Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer cells transcriptionally activate many genes that are important for uncontrolled proliferation and cell death. Deregulated transcriptional machinery in tumor cells usually consists of increased expression/activity of transcription factors. Ideally, cancer-specific killing can be achieved by delivering a therapeutic gene under the control of the DNA elements that can be activated by transcription factors that are overexpressed and/or constitutively activated in cancer cells. Additionally, tumor-specific translation of tumor-killing genes has been also exploited in cancer gene therapy. Based on these rationales, cancer-specific expression of a therapeutic gene has emerged as a potentially successful approach for cancer gene therapy. To achieve tumor-specific expression, cancer-specific vectors are generally composed of promoters, enhancers, and/or 5'-UTR that are responsive to tumor-specific transcription factors. A number of cancer-specific promoters have been reported, such as those of probasin, human telomerase reverse transcriptase, survivin, ceruloplasmin, HER-2, osteocalcin, and carcinoembryonic antigen. Evidences suggest that the enhancer element targeted by beta-catenin can be useful to target colon cancer cells. The 5'-UTR of the basic fibroblast growth factor-2 has been reported to provide tumor specificity. Moreover, a variety of therapeutic genes demonstrated direct antitumor effects such as those encoding proapoptotic proteins p53, E1A, p202, PEA3, BAX, Bik, and prodrug metabolizing enzymes, namely thymidine kinase and cytosine deaminase. As cancerous cells of different origins vary significantly in their genetic, transcriptional/translational, and cellular profiles, the success of a cancer gene therapy will not be promised unless it is carefully designed based on the biology of a specific tumor type. Thus, tremendous research efforts have been focused on the development of non-viral vectors that selectively target various tumors resulting in minimal toxicity in the normal tissues. Significant progresses were also made in the exploitation of various novel apoptotic, cytotoxic genes as therapeutic tools that suppress the growth of different tumors. Together, these recent advances provide rationales for future clinical testing of transcriptionally targeted non-viral vectors in cancer patients.
 ...
PMID:Cancer-specific gene therapy. 1609 14

Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Studies in recent years indicated that survivin(sur) expression was associated with the biological behaviors of gastric carcinoma. In the present study, targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell were investigated, the recombinant pSCT vector containing CD and TK genes driven by sur promoter was constructed and transfected into SGC-7901 cells. After adding the CCV and 5-FC, the effects of double suicide genes on cell growth, cell cycle and proliferation were determined by MTT assay and flow cytometry (FCM). The results showed that sur promoter could specifically drive the expression of double CD/TK gene in SGC-7901 cells, whereas not in the normal GES-1 cell. After using CCV and 5-FC, the growth of SGC-7901 cells was inhibited. G1 phase proportion was significantly higher in SGC-7901 cells transfected with double suicide genes than the untransfected cells. These results suggest that CD and TK double suicide genes driven by sur promoter could provide a new approach for enhancing selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.
 ...
PMID:Targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell. 2057 10

There are currently no effective therapies for cancer patients with advanced ovarian cancer, therefore developing an efficient and safe strategy is urgent. To ensure cancer-specific targeting, efficient delivery, and efficacy, we developed an ovarian cancer-specific construct (Survivin-VISA-hEndoyCD) composed of the cancer specific promoter survivin in a transgene amplification vector (VISA; VP16-GAL4-WPRE integrated systemic amplifier) to express a secreted human endostatin-yeast cytosine deaminase fusion protein (hEndoyCD) for advanced ovarian cancer treatment. hEndoyCD contains an endostatin domain that has tumor-targeting ability for anti-angiogenesis and a cytosine deaminase domain that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic drug, 5-fluorouracil. Survivin-VISA-hEndoyCD was found to be highly specific, selectively express secreted hEndoyCD from ovarian cancer cells, and induce cancer-cell killing in vitro and in vivo in the presence of 5-FC without affecting normal cells. In addition, Survivin-VISA-hEndoyCD plus 5-FC showed strong synergistic effects in combination with cisplatin in ovarian cancer cell lines. Intraperitoneal (i.p.) treatment with Survivin-VISA-hEndoyCD coupled with liposome attenuated tumor growth and prolonged survival in mice bearing advanced ovarian tumors. Importantly, there was virtually no severe toxicity when hEndoyCD is expressed by Survivin-VISA plus 5-FC compared with CMV plus 5-FC. Thus, the current study demonstrates an effective cancer-targeted gene therapy that is worthy of development in clinical trials for treating advanced ovarian cancer.
 ...
PMID:Targeted endostatin-cytosine deaminase fusion gene therapy plus 5-fluorocytosine suppresses ovarian tumor growth. 2256 48