Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751781 (NOD)
 6,696 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic stem cell (HSC) graft cell dose impacts significantly on allogeneic transplant. Similarly, HSC gene therapy outcome is affected by loss of repopulating cells during culture required for ex vivo retrovirus transduction. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a central role in marrow trafficking of HSCs, and maneuvers that enhance CXCR4 activation might positively impact outcome in settings of limiting graft dose. CD26/dipeptidyl peptidase IV (DPP-IV) is an ectoenzyme protease that cleaves SDF-1, thus reducing CXCR4 activation. We show that injection of irradiated nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with >or=2 micromol Diprotin A (a tripeptide specific inhibitor of CD26 protease activity) at the time of transplant of human granulocyte colony-stimulating factor (G-CSF) mobilized CD34(+) peripheral blood cells (CD34(+) PBCs) results in a >3.4-fold enhancement of engraftment of human cells. We also show that CD26 on residual stromal cells in the irradiated recipient marrow milieu, and not any CD26 activity in the human CD34(+) PBC graft itself, plays the critical role in regulating receptivity of this environment for the incoming graft. Human marrow stromal cells also express CD26, raising the possibility that Diprotin A treatment could significantly enhance engraftment of HSCs in humans in settings of limiting graft dose just as we observed in the NOD/SCID mouse human xenograft model.
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PMID:Diprotin A infusion into nonobese diabetic/severe combined immunodeficiency mice markedly enhances engraftment of human mobilized CD34+ peripheral blood cells. 1761 Mar 66

Mesothelioma, a highly aggressive cancer with poor prognosis and refractory to currently available therapies show increasing trends of its incidence in Japan and other developing countries. Although surgery is a gold standard for patients with early mesothelioma, most patients with advanced disease are not suitable for surgical resection and have option of palliative chemotherapy alone. One of the new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonal antibody therapy is under development. CD26, a 110-kDa transmembrane glycoprotein with known dipeptidyl peptidase IV activity, plays a role in tumor development and its expression was reported in various human malignancies. This study determined the preliminary selection criteria for humanized monoclonal anti-CD26 antibody therapy. Eighty-one epithelioid (49 differentiated and 32 less differentiated), 34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell lines were immunohistochemically examined using 8 different commercially available anti-CD26 antibodies for membranous and cytoplasmic expression. The cytoplasmic expression of CD26 was observed in all histological types of mesothelioma, while the membranous expression of CD26 was found in 88% of differentiated and 69% of less differentiated epithelioid mesothelioma, and none of sarcomatoid mesothelioma with anti-CD26 antibodies with rabbit polyclonal anti-DPP4 antibody and similar results were also obtained with goat polyclonal anti-DPP4/CD26 antibody. These antibodies absorbed with soluble human CD26 proteins do not show CD26 expression in mesothelioma tissue, suggesting these two antibodies localize true CD26 protein. Seven mesothelioma cell lines, including sarcomatoid types, also showed membranous expression of CD26 in cellblock preparation. CD26 vector transfection to CD26-negative MSTO-211H cells showed membranous expression of CD26 by flow cytometry, but not in tumor developed in NOD/SCID mice with inoculation of CD26 vector transfected MSTO-211H cells. We found that both rabbit and goat polyclonal antibodies are suitable for immunohistochemical evaluation of membranous expression of CD26 in mesothelioma.
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PMID:Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines. 2189 38