The epidermal growth factor receptor was analyzed in the membrane fraction from a series of human breast carcinomas using a radioligand assay. The results were compared to immunostaining with monoclonal antibodies on tissue sections. All tumors with detectable receptor levels as measured by ligand binding showed a positive staining with monoclonal antibodies. In such tumors more than 50 percent of the cells were receptor positive with varying intensity. Tumors classified as receptor negative with the radioligand assay could be divided into two major groups based on their immunostaining. The largest group showed no reactivity with monoclonal antibodies. In a second smaller group, a positivity was observed in small clusters of tumor cells while the majority of cells were negative. The staining intensity in such clusters was usually low. It seems possible that this heterogenous expression of the epidermal growth factor receptor is of significance with respect to clonal selection in tumor spreading.
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Nat Commun
January 2025
Biophysics Graduate Group, University of California, Davis, CA, USA.
P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.
View Article and Find Full Text PDFSemin Hematol
December 2024
Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:
Recent advancements in multiple myeloma (MM) treatment-including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and T cell-redirecting therapies like chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs)-have significantly improved patient outcomes. However, MM remains incurable, highlighting the need for novel therapeutic strategies. BsAbs, which simultaneously target a tumor-specific antigen and CD3 on T cells, have shown promising efficacy.
View Article and Find Full Text PDFJ Mol Diagn
February 2025
Daiichi Sankyo, Inc., Basking Ridge, New Jersey.
This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (HER2 [ERBB2])-mutated (HER2m) non-small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for HER2 mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02.
View Article and Find Full Text PDFRMD Open
January 2025
Clinical Epidemiology Division, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden.
Objective: To compare work loss after starting tumour necrosis factor inhibitors (TNFi), rituximab, abatacept or tocilizumab in patients with rheumatoid arthritis (RA).
Methods: We used data from the Swedish Rheumatology Quality Register to identify patients aged 19-62 years who were treated with TNFi (n=15 093), rituximab (n=2123), abatacept (n=1877) or tocilizumab (n=1720) between 2007 and 2020. Data on work loss (0-365 days per year) from sick leave and disability pension were retrieved from linkage to the Social Insurance Agency.
Metabolism
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, PR China. Electronic address:
Aims: Osteoclast energy metabolism is a promising target for treating diseases characterized by high osteoclast activity, such as osteoporosis. However, the regulatory factors involved in osteoclast bioenergetic processes are still in the early stages of being fully understood. This study reveals the effects of follicle-stimulating hormone (FSH) on osteoclast energy metabolism.
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