Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapeutic agents such as cytosine arabinoside (ARA-C) and adenine arabinoside (ARA-A) have been shown to eliminate or suppress replication of some DNA viruses. These effects were however associated with systemic side-effects to the treated hosts. We are currently exploring a strategy to construct conjugates between these antiviral agents and monoclonal antibodies directed against viral surface proteins. Such conjugates should enable specific delivery of the antiviral agents to their preferred site of action. In the present study, monoclonal antibodies to hepatitis B virus surface antigen (HBsAg) of the IgG2a and IgM isotypes were conjugated to ARA-C via a dextran bridge. The use of dextran enables the binding of a high number of drug molecules to the antibody with minimal loss of activity. Briefly, partially oxidized dextran was coupled to ARA-C and then to monoclonal anti-HBs. Following the conjugation process, the IgG2a anti-HBs-(dex)-ARA-C conjugate retained its capacity to bind to HBsAg fixed to a solid matrix as compared to non-conjugated homologous antibodies. Conjugates between ARA-C and IgM anti-HBs lost a significant degree of their binding activity to purified HBsAg. However, conjugates containing anti-HBs of both isotypes bound specifically to PLC/PRF/5 human hepatoma cells that express HBsAg on their cell surface. Conjugates containing non relevant monoclonal antibodies did not bind to target cells. Pharmacologic activity of the various compounds was assessed by an [3H]thymidine incorporation assay in hepatoma cells in culture. IgM and IgG2a containing conjugates caused suppression of [3H]thymidine incorporation into PLC/PRF/5 cells. This effect was more pronounced for conjugates containing monoclonal IgM anti-HBs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conjugates between monoclonal antibodies to HBsAg and cytosine arabinoside. 303 37

Hepatoma up-regulated protein (HURP) is a recently identified novel cell-cycle-regulated gene. The HURP gene is overexpressed in human hepatocellular carcinoma and transitional cell carcinoma. The cellular function of HURP is not fully understood. In this study, the NIH3T3 cells transduced with the exogenous HURP gene manifested the general characteristics of tumor cells, which had higher growth rate in low-serum media and advanced ability of colony formation on agarose-based plates. Transduced HURP was capable of specifically enhancing the chemosensitivity of deoxycytosine analogs, such as gemcitabine, ARA-C, and 5-AZA-CdR, but neither had an effect on the response of DNA intercalating agents, such as cisplatin, carboplatin, and doxorubicin, nor on the response of microtubule stabilizers, such as paclitaxel, docetaxel, and vinblastine. These results indicate that the HURP gene might be a potential oncogenic gene and capable of enhancing the chemosensitivity of deoxycytosine analogs in NIH3T3 cells.
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PMID:Enhanced transformation and chemosensitivity of NIH3T3 cells transduced with hepatoma up-regulated protein. 1636 48