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1.  Folate and colorectal cancer prevention 
British Journal of Cancer  2008;100(2):233-239.
Anti-folate chemotherapy agents such as methotrexate and fluorouracil reduce proliferation of neoplastic cells by inhibiting DNA synthesis. Paradoxically epidemiological data suggests an inverse relationship between dietary folate intake and incidence of colorectal cancer (CRC). On the basis of this and other putative health benefits around 35% of the North American population take folic acid supplements, in addition to natural food folates and fortified flour and cereal grains. Recently, randomised controlled trials investigating folic acid as a secondary preventative agent in colorectal neoplasia have shed further light on the relationship between folate and colorectal carcinogenesis, corroborating data from animal models indicating opposing effects dependent on the timing of exposure in relation to the development of neoplastic foci. A ‘dual-modulator' role for folate in colorectal carcinogenesis has been proposed in which moderate dietary increases initiated before the establishment of neoplastic foci have a protective influence, whereas excessive intake or increased intake once early lesions are established increases tumorigenesis. Functional polymorphic variants in genes encoding key enzymes in the folate metabolic pathway add a further layer of complexity to the relationship between folate and CRC risk. Here, we review the evidence concerning the efficacy and safety of folate as a potential CRC chemopreventive agent.
PMCID: PMC2634716  PMID: 19088716
folate; colorectal cancer; prevention
2.  Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma 
British Journal of Cancer  2007;97(10):1449-1456.
The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene–gene and gene–nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case–control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31–0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (Pinteraction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene–gene and gene–nutrient interactions.
PMCID: PMC2360236  PMID: 17971770
thymidylate synthase; polymorphism; folate; colorectal adenoma
3.  Combination chemotherapy with carboplatin, capecitabine and epirubicin (ECarboX) as second- or third-line treatment in patients with relapsed ovarian cancer: a phase I/II trial 
British Journal of Cancer  2006;94(1):74-78.
Platinum-based combination chemotherapy has been proven to be superior to single-agent platinum in the treatment of relapsed ovarian cancer after a treatment-free interval of more than 6 months. A response rate of 41% was previously reported by our group using a combination of epirubicin, cisplatin and 5-FU in patients who relapsed within 12 months, we therefore assessed a similar, but more convenient combination of epirubicin, carboplatin and capecitabine in this phase-I/II trial. In total, 18 patients with recurrent epithelial ovarian carcinoma, who had not received more than two lines of chemotherapy and the treatment-free interval exceeded 6 months were treated with carboplatin AUC5, epirubicin 50 mg m−2 and capecitabine at several dose levels on continuous 21 day cycles and 14 of 21 day cycles. Patients were assessed for toxicity and by CT and CA-125 for response. The overall response rate was 61.1%, with three complete and eight partial responses. Grade 3/4 haematological toxicity was seen in 10 out of 18 patients and caused dose reductions and treatment delays. The combination of epirubicin, carboplatin and capecitabine showed good activity but caused excessive toxicity. A phase-II trial using carboplatin and capecitabine is underway.
PMCID: PMC2361084  PMID: 16306873
capecitabine; carboplatin; epirubicin; ovarian cancer; relapse
4.  Textbook of Melanoma 
British Journal of Cancer  2004;90(11):2247-2248.
PMCID: PMC2409503
5.  Telomerase activity in human pleural mesothelioma 
Thorax  1998;53(11):915-918.
BACKGROUND—Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.
METHODS—Telomerase activity was semi-quantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.
RESULTS—Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.
CONCLUSIONS—Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.

PMCID: PMC1745102  PMID: 10193387
6.  Use of homoduplex ribosomal DNA spacer amplification products and heteroduplex cross-hybridization products in the identification of Salmonella serovars. 
When the hypervariable 16S-23S intergenic spacer regions found in prokaryotic ribosomal DNA (rDNA) are amplified from conserved adjacent sequences, homoduplex double-stranded DNA structures and heteroduplex structures containing substantial regions of single-stranded DNA are generated. The electrophoretic separation of these structures results in product profile patterns, which may be organized into highly correlated pattern groups of ribosomal spacer and heteroduplex polymorphism (RS/HP) types. In a test panel of 380 Salmonella strains that were analyzed by this procedure, 36 unique RS/HP types were observed. Of the 28 serovars in the test group, 21 showed single characteristic RS/HP types. The remaining seven serovars each contained multiple RS/HP types, which were also unique to individual serovars. Formation of heteroduplex structures with a substantially reduced electrophoretic mobility was observed in 29 of the 36 RS/HP pattern types. Because the mobility of these heteroduplex structures is sensitive to intergenic spacer sequence composition, the presence of these structures adds an additional diagnostic feature that is extremely useful in the differentiation of Salmonella serovars. The RS/HP types show sufficient diversity to be useful in the identification of many commonly observed Salmonella serovars. This analytical procedure is simple to perform and is well suited to rapid and inexpensive screening of large numbers of Salmonella strains.
PMCID: PMC168059  PMID: 8702266

Results 1-6 (6)