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T Ochiai

Publications and source records attributed to T Ochiai.

At least 55 records · Page 3Linked to original sources
PubMed2001

Additive and inhibitory effects of simultaneous treatment with growth factors on DNA synthesis through MAPK pathway and G1 cyclins in rat hepatocytes.

Several growth factors play an important role in liver regeneration. Once hepatic injury occurs, liver regeneration is stimulated by hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha, and heparin-binding epidermal growth factor-like growth factor (HB-EGF), whereas TGF-beta1 terminates liver regeneration. In this study, we analyzed the effect of a combination of HGF and epidermal growth factor (EGF) on mitogen-activated protein kinase (MAPK) activity and G1 cyclin expression in primary cultured rat hepatocytes. Treatment with a combination of HGF and EGF, in comparison with that of either HGF or EGF, induced tyrosine phosphorylation of both c-Met and EGF receptor (EGFR) independently and additively stimulated MAPK activity and cyclin D1 expression, resulting in additive stimulation of DNA synthesis. On the other hand, although TGF-beta1 treatment did not affect tyrosine phosphorylation of c-Met and EGFR, MAPK activity, and cyclin D1 expression, which were stimulated by HGF and EGF, DNA synthesis was completely inhibited through a marked decrease in cyclin E expression. These results indicate that potent mitogens, such as HGF, TGF-alpha, and HB-EGF, could induce the additive enhancement of liver regeneration cooperatively through an increase in Ras/MAPK activity followed by cyclin D1 expression, and that TGF-beta1 suppresses the growth factor-induced signals between cyclin D1 and cyclin E, resulting in the inhibition of DNA synthesis.

Animals↗
PubMed2001

Prophylactic excision of the gallbladder and bile duct for patients with pancreaticobiliary maljunction.

HYPOTHESIS: Pancreaticobiliary maljunction (PBM) is a high-risk factor for biliary tract carcinogenesis because of a continuous reflux of pancreatic juice into the biliary tract. It remains to be disclosed whether we should perform prophylactic excision of gallbladders and bile ducts. DESIGN: A person-year method. SETTING: A university hospital. PATIENTS: We studied 68 patients with PBM treated between August 1, 1974, and December 31, 1999. MAIN OUTCOME MEASURES: Relative risks (observed number-expected number ratios) of gallbladder and bile duct carcinomas according to type of bile duct dilation (ie, cystic dilation, diffuse dilation, and nondilation). RESULTS: Observed number-expected number ratios of gallbladder carcinomas were high: 291.3 in 43 patients with cystic dilation, 167.2 in 16 patients with diffuse dilation, and 419.6 in 7 patients with nondilation. Observed number-expected number ratios of bile duct carcinomas were 194.2 in 43 patients with cystic dilation before surgery and 142.8 in 39 patients with cystic dilation after long postsurgical follow-up. All these values were statistically significant (P<.01). CONCLUSIONS: The gallbladder carries a high risk for carcinogenesis in all types of dilation in patients with PBM. The bile duct carcinomas of PBM were exclusively identified by the type of cystic dilation. Prophylactic cholecystectomy should be recommended for all dilation types, and prophylactic excision of bile ducts including cholecystectomy should be performed in patients with PBM and cystic dilation. Complete excision of extrahepatic dilated bile ducts and careful follow-up for carcinogenesis in residual dilated bile ducts should be recommended for patients with PBM and cystic dilation.

Adult↗
PubMed2001

Serum p53 antibody as a useful marker for monitoring of treatment of superficial colorectal adenocarcinoma after endoscopic resection.

BACKGROUND: Mutation of the p53 gene is a genetic alteration found in human cancers. Overexpression of p53 has been found to induce antibody production in serum, and, recently, the simple detection of serum antibody has been made possible. The aim of this study was to evaluate the potential role of serum p53 antibody in the early diagnosis of superficial colorectal cancer and in the monitoring of its treatment after endoscopic resection. METHODS: In a prospective study, our subjects were 27 patients with superficial colorectal adenocarcinomas, whose results were compared with those in 38 patients with benign adenomas; all patients were treated by endoscopic resection. The correlation between serum p53 antibody levels before and within 3 weeks after resection was determined, using an immunoassay. Immunohistological staining for p53 was also performed, and its sensitivity was compared with that of two other tumor markers. RESULTS: Preoperatively, serum p53 antibody was detected in 63.0% (17/27) patients with adenocarcinoma and in 2.6% (1/38) patients with adenoma, showing a significant difference (P < 0.001). However, the two other markers carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9, showed no significant difference between superficial colorectal adenocarcinoma and adenoma. The serum p53 antibody status was strongly correlated with p53 immunostaining in adenocarcinoma (P = 0.0065), but there was no significant correlation in adenoma (P = 0.973). Sixteen (94.1%) of 17 seropositive adenocarcinoma patients, showed negative conversion after complete tumor resection, and all these 16 patients remained seronegative. CONCLUSION: The detection of serum p53 antibody is expected to serve as a new genetic marker, determined by serological analyses, for aiding in the early diagnosis of superficial colorectal cancer and indicating its local curability after endoscopic treatment.

Adenocarcinoma↗
PubMed2001

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer.

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer.

Aged↗
PubMed2001

Preclinical study of adenoviral p53 gene therapy for esophageal cancer.

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.

Adenoviruses, Human↗
PubMed2001

Long-term outcomes of immunosuppressed renal transplant recipients with malignancies.

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor.

Adult↗
PubMed2001

Fournier's gangrene: report of six cases.

Fournier's gangrene (FG) is a fatal infectious disease with necrotic fasciitis of the external genitalia. This disease persists to this day in spite of recent advances in antibiotics. Although fewer than 100 cases have been reported in Japan, we have treated six cases in the last 4 years. The patients consisted of five men and one woman, with an average age of 47.5 years. All patients received surgical treatment including incisions, aggressive debridement, drainage, irrigation, and antibiotic therapy. Two patients, who suffered from underlying diseases of diabetic nephropathy and inclusion body myositis, died. These findings confirm the fact that FG requires a prompt diagnosis and immediate surgical treatment.

Adult↗
PubMed2001

Successful surgical treatment of renal cell carcinoma in a transplanted kidney from a cadaveric donor: report of a case.

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence.

Adenocarcinoma↗
PubMed2001

Direct inhibitory effect of adrenomedullin, calcitonin gene-related peptide, calcitonin, and amylin on cholecystokinin-induced contraction of guinea-pig isolated caecal circular smooth muscle cells.

We recently reported the direct inhibitory effect of adrenomedullin on caecal circular smooth muscle cells via cAMP system. This study was designed to determine whether the structurally related peptides to adrenomedullin (i.e.; calcitonin gene-related peptide (CGRP), calcitonin, and amylin) can inhibit the cholecystokinin octapeptide (CCK-8)-induced contractile response by exerting a direct action on guinea-pig caecal circular smooth muscle cells, and to compare the inhibitory potency of these peptides. In addition, to elucidate each intracellular mechanisms, the effects of an inhibitor of cAMP-dependent protein kinase, inhibitors of particulate or soluble guanylate cyclase on the each peptide-induced relaxation were investigated. Adrenomedullin, CGRP, calcitonin, and amylin inhibited the contractile response produced by CCK-8 in a dose-dependent manner, with IC50 values of 0.14 nM, 0.37 nM, 5.4 nM, and 160 nM, respectively. An inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by all of these peptides. On the contrary, inhibitors of particulate or soluble guanylate cyclase did not have any significant effect on the relaxation produced by these peptides. In this study, we demonstrated the direct inhibitory effects of the structurally related peptides to adrenomedullin (i.e.; CGRP, calcitonin, and amylin) on the isolated caecal circular smooth muscle cells via cAMP system. The order of potency was as follows; adrenomedullin falling dots CGRP > calcitonin > amylin.

Adrenomedullin↗
PubMed2001

Bullous amyloidosis: the mechanism of blister formation revealed by electron microscopy.

BACKGROUND: Few electron microscopic studies of blister lesions in bullous amyloidosis have been reported, and the mechanism of blister formation remains to be elucidated. This study was designed to examine the nature of bullous amyloidosis ultrastructurally, and clarify the pathogenesis of blister formation. METHODS: We examined a 47-year-old woman with IgD-lambda type myeloma, suffering from bullous lesions on her hands and feet caused by trauma or rubbing. Light and electron microscopic studies were performed. RESULT: Ultrastructurally, amyloid deposits aggregated under the lamina densa. Keratinocyte protrusions penetrated the dermis through the gap in the lamina densa and enfolded amyloid deposits. Amyloid globules were found in enlarged intercellular spaces of keratinocytes. Desmosomes were sparsely distributed in some areas of the epidermis. CONCLUSION: These results indicate that keratinocytes enfold the amyloid globules and take them in the intercellular space of epidermis, and that the breakdown of the lamina densa and widening of the intercellular space between keratinocytes induce skin fragility. Trauma or rubbing of her hands and feet appears to act as the localized precipitating factor of blister formation in bullous amyloidosis.

Amyloid↗
PubMed2001

Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase).

Advanced esophageal cancers are highly malignant and frequently resistant to 5-fluorouracil (5-FU). Escherichia coli uracil phosphoribosyltransferase (UP) is a pyrimidine salvage enzyme that alters 5-FU metabolism and sensitivity. A recombinant adenovirus encoding the UP gene (AxCA.UP) has been applied in gastric cancer gene therapy to sensitize cancer cells to lower concentrations of 5-FU. We have generated a recombinant adenovirus (AxCA.UT) encoding UP and herpes simplex virus thymidine kinase fusion protein (UT) to examine whether it would enhance the antitumor activity of AxCA.UP treatment. AxCA.UT treatment significantly enhanced the sensitivity of human esophageal cancer cells to and significantly enhanced the growth inhibition effects of UP gene therapy in vitro. Moreover, both 5-FU and ganciclovir showed bystander effects on growth inhibition. In an in vivo study, the therapeutic outcome of AxCA.UT treatment significantly enhanced the antitumor activity of AxCA.UP treatment. These observations suggest that AxCA.UT may be useful in esophageal cancer gene therapy.

Adenoviridae↗
PubMed2001

A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir.

The c-erbB-2 gene is frequently overexpressed in human breast cancers as a result of gene amplification and/or elevated transcription. We therefore examined a possible usage of promoter regions of the c-erbB-2 gene to express a suicide gene preferentially in breast cancer cells. Previous studies did not reveal the minimal promoter region that enabled transcriptional activation specific to breast cancer cells. The present reporter gene assays using deletion mutants of the c-erbB-2 promoter region demonstrated that the 251-bp (-213/+38 from the transcriptional start site), but not the 125-bp, fragment (-87/+38) could direct transcription of the linked luciferase gene better than the SV40 immediate early promoter in breast cancer cells. In contrast, the 251-bp fragment-mediated promoter activity in nonbreast cancer cells and in normal fibroblasts was lower than the activity by the SV40 promoter. The 126-bp fragment (-213/-87) thereby contains a cis-acting element(s), which is responsible for the preferential transcriptional activity in breast cancer cells. An electrophoretic mobility shift assay suggested that a possible modification of a transcriptional factor was involved in the tumor specificity. Transfection with the plasmid DNA containing the herpes simplex virus thymidine kinase gene linked with the 251-bp promoter (p256-TK) resulted in increased sensitivity to ganciclovir in breast cancer, but not in nonbreast cancer cells. Administration of ganciclovir into nude mice bearing human breast tumors that were transfected with the p256-TK DNA suppressed subsequent growth of the transplanted tumors. These results suggest that delivery of a suicide gene linked with the 251-bp c-erbB-2 promoter can be a feasible therapeutic strategy specific to breast cancer.

Animals↗
PubMed2001

Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma.

By reviewing previous surgical specimens of hepatocellular carcinoma, 17 cases with hyperplastic foci (HPF) characterized by discernible increase in nuclear densities, could be histologically selected. Nuclear densities of HPF and control hepatic parenchyma were assessed quantitatively by counting the nuclear number of hepatic cells, and proliferating cell nuclear antigen labeling index was measured. HPF occurred multifocally, confined within a lobular unit, smoothly merging into surrounding hepatic parenchyma. Nuclear densities of HPF were 1.71 times greater than those of control hepatic parenchyma. The hepatocytes of HPF also showed significantly higher proliferative activities than those of control parenchyma. In addition, noticeable structural distortions, such as focal trabecular thickening or microacinar formation of hepatocytes, were sometimes observed in HPF. However, these HPF seemed to be distinguished from minute de novo hepatocellular carcinoma (HCC) or intrahepatic HCC metastasis, because of paucity of distinctive atypical changes, and intimate correlation with neighboring hepatocytes. Several adjacent HPF were aggregated to form a much larger unit of a hyperplastic area with loss of fibrous septa of liver cirrhosis. It was suggested that grossly detectable large regenerative nodules are produced via fusion of several adjacent HPF.

Adult↗
PubMed2001

Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability.

OBJECTIVE: To investigate the clinical use of p53 autoantibodies as a marker in the postoperative monitoring of colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 40 patients with colorectal cancer who had p53 autoantibodies in their serum preoperatively. INTERVENTIONS: Serial assay of p53 autoantibodies by ELISA before and after resection. MAIN OUTCOME MEASURES: Interpretation by a qualitative analysis. RESULTS: A significant correlation was observed between curability by surgical resection and postoperative disappearance of p53 autoantibodies. Twenty-seven (96%) of 28 patients, who had p53 autoantibodies and whose cancer was completely removed, had no such antibodies after resection and no recurrence after 7 to 26 months. CONCLUSIONS: Postoperative assays of p53 autoantibodies are potentially useful for predicting recurrence of colorectal cancer in patients who have p53 autoantibodies preoperatively.

Colorectal Neoplasms↗
PubMed2001

Staphylococcus aureus requires increased level of Ca(2+) or Mn(2+) to grow normally in a high-NaCl/low-Mg(2+) medium.

Mg2+-availability in Staphylococcus aureus cells decreased significantly with increasing NaCl concentration in growth media. Cells grew in a NaCl-free, Chelex resin-treated complex medium only if the medium was supplemented with 50 microM MgCl2, while, growth was limited when the medium was further supplemented with 1.0 M NaCl. Cells grown in such a high-NaCl/low-Mg2+ medium exhibited the morphologic abnormality of larger than normal cells. Both sufficient growth and normal cell morphology were restored by increasing Mg2+ concentration in a high-NaCl medium, or by supplementation with either CaCl2 or MnSO4 in a high-NaCl/low-Mg2+ medium. Supplementing with BaCl2, SrCl2 or FeSO4, however, had no effect. These results indicate that Ca2+ and Mn2+ might play some essential role in the growth of Staphylococcus aureus in a high-NaCl/low-Mg2+ environment.

Barium↗
PubMed2001

Overexpression of sialyl Lewis x antigen is associated with formation of extratumoral venous invasion and predicts postoperative development of massive hepatic metastasis in cases with pancreatic ductal adenocarcinoma.

The clinicopathological factors and expression of sialyl Lewis antigens which are the cell adhesion molecules to endothelial cells were compared in relation to the extent of the postoperative hepatic metastasis in 23 consecutive patients with pancreatic ductal adenocarcinoma whose clinical courses were carefully monitored and documented. The overall survival of cases with massive hepatic metastasis (MHM) was significantly poorer than that of those with local or no hepatic metastasis (p = 0.0453). Postoperative MHM was significantly correlated with the presence of duodenal invasion (p = 0.0418), the presence of portal vein invasion (p = 0.0435), the presence of extratumoral venous invasion (p = 0.0052) and high expression of sialyl Lewis x antigen (p = 0.0022). Multivariate analysis confined significant correlation between the high expression of sialyl Lewis x antigen and the development of MHM (p = 0.0402). Kaplan-Meier analysis revealed that the overall survival of patients with a high expression of sialyl Lewis x antigen was significantly poorer than that of patients with a low expression of the antigen (p = 0.0216). These results indicate that the overexpression of sialyl Lewis x antigen plays an important role in the development of MHM, and also predicts a poorer overall survival of these patients. Further studies with more cases are warranted to confirm these results.

Adult↗
PubMed2001

Combinatory anti-tumor effects of electroporation-mediated chemotherapy and wild-type p53 gene transfer to human esophageal cancer cells.

Delivery of electric pulses to an established solid tumor augments the permeability of cell membrane and increases the susceptibility of tumors to an anti-cancer agent that is administered in the vicinity of tumors. Forced expression of the wild-type p53 gene in tumor cells that have non-functional p53 gene(s) can also enhance their sensitivity to a DNA-damaging agent. To investigate the feasibility of electroporation-mediated therapy for cancer, electric pulses were delivered to human esophageal tumors developed in nude mice after they received an anti-cancer agent and/or plasmid DNA containing the wild-type p53 gene. The growth of esophageal tumors was suppressed with electroporation-mediated chemotherapy compared with the treatment with an anti-cancer agent or electroporation alone. Intratumoral injection of the wild-type p53 gene into p53-mutated esophageal tumors followed by electroporation also inhibited tumor growth. When mice were administered with the wild-type p53 gene and an anti-cancer agent, subsequent electroporation produced a synergistic therapeutic effect. Combinatory transfer of plasmid DNA and a pharmacological agent by electroporation is thereby a possible therapeutic strategy for the treatment of solid tumors.

Animals↗