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Biomedical subjects

Y Kanai

Publications and source records attributed to Y Kanai.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Evaluation of cerebral metabolism by multi-voxel proton magnetic resonance spectroscopy imaging in chronic unilateral internal carotid artery occlusion].

Proton magnetic resonance spectroscopy(1H-MRS) has less been used to analyze cerebral metabolism in ischemic lesions compared to single photon emission computed tomography or positron emission computed tomography. Recent advances in magnetic resonance imaging apparatus and the related software have made possible obtaining multi-voxel 1H-MRS in a single study. We examined multi-voxel 1H-MRS in patients with unilateral internal carotid artery(ICA) occlusion to study the relationship between cerebral metabolism and cerebral blood flow. Fifteen patients(male 11; female 4, 47-76; average 67.1 year-old) with chronic unilateral ICA occlusion and without any marked infarction were studied. 1H-MRS was obtained using a 1.5 T Siemens Magnetom Vision scanner. Multi-voxel spectra were recorded using a SE-2 D-CSI sequence(TR/TE = 1500/135 ms). The volume of interest was 90 x 90 x 20 mm3, placed axially above the lateral ventricle. The single voxel size was 10 x 10 x 20 mm3. N-acetyl aspartate/creatine ratios(NAA/Cr) were calculated on each voxel and were averaged in view of the cortex and the white matter. The regional cerebral blood flow(CBF) was measured by Xenon-CT method. Eight patients were also examined by acetazolamide challenge to evaluate the cerebrovascular reserve capacity. NAA/Cr ratios in normal subjects were 1.905 +/- 0.090(mean +/- standard deviation) in the cortex and 2.183 +/- 0.258 in the white matter in 40's(n = 6), 2.046 +/- 0.166 in the cortex and 2.039 +/- 0.288 in the white matter in 60's(n = 5). The study revealed 7 patients with normal NAA/Cr ratio and CBF, 5 with reduced NAA/Cr ratio and normal CBF, and 3 with reduced NAA/Cr ratio and CBF in the affected cortex. A low correlation coefficient of 0.46 was noted between NAA/Cr ratio and the cerebrovascular reserve capacity calculated by acetazolamide challenge in the affected cortex. In the range of less than +10%(lower limit) in percentile change of regional CBF after acetazolamide injection, NAA/Cr ratio was distributed between 1.600 and 2.044, which were normal or slightly under the lower limit(mean-2 x standard deviation). Multi-voxel 1H-MRS is useful for the evaluation of cerebral metabolism, because it enables to quantify different chemicals in many fields at one time and to compare its distribution with regional CBF. In patients with unilateral ICA occlusion, NAA/Cr ratio of the affected cortex varies depending on the collateral circulation and the contralateral ICA lesions. The Extracranial-Intracranial Bypass should be considered if the case with unilateral ICA occlusion reveals reduced CBF and normal or slightly decreased NAA/Cr ratio in the affected cortex.

Aged↗
PubMed2000

Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs.

Organic anion transporter 1 (OAT1) is a p-aminohippurate/dicarboxylate exchanger that plays a primary role in the tubular secretion of endogenous and exogenous organic anions. OAT1 is located in the basolateral membrane of the proximal tubular cells and mediates the uptake of various organic anions from the peritubular fluid. In this study, we investigated the transport of antiviral nucleoside analogs via rat OAT1 (rOAT1) using a heterologous expression system in Xenopus laevis oocytes. Oocytes injected with rOAT1 cRNA showed significantly higher uptake of zidovudine (AZT) and acyclovir (ACV) than control oocytes. rOAT1-mediated uptake of AZT and ACV was probenecid-sensitive and increased by the outwardly directed gradient of glutarate. The affinity of rOAT1 for AZT and ACV was determined to be 68 and 242 microM, respectively. Five other antiviral agents that we studied (zalcitabine, didanosine, lamivudine, stavudine, and trifluridine) were also shown to be transported by rOAT1, whereas foscarnet, a phosphate analog, was not. The aforementioned nucleoside analogs lack a typical anionic group and are not very hydrophobic. This study demonstrates extension of the substrate spectrum of rOAT1 and provides a molecular basis for the pharmacokinetics of antiviral nucleoside analogs.

Acyclovir↗
PubMed1999

Reduced mRNA expression of the DNA demethylase, MBD2, in human colorectal and stomach cancers.

A study was performed to evaluate the significance of aberrations of the newly identified DNA demethylase, MBD2, in human carcinogenesis. Levels of expression of DNA demethylase mRNA were examined by reverse transcription followed by real-time quantitative detection of the PCR products in 32 samples of colorectal cancer tissue, 24 stomach cancers, and the corresponding noncancerous mucosae. DNA demethylase mRNA levels normalized with glyceraldehydephosphate dehydrogenase (GAPDH) mRNA were reduced in 31 (97%) of the 32 colorectal cancers and in 22 (92%) of the 24 stomach cancers when compared with the levels in the corresponding noncancerous mucosae. The average levels of DNA demethylase mRNA expression normalized with GAPDH mRNA in each of the colorectal (0.81 +/- 0.55) and stomach (2.88 +/- 0.23) cancers were significantly lower than in the noncancerous mucosae (1.90 +/- 0.16 and 5.11 +/- 0.34, respectively, p < 0.0001). There was no significant association between the DNA demethylase mRNA level and malignant potential in both colorectal and stomach cancers. These data suggest that reduced expression of DNA demethylase may play a role at a certain step of multistage carcinogenesis. Reduction of DNA demethylase mRNA expression may be, if anything, one of the early events of carcinogenesis, but may not participate in the malignant progression of tumors.

Colorectal Neoplasms↗
PubMed1999

Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein.

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino acid transporter). The transporter designated BAT1 (b(0, +)-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y(+)L, and system x(-)C, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na(+)-independent transport of cystine as well as basic and neutral amino acids with the properties of system b(0,+). The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

ATP-Binding Cassette Transporters↗
PubMed1999

Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.

We have isolated a cDNA from rat small intestine that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property. The encoded protein, designated L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol. Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1 (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J. Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+ or Cl- and is inhibited by a system L-specific inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is a second isoform of the system L transporter. Compared with LAT-1, which prefers large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits remarkably broad substrate selectivity. It transports all of the L-isomers of neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2 mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, which mediates amino acid exchange. LAT-2-mediated transport is increased by lowering the pH level, with peak activity at pH 6.25, because of the decrease in the Km value without changing the Vmax value. Because of these functional properties and a high level of expression of LAT-2 in the small intestine, kidney, placenta, and brain, it is suggested that the heterodimeric complex of LAT-2 and 4F2 heavy chain is involved in the trans-cellular transport of neutral amino acids in epithelia and blood-tissue barriers.

Amino Acid Sequence↗
PubMed1999

Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain.

A cDNA encoding the new member of the multispecific organic anion transporter family, OAT3, was isolated by the reverse transcription-polymerase chain reaction cloning method. Degenerate primers were designed based on the sequences conserved among OAT1, OAT2, and organic cation transporter 1 (OCT1), and reverse transcription-polymerase chain reaction was performed using rat brain poly(A)+ RNA. The 536-amino acid protein sequence encoded by OAT3 showed 49, 39, and 36% identity to those of OAT1, OAT2, and OCT1, respectively. Northern blot analysis revealed that rat OAT3 mRNA is expressed in the liver, brain, kidney, and eye. When expressed in Xenopus laevis oocytes, OAT3 mediated the uptake of organic anions, such as p-aminohippurate (Km = 65 microM), ochratoxin A (Km = 0.74 microM), and estrone sulfate (Km = 2.3 microM) and a cationic compound, cimetidine. OAT3-mediated uptake of [3H]estrone sulfate was sodium-independent. para-Aminohippuric acid, estrone sulfate or ochratoxin A did not show any trans-stimulatory effect on either influx or efflux of [3H]estrone sulfate via OAT3. Organic anions such as sulfobromophthalein, probenecid, indocyanine green, bumetanide, piroxicam, furosemide, azidodeoxythymidine, 4, 4'-diisothiocyanostilbene-3,3'-disulfonic acid, and benzylpenicillin inhibited OAT3-mediated estrone sulfate uptake, while ouabain and digoxin did not. Organic cations such as tetraethylammonium, guanidine, verapamil, and quinidine did not interact with OAT3. Acidic metabolites of neurotransmitters derived from dopamine, epinephrine, norepinephrine, and serotonin inhibited the uptake of estrone sulfate via OAT3. These results suggest an important role of OAT3 in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain.

Amino Acid Sequence↗
PubMed1999

Bilateral Nonpalpable Breast Carcinomas in a Patient with BRCA2 Germ Line Mutation and Past History of Osteosarcoma.

A 34-year-old premenopausal woman developed asynchronous bilateral nonpalpable breast cancers at the age of 32 and 34 years. She had undergone amputation of her left lower leg because of osteosarcoma at the age of 16. Her mother had beendiagnosed with breast cancer at the age of 45. The clinicopathological features of the two breast tumors in this patient closely resembled each other; both were nonpalpable, and detectable only by helical CT scan. Histologically, they consisted mainly of an intraductal component with small grade 3 invasive foci. In addition, both tumors estrogen receptor (ER) status was negative, and both were positive for c-erbB-2 protein on immunohistochemical staining. A missense germ line mutation of BRCA2 (exon 25 codon 3118; Met3118Thr) was detected in this patient. These data may provide useful information on the carcinogenesis and biological behavior of breast cancers which develop in patients with BRCA2 germ line mutations.

Journal Article↗
PubMed1999

Assessment of DNA damage in individual hamster embryos by comet assay.

DNA damage induced by either light exposure or oxidative stress likely contributes to the compromised development in vitro of cultured preimplantation embryos. Using the comet assay, which entails microgel electrophoresis that can readily detect single-strand breaks in DNA, a significant increase in DNA damage was detected in individual one-cell hamster embryos that were treated with either ultraviolet light or hydrogen peroxide. In addition, an increase in DNA damage also was observed following exposure of one-cell embryos to visible light. When the embryos were placed in drops of culture medium that were covered with mineral oil and the dishes then placed in a portable incubator containing 5% CO(2) in air at 37 degrees C, visible and UV light irradiation for 30 min still induced extensive DNA damage when compared to control embryos that were kept in the dark. In contrast, infrared irradiation did not induce an increase in DNA damage. DNA damage also was measured in individual one- and two-cell stage embryos developed in vivo or in vitro. The extent of DNA damage in the cultured embryos was significantly greater than in embryos that developed in vivo. These results highlight the usefulness of the comet assay to assess DNA damage in individual preimplantation embryos and how the assay can be used to monitor culture conditions in vitro.

Animals↗
PubMed1999

DNA hypermethylation at the D17S5 locus and reduced HIC-1 mRNA expression are associated with hepatocarcinogenesis.

To examine the significance of aberrant DNA methylation in hepatocarcinogenesis, the DNA methylation status at the D17S5 locus and mRNA expression of a candidate tumor suppressor gene, HIC-1 (hypermethylated-in-cancer), which was identified at the D17S5 locus, in primary hepatocellular carcinomas (HCCs) and their corresponding noncancerous liver tissues were assessed. DNA hypermethylation at the D17S5 locus was detected in 44% of the noncancerous liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, but was not observed in noncancerous liver tissues showing no remarkable histological findings. The incidence of DNA hypermethylation at this locus was significantly higher in HCCs (90%) than noncancerous liver tissues (P <.001). Loss of heterozygosity at the D17S5 locus, which was preceded by DNA hypermethylation at the same locus, was detected in 54% of HCCs. The HIC-1 mRNA expression level of noncancerous liver tissues showing chronic hepatitis or cirrhosis was significantly lower than that of noncancerous liver tissues showing no remarkable histological findings (P <.01), and that of HCCs was even lower than that of noncancerous liver tissues (P <.05). Poorly differentiated HCCs showed lower expression levels than well- to moderately differentiated HCCs. Mutation of the p53 gene may be involved in HIC-1 inactivation. Moreover, wild-type p53 did not overcome DNA hypermethylation at the D17S5 locus to activate HIC-1 in HCCs. These data suggest that aberrant DNA methylation at this locus and reduced HIC-1 mRNA expression participate in hepatocarcinogenesis during both early developmental stages and malignant progression of HCCs.

Adult↗
PubMed1999

Microsatellite instability associated with hepatocarcinogenesis.

BACKGROUND/AIMS: The biological and clinicopathological significance of microsatellite instability in hepatocellular carcinoma still remains to be determined. The aim of this study was to assess the role of microsatellite instability in hepatocarcinogenesis. METHODS: Genomic DNA extracted from 38 fresh samples of hepatocellular carcinoma was amplified by polymerase chain reaction using 29 fluorescence-labeled microsatellite markers and analyzed using a semi-automated laser scanning system. Associations between the incidence of replication error and the clinicopathological features of hepatocellular carcinoma were evaluated. Since reference DNA was extracted from corresponding fresh samples of non-cancerous liver tissue, the incidence of microsatellite instability in non-cancerous liver tissues was not assessed in this study. RESULTS: Four (11%) hepatocellular carcinomas had a replication error in one or two microsatellite markers; they were all poorly differentiated hepatocellular carcinomas. The incidence of replication error correlated significantly with the histological differentiation of the tumor (p<0.05) and with portal vein involvement (p<0.05). All four hepatocellular carcinomas with replication errors showed loss of heterozygosity in one or more of the 29 markers we examined. No replication errors were detected in six markers in the coding regions of the BAX, insulin-like growth factor II receptor, transforming growth factor-beta type II receptor, E2F-4, hMSH3 and hMSH6 genes. CONCLUSIONS: The results of this study indicate that: (1) microsatellite instability is a rare event during hepatocarcinogenesis and may be specifically associated with progression of hepatocellular carcinoma; and (2) frame-shift mutation in the above six genes is not a common mechanism involved in progression of this cancer.

Aged↗
PubMed1999

Nrk: a murine X-linked NIK (Nck-interacting kinase)-related kinase gene expressed in skeletal muscle.

We report the cloning and expression pattern of a novel Ste20-type kinase gene, NIK-related kinase (Nrk), located on the mouse X chromosome. The full-length Nrk cDNA encodes a 1455-amino-acid polypeptide characterized by a N-terminal Ste20-type catalytic domain and a C-terminal regulatory domain characteristic of the group I GCK subfamily. The overall structure of the NRK protein is closely related to that of Nck-interacting kinase (Nik). In situ hybridization revealed that Nrk was predominantly expressed in skeletal muscle during mouse embryogenesis. Nrk gene expression was detected in the myotome at 10.5 dpc and, thereafter, was observed in developing skeletal musculature from 11.5 to 13.5 dpc. However, expression in skeletal muscle was not observed in adults.

Amino Acid Sequence↗
PubMed1999

Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity.

UNLABELLED: Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity. BACKGROUND: Cephaloridine (CER) has been used to elucidate the mechanisms of cephalosporin antibiotic-induced nephrotoxicity. Organic anion transporters have been thought to mediate CER uptake by the proximal tubule. The purpose of this study was to elucidate the possible involvement of organic anion transporter 1 (OAT1) in CER-induced nephrotoxicity. METHODS: A mouse terminal proximal straight tubule (S3) cell line stably expressing rat OAT1 (S3 rOAT1) was established and used in this study. The cellular uptake of [14C]-para-aminohippuric acid (PAH), a prototype organic anion, and that of [14C]-CER were measured. The effects of CER on the viability of the cells and the amount of lipid peroxidation were estimated. RESULTS: S3 rOAT1 expressed a functional organic anion transporter in the cytoplasmic membrane, and exhibited CER uptake activity. CER treatment resulted in a more significant decrease in the viability and a more significant increase in the amount of lipid peroxidation in S3 rOAT1 than in S3 cells transfected with an expression vector lacking the rOAT1 insert. Probenecid, an inhibitor of organic anion transport, and probucol, an antioxidant, significantly suppressed the decrease in viability and increase in the amount of lipid peroxidation in S3 rOAT1 treated with CER. The effects of various cephalosporin antibiotics on the uptake of [14C]PAH were correlated significantly with the effects of these drugs on cell viability. CONCLUSIONS: These results suggest that rOAT1 is, at least in part, responsible for the cellular uptake of CER and therefore CER-induced nephrotoxicity.

Animals↗
PubMed1999

Structural and functional characterization of the mouse Sox9 promoter: implications for campomelic dysplasia.

Mutations in SOX9 cause campomelic dysplasia (CD), a dominant skeletal dysmorphology and XY sex reversal syndrome. The CD phenotype is sensitive to dosage and expression levels of SOX9. Sox9 is expressed during chondrocyte differentiation and is up-regulated in male and down-regulated in female genital ridges during sex differentiation. In order to study the sex- and tissue-specific regulation of Sox9, we have defined the transcription start site and characterized the mouse Sox9 promoter region. The Sox9 proximal promoter shows moderately high nucleotide similarity between mouse and human. Transient transfection experiments using various deletion constructs of the 6.8 kb upstream region of mouse Sox9 fused to a luciferase reporter showed that the interval between 193 and 73 bp from the transcription start site is essential for maximal promoter activity in cell lines and in primary male and female gonadal somatic cells and liver cells isolated from 13.5 d.p.c. mouse embryos. This minimal promoter region was shown by DNase I hypersensitive site assay to be in an 'open' state of chromatin structure in gonads of both sexes, but not in the liver. Promoter activity was higher in testis than in ovary and liver, but deletion of the region from -193 to -73 bp abolished this difference. We conclude that the proximal promoter region is in part responsible for the sex- and tissue-specific expression of the Sox9 gene and that more distal positive and negative elements contribute to its regulation in vivo, consistent with the observation that translocations upstream from SOX9 can result in campomelic dysplasia.

3T3 Cells↗
PubMed1999

Primary low-grade lymphoma of mucosa-associated lymphoid tissue of the urinary bladder: a case report with special reference to the use of ancillary diagnostic studies.

We report a case of primary low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type of the urinary bladder. The patient, a 77-year-old woman, presented with a sense of urinary retention. An intravenous pyelogram and cystoscopy revealed a wide-based submucosal mass measuring 3 cm in the left wall of the urinary bladder. Histological findings of the tissue obtained by transurethral resection (TUR) showed a dense, monomorphic atypical lymphoid (centrocyte-like) infiltrate with reactive lymph follicles in the subepithelial tissue. Monocytoid and plasmacytoid features were readily evident in a population of these cells. Lymphoepithelial lesions involving the urothelium were also noticed in some areas. These features were strongly suggestive of primary low-grade lymphoma of the MALT type. The diagnosis was confirmed by immunohistochemical and flow cytometric studies, both of which showed a clear immunoglobulin restriction to lambda light chain and also by polymerase chain reaction-based assay using a formalin-fixed paraffin-embedded TUR tissue sample, which showed a clonal Ig heavy-chain gene rearrangement. Clinical staging procedures revealed that the tumor was localized in the urinary bladder. The patient has not received chemotherapy and is alive and well with no evidence of recurrence, 3 years after TUR. This case demonstrates that these ancillary tests are worth performing for confirmation of B-cell clonality in TUR tissue samples showing dense B-lymphocytic infiltration.

Aged↗
PubMed1999

Synovial sarcoma, histologically mimicking primitive neuroectodermal tumor/Ewing's sarcoma at distant sites.

We report a case of synovial sarcoma (SS) showing unusual histology at distant sites. A 47-year-old man was aware of a tumor on the sole of his left foot. After preoperative chemotherapy with a diagnosis of SS, wide excision was performed. During postoperative chemotherapy, multiple tumorous lesions developed in the bone (including the whole spine) and both lungs. The patient died 1 year later. Histologically, the excised tumor of the foot showed a biphasic cellular pattern typical of SS, whereas at autopsy the bone and lung lesions were composed only of undifferentiated small round cells with cytoplasmic fibrillar processes. Homer-Wright rosettes were also observed. Immunohistochemically, 80% of the bone and lung tumor cells expressed MIC2 protein homogeneously. To clarify whether the bone and lung round cell tumors were metastatic lesions or second malignancies, especially primary primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES), we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis of tumor type-specific fusion gene transcripts. The SYT/SSX fusion transcript was identified in both the foot and lung lesions, whereas the EWS/FLI1 transcript was not detected in either lesion. Therefore, we concluded that the multiple bone and lung tumors were poorly differentiated metastatic tumors, which arose from the SS of the foot. We also conclude that the identification of chimeric fusion transcripts can be successfully applied to poorly differentiated sarcomas and will help in the differential diagnosis of tumors that cannot be distinguished by conventional morphological examinations. Also, it should be remembered that cytoplasmic staining for MIC2 protein may occur in sarcomas other than PNET/ES.

12E7 Antigen↗
PubMed1999

Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma.

A study was conducted to clarify the contribution of beta-catenin accumulation and mutation of the beta-catenin gene to hepatocarcinogenesis. Beta-catenin accumulation was examined immunohistochemically in 38 paired samples of hepatocellular carcinoma (HCC) and corresponding non-cancerous liver tissue. Gene mutation was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing using intronic primers encompassing exon 3. Neither accumulation nor mutation was detected in non-cancerous liver tissues that showed no remarkable histological features, chronic hepatitis or liver cirrhosis. Accumulation of beta-catenin was seen in the nucleus, cytoplasm or cell membrane in 15 of 38 (39%) HCC samples, and gene mutation was seen in 9 of 38 (24%) HCC samples. Although there was a significant correlation between accumulation and mutation (P<0.01), six HCCs without mutation also showed accumulation. Samples of early HCC showed neither accumulation nor mutation, and accumulation and mutation were each correlated significantly with portal vein tumor involvement (P<0.05). The present results indicate that (1) mutation of exon 3 of the beta-catenin gene can lead to beta-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) beta-catenin accumulation and mutation of the beta-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.

Adult↗