Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.
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PMID:Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2. 872 15

It is well established that the normal human brain contains populations of neural stem/progenitor cells. Recent studies suggest that they migrate toward a variety of CNS tissue injuries. In an investigation of the potential role of neural stem cells in the pathogenesis of primary CNS lymphomas (NHL-CNS), we observed that neural stem/progenitor cells appeared to accumulate at the border of the tumors with the brain and in the advancing edge of the tumors, in a pattern similar to that seen with reactive gliosis. We identified neural stem/progenitor cells using standard immunohistochemical markers thereof, including CD133, nestin, Group II Beta-tubulin, Musashi1, and the transcription factor Sox2, in neurosurgically obtained specimens of NHL-CNS metastatic carcinoma , and metastatic melanoma . We had similar results with each of these markers but found that Sox2 antibodies provided the clearest and most robust labeling of the cells at the borders of these non-glial tumors. To exclude that the immunoreactive cells were actually neoplastic, double-label immunohistochemistry for Sox2 and CD20 (for NHL-CNS), Sox2 and cytokeratin (CAM5.2, for carcinomas), or Sox2 and HMB45 (for melanomas) showed that in each tumor type, Sox2-immunoreactive cells adjacent to and among the tumor cells were separate from neoplastic cells. Sox2/GFAP double-labeling revealed a consistent pattern of Sox2 immunopositivity both in reactive GFAP-immunopositive astrocytes and in GFAP-negative cells, at the interface of tumor and non-neoplastic brain. These results suggest that neural stem/progenitor cells migrate to non-glial neoplasms in the CNS, are a source of reactive astrocytes, and that Sox2 is a reliable immunohistochemical marker for these cells.
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PMID:Neural stem/progenitor cells react to non-glial cns neoplasms. 2571 58