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Biomedical subjects

Kazuhiro Yoshida

Publications and source records attributed to Kazuhiro Yoshida.

At least 37 records · Page 2Linked to original sources

Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells.

The effect on peritoneal metastasis of linoleic acid (LA) was examined using in vitro treatment of cancer cells and mouse peritoneal metastasis models. Firstly, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by LA in a dose-dependent manner with increment of apoptosis. LA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor gamma (PPARgamma) or 15-lipoxygenase-1, which converts LA to PPARgamma ligands. LA significantly inhibited invasion into type-IV collagen-coated membrane of MKN28 and Colo320 cells (p<0.05). BALB/c nu/nu mice inoculated with MKN28 and Colo320 cells into their peritoneal cavities were administrated with LA intraperitoneally (weekly, four times). The LA treatment significantly diminished the number of metastatic foci of both cells in the peritoneal cavity (p<0.05). Protein production in MKN28 and Colo320 cells treated with LA showed a decrease of epidermal growth factor receptor and an increase of Bax. These findings suggest that LA inhibits invasion and metastasis of human gastric and colon cancer cells by nondietary administration.

Animals↗

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer.

Cadherin-17 (CDH17), also called liver-intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.

Adenocarcinoma↗

An air-stable P-chiral phosphine ligand for highly enantioselective transition-metal-catalyzed reactions.

A new P-chiral phosphine ligand, (R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline, has been prepared by the reaction of enantiomerically pure tert-butylmethylphosphine-borane with 2,3-dichloroquinoxaline. This ligand, in contrast to most of the previously reported P-chiral ligands, is an air-stable solid and exhibits excellent enantioselectivities in both Rh-catalyzed asymmetric hydrogenations and Rh- or Pd-catalyzed carbon-carbon bond-forming reactions.

Journal Article↗

A new synthetic approach to phenol derivatives: use of ring-closing olefin metathesis.

Phenol derivatives, which are one of the most important classes of aromatic compounds in organic chemistry, were synthesized by ruthenium-catalyzed ring-closing olefin metathesis (RCM) of 1,4,7-trien-3-ones with versatile substitution patterns. The RCM reaction for producing phenol derivatives was also successful with 1,5,7-trien-3-one as another precursor. Most of the phenols prepared here could not be obtained easily by conventional methods.

Journal Article↗

A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma Assessment of enhancement patterns on dynamics computed tomography before resection.

BACKGROUND AND AIM: : The aim of this study was to identify computed tomography features that contribute to clinical diagnosis of hepatocellular-cholangiocarcinoma. METHODS: : We retrospectively reviewed the clinicopathologic features of 11 patients who underwent hepatectomy for hepatocellular-cholangiocarcinoma between January 1994 and December 2003 at Hiroshima City Hospital and investigated correlation of histopathologic features of surgical specimens with preoperative enhanced computed tomography findings. RESULTS: : Three computed tomography enhancement patterns were observed: an area of hyperenhancement in the early phase and hypoenhancement due to washout of contrast medium in the late phase, resembling hepatocellular carcinoma (Type I, n=4); peripheral enhancement in the early and late phases (Type II, n=2); an area of hyperenhancement in the early phase and an area of slight delayed enhancement in the late phase (Type III, n=4). Histopathologically, all tumors were of mixed morphology (Allen's Type C) comprising hepatocellular carcinoma and cholangiocarcinoma components with transitional features. Computed tomography findings conformed well to pathologic findings. The hepatocellular carcinoma component was predominant in Type I masses. Type II masses showed central necrosis. In Type III masses, the hepatocellular carcinoma-predominant component corresponded to the area of early-phase enhancement and the cholangiocarcinoma-predominant component to the area of late-phase enhancement. CONCLUSIONS: : In Type III tumors, hepatocellular and cholangiocellular components can be identified on the basis of dynamic computed tomography enhancement pattern.

Journal Article↗

Heme oxygenase-1 accelerates protumoral effects of nitric oxide in cancer cells.

We examined the biological effects of nitric oxide (NO) and its mediator, heme oxygenase-1 (HO-1), in cancer. Urogenital cancer cell lines, SKRC, T24 and DU145, were treated with various concentrations of sodium nitroprusside (SNP), a NO donor. The medium nitrite concentration was exponentially increased according to the concentration of SNP. Cell growth inhibition by NO was observed only at high nitrite concentrations (>20 microM) in DU145 and T24 cells. Nitrite did not inhibit the growth of SKRC cells at any of the concentrations used. Doxorubicin (DXR) inhibited cell growth in the three cell lines, whereas growth inhibition recovered in the presence of <10 microM nitrite. The recovery of DXR-induced growth inhibition was closely associated with an increase in Bcl-2 in the presence of <10 microM nitrite. Vascular endothelial growth factor (VEGF) secretion was also increased in the presence of <10 and <20 microM nitrite, respectively, in DU145 and SKRC or T24 cells. The expression of HO-1 was associated with sensitivity to NO-induced growth inhibition at constitutive levels, and was induced by SNP treatment. HO-1 inhibition by HO-1 antisense S-oligodeoxynucleotide treatment increased NO-induced growth inhibition, and decreased Bcl-2 expression or VEGF secretion in the three cell lines. These findings suggest that the NO/HO-1 system has protumoral effects.

Carcinoma, Renal Cell↗

Identification of the layers of the bladder wall on high-frequency endoluminal ultrasonography by a needle puncture experiment.

The purpose of this study was to identify the layers of the bladder wall on high-frequency endoluminal ultrasonography (ELUS). We performed a needle puncture experiment using five normal pig bladders. The histologic layer structure was compared with the ELUS images obtained using a 30-MHz miniature transducer. The bladder wall was depicted as five layers by ELUS and these corresponded to the histologic layers. The first layer (hyperechoic) was a margin echo that included the epithelium and the upper part of the lamina propria. The second layer (hypoechoic) corresponded to the lamina propria and the third layer (hyperechoic) was a margin echo that included the upper part of the muscle layer. The fourth layer (hypoechoic) corresponded to the muscle layer, and the fifth layer (hyperechoic) was a margin echo that included the upper part of the adventitia.

Animals↗

New ultrasonic cystofiberscope for staging bladder tumors.

We report on a new ultrasonic cystofiberscope for staging bladder tumors. The endoscope makes it possible to view endoscopic and ultrasound images of bladder tumors at any location, either alternately in full screen or simultaneously on the same monitor, with higher resolution. The cystofiberscope is useful for assessing the depth of bladder tumor invasion accurately.

Cystoscopes↗

DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage.

Hypermethylation of CpG islands is associated with the silencing of various tumor suppressor genes. Retinoic acid receptor-beta (RAR-beta), cellular retinol-binding protein 1 (CRBP1), and tazarotene-induced gene 1 (TIG1) have been linked to retinoic acid signaling. Little is known about the involvement of these three genes in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the methylation status of these genes and analyzed the role of methylation of their DNA in ESCC. Methylation-specific polymerase chain reaction (PCR) was performed to study the methylation of CpG islands in 28 ESCC (stages I, II, and III) and 10 samples of corresponding non-neoplastic mucosa. The mRNA expression levels of the three genes were measured by quantitative reverse transcription-PCR. DNA hypermethylation of RAR-beta was found in seven (25.0%) of the 28 ESCC, of CRBP1 in five (17.9%), and of TIG1 in five (17.9%). DNA methylation of RAR-beta was identified in one of 10 samples of corresponding non-neoplastic mucosa (10.0%), whereas no DNA methylation of CRBP1 or TIG1 was detected. In total, at least one of the three genes was hypermethylated in 12 (42.9%) ESCC. Reduced expression of RAR-beta, CRBP1, and TIG1 was found in 14 (50.0%), 15 (53.6%), and 13 (46.4%) ESCC, respectively. DNA methylation of each gene was significantly associated with reduced expression of the respective mRNA. No correlation was found between the DNA methylation status of RAR-beta and clinicopathological factors such as depth of invasion, lymph node metastasis, or tumor stage. In contrast, DNA methylation of both CRBP1 and TIG1 was observed only in stage III ESCC. These results show that inactivation of the retinoic acid signaling-associated genes RAR-beta, CRBP1, and TIG1 by DNA methylation occurs frequently in ESCC.

Carcinoma, Squamous Cell↗

Utility of extracorporeal traction with nylon thread for easier vesicourethral anastomosis in laparoscopic prostatectomy.

PURPOSE: Vesicourethral anastomosis in laparoscopic prostatectomy is a very difficult procedure. Our purpose in this study was to evaluate a new method using extracorporeal bladder neck traction with nylon thread for vesicourethral anastomosis during laparoscopic radical prostatectomy. MATERIALS AND METHODS: A total of 10 patients underwent laparoscopic radical prostatectomy by this technique, and we evaluated anastomosis time, operative time, and postoperative status of vesicourethral anastomosis. RESULTS: It was possible to shorten both anastomosis time and operative time by this procedure, and to obtain a hermetic anastomosis without higher risk of incontinence, stricture, or leakage. CONCLUSIONS: Extracorporeal bladder neck traction with nylon thread is a very useful procedure to carry out easier vesicourethral anastomosis, especially for a surgeon's initial experience in laparoscopic radical prostatectomy.

Anastomosis, Surgical↗

A single nucleotide polymorphism in the 5' untranslated region of the EGF gene is associated with occurrence and malignant progression of gastric cancer.

OBJECTIVE: Epidermal growth factor (EGF) has many biological functions and plays an important role in the progression of various tumors including gastric cancer. An A-G single nucleotide polymorphism (SNP) at position 61 in the 5'-untranslated region (UTR) of the EGF gene has recently been reported to be associated with different levels of EGF production. We examined whether this polymorphism is correlated with the development and malignant phenotypes of gastric cancer. METHODS: The study population included 200 gastric cancer patients and 230 healthy control subjects. The SNP in the 5'-UTR of the EGF gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The A allele was significantly less frequent in patients than in controls (p = 0.01). Individuals with the A/A or A/G genotype showed a significantly lower risk of gastric cancer than those with the G/G genotype [adjusted odds ratio (OR) = 0.56], whereas the same genotypes were associated with malignant progression of this cancer, e.g. deeper tumor invasion, increased lymph node metastasis and advanced clinical stage, and histological classification in gastric cancer patients (adjusted OR = 1.80, 1.98, 2.26 and 1.89, respectively). CONCLUSIONS: Our findings suggest that the A-G polymorphism of EGF is involved not only in the occurrence but also in the malignant progression of gastric cancer.

5' Flanking Region↗

Expression of p53 protein in esophageal squamous cell carcinoma: relation to hypoxia-inducible factor-1alpha, angiogenesis and apoptosis.

OBJECTIVES: Hypoxia-inducible factor (HIF)-1 is important in the control of transcription of several genes related to angiogenesis. We have previously reported that expression of HIF-1alpha correlates with venous invasion and clinical outcome in esophageal squamous cell carcinoma. p53 has been reported to interact with HIF-1alpha and induce ubiquitin-mediated proteosomal degradation of HIF-1alpha. The purpose of this study was to clarify whether the expression of p53 is associated with that of HIF-1alpha. METHODS: Expression of p53, HIF-1alpha and vascular endothelial growth factor (VEGF) was examined in 81 archival surgical specimens of human esophageal squamous cell carcinoma tissue. CD34 and single-stranded DNA were used to evaluate angiogenesis and apoptosis. RESULTS: Forty-seven of the 81 (58.0%) tumor specimens showed high levels of nuclear p53 immunoreactivity. Overexpression of p53 was observed in the early clinical stage of tumor development. Expression of p53 was not correlated with HIF-1alpha or VEGF expression, angiogenesis or apoptosis in esophageal carcinoma. CONCLUSIONS: These results suggest that mutations in p53 play a role in carcinogenesis but not in the progression of esophageal squamous cell carcinoma. HIF-1alpha may not only be regulated by p53 but also by other factors.

Aged↗

Random systematic sextant biopsy versus power doppler ultrasound-guided target biopsy in the diagnosis of prostate cancer: positive rate and clinicopathological features.

PURPOSE: To determine the efficacy of power Doppler ultrasound (PDU)in the diagnosis of prostate cancer, the rate of detection of cancer with PDU-guided target biopsy and sextant biopsy, the clinicopathological features of cancer positive specimens, and the relation between these two findings were studied. METHODS: From January 1998 through March 2000, 302 men suspected to have prostate cancer underwent sextant biopsy in association with additional PDU-guided target biopsy. Cases with positive biopsy results were divided into 9 groups as follows: T0: sextant biopsy was positive, but target biopsy was negative; S0: all sextant biopsies were negative, but target biopsy was positive; S1 approximately S6: both sextant biopsy and target biopsy were positive (number indicates number of positive sextant biopsy); Tx: sextant biopsy was positive, but no target biopsy was performed owing to a lack of echogenic abnormalities. The Gleason score (GS) and percent organ confined disease (%OCD) were compared between these 9 groups. RESULTS: Cancer was pathologically detected in 143 of 302 patients (47.4%). PDU detected 39 of 49 digital rectal examination-negative cancers (79.6%) and 5 of 13 transrectal ultrasound-negative isoechoic cancers (38.5%). Of 143 biopsy-positive cases, 6 were in the T0 group (4.2%), 10 in S0 (7.0%), 119 in S1 approximately S6 (83.2%), and 8 in Tx (5.6%). Target biopsy missed 14 (sum of T0 and Tx) cancers, and sextant biopsy missed 10 (S0). The average GS in the Tx group was significantly lower than that in the other groups; consequently, the %OCD was significantly higher. Retrospective analysis revealed that the failure to obtain cancer tissue in 4 of the 6 cases in the T0 group is most likely due to technical failure in obtaining specimens. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PDU were 90.2%, 77.4%, 78.2%, 89.8% and 83.4%, respectively. CONCLUSION: PDU in association with sextant biopsy is a useful tool for increasing the rate of detection of prostate cancer. Further advances in ultrasound technology may enable the detection of prostate cancer by target biopsy alone and consequently may reduce the number of unnecessary biopsies. However, PDU-guided target biopsy alone is insufficient for cancer detection at the present time because of possible technical failure in obtaining specimens and the existence of PDU-negative cancer. Although more evidence is required, PDU-negative cancer is suggested to be less aggressive clinically, possibly justifying a watch and wait policy.

Aged↗

[Three advanced gastric cancer patients successfully treated by combination therapy of docetaxel and TS-1].

We have experienced three gastric carcinoma cases successfully treated by the combination therapy of docetaxel and TS-1. Case 1: 66-year-old male with advanced gastric cancer invading the pancreas with metastasis to the liver and left neck lymph nodes. Case 2: 50-year-old female with scirrhous gastric carcinoma causing huge amount of malignant ascites. Case 3: 59-year-old male with recurrent gastric cancer of the remnant stomach presenting with obstruction and vessel involvement. Primary and metastatic diseases of these patients were remarkably improved with the combination therapy, indicating that the combination therapy of docetaxel and TS-1 can be a new therapeutic tool for advanced and recurrent gastric cancer patients.

Adenocarcinoma, Scirrhous↗

[A case of remnant gastric cancer with multiple bone metastasis and peritoneal dissemination; efficacy of combination therapy of docetaxel and TS-1].

A 69-year-old female underwent radical surgery for advanced gastric cancer (Stage IIIA) 7 years ago. She was diagnosed as remnant gastric cancer with multiple bone metastasis and peritoneal dissemination. Treatment with docetaxel and TS-1 was started with the following regimen: daily oral administration of 100 mg/body TS-1 for 14 days, followed by a 7 day rest and infusion of 40 mg/m2 docetaxel on day 1. Two months after the initial administration of docetaxel/TS-1, the sites of the remnant gastric cancer and bone metastasis were reduced in size, and the ALP returned to almost the normal level. The site of peritoneal dissemination had disappeared. Currently (nine months after diagnosis), she is undergoing therapy with TS-1. The combination of docetaxel and TS-1 can be a new tool for the management of gastric cancer with bone metastasis.

Adenocarcinoma↗

[A case report of bowel obstruction due to peritonitis carcinomatosa using combined administration with CPT-11 and CDDP].

We report here a case of recurrent gastric cancer that responded to third-line chemotherapy with CPT-11 and CDDP. The patient was a 61-year-old man with recurrent gastric cancer, who had administered TS-1 for first-line chemotherapy and paclitaxel for second-line chemotherapy. After such therapy, bowel obstruction was revealed due to peritoneal dissemination. The patient underwent third-line chemotherapy with CPT-11 and CDDP after drainage of gastrointestinal juice by nasogastric tube. The treatment schedule for CPT-11 and CDDP therapy consisted of CPT-11 60 mg/m2 div at day 1, day 15 and CDDP 60 mg/m2 div at day 1. It was repeated every 4 weeks. After first administration, the bowel obstruction was improved, so the treatment was continued for 8 months on an outpatient basis. These findings imply that this treatment can be a useful second-line or third-line chemotherapy for unresectable advanced or recurrent gastric cancer.

Ambulatory Care↗

[Clinical study of TS-1 for inoperative and recurrent gastric cancer and evaluation of long survival cases].

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 67 patients who were treated with TS-1 in our department between June 1999 and September 2004. The objective overall response rate was 41.0% (16/39; 95% confidence interval, CI, 25.3-56.7). By location, the response rate of peritoneal dissemination was high (57.1%), as were those of primary lesion (53.3%) and lymph nodes (42.9%). The prevalence of adverse reactions with a grade of 3 or 4 was 12.8%. The median survival rate (MST) was 276 days with 1-year and 2-year survival rates of 48.9% and 27.8%, respectively. This resulted in 6 long-term survival cases (over 2.5 years) after TS-1 therapy, and the longest survival time was 3y 5m after TS-1 therapy. PRs or long-term NCs after TS-1 therapy were likely to be important factors for long-term survival. In conclusion, TS-1 is safe and effective for patients with inoperable and recurrent gastric cancer, and is promising as a first-line treatment.

Adult↗