The expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. Reverse transcriptase-polymerase chain reaction of a surgically biopsied glioblastoma was carried out using the degenerative oligonucleotide primers corresponding to the sequences of the human facilitative glucose transporter family, and polymerase chain reaction products were hybridized with human GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5 cDNA probes. The results showed that a biopsied glioblastoma expressed GLUT1, GLUT3, and GLUT4 glucose transporter genes. Northern blot analysis of total RNA (10 micrograms) from a biopsied glioblastoma showed the transcripts of only GLUT1 and GLUT3, suggesting that the expression of insulin-responsive glucose transporter GLUT4 mRNA is relatively low. Immunoblot analysis of biopsied glioblastoma tissues by polyclonal antibodies against the C-terminal synthetic peptides of GLUT1, GLUT3, and GLUT4 showed a single band of each polypeptide. However, elevated expression of GLUT1 and GLUT3 glucose transporters was not observed in the glioblastoma. Astrocytic tumor tissues (n = 14) were also examined immunohistochemically. Reactive products for GLUT1 were observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. GLUT3 was positive in astrocytic tumor cells in all cases. Three of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells. These results suggest that the facilitative glucose transport may be altered in astrocytic tumor cells and thus display a significant change in glucose metabolism.

A 5-year-old girl with congenital central hypoventilation syndrome associated with Hirschsprung's disease (Ondine-Hirschsprung syndrome) representing a missense mutation in exon 12 of the receptor tyrosine kinase (RET) proto-oncogene is reported. Using a direct sequencing technique, genomic DNA obtained from the patient's peripheral leukocytes was analyzed for its nucleotide sequences in all 20 exons of the RET proto-oncogene, seven regions of the 1st to the 7th exon of the endothelin-B receptor gene and endothelin 3 gene, including sequences corresponding to proteolytic cleavage sites. The analysis revealed that adenine at the 2116th base in the 12th exon in the RET proto-oncogene was substituted by guanine, supposedly resulting in a mutation of Thr 706 to Ala. No other mutational change was observed in the gene examined in this case. Mutation analysis has not been described previously on the gene in this disease complex. Mutation in this case might impair the maturation of the tyrosine kinase protein and subsequently cause neurocristopathy supposedly originating from the neural crest.

This study provides further gene alterations as disease-causing mutations in Japanese cases of sporadic Hirschsprung disease. However, the low mutation rate of the susceptibility genes may indicate that Hirschsprung disease arises from a combination of genetic and environmental factors.

The polyamine biosynthetase, ornithine decarboxylase (ODC), involved in tumor promotion, was investigated in grossly normal mucosa obtained from surgically resected large bowel; 48 cases with and six cases without large bowel cancer. The mucosal ODC activity was significantly higher in 17 multiple tumor cases bearing adenocarcinoma(s) plus adenoma(s) than in 31 solitary tumor cases bearing one adenocarcinoma alone. It was higher in the mucosa of the two groups of cases than in the mucosa of individuals without large bowel cancer. Furthermore, the enzyme activity in left-sided cancer cases was significantly higher than that in right-sided cancer cases. Carcinoma tissue showed a remarkable high level of enzyme activity, compared with the normal mucosa. The results indicate the larger the number of tumors the higher the level of the ODC activity in the normal mucosa, particularly in left-sided cancer cases. It is concluded that the mucosal ODC may provide a good biological marker to detect individuals at higher risk for large bowel cancer due to exogenous or endogenous factors, and thus contribute to the prevention of mortality from large bowel cancer.

The relationship of prostaglandin E2, of which a large amount is produced in various neoplasms, and hematogenous distant metastases was investigated in a total of 44 colorectal cancer patients because of its varied pathophysiologic potentials. The authors found significantly high levels of PGE2 in local venous blood draining the carcinoma and in peripheral blood in cases with liver or lung metastasis, as well as a significantly large amount of PGE2 production in the carcinoma tissue. The results suggest that increased local blood PGE2 could enhance the metastasis formation, and increased peripheral blood PGE2 may be useful in the detection of such metastasis in colorectal cancer.