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Biomedical subjects

M Makuuchi

Publications and source records attributed to M Makuuchi.

At least 163 records · Page 9Linked to original sources
PubMed2000

Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma.

This study was designed to test the hypothesis that cyclin D1 overexpression is involved in the multistep process of gallbladder carcinogenesis and can be used to predict poor prognosis for patients with gallbladder carcinoma (GBC). Cyclin D1 expression was examined immunohistochemically in a series of specimens, including 8 normal epithelia, 8 benign adenomyoma lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Four of the 6 (67%) adenomas and 15 of the 37 (41%) adenocarcinomas demonstrated cyclin D1 overexpression (>5% nuclear staining), whereas all normal epithelia and adenomyoma lesions were negative for cyclin D1. Kaplan-Meier curves showed that cyclin D1 overexpression was significantly related to decreased overall survival (P < 0.05) in patients with GBCs. The Cox proportional hazards model identified cyclin D1 overexpression as an independent prognostic marker for death (P = 0.024; risk ratio, 4.2; 95% confidence interval, 1.2-14.7). To test whether cyclin D1 overexpression is a critical event in gallbladder neoplasms, cyclin-dependent kinase inhibitor p27Kip1 was introduced to ascertain how cyclin D1 affects clinical outcomes. Subsequently, neoplasms were divided into three groups on the basis of the combination of cyclin D1 expression and p27Kip1 status, which had been determined previously. Group 1 showed no abnormality in either cyclin D1 or p27Kip1 expression. Group 2 showed aberrant expression of one of the two proteins, whereas group 3 showed concurrent abnormalities in both proteins. Results indicated that overall survival was greatest in group 1, followed by a significant decrease in group 2 and a more precipitous decrease in group 3. In conclusion, cyclin D1 overexpression is an early event in gallbladder carcinogenesis and independently predicts decreased survival for patients with GBC.

Aged↗
PubMed2000

[Progress in surgery for hepatocellular carcinoma].

Before 1980, the surgical procedure for liver resection was limited to major hepatectomy. Anatomical resection for subsegmentectomy based on liver anatomy was established after 1980. Surgical techniques to resect nonpalpable and nonvisible tumors and devices to reduce blood loss in the resection plane of the liver are mandatory when performing subsegmentectomy. Intraoperative ultrasound has played a major role in the progress achieved. Hepatectomy procedures preservation of the inferior right hepatic vein, and preoperative portal vein embolization have also contributed to progress in the field of liver surgery.

Carcinoma, Hepatocellular↗
PubMed1999

Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma.

To determine the role of retinoblastoma (Rb) gene alteration in hepatocarcinogenesis, we examined Rb protein expression immuno-histochemically in a series of surgically resected specimens including non-cancerous liver tissues with cirrhosis or chronic hepatitis, large regenerative nodules, pre-cancerous adenomatous hyperplasias as well as primary and metastatic lesions of hepatocellular carcinoma (HCC). All of the non-cancerous liver tissues, large regenerative nodules and adenomatous hyperplasias showed normal Rb protein expression. Altered Rb protein expression was observed in 31 (lack of Rb protein in 16 and over-expression in 15) of the 81 primary HCCs (38%) and was significantly associated with tumor differentiation grade: altered Rb protein expression occurred in 1 of 23 (4%), 16 of 43 (37%) and 14 of 15 (93%) well-, moderately and poorly differentiated tumors (moderately vs. well-differentiated p < 0.01; poorly vs. moderately differentiated p < 0.001). Incidences of both Rb protein absence and over-expression were higher for moderately differentiated than for well-differentiated tumors and even higher for poorly differentiated tumors. Rb protein absence and over-expression were observed in 9 (39%) and 10 (44%) of the 23 metastatic lesions of HCC, respectively, and the incidence of altered Rb protein expression (absence or over-expression) was significantly higher than in primary lesions (83% vs. 38%, p < 0.001). Our observations suggest that elevated and absent Rb protein are closely associated with tumor progression and developing metastatic disease rather than tumor initiation in cases of HCC. Int. J. Cancer (Pred. Oncol.) 84:604-608, 1999.

Adolescent↗
PubMed1999

Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs.

The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growth factor receptor 2. The K-sam gene is located on human chromosome 10q26 and is preferentially amplified in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. During the course of studies on the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines. These deletions generate preferential expression of mRNAs encoding K-sam proteins lacking the carboxyl-terminal region containing the tyrosine residues at positions 780, 784, and 813. The carboxyl-terminal region has been reported to have a sequence required for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during the carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene. Sequence analysis of the DNA sequences surrounding the deletion junctions shows the presence of unique sequences and indicates the involvement of short homology-mediated recombination in the generation of these deletions.

3T3 Cells↗
PubMed1999

Novel exons located more than 200 kb downstream of the previously described 3' exon of the K-sam gene for generating activated forms of KGF receptor.

The K-sam gene was first identified as an amplified gene in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. We have recently found and reported that the carboxyl-terminal exons of K-sam are frequently deleted in the scirrhous type of gastric cancer. The deletion generates preferential expression of at least six novel K-sam-II mRNAs: K-sam-IIH1, -IIH2 and -IIH3/O4, and K-sam-IIO1, -IIO2, and -IIO3, which encode novel proteins lacking the transformation-inhibitory sequence or activated K-sam proteins. In this study, we investigated expression of the previously described K-sam-IIC1 and -IIC3 mRNAs and the novel six K-sam-II mRNAs in 14 gastric cancer cell lines, 7 breast cancer cell lines, and 20 human normal tissues. All the six novel K-sam-II mRNAs were expressed preferentially in the cell lines derived from the scirrhous type of gastric cancers but not in the 7 breast cancer cell lines and the 20 human normal tissues. We further determined the positional relationship of four exons of H1, O1, O2, and O3 out of the six exons of H1, H2, H3/O4, O1, O2, and O3, and found that these four novel K-sam exons were located more than 200 kb downstream of the previously described carboxyl-terminal exon of the K-sam gene. Expression of K-sam-IIH1, -IIO1, and -IIO2 mRNAs encoding activated K-sam products in the scirrhous type of gastric cancer cell lines HSC39, OCUM2M, HSC59, and HSC60 was not due to the deletion of the C1 exon of K-sam.

Amino Acid Sequence↗
PubMed1999

Portal venoplasty for recipients in living-related liver transplantation.

BACKGROUND: In living-related liver transplantation (LRLT) in small children, standard end-to-end portal vein (PV) anastomosis is usually difficult because of a inadequate total PV length, or because of a size mismatch between the graft and the recipient PV. In this report, we present our new portal venoplasty technique for the recipient PV. METHODS: After dissection of the recipient PV, the wall between the right and left branches of the PV is severed longitudinally as in the branch patch technique. The anterior and posterior edges of both branches are joined using running sutures, to form a longer and wider PV for anastomosis. RESULTS: This new portal venoplasty technique was used in 7 of 28 child cases, and gave good results without thrombosis or other complications. CONCLUSIONS: Our new portal venoplasty technique is useful in LRLT in small children when the recipient or graft PV is not long enough.

Adult↗
PubMed1999

Enhancement of hepatitis C virus replication by Epstein-Barr virus-encoded nuclear antigen 1.

Based on our recent observation that Epstein-Barr virus (EBV) is detected in 37% of the tissues of hepatocellular carcinoma, and especially frequently in cases with hepatitis C virus (HCV), the effect of EBV infection on the replication of HCV was investigated. EBV-infected cell clones and their EBV-uninfected counterparts in cell lines MT-2 (a human T-lymphotropic virus type I-infected T-cell line), HepG2 (a hepatoblastoma cell line) and Akata (a Burkitt's lymphoma cell line) were compared in terms of their permissiveness for HCV replication following inoculation of HCV derived from patients who were HCV carriers. The results indicated that EBV-infected cell clones, but not their EBV-uninfected counterparts, promoted HCV replication. EBV-encoded nuclear antigen 1 (EBNA1), which is invariably expressed in EBV-infected cells, supported HCV replication. Deletion analysis of the EBNA1 gene showed good correlation between transactivation activity and the activity supporting HCV replication. The present findings suggest that EBV acts as a helper virus for HCV replication.

Base Sequence↗
PubMed1999

Angiotensin II stimulates platelet-derived growth factor-B chain expression in newborn rat vascular smooth muscle cells and neointimal cells through Ras, extracellular signal-regulated protein kinase, and c-Jun N-terminal protein kinase mechanisms.

Platelet-derived growth factors (PDGFs) have been implicated in the pathogenesis of vascular proliferative disorders. Vascular smooth muscle cells (VSMCs) are one of the cell types that produce PDGF-B chain in proliferative lesions, although the mechanism of regulation of PDGF-B chain production in these cells is not well understood. In the present study, we demonstrate that angiotensin II (Ang II), which is also implicated in vascular stenosis after angioplasty and atherosclerosis, markedly stimulates PDGF-B chain mRNA expression in cultured newborn rat medial VSMCs and neointimal VSMCs via an AT(1), but not in adult rat VSMCs. In newborn rat VSMCs, Ang II activates extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase. The mitogen-activated protein/ERK (MEK) inhibitor PD98059, but not the p38 inhibitor SB203580, abrogates Ang II-induced PDGF-B mRNA expression. Transient transfection analysis using a PDGF-B promoter-luciferase gene reporter construct reveals that Ang II induces transcriptional activation of PDGF-B chain gene, which is abolished by the expression of a dominant negative form of either ERK or JNK, but not of p38. The expression of a dominant negative form of Ras abolishes the stimulatory effects of Ang II on ERK activity and PDGF-B mRNA expression. In adult rat VSMCs, Ang II activates ERK and JNK, but weakly induces Egr-1, a transcription factor implicated in PDGF-B chain gene expression, compared with newborn VSMCs. These data indicate that Ang II activates PDGF-B chain gene expression in VSMCs through mechanisms involving Ras-ERK and JNK.

Aging↗
PubMed1999

Versatility of the inferior epigastric artery as an interpositional vascular graft in living-related liver transplantation.

We have used the recipient inferior epigastric artery as an interpositional vascular graft in living-related liver transplantation cases with hepatic artery obstruction, enabling us to restore the arterial inflow sufficiently to the transplanted liver. The inferior epigastric artery is easy to access during abdominal surgery. Easy to harvest, it is anatomically constant and has a caliber equivalent to that of the hepatic artery. Donor site morbidity is negligible. There is no risk of rejection because of the autograft. There has been no report on the availability of the inferior epigastric artery for hepatic artery reconstruction. We consider this vessel as a good option for an arterial conduit in case of the inadequacy or thrombosis of the hepatic artery in living-related liver transplantation.

Adolescent↗
PubMed1999

Detection of Epstein-Barr virus (EBV) in hepatocellular carcinoma tissue: a novel EBV latency characterized by the absence of EBV-encoded small RNA expression.

In this study, we investigated the presence of Epstein-Barr virus (EBV) in liver tissue from 35 patients with hepatocellular carcinoma (HCC). EBV DNA was detected in 13 patients (37%) by Southern blot hybridization. In 10 of these patients, EBV DNA was present in tumor tissue only, whereas in the other 3, it was detected in both tumor and nontumor tissues. The quantity of EBV DNA detected was equivalent to 1-10 viral DNA molecules/100 cells. EBV-determined nuclear antigen was detected in 7-13% of the carcinoma cells in three tumor tissue samples that contained approximately one copy of the EBV genome/10 cells. A single terminal fragment of EBV DNA was identified in these tissues, suggesting that the EBV-infected cells in HCC represent clonal proliferation. Western blotting and reverse transcription-polymerase chain reaction analyses demonstrated that these three tumor tissue specimens were positive for EBV-determined nuclear antigen 1 and BamHI A transcripts but were negative for the other latent EBV products, including EBV-encoded small RNA. The results indicated that there is a high EBV load in HCC tissue and that all of the HCC tissue examined showed a novel pattern of EBV latency characterized by absence of EBV-encoded small RNA expression.

Adult↗
PubMed1999

Expression of the MAGE gene family in human hepatocellular carcinoma.

BACKGROUND: The 12 members of the MAGE gene family encode tumor specific antigens that are recognized by autologous cytotoxic T lymphocytes (CTL). The MAGE genes are expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on their expression in hepatocellular carcinoma (HCC). The authors thus studied the expression of the MAGE gene family in human HCC and discuss the possibility of specific immunotherapy using MAGE peptides. METHODS: Tumor tissue samples of HCC and paired nontumor tissues of the liver were obtained from 22 HCC patients. Total RNA was extracted and cDNA was synthesized. Polymerase chain reaction amplification using each MAGE gene specific primer was then performed to detect the expression of each MAGE gene. Immunoblotting and immunohistochemical analysis were performed to confirm the expression of MAGE-3 gene product in HCC. RESULTS: The expression rate of each MAGE gene was as follows: MAGE-1 and -3 were expressed in approximately 68% of the tumors; MAGE-8 was expressed in 46%; and MAGE-2, -6, -10, -11, and -12 were expressed in approximately 30%. Nineteen (86%) of 22 tumors expressed at least 1 MAGE gene. On the other hand, no expression was detected in the noncarcinomatous liver tissue specimens. Actual expression of the gene product of MAGE-3 was detected in 50% of tumors. Clinicopathologic data on the MAGE positive and negative cases were compared. Significant differences were observed between MAGE expression status and a few clinicopathologic factors; however, further investigation is required to elucidate these correlations completely. CONCLUSIONS: These findings demonstrated that MAGE gene expression is frequent in HCC, thus suggesting that HCC patients may be good candidates for specific immunotherapy using MAGE peptides.

Aged↗
PubMed1999

No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach.

BACKGROUND: Low resectability rates and significant morbidity and mortality rates often make surgery for hepatocellular carcinomas (HCCs) unfeasible. HYPOTHESIS: Our policy for surgical treatment of cirrhotic and noncirrhotic patients with HCC is adequate and safe. DESIGN: Prospective validation cohort study. SETTING: University hospital. PATIENTS: One hundred seven consecutive patients with HCCs. Associated cirrhosis was present in 64 (59.8%), and only 7 (6.5%) had normal livers. INTERVENTIONS: The presence of ascites, serum bilirubin level, and indocyanine green retention rate at 15 minutes were considered when selecting patients for surgery. Preoperative recovery of liver function was achieved with portal venous branch embolization, liver volumetry, bed rest, and control of serum aminotransferase levels. The surgical techniques mainly involved bloodless dissection using intraoperative ultrasonography and intermittent warm ischemia. The main perioperative care regimen was fresh frozen plasma infusion and strict limitation of blood transfusion. MAIN OUTCOME MEASURES: The 30-day postoperative mortality and morbidity rates. RESULTS: All the patients underwent surgery (37 major resections, 45 segmentectomies, and 25 limited resections), with no 30-day postoperative mortality, overall morbidity of 26.2%, and no major complications. Multiple logistic regression analysis revealed that only the type of operation was associated with a significantly higher morbidity risk (P = .05). CONCLUSION: With high resectability, low morbidity, and no mortality, our policy represents a solution to the drawbacks of surgical resection for treatment of HCCs, especially in patients with associated liver cirrhosis.

Adolescent↗
PubMed1999

Steatosis and intrahepatic hepatitis C virus in chronic hepatitis.

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0. 013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C.

Aged↗
PubMed1999

Preoperative portal vein embolization: an audit of 84 patients.

Preoperative portal vein embolization (PVE) was performed in 84 patients before extensive liver resection for various diseases. By the criteria of liver volumetric determination, some patients were candidates for PVE, whereas others were not, even though the same surgical procedure, such as extended right lobectomy (ERL), was scheduled. PVE using gelatin sponge powder induced hypertrophy in the nonembolized lobe (0%-171%; median, 30%) and proportional atrophy in the embolized lobe in 2 weeks without eliciting any major inflammatory or necrotic reaction, as evidenced histologically and by the minimal elevations in the serum aspartate transaminase (AST) and alanine transaminase (ALT) values. Alterations in the total bilirubin level and prothrombin time were also insignificant and transient, indicating that hepatocyte functions were not impaired by PVE. Not all patients who undergo PVE proceed with the scheduled hepatic resection procedure, so it is a great advantage that gelatin sponge causes minimal damage compared with other embolizing materials such as cyanoacrylate and absolute ethanol, which have been reported to induce an inflammatory reaction or histological alteration. Our multiple regression analysis showed that three factors, diabetes mellitus, a high total bilirubin level at the time of PVE, and being male, each reduced the extent of hypertrophy in the nonembolized lobe (r2 =.30). By contrast, cholestasis appeared to accelerate the process of atrophy in the embolized lobe (r2 =.16). In conclusion, PVE by gelatin sponge powder is a safe and effective preoperative maneuver that induces hypertrophy of the section of the liver that will remain after partial hepatectomy.

Adult↗
PubMed1999

Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy.

Fine-needle biopsy (FNB) is associated with problems, such as tumor seeding, which are probably underestimated. The aim of this study was to validate prospectively the accuracy of our diagnostic work-up without FNB, for defining indications for surgery in a cohort of patients with focal liver lesions (FLLs). Between January 1997 and December 1998, 160 consecutive patients carrying 225 FLLs admitted to our department were evaluated prospectively. Preoperative diagnoses were established by means of clinical histories, serum tumor marker levels, ultrasonography, and spiral computed tomography (CT). Angiography, magnetic resonance imaging (MRI), and Lipiodol-CT were performed when it was considered necessary to plan the surgical strategy. All the patients underwent surgery and results of pathological examinations were obtained for all of them. The preoperative diagnoses of 221 of the 225 lesions (98.2%) were confirmed, and the indications for liver resection in 156 of the 160 patients (97.5%) were correct. The respective accuracy, sensitivity, specificity, and positive and negative predictive values were 99.6%, 100%, 98.9%, 99.3%, and 100% for diagnosis of hepatocellular carcinoma (HCC); 99.1%, 100%, 98.8%, 96.9%, and 100% for metastases; 99.6%, 100%, 99.5%, 91%, and 100% for cholangiocellular carcinomas (CCCs); all 100% for mixed HCC-CCCs; and 98.7%, 57.1%, 100%, 100%, and 98.6% for benign tumors. In view of these results, the fact that the real risks of FNB have yet to be established and the possibility that tumor seeding has a major impact on patient prognosis, the use of FNB should be drastically limited.

Angiography↗
PubMed1999

Decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma.

This study was undertaken to identify potential abnormalities of p27(Kip1) and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27(Kip1) and cyclin D1 levels for patients with this disease. Decreased p27(Kip1) expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27(Kip1) and cyclin D1 overexpression were associated with relapse (P =.0005 for p27(Kip1) and P =.0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27(Kip1) and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27(Kip1), P =.0419 and P =.002 for overall and disease-free survival; for cyclin D1, P =.0392 and P =.0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27(Kip1) and cyclin D1 overexpression as independent markers predicting death from relapse (P =.0371, risk ratio: 3.891 for p27(Kip1); P =.0429, risk ratio: 8.31 for cyclin D1). Decreased p27(Kip1) was associated with cyclin D1 overexpression (P =.0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27(Kip1) and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27(Kip1) and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma.

Aged↗
PubMed1999

Surgery for descending thoracic aortic anastomotic aneurysms with a temporary external bypass method.

The surgical treatment of descending thoracic aortic anastomotic aneurysms is technically challenging. The purpose of this study was to evaluate the use of a temporary external bypass method as an intraoperative measure in the surgical treatment of anastomotic aneurysms of the descending thoracic aorta. An analysis of five consecutive patients who had undergone surgery for a collective seven descending thoracic aortic anastomotic aneurysms in our university hospital over a period of 14 years was conducted. A temporary bypass technique was used as an intraoperative measure in all the operations, four of which were performed with a right axillary to left external iliac artery bypass, while other sites were used in the remaining three. Systemic heparinization was able to be avoided in six operations and was markedly reduced in the remaining one. Although the major postoperative complication was coagulated hemothorax after six procedures, all patients recovered well and are still alive after a mean follow-up period of 8.2+/-1.5 (SEM) years. The results of this analysis led us to conclude that our temporary bypass method for treating descending thoracic aortic anastomotic aneurysm prevented the risks of anticoagulant administration for circulatory support, which contributed to the success of the operation. This method can be used as adjunct treatment for anastomotic aneurysms in the descending thoracic aorta.

Adult↗