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Biomedical subjects

Hiromitsu Saisho

Publications and source records attributed to Hiromitsu Saisho.

At least 19 recordsLinked to original sources
PubMed2007

Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.

PURPOSE: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m(2)/day. RESULTS: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80 mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. CONCLUSIONS: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.

Aged↗
PubMed2007

Contrast-enhanced three-dimensional fusion sonography of small liver metastases with pathologic correlation.

PURPOSE: To demonstrate that liver metastases with a diameter of < or =40 mm show characteristic features on three-dimensional (3D) fusion sonographic images and that these sonographic findings can be correlated with histopathologic features of surgical specimens. METHODS: Liver metastases measuring < or =40 mm were examined via contrast-enhanced 3D fusion sonography. The characteristic sonographic findings of 17 tumor nodules in 11 patients with a histopathologically confirmed diagnosis of liver metastases were investigated, and their correspondence to the pathologic features were examined in 12 resected nodules. RESULTS: On sonograms, central vessels were visualized in all 17 tumor nodules and peripheral vessels were visualized in 12 nodules. On histopathologic examination, the portal triad vessels corresponded to the central vessels and were located at the center of the tumors. A thin layer of peritumoral hepatocytes showing various changes was also observed, and a group of tiny vessels were seen running along this layer of cells. CONCLUSIONS: Liver metastases measuring 40 mm or less in diameter were characterized by the presence of both central and peripheral vessels on contrast-enhanced 3D fusion sonography. There was good correlation between sonographic and histopathologic findings.

Adult↗
PubMed2006

Signaling pathway of insulin-like growth factor-II as a target of molecular therapy for hepatoblastoma.

AIM: To address the possibility that insulin-like growth factor (IGF)-II is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-II was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-II. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS: IGF-II stimulated cells proliferated to 2.7 (269%+/-76%) (mean+/-SD) (Huh-6) and 2.1 (211%+/-85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44%+/-11% (Huh-6) and 39%+/-5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30%+/-5% (Huh-6), 44%+/-0.4% (HepG2), 49%+/-1.0% (Huh-6) and 46%+/-1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33%+/-11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION: IGF-II was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.

Androstadienes↗
PubMed2006

Multidetector helical CT plus superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions in cirrhotic liver: a comparison with multi-phase CT during hepatic arteriography.

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller (p<0.05); however, for lesions larger than 10mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10mm.

Carcinoma, Hepatocellular↗
PubMed2006

Analysis of genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine in gastric cancer cell lines.

In gastric cancer, increasing numbers of genes have been reported to be silenced by aberrant methylation. However, global analysis of epigenetic inactivation in cancer cells has rarely been performed. For screening the genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine (DAC), cDNA microarray analysis (AceGene(R), containing 30,000 genes) was performed using gastric cancer cell lines (AGS, MKN74, MKN1, MKN45 and Kato3) treated with DAC. The candidate upregulated genes were confirmed by real-time PCR, and the methylation status of 5'CpG islands was determined by bisulfite DNA sequencing or methylation-specific PCR. Among the upregulated genes considered to have CpG island in their promoter regions, we selected 5 genes (BCL2L10, DKK1, DNAJD1, GAGED2 and NMU) that exhibited a greater than 3-fold increase in at least 2 cell lines. Of these, we could determine the methylation status of 5'CpG islands of BCL2L10, DKK1 and DNAJD1. 5'CpG of BCL2L10 and DNAJD1 was hypermethylated in 4 of 5 gastric cancer cell lines, whereas 5'CpG of DKK1 was hypermethylated in only 1 cell line. MSP analysis for BCL2L10 revealed that the CpG island was demethylated after DAC treatment. In addition, we observed that overexpression of BCL2L10 could promote apoptosis and growth-inhibitory effect in gastric cancer cell lines. In conclusion, some of the genes upregulated by DAC treatment may be transcriptionally repressed by promoter hypermethylation. These genes might be related to gastric carcinogenesis. In particular, the suppression of BCL2L10, which could induce apoptosis and inhibit proliferation of cancer cells, might be one of the underlying mechanisms for gastric carcinogenesis.

Azacitidine↗
PubMed2006

Doppler study of hepatic vein in cirrhotic patients: correlation with liver dysfunction and hepatic hemodynamics.

AIM: To elucidate the significance of Doppler measurements of hepatic vein in cirrhotic patients and to correlate with liver dysfunction and hepatic hemodynamics. METHODS: One hundred patients with liver cirrhosis and 60 non-cirrhotic controls were studied. Doppler waveforms were obtained from right hepatic vein and flow velocity measured during quiet respiration. Doppler measurements were also obtained from portal trunk, right portal vein and proper hepatic artery. RESULTS: Hepatic vein waveforms were classified into three classical patterns. Flat waveform was uncommon. Mean hepatic vein velocity was significantly higher in cirrhotic patients (12.7 +/- 6.4 vs 5.1 +/- 2.1 and 6.2 +/- 3.2 cm/s; P<0.0001). The poorer the grade of cirrhosis, the higher was the mean velocity. Maximum forward velocity was never greater than 40 cm/s in controls. Degree of ascites was found to be highly correlated with mean velocity. "Very highq group (>=20 cm/s) presented clinically with moderate to massive ascites. Correlations between right portal flow and mean velocity was significant (P<0.0001, r = 0.687). CONCLUSION: Doppler waveforms of hepatic vein, which is independent of liver dysfunction, should be obtained during normal respiration. Mean hepatic vein velocity reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of liver cirrhosis.

Aged↗
PubMed2006

Role of Clast1 in development of cerebellar granule cells.

We have identified the murine Clast1/LR8 gene by subtraction of cDNA derived from CD40 ligand-activated and naive B cells. The Clast1 gene is ubiquitously expressed in various organs of adult mice. However, its physiological function was largely unknown. To study a role of Clast1, we established Clast1-deficient (Clast1-KO) mice. Here, we reveal that approximately 65% of Clast1-KO mice showed severe ataxia. The Clast1-KO cerebellum with ataxia is small in size and revealed a severely aberrant lobulation, loss of the internal granule cell layer, and the disorganized Purkinje cells. Clast1 mRNA is expressed in the cerebellar granule cells of normal adult mice. Developmentally, Clast1 mRNA is also detected in the external germinal layer of the embryonic cerebellum, indicating its expression in granule cell precursors. Histopathological analysis of the developing Clast1-KO cerebellum demonstrated the reduced number of cells in the external germinal layer. Thus, Clast1 is required for development of cerebellar granule cells.

Animals↗
PubMed2006

Consensus of primary care in acute pancreatitis in Japan.

The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital. Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as the diagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltration. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.

Acute Disease↗
PubMed2006

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5-Aza-2'-deoxycytidine.

BACKGROUND: 5-Aza-2'-deoxycytidine (5-AzaC) is known well for its demethylation effect and is a promising anticancer agent. However, to the authors' knowledge, serial changes in gene expression over time after 5-AzaC treatment have not been studied to date. To clarify the categories of genes that are up-regulated or down-regulated after 5-AzaC treatment, the authors surveyed the genes that had expression levels changed by 5-AzaC treatment in 6 hepatoma cell lines (Hep3B, HLE, Huh7, HepG2, PLC/PRF/5, and Huh6). METHODS: Cell lines were grown in medium that contained 1 microM of 5-AzaC. Changes in messenger RNA levels were monitored from 24 hours up to 120 hours after 5-AzaC treatment using an in-house microarray that consisted of 4608 combinational DNAs. Using clustering analysis to identify the genes that had gradually changed expression levels and to exclude the substantial experimental noise by microarray analysis, the authors focused on 206 up-regulated genes and 248 down-regulated genes. RESULTS: According to their functional characterization, genes that were involved in the cytoskeleton and the extracellular matrix were enriched significantly in the up-regulated genes. Conversely, genes that were involved in metabolism were enriched significantly in the down-regulated genes. CONCLUSIONS: The current results demonstrated that 5-AzaC can regulate the expression of groups of genes with characteristic functions.

Azacitidine↗
PubMed2006

State of hepatitis C viral replication enhances activation of NF-kB- and AP-1-signaling induced by hepatitis B virus X.

We examined the effect of hepatitis B virus X (HBx) on NF-kB- and AP-1- mediated transcription in human hepatocellular carcinoma cell lines, Huh-7 with or without subgenomic hepatitis C virus (HCV) RNA. Expression of HBx in Huh-7 cells with HCV resulted in 4.9 times increased NF-kB-activation and 3.8 times AP-1-activation whereas that without HCV resulted in 2.4 times increased NF-kB-activation and 2.3 times AP-1-activation. Interestingly, the expression of the matured form of HCV core protein, Core173, did not activate NF-kB- or AP-1-transcription in either Huh7 with or without HCV replicon. HBx protein might play an important role in HCV-related hepatocarcinogenesis.

Blotting, Western↗
PubMed2006

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma.

AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Objective assessment of the antispasmodic effect of shakuyaku-kanzo-to (TJ-68), a Chinese herbal medicine, on the colonic wall by direct spraying during colonoscopy.

AIM: To objectively evaluate the effect of TJ-68 on colonic spasms during colonoscopy. METHODS: One hundred and one patients subjected to screening colonoscopy were randomly assigned to two groups: TJ-68 in 51 subjects and saline as the control in 50. The endoscope was inserted into the sigmoid colon, then a spastic region was identified and the tip of the colonoscope was positioned at a distance of about 10 mm from the spastic region. The endoscopic view was recorded before and after direct spraying of the TJ-68 solution or warm saline. The intraluminal area of the spastic region was serially measured using a computer image analyzer and expressed as pixel counts. The area under the curve (AUC) was calculated from the pixel curve. Statistical significance was assessed by Wilcoxon's test and Mann-Whitney U test. RESULTS: The mean AUC of the spastic region before and after TJ-68 spraying was 29,128 and 121,943 pixels, respectively, while with saline, it was 31,635 pixels and 48,617 pixels, respectively. Thus, the AUC significantly increased after TJ-68 spraying compared with the spraying of saline (P<0.001). CONCLUSION: Direct spraying of TJ-68 on the colonic mucosa suppressed colonic spasm and it may be useful during colonoscopy when anticholinergic agents are contraindicated.

Aged↗
PubMed2006

Long-term outcome of endoscopic metallic stenting for benign biliary stenosis associated with chronic pancreatitis.

AIM: Endoscopic metal stenting (EMS) offers good results in short to medium term follow-up for bile duct stenosis associated with chronic pancreatitis (CP); however, longer follow-up is needed to determine if EMS has the potential to become the treatment of first choice. METHODS: EMS was performed in eight patients with severe common bile duct stenosis due to CP. After the resolution of cholestasis by endoscopic naso-biliary drainage three patients were subjected to EMS while, the other five underwent EMS following plastic tube stenting. The patients were followed up for more than 5 years through periodical laboratory tests and imaging techniques. RESULTS: EMS was successfully performed in all the patients. Two patients died due to causes unrelated to the procedure: one with an acute myocardial infarction and the other with maxillary carcinoma at 2.8 and 5.5 years after EMS, respectively. One patient died with cholangitis because of EMS clogging 3.6 years after EMS. None of these three patients had showed symptoms of cholestasis during the follow-up period. Two patients developed choledocholithiasis and two suffered from duodenal ulcers due to dislodgement of the stent between 4.8 and 7.3 years after stenting; however, they were successfully treated endoscopically. Thus, five of eight patients are alive at present after a mean follow-up period of 7.4 years. CONCLUSION: EMS is evidently one of the very promising treatment options for bile duct stenosis associated with CP, provided the patients are closely followed up; thus setting a system for their prompt management on emergency is desirable.

Adult↗
PubMed2006

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.

Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.

Apoptosis↗
PubMed2006

Peroral cholangioscopy for the diagnosis and treatment of biliary diseases.

Peroral cholangioscopy with duodenoscopic assistance can allow direct visualization of the bile duct. Several clinical studies suggest the utility of peroral cholangioscopy for the management of various bile duct lesions. Although direct visual observation may be a useful adjunct to endoscopic retro-grade cholangiopancreatography (ERCP) for distinguishing malignant from benign bile duct lesions, the assessment of diagnostic accuracy needs further controlled clinical studies. Intracorporeal lithotripsy with the use of a peroral cholangioscope may be a safe and effective method for difficult-to-treat bile duct stones, including intrahepatic stones. At present, however, the fragility of the fiberscope equipment and technical difficulties hold back its popularity. Preliminary data obtained by using a new videoscope, which provides excellent quality images, are encouraging. Furthermore, it is expected that this videoscope will have longer durability of optical images and better manipulation than previous fiberscopes.

Biliary Tract Diseases↗
PubMed2006

Study of hemodynamic changes in portal systemic shunts and their relation to variceal relapse after endoscopic variceal ligation combined with ethanol sclerotherapy.

BACKGROUND: Among the factors influencing variceal relapse after endoscopic treatment, portal hemodynamic changes, especially in portal systemic shunts, could be the most important factor because hemodynamics are directly related to the development of esophageal varices. We aimed to clarify the influence of endoscopic treatment for esophageal varices on portal systemic shunts as well as its predictive value for variceal relapse. METHODS: Fifty patients who underwent combined endoscopic variceal ligation and injection sclerotherapy were examined with sonography and portography. RESULTS: Decrease of diameter, hepatopetal flow direction in the left gastric vein, or the presence of non-varices portal systemic shunt were sonographic findings related to a low incidence of variceal relapse. The presence of blood flow in and around the esophagus on venograms was highly predictive for variceal relapse. In patients with such venograms, non-varices portal systemic shunts did not develop. CONCLUSIONS: Sonographic assessment of hemodynamic changes in portal systemic shunt could be useful for estimating the results of endoscopic treatment for esophageal varices.

Esophageal and Gastric Varices↗
PubMed2006

Placement of the Bravo wireless pH monitoring capsule onto the gastric wall under endoscopic guidance.

BACKGROUND: The Bravo system was designed mainly to monitor esophageal pH, and there have been no reports on gastric pH monitoring using this system. OBJECTIVE: To place the Bravo capsule on the gastric wall and monitor gastric pH. DESIGN: Experimental clinical trial with the cooperation of volunteers. SETTING: Academic medical center. PATIENTS: Eleven volunteers (9 men, 2 women; mean age 38 years; 3 had symptoms of GERD). INTERVENTIONS: The Bravo system was introduced into the esophagus and stomach along a thin endoscope and capsules were attached, one each to the esophageal and gastric walls under direct vision through the endoscope. Esophageal and gastric pHs were simultaneously monitored. RESULTS: The 2 capsules were successfully placed in 10 of the 11 subjects, and both esophageal and gastric pHs were monitored for 48 hours in 9 subjects. Mild to moderate precordial pain was observed in 7 subjects, but no other complications or side effects were observed in this study. The gastric pH of 10 subjects increased after meals and returned to baseline pH 2 hours later. Decrease of esophageal pH was observed 1 hour after a meal in the symptomatic subjects and corresponded to the time when gastric pH decreased secondary to the increase of pH with meals. CONCLUSIONS: The Bravo capsule is easily placed on the gastric wall under endoscopic assistance and enables long ambulatory monitoring of gastric pH.

Adult↗