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Biomedical subjects

G Nakagawara

Publications and source records attributed to G Nakagawara.

At least 19 recordsLinked to original sources
PubMed2000

Effects of micro-encapsulation on morphology and endocrine function of cryopreserved neonatal porcine islet-like cell clusters.

BACKGROUND: For the success of clinical islets transplantation, the development of a long-term storage method is necessary. However, the structure of digested islets is scanty for culture and cryopreservation. In this study, the effect of micro-encapsulation to cryopreserved porcine islet-like cell clusters (ICCs) was investigated. METHODS: The ICCs prepared from neonatal pigs by collagenase digestion and culture technique were cryopreserved and micro-encapsulated in 5% agarose membranes. After cryopreservation, ICC cultured without encapsulation (group A) and cultured with encapsulation (group B) were assessed by comparison with no cryopreserved ICC (control) both in vitro by static incubation test and in vivo in a xenotransplantation study. RESULTS: Micro-encapsulation was able to maintain the fine morphology and the number of ICCs of group B after 7 days of culture. There were not significant differences in insulin secretion of group B and control on day 1 and 7 of culture (1 day:11+/-0.99, 7 days: 5.30+/-1.08 microU/ICC/hr NS versus control). On day 7 of culture, the retrieval rate of group B (105.2+/-9.8%) is obviously higher compared with group A (63.0+/-6.3%). In the xenotransplatation model, the ICCs of group B showed long survival time (7.9+/-0.4 weeks) and good transplantation effect. CONCLUSION: Our study suggests that micro-encapsulation is one of the useful method for cryopreserved ICC to maintain the fine morphology and effectively recover the endocrine function.

Animals↗
PubMed1999

Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis.

A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.

Adenoma↗
PubMed1999

Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.

Adult↗
PubMed1998

Clinical significance of serum levels of CD44 variant exons 8-10 protein in colorectal cancer.

We examined serum levels of a CD44 splice variant that contained variant exons 8-10 (CD44v8-10) as a tumor marker in colorectal cancer patients. We performed enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer patients and 10 healthy controls. Serum CD44v8-10 levels were significantly higher in the colorectal cancer patients than in the healthy controls (0.209 +/- 0.098 versus 0.114 +/- 0.019 OD; P < 0.01). There was a close correlation between immunohistochemical expression and serum CD44v8-10 levels. Surgical resection of the tumors resulted in a reduction of serum CD44v8-10 levels. There was no significant correlation between serum CD44v8-10 level and serosal invasion or histologic type. However, a significant correlation was observed between serum CD44v8-10 level and lymphatic or venous invasion. In addition, serum CD44v8-10 levels were significantly higher in carcinomas associated with lymph node or liver metastasis than in those without metastasis. These findings suggest the usefulness of serum CD44v8-10 level in the prediction of colorectal cancer metastasis.

Biomarkers, Tumor↗
PubMed1998

Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers.

Using a bacterial fusion protein, a deleted colorectal carcinoma (DCC)-specific monoclonal antibody (MAb) 127-22 was established. Although MAb 127-22 reacted with almost all normal tissues, it did not react or only weakly reacted with many cancer cell lines, including colonic cancer lines, in flow cytometry. In Western immunoblots, the MAb reacted with a single 190-kDa molecule in a myeloma line Ara-10 extract. This component was scarcely detected in colonic cancer cell lines. Immunoblots of samples from 25 pairs of colonic cancers and adjacent normal tissues and from five adenoma tissues revealed that all normal colonic and adenoma tissues significantly expressed the DCC protein, whereas colonic cancer tissues showed poor expression. These results indicate not only deletion of and lowered mRNA expression of the DCC gene, but also marked reduction of DCC protein occurred in colonic cancer tissues. In addition, colonic cancer patients with liver metastasis expressed significantly lower levels of DCC than those without, suggesting the prognostic value of DCC expression.

Animals↗
PubMed1998

Preservation of pancreatic islets in rodent models.

Islet-cell transplantation has some advantages over vascularized pancreas transplantation, but data from clinical islet cells transplantation have shown that some serious problems need to be overcome. One of them is the storage of islet cells. We investigated methods of preserving islet cells using culture-preservation and cryopreservation. Cryopreservation is thought to be effective for long-term preservation of large quantities of islet cells, because they can be cryopreserved without loss of their physiologic activity using a relatively rapid cooling rate of 25 degrees C/min. Moreover, in the allogenic transplantation models of cryopreservation of dissociated islet cells, there was a significant prolongation of survival time. These results suggest that cryopreservation of islet cells involves not only variable preservation methods but may also lead to a modification of graft immunogenicity.

Animals↗
PubMed1998

Usefulness of metyrapone treatment to suppress cancer metastasis facilitated by surgical stress.

BACKGROUND: One causative factor of tumor metastasis enhanced by surgical stress is thought to be hypersecretion of endogenous glucocorticoids. This study evaluated the effectiveness of metyrapone treatment and adrenalectomy in preventing the harmful effects of glucocorticoids in the enhancement of tumor metastasis resulting from surgical stress. METHODS: The effect of dexamethasone on pulmonary metastasis of MRMT-1 cells and on the number of peripheral lymphocytes was evaluated in rats. To evaluate the suppressive effect of adrenalectomy and metyrapone treatment on operation-induced enhancement of metastasis, several parameters such as induction of pulmonary metastasis, serum corticosterone levels, and the number of blood lymphocytes and apoptotic thymocytes were determined. RESULTS: With dexamethasone treatment, the number of peripheral lymphocytes rapidly decreased; in contrast, pulmonary metastasis increased. The serum corticosterone level was doubled at 1 hour, apoptotic thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at 6 hours, and blood lymphocyte numbers were decreased at 3 hours after laparotomy, which facilitated about a 10-fold increase in the pulmonary metastasis. These changes were almost completely suppressed by preoperative adrenalectomy and metyrapone treatment. CONCLUSIONS: Preoperative metyrapone treatment, which suppresses hypersecretion of endogenous glucocorticoids as a result of operation, modulates the enhancement of cancer metastases and may be an effective treatment.

Adrenalectomy↗
PubMed1998

[Telomerase activity in colorectal carcinoma and its relationship to clinicopathological findings].

Telomerase is thought to be responsible for cell immortality. The telomerase activity in carcinomas has been remarked since 1995. We examined telomerase activity in colorectal carcinoma by TRAP (Telomeric repeat amplification protocol) assay, and investigated its relationship to clinicopathological findings. We could analyse telomerase activities in 33 cases (66%) of 50 colorectal carcinomas, whereas the activity was not found in all 13 cases of noncancerous colorectal mucosa. There was no relation between the telomerase activity and the clinicopathological findings or metastatic status. We confirmed telomerase activities in much of colorectal carcinomas in spite of their progression. The carcinoma cells might be immortal from their early stage of progression by means of telomerase activity.

Colorectal Neoplasms↗
PubMed1998

[A case of stage IV (N4) esophageal cancer successfully treated with concurrent chemoradiotherapy].

A 71-year-old man with inoperable intrathoracic esophageal cancer was treated by concurrent chemoradiation. A dose of 48 Gy (neck) and 60.6 Gy (mediastinum) and four courses of 5-FU (500 mg/day)-CDDP (50 mg/week) were delivered. The esophageal tumor and metastatic lymph nodes of the neck showed a complete response (CR) to the treatment, whereas paraaortic lymph nodes evidenced no change (NC). The patient is doing well without symptoms at 13 months after treatment. The chemoradiotherapy produced effective improvement and quality of life in this patient.

Aged↗
PubMed1997

The role of lymph node dissection in the treatment of gallbladder carcinoma.

BACKGROUND: Lymph node involvement is an important prognostic factor in gallbladder carcinoma (GBC). The lymph node involvement pattern, extent, and indications for systematic lymph node dissection for patients with advanced GBC were investigated. METHODS: Forty-one patients with GBC who underwent radical resection with systematic regional lymph node dissection over the past 11 years were analyzed. RESULTS: The lymph node metastasis rate was 63.4% overall, 0% in pT1 disease, 61.9% in pT2 disease, and 81.3% in pT3/pT4 disease. When reviewed according to site, the rate was 41.5% in pericholedochal lymph nodes, 22.0% in the lymph nodes around the common hepatic artery and the portal vein, 36.6% in the posterior pancreaticoduodenal lymph nodes, 28% (5/18) in the celiac lymph nodes, 19% (3/ 16) in the superior mesenteric artery (SMA) lymph nodes, and 26% (7/27) in the aortocaval paraaortic lymph nodes. Patients with severe hepatoduodenal ligament invasion had high rates of paraaortic lymph node involvement. The mortality rate was 2.4% (1 of 41 patients) and the 5-year survival rate was 33.1% overall, 100% in patients with pT1 disease, 49.8% in patients with pT2 disease, and 0% in patients with pT3/pT4 disease. The 5-year survival rate for pT2 disease according to lymph node involvement was 72.7% in patients with pN0+ pN1+ positive posterior pancreaticoduodenal lymph nodes and positive lymph nodes around the common hepatic artery in the N2 patients and 0% in the patients with positive celiac and SMA lymph nodes in the N2 patient group or the positive paraaortic lymph node group (P < 0.05). CONCLUSIONS: These results suggest that systemic dissection of N1 lymph nodes, posterior pancreaticoduodenal lymph nodes, and lymph nodes around the common hepatic artery and the portal vein in N2 patients is necessary to improve the prognosis of those patients with pT2 disease without moderate or severe hepatoduodenal ligament invasion.

Adult↗
PubMed1996

Expression of a CD44 variant containing exons 8 to 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients.

PURPOSE: To determine the expression of the CD44 variant containing a variant exon 8 to 10 product (CD44v8-10) in colorectal cancer and to evaluate its prognostic value. MATERIALS AND METHODS: CD44v8-10 was studied in resected tumors and normal mucosae obtained from 215 colorectal cancer patients (118 colon cancer and 97 rectal cancer). The expression of CD44v8-10 was analyzed immunohistochemically using the anti-CD44v8-10 monoclonal antibody (mAb) 44-1V. RESULTS: One hundred of 215 cancer tissues expressed CD44v8-10. Positive staining was intense mainly on the cell membranes. There was no significant correlation between expression of CD44v8-10 and histologic type, primary tumor, lymphatic invasion, venous invasion, or peritoneal invasion. There were significant correlations between CD44v8-10 immunoreactivity and both lymph node and hematogenous metastasis. Patients with CD44v8-10-positive tumors had a greater relative risk of death compared with those whose tumors were CD44v8-10-negative. Among 169 patients who underwent curative resection, CD44v8-10 expression correlated with a high recurrence rate. The 5- and 10-year survival rates were 90.3% of patients with CD44v8-10-negative tumors, and 72.1% and 58.0% of those with CD44v8-10-positive tumors, respectively; these differences between the two groups of patients were significant (P < .01). In multivariate analysis using the Cox regression model, CD44v8-10 expression emerged as an independent prognostic indicator. CONCLUSION: The results suggest that CD44v8-10 plays a role in metastasis of colorectal cancer, and tha CD44v8-10 expression may be a biologic marker of prognostic significance.

Antibodies, Monoclonal↗