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O Tominaga

Publications and source records attributed to O Tominaga.

27 records · Page 2Linked to original sources
PubMed1996

Parallel evolution in radiation of Ohomopterus ground beetles inferred from mitochondrial ND5 gene sequences.

Molecular phylogenetic analyses using mitochondrial NADH dehydrogenase subunit 5 (ND5) gene sequences representing all 15 species and the majority of subspecies or races of the Ohomopterus ground beetles from all over the Japanese archipelago have uncovered a remarkable evolutionary history. Clustering of the species in the molecular phylogenetic tree is linked to their geographic distribution and does not correlate with morphological characters. Taxonomically the "same" species or the members belonging to the same species-group fall out in more than two different places on the ND5 tree. Evidence has been presented against a possible participation of ancestral polymorphism and random lineage sorting or of hybrid individuals for the observed distribution of mitochondrial DNA haplotypes. The most plausible explanation of our results is that parallel evolution took place in different lineages. Most notably, O. dehaanii, O. yaconinus, and O. japonicus in a lineage reveal almost identical morphology with those of the "same" species (or subspecies) but belonging to the phylogenetically remote lineages.

Animals↗
PubMed1995

The relationship of macroscopic shape of superficial esophageal carcinoma to depth of invasion and regional lymph node metastasis.

BACKGROUND: There has been considerable controversy with regard to surgical strategies for the treatment of superficial esophageal carcinoma, which is characterized by tumor confined within the epithelium (EP), muscularis mucosae (MM), or submucosa (SM). The relationships among macroscopic shape, depth of invasion, and lymph node involvement in superficial tumors were investigated to devise therapeutic strategies for patients with such disease. METHODS: Thirty-three patients with superficial primary esophageal cancer underwent esophagectomy with regional lymph node dissection (3 EP, 6 MM, and 24 SM). Tumors were divided into two types according to macroscopic characteristics: (1) tumors with elevated components and (2) flat or depressed tumors without an elevated component. RESULTS: Tumors with an elevated component (n = 19) showed invasion of the deep layer, and a high incidence of lymph node metastasis. Conversely, tumors without an elevated component (n = 14) showed varied depths of invasion, and, with one exception, had no lymph node involvement. CONCLUSIONS: The existence of an elevated component in superficial esophageal cancer is an important macroscopic feature suggesting submucosal invasion and a high probability of lymph node involvement. More intensive treatment should be adopted for such tumors, whereas localized resection may be feasible for tumors without an elevated component.

Esophageal Neoplasms↗
PubMed1993

Frequently elevated content of immunochemically defined wild-type p53 protein in colorectal adenomas.

Mutations of the p53 tumour-suppressor gene are considered to be rare in human colorectal adenomas, a premalignant state of the digestive tract. We have analysed a series of 32 exophytic tumours of the colon and rectum for the presence of p53 protein. In 26 of the 28 pure adenomas, the presence of significant levels of p53 proteins was established by a sensitive two-point enzyme-linked immunosorbent assay. The detectability of p53 protein was frequently limited to PAb 1801, recognizing an N-terminal epitope. Immunoblotting of the fractions captured by the monoclonal antibodies revealed that PAb 421 reacted exclusively with a 53-kDa species, whereas an additional 48-kDa band was detected after incubation with PAb 1801. In the adenomas, the mutant conformation-specific PAb 240 was always negative and no mutations were detected on exons 5-8 in three large and highly dysplastic lesions, selected for their high p53 protein content. The remaining four of the 32 tumours presented foci of cancer. Three of these were shown to contain 'mutant' PAb 240-reactive p53, and gene mutations were identified in two by denaturing gradient gel electrophoresis and sequencing of the amplified products. Intense p53 nuclear immunohistochemical staining was associated with the malignant areas. We conclude that a novel mechanism affecting the regulation of p53 protein could occur in colorectal adenomas.

Adenoma↗
PubMed1992

Increased p53 protein content of colorectal tumours correlates with poor survival.

Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our methods of detection of the p53 protein in a series of 78 colorectal cancers stored in a tumour bank from 1985 to 1989, for which the median follow-up was 42 months. Nuclear-attached p53 was quantified by flow cytometry and soluble p53 was assayed by ELISA. Both assays used a monoclonal antibody considered to be specific for a conformational epitope present only on the mutated protein. Fifty of the 78 tumours (64%) were found to present significant levels of p53 attached to the nucleus. A further two tumours contained high levels of p53 only in their soluble fraction. Thus, 52 out of 78 cancers (67%) were considered to be positive for p53. The p53 content correlated with 17p loss (P < 0.002), hyperdiploid DNA content (P < 0.001) and tumour site (P < 0.03), but not Dukes' stage (P = 0.15). p53 negative cases had a better overall survival than p53 positive ones (P < 0.03). When the 14 stage D tumours were excluded from the analysis, p53 was no longer significantly predictive of survival (P < 0.07), but remained predictive of recurrence (P < 0.02) and metastasis (P < 0.03). Multivariate analysis was not performed because of the small number of cases. Overall, disease-free and metastasis-free survival were compared to the positivity obtained either with pAb 421 and/or 1801 or pAb 240 since all three were used in the flow cytometric analysis, defining subsets of 421-, 1801+ and 421-, 1801-, 240+. The presence of nuclear protein presenting the mutation-specific epitope, recognised by pAb 240, was found to be the most discriminant. It must be noted that univariate survival analysis demonstrated that more than 80% of patients with p53-negative tumours were alive at 3 years vs less than 50% in the p53-positive group. A large prospective study should be conducted to define the exact prognostic significance of the p53 content of colorectal carcinomas.

Adenocarcinoma↗
PubMed1992

p53 from basic research to clinical applications.

Mutations on the TP53 tumor suppressor gene and allele loss on chromosome 17p, where this gene has been located, are among the most frequent alterations yet identified in human malignancies. The p53 protein is highly conserved through evolution and expressed in most normal tissues. Wild-type p53 has been shown to control normal cell proliferation possibly through transcriptional regulation. The wild-type TP53 gene can suppress cell transformation and neoplastic cell growth. In contrast, mutant TP53 has lost the tumor suppressing ability and, in most cases, has gained a transformation promoting ability. Many different TP53 mutations have common conformational and functional consequences on the p53 protein. However, all the TP53 mutants are not necessarily equivalent in terms of biological activity: some mutations confer a strong transforming ability, while others lead to truncated products with probably no biological function. Some mutants may exhibit a dominant behavior over wild-type TP53, others may be recessive. Point mutations of TP53 tend to occur on evolutionary conserved positions. However, the TP53 mutational spectrum differs among cancer types, and this fact may reflect different exogenous mutagens and endogenous factors contributing to human carcinogenesis. In defined types of malignancies, the tumors with TP53 alteration or tumors with allele loss on 17p are associated with more aggressive phenotypes than those without these alterations. For these malignancies, the monitoring of TP53 alteration should now be included in therapeutic trials. Germ line mutations on TP53 may also occur. Individuals with constitutional TP53 mutation have a predisposition to a wide variety of neoplasms. Further characterization of this predisposition will enable the definition of the best follow-up for these at-risk patients.

Animals↗
PubMedDate not supplied

p21Waf1/Cip1 expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kip1, p53, or Rb.

BACKGROUND: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). METHODS: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. RESULTS: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. CONCLUSIONS: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.

Adult↗
PubMedDate not supplied

Three generations of hereditary chronic pancreatitis.

The patient was a 22 year-old male. Hereditary chronic pancreatitis was suspected as a diagnosis since his mother's uncle had been operated on for chronic pancreatitis 14 years previously at the age of 64 years and his mother had been operated on for chronic pancreatitis with calculi 5 years previously at the age of 40 years. Surgery was needed, since: 1) he had experienced abdominal pain for 8 years; 2) endoscopic retrograde cholangiopancreatography (ERCP) revealed a marked irregular dilatation in the main pancreatic duct and a marked irregular dilatation and protein plugs in the ductule of the tail of the pancreas; and, 3) pancreatic functional diagnostic (PFD) test examination showed a 75% decrease in exocrine function. If a surgical procedure had not been performed, the patient would likely have experienced calculi formation in the pancreas and a further decrease in exocrine function. Since the patient was very young and had many protein plugs in the dilated ductule of the tail of the pancreas, we decided to perform a spleen-preserving Puestow's procedure with removal of the tail of the pancreas. Clinical and pathological findings of hereditary pancreatitis are reviewed.

Adult↗
PubMedDate not supplied

Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer.

BACKGROUND/AIMS: In planning adjuvant treatment of colorectal cancer, it is of critical importance to optimize the treatment by identifying subsets of patients that will respond or not to chemotherapy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are key enzymes involved in the biochemical functions of the antimetabolite 5-fluorouracil (5-FU). In searching for the factors determining the 5-FU sensitivity of colorectal cancer, TS and DPD were analyzed in relation to the inhibitory effect of 5-FU on cell proliferation in a series of human colorectal cancer cell lines. METHODOLOGY: TS and DPD protein expressions were quantified in 5 human colorectal cancer cell lines, using TS binding assay and Western blotting, respectively. Cellular growth inhibition was assessed by MTT assay after 48 hours of continuous exposure to 5-FU or cisplatin (CDDP). RESULTS: TS protein expression was detected in all but one of the cell lines studied and varied within a 17-fold range, while DPD protein expression was detectable in only one cell line (CaR1). CaR1, which expressed the highest level of DPD and no detectable TS, showed remarkable resistance to 5-FU. The other colorectal cancer cell lines with undetectable DPD expression were sensitive to 5-FU. There was no correlation between TS expression and 5-FU sensitivity. All of the cell lines studied showed similar sensitivity to CDDP. CONCLUSIONS: These data suggest that DPD, but not TS, expression predicts 5-FU sensitivity in colorectal cancer cell lines.

Antimetabolites, Antineoplastic↗