Search PubMed⌕ Search

Biomedical subjects

Kazuhiro Yoshida

Publications and source records attributed to Kazuhiro Yoshida.

At least 91 records · Page 5Linked to original sources
PubMed2003

DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma.

The SWI/SNF proteins are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression. Recent studies have shown that members of the SWI/SNF superfamily can function as tumor suppressor genes. DNA methylation and transcriptional inactivation of the HLTF gene, which is a homologue to the SWI/SNF genes, have been observed in colon cancer. In the present study, we studied the DNA methylation status of the HLTF gene by methylation-specific PCR in 50 gastric carcinoma tissues, and seven gastric carcinoma cell lines and compared the methylation status with the levels of HLTF mRNA expression. DNA methylation of the HLTF gene was found in 25 (50%) of 50 gastric carcinomas, and levels of HLTF mRNA were associated with methylation status of HLTF (P = 0.027; Mann-Whitney U test). No correlations were found between HLTF mRNA levels and DNA methylation and T grade, N grade, tumor stage, or histological type. In corresponding non-neoplastic mucosae, DNA methylation of the HLTF gene was found in 1 (7%) of 15 samples. The methylated allele was not detected in any of 10 normal gastric mucosae from 10 healthy volunteers. Among seven gastric carcinoma cell lines, the KATO-III cell line showed loss of HLTF mRNA expression associated with DNA methylation. This loss was rectified by treatment with both Aza-2'-deoxycytidine, a demethylating agent, and trichostatin A, a histone deacetylase inhibitor. Chromatin immunoprecipitation assay revealed that the acetylation levels of histones H3 and H4 in the 5' CpG island of the HLTF gene were inversely associated with DNA methylation status. These results suggest that transcriptional inactivation of HLTF by aberrant DNA methylation and histone deacetylation may be involved in stomach carcinogenesis through down-regulation of HLTF expression.

Acetylation↗
PubMed2003

Promoter methylation of cyclin D2 gene in gastric carcinoma.

Methylation of CpG island in the promoter has been recognized as an important mechanism for regulation of gene expression. Although considerable work has been done on the epigenetic control of tumor suppressor genes, little is known about the potential role of promoter CpG demethylation in the activation of oncogenes. The cyclin D2 gene is overexpressed in a subset of gastric carcinoma. To determine whether hypomethylation of cyclin D2 is involved in stomach carcinogenesis, we studied methylation of CpG islands in the cyclin D2 gene by methylation-specific PCR in 34 gastric carcinoma specimens, 21 corresponding non-neoplastic mucosae, and 8 gastric carcinoma cell lines. We also measured levels of cyclin D2 mRNA in 23 of the gastric carcinoma cases and in the gastric carcinoma cell lines. Hypomethylation of the cyclin D2 promoter was found in 24 (71%) of the 34 tumor tissues and in 6 (29%) of the 21 corresponding non-neoplastic mucosa, the incidence being significantly different (p=0.002; Fisher's exact test). Moreover, hypomethylation of cyclin D2 was more common in stage III and IV tumors than in stage I and II tumors (p=00.014; Fisher's exact test). All of three cell lines with promoter hypomethylation expressed detectable levels of cyclin D2 mRNA. Treatment of cyclin D2-negative cells lines harboring promoter hypermethylation with demethylating agent, 5-Aza-2'-deoxycytidine, led to a reactivation of cyclin D2 expression. These results suggest that DNA hypomethylation is a mechanism underlying the increased expression of cyclin D2 in cancer cells and that demethylation of cyclin D2 may be involved in development and progression of gastric carcinoma.

Adult↗
PubMed2003

[Weekly docetaxel therapy is useful for gastric carcinoma as a second-line chemotherapy].

In the present study, we demonstrate the results of weekly administered docetaxel treatments as a second-line chemotherapy after TS-1 treatment in 4 gastric cancer patients. Twenty-five mg/m2 of docetaxel was administered once a week for 3 weeks followed by a 1-week rest period as one cycle. The treatment was continued for 2 to 16 weeks. In case 1, a 60% reduction of the primary tumor was observed for 20 weeks. In cases 2 and 3, the decrease of tumor marker was observed. In one case, progression of the tumor was observed and the treatment was not performed. As for adverse effects, no hematological toxicity was observed; however, in one case, grade 2 hair loss, pleural effusion and grade 2 nail changes were observed. These results indicate that the weekly docetaxel therapy is useful for gastric carcinoma patients, as it reduces the hematologic toxicities and improves the quality of life of the patients in the outpatient setting.

Aged↗
PubMed2002

Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers.

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD expression levels are believed to correlate with the 5-FU sensitivity of malignant tumors. In colorectal cancer (CRC), a few previous studies demonstrated that females could benefit more from adjuvant chemotherapy. However, it is still unknown why the effectiveness of postoperative chemotherapy is affected by gender. The objective of this study was to clarify the beneficial differences in 5-FU chemotherapy between genders in patients with the CRC based on DPD expression. Ninety-seven tumor specimens and 92 adjacent normal tissue specimens from 97 patients with the CRC and no prior therapy were obtained. The DPD expression in the tissues was quantified and analyzed based on clinicopathological factors. In the tumor tissue, the DPD expression in females was significantly lower than that in males. In the normal tissues, however, there were no significant differences in DPD expression between genders. In the treatment of CRC, cases who will benefit most because of 5-FU sensitivity; i.e. cases with lower DPD expression, must be given priority. Based on DPD expression, female gender seems to be a predictive factor for a better response to chemotherapy with 5-FU.

Adult↗
PubMed2002

Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma.

Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer.

Adenocarcinoma↗
PubMed2002

Rhodium-catalyzed asymmetric 1,4-addition of aryltitanium reagents generating chiral titanium enolates: isolation as silyl enol ethers.

The addition of aryltitanium triisopropoxide (ArTi(OPr-i )3) to alpha,beta-unsaturated ketones proceeded with high enantioselectivity (94-99.8% ee) in the presence of 3 mol % of [Rh(OH)((S )-binap)]2 in THF at 20 degrees C to give high yields of the titanium enolates as 1,4-addition products. The titanium enolates were converted into silyl enol ethers by treatment with chlorotrimethylsilane and lithium isopropoxide.

Journal Article↗
PubMed2002

A new type of catalytic tandem 1,4-addition-aldol reaction which proceeds through an (oxa-pi-allyl)rhodium intermediate.

The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta-unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol reaction products with high syn selectivity. The reaction proceeds through the catalytic cycle consisting of 1,4-addition of an organorhodium species to an alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi-allyl)rhodium intermediate to an aldehyde.

Journal Article↗
PubMed2002

Effect of adjacent chiral tertiary and quaternary centers on the metal-catalyzed allylic substitution reaction.

The metal-catalyzed allylic substitution reaction of 5a,b and 6a was examined. Reaction with stabilized nucleophiles led to exclusive attack at the less-hindered allylic terminus, and the stereoselectivity varied with the bidentate ligand used but favored retention. The yields and reaction times were improved with the use of microwaves. Alkylation via transmetalation was only observed with phenyl- and vinylstannatranes and gave regio- and stereoselectivity opposite those observed with the stabilized anions. The epimeric carbonates 5a and 5b displayed very different reactivities. Catalysts containing metals other than palladium were completely unreactive and led to recovered starting material.

Alkenes↗
PubMed2002

[Allergic rhinitis epidemiology in Japan].

We epidemiologically surveyed allergic rhinitis nationwide, mailing questionnaires to 9,471 otorhinolaryngologists and their families nationwide in June 1998 responses by the end of September 1998: 42.8%, providing 17,301 subjects. Few differences were seen in the age composition between the subject population and the general Japanese population. Cedar pollinosis morbidity after adjustment for population distribution was 17.3%, higher overall on the Pacific Ocean side and in central districts of Japan compared to districts on the Sea of Japan and the Inland Sea and lower in high or low latitudes. By age, morbidity increased sharply among subjects in their teens and decreased among subjects in their 60s. Morbidity was high in districts of heavy cedar pollen dissemination. By housing, morbidity was high in the suburbs, followed by residential areas and cities. Pollinosis due to causes other than cedar pollen showed results similar to those for cedar pollinosis in morbidity by age and the relationship between the housing environment and morbidity, with morbidity after population distribution adjustment 11.7%. Morbidity of perennial allergic rhinitis after adjustment for population distribution was 19.8% was slightly higher than that of pollinosis. By age, morbidity increased sharply at 5 to 9 years of age, being highest in the young than in cedar pollinosis; no decrease in morbidity after age 60 was seen. Unlike cedar pollinosis, perennial allergic rhinitis showed no difference in morbidity by area or housing environment. The present survey using otorhinolaryngologists and their families nationwide as subjects enabled us to find areawise differences in morbidity for cedar pollinosis and perennial allergic rhinitis. Ours is useful epidemiologically in allergic rhinitis mainly for cedar pollinosis in Japan because it is superior to other questionnaires in response and because reply reliability is high.

Adolescent↗
PubMed2002

[A case of ganglioneuroblastoma occurring in the superior mediastinum in an adult].

We report a case of ganglioneuroblastoma occurring in the superior mediastinum in adult. A 63-year-old man was admitted to our hospital for detailed investigation of an abnormal shadow on his chest radiograph. Chest radiography and CT imaging showed a left superior mediastinal tumor. Histopathologically, the tumor was identified as a ganglioneuroblastoma. Although ganglioneuroblastomas occur predominantly in children, 3 cases have been reported in adults in Japan. Incidentally, this is the first reported case of ganglioneuroblastoma occurring in the superior mediastinum in Japan.

Ganglioneuroblastoma↗
PubMedDate not supplied

Absolute stereochemistry of chiral C60 fullerene bis-adducts.

To determine the absolute configuration of chiral fullerene bis-adducts, we have studied the double Bingel reaction of C60 with chiral tether (2S,3S)-(-)-9 derived from (R,R)-(+)-tartaric acid, and have succeeded in isolating two possible chiral bis-adducts 10a (5%) and 10b (2%) in addition to the Cs-symmetrically added derivative 10c (40%). The CD spectra of chiral bis-adducts [CD(+)281]-10a and [CD(-)281]-10b show very intense Cotton effects, which are almost of mirror image, indicating that their chiral C60 pi-electron systems are enantiomeric each other. The 1H and 13C NMR spectra of 10a and 10b indicate that they have C2-symmetrical structures, and the vicinal coupling constants between two equivalent protons H-2 and H-2' were determined as 1.2 Hz for 10a and 1.8 Hz for 10b, respectively by the 13C satellite band method. From the conformational analyses, the absolute configurations of these chiral C60 fullerene bis-adducts were unambiguously determined as [CD(+)281]-(S,S,fC)-10a and [CD(-)281]-(S,S,fA)-10b, respectively.

Journal Article↗
PubMedDate not supplied

Current status and future perspectives of post-operative adjuvant therapy for gastric carcinoma.

The clinical benefit of post-operative adjuvant immunochemotherapy for survival of patients with gastric carcinoma is unclear, although a number of prospective randomized controlled studies have been conducted. The current status and future perspectives of post-operative adjuvant chemotherapy in gastric carcinoma have been evaluated in terms of survival benefit. The results of randomized clinical studies vary in accordance with the regimen and sample size. A meta-analysis, however, indicated a survival benefit in patients treated with post-operative adjuvant chemotherapy including mitomycin, anthracyclines, cyclophosphamide, alkylating agents and 5-fluorouracil (odds ratio: 0.8 to approximately 0.82, 95% CI<1.0). The survival benefit was observed in patients with stage II and stage III gastric carcinoma, but not those with stage I. Further, the survival benefit in node-positive and high histological grade subgroups was superior to that in node-negative and low histological grade subgroups. Although combination therapy with mitomycin, 5-fluorouracil and non-specific immunomodulators, such as PSK and OK-432, appeared to improve overall survival without immunomodulators, the survival effect of immunomodulators is still not clear. There are several possible reasons why the survival benefit of adjuvant chemotherapy or immunochemotherapy is small and marginal compared to surgery alone: (i) low efficacy of the chemotherapy regimen; (ii) small sample size; and (iii) differences in chemosensitivity of treated patients based on genetic background. The determination of subgroups responsive to chemotherapy and the development of a rationale-based and molecular-targeted chemotherapy are required to clearly demonstrate whether there is a survival benefit of post-operative adjuvant chemotherapy in gastric carcinoma.

Chemotherapy, Adjuvant↗
PubMedDate not supplied

Expression and distribution of human telomerase catalytic component, hTERT, in human breast tissues.

BACKGROUND: Activation of telomerase is essential in a variety of malignant tumors. However, the regulation of its activation and the expression of human telomerase reverse transcriptase (hTERT) are not fully understood in breast tissues. MATERIALS AND METHODS: In order to clarify this point, the telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay and quantified by hybridization protection assay (HPA) and, moreover, the expressions of hTERT mRNA and protein were examined by RT-PCR and immunohistochemistry, respectively. RESULTS: Telomerase activity and the expression of hTERT mRNA were detected in 41(75%) and 37(67%) cases among 55 breast carcinomas, respectively. However, the telomerase ZV activity was detected in only 14(40%) among 35 benign breast tumors. Strong correlation was observed between telomerase activity and hTERT mRNA expression, as described previously. Moreover, the strong expression of hTERT protein in the nucleus of the cell was detected in 30 (57%) cases among 53 breast carcinomas and weak expression of the protein was also detected in 11 (35%) cases among 31 benign breast tumors by immunohistochemistry. There were 12 breast carcinomas which had no telomerase activity. Three of them had hTERT mRNA and protein and in 3 other cases, only hTERT protein was detected. Five cases had the expression of mRNA but not the protein and it was only one case which had no activity and expression of hTERT mRNA and protein. However, in benign tumors, 14 (87.5%) cases among 16 TRAP-negative tumors had no mRNA and protein expression. CONCLUSION: These results indicate that complicated regulation might be involved in the regulation of telomerase activity and also the activation of the gene may be important in the carcinogenesis of human breast carcinomas.

Breast Neoplasms↗
PubMedDate not supplied

Induction mechanism of apoptosis by troglitazone through peroxisome proliferator-activated receptor-gamma in gastric carcinoma cells.

BACKGROUND: It has been reported recently that the antidiabetic thiazolidinediones not only induce fibroblast differentiation but also inhibit the growth of carcinoma cells. MATERIALS AND METHODS: In the present study, in order to elucidate the further mechanism of growth inhibition by troglitazone, the expression of cell cycle regulators and apoptotic regulators were examined by cDNA microarrays and Western blot analysis by gastric carcinoma cells. RESULTS: Six gastric carcinoma cell lines (TMK-1, MKN-1,7,28,45,74) were treated with 0.1, 1, 10, 100 microM of troglitazone in vitro. The growth of 5 cell lines were inhibited by troglitazone in a time- and dose-dependent manner. Interestingly, the expression of cyclin D mRNA and protein was decreased and that of p27 was increased in TMK-1 cells at 12 hours after troglitazone treatment, suggesting the induction of cell cycle arrest of the cells. On the other hand, DNA ladder formation was observed at 12 hours after treatment. Moreover, the expression of cytochrome C, caspases 3 and 8 and PARP genes was increased after treatment and the gradual reduction of Bcl-XL protein was observed, which indicate that the apoptotic signals were induced after treatment by troglitazone. CONCLUSION: These results suggest that the thiazolidinediones can be a new therapeutic tool for gastric carcinoma via cell cycle regulation and apoptosis.

Antineoplastic Agents↗
PubMedDate not supplied

Quantitative detection of carcinoembryonic antigen messenger RNA in the peritoneal cavity of gastric cancer patients by real-time quantitative reverse transcription polymerase chain reaction.

BACKGROUND: Peritoneal dissemination is the most frequent cause of recurrence in gastric cancer patients after gastrectomy. We have previously demonstrated the prognostic factors in gastric cancer including growth factors and their receptors and intra-peritoneal CEA (1,2). MATERIALS AND METHODS: In the present study, to elucidate whether CEA mRNA in peritoneal lavage is a good marker for the prediction of peritoneal recurrence of gastric cancer patients, quantitative real-time RT-PCR with primers specific for CEA was performed by peritoneal lavage of 124 gastric cancer patients collected at the time of operation. RESULTS: CEA crossing-point values (CEA-CP) were significantly correlated with the depth of tumor invasion and the values were cut-off at 27.11, which was the minimum value of mucosal cancer patients. The CEA-CP was significantly correlated with lymph node metastasis, lymphatic invasion, venous invasion, stages and overall survivals. In prediction of peritoneal recurrence by CEA-CP, sensitivity and specificity were 76.9% and 67.7%, respectively. Cytology predicted peritoneal recurrence with 23.1% sensitivity and 98.1% specificity. CONCLUSION: Quantitative RT-PCR of CEA mRNA of peritoneal lavage is a useful factor for prognosis and predicting peritoneal recurrence.

Biomarkers, Tumor↗