Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using monospecific immune antiserum the expression of beta-lactamase bacterial gene (from the plasmid pBR322) in transformed TK+ Chinese hamster cells was studied. It is shown that in some TK+-clones the beta-lactamase gene is expressed and this expression is stimulated by an inhibitor of DNA methylation-5-azacytidine. Two physically linked genes (the Herpes simplex thymidine kinase gene, and the beta-lactamase gene) introduced into the Chinese hamster cells on the same plasmid are found to be expressed independently.
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PMID:[Expression in Chinese hamster transformant TK+-cells of the bacterial gene for beta-lactamase]. 241 Oct 34

There has been little investigation of bacteria as gene delivery vectors. Here, we demonstrate that genetically engineered Salmonella have many of the desirable properties of a delivery vector, including targeting of multiple tumors from a distant inoculation site, selective replication within tumors, tumor retardation, and the ability to express effector genes, such as the herpes simplex virus thymidine kinase (HSV TK). When wild-type Salmonella were introduced into melanoma-bearing mice, the bacteria were found within the tumor at levels exceeding 10(9) per g, although as pathogens, they caused the death of the mice. However, when attenuated, hyperinvasive auxotrophic mutants were used, the tumor-targeting and amplification phenomena were retained, whereas their pathogenicity was limited. With such attenuated strains, the tumor:liver ratios ranged between 250:1 and 9000:1. When these auxotrophs were inoculated i.p. into C57B6 mice bearing B16F10 melanomas, they suppressed tumor growth and prolonged average survival to as much as twice that of untreated mice. A plasmid containing the HSV TK gene with a beta-lactamase secretion signal was constructed that, when expressed, resulted in translocation to the periplasm and phosphorylation of the prodrug ganciclovir. Melanoma-bearing animals inoculated with HSV TK-expressing Salmonella showed ganciclovir-mediated, dose-dependent suppression of tumor growth and prolonged survival in addition to that seen with bacteria alone. The results demonstrate that attenuated Salmonella would be useful both for inherent antitumor activity and delivery of therapeutic proteins to cancer cells in vivo.
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PMID:Tumor-targeted Salmonella as a novel anticancer vector. 937 66