Publications by authors named "Sagun Shrestha"
Epithelial-to-mesenchymal transition (EMT) is a major axis of phenotypic plasticity not only in diseased conditions such as cancer metastasis and fibrosis but also during normal development and wound healing. Yet-another important axis of plasticity with metastatic implications includes the cancer stem cell (CSCs) and non-CSC transitions. However, in both processes, epithelial (E) and mesenchymal (M) phenotypes are not merely binary states.
View Article and Find Full Text PDFArticle Synopsis
- - Cancer cells can adapt their characteristics (phenotypes) to better survive in changing environments through a process called phenotypic plasticity, which provides them with a competitive edge.
- - Recent insights suggest that new traits in cancer cells can arise not just from genetic changes but also from non-genetic factors related to their ability to change phenotype, leading to a diverse population that complicates treatment.
- - Understanding how cancer cells modify their phenotypes through both competition and cooperation, particularly in the context of their environment and interactions, is crucial for developing innovative cancer therapies and strategies.
Sepsis among Patients Admitted to the Intensive Care Unit of a Tertiary Care Centre.
JNMA J Nepal Med Assoc
September 2023
Introduction: Sepsis is a life-threatening dysfunction and is one of the common causes of admission in intensive care units. Early diagnosis and management improves the outcome of patients. The aim of this study was to find out the prevalence of sepsis among patients admitted to the intensive care unit of a tertiary care centre.
View Article and Find Full Text PDFSeveral studies in the last few years have determined that, in contrast to the prevailing dogma that drug resistance is simply due to Darwinian evolution-the selection of mutant clones in response to drug treatment-non-genetic changes can also lead to drug resistance whereby tolerant, reversible phenotypes are eventually relinquished by resistant, irreversible phenotypes. Here, using KRAS as a paradigm, we illustrate how this nexus between genetic and non-genetic mechanisms enables cancer cells to evade the harmful effects of drug treatment. We discuss how the conformational dynamics of the KRAS molecule, that includes intrinsically disordered regions, is influenced by the binding of the targeted therapies contributing to conformational noise and how this noise impacts the interaction of KRAS with partner proteins to rewire the protein interaction network.
View Article and Find Full Text PDFDrug resistance remains one of the major impediments to treating cancer. Although many patients respond well initially, resistance to therapy typically ensues. Several confounding factors appear to contribute to this challenge.
View Article and Find Full Text PDFOnline education has been adopted widely to address the educational chaos created by the Covid-19 pandemic. Reports on its constraints and challenges appear daily in the global media. However, accounts of teachers' and students' experiences of this abrupt shift in pedagogical modality are conspicuously absent in the available literature.
View Article and Find Full Text PDFPurpose: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported.
Methods: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks.