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Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.
NPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFThe public health risks of counterfeit pills.
Lancet Public Health
January 2025
Department of Family Community Medicine, University of California, San Francisco, San Francisco, CA, USA.
Synthetic illicit drugs, such as nitazenes and fentanyls, are becoming commonplace in countries around the world, including in Europe, Australia, and Latin America, which raises concern for overdose crises like those seen in North America. An important dimension of the risk represented by synthetic drugs is the fact that they are increasingly packaged in counterfeit pill form. These pills-often indistinguishable from authentic pharmaceuticals-have substantially widened the scope of populations susceptible to synthetic drug overdose in North America (eg, among adolescents experimenting with pills or tourists from the USA seeking psychoactive medications from pharmacies in Mexico).
View Article and Find Full Text PDFClinical Management of Human Herpesvirus-8 related illnesses in solid organ transplant recipients.
J Infect
January 2025
Department of Oncology and National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, UK; Centre for Immunology and Vaccinology, Department of Infectious Diseases, Imperial College, London, UK. Electronic address:
In solid organ transplant recipients (SOTRs), the oncogenic virus human herpesvirus-8 (HHV-8) also named Kaposi sarcoma herpesvirus (KSHV) causes four clinical diseases: Kaposi Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman Disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). This review outlines these clinical scenarios and discusses their management. Although HHV8 related disease in SOTR was first described more than three decades ago, there is a lack of data on treatment so much of the guidance is based on evidence in other immunodeficient patients, particularly people living with HIV.
View Article and Find Full Text PDFA Guide to Pathophysiology, Signaling Pathways, and Preclinical Models of Liver Fibrosis.
Mol Cell Endocrinol
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY,11439, USA. Electronic address:
Liver fibrosis is potentially a reversible form of liver disease that evolved from the early stage of liver scarring as a consequence of chronic liver injuries. Recurrent injuries in the liver without any appropriate medication cause the injuries to get intense and deeper, which gradually leads to the progression of irreversible cirrhosis or carcinoma. Unfortunately, there are no approved treatment strategies for reversing hepatic fibrosis, making it one of the significant risk factors for developing advanced liver disorders and liver disease-associated mortality.
View Article and Find Full Text PDFDetecting novel plant pathogen threats to food system security by integrating the Plant Reactome and remote sensing.
Curr Opin Plant Biol
January 2025
Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA.
Plant diseases constantly threaten crops and food systems, while global connectivity further increases the risks of spreading existing and exotic pathogens. Here, we first explore how an integrative approach involving plant pathway knowledgegraphs, differential gene expression data, and biochemical data informing Raman spectroscopy could be used to detect plant pathways responding to pathogen attacks. The Plant Reactome (https://plantreactome.
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