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Kazuhiro Yoshida

Publications and source records attributed to Kazuhiro Yoshida.

At least 73 records · Page 4Linked to original sources
PubMed2004

Frequent loss of RUNX3 expression by promoter hypermethylation in gastric carcinoma.

The RUNX3 gene is a member of the Runt domain family of transcription factors that are master regulators of gene expression in major developmental pathways. Recently, lack of RUNX3 function was found to be associated with genesis and progression of gastric carcinoma. We studied methylation of CpG islands in the RUNX3 gene by methylation-specific PCR in 80 gastric carcinoma specimens, 45 corresponding non-neoplastic mucosae, and 7 gastric carcinoma cell lines. We also measured levels of RUNX3 mRNA in 50 of the gastric carcinoma cases by quantitative RT-PCR and in the gastric carcinoma cell lines by RT-PCR. Hypermethylation of the RUNX3 promoter was found in 57 (71%) of 80 gastric carcinomas, and promoter hypermethylation of RUNX3 occurred more frequently in intestinal and diffuse-adherent type tumors than in diffuse-scattered type tumors (p = 0.046). Reduced RUNX3 expression was associated with promoter hypermethylation (p = 0. 036), however, there was no correlation between RUNX3 mRNA expression levels and T grade, N grade, tumor stage, or histological type. In corresponding non-neoplastic mucosae, hypermethylation of the RUNX3 promoter was found in 38 (84%) of 45 specimens. Among seven gastric carcinoma cell lines, three cell lines (MKN-28, MKN-74, TMK-1) with diminished expression of RUNX3 had promoter methylation and three cell lines (MKN-1, MKN-7, MKN-45) with RUNX3 expression showed no promoter methylation. Our results overall suggest that transcriptional inactivation of RUNX3 by promoter hypermethylation may participate in the stomach carcinogenesis.

Adenocarcinoma↗
PubMed2004

Transitional cell carcinoma of the bladder in four patients on maintenance hemodialysis.

We report four patients on maintenance hemodialysis (HD) with transitional cell carcinoma (TCC) of the bladder. Three patients underwent transurethral resection (TUR) of their tumors, which were grade 2 or 3, stage pT1 TCC. Among them, one patient underwent repeat TUR for recurrent superficial TCC. The remaining one patient underwent total cystectomy for grade 3, stage pT4 TCC and squamous cell carcinoma of the bladder. Subsequently, he died suddenly without evidence of local recurrence or systemic metastasis. We discuss the relationship between the duration of HD and the tumor grade and stage of primary bladder TCC in maintenance HD patients.

Aged↗
PubMed2004

[Telomerase activity in gastrointestinal, bladder and breast carcinomas and their clinical applications].

Telomere ends are known to be shortened at every division of the cells. Telomerase is a ribonucleoprotein which compensate for the telomere ends and indispensable for the immortalization of the cells. It is reported that the enzyme is activated in a variety of cancer cells. In the present report, the enzyme was activated in more than 70% of gastrointestinal, bladder and breast cancer by TRAP assay. Moreover, in order to elucidate whether the enzyme activity is useful for the non-invasive detection of exfoliated cancer cells in the colon bowel washings, urine and fine needle aspirate of the breast tumors, TRAP assay was performed. In most of the cases, the positive findings were observed which support that the enzyme activity is useful for the clinical application. The expression of mRNA and protein for hTERT was detected in cancer cells, however, the assay contains the pitfall including the Taq inhibitor or telomerase inhibitor. Moreover, the activity is also detected although it is weak, in the benign or premalignant lesions. Further analysis is required for the clinical application of the method.

Adult↗
PubMed2004

Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality.

Maspin, a serine protease inhibitor related to the serpin family, was originally identified in normal mammary epithelium. Reduced expression of maspin is related with development, invasion and metastasis of certain human cancers. In the present study, the expression of maspin was examined in gastric mucosa, adenoma and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa, maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic glandular cells and pyloric glandular cells. Maspin expression was lost in 71% (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss of maspin expression was significantly associated with poorly differentiated histology, advanced stage and deep invasion (P<0.001). There was an inverse correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA expression was lost in all of 8 gastric carcinoma cell lines that was retrieved after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell lines. These results suggest that loss of maspin expression partly due to DNA methylation may participate in tumor development and progression of gastric carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a biological marker of high-grade malignancy.

Adenoma↗
PubMed2004

[Combination chemotherapy of TS-1 and docetaxel on advanced and recurrent gastric cancer].

In the present article, we have summarized the clinical trials on docetaxel and the phase I study of docetaxel and combination therapy. Patients with a performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40 mg/m2 by iv infusion over 1 hour on day 1 and TS-1 at the full dose of 80 mg/m2 daily for two weeks every three weeks. Nine patients were treated with increasing dose levels of docetaxel as follows: (docetaxel/TS-1, mg/m2): 40/80 (level 1), 50/80 (level 2) and 60/80 (level 3), and all the cases were found to be assessable for drug safety, while 7 were assessable for response. The MTD was reached at the 50/80 mg/m2 dose level in three patients out of six, who experienced a dose limiting toxicity (DLT). On the other hand, partial response was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The drug combination showed a good safety profile, and the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

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

The patient was a 58-year-old man who suffered from non-resectable gastric cancer, staged intraoperatively for peritoneal dissemination and paraaorta lymph node metastasis at another hospital in December 2002. He was initially treated with TS-1 as an outpatient. However, he was readmitted on March 4, 2003 for hematuria, general fatigue, jaundice and dyspnea. He was diagnosed with gastric cancer duodenum invasion, obstructive jaundice and lymphangitis carcinomatosa, and began weekly TXL as second-line chemotherapy on March 26. TXL (70 mg/ m2) was infused once a week for 3 weeks followed by a 1-week interval as one cycle. One week after the first infusion therapy, the jaundice and dyspnea were greatly improved. CT scan showed the lymphangitis carcinomatosa had disappeared and paraaorta lymph node metastasis was reduced to 60% after one cycle of the treatment. The toxic events were leukopenia (grade 1) and alopecia (grade 1).

Adenocarcinoma, Scirrhous↗
PubMed2003

Chirality-organized ferrocene receptor bearing podand dipeptide chains (-L-Ala-L-Pro-NHPyMe) for the selective recognition of dicarboxylic acids.

[structure: see text] The ferrocene receptor bearing the podand dipeptide chains (-l-Ala-l-Pro-NHPyMe) was found to provide a chirality-organized binding site through two intramolecular interchain hydrogen bonds between CO (Ala) and NH (another Ala) of each podand dipeptide chain. The size-selective and chiral recognition of dicarboxylic acids was achieved by multipoint hydrogen bonds of the binding site.

Dipeptides↗
PubMed2003

Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis.

PURPOSE: The purpose of this study was to identify a mediator produced by human colon cancer cells that is responsible for the induction of hyperplasia in the adjacent mucosa. EXPERIMENTAL DESIGN: Seventy human colon cancer surgical specimens were immunostained to determine the presence of cytokines that can induce hyperplasia in the adjacent mucosal. Human colon cancer cells with low and high metastatic potential were implanted into the cecal wall of nude mice. The resulting lesions were studied by immunohistochemistry to detect possible mediators of mucosal hyperplasia. RESULTS: Immunostaining of 70 colon cancer specimens from 70 patients suggested that mucosal hyperplasia and distant metastasis were associated with the expression of interleukin (IL)-15 and, to a lesser extent, transforming growth factor alpha. The production of IL-15 by colon cancer cells was not associated with the infiltration of natural killer cells into the tumors. Cecal tumors produced in nude mice by human colon cancer cells with low and high metastatic potential (KM12C and KM12SM cells, respectively) expressed similar levels of transforming growth factor alpha, and expression of IL-15 was detected only in the metastatic KM12SM cells and was associated with hyperplasia of the surrounding mucosa. The expression of the IL-15 receptor in rat intestinal epithelial cells (IEC6 cells) was confirmed by immunoblotting with antibodies against IL-15 receptor alpha and IL-2 receptor beta and gamma subunits and by a binding assay using (125)I-labeled IL-15 (K(d) = 0.011 nM). IL-15 stimulated proliferation of the IEC6 cells, even under serum starvation. Treatment of IEC6 cells with IL-15 decreased doxorubicin-mediated cytotoxicity. In IEC6 cells treated with either IL-15- or KM12SM-conditioned medium, immunoblotting revealed a decrease in the production of p21Waf1, Bax, and Bak and an increase in the production of cyclin E, proliferating cell nuclear antigen, the phosphorylated active form of AKT, basic fibroblast growth factor, and vascular endothelial growth factor, changes associated with cell growth, survival, and induction of angiogenesis. CONCLUSIONS: These data indicate that IL-15 produced by metastatic colon carcinoma cells can induce hyperplasia in the mucosa adjacent to colon cancer, thus contributing to angiogenesis and progression of the disease.

Animals↗
PubMed2003

A chiral chelating diene as a new type of chiral ligand for transition metal catalysts: its preparation and use for the rhodium-catalyzed asymmetric 1,4-addition.

As a new type of chiral ligand, a C2-symmetric norbornadiene derivative (1R,4R)-2,5-dibenzylbicyclo[2.2.1]hepta-2,5-diene (1) was prepared and used for the rhodium-catalyzed asymmetric addition of organoboron and -tin reagents to alpha,beta-unsaturated ketones, which gave high yields of the 1,4-addition products with up to 99% enantioselectivity.

Journal Article↗
PubMed2003

Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma.

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.

Adenocarcinoma↗
PubMed2003

Expression of thrombospondin-1 is correlated with microvessel density in gastric carcinoma.

Thrombospondin-1 (TSP-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of TSP-1 on neovascularization according to organ or histological type. Wild-type p53 protein has been shown to induce TSP-1 expression. We examined the expression of TSP-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. We also performed reverse-transcriptase polymerase chain reaction analysis for the TSP-1 mRNA expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. Strong expression of TSP-1 protein was detected in 30 (38%) of the 80 cases. Positive staining for TSP-1 was seen in the cytoplasm of the cancer cells. TSP-1 mRNA expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. Microvessel counts were significantly higher in tumors with strong TSP-1 protein expression than in those without expression or weak expression of TSP-1 ( P=0.011). No significant correlation was found between TSP-1 expression and p53 staining and clinicopathological factors. Our results support an idea that increased TSP-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that TSP-1 may play diverse roles in each organ.

Adenocarcinoma↗
PubMed2003

A new cine-substitution of alkenyl sulfones with aryltitanium reagents catalyzed by rhodium: mechanistic studies and catalytic asymmetric synthesis of allylarenes.

The reaction of alkenyl sulfones with aryltitanium triisopropoxide (ArTi(OPr-i )3) in the presence of 3 mol % of [Rh(OH)((S)-binap)]2 in THF at 40 degrees C gave high yield of cine-substitution products. The catalytic cycle was established by deuterium-labeling studies, and it was applied to catalytic asymmetric synthesis of allylarenes which proceeds with over 99% enantioselectivity.

Journal Article↗
PubMed2003

Generation of chiral boron enolates by rhodium-catalyzed asymmetric 1,4-addition of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) to alpha,beta-unsaturated ketones.

Asymmetric 1,4-addition of 9-phenyl-9-borabicyclo[3.3.1]nonane (2m) to 2-cyclohexenone (1a) proceeded with high enantioselectivity in toluene at 80 degrees C in the presence of 3 mol % of a rhodium catalyst generated from [Rh(OMe)(cod)]2 and (S)-binap to give a high yield of boron enolate (S)-3am, which is 98% enantiomerically pure. Reaction of the boron enolate 3am with electrophiles, methanol-d, propanal, and allyl bromide, gave the corresponding 2-substituted (3S)-3-phenylcyclohexanones with perfect regio- and diastereoselectivity.

Journal Article↗
PubMed2003

Future prospects of personalized chemotherapy in gastric cancer patients: results of a prospective randomized pilot study.

In the present study, in order to evaluate the feasibility of personalized chemotherapy, a prospective randomized pilot study was performed in 30 advanced or recurrent gastric cancer patients. As we have demonstrated previously, the expressions of mRNA from tumor biopsy samples for seven molecular markers, i.e., dihydropyrimidine dehydrogenase (DPD), glutathione S-transferase (GST)-pi, beta-tubulin (tub), O6-methylguanine-DNA methyltransferase (MGMT), multiple drug-resistant protein (MRP)-1, NADPH/quinone oxidoreductase (NQO)-1, and cytochrome p450 (P450), were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis and therapy was recommended in a flow chart that depended on the level of expression of these predictive molecular markers. We chose 12 therapeutic plans, including best supportive care (BSC). We treated 15 patients according to the gene expression profiles, and the remaining 15 patients (controls) were treated without recommended regimens, and the therapy was continued after the expression profiles were checked. Interestingly, 11 of 26 lesions (42.3%) responded after treatment given according to gene expression analysis; however, no clinical response was detected in the control group. The prediction of the response, including resistance, was successful in 75.9% by the gene expression profiles. Moreover, the survival of the patients with the recommended treatment was better than that of patients without a recommended protocol. These results indicate that personalized treatment may be beneficial for gastric cancer chemotherapy and further randomized trials should be carried out in the future.

Adult↗
PubMed2003

Laparoscopic radical prostatectomy: initial 30-case experience.

BACKGROUND: We carried out this study to clarify whether the operative methods of laparoscopic prostatectomy established in France could become standard therapy. The purpose was to evaluate the technical feasibility, oncological efficacy, and intraoperative and postoperative morbidity of laparoscopic prostatectomy performed by a general urologist. METHODS: Between June 2000 and August 2002, 30 patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy performed as previously reported by Guillonneau and colleagues. Oncological data were assessed by pathological examination and by postoperative prostate-specific antigen (PSA) levels. All prostatectomy specimens were processed according to the Stanford protocol. Prostate features, including tumor weight; Gleason score; and the tumor status of the capsule, seminal vesicles, and surgical margins were studied. RESULTS: Complete laparoscopic removal of the prostate and seminal vesicles was achieved in all 30 patients. Operating time averaged 325.5 min (range, 165 to 880 min). The transfusion rate for the patients in the series was 50%, using own-blood transfusion (800-1200 ml). No patient required an allogenic blood transfusion. Only 2 of the 30 patients had a positive surgical margin that involved the urethra. There were three complications: bladder injury, rectal injury, and ileus associated with a drainage tube. No vascular, nervous system, or urethral complications were found. CONCLUSION: These preliminary results demonstrated that radical prostatectomy can be performed laparoscopically by general urologists. Laparoscopy offered better luminosity and magnification than conventional procedures, permitting precise dissection. Thus, laparoscopic prostatectomy could be a standard operation for patients with clinically organ-confirmed prostate cancer.

Aged↗
PubMed2003

DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype.

Hypermethylation of CpG islands is associated with silencing of various tumor suppressor genes. Recent studies on colorectal and gastric cancer have identified a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. For determination of association between DNA methylation pattern or histological type and CIMP status in gastric carcinoma, CpG islands in the promoters of hMLH1 and CDH1 genes, CpG islands overlapping exon 1 of MGMT and p16(INK4a) genes, and a non-CpG island in exon 1 of the RAR-beta gene were studied. The presence of the CIMP was determined by monitoring five methylated in tumor (MINT ) loci in 103 gastric carcinomas. Among the 103 gastric carcinomas, DNA hypermethylation was detected in the following frequencies: 14 (14%) for hMLH1, 26 (25%) for MGMT, 26 (25%) for p16(INK4a), 54 (52%) for CDH1, and 53 (52%) for RAR-beta. Forty-two (41%) of 103 gastric carcinomas were positive for the CIMP. CIMP and hypermethylation of p16(INK4a) gene were found more frequently in intestinal and diffuse-adherent types than in diffuse-scattered type (P = 0.013 and 0.017, respectively). In contrast, hypermethylation of the CDH1 and RAR-beta genes was more common in the diffuse-scattered type than in the other types (P = 0.008 and 0.007, respectively). In intestinal- and diffuse-adherent-type gastric carcinomas, we found significant associations between the presence of the CIMP and hypermethylation of several genes: hMLH1 (P = 0.006), p16(INK4a) (P = 0.018), CDH1 (P = 0.024), and RAR-beta (P = 0.044). Our overall results suggest that in some intestinal- and diffuse-adherent-type gastric carcinomas, DNA hypermethylation affects non-specific gene promoters concordantly, at least in part, whereas in diffuse-scattered-type gastric carcinoma, DNA hypermethylation affects specific genes such as CDH1 and RAR-beta.

CpG Islands↗