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Biomedical subjects

Kiyoshi Hasegawa

Publications and source records attributed to Kiyoshi Hasegawa.

At least 19 recordsLinked to original sources
PubMed2007

Regulation of the phosphatidylinositol 3-kinase-Akt and the mitogen-activated protein kinase pathways by ursolic acid in human endometrial cancer cells.

The phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the mitogen activated protein kinase (MAPK) pathway are important in the development and proliferation of various human cancers. It has been found recently that ursolic acid treatment affects growth and apoptosis in cancer cells. We sought to determine whether prominent signaling pathways, including the PI3K-Akt pathway and the MAPK (JNK, P38, and P44/42) pathway mediate these effects. Endometrial cancer cells often have high levels of phosphorylated Akt seen in conjunction with a PTEN mutation or deletion. Elevation in Akt protects the cancer cell from apoptosis. Ursolic acid treatment moderately decreased PI3K levels in SNG-II cells. Treatment also decreased phospho-Akt and phospho-P44/42 in a dose- and time-dependent fashion, dramatically in SNG-II cells and moderately in HEC108 cells. This effect was most pronounced following treatment with 50 mum ursolic acid for 72 h. Our study found inhibition of both the PI3K-Akt pathway and the MAPK pathway in two endometrial cancer cell lines, SNG-II and the poorly differentiated HEC108 cell line.

Cell Line, Tumor↗
PubMed2006

Late-onset acute rejection after living donor liver transplantation.

AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids. METHODS: Adult living donor liver transplantation recipients (n=204) who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 mo. RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR. CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

Adolescent↗
PubMed2006

Combined biological and photocatalytic treatment for the mineralization of phenol in water.

Phenol is degraded by biological treatment, however mineralization requires long time. To decrease the time and operational cost necessary for the mineralization of phenol, an optimum operation condition of the combined biological-photocatalytical treatment was investigated. The mineralization of phenol (50 mg l(-1)) was conducted in a flow-type biomembrane tank combined with a batch-type TiO2-suspended photocatalytic reactor. Phenol was degraded biologically to the concentration of 6.8 mg l(-1), an effective concentration for further photocatalytic treatment. After the biological treatment, the biotreated phenol was treated photocatalytically to complete the mineralization of phenol. The combined treatment shortened the mineralization time compared to the biological treatment and electric cost compared to the photocatalytic treatment only. The combined treatment may be suitable for a short-time mineralization of phenol in wastewater.

Catalysis↗
PubMed2006

Photocatalytic degradation of phenol by visible light-responsive iron-doped TiO2 and spontaneous sedimentation of the TiO2 particles.

Fe-doped TiO2 was prepared by the calcination of Fe(x)TiS(2) (x=0, 0.002, 0.005, 0.008, 0.01) and characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV-visible diffuse reflectance spectra. All the Fe-doped TiO2 were composed of an anatase crystal form and showed red shifts to a longer wavelength. The activity of the Fe-doped TiO2 for the degradation of phenol was investigated by varying the iron content during UV (365nm) and visible light (405nm and 436nm) irradiation. The degradation rate depended on the Fe content and the Fe-doped TiO2 was responsive to the visible light as well as the elevated activity toward UV light. The molar ratio of 0.005 was the optimum for both the UV and visible light irradiations. The result was discussed on the basis of the balance of the excited electron-hole trap by the doped Fe(3+) and their charge recombination on the doped Fe(3+) level. The Fe-doped TiO2 (x=0.005) was more active than P25 TiO2 under solar light irradiation. The suspended Fe-doped TiO2 spontaneously precipitated once the stirring of the reaction mixture was terminated.

Catalysis↗
PubMed2006

Pancreaticoduodenectomy after esophageal and gastric surgery preserving right gastroepiploic vessels.

Secondary pancreaticoduodenectomy was performed in 2 patients, 1 who had undergone proximal gastrectomy for a gastric carcinoma and 1 who had undergone subtotal esophagectomy with stomach tube reconstruction for an inferior thoracic esophageal carcinoma. To prevent ischemia and congestion of the remnant stomach, the inflow and outflow pathways to the stomach, such as the right gastroepiploic artery and vein, were preserved. In this article, we describe the preservation procedures and discuss the problems of the secondary abdominal surgical procedure.

Carcinoma↗
PubMed2006

Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.

Adult↗
PubMed2006

Portal vein reconstruction in adult living donor liver transplantation using cryopreserved vein grafts.

No data are available for the management of venous jump or interposition conduits for portal vein (PV) reconstruction in adult living donor liver transplantation (LDLT). The feasibility of using cryopreserved vein grafts as PV conduits was examined. Cryopreserved vein (n = 23) was used as a patch, interposition, or jump graft. The patency results were compared with those of anastomosis without vein patch (n = 217) or those with vein autografts (n = 10). The 5-yr primary and secondary patency rates of the cryopreserved vein grafts were 58% and 79%, respectively. In conclusion, our data indicate that the use of cryopreserved vein grafts should be limited as conduits in PV reconstruction in adult LDLT.

Adult↗
PubMed2006

Living donor liver transplantation for epithelioid hemangioendothelioma: Report of a case.

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor, generally considered to have low-grade malignancy. Little is known about its clinical behavior and the therapeutic strategy is not established. We report the case of a 36-year-old woman who underwent living donor liver transplantation for EH with splenic metastases and died of recurrence 8 months later. To determine if transplantation improves the prognosis of patients with EH, we must re-evaluate its indications.

Adult↗
PubMed2006

Estimation of standard liver volume in Japanese living liver donors.

BACKGROUND: Standard liver volume (SLV) is an important concept in adult living liver donor transplantation. The purpose of this study was to re-evaluate and modify the authors' previous formula for predicting total liver volume (TLV). METHODS: The TLV of 301 Japanese living donors was measured by computed tomography. This TLV was then compared with the liver volume calculated using established formulas. The correlation between TLV and several factors including body surface area (BSA) were analyzed and a new equation (SLVn) to better approximate TLV was determined. Factors related to the difference between TLV and SLVn were examined. RESULTS: Average TLV was 1196.3 +/- 221.0 cm3. Urata's formula underestimated TLV by 17.6 cm3 and the other formulas overestimated it by 120.4-244.9 cm3. TLV could be approximated by BSA; SLVn (cm3) = -404.8 + 961.3 x BSA (m2, R2 = 0.58). SLVn tended to overestimate the TLV of older donors and to underestimate TLV of thin donors. CONCLUSIONS: A new simple formula is presented that might be a better fit for calculating TLV in Japanese adults. This formula might be useful for evaluating the size of an adequate graft.

Adolescent↗
PubMed2005

Hepatic gene induction in murine bone marrow after hepatectomy.

BACKGROUND/AIMS: Bone marrow cells are highly plastic and differentiate into various cell types, including hepatocytes. To explore the mechanisms underlying these processes, we focused on the initial responses of bone marrow to hepatectomy, using a mouse model. METHODS: To evaluate hepatic differentiation in bone marrow cells we measured hepatocyte-related gene expression in mice undergoing partial hepatectomy with or without pretreatment for 1 week with 2-acetyl aminofluorene (AAF). RESULTS: Hepatectomy induced several genes related to early hepatic differentiation in bone marrow. Expression of these genes was enhanced by the administration of AAF, whereas genes specific for mature hepatocytes were not detected. We characterised the bone marrow cell population expressing hepatocyte differentiation genes. alpha-fetoprotein mRNA was induced in Lin- and either CD34+, c-kit+, Sca-1+, CD49f+ or CD45+ cells. The genes upregulated in the liver after AAF treatment and hepatectomy were identified using oligonucleotide microarrays. These included genes associated with the acute phase response. Dexamethasone inhibited the expression of early hepatic differentiation genes in the bone marrow of AAF/PHx mice. CONCLUSIONS: Early hepatic differentiation genes were induced in bone marrow in response to hepatectomy, especially when regeneration of the remnant liver was suppressed. Circulating signals generated in the AAF/PHx liver might activate this differentiation.

2-Acetylaminofluorene↗
PubMed2005

Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

Adult↗
PubMed2005

Prognostic impact of anatomic resection for hepatocellular carcinoma.

OBJECTIVES: To evaluate the prognostic impact of anatomic versus nonanatomic resection on the patients' survival after resection of a single hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA: Anatomic resection is a reasonable treatment option for HCC; however, its clinical significance remains to be confirmed. METHODS: Curative hepatic resection was performed for a single HCC in 210 patients; the patients were classified into the anatomic resection (n = 156) and nonanatomic resection (n = 54) groups. In 84 patients assigned to the anatomic resection group, segmentectomy or subsegmentectomy was performed. We evaluated the outcome of anatomic resection, including segmentectomy and subsegmentectomy, in comparison with that of nonanatomic resection, by the multivariate analysis taking into consideration 14 other clinical factors. RESULTS: Both the 5-year overall survival and disease-free survival rates in the anatomic resection group were significantly better than those in the nonanatomic resection group (66% versus 35%, P = 0.01, and 34% versus 16%, P = 0.006, respectively). In the segmentectomy and subsegmentectomy group, the 5-year overall and disease-free survival rates were 67% and 28%, respectively, both of which were also higher than the corresponding rates in the nonanatomic resection group (P = 0.007 and P = 0.001, respectively). The results of multivariate analysis revealed that anatomic resection was a significantly favorable factor for overall and disease-free survivals: the hazard ratios were 0.57 (95% confidence interval, 0.32-0.99, P= 0.04), and 0.65 (0.43-0.96, P = 0.03). CONCLUSION: Anatomic resection for a single HCC yields more favorable results rather than nonanatomic resection.

Adolescent↗
PubMed2005

Ultrasonically assisted retrohepatic dissection for a liver hanging maneuver.

OBJECTIVE: To establish a safer and technically easier retrohepatic dissection for the liver hanging maneuver with the assistance of intraoperative ultrasound (IOUS). SUMMARY BACKGROUND DATA: The liver hanging maneuver described by Belghiti et al is an innovative suspending technique of the liver and is useful in difficult major right hepatectomies or in donor operations for living donor liver transplantation. The most important complication of this procedure is injury to the short hepatic veins and subsequent massive bleeding with an incidence of 4% to 6%. METHODS: After the cranial dissection of the suprahepatic inferior vena cava (IVC) between the middle and left hepatic veins, a long light curved Kelly clamp is inserted from the caudal edge behind the caudate lobe and passed cranially along the anterior midline of the IVC. On the midway of the dissection, the proper hepatic vein draining the caudate lobe (PrCV) is visualized. A safe dissection path is confirmed by IOUS, identifying the position of the clamp tip, PrCV, and the caudal end of the cranial retrohepatic dissection. When IOUS shows that the clamp tip has reached the caudal end of the cranial dissection, the operator can feel the clamp tip with his/her finger and the retrohepatic dissection is completed. RESULTS: From September 2003 to July 2004, 50 donor operations were performed for adult living donor liver transplantation. Retrohepatic dissection was feasible in 40 cases (80%). Of these, a US-assisted retrohepatic dissection was performed in 34 donors. PrCVs were visualized by IOUS in 48 donors (96%). The location of these PrCVs varied significantly (60 degrees -175 degrees from the right edge of IVC), and there were no distinct landmarks for identifying the location of PrCVs and safe dissecting course (55 degrees -130 degrees ). IOUS found that the dissecting clamp was heading to the PrCV in 3 cases and the direction of dissection was shifted to avoid injury. No substantial bleeding or no other complication related to retrohepatic dissection was encountered in any of the cases. CONCLUSIONS: With the aid of IOUS, the whole course of the blind dissection between the anterior surface of the IVC and the liver could be clearly visualized. IOUS could also identify the PrCV, the most dangerous point in the retrohepatic dissection.

Adult↗
PubMed2005

Living donor liver transplantation for primary biliary cirrhosis: retrospective analysis of 50 patients in a single center.

Summary Although living donor liver transplantation (LDLT) is accepted as an alternative therapy for primary biliary cirrhosis (PBC), the postoperative results are not well known. Fifty patients with PBC underwent LDLT at Tokyo University Hospital. Their clinical records were retrospectively analyzed. Postoperative death occurred in four patients within 2 months (mortality, 8%), while later death occurred in three patients. In the median follow-up period of 35 months (range 4-84 months), the 1, 3, and 5-year overall survival rates were 90%, 88%, and 80%, respectively. The laboratory data indicated that graft function was sufficient. No recurrence of PBC was confirmed. Multivariate analysis indicated that an updated Mayo score of <10 was a significantly favorable factor for short hospitalization (hazard ratio, 9.52; 95% confidence interval, 1.14-79.5; P = 0.03). In conclusion, LDLT provides a satisfactory long-term survival with the PBC patients.

Adult↗
PubMed2005

Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor.

A role for cyclooxygenase-2 (COX-2) in the development and progression of various tumors has been identified. Selective COX-2 inhibitors produce anti-proliferative effects in various cancer cell lines that express COX-2. However, the mechanisms underlying anti-tumor effects are unclear. Furthermore, few studies have studied COX-2 expression in gynecological cancers, especially endometrial cancer. The current study had two goals. We investigated the correlation between COX-2 expression and clinicopathological factors of uterine endometrial cancer. We also investigated effects of treatment with etodolac, a selective COX-2 inhibitor, on the uterine endometrial cancer cell line TMG-L, which expresses COX-2. We conclusively confirmed expression of COX-2 mRNA and protein in endometrial cancer that exceeded levels of COX-2 seen in normal endometrium. However, no significant correlations were observed between COX-2 expression in endometrial cancer tumor samples and clinicopathological factors or disease-free survival rate of patients with endometrial cancer. Study of COX-2 inhibition of TMG-L cells showed that etodolac produced dose-dependent inhibition of cell proliferation through G1 phase cell-cycle arrest. Etodolac-induced cell-cycle arrest might be caused by increases in p53 and P21WAF1 protein expression. Production of basic-fibroblast growth factor (bFGF, a pro-angiogenesis factor) was inhibited by etodolac in a dose-dependent manner. Furthermore, telomerase activity was inhibited and expression of hTERT mRNA was significantly inhibited with etodolac, leading to the conclusion that anti-tumor effects of etodolac on TMG-L cells are due to inhibition of both angiogenesis and telomerase activity. These results strongly suggest that COX-2 inhibitors have potential as therapeutic (and possibly, chemopreventive) agents for endometrial cancers that overexpress COX-2.

Cell Cycle↗
PubMed2005

Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells.

We studied the effect of ursolic acid, a pentacyclic triterpene acid, on the growth of poorly differentiated type endometrial cancer HEC108 cells in vitro. Ursolic acid strongly inhibited the growth of HEC108 cells in a dose- and time-dependent manner. Morphological changes characteristic of apoptosis were observed in ursolic acid-treated cells, such as the presence of apoptotic bodies and fragmentation of DNA to oligonucleosomal-sized fragments. Investigation of caspase activity in ursolic acid-treated HEC108 cells showed that exposure at 50, 75 or 100 microM induced marked increases in caspase-3 activity (after 24 h) to 5.00, 11.76 or 12.75 times that of control levels, while cleaved caspase-3 levels increased in dose-dependent manner after 24 h. Activation of caspase was shown to lead to the cleavage of target proteins such as PARP. Ursolic acid treatment also resulted in a cleavage of poly(ADP-ribose) polymerase in a dose-dependent manner. Testing whether caspase-3 activation and DNA polymerase activity were inhibited by the addition of Ac-DEDV-HOC during ursolic acid treatment showed that 50 microM Ac-DEDV-HOC inhibited caspase-3 activity in treated cells. A mitochondrial pathway has been suggested to be involved in ursolic acid-induced apoptosis because the treatment induces mitochondria cytochrome c release. Experimentally, we found that anti-apoptotic Bcl-2 protein levels decreased after ursolic acid treatment, while Bax expression increased. Our results indicated that ursolic acid induced apoptotic processes in these poorly differentiated endometrial cancer cells occurs through mechanisms involving mitochondrial pathways and Bcl-2 family proteins.

Antineoplastic Agents, Phytogenic↗
PubMed2004

p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma.

PURPOSE: The tumor suppressor gene p16INK4A is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16INK4A methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. EXPERIMENTAL DESIGN: We studied the methylation status and mRNA and protein expression of p16INK4A in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. RESULTS: p16INK4A hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16INK4A methylation was significantly associated with mRNA and protein expression (P <0.001 and P=0.003, respectively). All of the p16INK4A-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16INK4A methylation (P=0.006). The frequency of p16INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P=0.1). Aberrant methylation of p16INK4A was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P=0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16INK4A hypermethylation and those without. CONCLUSIONS: Our observations suggest that p16INK4A hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16INK4A hypermethylation in hepatocarcinogenesis.

Adult↗