Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A certain number of pediatric cancer patients still succumb to relapse following conventional treatment of their malignancies. One of the mechanisms of relapse is escape from immunity. Adoptive cellular immunotherapy with effector cells has the potential to overcome this escape. In adults, the CD3+ CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. This effector cell type may work in children as well. No similar studies with children have been published. We speculated that expanded CD3+ CD56+ cells obtained from pediatric cancer patients during remission would act similarly against various pediatric tumor cell lines; therefore, we undertook the present study to find support for our speculation. This study was undertaken to generate and expand CD3+ CD56+ CIK cells from normal peripheral blood mononuclear cells (PBL) obtained from 6 children with cancer (2 with acute lymphoblastic leukemia, 2 with large cell lymphoma, and 2 with osteosarcoma) in remission after intensive chemotherapy and to study the cytotoxic activities of these cells against chronic myeloid leukemia cell line K562 t(9;22), 4 pediatric tumor cell lines [infant acute lymphoblastic leukemia RS4 t(4;11), TEL/AML acute lymphoblastic leukemia REH t(12;21), alveolar rhabdomyosarcoma Rh-Cr t(2;13), and Ewing sarcoma EW-Le t(11;22)], and 2 pediatric glioblastoma multiforme cultured cell lines (G74 and G77). CIK cells were generated and expanded in culture medium to which interferon gamma, monoclonal antibody against CD3, and interleukin 2 were added at appropriate times. Cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cell cytotoxicity against various pediatric tumor cell lines. The results show that after 21 days in culture CD3+ CD56+ CIK cells derived from the 6 pediatric patients accounted for a median of 28.3% of the entire culture (range, 10.7%-36.4%). Before expansion no such cells were found in any of the 6 children. Median lytic activity rates of CIK cells were 45.5% to 64.5%, rates that contrasted drastically to the lytic activity rates of PBL, which were only 8% to 12%. The findings of the present study are encouraging. They provide information for developing adoptive immunotherapy for future clinical trials with pediatric cancer patients, particularly those patients with minimal residual disease after intensive chemotherapy or stem cell transplantation (especially nonmyeloablative transplantation procedures).
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PMID:Generation of CD3+ CD56+ cytokine-induced killer cells and their in vitro cytotoxicity against pediatric cancer cells. 1262 54

Urotensin-II (U-II) was identified as the natural ligand of the G protein-coupled receptor GPR14, which has been correspondingly renamed Urotensin-II receptor (U2R). The tissue distribution of U2R and the pharmacological effects of U-II suggest a novel neurohormonal system with potent cardiovascular effects. We here report the human rhabdomyosarcoma cell line TE-671 as the first natural and endogenous source of functional U2R in an immortalized cell line. In TE-671 cells, U-II stimulated extracellular signal regulated kinase phosphorylation and increased c-fos mRNA expression. Furthermore, we demonstrate that the expression of U2R mRNA and functional U-II high affinity binding sites are serum-responsive and that they are specifically up-regulated by interferon gamma (IFNgamma). We propose that IFNgamma contributes to the previously observed increase of U2R density in the heart tissue of congestive heart failure (CHF) patients and we suggest that U2R up-regulation, as a consequence of an inflammatory response, could lead to a clinical worsening of this disease.
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PMID:The expression of urotensin II receptor (U2R) is up-regulated by interferon-gamma. 1475 94