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Biomedical subjects

Koji Hashimoto

Publications and source records attributed to Koji Hashimoto.

103 records · Page 6Linked to original sources

Hepatic artery reconstruction in living-donor liver transplantation: a review of its techniques and complications.

BACKGROUND: Hepatic arterial reconstruction is one of the most difficult procedures in living-donor liver transplantation (LDLT) because the artery used is generally small in diameter and has a short stalk. If hepatic artery thrombosis (HAT) occurs, the recipient clinical course will be unstable. The introduction of microvascular hepatic arterial reconstruction has significantly decreased the incidence of HAT. METHODS: Fifty-two cases of LDLT were performed from October 1995 to May 2001 in our institution. Hepatic arterial reconstruction was performed under microscopic guidance. RESULTS: HATs were recognized in 2 cases (3.8%), both of which needed reoperation. CONCLUSIONS: Surgeons who perform hepatic arterial reconstruction in LDLT should be highly trained in microvascular techniques to decrease the incidence of HAT. This commentary reviews the surgical techniques of hepatic arterial reconstruction and possible complications that may arise in a reconstructed hepatic artery.

Hepatic Artery↗

SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein.

Wild-type measles virus (MV) strains use human signaling lymphocyte activation molecule (SLAM) as a cellular receptor, while vaccine strains such as the Edmonston strain can use both SLAM and CD46 as receptors. Although the expression of SLAM is restricted to cells of the immune system (lymphocytes, dendritic cells, and monocytes), histopathological studies with humans and experimentally infected monkeys have shown that MV also infects SLAM-negative cells, including epithelial, endothelial, and neuronal cells. In an attempt to explain these findings, we produced the enhanced green fluorescent protein (EGFP)-expressing recombinant MV (IC323-EGFP) based on the wild-type IC-B strain. IC323-EGFP showed almost the same growth kinetics as the parental recombinant MV and produced large syncytia exhibiting green autofluorescence in SLAM-positive cells. Interestingly, all SLAM-negative cell lines examined also showed green autofluorescence after infection with IC323-EGFP, although the virus hardly spread from the originally infected individual cells and thus did not induce syncytia. When the number of EGFP-expressing cells after infection was taken as an indicator, the infectivities of IC323-EGFP for SLAM-negative cells were 2 to 3 logs lower than those for SLAM-positive cells. Anti-MV hemagglutinin antibody or fusion block peptide, but not anti-CD46 antibody, blocked IC323-EGFP infection of SLAM-negative cells. This infection occurred under conditions in which entry via endocytosis was inhibited. These results indicate that MV can infect a variety of cells, albeit with a low efficiency, by using an as yet unidentified receptor(s) other than SLAM or CD46, in part explaining the observed MV infection of SLAM-negative cells in vivo.

Animals↗

Peroxisome proliferator-activated receptor gamma ligand inhibits cell growth and invasion of human pancreatic cancer cells.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in certain human cancers; ligand-induced PPARgamma activation can result in growth inhibition and differentiation in these cells. However, the precise mechanism for the antiproliferative effect of PPARgamma ligands is not entirely known. AIM OF STUDY: The purpose of this study was to examine the effect of PPARgamma ligands on pancreatic cancer cell growth and invasiveness. METHODS: The effect of two PPARgamma ligands, 15 deoxy-delta12,14 prostaglandin J2 (15d-PGJ2) and ciglitazone, on the growth of four human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, Panc-1, and L3.6) was assessed. Expression of cell-cycle and apoptotic-related proteins was measured. Finally, the effect of 15d-PGJ2 on pancreatic cancer cell invasiveness and matrix metalloproteinase expression was determined. RESULTS: Both 15d-PGJ2 and ciglitazone inhibited the growth of all four pancreatic cancer cell lines in a dose- and time-dependent fashion. Treatment of BxPC-3 cells with 15d-PGJ2 resulted in a time-dependent decrease in cyclin D1 expression associated with a concomitant induction of p21waf1 and p27kip1. In addition, 15d-PGJ2 treatment induced apoptosis through activation of caspase-8, -9, and -3. Moreover, pancreatic cancer cell invasiveness was significantly suppressed after treatment with a nontoxic dose of 15d-PGJ2, which was associated with a reduction of MMP-2 and MMP-9 protein levels and activity. CONCLUSIONS: These results demonstrate that PPARgamma ligands have the dual advantage of inhibiting pancreatic cancer cell growth while reducing the invasiveness of the tumor cells, suggesting a potential role for these agents in the adjuvant treatment of pancreatic cancer.

3T3 Cells↗

Oral UFT (uracil plus futrafur) for neoadjuvant chemotherapy of gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has become one of the topics of interest in chemotherapy of gastric cancer; the present study assessed the clinical benefits of neoadjuvant chemotherapy with oral uracil and futrafur (UFT) for gastric cancer.METHODS: Between 1991 and 1997, 82 patients with gastric cancer (36 with early and 46 with advanced cancers) received UFT at 300-600 mg/day orally for 1-6 weeks before surgery. Objective responses, histological effects, and postsurgical survival rates were assessed.RESULTS: In 69 of the 82 patients, the objective responses of the primary lesions were assessed by endoscopy or upper gastrointestinal series examination, and 2 complete responses (CR)s, 25 partial responses (PRs), and 42 no changes (NCs) were seen (39.1% response). Histological effects were evaluated in 82 patients, and 2 grade 3, 11 grade 2, 11 grade 1b, 27 grade 1a, and 31 grade 0 effects were seen. A longer period of UFT administration was associated with a CR or PR. However, the objective responses did not correlate with the histological effects. All the patients underwent gastrectomy, and during the median follow-up period of 41 months, 3-year survival rates were 97.1% for pTNM stage 1, 75% for stage 2, 86.7% for stage 3, and 41.6% for stage 4. The survival rates of stage 3 and stage 4 patients were higher than those of the historical controls in our department. However, CR or PR did not correlate with the improvement in survival. Side effects before surgery were not serious; they included slight myelotoxicity, liver dysfunction, and anorexia; however, 3 patients (3.7%) had suture insufficiency, 3 patients (3.7%) had methicillin-resistant Staphylococcus aureus (MRSA) enteritis, and 7 patients (8.5%) had liver dysfunction.CONCLUSIONS: Preoperative chemotherapy for gastric cancer with oral UFT was safe and resulted in a good local response (macro- and microscopically) which may indicate the possibility of improved survival with neoadjuvant chemotherapy with UFT. Furthermore, preoperative chemotherapy with oral UFT is easy and patients can receive this treatment on an outpatient basis.

Journal Article↗

Implication of HER-2/neu overexpression for the efficacy of oral fluoropyrimidine-based adjuvant chemotherapy in the patients with estrogen receptor negative breast cancer after surgery.

BACKGROUND: The implications of HER-2/neu overexpression for the efficacy of adjuvant chemotherapy (ACT) and endocrine therapy (AET) have been controversial. The present study retrospectively assessed the effects of HER-2/neu overexpression on the efficacy of oral fluoropyrimidine-based ACT and AET after breast cancer surgery. PATIENTS AND METHODS: The expression of HER-2/neu protein and estrogen receptor (ER) in 217 primary breast cancers was assessed immunohistochemically using the HercepTest and an anti-ER monoclonal antibody. The overexpression of HER-2/neu was classified into 4 categories (0-3+) according to standard criteria, and 3+ was categorized as HER-2/neu-overexpression. Of the 217 patients, 26 received surgery alone (SA), 32 received ACT, 20 received AET alone and 139 received both AET and ACT. The regimen of the ACT included oral fluoropyrimidines in all patients. RESULTS: HER-2/neu (3+) overexpression and ER expression were seen in 31.8% (69 out of 217) and 47.5% (103 out of 217) of the patients, respectively. The survival of the HER-2/neu (3+) group was significantly lower than other groups (p = 0.0134), especially in the ER (+) patients (p = 0.0229). However, in the ER (+) patients, HER-2/neu overexpression had no significant effect. The effects of HER-2/neu overexpression and ER expression on the efficacy of the ACT and AET were analyzed by patient survival. In the ER (-) patients, the ACT (+) group had a significantly higher survival rate than the ACT (-) group (p = 0.0459), and this was noted especially in the HER-2/neu-overexpressing cases (p = 0.0485). In the ER (+) patients, ACT and AET did not have any significant influence on the survival regardless of the HER-2/neu status. CONCLUSION: Fluoropyrimidines-based ACT improves the long-term outcome of patients with HER-2/neu-overexpression (3+) and ER (-) breast cancer after surgery.

Administration, Oral↗

A self-expandable metallic stent in combination with cholangioscopic microwave coagulation therapy and chemotherapy with oral TS-1 against obstructive jaundice due to recurrent gastric cancer: a case report of successful treatment.

Obstructive jaundice is a terminal symptom of gastric cancer. A 45-year-old female patient had a recurrent gastric cancer at the pancreas head and it caused obstructive jaundice. She was treated with percutaneous transhepatic cholangio-drainage, followed by radiotherapy and chemotherapy with cisplatin, epirubicin and 5-FU, which resulted in a prominent response and a self-expandable metallic stent was placed into the bile duct. After 11 months, however, the tumor recurred and the bile duct was obstructed again by an invading tumor. She was retreated with percutaneous transhepatic cholangio-drainage for jaundice, followed by chemotherapy with oral TS-1. Her recurrent tumor dramatically responded again, and cholangioscopic microwave coagulation therapy was applied for the first time through a cholangio-drainage route and an additional metallic stent was inserted into the bile duct. After these therapies she has been disease--free for more than 2 years. In conclusion, the placement of a self-expandable metallic stent in combination with cholangioscopic microwave coagulation therapy and TS-1 was very effective in managing the obstructive jaundice due to the local recurrence of gastric cancer.

Administration, Oral↗

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation.

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.

Adult↗

The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome.

BACKGROUND: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated in about half of invasive ductal carcinoma (IDC) of the pancreas, but the expression of DPC4-mRNA remains to be evaluated. The present study assessed the comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their implication for patient outcome. MATERIALS AND METHODS: In the freshly separated specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs, the expression of mRNA was assessed by in situ hybridization and the expression of pDpc4 was assessed by immunohistochemistry. RESULTS: In the freshly separated specimens, DPC4-mRNA was expressed in 71% of the IDC, but pDpc4 expression was lost in 76% of the IDC. In 88 resectable IDCs, pDpc4 expression was lost in 75 (85.2%) and loss of pDpc4 expression was significantly correlated with the grade of nodal involvement (p =0.0265). Furthermore, the survival rate of the pDpc4 (-) group was significantly lower than that of the pDpc4 (+) group (p=0.0391). Adjuvant chemotherapy (ACT) significantly improved the survival rate and, in the ACT group, pDpc4 (-) patients had a significantly lower survival rate than the pDpc4 (+) patients. CONCLUSION: In human pancreatic IDC, although DPC4-mRNA was usually expressed, the expression of pDpc4 was lost. The expression of pDpc-4 is an indicator of better prognosis and response to ACT.

Aged↗

A randomized consent design trial of neoadjuvant chemotherapy with tegafur plus uracil (UFT) for gastric cancer--a single institute study.

OBJECTIVE: Various forms of neoadjuvant chemotherapy (NAC) have been applied in the treatment of gastric cancer. The present study was designed to assess the survival benefits of NAC with UFT (tegafur plus uracil) for gastric cancer, as a randomized consent trial as described by Zelen. PATIENTS AND METHODS: The present study included 295 patients with resectable gastic cancer between 1991 and 1999. After the patients had been pre-randomized into two groups, a control (no-NAC) group (n=120) and a treatment group (n=175), the treatment group patients were then further stratified into two groups, namely those who wished to join the control group and those who wished to receive NAC with UFT (NAC-UFT group). Patient outcome was surveyed in January 2003. RESULTS: Randomization did not necessarily result in an appropriate registration of the patients, and ultimately 193 patients were included in the control group and 102 patients received NAC-UFT. The NAC-UFT was well tolerated by the patients and side-effects were not severe. However, the NAC-UFT group included the patients with significantly higher stages of cancers than the control group. The survival benefit of NAC-UFT was seen in stage 2 or 3 patients, and multivariate analysis also revealed that NAC-UFT was a significant prognostic variable, as were pT, pN, M and the level of nodal dissection, but patient age, gentler and histological grade were not significant variables. CONCLUSION: NAC-UFT may be beneficial in the improvement of survival rate after gastric cancer surgery and this treatment modality is worthy of further study with a larger patient sample size.

Aged↗

Expression of retinoblastoma and p53 pathway-related proteins in resectable invasive ductal carcinoma of the pancreas: potential cooperative effects on clinical outcome.

BACKGROUND: The retinoblastoma protein (RB) is an important cell cycle regulator. RB also plays an important role in the regulation of apoptosis, which is mediated by interaction of p53 signaling mediators. The present study was designed to assess the clinicopathological significance of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) expression in resectable invasive ductal carcinoma (IDC) of the pancreas. MATERIALS AND METHODS: The present study included 79 pancreatic IDC patients, who received surgery between 1982 and 2002. The expression of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) were analyzed by immunohistochemistry. RESULTS: RB was expressed in 45 (57%) of the 79 patients. RB expression correlated significantly with histological grade and grade of nodal involvement. The positive rate of p53, p21WAF1/CIP1 and Bax expression was 49%, 48% and 67%, respectively. RB expression alone did not have a significant effect on patient survival. However, coexpression analysis of RB and p53 pathway-related proteins indicated that, in the patients with RB (+) IDC, the p21WAF1/CIP1 (+) group had a significantly higher survival rate than the p21WAF1/CIP1 (-) group. On the other hand, in the patients with RB (-) IDC, the Bax (+) group had a significantly higher survival rate than the Bax (-) group. Multivariate analysis indicated that, in the RB (-) group, pTNM stage, adjuvant chemotherapy and Bax expression were significant variables. CONCLUSION: The evaluation of RB expression combined with the mediators of the p53 pathway, p21WAF1/CIP1 and Bax, may provide more accurate information regarding clinical outcome, beyond that which is provided by RB expression alone.

Adult↗

Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.

BACKGROUND: The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas. PATIENTS AND METHODS: This study included 91 pancreatic IDC patients who received a pancreatectomy between 1982 and 2003. The expression of KIT and TGF-beta1 was analyzed by immunohistochemistry. RESULTS: KIT and TGF-beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression correlated inversely with nodal involvement, but KIT expression did not correlate with any clinicopathological factors. KIT expression had no significant influence on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co-expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+) IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a significant effect on the efficacy of adjuvant chemotherapy (ACT). In multivariate analysis, TGF-beta1 expression was one of the significant variables for survival in IDC patients overall, but KIT expression was not. CONCLUSION: TGF-beta1 expression is suggested to have a significant influence on c-kit-mediated cell proliferation in human pancreatic IDCs.

Adult↗

Immunohistochemical expression of HER-1 and HER-2 in extrahepatic biliary carcinoma.

The clinicopathological significance of HER-1- and HER-2-overexpressions (OE) (HercepTest score 2+ or 3+) in biliary cancer and their relationship to the efficacy of adjuvant chemotherapy (ACT) were assessed. In 72 biliary cancer (28 gallbladder and 44 bile duct cancer), HER-1 and HER-2 were stained immunohistochemically in formalin-fixed, paraffin-embedded specimens. The ACT included uracil and tegafur (UFT)-based chemotherapies. Out of the 72 cancer, OE was observed in 31 specimens (43%) for HER-1 and 47 (65%) for HER-2. However, their OEs were not correlated with each other. HER-2-OE was inversely correlated with the clinical stage (p=0.0482). HER-1-OE was correlated with distant metastasis (p=0.0263), but not with the clinical stage. Neither the OE of HER-1 or HER-2, nor their co-expression, showed any significant effect in term of patient survival. In the HER-1-OE (-) patients, the survival rate of the ACT group was significantly higher than that of the surgery-alone (SA) group (p=0.0423), but in the HER-1-OE (+) patients, there was no statistical difference in survival rate between the ACT and the SA group. In contrast, HER-2-OE had no significant effect on the efficacy of ACT. Multivariate analysis also demonstrated that the histological grade and ACT were significant variables, but T, N, M and HER-1 and HER-2 were not significant variables. In conclusion, neither HER-1-OE or HER-2-OE were prognostic factors of the biliary cancer. However, HER-1-OE may be a useful marker for the indication of ACT.

Adult↗