Prostate cancer is one of the most common cancers in men and a leading cause of cancer death worldwide, displaying a broad range of heterogeneity in terms of clinical and molecular behavior. Increasing evidence suggests that classifying prostate cancers into distinct molecular subtypes is critical to exploring the potential molecular variation underlying this heterogeneity and to better treat this cancer. In this study, the somatic mutation profiles of prostate cancer were downloaded from the TCGA database and used as the source nodes of the random walk with restart algorithm (RWRA) for generating smoothed mutation profiles in the STRING network. The smoothed mutation profiles were selected as the input matrix of the Graph-regularized Nonnegative Matrix Factorization (GNMF) for classifying patients into distinct molecular subtypes. The results were associated with most of the clinical and pathological outcomes. In addition, some bioinformatics analyses were performed for the robust subtyping, and good results were obtained. These results indicated that prostate cancers can be usefully classified according to their mutation profiles, and we hope that these subtypes will help improve the treatment stratification of this cancer in the future.
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http://dx.doi.org/10.1038/s41598-017-00872-8 | DOI Listing |
J Biomol Struct Dyn
December 2024
Amity Institute of Biotechnology, Amity University, Kolkata, India.
The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.
View Article and Find Full Text PDFJ Clin Res Pediatr Endocrinol
December 2024
Department of Pediatric Endocrinology, Ankara University Faculty of Medicine, Ankara, Turkiye.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. Between 90% and 99% of cases of CAH are caused by 21-hydroxylase deficiency (21OHD) caused by mutations in CYP21A2. Although 21OHD has been historically divided into classical and non-classical forms, it is now thought to show a continuous phenotype.
View Article and Find Full Text PDFG protein-coupled receptors (GPCRs) remain a focal point of research due to their critical roles in cell signaling and their prominence as drug targets. However, directly linking drug efficacy to receptor-mediated activation of specific intracellular transducers and the resulting physiological outcomes remains challenging. It is unclear whether the enhanced therapeutic window of certain drugs - defined as the dose range that provides effective therapy with minimal side effects - stems from their low intrinsic efficacy across all signaling pathways or ligand bias, wherein specific transducer subtypes are preferentially activated in a given cellular system compared to a reference ligand.
View Article and Find Full Text PDFMedComm (2020)
January 2025
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Department of Medical Oncology Breast Tumor Centre Phase I Clinical Trial Centre, Clinical Research Design Division, Clinical Research Center Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou Guangdong China.
This multicenter, single-arm, phase II clinical trial (NCT04034589) evaluated the efficacy and safety of pyrotinib combined with fulvestrant in patients with HR-positive/HER2-positive metastatic breast cancer who had experienced trastuzumab treatment failure. A total of 46 patients were enrolled, receiving pyrotinib orally once daily and fulvestrant intramuscularly on days 1 and 15 of cycle 1, followed by monthly doses on day 1. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, ;China.
Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and the development of accurate predictive models for prognosis and drug sensitivity remains challenging.
Methods: We integrated laboratory data and public cohorts to conduct a multi-omics analysis of HCC, which included bulk RNA sequencing, proteomic analysis, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics sequencing (ST-seq), and genome sequencing. We constructed a tumor purity (TP) and tumor microenvironment (TME) prognostic risk model.
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