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Biomedical subjects

Yutaka Ogata

Publications and source records attributed to Yutaka Ogata.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat.

We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24-weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat.

Administration, Oral↗
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

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↗
PubMed2005

Effects of antineoplaston AS2-1 against post-operative lung metastasis in orthotopically implanted colon cancer in nude rat.

We have investigated the efficacy and mechanisms of antineoplaston AS2-1 against post-operative lung metastasis following removal of implanted human colon cancer in nude rat. The influence of AS2-1 on in vitro KM12SM human colon carcinoma cell activities (growth, cell cycle, and apoptosis) was evaluated. AS2-1 was administered perorally after removal of the implanted KM12SM cecal cancer in nude rat. AS2-1 inhibited KM12SM cell proliferation through G1 cell arrest and, at a higher concentration, induction of apoptosis. AS2-1 showed significant reduction in lung metastasis at 5 weeks after cecal removal. The survival rate in the AS2-1 group was significantly higher than that in the control. TUNEL staining on the lung metastatic tumors revealed that the apoptosis index (AI) in the AS2-1 group was significantly higher. Antineoplaston AS2-1 showed an antimetastatic effect against post-operative lung metastases from colon cancer through G1 cell arrest and the subsequent induction of apoptosis.

Animals↗
PubMed2004

Oncologic and functional results of total mesorectal excision and autonomic nerve-preserving operation for advanced lower rectal cancer.

PURPOSE: Total mesorectal excision contains two different procedures: autonomic nerve preservation, and autonomic nerve sacrifice. It is unclear whether autonomic nerve preservation is suitable curative procedure. We clarify the significance of autonomic nerve preservation for an advanced lower rectal cancer. METHODS: All 403 patients curatively resected between 1975 and 1999 were clinicopathologically studied. Between 1975 and 1984, all patients routinely received total mesorectal excision without autonomic nerve preservation (TME-P(-) group). Since 1985, total mesorectal excision with autonomic nerve preservation has been performed in 81 percent of patients (TME-P(+) group). The remaining patients received TME-P(-) because of suspicious invasion to autonomic nerve plexus. All clinical and pathologic data were entered into a computer database. Long-term follow-up was used to analyze the oncologic and functional results of TME-P(+) group compared with TME-P(-) group. RESULTS: The follow-up rate was 98.1 percent. In either Dukes A+B or Dukes C disease, the TME-P(+) group did not increase local recurrence or decrease ten-year disease-free survival compared with the TME-P(-) group of Period 1975 to 1984. The TME-P(-) group of Period 1985 to 1999 had the highest distant metastasis and the lowest survival rates than any other groups. Urinary or sexual function was well preserved in the TME-P(+) group. CONCLUSIONS: Autonomic nerve preservation is oncologically and functionally excellent and suitable for almost all patients with advanced lower rectal cancer. Intensive chemotherapy is needed for patients whose autonomic nerves were killed in suspicion of nerve invasion.

Adult↗
PubMed2004

Biological features of sporadic colorectal carcinoma with high-frequency microsatellite instability: special reference to tumor proliferation and apoptosis.

BACKGROUND: We evaluated the relationship between biological behavior and microsatellite instability (MSI) status, with or without p53 status, in sporadic colorectal carcinoma. METHODS: MSI was analyzed with regard to biological features such as cellular proliferation and apoptotic cell death, in addition to clinicopathological features, in 87 patients with sporadic colorectal carcinoma. RESULTS: Fourteen (16.1%) of 87 tumors showed instability at two or more of the five loci examined (high-frequency MSI [MSI-H]). Four demonstrated instability at one locus (low-frequency MSI [MSI-L]), and 69 showed no instability (microsatellite-stable [MSS]). The MSI-H tumors tended to be located in the proximal colon and more often were mucinous carcinoma. The MSI-H tumors also tended to be in patients with multiple colorectal carcinomas and to demonstrate, rarely, an infiltrating growth pattern or venous invasion. The incidence of p53 protein overexpression in the MSI-H tumors was significantly lower than that in the MSI-L/MSS tumors (21% vs 54%). There was no significant difference in the proliferating-cell nuclear antigen (PCNA) labeling index (PI) or apoptotic index (AI) between the MSI-H and MSI-L/MSS tumors. The AI in the MSI-H tumors with p53 overexpression was significantly lower than that in the MSI-H tumors without p53 overexpression, and was also significantly lower than that in the MSI-L/MSS tumors with p53 overexpression. In the MSI-H tumors with p53 overexpression, no expression of BAX protein was found, and there was high expression of bcl-2 protein, resulting in a low BAX/bcl-2 ratio. CONCLUSION: In sporadic colorectal carcinoma, an MSI-H tumor with p53 protein overexpression may display aggressive biological features.

Adenocarcinoma↗
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↗
PubMed2003

Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: long-term follow-up study.

To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) in squamous cell carcinoma in the thoracic esophagus, particularly as a prognostic factor, we have investigated the correlation between VEGF expression in tumor cells and microvessel density (MVD), pathologic factors, and survival. A total of 92 specimens, each from a thoracic esophageal squamous cell cancer patient who underwent transthoracic curative R0 esophagectomy between 1991 and 1994, were examined immunohistochemically using anti-human VEGF and anti-human von Willebrand factor antibodies. The incidence of VEGF expression in the tumor cells was relatively low, at 23.9% of all specimens. There was no significant correlation between VEGF expression and histopathologic factors. The MVD at the tumor margin in patients with VEGF-positive tumor cells was significantly greater than that in VEGF-negative cases (35.2 +/- 8.9 vs. 22.7 +/- 8.2). The survival rate for patients with VEGF expression was significantly lower than that of those without VEGF expression; the same situation was found in node-positive patients but not in node-negative patients. In addition, multivariate analysis revealed that VEGF expression was an independent prognostic factor in node-positive patients. VEGF may be implicated in the definition of the malignant phenotype of squamous cell esophageal cancer via tumor angiogenesis. Accordingly, VEGF expression in the tumor cells could be a useful prognostic factor for esophageal cancer, particularly in node-positive patients.

Carcinoma, Squamous Cell↗
PubMed2003

Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: report of a case.

We report a case of survival for nearly 8 years after treatment of unresectable multiple liver metastases from colon cancer, using microwave ablation and the nontoxic antitumor agent, the antineoplastons. A 72-year-old man diagnosed with adenocarcinoma of the ascending colon and 14 bilateral liver metastases underwent a right hemicolectomy combined with microwave ablation of six metastatic liver tumors. We also decided to give antineoplastons to inhibit metastatic tumor growth and recurrence. Antineoplaston A10 was given intravenously, followed by oral antineoplaston AS2-1. Computed tomography scans done 1 and 4 years after the initial diagnosis showed recurrent tumors in S(4) and S(7), respectively. The patient underwent a second and a third microwave ablation of the recurrent tumors, and has survived for nearly 8 years without suffering any serious adverse effects. He is currently free from cancer. This case report demonstrates the potential effectiveness of the nontoxic antitumor agent, the antineoplastons, for controlling liver metastases from colon cancer.

Adenocarcinoma↗
PubMed2002

Expression of tumor rejection antigens in colorectal carcinomas.

BACKGROUND: The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients. METHODS: The SART2 and SART3 antigens were investigated by Western blotting in colorectal carcinoma cell lines and in cancer tissues. For induction of CTLs, peripheral blood mononuclear cells (PBMCs) of HLA A-24-positive cancer patients were stimulated in vitro with peptides. RESULTS: The 140 kD SART3 antigen was expressed in both the cytosol and nuclear fractions of all six colon carcinoma cell lines, 27 of 41 (65.9%) cytosol fractions, 30 of 41 (73.2%) nuclear fractions of colorectal carcinoma tissue samples, and in 0 of 7 non-tumorous tissues. The 100 kD SART2 antigen was expressed in the cytosol fractions of 2 of 6 colon carcinoma cell lines, 5 of 20 (25%) cytosol fractions of colorectal carcinoma tissue samples, and in 0 of 7 non tumorous tissues. HLA-A24-restricted CTLs cytotoxic to colon carcinoma cells were induced from PBMCs of colon carcinoma patients by stimulation with the two immunogenic peptides of SART3. CONCLUSIONS: The SART3 antigen could be an appropriate target molecule for specific immunotherapy for colorectal carcinoma patients.

Aged↗
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↗
PubMed2002

Endoluminal ultraflex stent for palliative treatment of malignant rectosigmoidal obstruction.

Rectosigmoidal obstruction due to a malignant tumor usually requires emergency surgical treatment, and colostomy is usually inevitable. This report describes our experience with the use of endoluminal self-expanding metallic stents in the treatment for rectosigmoidal obstruction in patients with unresectable recurrent colorectal cancer or intra-abdominal dissemination. A total of 5 cases were included (4 male and 1 female) with a mean age of 70.8 (range, 63-80) years. A self-expanding noncovered Ultraflex, 10 cm in length and 22 mm in diameter, was emplaced at the site of the obstruction under both endoscopic and fluoroscopic guidance. Each patient had a recurrent malignancy (colorectal cancer, 3; ovarian cancer, 1; gastric cancer, 1). No subsequent surgery was planned due to ascites or extensive intra-abdominal dissemination. There was no mortality related to the procedure. Immediate decompression with symptomatic relief was achieved. One stent later became obstructed due to tumor ingrowth, and in two cases there was intermittent bleeding from the tumor and these were treated by argon plasma coagulation (APC) endoscopically. The use of self-expanding Ultraflex stent provides good palliation for unresectable advanced tumors that cause left colonic obstruction.

Aged↗
PubMed2002

[Efficacy of postoperative adjuvant chemotherapy for colorectal cancer].

We attempted postoperative adjuvant chemotherapy for stage II or III colorectal cancer. To investigate the efficacy of the adjuvant chemotherapy, we retrospectively reviewed all 293 colorectal cancer patients who underwent curative resection between 1990 and 1996 in Kurume University Hospital. The patients were divided into two groups according to whether or not they received postoperative adjuvant chemotherapy. Patients in Group 1 (n = 156) underwent resection followed by administration of oral fluorouracil. Some also received intravenous 5-FU or MMC after surgery. Patients in Group 2 (n = 95) underwent surgery alone. The disease-free survival rate in Group 1 was significantly higher than that in Group 2, but only for those with rectal cancer, with no significant difference for those with colon cancer. The results were also analyzed according to tumor stage, degree of lymphatic and venous invasion, and histological grading. Findings were similar between the two groups for those with stage II, stage IIIa, a low grade of lymphatic and venous invasion, and well-differentiated adenocarcinoma. Postoperative adjuvant chemotherapy in colorectal cancer might reduce the risk of recurrence, particularly in cases of rectal cancer. However, postoperative adjuvant chemotherapy was insufficient for those with highly advanced cancer or a biologically aggressive tumor.

Aged↗