Biomedical subjects

Michiya Kobayashi

Publications and source records attributed to Michiya Kobayashi.

At least 37 records · Page 2Linked to original sources

PubMed2006

STI571 (Glivec) induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1, via endoplasmic reticulum stress response.

STI571 is a specific inhibitor of tyrosine kinases, such as BCR-ABL, platelet-derived growth factor receptor, and c-KIT, and has recently been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). This study demonstrated that STI571 induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1. In these cells, STI571 induced pro-caspase-12 or pro-caspase-7 cleavage and it affected caspase-3 activity and induced the endoplasmic reticulum (ER)-resident chaperone, glucose-regulated protein 78. The STI571-induced cell death was blocked by the protein synthesis inhibitor, cycloheximide. Together, these results suggest that STI571 induces cell death in GIST-T1 cells, at least in part, via the ER stress response.

Antineoplastic Agents↗

PubMed2006

Management of intra-abdominal abscess due to surgical site infection.

Intra-abdominal abscesses are one of the major complications that occur after Gastrointestinal Surgery. Therapeutic modalities include drainage and irrigation. This study describes the development of a new drainage and continuous irrigation system that results in less skin irritation and reduced dressing changes. This system involved the use of the Surgidrain open top (ALCARE, Tokyo, Japan), which consists of a sealing sheet with a drainage lumen and plastic cap. A double-lumen tube was inserted into the abscess cavity through a slit in the plastic cap. The abscess cavity could, therefore, be irrigated continuously through one lumen of the double-lumen tube, and most of the fluid could be drained through the second lumen of the double-lumen tube. Overflow fluid was drained through the Surgidrain open top drainage lumen. This system enabled better protection against skin complications and the ability to easily flush the abscess intermittently.

Abdominal Abscess↗

PubMed2005

Clinicopathological study of cardiac tamponade due to pericardial metastasis originating from gastric cancer.

AIM: To review the cases reported in the literature, examined their clinicopathological features, and evaluated the efficacy of different therapeutic modalities for this rare condition. METHODS: A search of the MEDLINE database revealed 16 cases of pericarditis carcinomatosa (PC) originating from GC reported in the literature between 1982 and 2005. Additional detailed data were obtained from the authors of these studies for subsequent clinicopathological investigation. We have also described about a case study from our own clinic. RESULTS: The mean age of cases with pericarditis carcinomatosa originating from GC was 54 years. Females were diagnosed at a younger age (46.3 years) compared to males (58 years). The mean survival period after diagnosis was 4.5 mo. No statistical differences in the length of survival time were found between different therapeutic modalities, such as drainage, and local and/or systemic chemotherapy after drainage. However, three cases who underwent systemic chemotherapy survived for more than 10 mo. Cases that developed metachronous cardiac tamponade for more than 2 years after the diagnosis of GC generally survived for a longer period of time, although this was not statistically significant. Multivariate analysis revealed that low levels of carcinoembryonic antigen (CEA), and CEA and/or cancer antigen 19-9 (CA 19-9) were associated with longer survival. CONCLUSION: Cases with low levels of CEA, and CEA and/or CA 19-9 should undergo systemic chemotherapy with or without local chemotherapy after drainage.

Adult↗

PubMed2005

A randomized phase III trial of post-operative adjuvant oral fluoropyrimidine versus sequential paclitaxel/oral fluoropyrimidine; and UFT versus S1 for T3/T4 gastric carcinoma: the Stomach Cancer Adjuvant Multi-institutional Trial Group (Samit) Trial.

Paclitaxel, S1 and their combined sequential administration is proposed to be examined installing UFT as an active control of adjuvant chemotherapy for curatively resected T3-4 gastric cancer in a multicenter Phase III trial. The primary endpoint is disease-free survival and the secondary endpoints are incidence of adverse events, overall survival and compliance. The sample size is 370 per treatment arm (1480 in total) for two hypotheses of the superiority of sequential use of paclitaxel followed by oral fluoropyrimidines to fluoropyrimidines (UFT/S1) alone and the non-inferiority of S1 to UFT to be tested by two-by-two factorial design. Abdominal CT or US is performed every 3 months in the first 2 years and every 6 months thereafter for 3 years in total to ensure recurrence data collection. This trial could appraise sequential combination therapy and efficacy of new drugs as adjuvant for gastric cancer treatment.

Administration, Oral↗

PubMed2005

Metastatic bone cancer as a recurrence of early gastric cancer -- characteristics and possible mechanisms.

The surgical outcome of most early gastric cancer (EGC) is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed. Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan. This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Post-operative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases.

Bone Neoplasms↗

PubMed2005

Phenolsulfonphthalein transport by potential-sensitive urate transport system.

The purpose of this study was to elucidate the transporter-mediated secretion systems for phenolsulfonphthalein in brush-border membranes. In human and rat renal brush-border membranes, a potential-sensitive transport system has been shown to be involved in the efflux of organic anions. The uptake of phenolsulfonphthalein into rat renal brush-border membrane vesicles was stimulated by an inside-positive membrane potential. This potential-sensitive uptake of phenolsulfonphthalein was inhibited by probenecid, pyrazinoate and urate. p-Aminohippurate had no effect on the potential-sensitive uptake of phenolsulfonphthalein. Moreover, urate competitively inhibited the uptake of phenolsulfonphthalein. On the other hand, the uptake of phenolsulfonphthalein was slightly increased in the presence of an outward Cl- gradient. These results suggest that phenolsulfonphthalein has high affinity for the potential-sensitive urate transport system but has low affinity for an anion exchanger.

Animals↗

PubMed2005

Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials.

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55-0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58-0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Phase I evaluation of continuous 5-fluorouracil infusion followed by weekly paclitaxel in patients with advanced or recurrent gastric cancer.

OBJECTIVE: We conducted a phase I trial of escalating doses of weekly paclitaxel (Taxol) in combination with a fixed systemic administration of 5-fluorouracil (5-FU) in patients with advanced or metastatic gastric cancer. METHODS: Patients with advanced or recurrent gastric cancer were treated with escalating doses of weekly paclitaxel as a 60 min intravenous (i.v.) infusion, along with a fixed dose of continuous 5-FU infused over 5 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel. RESULTS: Eighteen patients received combination therapy at four dose levels of weekly Taxol, ranging from 60 to 90 mg/m2/week. Dose-limiting toxicities > grade 3 were observed at the 90 mg/m2/week dose level. Toxicities included anemia, neutropenia, thrombocytopenia, nausea and alopecia. Two episodes of grade 4 neutropenia occurred in two of the three patients receiving this dose. At each dose level, pharmacological studies documented the persistence of significant serum paclitaxel levels over 24 h after drug administration. The maximum tolerated dose (MTD) for this regimen was 90 mg/m2/week of paclitaxel for 3 weeks plus 600 mg/m2/day of continuous 5-FU for 5 days. CONCLUSIONS: The combination of weekly paclitaxel and 5-FU demonstrated an acceptable toxicity profile and feasible pharmacokinetic results suggesting its practical applicability. Based on these findings, the recommended dose and schedule for phase II study of combination chemotherapy is paclitaxel 80 mg/m2/week x 3 over 4 weeks, and continuous 5-FU 600 mg/m2/day x 5 days every 4 weeks.

Adult↗

PubMed2005

Adenosquamous carcinoma of the extrahepatic biliary tract: clinicopathological analysis of Japanese cases of this uncommon disease.

BACKGROUND: We analyzed the clinicopathologic variables and postoperative outcomes in patients with extrahepatic adenosquamous carcinoma to identify important factors for predicting postresection prognosis. METHODS: Thirty-six patients in Japan who underwent surgical resection for adenosquamous carcinoma of the extrahepatic biliary tract, with curative intent by the end of 2003, were studied. A retrospective review, with univariate and multivariate analyses, was performed on the clinical records of patients who underwent surgical exploration for adenosquamous carcinoma of the common bile duct. The clinical and pathologic factors that influenced patient survival were analyzed. RESULTS: The operative mortality rate in the patient cohort was 3%. The overall 1-, 3-, and 5-year survival rates were 57%, 26%, and 16%, respectively, and the median survival was 13 months. Univariate and multivariate analyses revealed that independent negative prognostic factors in resected specimens were: (1) the presence of pancreatic invasion, (2) the presence of n2 and n3 lymph node metastasis, and (3) curability C status. The presence of an abnormal arrangement of the pancreatobiliary ductal system and pathological serosal invasion of the tumor tended to be associated with poor survival. CONCLUSIONS: Curative surgical resection for adenosquamous carcinoma remains the only effective treatment, because it offers the chance of long-term survival. New adjuvant strategies are required for improvements in patient outcomes.

Adult↗

PubMed2005

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Animals↗

PubMed2005

Localization of thymidine phosphorylase in breast cancer tissue.

Thymidine phosphorylase levels are higher in some human cancer tissues than in adjacent normal tissue. However, the ultrastructural localization of thymidine phosphorylase in cancer tissue has been demonstrated only in advanced gastric and colorectal cancer. We investigated the localization of thymidine phosphorylase in breast cancer tissue by immunohistochemistry and its ultrastructural localization by immunoelectron microscopy. Surgically resected specimens from 30 cases of breast cancer were analyzed. Immunohistochemical analysis revealed that cancer cells were positive in 13 cases. However, there were 21 cases that showed thymidine phosphorylase-positive inflammatory cells in cancer tissue. Thymidine phosphorylase-positive staining was detected among both cancer cells and inflammatory cells in 11 cases. Thymidine phosphorylase was diffusely positive in the cytoplasm of cancer cells and specifically positive in mitochondria of neutrophils and specific cytoplasmic granules of macrophages in cancer tissue by immunoelectron microscopy. These findings suggest that thymidine phosphorylase is produced by macrophages and is present in mitochondria of neutrophils and cytoplasmic granules of cancer cells.

5'-Nucleotidase↗

PubMed2005

The change of proliferating cell nuclear antigen and apoptosis of the MM46 mammary cancer cells of the mouse after single high-dose irradiation.

The effects of intraoperative radiotherapy on tumor cells were elucidated by immunohistochemical examination of changes in the level of proliferating cell nuclear antigen. In addition, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method was used to examine the level of apoptosis in mouse MM46 tumor cells after a single high dose of irradiation (30 Gy, 6 MeV). A significant decrease in the number of tumor cells compared to controls was observed on the 3rd, 7th, and 14th days following irradiation, but not on the 1st day. Consistent with these results, the proliferating cell nuclear antigen labeling index of irradiated cells decreased significantly on the 3rd, 7th, and 14th days following irradiation, but not on the 1st day. By comparison, the regrowth area on day 14 only showed no difference compared to the control group. The apoptotic index increased on the 7th and 14th day after irradiation, but at a lower rate than the observed decrease in the level of proliferating cell nuclear antigen. We speculate that the major mechanism of single high-dose radiation effect is inhibition of DNA synthesis.

Animals↗

PubMed2005

Primary gastric small cell carcinoma: report of a case and review of the literature.

A 52-year-old man suffering from a pure-type primary gastric small cell carcinoma was treated with surgery and combination chemotherapy. The small cell carcinoma, approximately 6.5 cm in diameter, was situated in the posterior wall of the antrum and there were no distant metastases. Total gastrectomy and regional lymph node dissection was carried out. Histological examination revealed a solid pattern of proliferation of small cells with hyperchromatic, round nuclei and scant cytoplasm. Neoplastic cells infiltrated into the subserosal layer with severe lymphatic and vascular invasion. Regional lymph node cells were mostly replaced by tumor cells that stained positive for Grimelius, neuron-specific enolase (NSE), and synaptophysin. Accumulations of electron-dense core granules in the small neoplastic cells were seen by electron microscopy. Following surgery, the patient was treated with adjuvant chemotherapy consisting of cisplatin and etoposide. The patient is alive and recurrence free 3 years after surgical operation. We review 107 published cases of primary gastric small cell carcinoma, an extremely rare disease first reported in 1976. Small cell carcinoma is an aggressive, malignant tumor. Intensive chemotherapy is essential for patient survival even when curative surgical resection is carried out.

Carcinoma, Small Cell↗

PubMed2005

An immunocytochemical study of regeneration of gastric epithelia in rat experimental ulcers.

We experimentally observed the process of regeneration of gastric mucosal cells in ulcers induced by surgical removal of the fundic mucosa of rats. The techniques utilized were immunocytochemistry, laser confocal microscopy, and transmission electron microscopy (TEM). Routine TEM and PAS reaction were used for parietal cells, chief cells, and mucous cells. As markers of parietal cells, H+-K+ ATPase, Na+-K+ ATPase, carbonic anhydrase, and aquaporin 4 (AQP4) were used, and for chief cells pepsinogen was used. Healing process of mucosal defect was as follows. On day 2 after the operation, the single-layered regenerating epithelium (RE) originating from the marginal epithelium of the ulcer extended over the granulation tissue of the ulcer base towards the center. Regenerating glands (RGs) appeared in the ulcer margin. The cells appearing first in the RE were undifferentiated cells that had a high nucleus: cytoplasm ratio and abundant free ribosomes. On day 5, the ulcer was almost filled with RGs. Most cells stained positive for PAS reaction. A few immature parietal cells stained weakly with H+-K+ ATPase, Na+-K+ ATPase, carbonic anhydrase, and aquaporin-4 antibodies, and a few immature chief cells stained weakly with pepsinogen antibody were also observed on day 5. On day 10, the ulcer was filled with RGs. The RGs in the periphery of the ulcer stained positive for markers of mature parietal cells and chief cells, whereas the center of the ulcer was composed of immature parietal cells and chief cells. By day 25, the mucosal defect was filled with normal gastric glands formed by maturation of the RGs. The undifferentiated cells that first appeared in the ulcer margin seem to differentiate to special functioning cells of the stomach 5-10 days after ulcer formation.

Animals↗

PubMed2005

Confirmation of the posterior gastric artery using multi-detector row computed tomography.

BACKGROUND: The blood supply of the stomach is well characterized. Although the posterior gastric artery (PGA) is the second most important artery supplying the upper third of the stomach, the main features and clinical importance of the PGA have not been established. The aim of this study was to use multi-detector row computed tomography (MD-CT) to investigate the features of the PGA with respect to its incidence, location and size, and to correlate the findings with clinical practice. METHODS: In August 2004, 50 preoperative patients (33 men and 17 women) were evaluated prospectively by MD-CT. Informed consent for the present study was accepted at Kochi Medical School. The length of the PGA, from the root of the splenic artery, and the internal diameter of the PGA were examined. Correlations between body mass index (BMI) and the observed features of the PGA were investigated. RESULTS: The PGA was recognized in all patients. In 49 (98%) patients, the PGA branched from the splenic artery. In 1 (2%) patient, the PGA originated from the root of the celiac trunk. The PGA was discernible for a length of 4.2-14.3 cm (mean, 9.1 cm) from the root of the splenic artery, and the internal diameter of the PGA was 0.5-2.1 mm (mean, 1.0 mm). BMI did not correlate with PGA length or internal diameter. CONCLUSION: Our current study suggested that the anatomical and clinical features of the PGA can be shown by clinical methods, and that these features are useful in planning surgical treatment.

Adult↗

PubMed2005

Relationship between loperamide-induced sedative effect and digoxin pharmacokinetics in healthy Japanese subjects.

PURPOSE: Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or decline in the P-glycoprotein (P-gp) function. The aim of this study was to determine the loperamide-induced sedative effect quantitatively and to investigate possible alterations in the pharmacokinetics of digoxin, a substrate for P-gp, in Japanese subjects. METHODS: Loperamide hydrochloride (2 mg) was administered orally to 26 subjects and the critical flicker-fusion frequency threshold (CFF) values were measured every 30 min separately by portable instrument. Further, digoxin (0.25 mg) was administered to 8 subjects, and the plasma concentration was determined. RESULTS: In five subjects who complained of drowsiness, the CFF values more remarkably decreased compared with those in the other subjects. The Tmax and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and Cmax was higher than those in four subjects with marginal effect. Moreover, there were good correlations between the CFF value-time profile and the Cmax, Tmax, and MRT of digoxin. CONCLUSIONS: The determination of the CFF value after oral administration of loperamide will be useful for evaluating varied P-gp function and for anticipating individual variations in the disposition of P-gp substrates in humans.

Adult↗

PubMed2005

A clinicopathologic study of primary adenosquamous carcinoma of the liver.

BACKGROUND: Adenosquamous carcinoma (ASC) is a rare tumor of the liver, which carries a poor prognosis. In this study, we reviewed reported cases of ASC and examined their clinicopathologic features. MATERIALS AND METHODS: A computer MEDLINE search found 65 histologically defined primary ASC cases reported in the literature from 1975 to 2003, including our case. Of these, detailed data were obtained for 42 cases, and these were subsequently investigated clinicopathologically. RESULTS: Among the 42 cases, 34 were reported to have died of ASC and 5 cases were alive at the time of the study. The mean survival of these 34 cases was 8.7 months. Multivariate analysis revealed that lymph node metastasis and the elevation of total bilirubin were associated with poor survival after surgery, and lymph node metastasis, intrahepatic metastasis, location of tumor in the right lobe, and the pathologic stage were significant factors for all cases. CONCLUSION: The current study highlights the prognostic factors of ASC of the liver, showing that the prognosis for patients with ASC is poor.

Carcinoma, Adenosquamous↗

PubMed2005

STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1.

The gastrointestinal stromal tumor cell line, GIST-T1, has a heterogenic 57-base pair deletion in exon 11 of the c-kit mutation, and the c-KIT protein in the GIST-T1 cells constitutively activated. We report that STI571 (Glivec; Novartis, Basel, Switzerland), a specific inhibitor of c-KIT, inhibits the clustering of c-KIT at the cell membrane of the GIST-T1 cells. Furthermore, STI571 prevents the interaction between c-KIT and the molecular chaperone, heat shock protein 90 (Hsp90). Geldanamycin, an inhibitor of Hsp90, also prevents interaction between c-KIT and Hsp90, and inhibits tyrosine phosphorylation of c-KIT. Our results indicate that c-KIT molecules are assembled on the cell surface of the GIST-T1 cells, and that the interaction between c-KIT and Hsp90 plays an important role in c-KIT activation.

Benzamides↗