We evaluated efficacy, @entity137 and potential synergism of adenoviral-mediated @entity1014 kinase (tk)- @entity4540 (GCV) gene therapy in combination with 4 cytotoxic chemotherapeutic agents ( @entity632 , @entity900 , @entity1138 , and @entity1499 ) in 3 @entity1 @entity150 cell lines. Cell lines were exposed to (1) 10 different concentrations of adenovirus expressing tk plus GCV; (2) 8 different concentrations of either @entity632 , @entity1499 , @entity1138 or @entity900 ; or (3) combination treatment consisting of either low-, medium- or high-dose tk-GCV gene therapy plus 8 different concentrations of a single chemotherapeutic agent. Cell survival was determined using a @entity98 -based cell proliferation-assay. For most combinations, adding chemotherapy to tk-GCV gene therapy did not result in any therapeutic benefit. In some scenarios, we observed modest improvement with combinations of high-dose tk-GCV gene therapy and high-dose standard chemotherapy over tk-GCV monotherapy. Low concentrations of @entity1499 enhanced the antitumor effects of low- and medium-dose tk-GCV gene therapy. Low level negative interference between tk-GCV gene therapy and chemotherapy occurred in some combinations but was overall negligible. In general, adding chemotherapy to tk-GCV gene therapy did not demonstrate significant therapeutic benefit in vitro. High doses of chemotherapeutic agents should be used in combination with tk-GCV gene therapy in order to take advantage of the occasional instance where modest improvement occurred with combination therapy. Additional studies exploring the role of @entity1499 in enhancing the tk-GCV system are required. Investigation of other, potentially more synergistic chemotherapeutic agents in combination with tk-GCV is warranted.

Combination of adenovirus-mediated XXXX kinase gene therapy with cytotoxic chemotherapy in @entity150 in vitro.

@entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity1138 :: ('MESH:D016685', 'Chemical') :: ['mitomycin C'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity150 :: ('MESH:D001749', 'Disease') :: ['bladder cancer'] @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine'] @entity4540 :: ('MESH:D015774', 'Chemical') :: ['ganciclovir'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate']
@entity1014 :: (MESH:D013936,Chemical) :: ['thymidine']
