0000000000479054
AUTHOR
Rosario Sanguedolce
Could a variant structural form of thymidylate synthase gene of metastatic colorectal cancer patients be related with the poor response to 5 Fu treatment?
Background: Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and is the target of 5-fluorouracil (5-Fu). TS levels vary considerably among tumors and the response to 5-FU is influenced by the intratumoral activity of the enzyme, with high levels generally being associated with a poor response. Response to 5-FU also depends on TS structure and some researchers showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines so the aim our study is to analyze the whole coding regions of the TS gene to evaluate a possible mechanism of 5 Fu resistance. Materials and Methods: We performed the TS-DNA gene sequence in 68 colorectal cancer (CRC) …
RELATIONSHIP BETWEEN THE THYMIDYLATE SYNTHASE, p53 LEVELS AND THE TREATMENT BY CMF DRUG COMBINATION VERSUS TAXANES IN THE LOCALLY ADVANCED CARCINAMO OF THE BREAST
Low cell proliferation marker and low thymidylate synthase levels in the highly aggressive signet ring cell variant histotype of colorectal carcinoma
Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and lts Possible Relation with the S-Fluorouracil Drug Response
Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity*. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) san-rples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA …
RELATIONSHIP BETWEEN THYMIDYLATE SYNTHASE EXPRESSION AND p53 LEVELS WITH THE TREATMENT BY CYCLOPHOSPHAMIDE, 5-FLUOROURACIL CHEMOTHERAPY (CMF) VERSUS DOCETAXEL IN THE LOCALLY ADVANCED CARCINOMA OF THE BREAST.
Relationship between Thymidylate synthase and p53 and response versus taxane adjuvant chemotherapy for breast carcinoma
Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients wit…
Difference in ki67 and Thimidylate Synthase expressin in primary tumour compared with metastatic nodes in breast cancer patients
DIFFERENCE IN KI67 AND THYMIDYLATE SYNTHASE, P53 LEVELS AND THE TREATMENT BY CMF DRUG COMBINATION VERSUS TAXANES IN THE LOCALLY ADVANCED CARCINOMA OF THE BREAST
Difference in ki67 and thymidylate synthase expression in primary tumour compared with metastastic nodes in breast cancer patients. european society for the study of purine and pyrimidine metabolism in man
Decreased expression of thymidylate synthase and low proliferation index by Ki67 in "signet ring cell component of colorectal carcinoma"
Relationship between the thymidiylate synthase, P53 levels and the treatment by CMF drug combination versus taxanes in the locally advanced carcinoma of the breast
Expression of a specific Thymidylate synthase polimorfic allele in metastatic colorectal patients is regulated by Myeloid Zinc Finger 1.
Thymidylate Synthase (TS) is the target enzyme for fluoropyrimidine anticancer drugs. Its expression is regulated by the number of functional upstream stimulatory factor (USF) E box consensus elements present on its 5’ untranslated region. To date are known different polymorphisms, the first one consisting of 2 or 3 repeat of a 28 bp sequence, a further single nucleotide polymorphism (SNP) consisting in a G>C substitution within the second repeat of 3R (3RG>3RC) and recently it has been identified an additional SNP a G>C substitution at the 12th nucleotide in the first repeat of the 2R allele (2RG>2RC). These polymorphisms can influence TS expression, in particular 3R/3R genotype and the pr…
Relationdhip between the thymidylate synthase, P53 levels and the treatment by CMF drug combination versus taxanes in the locally advanced carcinoma of breast
Possible role of differential metalloproteinase 1 expression in signet ring cell and intestinal colorectal carcinoma histotypes
Background: Pure signet ring cell colorectal carcinoma ( SRCC) is an infrequent and highly malignant histological variant of colorectal cancer (CRC), while it is present as a histological component in colorectal carcinomas more frequently. Materials and Methods: The aim of this was to widen the knowledge of the biological factors involved in the pathogenesis and aggressiveness of SRCC by the identification and evaluation of possible molecular abnormalities. By means of immunohistochemistry the expression of the proteolytic degradation enzyme matrix metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens I, II, III and of the adhesion proteins E-cadherin, B-catenin an…
Relationship between the thymidylate synthase, p53 levels with the treatment by Cyclophosphamide, Metotrexate, 5-Fluorouracil chemotherapy (CMF) versus Docetaxel (TXT) in the locally advanced carcinoma of breast.
Decreased expression of thymidylate synthase and low proliferation index assessed by ki67 in " signet ring cell component" of colorectal carcinomas
DIFFERENT EXPRESSION OF E-CADERINE, BETA CATENIN AND FIBRONECTIN IN SIGNET RING CELL AND INTESTINAL CARCINOMA.
"Antitumor effects of the novel NF-kB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on human hepatic cancer cells: analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production”.
We tested the novel NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) in the hepatic cancer (HCC) HepG2, HA22T/VGH and HuH-6 cells. The sensitivity to the cell growth inhibitory and apoptotic effects of the agent increased along with the levels of constitutively activated NF-kappaB, which were low in HepG2 and higher in HA22T/VGH and HuH-6. In HA22T/VGH, DHMEQ exhibited synergy with cisplatin. In the same cells, DHMEQ exerted dose-dependent decreases in the nuclear levels of activated NF-kappaB and attenuated NF-kappaB activation by cisplatin. It down-regulated Bcl-XL mRNA in a dose-dependent manner and up-regulated that of Bcl-XS. It also decreased interleukin 6 (IL-6), NAIP and, …
Differing expression of metalloprotease and of adhesion molecules in signet-ring cell and intestinal colorectal carcinoma.
Abstract. Background: Pure signet-ring cell colorectal carcinoma (SRCC) is an infrequent and highly malignant histological variant of colorectal cancer (CRC), while it is present as a histological component in colorectal carcinomas more frequently. Materials and Methods: The aim of this work was to widen the knowledge of the biological factors involved in the pathogenesis and aggressiveness of SRCC by the identification and evaluation of possible molecular abnormalities. By means of immunohistochemistry the expression of the proteolytic degradation enzyme matrix metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens I, II, III and of the adhesion proteins Ecadherin,…