In gastrointestinal (GI) cancers such as colorectal, liver, and gastric cancer, microbial metabolites can drive tumorigenesis by promoting inflammation, DNA damage, and immune evasion.
View Article and Find Full Text PDFFungal Biocontrol Agents in the Management of Postharvest Losses of Fresh Produce-A Comprehensive Review.
J Fungi (Basel)
January 2025
Gastro-Intestinal Microbiology and Biotechnology Unit, Agricultural Research Council-Animal Production, Private Bag X02, Irene, Pretoria 0062, South Africa.
Postharvest decay of vegetables and fruits presents a significant threat confronting sustainable food production worldwide, and in the recent times, applying synthetic fungicides has become the most popular technique of managing postharvest losses. However, there are concerns and reported proofs of hazardous impacts on consumers' health and the environment, traceable to the application of chemical treatments as preservatives on fresh produce. Physical methods, on the other hand, cause damage to fresh produce, exposing it to even more infections.
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