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M Cantor

Publications and source records attributed to M Cantor.

14 recordsLinked to original sources
PubMed2006

CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies.

BACKGROUND: The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation. AIM: To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation. MATERIALS AND METHODS: We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts. RESULTS: There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having >or=4/5 methylated loci, and 17% (78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS. Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63% and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p<10(-5)) and non-CIMP MSS tumours (6.6%, p<10(-4)), respectively). CONCLUSION: CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.

Colorectal Neoplasms↗
PubMed2001

Missing value estimation methods for DNA microarrays.

MOTIVATION: Gene expression microarray experiments can generate data sets with multiple missing expression values. Unfortunately, many algorithms for gene expression analysis require a complete matrix of gene array values as input. For example, methods such as hierarchical clustering and K-means clustering are not robust to missing data, and may lose effectiveness even with a few missing values. Methods for imputing missing data are needed, therefore, to minimize the effect of incomplete data sets on analyses, and to increase the range of data sets to which these algorithms can be applied. In this report, we investigate automated methods for estimating missing data. RESULTS: We present a comparative study of several methods for the estimation of missing values in gene microarray data. We implemented and evaluated three methods: a Singular Value Decomposition (SVD) based method (SVDimpute), weighted K-nearest neighbors (KNNimpute), and row average. We evaluated the methods using a variety of parameter settings and over different real data sets, and assessed the robustness of the imputation methods to the amount of missing data over the range of 1--20% missing values. We show that KNNimpute appears to provide a more robust and sensitive method for missing value estimation than SVDimpute, and both SVDimpute and KNNimpute surpass the commonly used row average method (as well as filling missing values with zeros). We report results of the comparative experiments and provide recommendations and tools for accurate estimation of missing microarray data under a variety of conditions.

Algorithms↗
PubMed1988

Phospholipids and UDP-glucuronosyltransferase. Structure/function relationships.

The activation of delipidated microsomal UDP-glucuronosyltransferase from pig liver (GT2P type of enzyme) was studied as a function of several structural modifications of 1-palmitoyl-sn-glycero-3-phosphocholine, which is known to be a good activator of the enzyme. The following types of compounds were tested: substitution of H for OH at position 2; substitution of an ether for an acyl link at position 1; variation of the phosphorus-nitrogen or acyl ester-phosphate ester distances; removal of the glycerol backbone; optical isomers; and substitution of phosphoethanolamine for phosphocholine. Although there were variations in the extent to which these compounds activated delipidated enzyme, all the above types of lipids were effective in this regard. By contrast, lipids with a net negative charge did not activate the enzyme. They inhibited it reversibly. Positively charged lipids, even those lacking a phosphate group, were effective activators. These results indicate that GT2P is unlikely to interact with specific chemical groups of its phospholipid milieu. Effective activation appears instead to depend on the physical properties of the lipid environment.

Animals↗
PubMed1987

Gastric carcinogenesis: a model for the identification of risk factors.

In a series of extensive studies on gastric carcinogenesis, we have used Sprague-Dawley rats to examine the morphologic, histochemical, and biochemical effects of risk and protective factors on N-methyl-N'-nitro-N-nitroso guanidine (MNNG)-induced tumors in an attempt to link early observations with the end-point lesion, gastric cancer. We have observed that the putative risk factors sodium chloride (NaCl); a mixture of bile acids; aspirin; alcohol; and nitrite enhance MNNG-induced neoplasia of the gastric mucosa. On the other hand butylated hydroxyanisol (BHA), Se and difluromethylornithine (DFMO) were protective and inhibited the induction of gastric mucosal neoplasia. In most cases, early changes detected by a number of criteria correlated with the end-point, gastric neoplasia. This model appears to be useful in screening and evaluating chemicals for risk for or protection against gastric cancer.

Animals↗
PubMedDate not supplied

Gastric and oesophageal carcinogenesis: models for the identification of risk and protective factors.

Male weanling rats of the Charles River Sprague-Dawley strain were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the water for 3 months at the concentration of 75 ml/litre. Other real or potential risk factors were administered, alone or in combination with MNNG. When MNNG was administered in combination with NaCl, bile acids, aspirin or BHA, forestomach tumours were enhanced. MNNG-induced tumours were inhibited by selenium or by difluoromethylornithine, an ornithine decarboxylase inhibitor. BHA alone caused forestomach tumours. When BHA was administered by dietary means or by gavage, alone or in combination with MNNG, the gavage method resulted in greater tumorigenesis than dietary exposure. This increase was associated with increased [3H]thymidine labelling of forestomach epithelium and increased hyperplasia. Oesophageal carcinogenesis induced by methylbenzylnitrosamine (MBN) was enhanced by zinc deficiency, alcohol and 13-cis-retinoic acid. Zinc deficiency also resulted in oesophageal tumours in rats exposed to the hepatocarcinogen dimethylnitrosamine. Riboflavin deficiency injured oral and oesophageal epithelium and increased sensitivity to MBN-induced oesophageal tumours.

Administration, Oral↗