Activation of the beta-catenin gene by interstitial deletions involving exon 3 as an early event in colorectal tumorigenesis

beta-Catenin has been identified as an oncogene in several tumors including colorectal cancers. beta-Catenin gene is activated by interstitial deletions involving exon 3 in colorectal carcinomas of Japanese population, in contrast to amino acid substitutions detected among Caucasian population. The aim of this study was to examine the type and frequency of beta-catenin gene mutation during early stages of colorectal tumorigenesis. We screened 100 colorectal adenomas for somatic mutations in the beta-catenin gene by single-strand conformation polymorphism method, as well as polymerase chain reaction amplification. In cases with mutations, sequencing analyses and immunohistochemical staining were also performed. Somatic interstitial deletions of 272-413 bp, each of which included all parts of exon 3, were detected in three tumors. However, no adenoma carried missense mutations. We confirmed accumulation of aberrant beta-catenin protein in cytoplasm and nuclei of adenoma cells by immunohistochemical analysis. Our results suggested that activation of the beta-catenin gene by interstitial deletions involving exon 3 might be less frequent compared with frequent alterations of adenomatous polyposis coli (APC) gene, but could be an early event in colorectal tumorigenesis equivalent to APC gene alterations in the Japanese population.     

Genetic polymorphism in CYP17 and breast cancer risk in Japanese women

A case–control study was conducted to investigate the association of two genetic polymorphisms (1931T/C and 1951G/A) in the promoter region of the CYP17 gene with breast cancer risk in Japanese women. No significant association was observed between CYP17 polymorphism^1951G/A and breast cancer risk (odds ratio (OR)=1.71, 95% confidence interval (CI): 0.28–1.84). In contrast, a significant increase in breast cancer risk (OR=1.82, 95% CI: 1.07–3.12) was observed in CYP17^1931C/C homozygotes compared with CYP17^1931T/C heterozygotes and CYP17^1931T/T homozygotes when women aged 55 years were considered, but such a significant increase was not observed when women aged 54 years were considered (OR=0.96, 95% CI: 0.56–1.63). These results suggest that CYP17 polymorphism^1931T/C would be useful in the selection of Japanese women at a high risk for developing breast cancer at the age of 55 years.     

Immunohistochemical localization of neurotensin and beta-endorphin in the rat anterior pituitary gland

Nakane's enzyme-labeled antibody technique revealed that cells containing neurotensin-like immunoreactivity were widely distributed in the anterior lobe of the pituitary body. Immunohistochemical studies on serial sections showed that a part of neurotensin positive anterior lobe cells contained beta-endorphin-like peptide simultaneously. The results show that beta-endorphin and neurotensin occur together in certain pituitary cells and this is an evidence of coexistence of more than one peptide within one anterior pituitary cell.     

Integration of human herpesvirus 6 in a Burkitt's lymphoma cell line

Human herpesvirus 6 (HHV-6) genome has been found in several human lymphoid malignancies, but configuration of the HHV-6 genome has not been well delineated. We established the HHV-6-positive, Epstein-Barr virus-negative Burkitt's lymphoma cell line Katata. In this study we investigated the status of the HHV-6 genome in Katata cells. Neither linear nor circular HHV-6 DNA was detected by Gardella gel analysis. The fluorescence in situ hybridization technique enabled us to directly visualize the integrated HHV-6 DNA at the single-cell level. Only one integrated site of viral DNA was detected in metaphase chromosomes and it was preferentially located at the long arm of chromosome 22 (22q13). Treatment of the cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or with calcium ionophore A23187 led to induction of the HHV-6 immediate-early gene as well as the late gene. Sodium n-butyrate also gave rise to expression of the HHV-6 genes. The TPA inducibility was synergistically enhanced when combined with A23187 or n-butyrate. Our study provides, for the first time, an in vitro model system of latent HHV-6 infection whose genome is integrated into host DNA of lymphoma cells.     

A case of oral florid papillomatosis combined with gastroduodenal polyposis

A 49-year-old man developing numerous papillary or partly cauliflower-like tumors over the lips, oral angles, gingiva and tongue starting 15 years earlier and associated with multiple gastroduodenal polyps of various sizes revealed by X-ray examination is presented. Histologically, the oral lesions consisted of marked proliferation of mature squamous cells without appreciable cellular atypism or submucosal invasion. Electron microscopic study failed to detect any virus-like particles, and negative reaction was obtained in immunohistological study for papilloma virus. The association of gastroduodenal polyposis with oral florid papillomatosis has appeared very rarely in the literature. Although the relationship between the two lesions remains unknown, it was assumed in the present case that all lesions would represent an entity of a hamartomatous nature.     

Evaluation of a combination chemotherapy with docetaxel and nedaplatin for patients with oral squamous cell carcinomas

The purpose of this study was to evaluate the effectiveness and safety of combination chemotherapy with docetaxel (TXT) and nedaplatin (CDGP) for patients with oral squamous cell carcinomas. Eight patients were enrolled in this study (4 men and 4 women, with a mean age of 61.7 years). TXT and CDGP were administered at a dose of 60 mg/m(2) and 70 mg/m(2) by drip infusion for 120 minutes, respectively. Three patients received one more administration 4 weeks after the first one. The locoregional response was evaluated 4 weeks after the final administration of TXT and CDGP. As a result, the locoregional response rate after 1 course was 62.5% including 25.0% of complete response (CR). The response rate after 2 courses was 100.0% with 66.7% of CR. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that four cases were Grade IIa, two cases Grade IIb, and two cases Grade IV. The severe adverse events were neutropenia and leukopenia, which were effectively managed with granulocyte colony-stimulating factor (G-CSF). No other severe side effects were recognized. The present study suggested that the combination chemotherapy with TXT and CDGP would be an effective and safe regimen in neo-adjuvant chemotherapy for oral squamous cell carcinomas.