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Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 163 records · Page 9Linked to original sources
PubMed1999

[A case report of hepatocellular carcinoma with hepatic and portal venous tumor thrombus and multiple intrahepatic metastasis who survived over 1 year after the operation with combined locoregional chemotherapy].

Hepatocellular carcinoma (HCC) with vascular invasion and/or intrahepatic metastasis (IM) has a poor prognosis, so advanced HCC may be considered as a contraindication for hepatectomy. We experienced a case of HCC with hepatic venous and portal venous tumor thrombus and multiple IM who survived over 1 year after the operation with combined locoregional chemotherapy. (Case): A 67-year-old male patient was diagnosed with HCC with extracapsular invasion after transarterial embolization (TAE). CT scan revealed the HCC had a right portal venous tumor thrombus and multiple IM. Posterior lobectomy and thrombectomy of hepatic venous and portal venous tumor thrombus and placement of portal venous catheter ware performed. From the first day after operation the patient received continuous intravenous and intraportal 5-FU for 3 weeks. At the first month after operation, TAE and PEIT were given against residual IM. After discharge the patient received hepatic arterial infusion chemotherapy (MTX/CDDP/5-FU/Leucovorin). Fourteen months after operation, the patient is surviving in good physical condition.

Aged↗
PubMed1999

[A case report: effective trans-arterial neoadjuvant chemotherapy with docetaxel for a local advanced breast cancer patient].

Recently, there have been some reports about the effectiveness of docetaxel for breast cancer patients who had polychemotherapy previously in vein. We report here a case of a 47-year-old woman, who had been diagnosed as local advanced breast cancer. She was given trans-arterial chemotherapy with docetaxel after four series of CEF (cyclophosphamide, epirubicin, fluorouracil) therapy resulted in PD (progressive disease). Local disease was successfully controlled, and she could undergo standard radical mastectomy.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Molecular mechanism involved in increased expression of sialyl Lewis antigens in ductal carcinoma of the pancreas.

Increased expression of sialyl Lewis antigens, sLe(a) and sLe(x), is frequent during malignant transformation and tumor progression of gastrointestinal cancers and it is assumed to be correlated with the increased metastatic potential of tumor cells and, consequently, with poor patient survival. To determine the influence of the increased expression of these antigens in disease progression of ductal carcinoma of the pancreas, immunohistochemical expressions of sLe(x) and sLe(a) in 51 ductal carcinomas of the pancreas were examined. We also examined the expression of glycosyltransferase genes, which are involved in the synthetic pathways of these antigens to understand the molecular mechanism involved in the increased expression of these antigens. Of the 51 primary ductal carcinomas of the pancreas, 40 (78.4%) were sLe(a)-positive and 11 (21.6%) were sLe(a)-negative; 16 (31.4%) were sLe(x)-positive and 35 (68.6%) were sLe(x)-negative. Although there were no significant differences in any examined clinicopathological factors such as age, sex, histological type, tumor size, presence of lymph node metastasis, or presence of vessel invasion between the positive and negative groups with both the sLe(a) and sLe(x) antigens, patient survival tended to be worse in the antigens-positive group than in the antigens-negative group. Increased expression, however, was not dependent on the increased expression of a single glycosyltransferase gene examined among five such genes, which are postulated to be responsible for the synthesis of the sLe(a) and sLe(x) epitopes in the glycosylation pathway. Furthermore, the increased expression of these antigens was not closely associated with mutations status of the K-ras or p53 genes. These findings suggested that increased expression of sialyl Lewis antigens are involved in pancreatic tumorigenesis and that the accumulation of genetic alterations or epigenetic changes is responsible for the molecular mechanisms of increased expression of the sLe(a) and sLe(x) antigens in ductal carcinomas of pancreas.

Adenocarcinoma↗
PubMed1999

Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma.

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), but little is known about the prognostic value of COX-2 in HCC or its associated nontumor liver tissue. We examined the expression of COX-2 protein by immunohistochemistry in 53 patients with HCCs whose corresponding nontumor tissues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrhosis (n = 32). Samples of nine histologically normal livers and eight precancerous dysplasias were also analyzed. The level of COX-2 increased from normal liver to chronic hepatitis to cirrhosis. The majority of cirrhotic livers (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%). In HCC, 17% of samples displayed a high COX-2 expression, and 37% of samples expressed COX-2 at a moderate level. Concordant results were obtained with reverse transcription-PCR and Western blot analyses. Clinicopathological survey indicated a significant correlation between COX-2 expression and differentiated carcinoma (P = 0.019). Although there was no correlation between COX-2 expression in HCC and prognosis, a striking difference was found between COX-2 expression in nontumor tissue and shorter disease-free survival (P = 0.0132). Moreover, high COX-2 expression in nontumor tissue was significantly correlated with the presence of active inflammation (P < 0.0001). The present findings suggest that COX-2 expression in nontumor tissue may play a positive role in relapse of HCC after surgery.

Blotting, Western↗
PubMed1999

Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system.

We applied a differential display method to screen mRNAs isolated from a newly established cell line that carried a wild-type p53 transgene under control of the lactose operon. To investigate the p53 signaling pathway, we looked for genes whose expression was significantly induced or suppressed by induction of wild-type p53 protein, and identified seven. DNA sequence analyses revealed that the two genes that were upregulated encoded isozyme 6 of aldehyde dehydrogenase (ALDH6) and subunit I of cytochrome c oxidase (COI). The five genes that were downregulated encoded protein-tyrosine kinase (Syk), high mobility group chromosomal protein 17 (HMG-17), transferrin receptor, human alpha-tubulin, and sds22-like protein. The results indicated that genes related to cell cycle regulation, cell respiration, and cytoskeletal structure are involved in the process of growth arrest induced by wild-type p53.

Cell Cycle↗
PubMed1998

Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene.

The human pancreatic secretory trypsin inhibitor (PSTI) genes introduced into mice are specifically expressed in pancreas. The 1.0 kilobase pairs of PSTI 5'-flanking sequence directed preferential expression of a linked reporter chloramphenicol acetyltransferase, which was active in a PSTI-expressing pancreatic cell line (AR42j) but not in a PSTI-nonexpressing fibroblast cell line (XC). Two positively acting elements were found, Region I (-161/-116) and Region II (-103/-74), as defined by transfection and binding assays with AR42j cells. Region II is sufficient for the pancreas-specific expression, but the presence of both Regions I and II is needed for the maximum activity. Sequence studies also revealed that these two elements differ from the previously identified recognition sequence for pancreas transcription factor 1 (PTF1). When the same set of experiments was done with XC cells, one negatively acting element was identified, Region IV (-154/-137). Interestingly, Regions I and IV share a core sequence (-149/-139), CAATCAATAAC. These results suggest that this novel element regulates the human PSTI gene expression positively in pancreatic cells but negatively in nonpancreatic cells.

Animals↗
PubMed1998

Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin.

We isolated a novel gene, APCL, that showed significant homology to the adenomatous polyposis coli (APC) tumor suppressor gene. This novel gene, located on chromosome 19p13.3, encodes a protein of 2303 amino acids that is expressed specifically in the brain. The predicted protein of APCL contains five copies of a 20-amino-acid motif (FXVEXTPXCFSRXSSLSSLS). Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. A reporter-gene assay revealed that APCL could also regulate interaction of beta-catenin with T cell-specific transcription factor, although less actively than APC. These results suggest that the APCL protein may be involved in the Wnt/Wingless signal pathway, and the identification of a novel relative of APC may provide new insights into the function of APC.

Amino Acid Sequence↗
PubMed1998

Association between genetic polymorphisms of glutathione S-transferase P1 and N-acetyltransferase 2 and susceptibility to squamous-cell carcinoma of the esophagus.

We examined the effect of genetic polymorphisms of phase-II enzymes, glutathione S-transferase P1 (GSTP1) and N-acetyltransferase2 (NAT2) on susceptibility to esophageal squamous-cell carcinoma To determine the genotypes of the 2 polymorphisms, PCR-based analysis was performed on samples from 66 Japanese patients who had been histologically diagnosed as having esophageal squamous-cell carcinoma, and 164 healthy Japanese controls. The frequency of the AA genotype of GSTP1 was significantly higher in esophageal-cancer patients than in the controls according to logistic-regression analysis (92% of the patients and 68% of the controls; odds ratio (OR), 8.0; p = 0.0013). Also, more patients had the slow and intermediate acetylator genotypes of NAT2 than the controls (15% and 38% vs. 10% and 32% respectively; OR of the slow acetylator genotype, 4.2; p = 0.032; OR of the slow plus intermediate acetylator genotypes, 2.9; p = 0.015). Polymorphisms of GSTP1 and NAT2 may serve as genetic biomarkers for predicting susceptibility to esophageal squamous-cell carcinoma.

Adult↗
PubMed1998

Shear stress down-regulates gene transcription and production of adrenomedullin in human aortic endothelial cells.

Vascular endothelial cells are potent modulators of vascular tone in response to shear stress. Levels of vasoactive peptides such as adrenomedullin (AM), endothelin-1 (ET-1), C-type natriuretic peptide (CNP), and nitric oxide (NO) are affected by fluid shear stress. AM, a potent vasodilator and suppressor of smooth muscle cell proliferation, contains the shear stress responsive element (SSRE) "GAGACC" in its promoter region. To examine the role of AM in the shear stress response, cultured human aortic endothelial cells (HAoECs) were exposed to fluid shear stresses of 12 and 24 dynes/cm2 in a cone-plate shear stress loading apparatus for various time periods, and the levels of AM gene expression and peptide secretion from HAoECs were measured by Northern blotting analysis and radioimmunoassay (RIA), respectively. Both AM gene transcription and AM peptide levels were down-regulated by fluid shear stress in a time- and magnitude-dependent manner. Our results demonstrate that the normal level of arterial shear stress down-regulates AM expression in HAoECs, suggesting that AM participates in the modulation of vascular tone by fluid shear stress.

Adrenomedullin↗
PubMed1998

Diagnostic value of plasma thrombin-antithrombin III complex and D-dimer concentration in patients with varicose veins for exclusion of deep-vein thrombosis.

The aim of this study was to evaluate the usefulness of determining plasma D-dimer (DD) and thrombin-antithrombin III complex (TAT) levels in the diagnostic workup for the screening of deep-venous thrombosis (DVT) among varicose vein patients. One hundred forty consecutive patients being treated for DVT or varicose veins underwent color-flow duplex scanning, and 25 patients had DVT and the remaining 115 had primary varicose veins. When DD and TAT were analyzed statistically in combination, it was determined that the combination of either positive DD (cutoff level 1.0 microg/ml) or positive TAT (cutoff level 3.0 microg/l) had a sensitivity of 100% for DVT with a specificity, positive predictive value, and negative predictive value of 79%, 51%, and 100%, respectively. This study demonstrates plasma levels of DD (less than 1.0 microg/ml) and TAT (less than 3.0 microg/l) in combination to be useful for the exclusion of DVT among patients with varicose veins. Patients with negative hematological data may safely undergo surgical treatment for varicose veins without further evaluation such as duplex scanning or contrast venography.

Antithrombin III↗
PubMed1998

Identification of a novel gene marker specific for epithelial cells by utilizing a 3'-directed cDNA library.

To achieve reliability of molecular diagnosis using reverse transcription-PCR (RT-PCR), we established a unique method to search for a novel gene marker specific for colonic epithelial cells. Of eight candidate genes selected from a 3'-directed cDNA library in colonic mucosa, two genes were expressed in normal mucosa and cancer of the colon but not in either normal lymph node or normal liver tissue. Known sequences of these genes were reported to be located in the 3' noncoding region, and an additional sequence just upstream to gs04094 (one of the candidate genes) was determined. According to the newly identified sequence, we designed a new set of primers so that we could distinguish the DNA fragment amplified in RT-PCR from that in genomic PCR. RT-PCR using these primers demonstrated that gs04094 was expressed in all of 10 primary colon cancers and 4 liver metastases from colon cancer but in none of 5 normal lymph nodes, 10 peripheral blood samples, and 2 normal liver tissues. Sensitivity of this method was so high as to detect gs04094 mRNA in 10(-6) microg of colon cancer RNA per 1 microg of normal lymph node RNA. Thus, our strategy to search for a novel gene marker using 3'-directed cDNA library proved to be highly efficient.

Animals↗
PubMed1998

Plasma heparin-binding EGF-like growth factor levels in patients after partial hepatectomy as determined with an enzyme-linked immunosorbent assay.

We recently showed that heparin-binding EGF-like growth factor (HB-EGF) has hepatotrophic effects. In this study, we developed an ELISA system with high specificity and sensitivity for human plasma HB-EGF. In 14 patients who underwent partial hepatectomy, plasma HB-EGF levels were measured serially after surgery. In patients who underwent gross hepatectomy (lobectomy and segmentectomy), plasma HB-EGF levels increased, reaching maximal levels approximately 5 to 7 days after surgery. In patients who underwent minor hepatectomy (subsegmentectomy), plasma HB-EGF levels did not increase. Maximal plasma HB-EGF levels were significantly higher in patients who had a percent increased volume of the remaining liver (%ILV) above 20% than those who had a %ILV below 20% (32.4 +/- 19.6 pg/ml vs 7.4 +/- 2.7, P < 0.05). The plasma HB-EGF values did not correlate with WBC counts, C-reactive protein, or alanine aminotransferase. Plasma HB-EGF may be a marker for liver regeneration after hepatectomy in humans.

Aged↗
PubMed1998

Direct antigen presentation through binding of donor intercellular adhesion molecule-1 to recipient lymphocyte function-associated antigen-1 molecules in xenograft rejection.

Cellular interactions that lead to graft rejection were examined in a rat-to-mouse xenogeneic combination using species-specific monoclonal antibodies (mAbs) against donor and recipient intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) molecules, respectively. Although both mAbs displayed moderate blocking activity in an in vitro mixed lymphocyte response assay, strong suppression was observed when anti-donor (rat) ICAM-1 mAb was combined with anti-recipient (mouse) LFA-1 mAb. Likewise, significant prolongation of islet xenograft survival was observed with these mAbs. Thus, 0.05 mg of anti-mouse LFA-1 mAb and anti-rat ICAM-1 mAb given on days 0 and 1 produced significant prolongation of graft survival over the control (51+/-20 days vs. 10+/-3 days, P<0.0001), but not when anti-mouse ICAM-1 mAb was combined with anti-mouse LFA-1 mAb (13+/-3 days). In this species combination, mouse T cells were able to proliferate in the presence of rat antigen-presenting cells (APCs) in a cell number-dependent manner, but not in the presence of mouse APCs. The binding assay showed that LFA-1 molecules on mouse T cells can bind immobilized rat ICAM-1 molecules. These results suggest that rat ICAM-1 molecules on APCs can interact with mouse LFA-1 molecules on T cells across a species barrier and that this binding generates the consequent immune responses leading to rejection. mAb treatment against these adhesion molecules of recipient as well as donor is crucial for preventing rejection in a xenogeneic transplantation model.

Animals↗
PubMed1998

Three novel missense mutations in unrelated Japanese patients with type I and type II protein S deficiency and venous thrombosis.

A molecular analysis of protein S deficiency in three unrelated Japanese patients was performed. An approximately 50% reduction in both functional and immunologic levels of protein S was detected in the plasmas from two unrelated patients, designated protein S Osaka 1 and protein S Osaka 2. An approximately 50% reduction in the functional level, but a normal immunologic level of protein S, was detected in plasma from a third patient, designated protein S Osaka 3. All of the exons and exon/intron junctions of the protein S gene were studied using a strategy combining polymerase chain reaction amplification and rapid non-radioactive single-strand conformational polymorphism analysis. We identified a G-to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation resulted in the substitution of Gly for Ser at position 295 in the sex hormone-binding globulin-like region. In protein S Osaka 2, a G-to-C change at the position of the 3' end of exon III was identified, leading to the amino acid substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3, an A-to-G change in exon II was identified, leading to the substitution of Lys9 by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu mutation causes type II deficiency.

Adult↗
PubMed1998

PyNPase expression in human colon cancer.

Although colorectal cancer tissue is rich in pyrimidine nucleoside phosphorylase (PyNPase), there is no consensus as to whether cancer cells or stromal cells predominately express PyNPase. We micro-dissected OCT compound embedded frozen tissue sections into epithelial and stromal components and then analyzed the extracted samples separately. The PyNPase expression level was higher in stromal cells than in cancer cells and the difference increased with inflammation induced by the immunostimulator OK432. These results suggest that stromal cells are the major PyNPase source in colorectal cancer.

Adult↗
PubMed1998

Determination of a safe vascular clamping method for liver surgery: evaluation by measuring activation of calpain mu.

OBJECTIVE: To determine the safest method of hepatic vascular clamping associated with the least ischemia-reperfusion injury of the liver during liver surgery. SETTING: University laboratories. SUBJECTS: Sixty-five adult male Wistar rats. METHODS: The hilar area of the left lateral and median lobes of rat liver was clamped for 10 minutes (group 1), 15 minutes (group 2), or 20 minutes (group 3) followed by 5 minutes of reperfusion. The procedure was repeated for a total period of ischemia of 60 minutes in each group. Control rats underwent laparotomy without vascular clamping. In addition to histological examination, we determined calpain mu activity, a marker of liver injury, by Western blotting using specific antibodies against the intermediate (activated) and proactivated forms of calpain mu. Measurements were performed at the end of ischemia and after 2 hours of reperfusion. We also determined the degradation of talin, an intracellular substrate of calpain mu, by Western blotting. RESULTS: The level of adenosine triphosphate and energy charge at 2 hours after reperfusion did not change after ischemia-reperfusion irrespective of the duration of ischemic cycle. After 60 minutes of intermittent ischemia followed by 2 hours of reperfusion, cell membrane bleb formation, calpain mu activation, and talin degradation were detected in groups 2 and 3 but not in group 1. CONCLUSION: The safest method of hepatic vascular clamping that produces a minimum or no ischemia-reperfusion injury is 60 minutes of 6 cycles of 10-minute vascular clamping interrupted by 5 minutes of reperfusion.

Animals↗
PubMed1998

Allelic imbalance of insulin-like growth factor II gene expression in cancerous and precancerous lesions of the liver.

Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression is often seen in hepatocellular carcinoma (HCC). To investigate the role of allelic imbalance in hepatocarcinogenesis, we have studied allelic expression status of the IGF II gene in dysplastic nodules, which are precancerous lesions of HCC, as well as in HCCs of different histological grade, and the influence of the allelic imbalance on IGF II gene expression has also been examined. Allelic imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well-differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene expression level, which was studied by a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the dysplastic nodules than the control livers, but a significant increase in the IGF II gene expression was not observed in well- and moderately differentiated HCCs as compared with the control livers. These results demonstrate that the allelic imbalance of the IGF II gene expression is seen in the early stage (precancerous lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an increased expression of the IGF II gene in the precancerous lesions might suggest a possible involvement of an IGF II autocrine loop in the pathogenesis of these lesions.

Alleles↗