The H2 complex has an important role in determining susceptibility to viral and chemical leukemogenesis in inbred mice. This also applies to transplantable leukemias, within the syngeneic system. In this respect H2K is sensitive, H2d is relatively sensitive, and H2b is absolutely resistant to leukemia induction and transplantation. In our present study we investigated the effect of Cyclophosphamide, (a known chemical leukemogen) on onco/suppressor gene expression in CBA/Ca mice, very shortly after treatment with chemical carcinogen without any manifestation of tumour/leukemia symptoms. Here we describe, in a "short-term" experiment, the gene expression of Ha-ras, c-myc and p53 which was similar to the leukemia induction in a "long-term" experiment. H2K showed marked elevation in terms of onco/suppressor gene expression. H2b expression was modest and H2d turned out to be more or less silent. The results obtained from a short term gene expression investigation shows similarity to those obtained earlier from long term leukemia inducing experiments.

Animals↗

PubMedDate not supplied

Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1 enzymes.

Chemical carcinogens generally require metabolic activation in order to be able to bind to DNA and contribute to cancer causation. Most of the human metabolizing enzymes are genetically polymorphic, and these polymorphisms may affect the enzyme activity or inducibility. In our present study we investigated the connection between genetic polymorphism of cytochrome P450 1A1, 2E1 (phase I enzymes) and glutathione-S-transferase M1 (a phase II enzyme) and colorectal cancer occurrence in a Hungarian population. The CYP 2E1 c2 allele proved to be in significant association with colorectal cancer (OR: 1.91, 95% CI: 1.05-3.52), the CYP 1A1 Val allele was also overrepresented among colon cancer patients (OR: 1.57, 95% CI: 0.90-2.74), and the frequency of GSTM1 homozygous 0 genotype showed only minor difference (OR: 1.19, 95% CI: 0.75-1.35). Combined analysis of the polymorphisms showed that individuals carrying all the three "high-risk" alleles have a strikingly increased risk for sporadic colorectal cancer (OR: 4.62, 95% CI: 1.23-25.68).

Adenocarcinoma↗

PubMedDate not supplied

Phonological and semantic information in word and nonword reading in a deep dyslexic patient.

Deep dyslexia is diagnosed when brain-injured, previously literate adults make reading errors that include hallmark semantic paralexias (e.g., reading HEART as BLOOD) and are also impaired at reading nonwords (e.g., FRIP). The diversity of these symptoms have led most researchers to conclude that there are multiple sources of impairment in this syndrome and that one of the most critical is a failure to process phonological information at a sublexical level. The patient (SD) reported in this study fits the deep dyslexia profile to the extent that she makes several semantically related reading errors. She also shows the classic frequency and image ability effects of the syndrome. However, as we report, she does read some nonwords correctly and she shows a strong advantage for naming when phonemic cues are presented. We discuss the performance of SD, on these preliminary tasks, in terms of a phonological selection impairment.

Dyslexia↗

PubMedDate not supplied

1-Nitropyrene induces elevated expression of oncogenes and tumor suppressor genes 24 hours after treatment in CBA/Ca mice.

In an earlier experiment we found that 1-nitropyrene treatment causes an increase in the expression of certain onco/suppressor genes in different organs of CBA/Ca mice. In order to further study the kinetics and significance of these gene expression changes, we determined the effect of 1-nitropyrene treatment on the expression of c-myc, p53, Ha-ras, N-ras, and Ki-ras genes, 24 hours after treatment. Expression of the ras family did not change during the studied interval, while elevated expression of c-myc and p53 genes was observed in the spleen, bone marrow and lymph nodes (only c-myc in the latter). The results suggest a different pattern for the involvement of the ras genes in 1-nitropyrene-caused carcinogenesis, and also underlines the differences in the organ specificity of chemical carcinogens in humans and in experimental animals. In the present study, we also confirmed the in vivo applicability of early gene expression changes as biomarkers of carcinogenic exposure.

Animals↗

PubMedDate not supplied

The prognostic value of the presence of mutations at the codons 12, 13, 61 of K-ras oncogene in colorectal cancer.

The predictive and prognostic value of the c-K-ras mutation is still unequivocal despite extensive and intensive studies. Investigation of the occurrence of mutations in 88 colorectal cancer patients' specimens using the polymerase chain reaction (PCR) is reported: age: 61.9 years (27-80), gender: 48 male, 42 female, Dukes' stages: 43 at B, 35 at C, 10 at D, primary of tumour: 52 colon, 36 rectal adenocarcinoma. Mutation of one of the three ras-codons was detectable in the 54 cases, more frequently at the Dukes' stage C (p < 0.05). The ras-mutation correlated to a more elevated death-rate in the Dukes' B and C stages (p < 0.01). Mean survival time and time to progression were significantly longer at the Dukes' stage B if mutation was not detected (p < 0.01). The genetic alteration occurred significantly more frequently at tumours of the right-side colon, than the left side (p < 0.02) or rectum (p < 0.05). However, in the age group of 41-50 years, it was more significantly identified in the cases of rectal cancer (p < 0.01). At the age of 51-60 years mutations were detected in men at a higher rate (p < 0.05). The mutation of the codon 13 appeared more frequently in the cases of local recurrences (p < 0.05). The occurrence of the ras-oncogene is a sign of an extremely malignant potential of tumour. This fact manifested itself in the time to progression and mean survival time of patients at the same clinical or pathological stage. The higher frequency of genetic alterations at the proximal colon may be the reason for more unfavourable prognosis of the disease localised to this site. Reconstructing the molecular events, the presence of the ras mutation proved to be an important element for prognosis of the disease and should be a basis of potentially individualised therapeutic intervention.

Biomarkers, Tumor↗

PubMedDate not supplied

C-myc amplification and cluster analysis in human gastric carcinoma.

The tumour samples ot 23 patients (9 male, 14 female, aged 28-85) were randomly selected for the study. DNA was isolated from paraffin embedded tissue for quantitative dot-blot hybridization, in order to determine the amplification values for the c-myc and K-ras oncogenes. The clinical and histological parameters studied were as follows: grade, TNM staging system, Lauren's histological type, localization and the severity of the disease. Amplified c-myc was found in 6 cases. Amplification was concomitant with c-myc overexpression detected with immunohistochemical staining. The amplification--9.1-fold on the average (ranging from 2.12 to 18.2) was significantly associated with the presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but with none of the other parameters. No case with K-ras amplification was recorded. The result of the multivariate cluster analysis proved that age was the decisive factor in the segregation process. This age-related distribution (69 vs. 40, p < 0.001), however, did not coincide with either the incidence of distant metastasis or c-myc amplification.

Adenocarcinoma↗