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Nobuya Ishibashi

Publications and source records attributed to Nobuya Ishibashi.

15 recordsLinked to original sources
PubMed2006

Upregulation of thymidine phosphorylase in rectal cancer tissues by mitomycin C.

BACKGROUND AND OBJECTIVES: We have investigated the regulation by mitomycin C (MMC) of thymidine phosphorylase (dThdPase) and dihydropyrimidine dehydrogenase (DPD), which enhances or reduces the efficacy of capecitabine and its metabolite 5'-deoxy-5-fluorouridine (5'-DFUR), in rectal cancer tissues. MATERIALS AND METHODS: In 31 patients with a rectal cancer, tumor biopsies were performed before and after pre-operative venous administration of 4 mg/m2, 6 mg/m2, or 10 mg/m2 of MMC. The dThdPase and DPD levels in the biopsy and surgical specimens were measured using ELISA, and immunostaining for dThdPase was performed. RESULTS: The fitting multiple linear regression models indicated that the dThdPase levels increased after MMC administration, in particular in the patients with a pre-treatment dThdPase level less than 56.2 U/mg protein (median value). The time course analysis indicated that the increase in the dThdPase level by 4 mg/m2 of MMC administration continued for 3 weeks. The dThdPase/DPD ratio was increased after MMC administration in patients with a pre-treatment dThdPase/DPD ratio less than 1.79 (median value). MMC enhanced the expression of dThdPase protein both in the tumor cells and in the stromal cells. The disease free-survival rate in the Dukes B or C patients with a high dThdPase/DPD ratio in surgical specimen who received 5'-DFUR based adjuvant chemotherapy tended to be higher than that in those with a low dThdPase/DPD ratio. CONCLUSION: MMC may upregulate the dThdPase level and the dThdPase/DPD ratio in rectal cancer tissues. Combined use of MMC with capecitabine or 5'-DFUR may offer a more effective colorectal cancer therapy.

Adult↗
PubMed2006

Modulation of inflammatory response in sepsis by proteasome inhibition.

The Ubiquitin-proteasome system has recently been shown to be involved in the regulation of cytokine expression. We tested the hypothesis of whether the in vivo administration of proteasome inhibitor MG-132 can modulate cytokine response and mortality in sepsis. Sepsis was induced in mice by caecal ligation and puncture (CLP). Animals were divided into four groups: control, CLP, CLP and 1 microg MG-132/g of b.w. intraperitoneally, and CLP and 10 microg MG-132/g of b.w. Plasma levels of interleukin (IL)-1, tumour necrosis factor-alpha (TNF-alpha, IL-6 and IL-10 were determined by ELISA 6 h after the induction of sepsis. CLP induced significant increase in plasma levels of all measured cytokines. MG-132 treatment resulted in lower increase in IL-1, TNF-alpha and IL-10 levels. IL-6 was not significantly affected. A mortality study revealed prolonged survival in MG-132 treated mice. We conclude that MG-132 treatment decreases inflammatory response and prolongs survival in the CLP model of sepsis.

Animals↗
PubMed2006

The expression of vascular endothelial growth factor determines the efficacy of post-operative adjuvant chemotherapy using oral fluoropyrimidines in stage II or III colorectal cancer.

The aim of this study was to determine any correlation between the efficacy of post-operative adjuvant chemotherapy using oral fluoropyrimidines and the vascular endothelial growth factor (VEGF) expression in primary colorectal cancer tissues. The data were reviewed retrospectively on 342 patients with colorectal cancer at stage II or III, who underwent potentially curative resection between 1988 and 1998. Of these, 225 received post-operative administration of oral fluoropyrimidines such as UFT and 5'-DFUR, while the other 117 patients underwent surgery alone. Immunostaining for VEGF was performed using colorectal tumours. Overall, VEGF was positively expressed in primary tumour cells in 48% of patients. The disease-free survival rate and the overall survival rate in the chemotherapy group were higher than those in the surgery-alone group, although not significantly. However, the disease-free survival rate and the overall survival rate were similar between the two groups in patients with a tumour positive for VEGF. Multivariate analysis revealed that the VEGF expression was an independent factor for post-operative recurrence, and the VEGF expression and post-operative adjuvant chemotherapy were an independent factor for overall survival, in addition to the lymph node metastasis and the venous invasion. In conclusion, the efficacy of post-operative adjuvant chemotherapy using oral fluoropyrimidines may not be as great for patients with a tumour positive for VEGF having a greater risk of post-operative recurrence. The results support further investigation on efficacy of molecular targeting therapy for VEGF in combination with oral fluoropyrimidines as post-operative adjuvant therapy in colorectal cancer positive for VEGF.

Administration, Oral↗
PubMed2005

The MMP-9 expression determined the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines in stage II or III colorectal cancer.

BACKGROUND: The aim of this study was to determine any correlation between the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines and the matrix metalloproteinase 9 (MMP-9) expression in primary colorectal cancer tissues. PATIENTS AND METHODS: The data on 307 patients with colorectal cancer at stage II or III, who underwent potentially curative resection with lymphadenectomy, were reviewed. Of these, 188 received postoperative administration of oral fluoropyrimidines such as UFT and 5'-DFUR (chemotherapy group), while the other 119 patients underwent surgery alone (surgery-alone group). Immunostaining for MMP-9 was performed using surgical specimens of all 307 primary tumors and 18 recurrent tumors. RESULTS: Overall, MMP-9 was positively expressed in the primary tumor in 44% of patients. Multivariate analysis revealed that the MMP-9 expression was a worse prognostic factor with a second highest hazard ratio for recurrence. The disease-free survival rate in the chemotherapy group was significantly higher than that in the surgery-alone group. However, no significant difference in disease-free survival rate between the two groups was found in patients with a tumor positive for MMP-9. There was a strong positive correlation of MMP-9 expression between the primary tumors and the recurrent liver or lung tumors. CONCLUSIONS: The efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5'-DFUR may not be as great for patients with a tumor positive for MMP-9 having a greater risk to postoperative recurrence.

Administration, Oral↗
PubMed2005

Repeat pulmonary resection for isolated recurrent lung metastases yields results comparable to those after first pulmonary resection in colorectal cancer.

Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.

Adult↗
PubMed2005

The benefit of post-operative adjuvant chemotherapy using oral fluoropyrimidines in rectal cancer.

Recent meta-analysis has shown that oral fluoropyrimidenes is effective as post-operative adjuvant therapy in stage II or III colorectal cancer. However, because the efficacy of oral fluoropyrimidines was expected to be mild, it is important to know patients who respond to this mild chemotherapy for reasonable adjuvant therapy for rectal cancer. To clarify the benefit and problems of the post-operative adjuvant chemotherapy using oral fluoropyrimidines, the clinicopathological data of 169 rectal cancer patients treated with or without the post-operative chemotherapy were analyzed retrospectively. Patients in chemotherapy group (n = 100) underwent curative resection with lymphadenectomy were followed by administration of oral fluoropyrimidine. Other 69 patients underwent surgery alone. The disease-free survival rates were compared between the two groups. The disease-free survival rate in the chemotherapy group was significantly higher than that in the surgery alone. However, no significant difference in disease-free survival rate was found for those with tumor which was associated with metastasis of mesenteric lymph node or node belonging to the internal iliac artery, and tumor with lymphatic invasion or venous invasion. Post-operative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5'-DFUR might not reduce the risk of recurrence in rectal cancer with metastasis of mesenteric lymph node or node belonging to the internal iliac artery, and with lymphatic permeation and venous invasion.

Administration, Oral↗
PubMed2005

Prognostic factors after potentially curative resection in stage II or III colon cancer.

It is important to identify factors that are predictive of outcome after a curative resection in colon cancer in order to optimize adjuvant therapy. To investigate these prognostic factors we conducted a retrospective analysis of our clinicopathological data. A total of 190 patients with a pathological stage II or III colon cancer underwent potentially curative resection with lymphadenectomy at our hospital between 1990 and 1998. These patients received no preoperative chemotherapy, immunotherapy or radiotherapy. Postoperative adjuvant chemotherapy using oral fluoropyrimidines was performed in 127 patients, and the other 63 patients underwent surgery alone. Univariate and multivariate analyses for prognostic factors were carried out. The univariate analysis revealed that invasion to adjacent organs, N1-2, positive mesenteric lymph node metastasis (MLN+), lymphatic permeation (ly)1-3, venous invasion (v)1-3, and v2-3 were each significant factors indicating worse disease-free survival, and that N1-2, MLN+, ly1-3, v1-3 and v2-3 were each significant factors for worse overall survival. In the multivariate analysis, MLN+ and vl-3 were significant factors for worse disease-free survival, and for worse overall survival. In conclusion, stage II or III colon cancer patients positive for mesenteric lymph node metastasis or for venous invasion have a greater risk of recurrence and death after potentially curative resection. Postoperative adjuvant chemotherapy using oral fluoropyrimidines did not significantly reduce the risk of recurrence and death in these patients. More effective adjuvant chemotherapy than oral fluoropyrimidine should be considered, especially in such high-risk patients.

Adult↗
PubMed2004

Clipless hand-assisted laparoscopic total colectomy using Ligasure Atlas.

Hand-assisted laparoscopic total colectomy for ulcerative colitis has allowed less invasive operations in acute severe colitis and poor risk, and has not yet been widely applied for the reason of prolong the operating time in comparison with open surgery. We present the advantages of the use of the LigaSure Atlas vessel sealing for vascular control during laparoscopic surgery. A retrospective study was conducted to compare 15 patients who underwent hand-assisted laparoscopic total colectomy using an ultrasonic coagulator from January 1988 to September 2002 (US group) with 18 patients who were operated using LigaSure Atlas (LS group) from October 2002 to December 2003. There was no significant difference in the background factors of patients between both groups. The operating time was 225 +/- 58 min in the LS group and less than 280 +/- 105 min in the US group. Intraoperative blood loss was 91 +/- 22 ml in the LS group and less than 212 +/- 178 ml in the US group. Postoperative bleeding did not occur in the LS group, but occurred in 1 patient in the US group (6.6%) and this patient required re-operation. Postoperative seroma formation in the abdomen was found in 3 patients of the US group (20%). The procedure using LigaSure Atlas reduced the operating time, intraoperative bleeding and operator's stress in comparison with standard ultrasonic coagulation.

Adult↗
PubMed2004

Transforming growth factor-beta1 expression and the role of angiotensin-converting enzyme inhibitor on perianastomotic intimal hyperplasia in polytetrafluoroethylene graft implanted in rabbit carotid artery.

The purpose of this study was to evaluate the relationship between intimal hyperplasia and transforming growth factor-beta1 (TGF-beta1) mRNA expression in synthetic arterial grafts and also to clarify the effect of angiotensin-converting enzyme inhibitor (ACEI) on perianastomotic intimal hyperplasia and TGF-beta1 mRNA expression. Thirty New Zealand White rabbits were randomly divided into two groups (15 each); one group was administered Captopril 10 mg/kg/day per os as an ACE inhibitor, and the other group received on saline as a vehicle from 7 days prior to operation until the graft was harvest (1, 8, or 14 weeks). A 10-mm segment of an expanded polytetrafluoroethylene graft (3 mm in diameter) was implanted in the right common carotid artery of the rabbits; 15 rabbits had by-pass grafting alone (Graft Alone group) and the other 15 rabbits had by-pass graft along with the ACEI (Graft plus ACEI group). The artery grafts were harvested. The intima to media height ratio (IMHR) and the TGF-beta1 mRNA expression level in perianastomotic graft tissue by reverse transcription-polymerase chain reaction (RT-PCR). The IMHRs gradually increased from 1 to 14 weeks in both groups (vs. 1 wk in each group, p<0.05). The IMHRs of the Graft plus ACEI group were comparable to those of Graft Alone group at 1 week, but significantly lower at 8 and 14 weeks (vs. Graft Alone group, p<0.05). The TGF-beta1 mRNA expression levels of the Graft plus ACEI group were clearly lower than those of the Graft Alone group at 1 and 8 weeks (vs. Graft Alone group, p<0.05), but similar at 14 weeks. TGF-beta1 in the synthetic artery graft of the Graft Alone group was up-regulated as early as 1 week after the operation, when no definitive development of a quantifiable neointima was observed. The TGF-beta1 mRNA expression of the Graft Alone group was highest at 8 weeks and lowest at 14 weeks (vs. 1 week, *p<0.05), but such time-dependent changes were not observed in the Graft plus ACEI group. The results indicated that ACEI reduced intimal hyperplasia in the grafts of the Graft plus ACEI group and also suppressed TGF-beta1 mRNA expression in perianastomotic intimal hyperplasia tissues to the normal artery level. Perianastomotic intimal hyperplasia in synthetic arterial graft is considered to be related to TGF-beta1, the expression of which is locally mediated by angiotensin II and, therefore, suppressed by ACEI.

Anastomosis, Surgical↗
PubMed2003

[Autologous tumor specific immunotherapy of refractory cancers with ex vivo-generated T cells stimulated by autologous tumor cell].

OBJECTIVES: Autologous tumor-cell stimulated cytotoxic T lymphocytes (AuTLs) were prepared from peripheral blood T cells and the T cells were activated ex vivo over a 2-week culturing process in the presence of IL-2 and autologous biopsied tumor-cells from advanced cancer patients. These AuTLs may have potential for efficacy as a locoregional therapy in patients with refractory cancer. METHODS: Twenty-nine of 35 cancer patients (13 esophagus, 5 lung, 3 stomach, 4 breast, 1 melanoma) were enrolled in an early Phase II clinical trial. The patients received direct locoregional intratumoral injection of AuTLs biweekly through medical endoscope or intraarterial infusion reservoir system. Mean 0.25 x 10(9) AuTLs were injected 1 x /2 weeks for 6 weeks. RESULTS: Adverse events related to AuTL were minimal. AuTLs specific for autologous tumor cells were observed in 12 of 29 patients. Seven of these 12 patients (58.3%) had partial response (PR) or stable disease (SD). In contrast, 8 of 23 (34.8%) remaining patients treated by non-specific AuTLs had SD. Infiltration of T effector cells was significantly increased on the biopsied tumor specimens in the immunohistological studies. Furthermore, 11 patients receiving systemic infusion of non-specific LAK/NK T cells without autologous tumor-cell stimulation only had 2 SDs (18.2%). CONCLUSIONS: Our results demonstrated the clinical potential of intra-peritumoral administration of AuTLs. Thus, locoregional immunotherapy with autologous tumor specific AuTLs may be more effective than systemic adoptive immunotherapy using intravenous infusion of autologous tumor non-specific LAK/NK T cells for the treatment of solid cancers.

Breast Neoplasms↗
PubMed2002

Glutathione peroxidase inhibits cell death and glial activation following experimental stroke.

Stroke is a leading cause of morbidity and mortality in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia-reperfusion (I-R). Growing evidence indicates that reactive oxygen species (ROS) contribute significantly to this process, though their exact mechanism of action is mostly unknown. We have examined the mechanism of protection against I-R injury in transgenic mice that overexpress human glutathione peroxidase (hGPx1), using a focal cerebral I-R model. In this model, transgenic animals show significant reduction of necrotic as well as apoptotic cell death in vulnerable brain regions as demonstrated by TUNEL staining, DNA laddering and ELISA assays. We also observed decreased astrocytic and microglial activation in ischemic brains of animals overexpressing hGPx1. In wild-type mice, neuronal cell death was accompanied with compromise of vascular integrity, edema and neutrophil infiltration, whereas GPx1 mice revealed significant preservation of tissue structure and decreased infiltration of acute inflammatory cells. These results indicate that glutathione peroxidase-sensitive ROS play an important role in regulation of cell death during cerebral I-R as well as in brain inflammatory reactions.

Animals↗
PubMed2002

Inflammatory response and glutathione peroxidase in a model of stroke.

Stroke is one of the leading causes of death in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia/reperfusion (I/R). Experimental data indicate an important role for oxidative stress and the inflammatory cascade during I/R. We are testing the hypothesis that the mechanism of protection against I/R damage observed in transgenic mice overexpressing human antioxidant enzymes (particularly intracellular glutathione peroxidase) involves the modulation of inflammatory response as well as reduced sensitivity of neurons to cytotoxic cytokines. Transgenic animals show significant reduction of expression of chemokines, IL-6, and cell death-inducing ligands as well as corresponding receptors in a focal cerebral I/R model. Reduction of DNA binding activity of consensus and potential AP-1 binding sites in mouse Fas ligand promoter sequence was observed in nuclear extracts from transgenic mice overexpressing intracellular glutathione peroxidase compared with normal animals following I/R. This effect was accompanied by modulation of the c-Jun N-terminal kinase/stress-activated protein kinase pathway. Cultured primary neurons from the transgenic mice demonstrated protection against hypoxia/reoxygenation injury as well as cytotoxicity after TNF-alpha and Fas ligand treatment. These results indicate that glutathione peroxidase-sensitive reactive oxygen species play an important role in regulation of cell death during cerebral I/R by modulating intrinsic neuronal sensitivity as well as brain inflammatory reactions.

Animals↗
PubMed2002

Effect of prophylactic intracerebroventricular injection of methylprednisolone on nitrogen and catecholamine excretion in the urine after laparotomy in rats.

BACKGROUND: This study was carried out to determine whether the prophylactic injection of glucocorticoid into the intracerebroventricular (i.c.v.) space reduced TNF-alpha and IL-1beta mRNA synthesis in the brain after laparotomy, resulting in a reduction of nitrogen excretion in the urine. PATIENTS AND METHODS: Male SD rats (body wt., 225-250 g, n = 114) were catheterized into the i.c.v. space on day 0. On day 4, the rats were assigned to four groups: (1) Control, (2) laparotomy (Trauma), (3) intraperitoneal (i.p.) injection of methylprednisolone (MP) plus laparotomy (IPMP), and (4) i.c.v. injection of MP plus laparotomy (ICVMP). Either 3 or 24 h after surgery, the animals were sacrificed. TNF-alpha and IL-1beta mRNA levels in tissues, including the brain cortex and hypothalamus, were measured by RT-PCR. The amounts of nitrogen and catecholamine excretion in the 24-h urine were determined. RESULTS: The i.p. injection of MP reduced TNF-alpha and IL-1beta mRNA levels in all the tissues 3 h after laparotomy compared with those of the Trauma group. The icv injection of MP prevented elevation of the TNF-alpha and IL-1beta mRNA levels in the brain (cortex, TNF-alpha, ICVMP 0.43 +/- 0.06, P < 0.05, vs Trauma; cortex, IL-1beta, ICVMP 0.25 +/- 0.09, P < 0.05, vs. Trauma; hypothalamus, TNF-alpha, ICVMP 0.31 +/- 0.04, P < 0.05, vs. Trauma; hypothalamus, IL-1beta, ICVMP 0.25 +/- 0.14, P < 0.05, vs. Trauma), but did not inhibit an increase in TNF-alpha and IL-1beta mRNA levels in the liver and skeletal muscle. Both nitrogen and catecholamine excretions in the urine were decreased by ip and by i.c.v. injection of MP compared to those of the Trauma group (nitrogen, ICVMP 559.3 +/- 52.0 mg/day, P < 0.05, vs. Trauma; catecholamine, ICVMP 13.8 +/- 1.8 microg/day, P < 0.05, vs. Trauma). CONCLUSION: A reduction in TNF-alpha and IL-1beta mRNA synthesis in the brain due to prophylactic injection of MP into the icv space reduced the catabolic response after laparotomy.

Animals↗
PubMed2002

Laparoscopic intraperitoneal repair of postoperative ventral incisional hernia using Composix mesh.

This report describes the technique and early results obtained with a simple laparoscopic intraperitoneal onlay Composix mesh repair for postoperative ventral hernia. Composix mesh is constructed from one layer of polypropylene mesh and another layer of expanded polytetrafluoroethylene (ePTFE). From March 2000 to October 2001, we performed laparoscopic repair of postoperative ventral hernia in 9 patients. Four (44%) of these patients had a history of at least one failed hernia repair. The size of the abdominal wall defect varied from 4 x 5 cm to 10 x 12 cm (median, 8 x 9 cm). In all cases, the Composix mesh (Bard Inc. USA) was stapled to the peritoneal surface of the abdominal wall, leaving the sac in situ. No death occurred as a result of surgery. Intraoperative small bowel injury occurred in one patient (11.1%) for whom surgery was converted to laparotomy and small bowel resection. No infection was observed. The length of hospital stay varied from 5 to 10 days (median, 5.6 days). During the follow-up period of 8 to 15 months (median, 2 months), there was no recurrence of hernia. Laparoscopic Composix mesh onlay repair is a safe, easy, and effective procedure with minimal discomfort and a low early recurrence rate.

Adult↗