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Hirokazu Noshiro

Publications and source records attributed to Hirokazu Noshiro.

17 recordsLinked to original sources
PubMed2007

Hedgehog signaling pathway is a possible therapeutic target for gastric cancer.

BACKGROUND AND OBJECTIVES: It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer. METHODS: Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation. RESULTS: Nuclear localization of Gli1 was higher in 28 undifferentiated-type tumors than in 30 differentiated-type tumors. Eighteen of the fifty-eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated-type part than in the differentiated-type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro. CONCLUSIONS: The Hh pathway may be a useful therapeutic target for such as undifferentiated-type gastric cancer with lymph node metastasis.

Adenocarcinoma↗
PubMed2006

Complete extirpation of a bronchogenic cyst causing recurrent laryngeal nerve palsy by thoracoscopy: report of a case.

We excised a bronchogenic cyst causing recurrent laryngeal nerve palsy using thoracoscopic surgery. A 28-year-old woman presented after the sudden onset of hoarseness, and laryngoscopic examination showed left vocal cord palsy. Computed tomography and magnetic resonance imaging showed a cystic mass, 4 cm in diameter, in the aortopulmonary window. Thoracoscopic examination revealed that the mass was adhered to the recurrent laryngeal nerve below the aortic arch. We extirpated the cyst via thoracoscopy without any injury to the nerves or major blood vessels. This case illustrates the benefits of thoracoscopic surgery for providing good visualization of the perineural structures and as a safe surgical treatment for a cystic mass in the aortopulmonary window.

Adult↗
PubMed2005

A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.

Alleles↗
PubMed2004

Interleukin 1beta enhances invasive ability of gastric carcinoma through nuclear factor-kappaB activation.

PURPOSE: We examined the role of interleukin (IL)-1beta in activation of nuclear factor kappaB (NF-kappaB) and the biological function of activated NF-kappaB in gastric carcinoma cells. EXPERIMENTAL DESIGN: Human gastric carcinoma cell line GCTM-1 was used to examine NF-kappaB activation by immunostaining and electrophoretic mobility shift assay. Matrix metalloproteinase (MMP)-9 expression, which plays an important role in tumor invasion, was assessed by semiquantitative reverse transcription-PCR, Western blotting, and immunostaining. The invasive ability of GCTM-1 cells was measured by Matrigel invasion assay. In vivo expression of IL-1beta and MMP-9 and activation of NF-kappaB in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically. RESULTS: IL-1beta enhanced NF-kappaB activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-kappaB inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1beta-treated GCTM-1 cells. IL-1beta did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1beta and nuclear NF-kappaB was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1beta were tumor-infiltrating macrophages in two specimens and gastric carcinoma cells in one specimen. CONCLUSIONS: One of the molecules that may play a role in NF-kappaB activation in some gastric carcinomas is IL-1beta. The present results suggest that IL-1beta increases the invasive ability of carcinoma cells through activation of NF-kappaB and the resulting MMP-9 expression.

Base Sequence↗
PubMed2003

Cyclosporin-A enhances docetaxel-induced apoptosis through inhibition of nuclear factor-kappaB activation in human gastric carcinoma cells.

PURPOSE: We sought to determine whether cyclosporin-A (CsA) enhances docetaxel [Taxotere (TXT)]- induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relation between this apoptosis and nuclear factor-kappaB (NF-kappaB) activation. EXPERIMENTAL DESIGN: Two human gastric carcinoma cell lines (GCTM-1 and MK-1), a human embryonic pulmonary fibroblast cell line, and human umbilical vein endothelial cells were used as drug targets. Apoptotic cell death was verified morphologically by nuclear fragmentation assay with Hoechst staining. Electrophoretic mobility shift assays were performed to check for nuclear translocation of NF-kappaB. The therapeutic effects of a combination of TXT and CsA were assessed in a mouse peritoneal dissemination model. RESULTS: A combination of CsA (5 micro M) and TXT (10 nM) significantly enhanced apoptotic cell death in both carcinoma cell lines but not in nonmalignant cell lines in comparison with the single-agent treatment alone. This effect was not related to drug uptake, efflux, or MDR1 expression. These effects were also observed in freshly obtained TXT-resistant gastric carcinoma cells isolated from a patient with malignant ascites. TXT alone induced NF-kappaB activation in both carcinoma cell types, and this activation was suppressed by CsA. A combination of TXT and NF-kappaB decoy, a well-known NF-kappaB inhibitor, also enhanced apoptotic cell death in the carcinoma cells. A combination of CsA and TXT significantly suppressed peritoneal dissemination in vivo relative to the single-agent effect. CONCLUSIONS: Treatment with CsA and TXT in combination may be an effective therapeutic strategy for patients with gastric carcinoma.

Adenocarcinoma↗
PubMed2003

Interferon-gamma suppresses transforming growth factor-beta-induced invasion of gastric carcinoma cells through cross-talk of Smad pathway in a three-dimensional culture model.

We reconstituted a three-dimensional gastric carcinoma model similar to invasive gastric carcinoma tissue. This model consists of a human gastric carcinoma cell line, GCTM-1, a human fibroblast cell line, TIG-1-20, and transforming growth factor-beta (TGF-beta)-containing type I collagen gel. Using this model, we were able to observe the growth of the two cell types, especially carcinoma cell invasive growth, in real time for more than 30 days. TGF-beta and TIG-1-20 were essential for GCTM-1 invasive growth and proliferation, respectively. TGF-beta induced the enhanced expression of matrix metalloproteinase 9 (MMP9) and urokinase-type plasminogen activator (uPA) in GCTM-1 at both the protein and enzymatic activity levels. The TGF-beta-induced invasion of GCTM-1 was inhibited by MMP9- or uPA-antisense (AS) oligonucleotide transfection to GCTM-1. When exogenous interferon-gamma (IFN-gamma) was added to this model, TGF-beta-dependent GCTM-1 invasion was significantly inhibited, concomitant with the decreased expression of MMP9 and uPA. The intracellular signal transduction of Smad was examined to analyse the mechanism of the inhibitory effect of IFN-gamma. TGF-beta accelerated the phosphorylation of Smad2/3 and nuclear translocation of the Smad2/3-Smad4 complex in GCTM-1, but these TGF-beta-induced effects were significantly inhibited by IFN-gamma-induced Smad7 expression. When GCTM-1 was cotransfected with AS oligonucleotide of Smad2 and Smad3, the TGF-beta-induced invasion of GCTM-1 disappeared. In addition, the inhibitory effect of IFN-gamma on TGF-beta-dependent GCTM-1 invasion vanished by the AS oligonucleotide of Smad7 transfection. These results indicate that IFN-gamma inhibits TGF-beta-dependent GCTM-1 invasion through cross-talk in the Smad pathway. IFN-gamma may be a new therapeutic tool for TGF-beta-expressed invasive carcinomas.

Cell Line↗
PubMed2003

Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma.

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65-7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.

Aged↗
PubMed2003

Laparoscopic gastric surgery in a Japanese institution: analysis of the initial 100 procedures.

BACKGROUND: Although endoscopic surgical procedures are popular in various fields, reports on its use in gastric surgical procedures are limited. This study was designed to review our initial experience with laparoscopic gastric surgical techniques to evaluate indications and surgical results. STUDY DESIGN: We undertook a retrospective analysis of 100 patients (66 men and 34 women, mean age 63 years) who underwent laparoscopic gastric surgical procedures between 1995 and 2001. Procedures performed were distal gastrectomy (n = 76), wedge resection (n = 20), and intragastric surgical procedures (n = 4). Patients were divided into two groups according to the date of the procedure, from the earliest to the most recent. RESULTS: There were 85 patients with gastric cancers, 14 submucosal tumors, and 1 duodenal ulcer. In 8 cases conversion was made to an open surgical procedure. Operation times required for distal gastrectomy, wedge resection, and intragastric surgical procedures were 330 +/- 69, 144 +/- 34, and 298 +/- 106 min, and blood loss was 354 +/- 251, 56 +/- 94, and 33 +/- 58 g, respectively. Complications included transient anastomotic stenosis (n = 5), leakage (n = 4), and bleeding (n = 1) after distal gastrectomy, and bleeding (n = 1) after intragastric surgical procedures. There were no complications after wedge resection. Comparing the first and second halves of the series, the percentage of distal gastrectomy significantly increased from 66% to 86% (p = 0.02) and the number of dissected lymph nodes at this procedure increased from 20 +/- 13 to 33 +/- 17 (p < 0.01). CONCLUSIONS: Laparoscopic gastric surgical procedures are safe and feasible for early gastric cancers and submucosal tumors. Technical advances in lymph node dissection have made distal gastrectomy a leading and increasingly popular laparoscopic procedure for early gastric cancer.

Aged↗
PubMed2003

Laparoscopy-assisted distal gastrectomy for early gastric cancer: is it beneficial for patients of heavier weight?

OBJECTIVE: In this retrospective review, we evaluated the advantages and disadvantages of LADG for patients of heavier weight with early gastric cancer. SUMMARY BACKGROUND DATA: LADG has been used to treat early gastric cancer. We and others have reported less operative blood loss, less pain, early recovery of bowel activity, early restart of oral intake, and a shorter hospital stay with LADG compared with a conventional open method. There is, however, little information on the advantages of LADG for obese patients with early gastric cancer. METHODS: Between January 1996 and March 2002, 76 patients with preoperatively diagnosed early gastric carcinoma underwent LADG in our department. We classified these patients into 2 groups on the basis of body mass index (BMI). Nineteen patients had a high-BMI (>/= 24.2 kg/m2), and 57 patients had a normal-BMI (<24.2 kg/m2). We collected data by retrospectively reviewing the medical charts. RESULTS: Extension of the minilaparotomic incision or conversion to laparotomy was needed in 6 (32%) of the 19 patients in the high-BMI group, whereas only 3 (5%) of 57 patients in the normal-BMI group required either. In the high-BMI group, Roux-en-Y anastomosis rather than Billroth I anastomosis was adopted more often than in the normal-BMI group, due to the difficulty of the reconstruction (58% versus 4%, P = 0.001). Significantly longer operative time (370 +/- 61 minutes versus 317 +/- 58 minutes, P = 0.015) and prolonged recovery of bowel activity (3.5 +/- 1.0 days versus 2.6 +/- 1.0 days, P = 0.007) were observed in the patients in the high-BMI group. CONCLUSIONS: In the current study, LADG in patients of heavier weight was accompanied by more technical difficulties, and the disadvantages of longer operative time and delayed recovery of bowel activity was observed in patients of heavier weight. Heavier weight appears to be an ominous factor in the successful completion of LADG and should be considered in the decision to use LADG. There are still benefits of a decreased incidence of serious wound and hernia complications in successful cases.

Aged↗
PubMedDate not supplied

Effects of streptococcal preparation OK-432 on liver regeneration and energy status after partial hepatectomy under ischemia/reperfusion in rats.

BACKGROUND/AIMS: Activation of reticuloendothelial system functions by the treatment with OK-432 has been reported to enhance liver regeneration. However, its effect on liver regeneration has not been studied after hepatectomy under ischemia/reperfusion which is in clinical use. The aim was to examine the effect of OK-432 on regeneration and energy status of the liver after hepatectomy under ischemia/reperfusion in rats. METHODOLOGY: Rats were randomly divided into two groups; OK-432 pretreatment and saline treatment (control) group. In the OK-432 group, OK-432 (2.5 mg/kg body weight) was administered intraperitoneally 24 hours before hepatectomy. In the control group, the same volume of physiological saline was administered in the same manner. Seventy percent hepatectomy was performed in both groups during the second 15-minute ischemia period after an initial 15-minute ischemia and 15-minute reperfusion periods. The survival after hepatectomy, relative liver weight, deoxyribonucleic acid synthesis rate, and hepatic adenine nucleotide and energy charge levels were examined immediately after hepatectomy and on postoperative days 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and hyaluronic acid were also measured. RESULTS: All rats survived and the relative liver weight and deoxyribonucleic acid synthesis rate were not significantly different in the two groups. Serum total bilirubin and glutamic pyruvic transaminase levels were not significantly different in both groups. The serum concentration of hyaluronic acid immediately after hepatectomy was significantly higher in the OK-432 group than in the control group. The pretreatment with OK-432 had no significant effect on the levels of adenine nucleotides and energy charge in the liver. CONCLUSIONS: Under ischemia/reperfusion, pretreatment with OK-432 has no significant effect on regeneration and energy status of the liver after hepatectomy.

Adenine Nucleotides↗
PubMedDate not supplied

Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis.

BACKGROUND/AIMS: Association of cholangiocellular carcinoma in patients with hepatolithiasis has been reported. However, its incidence depending on the kind of stones is obscure. The aim was to examine the association rate of cholangiocellular carcinoma in patients with hepatolithiasis with a special reference to the kind of intrahepatic stones. METHODOLOGY: One hundred and thirty-nine patients with hepatolithiasis who have been treated from 1973 to 1997 were retrospectively reviewed to examine the characteristics of cholangiocellular carcinoma. The type and location of intrahepatic calculi were analyzed. RESULTS: Cholangiocellular carcinoma was found in 8 of 139 patients, the incidence being 5.8%. The incidence of carcinoma was more than twice in patients whose stones were located in intrahepatic bile duct only (9.3%; 5/54) than in those located in both intrahepatic and extrahepatic bile duct (3.5%; 3/85). Of 121 patients excluding 18 whose calculi were not available for classification, the kind of intrahepatic calculi was brown pigment in 106 patients (87.6%), cholesterol in 10 (8.3%), black pigment in 4, and fatty acid calcium in one. Cholangiocellular carcinoma was associated in 3 (2.8%) of 106 patients with brown pigment stones, 3 (30%) of 10 with cholesterol stones, in one with fatty acid calcium stones, and one patient whose stone was not available for analysis. The association rate of cancer was significantly (P < 0.01) higher in patients with cholesterol stones than those with brown pigment stones. One patient survived for 24 months after left lobectomy but the others died within six months. CONCLUSIONS: An early and attentive evaluation for the possible presence of cholangiocellular carcinoma is mandatory not only in patients with brown pigment stones but also in those with intrahepatic cholesterol stones.

Adult↗
PubMedDate not supplied

Candidate host marker for peritoneal dissemination.

BACKGROUND: Mesothelial cell injury is common in peritoneal dissemination (PD) of cancer cells. The plasminogen activator system, including urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1), plays an important role in repair of the peritoneum damaged by several types of peritonitis. We investigated and compared the expression of uPA and PAI-1 in the peritoneum of cancer patients with and without PD. MATERIALS AND METHODS: Cancer cell-positive peritoneum and cancer cell-negative peritoneum specimens were obtained from 11 patients with PD, while peritoneum specimens were also obtained from 24 patients without PD. The presence or absence of cancer cells in the peritoneal tissues was confirmed by both hematoxylin-eosin staining and reverse transcriptase-polymerase chain reaction (RT-PCR) detection of carcinoembryonic antigen (CEA) mRNA. uPA and PAI-1 mRNA expression in these peritoneal tissues was determined by RT-PCR and the proteins were localized immunohistochemically. The results were compared statistically. RESULTS: uPA mRNA was expressed in the cancer cell-positive peritoneum from 9 of the 11 (81.8%) patients with PD; PAI-1 mRNA was expressed in the peritoneal tissue from 10 of (91.9%) these patients. Either uPA or PAI-1 mRNA was expressed in the cancer cell-negative peritoneum from 8 (72.7%) of the 11 patients with PD, whereas uPA mRNA was expressed in none of the peritoneal tissues from the 24 patients without PD and PAI-1 mRNA was expressed in specimens from 4 (16.7%) of these patients. Immunohistochemical analysis revealed uPA and/or PAI-1 in the mesothelial cells and submesothelial fibroblasts in cancer cell-negative peritoneum from the patients with PD but not in peritoneum from the patients without PD. CONCLUSION: uPA transcription in the peritoneum may be a host marker indicating the existence of PD.

Adult↗
PubMedDate not supplied

Factors affecting surgical outcome for gallbladder carcinoma.

BACKGROUND/AIMS: The outcome of advanced gallbladder carcinoma is dismal despite aggressive surgery. The aim of this study was to evaluate the surgical outcome and prognostic factors for patients with gallbladder carcinoma and to identify patients who may benefit from radical surgery. METHODOLOGY: Fifty-six patients who underwent surgical resection of gallbladder carcinoma were retrospectively reviewed. Their tumor markers, operative management, pathological factors and survival were analyzed. RESULTS: The serum carcinoembryonic antigen level was elevated in 9 of 51 patients (18%) with data available as was the serum carbohydrate antigen 19-9 level in 14 of 47 patients (30%). Univariate analysis showed that jaundice, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, the number, size, macroscopic type, and histological grade of the tumor, the depth of tumor invasion (pT), pathological stage, lymph node metastasis (pN), lymphatic invasion, vascular invasion, perineural infiltration, curability of lymph node dissection and surgical margins have prognostic significance for survival. Multivariate analysis revealed jaundice, high histological grade, pT3 or pT4, and surgical margins were independent prognostic factors for survival. CONCLUSIONS: Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels are potential predictors and informative for survival. There are still difficulties to treat gallbladder carcinoma infiltrating beyond subserosa or revealing jaundice.

Aged↗
PubMedDate not supplied

Liver cyst with biliary communication successfully treated with laparoscopic deroofing: a case report.

A 71-year-old Japanese woman complained of right upper abdominal fullness and pain. Computed tomography revealed a huge cyst in the right lobe of the liver, measuring 16 cm in diameter. She underwent laparoscopic deroofing of the liver cyst. On operation, needle aspiration of the cyst yielded clear serous fluid without any bile contamination. However, after the cyst was deroofed with laparoscopic coagulating shears, bile leakage was recognized from a tiny orifice in the cyst cavity. A catheter was inserted via the orifice for cholangiography, which demonstrated a communication with the biliary tract. The orifice was easily closed with a laparoscopic suturing device. Operation time was 5 hours and 30 minutes, and blood loss was 300 grams. Pathological examination of the liver cyst was consistent with a simple cyst. The postoperative course was uneventful, and the patient has had no recurrence to date at 13 months. Laparoscopic deroofing is a recommended treatment for a liver cyst even in the presence of cystobiliary communication.

Aged↗
PubMedDate not supplied

Nuclear factor-kappaB p65 is a prognostic indicator in gastric carcinoma.

BACKGROUND: In common with other investigators, we have reported the constitutive activation of transcription factor nuclear factor-kappaB (NF-kappaB) in a variety of carcinomas, but there is no definite information on its clinical significance. MATERIALS AND METHODS: NF-kappaB p65 activation was determined by immunohistochemical analysis of surgically resected specimens from 63 gastric carcinomas. The 63 patients were divided into a high NF-kappaB group (21 patients) and a low NF-kappaB group (42 patients). Forty-seven of the 63 patients underwent curative resection. The 47 patients consisted of 13 high NF-kappaB patients and 34 low NF-kappaB patients. RESULTS: The high NF-kappaB group demonstrated a shorter overall survival rate compared with the low NF-kappaB group (p=0.015). In the 47 patients who underwent curative resection, the high NF-kappaB group also showed a poor survival prognosis (p=0.032). Multivariate analysis indicated that NF-kappaB activation is a potential prognostic factor in gastric carcinoma. CONCLUSION: Constitutive activation of NF-kappaB p65 may be a new prognostic parameter in gastric carcinoma.

Aged↗