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Biomedical subjects

O Tominaga

Publications and source records attributed to O Tominaga.

At least 19 recordsLinked to original sources
PubMed2002

Carcinoembryonic antigen mRNA in abdominal cavity as a useful predictor of peritoneal recurrence of gastric cancer with serosal exposure.

Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.

Abdominal Cavity↗
PubMed2001

Detection of p73 antibodies in patients with various types of cancer: immunological characterization.

p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino- and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells.

Antibodies, Neoplasm↗
PubMed2000

Formation of the Japanese Carabina fauna inferred from a phylogenetic tree of mitochondrial ND5 gene sequences (Coleoptera, carabidae).

Phylogenetic analyses based on the mitochondrial ND5 gene comparisons and the geohistory of the Japanese Islands suggest that each Japanese species belonging to the subtribe Carabina has its own history for the establishment of its present habitat in the Japanese Islands. It can be roughly classified into two categories: (1) species which were derived from the ancestry that inhabited ancient Japan at the time of its split from the Eurasian Continent [ca. 15 million years ago (MYA)], followed by diversification within the Japanese Islands; and (2) species which invaded Hokkaido from the Eurasian Continent through land-bridges from Sakhalin and/or the Kuriles or from western Japan from the Korean Peninsula during the glacial era (<2 MYA).

Animals↗
PubMed2000

Pattern of morphological diversification in the Leptocarabus ground beetles (Coleoptera: Carabidae) as deduced from mitochondrial ND5 gene and nuclear 28S rDNA sequences.

Most of the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene and a part of nuclear 28S ribosomal RNA gene were sequenced for 14 species of ground beetles belonging to the genus Leptocarabus. In both the ND5 and the 28S rDNA phylogenetic trees of Leptocarabus, three major lineages were recognized: (1) L. marcilhaci/L. yokoael/Leptocarabus sp. from China, (2) L. koreanus/L. truncaticollis/L. seishinensis/L. semiopacus/L. canaliculatus/L. kurilensis from the northern Eurasian continent including Korea and Hokkaido, Japan, and (3) all of the Japanese species except L. kurilensis. Clustering of the species in the trees is largely linked to their geographic distribution and does not correlate with morphological characters. The species belonging to different species groups are clustered in the same lineages, and those in the same species group are scattered among the different lineages. One of the possible interpretations of the present results would be that morphological transformations independently took place in the different lineages, sometimes with accompanying parallel morphological evolution, resulting in the occurrence of the morphological species belonging to the same species group (= type) in the different lineages.

Animals↗
PubMed2000

Bcl-X(L) antisense sensitizes human colon cancer cell line to 5-fluorouracil.

Resistance to 5-fluorouracil (5-FU) has been frequently found in the treatment of digestive tract cancer patients. Our previous study suggested that high expression of endogenous Bcl-X(L), might be associated with resistance to 5-FU in colorectal cancer. The aim of this study is to analyze the role of Bcl-X(L) in 5-FU resistance and to explore a new therapeutic strategy using Bcl-X(L) antisense. First, western blot analysis shows that Bcl-X(L) rather than Bcl-2 is overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells, with undetectable endogenous Bcl-XL expression, were transfected with Bcl-XL gene, they acquired high resistance to 5-FU. Finally, antisense oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl-X(L) mRNA (AS1) prove to be the most effective in DLD1 cells with high endogenous Bcl-X(L) expression. Bcl-X(L) protein expression was decreased in a dose-dependent manner when the cells were treated with AS1 ODNs, while non-sense and sense controls and 5-FU had no effect on Bcl-X(L) protein. 5-FU treatment induced a level of apoptosis 10-fold higher in DLD1 cells than in untreated control cells, while the same dose of 5-FU induced a 55-fold higher level of apoptosis in DLD1 cells treated with Bcl-XL antisense oligodeoxynucleotides (P = 0.0003). Moreover, AS1 ODNs coupled with 5-FU decreased viable colon cancer cells 40% more than did 5-FU alone (P < 0.05). These results suggest that Bcl-X(L) is an important factor for 5-FU resistance and the suppression of Bcl-X(L) expression by the specific antisense ODNs can increase the sensitivity of colon cancer cells to 5-FU.

Adenocarcinoma↗
PubMed2000

Differentiation within the genus Leptocarabus (excl. L. kurilensis) in the Japanese Islands as deduced from mitochondrial ND5 gene sequences (Coleoptera, Carabidae).

The phylogenetic trees have been constructed for the mitochondrial ND5 gene sequences from the Japanese Leptocarabus ground beetles, which contain 101 specimens collected from nearly the complete distribution ranges of them consisting of five morphological species, i.e., Leptocarabus procerulus, L. kumagaii, L. hiurai, L. kyushuensis and L. arboreus. On the trees, there are recognized two major lineages, each of which is further divided into two or more sublineages. The phylogenetic lines are geographically linked. Two or more species occur in a single lineage, and the same species appear in different lines. We suggest that transformation from one type of morphology to another took place in parallel in various periods of evolution of the Japanese Leptocarabus. From the phylogenetic tree and the dating from the nucleotide substitution rate and the geohistorical data it is inferred that the ancestry of all the Japanese Leptocarabus species was derived from a protoform of L. kyushuensis inhabited the ancient Japan area, followed by separation into two lineages after split of the Japanese Islands from the Eurasian Continent. They then propagated distribution to occupy their own habitat ranges, during which the morphological transformation took place in some lineages.

Animals↗
PubMed1999

Pulmonary blastoma: report of a case.

We herein describe a 27-year-old male presenting with a pulmonary blastoma. The patient was admitted to our hospital with the chief complaints of fever and left back pain. Chest roentgenograms showed a tumor measuring 10 cm in diameter in a lower lobe of the left lung. Computed tomography and magnetic resonance imaging revealed a well demarcated and heterogeneously enhanced tumor. Although a histological diagnosis could not be obtained by a transbronchial biopsy, image analyses led us to suspect it to be malignant. The patient underwent a left lower lobectomy with lymph node dissection. A histopathological examination revealed the tumor to be a biphasic type of pulmonary blastoma. Because of the rapid progress of the tumor and the difficulty in making a preoperative diagnosis in such cases, an immediate surgical resection is therefore recommended in cases with even the slightest suspicion of malignancy.

Adult↗
PubMed1999

Evolution of the carabid ground beetles.

The phylogenetic relationships of the carabid ground beetles have been estimated by analysing a large part of the ND5 gene sequences of more than 1,000 specimens consisting of the representative species and geographic races covering most of the genera and subgenera known in the world. From the phylogenetic analyses in conjunction with the mtDNA-based dating, a scenario of the establishment of the present habitats of the respective Japanese carabids has been constructed. The carabid diversification took place ca. 40 MYA as an explosive radiation of the major genera. During evolution, occasional small or single bangs also took place, sometimes accompanied by parallel morphological evolution in phylogenetically remote as well as close lineages. The existence of silent periods, in which few morphological changes took place, has been recognized during evolution. Thus, the carabid evolution is discontinuous, alternatively having a phase of rapid morphological change and a silent phase.

Animals↗
PubMed1998

Quantification and characterization of total cellular p53 protein in colorectal cancer.

Immunochemical methods were developed for the optimal detection and characterization of total cellular p53 protein expression, both in the nuclear-attached and soluble fractions of colorectal cancers, in order to improve the correlation between protein deregulation and gene status. Seventy colorectal carcinomas were studied using 3 monoclonal antibodies in a sensitive analyzing system combining flow cytometry (nuclear-bound fraction) and enzyme-linked immunosorbent assay (ELISA; soluble fraction). DNA indices were calculated on the DNA histograms and mutations of the p53 gene were searched for in a subset of 41 cases. Three p53 expression patterns were found: 35 tumors were classified as pattern "A," characterized by high p53 expression including "mutant" conformation and missense mutations of the gene (16/17 cases tested), pattern "B" consisted of 15 tumors with total absence of p53 expression corresponding to nonsense mutations of the gene (8/9 cases tested), and pattern "C" of 20 tumors presenting low or undetectable nuclear-bound p53 but intermediate p53 protein content (pAb (1801+) in the soluble fraction. The latter pattern was associated with wild-type genes (14/15 cases tested), and with tumors that were often localized in the right colon compared to pattern "A" and "B" tumors (45% versus 8%, P < 0.009) and were frequently near-diploid (80% versus 29%, P < 0.0002). No correlation was found between tumor stage and the patterns of p53 expression. The results indicate that both flow cytometry (FCM) and ELISA seem necessary for the proper characterization of the p53 expression pattern, thus achieving a high degree of concordance with molecular analysis of gene mutations.

Adenoma↗
PubMed1998

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(-) tumors were radioresistant, and the majority of p53(-) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(-), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(-) group (P < 0.01), and patients with radioresistant, p53(+), or p21(-) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(-), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Adult↗
PubMed1998

Primary iliopsoas abscess successfully treated by ultrasonographically guided percutaneous drainage.

We report a case of primary iliopsoas abscess successfully treated by ultrasonographically guided percutaneous drainage. A 56-year-old man presented at our hospital with lumbago, right-sided back pain, fever (temperature 38.5 degrees C) and chills. On physical examination, we found dark red skin, swelling, and tenderness localized at the right side at the back of his waist. Laboratory examination showed leukocytosis (white blood cell count 9700/mm3) with a leftward shift and elevated C-reactive protein (5.2 mg/dl). Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging revealed a hypodense lesion in the right iliopsoas muscle extending to the subcutaneous tissue. About 50 ml of thick yellow pus was obtained by ultrasonographically guided aspiration drainage. A drain catheter was inserted in the abscess cavity. Laboratory findings improved and clinical symptoms abated rapidly after drainage. On the twenty-first day after drainage, US and CT showed that the abscess was no longer present. The patient was discharged after 32 days of hospitalization. As possible primary diseases causing iliopsoas abscess, such as digestive tract disease, tuberculosis, and osteomyelitis, were not found, we diagnosed the disease as primary iliopsoas abscess. Although surgical drainage has been performed in most reported cases of iliopsoas abscess, this case report shows that ultrasonographically guided percutaneous drainage is also effective for treating primary iliopsoas abscess if it is diagnosed early enough.

C-Reactive Protein↗
PubMed1998

Screening for APC mutations based on detection of truncated APC proteins.

Mutation of the adenomatous polyposis coli (APC) gene is frequently found in colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP patients. Analysis of APC mutation is time-consuming and costly due to the large size of the APC gene. As the majority of APC mutations result in the truncation of gene products, the detection of truncated APC proteins may be used as a screening method for APC mutations. The aim of this study is to establish a practical method of detecting truncated APC proteins for the screening of APC mutations. APC proteins in human colorectal cancer cell lines were analyzed by western blotting. Truncated APC proteins were expressed in all of the colorectal cancer cell lines studied. Two species of truncated APC proteins were expressed in two cell lines. Western blotting is a rapid, reliable screening method for APC mutations and provides information on both alleles.

Antibodies, Monoclonal↗
PubMed1998

5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins.

Recently, apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis, but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (IC50) doses, was used to induce apoptosis, which was confirmed by morphological analysis and enzyme-linked immunosorbent assay (ELISA). Bcl-2, Bcl-X(L), Bax, Bad, Bak and p53 protein expression was analysed by Western blotting. Using five human colon cancer cell lines, we found that equitoxic (IC50) doses of 5-FU induced apoptosis in both wild-type p53 and mutant p53 cells. Analysis of the steady-state levels of Bcl-2 family proteins showed high expression of Bcl-X(L) in all of the cell lines except Colo320. Bcl-2 was expressed in two of them. Bax presented with the lowest basal expression and Bad showed homogeneous expression. On the other hand, Bak expression varied more than fivefold among these cells. In cells containing wild-type p53 (e.g. LoVo), 5-FU-induced apoptosis was accompanied by increased expression of Bax and Bak without consistent modulation of other bcl-2 family proteins. In contrast in cells containing mutant p53 (e.g. DLD1), Bak expression was remarkably increased. There was a significant correlation between chemosensitivity and Bcl-X(L) to Bax ratio, rather than Bcl-2 to Bax. In conclusion, these results suggest that some members of the Bcl-2 family of proteins, in human colon cancer cell lines, are modulated by 5-FU and that the ratio of Bcl-X(L) to Bax may be related to chemosensitivity to 5-FU.

Apoptosis↗
PubMed1998

Origin and diversification of hindwingless Damaster ground beetles within the Japanese islands as deduced from mitochondrial ND5 gene sequences (Coleoptera, Carabidae).

Genealogical trees have been constructed using mitochondrial ND5 gene sequences of 78 Damaster (s. str.) specimens from all over the Japanese Islands. Eight lineages (called races in this paper) have been recognized. The races are tightly linked to geography with sharp distribution boundaries between them. The races and their distribution ranges do not coincide with those of classical morphology. Based on the observed distribution of the mitochondrial DNA haplotypes and the geohistorical data, we propose a diversification scenario of Damaster.

Animals↗
PubMed1998

Quantitative analysis of the cyclin expression in human esophageal cancer cell lines.

To study the altered mechanisms of cell cycle regulation in esophageal cancer, the expressions of cyclins involved in G1/S transition were analyzed in a series of 26 human esophageal cancer cell lines. To evaluate and compare the levels of cyclin expression, flow cytometric analysis was performed using human lymphocytes as control. Increased expressions of cyclin A, D1, D3 and E were found in 23.1% (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines, respectively. All cell lines studied expressed less cyclin D2 than lymphocytes and the majority of the cell lines expressed cyclin D3 at levels similar to those of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E. Expressions of cyclin D1 and E were significantly elevated as compared to those of cyclin A, D2 and D3. These results suggest that increased expressions of the positive cell cycle regulators cyclin D1 and E may play an important role in esophageal carcinogenesis.

Biomarkers, Tumor↗
PubMed1997

A case of advanced gastric cancer resembling submucosal tumor of the stomach.

We report a case of primary gastric carcinoma with a macroscopic appearance indistinguishable from that of a submucosal tumor. A 48-year-old man visited our hospital with a chief complaint of epigastric discomfort. Endoscopic examination revealed a protruding lesion with a well defined margin on the anterior wall of the gastric antrum. Most of the tumor surface was covered with apparently normal gastric mucosa and a shallow recess with mild erosion was observed on the top. Abdominal ultrasonography showed a hypoechoic lesion with an irregular margin under the gastric mucosa. Laboratory examination revealed an elevated CA19-9 level of 106.9 U/ml. In spite of repeated bouling biopsies, no histological diagnosis could be obtained before surgery. However, gastrectomy with regional lymph node dissection was performed because of the high likelihood of gastric cancer, in view of the markedly elevated CA19-9 level and irregular tumor margin demonstrated by abdominal ultrasonography. The tumor was diagnosed histologically as papillo-tubular adenocarcinoma invasive to the serosa with marked vessel infiltration. No metastasis was found in the regional lymph nodes. Gastric cancer resembling submucosal tumor is rare and often difficult to diagnose. Careful estimation of the possibility of gastric cancer and the informed consent of the patient are critically important, in cases of suspected primary gastric cancer resembling submucosal tumor, in order to decide the form of treatment.

Adenocarcinoma, Papillary↗
PubMed1997

Expressions of cell cycle regulators in human colorectal cancer cell lines.

To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both a p53-dependent and a p53-independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.

Cell Cycle↗