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Biomedical subjects

C Iguchi

Publications and source records attributed to C Iguchi.

14 recordsLinked to original sources
PubMed2001

Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The Bcl-2 can work to protect cells from apoptosis, which is induced by p53 gene. These facts suggest the significant role of these genes in the genesis and progression of various tumors. The present study was designed to assess the significance of p53 and Bcl-2 protein (pBcl-2) expression on resectable invasive ductal carcinoma (IDC) of the pancreas. METHODS: The present study included 63 IDCs, which were resected between 1982 and 1998. pBcl-2 and p53 were stained immunohistochemically with monoclonal antibodies. RESULTS: pBcl-2 was expressed in 16 (25.4%), and p53 was positively expressed in 32 out of 63 IDCs (50.8%); however, expression of pBcl-2 did not necessarily correlate with that of p53. Although p53 expression did not show any significant influence on the patients' survival, pBcl-2(+) patients showed a higher survival than pBcl-2(-) patients for both p53(+) and p53(-) patients, which suggested that pBcl-2 expression had a more significant effect on the survival of patients than p53 expression. On the other hand, there were no differences in the survival curve between the adjuvant chemotherapy (ACT) group and the surgery alone (SA) group. pBcl-2 expression had no influence on the effect of ACT, the ACT group showed a significantly better survival than the SA group for p53(+) IDC patients. CONCLUSIONS: pBcl-2 expression is a beneficial prognostic factor for patients with IDC, whereas p53 expression may be beneficial in the prediction of the effects of adjuvant chemotherapy on patients with IDC. J. Surg. Oncol. 2001;76:188-196.

Adult↗
PubMed2001

Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas.

The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis, pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI. pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.

Adult↗
PubMed1999

Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas.

p53 tumor-suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The cyclin-dependent kinase inhibitor WAF/1-p21 is induced by wild-type p53 and has been implicated as a downstream mediator of the growth-suppressing and apoptosis-promoting function of wild-type p53, suggesting an impact on the effectiveness of chemotherapy. This study was designed to assess the significance of p53 and WAF/1-p21 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients underwent surgery alone, and 30 patients received postsurgical adjuvant chemotherapy. p53 and WAF/1-p21 were stained immunohistochemically with anti-p53 monoclonal antibody (mAb) and anti-WAF/1-p21 mAb. p53 was positively expressed in 29 (50%) of 58 primary lesions, and p21 was expressed in 24 (41%) lesions; however, p21 expression did not necessarily correlate with p53 expression. The survival curve of the patients with p53(+) IDC was significantly lower than that of those with p53(-) IDC, and p21(+) patients showed a higher survival curve than did p21(-) patients, but this difference was not statistically significant. When p53 and p21 expression were analyzed in combination, the patients with p53(+)p21(-) IDC were found to have a significantly poorer prognosis than others. On the other hand, the survival curve of the adjuvant chemotherapy group was also higher than that of the surgery-alone group, but this difference was not significant. In a multivariate analysis, p21 expression was a significantly low risk factor for death due to IDC overall, and adjuvant chemotherapy was found to decrease the risk of death from IDC in p53(+) patients. Evaluation of expression of p53 and WAF/1-p21 may be beneficial in the prediction of the patient's prognosis as well as prediction of the effects of adjuvant chemotherapy in pancreatic cancer patients.

Adult↗
PubMed1999

[A case of recurrent ampullary carcinoma of the papilla of Vater, in which a complete response was induced by combination therapy using radiotherapy and oral chemotherapy employing UFT and cyclophosphamide].

A 38-year-old male patient underwent a pylorus-preserving pancreatoduodenectomy for an ampullary carcinoma of the papilla of Vater. One year after surgery a regular examination with CT and an echogram revealed a solitary recurrent tumor at a lymph node near the superior mesenteric artery. He was treated with radiotherapy at a total of 60 Gy and chemotherapy with UFT at 300 mg/day daily and oral administration of cyclophosphamide at 50 mg/day every other day. Four months after the initiation of the therapy the tumor had completely disappeared and the objective response was evaluated as a CR. The patients is now disease-free and continues to be treated with oral UFT and cyclophosphamide on an outpatient basis.

Administration, Oral↗
PubMed1998

A Case of Multiple Juvenile Papillomatosis of the Breast and Its Immunohistochemical Pathology.

Juvenile papillomatosis(JP)is a benign proliferative disease of the breast affecting young women. Some patients with JP develop breast carcinoma. We recentlytreated and followed a case of JP in a 16-year-old female, and studied its immunohistochemical characteristics. The patient noticed a small tumor, 5 mm in diameter, in the periareolar region on the medial side of the right breast. She underwent an excisional biopsy and pathology demonstrated JP. However, 6 months later, two new lesions were discovered by routine echogram examination, and were later excised. Immunohistochemistry demonstrated that the JP tumors were negative for estrogen receptor, but positive for progesterone receptor, epidermal growth factor receptor and erbB-2. In addition, tests for p53 were negative and Rb protein was normally expressed. Immunohistochemical analysis suggested that an abnormality in estrogen receptor is important in the pathogenesis of JP, and that the patient had a relatively high risk of developing breast carcinoma, since her JP is multicentric and recurrent. The present study also suggests that immunohistochemical pathology may be beneficial in assessing the malignant potential of JP.

Journal Article↗
PubMedDate not supplied

Intraperitoneally implanted artificial pancrease with transkaryotic beta-cells on microcarrier beads in a diffusion chamber improves hyperglycemia after 90% pancreatectomy in rats.

BACKGROUND: Considering the difficulties in pancreas transplantation, the development of an artificial pancreas would be of great value. We have established a transkaryotic artificial beta-cell line, CHO/I, produced by transfecting the human proinsulin gene into the Chinese hamster ovary (CHO) cell line. The present study was designed to assess the value of an artificial pancreas using a diffusion chamber containing CHO/I cells. MATERIALS AND METHODS: Wistar rats rendered diabetic by 90% pancreatectomy were treated by implanting a diffusion chamber containing CHO/I cells cultured on microcarrier beads. RESULTS: The diffusion chamber containing microcarrier beads produced 100-folds more CHO/I cells than the chamber alone, as calculated from the secreted IRI in vitro. When diffusion chambers containing CHO/I cells on microcarrier beads were implanted into the peritoneal cavity of the 90% pancreatectomized rats, the fasting serum IRI level increased and the fasting blood glucose decreased to the normal level for 12 weeks. An intraperitoneal glucose tolerance test demonstrated, however, that the diffusion-chamber-implanted rats did not respond to glucose loading. CONCLUSION: An artificial pancreas using a diffusion chamber containing human proinsulin gene transfected cells might be a promising model for future clinical application.

Animals↗
PubMedDate not supplied

Reduced invasiveness and metastasis of Chinese hamster ovary cells transfected with human interleukin-17 gene.

Human IL-17 (hIL-17) stimulates epithelial, endothelial, fibroblastic cells and macrophages to secrete various cytokines. The present study was designed to assess the effects of the transfection of the hIL-17 gene in Chinese hamster ovary (CHO) cells. A complementary DNA (cDNA)-encoding hIL-17 was obtained by polymerase chain reaction (PCR) amplification from human CD4+ T-cell cDNA and inserted into the plasmid pRc/CMV to construct an expression vector for hIL-17. CHO cells were transduced with hIL-17 DNA-carrying cytomegalovirus (CMV)-based retroviral vectors. A clone with a high mRNA expression of hIL-17 (CHO/IL-17) was selected by Northem blotting. There was no significant difference in the in vitro growth of cells among parent CHO cells, vector-only transfected cells (CHO/neo) and CHO/IL-17 cells. A Matrigel invasion chamber assay, however, demonstrated significantly lower invasiveness by CHO/IL-17 cells than by either the parent CHO or the CHO/neo cells. There was no difference in the in vivo growth among the cells, when subcutaneously transplanted into nude mice. When injected into the tail vein, however, the number of metastatic nodules in the lungs of CHO/IL-17-injected mice was significantly smaller than that of CHO- or CHO/neo-injected mice. Furthermore, NK activity of spleen cells was significantly higher in nude mice transplanted with CHO/IL-17 cells than in mice transplanted with parent CHO or CHO/neo cells. In conclusion, the hIL-17-gene-transfected CHO cells showed a significantly lower metastatic potential to the lung by directly modulating the invasiveness and metastasis of CHO cells as well as by enhancing NK activity.

Animals↗
PubMedDate not supplied

Induction of tumor-specific antitumor immunity after chemotherapy with cisplatin in mice bearing MOPC-104E plasmacytoma by modulation of MHC expression on tumor surface.

Chemotherapy sometimes results in induction of specific antitumor immunity. We investigated the mechanisms responsible for the induction of antitumor immunity in mice bearing MOPC-104E plasmacytoma after chemotherapy with cisplatin (CDDP), especially the effects of CDDP on the expression of MHC on the tumor surface. BALB/c mice were subcutaneously (s.c.) inoculated with MOPC-104E cells on day 0, then intravenously (i.v.) treated with CDDP at 3.6 mg/kg on day 7. The tumors disappeared completely on day 35 and the mice rejected a second challenge with MOPC-104E, but did not reject syngeneic Meth-A fibrosarcoma. The tumors did not regress, however, when MOPC-104E was s.c. transplanted in nude mice, or when anti-T-cell monoclonal antibodies were i.v. injected into BALB/c mice before CDDP treatment on day 6. To determine which of the mice or tumor were affected by CDDP, BALB/c mice were inoculated with CDDP-treated (12.5 micrograms/ml for 3 hours in vitro) MOPC-104E cells on day 0, 7 and 14. The potential to reject MOPC-104E was lower in mice immunized with ethanol-treated MOPC-104E cells than in those immunized with CDDP-treated cells. CDDP-treated or -untreated MOPC-104E cells ultrasonicated and fractionated into soluble and insoluble fractions by centrifuging, also induced antitumor immunity. Flow cytometry demonstrated that the expression of MHC-class-I antigens H-2Dd and H-2Kd was enhanced after CDDP-treatment, but that of class-II antigens I-Ad and I-Ed was not, suggesting that CDDP induced tumor-specific antitumor immunity by enhancing the expression of MHC-class-I antigens.

Animals↗
PubMedDate not supplied

p53 expression affects the efficacy of adjuvant chemotherapy after resection of invasive ductal carcinoma of the pancreas.

p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair, suggesting its involvement in the mechanisms of drug resistance or chemosensitivity. The present study assessed the implication of p53 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients received surgery alone and 30 patients received postsurgical adjuvant chemotherapy. p53 protein was stained immunohistochemically with anti-p53 monoclonal antibody. p53 was positively expressed in 29 out of 58 primary lesions (50%), and the survival curve of the patients with p53 (+) pancreatic cancer is lower than that of those with p53 (-) cancer. On the other hand, the survival curve of adjuvant chemotherapy group was also higher than that of surgery alone group, and furthermore, in patients with p53 (+) cancer, the survival curve of adjuvant chemotherapy group was significantly better than that of the surgery alone group. A multivariate analysis showed that p53 expression or adjuvant chemotherapy is not a significant risk-factor for prognosis, but that adjuvant chemotherapy is a significant risk factor for the patients with p53 (+) pancreatic cancer, which suggests that p53 expression affects the efficacy of chemotherapy. p53 expression may be beneficial as an indicator for introduction of adjuvant chemotherapy in pancreatic cancer patients.

Adult↗