Malignant fibrous histiocytoma (MFH), a high-grade, undifferentiated sarcoma, is highly aggressive, resistant to radiochemotherapy and associated with poor prognosis. There are no specific immunohistochemical markers for its diagnosis. The MFH cell line SFT7913 served as and immunogen for the generation of the FU3 monoclonal antibody in our laboratory. FU3 reacted strongly with MFH cells and with perivascular mesenchymal cells. In this study, we demonstrated that the antigen recognized by FU3 was identical to aminopeptidase N (APN/CD13) using FU3 immunoaffinity chromatography and N-terminal amino acid sequencing. Frequent (80%) and high-grade (>50% of cells) expression of APN/CD13 was observed in MFH, although low-grade expression was seen in some other sarcomas. Moreover, small interfering RNA (siRNA) that specifically targets APN/CD13 significantly suppressed MFH cell invasion in vitro. The newly developed monoclonal antibody FU3 specifically recognizes CD13 on MFH cells. Decreased expression of CD13, mediated by siRNA-mediated knockdown, attenuated the invasive capacity of MFH cells. Thus, results indicate that APN/CD13 could be an important diagnostic biomarker and therapeutic target for MFH.
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http://dx.doi.org/10.3892/ijo.2013.1940 | DOI Listing |
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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