Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu/nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0. 05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RARalpha, RXRalpha, and RXRbeta were similar in the two cell lines, while RARbeta expression was higher in SCC-2 over SCC-38, and RARgamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.
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PMID:Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors. 1054 87

Expression of genes such as cytokeratin 19 (CK19), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) has been investigated at mRNA level in peripheral blood of carcinoma patients to detect the presence of circulating tumor cells (CTC). We performed this study because recent literature emphasizes that the importance of CK19, 20 and EGFR mRNAs in CTC as prognostic factors remains unclear especially for breast, head and neck and colon cancer patients. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization was performed in blood samples from 47 subjects (12 colorectal, 15 head and neck and 20 breast carcinoma patients), as well as in 35 healthy donors. The CK19 expression was found in 36/47 patients (9 colorectal, 9 head and neck and 18 breast cancer), two patients (one affected by colorectal and one by head and neck cancer) were positive for CK20 whereas EGFR was found expressed in 9 patients (3 colorectal, 5 head and neck and one breast cancer). Seven of 35 and 4/35 healthy donors displayed positivity for the expression of CK19 and CK20 genes respectively, whereas no EGFR mRNA was found in this group. The correlation of the detection of CTC in peripheral blood with progression of the disease in a follow-up period of 40 months did not show any prognostic value to the presence of mRNAs of these biomarkers in blood. We believe that research should be addressed, at least for breast cancer, to the identification of occult metastases in sentinel lymph nodes, such as recently performed in melanoma patients.
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PMID:Detection of CK19, CK20 and EGFR mRNAs in peripheral blood of carcinoma patients: correlation with clinical stage of disease. 1246 72