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Guy Rosner

Publications and source records attributed to Guy Rosner.

4 recordsLinked to original sources

The changing incidence and sites of colorectal cancer in the Israeli Arab population and their clinical implications.

Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly proximal cancer, but increasing CRC is now noted. We examined this trend and CRC site and compared them to the total Jewish population and to the low-risk Jews of Asian-African origin. Israel Cancer Registry CRC data, 1982-2002, for Arabs and Jews was computed by gender, age and site: rectal cancer included recto-sigmoid junction; "right-sided" CRC included the proximal colon up to and also the splenic flexure. During 1982-2002, Arab CRC trends increased significantly in both sexes due to left-sided CRC (women, p = 0.01; men, p = 0.02) and rectal cancers (p = 0.05). Left-sided CRC increased significantly in both men and women aged > or = 65 years (p = 0.02). Comparing 1982-1984 to 2000-2002, the proportion of right-sided CRC decreased in both genders (p < 0.01) from 39.4 to 27.1% of male CRC, and from 44.8 to 31.3% in females. In general, this pattern of increasing rectal and left-sided CRC had been seen over a decade earlier in Jews of Asian-African origin and then their trend reversed during the last decade. In conclusion, there is a recent trend for left-sided CRC in Israeli Arabs, probably related to their changing life style. These results should influence their cancer preventive lifestyle recommendations, and CRC screening and diagnostic methodologies used.

Age Distribution↗

Array-based comparative genome hybridization in clinical genetics.

Abnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array-based comparative genomic hybridization (array-CGH) is a high-resolution, whole-genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false-negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false-positive rate of 0.2% was calculated for clone-by-clone analysis, whereas the per patient false-positive rate was 20%. Array-CGH is a powerful tool for the rapid and accurate detection of genetic disorders associated with copy number abnormalities and can significantly improve clinical genetic diagnosis and care.

Abnormalities, Multiple↗

Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis C.

OBJECTIVE: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. METHODS: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, 'fast fibrosers' and 'slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. RESULTS: Forty-two patients were classified as 'fast fibrosers' and 33 patients as 'slow fibrosers'. The frequency of CYP2D6*4 allele in the 'fast fibrosers' (34.5%) was significantly higher compared with the 'slow fibrosers' (15%) (P-value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the 'slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). CONCLUSION: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients.

Adult↗

[Anoikis--a specific form of programmed cell death].

Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation and engraftment. Apoptosis triggered by cell detachment from the extracellular matrix, which occurs during hepatocyte isolation, is a phenomenon termed "anoikis". It's importance in the normal physiologic development of the human body, as well as in disease states, has been described. Cancer cells harbor anoikis resistance allowing spread to occur. Activation of the protein Fas associated death domain/MORT1 initiates the apoptosis cascade, with further downstream activation of caspase 8, Bid, cytochrome c and the executioner caspases. The anti-apoptotic protein family (bcl-2) and integrins, in particular beta 1 integrin, balance the pro apoptotic signals. The family of caspase enzymes, currently including 14 members, is subdivided by the prodomain length, specific substrate and phylogenetic analysis, and plays a crucial role in the apoptotic cascade. Therefore, understanding the molecular biology of apoptosis and specifically the "form" termed anoikis, has advanced clinical implications in cancer and cell therapy research.

Anoikis↗