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Takeshi Suda

Publications and source records attributed to Takeshi Suda.

At least 19 recordsLinked to original sources
PubMed2006

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma < or =4 cm.

AIM: To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (< or =4 cm) in terms of long-term outcomes. METHODS: A retrospective analysis of 149 patients with HCC < or =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo. RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into < or =2 cm vs >2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors>2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors < or =2 cm (P=0.017) were independently associated with better survival. CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC < or =4 cm compared with percutaneous ablation. Of the patients with HCC < or =4 cm, those with tumors >2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.

Adult↗
PubMed2006

Involvement of Drosophila Sir2-like genes in the regulation of life span.

In Drosophila melanogaster, the Sir2 gene and four Sir2-like genes have been found to be homologous to yeast SIR2 genes. To examine whether the fly Sir2, CG5216, and two Sir2-like genes, CG5085 and CG6284, affect life span, we suppressed their expression using RNAi. Decreased expression of the Sir2 and Sir2-like genes in all cells caused lethality during development. Suppression of the Sir2 in neurons and ubiquitous silencing of the Sir2-like genes shortened life spans. The effects were severer at 28 degrees C than at 25 degrees C. These results suggest that Sir2-like genes as well as Sir2 are involved in the regulation of life span in Drosophila.

Animals↗
PubMed2006

[Bone metastasis of gastric cancer].

We evaluated 19 patients with bone metastasis after surgery for gastric cancer. In a number of cases, the located in the tumor was U and M region, of macroscopic 3, and the histological type was poorly-differentiated adenocarcinoma with high-grade of lymphatic invasion. The major symptom was lumbago and back pain. The serum AFP level was high in 73.7% of the cases, and LDH was high in 47.7%. The metastatic lesion was predominantly seen in the bone with red pulp such as lumbar and thoracic vertebra and rib. The median survival time was 189 days (range: 24-509) with a poor prognosis. However, newly developed anticancer drugs were very effective for some cases, indicating that such chemotherapy should be tried for cases with bone metastasis.

Adenocarcinoma↗
PubMed2005

[The efficacy of intra-peritoneal chemotherapy for the patients with cytology positive gastric cancer].

In this study, we assessed efficacy of repeated intra-peritoneal chemotherapy with CDDP for patients with cytology positive gastric cancer. The median survival time was 338 days, 1-year survival was 60% and 2-year survival was 45% of the patients. The POCY1 patients with repeated intra-peritoneal chemotherapy yielded a tendency to extend the survival rate than the patients without repeated intra-peritoneal chemotherapy (p = 0.06). But, no differences were found between the survival rate of P1CY1 patients with or without repeated intra-peritoneal chemotherapy. The patients using more than 3 anti-cancer drugs yielded a tendency to have a better prognosis than the patients using 2 or less anti-cancer drugs (p = 0.09). There was a possibility to which the multidiscipline treatment was effective for the POCY1 gastric cancer patients.

Adult↗
PubMed2004

Molecular cloning and characterization of a human multisubstrate specific nucleotide-sugar transporter homologous to Drosophila fringe connection.

Nucleotide-sugar transporters are crucial components in the synthesis of glycoconjugates. We identified a novel human nucleotide-sugar transporter gene, hfrc1, which is homologous to Drosophila melanogaster fringe connection, Caenorhabditis elegans sqv-7, and human UGTrel7. HFRC1 was localized within the Golgi apparatus following its transient expression in HCT116 cells. In human tissues, hfrc1 and UGTrel7 exhibited similar tissue distributions, although hfrc1 transcripts showed a 10 times greater abundance than those of UGTrel7. The heterologous expression of HFRC1 in the yeast revealed the multisubstrate specific transport activity of HFRC1 (for UDP-N-acetylglucosamine (UDP-GlcNAc), UDP-glucose (UDP-Glc), and GDP-mannose (GDP-Man), with apparent K(m) values of 8.0, 2.1, and 0.14 microm, respectively). In the mammalian cells, HFRC1 transported UDP-GlcNAc and UDP-Glc, but not GDP-Man. Overexpression of the hfrc1 gene in HCT116 cells modulated the cell surface heparan sulfate expression status. These results suggest that HFRC1 takes part in the synthesis of heparan sulfate by regulating the level of UDP-GlcNAc, a donor substrate for the heparan sulfate synthases.

Amino Acid Sequence↗
PubMed2004

Liver metastasis 30 years after enucleation of the left eyeball for choroidal melanoma.

Here, we report a case of 70-year-old female with metastatic choroidal melanoma in the liver, which was detected 30 years after enucleation of the left eyeball. At first, two hypovascular tumors (4cm and 1cm in diameter) were detected in the liver as high-density areas on plain computed tomography (CT). They were demonstrated as hyper- and hypo-intensity lesions on T1- and T2-weighted image of magnetic resonance imaging (MRI), respectively, with superparamagnetic iron oxide uptake. During about 2-years follow-up, the larger tumor did not change significantly in size and in the character. However, the smaller one grew up in size and changed its nature to hypervascular and hyper-intensity on T2-weighted image of MRI. These hypervascular tumors increased in number and in size rapidly. The specimens obtained with tumor biopsy revealed epithelioid tumor cells positive for HMB45 immunohistochemical stain with and without brown pigment, and the tumors were diagnosed as melanoma. The patient underwent transcatheter arterial chemoembolization with cisplatin and epirubicin hydrochloride, and subsequent transcatheter arterial infusion chemotherapy with cisplatin, nimustine and dacarbazine. Unfortunately, however, the tumor rapidly progressed and she died. We discuss the imaging of the melanoma metastasized to the liver with the estimation of doubling time (DT) of the tumors.

Journal Article↗
PubMed2004

Increased hTR expression during transition from adenoma to carcinoma is not associated with promoter methylation.

Human telomerase RNA component (hTR) expression, which increases in the majority of cancer cells with an acquisition of telomerase activity, was concomitantly evaluated with methylation status and human telomerase reverse transcriptase (hTERT) expression in colorectal cancers and precursor lesions. hTR and hTERT expressions were detected by in situ hybridization and reverse transcription following polymerase chain reaction, respectively, in 15 colonic adenomas, 19 sporadic colonic cancers at various histological stages, and 3 normal colonic mucosa samples. The methylationstatus of hTR was evaluated by methylation-specific polymerase chain reaction following restriction endonuclease digestion and direct sequencing. hTERT expression was detected in 16 of 19 cancers. hTR expression was detected in all cancers including two cases of intramucosal carcinoma. No hTR signals were detected in the normal epithelium or in the adenomas with severe atypism. CpG dinucleotides in the 5'-untranslated region of hTR were completely unmethylated from -204 to -3 and mosaically methylated from -290 to -272, irrespective of the atypism. These results suggest that hTR expression is increased at the adenoma-to-carcinoma transition stage but is not always associated with hTERT expression. Hypomethylation of the hTR promoter region is not likely to be the main mechanism regulating hTR expression.

Adenocarcinoma↗
PubMed2003

Interferon can block telomere erosion and in rare cases result in hepatocellular carcinoma development with telomeric repeat binding factor 1 overexpression in chronic hepatitis C.

PURPOSE: The purpose of this study was to evaluate whether IFN therapy for chronic hepatitis C could overcome telomere reduction in the liver, a possible risk factor for hepatocellular carcinoma (HCC) development. EXPERIMENTAL DESIGN: Relative telomeric repeat content (RTC) in the liver was measured before and after IFN therapy in 21 chronic hepatitis C cases. Liver samples were obtained at average intervals of 12, 75, and 32 months in eight complete responders (CRs) and one biochemical responder (BR), four CRs in whom HCC developed after an eradication of hepatitis C virus, and eight nonresponders, respectively. Telomeric repeat binding factor 1 (TRF1) was immunostained in specimens from CRs and a BR. RESULTS: Although the average RTC of 0.96 +/- 0.14 (mean +/- SD) significantly decreased to 0.85 +/- 0.12 after IFN therapy in nonresponders (P = 0.023), the value of 0.91 +/- 0.14 before IFN therapy in CRs and a BR increased significantly to 1.0 +/- 0.085 (P = 0.031). TRF1 expression was barely detectable and attenuated after IFN therapy, except in CRs developing HCC, in which frequent staining appeared, and the RTC evidently decreased from 0.97 +/- 0.11 to 0.63 +/- 0.0092 in corresponding noncancerous liver tissues. CONCLUSIONS: It is strongly suggested that successful IFN therapy blocks telomere erosion, except in rare cases in which telomere reduction continues with overexpression of TRF1. Successive RTC evaluation in the liver may distinguish a risky case from a clinically cured one.

Antineoplastic Agents↗
PubMed2003

Sensitive and specific detection of circulating cancer cells in patients with hepatocellular carcinoma; detection of human telomerase reverse transcriptase messenger RNA after immunomagnetic separation.

PURPOSE: We evaluated whether detection of human telomerase reverse transcriptase (hTERT) mRNA after immunomagnetic separation is useful to detect circulating cancer (CC) cells. EXPERIMENTAL DESIGN: Two ml of peripheral blood were collected from 55 cases with hepatocellular carcinoma (HCC), 20 cases with chronic liver diseases devoid of cancer, and 20 healthy volunteers. Then 1500 and 500 micro l were subjected to immunomagnetic separations using Ber-EP4 and anti-CD45 antibodies, harvested and supernatant cells were collected as epithelial and nonleukocyte fractions, respectively. Samples of each fraction were subjected to reverse transcription-PCR detecting beta-actin, interleukin-2 receptor (IL-2r), alpha-fetoprotein, and hTERT mRNAs. The cases were judged to be positive, equivocal, or negative for CC cells when hTERT positivity with IL-2r negativity, hTERT positivity with IL-2r positivity, or hTERT negativity was seen in epithelial and/or nonleukocyte fractions, respectively. RESULTS: The dilution experiments revealed that our system could detect 10(0-1) HeLa cells involved in 2 ml of blood. The Ber-EP4-harvested cells from cases with distant metastasis were positive for immunostaining using Hep Par 1 monoclonal antibody. CC cells were judged to be positive in 29 of 55 (53%) HCC cases. On the contrary, no cases without HCC were determined to be positive. The frequency of positivity was significantly correlated with disease extent of HCC. CONCLUSIONS: These results strongly suggest that detection of hTERT mRNA after immunomagnetic separation is a specific and sensitive tool to detect CC cells and that it would provide useful source for further investigation of cancer metastasis.

Aged↗
PubMed2003

Telomere length variation and maintenance in hepatocarcinogenesis.

BACKGROUND: Despite the recent discovery of interchromosomal telomere length variation, a role for heterogeneity in telomere maintenance has yet to be established. This study investigated the significance of telomere length variation between chromosomes with respect to the association of cancer progression and telomere length regulation. METHODS: Terminal restriction fragment (TRF) was evaluated in 20 surgically resected hepatocellular carcinoma specimens (HCC), corresponding noncancerous liver tissue specimens (NCL), and in 10 liver tissue specimens with chronic liver diseases devoid of cancer (DOC). Average TRF length (TRF-A) was defined as the point of maximum intensity. Shorter and longer TRF lengths (TRF-S and TRF-L) were defined as the length above which 90% of TRF distribution was involved. A ratio, (TRF-L-TRF-S)/TRF-A, was defined as telomere length dispersion. RESULTS: The dispersion was significantly larger in HCC than in NCL specimens (P = 0.012) and in NCL than in DOC (P = 0.048). TRF-A and TRF-S were significantly shorter in HCC than in NCL (P = 0.0026, P = 0.0010). In seven patients in whom HCC recurred within 1 year, TRF-A and TRF-S were significantly shorter than in 10 patients in whom recurrence occurred after 1 year (P = 0.018, P = 0.0097). Telomeric repeat binding factor 1 was up-regulated in HCC with elongated TRF-L, whereas expression of human telomerase reverse transcriptase was greater in HCC with a shorter TRF-S. CONCLUSIONS: These results suggest that telomere length varied through chronic liver diseases by preferentially increasing shorter telomeres, whose length is a good indicator for malignant potential of HCC. Telomere length variation may be a crucial code in telomere maintenance through hepatocarcinogenesis.

Aged↗
PubMed2003

Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter.

Nucleotide sulfate, namely 3'-phosphoadenosine 5'-phosphosulfate (PAPS), is a universal sulfuryl donor for sulfation. Although a specific PAPS transporter is present in Golgi membrane, no study has reported the corresponding gene. We have identified a novel human gene encoding a PAPS transporter, which we have named PAPST1, and the Drosophila melanogaster ortholog, slalom (sll). The amino acid sequence of PAPST1 (432 amino acids) exhibited 48.1% identity with SLL (465 amino acids), and hydropathy analysis predicted the two to be type III transmembrane proteins. The transient expression of PAPST1 in SW480 cells showed a subcellular localization in Golgi membrane. The expression of PAPST1 and SLL in yeast Saccharomyces cerevisiae significantly increased the transport of PAPS into the Golgi membrane fraction. In human tissues, PAPST1 is highly expressed in the placenta and pancreas and present at lower levels in the colon and heart. An RNA interference fly of sll produced with a GAL4-UAS system revealed that the PAPS transporter is essential for viability. It is well known that mutations of some genes related to PAPS synthesis are responsible for human inherited disorders. Our findings provide insights into the significance of PAPS transport and post-translational sulfation.

Amino Acid Sequence↗
PubMed2003

Studies on the correlation among the fucosylation index, concentration of alpha-fetoprotein and des-gamma-carboxy prothrombin as prognostic indicators in hepatocellular carcinoma.

Our previous results showed that the fucosylation index (FI) was considered to be a useful prognostic factor in patients with hepatocellular carcinoma (HCC). On the other hand, serum concentrations of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were regarded as prognostic indicators. However, the relationship among FI, AFP, and DCP as prognostic factors remained unknown. The aim of this study was to elucidate the correlation among these three prognostic factors. One hundred and seventy-six patients with HCC from 1990 to 1998, who showed increment of serum AFP concentrations more than 30ng/ml before treatment, were examined in the present study. FI was determined in these patients by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. FI of AFP was defined as the percentage of the L. culinaris agglutinin (LCA)-reactive species in total AFP (same as L3 fraction). Serum concentrations of DCP were also measured. Enrolled patients with HCC underwent transcatheter arterial embolization, chemoembolization, percutaneous ethanol injection, and/or percutaneous microwave coagulation therapy. The current patients status was the one which was confirmed at the end of March 2001. Analysis by the Cox's proportional hazards model showed that FI, AFP, and DCP were significant prognostic factors. When the tentative demarcation levels of FI, AFP, and DCP were set at 18%, 200ng/ml, and 0.06arbitrary units (AU)/ml, respectively, the following results for the prognostication of patients with HCC were obtained. First, the survival rates in the groups with one out of the three optional markers over the demarcation level were significantly lower than the survival rates of other groups, whose optional one marker was equal to or less than the demarcation level, respectively. Next, the survival rates in the groups in which two out of three optional markers were over the demarcation levels were lower than the survival rates of other groups, whose optional two markers were equal to or less than the demarcation levels, with high significance. On the contrary, there was absence or attenuation of statistically significant differences in the survival rates between the groups in which two of the three optional markers showed no accordant results (high FI and low AFP versus low FI and high AFP, low FI and high DCP versus high FI and low DCP, high DCP and low AFP versus low DCP and high AFP). Finally, we compared the survival rates between the HCC groups, whose optional one marker was over the demarcation level and whose remainders were equal to or less than the demarcation levels and another HCC group whose optional one marker was equal to or less than the demarcation level and whose remainders were over the demarcation levels to reconfirm the weight of each prognostic factor. These comparisons together with Cox's analysis showed that the weight of each prognostic factor in the survival rates is consecutively ordered as DCP, FI, and AFP. The present study indicates that measurements of FI, AFP, and DCP from the sera before the initial treatment improve prognostic estimates and appraisal of the therapeutic outcome in patients with HCC.

Journal Article↗
PubMed2002

Interchromosomal telomere length variation.

Despite the recent discovery of interchromosomal telomere length variation, a role for heterogeneity in telomere maintenance has yet to be established. This study aimed to clarify relative telomere length differences between chromosomes. Combined chromosomal sorting and telomeric repeat content analysis in GM130B cells, the relative telomeric repeat content in each chromosome, were calculated. Each chromosome could be isolated except for chromosomes 1 and 2 and chromosomes 9 to 12, which were isolated in a group. Telomere length was correlated with the size of the corresponding chromosome. Concomitant relative telomeric repeat content analysis in each chromosome and terminal restriction fragment analysis using the whole genome revealed that the terminal restriction fragments of each chromosome were heterogenously distributed through the smear of the fragments. This is the first description of an association between telomere length and chromosome size.

Chromosomes↗
PubMed2002

The fucosylation index of serum alpha-fetoprotein as useful prognostic factor in patients with hepatocellular carcinoma in special reference to chronological changes.

Aim of this study was to establish fucosylation index (FI) of alpha-fetoprotein (AFP) before and after initial treatment as a useful prognostic factor in patients with hepatocellular carcinoma (HCC). One hundred ninety-seven patients with HCC from 1990 to 2000, in whom an increment of serum AFP concentrations more than 30 ng/ml was observed before treatment, were examined in the present study. Enrolled patients with HCC underwent transcatheter arterial embolization, chemoembolization, percutaneous ethanol injection and/or percutaneous microwave coagulation therapy. The current patients status was confirmed as of the end of March 2001. FI was determined by crossed immunoaffinoelectrophoresis in the presence of Lens culinaris agglutinin (LCA). FI of AFP was defined as the percentage of the LCA-reactive species in total AFP (same as L3 fraction). When the tentative discriminating line of FI was set at 18%, the mean survival rate in the HCC group, whose FI-1 (before treatment) was higher than 18% (high FI), was significantly lower than that in another HCC group, whose FI-1 was equal to or less than 18% (low FI) by the generalized Wilcoxon test and the log rank test (P<0.0001). There were statistical significant differences of survival rate when FI-2 (2 months after treatment) and FI-3 (at the time of HCC recurrence or 2 years after treatment in the case of no recurrence) were introduced in the same analysis. Additionally, statistical significant differences of survival rates were obtained between HCC groups with high and low FI-1 when the patient stage was limited to II, III, IVA or IVB. The HCC group, FI-1, FI-2 and FI-3 of which were persistently equal to or less than 18%, showed considerably better prognosis than the group, whose FI-1, FI-2 and FI-3 were persistently higher than 18%. The univariate analysis in the prognostic factor by the Cox's proportional hazards model showed that FI-1, FI-2 and FI-3 were independent prognostic factors. The present study indicates that measuring FI from the sera before and after the treatment serves as a new prognostic indicator and may improve prognostic estimates and appraisal of therapeutic outcome in patients with HCC.

Journal Article↗
PubMed2002

Bile duct involvement in a case of autoimmune pancreatitis successfully treated with an oral steroid.

In the case reported here, the characteristic features of AIP were evaluated by ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography, initially in the intrahepatic- and extrahepatic bile ducts, and later in the pancreas. In addition, histological examination revealed lymphocytic sclerosis around the intralobular bile ducts, as is reported in AIP, without chronic nonsuppurative destructive cholangitis or onion-skin-like appearance. Immunohistochemistry identified the infiltrating lymphocytes as T cells. Although hypergammaglobulinemia was observed with elevation of hepatobiliary and pancreatic enzymes, no other serological or physiological abnormalities suggestive of other systemic autoimmune diseases were detected. These findings progressed over a three-month period and were dramatically resolved within one month by steroid therapy. These observations support a novel clinical entity characterized by the presence of bile duct lesions similar to the pancreatic involvement seen in AIP that is distinct pathophysiologically, histologically, and therapeutically from the so-called autoimmune cholangitis or primary sclerosing cholangitis.

Administration, Oral↗
PubMed2002

Remote development of hepatocellular carcinoma in patients with liver cirrhosis type B serologically cured for HBs antigenemia with long-standing normalization of ALT values.

In this report, we examine two patients with chronic hepatitis B virus (HBV) infection that had been diagnosed as precirrhosis or liver cirrhosis more than a decade previously. These patients had been cleared of HBsAg and had developed anti-HBs at a later time, yet hepatocellular carcinoma (HCC) eventually occurred. Both patients had been found negative for HBV DNA, using sensitive methods. Interestingly, a nontumor specimen of the liver obtained at surgical resection showed a marked reduction of fibrosis when compared to the histology observed when the patient was diagnosed as precirrhosis. Our findings suggest that the fibrosis from liver cirrhosis had been absorbed to a large extent during the long-term absence of active viremia and the normalization of alanine aminotransferase (ALT) levels. However, the cancer-prone biological characteristics of liver cirrhosis remained. Thus, patients with liver cirrhosis due to past chronic hepatitis B should be monitored carefully for the development of HCC even if HBV infection has been serologically resolved.

Adult↗
PubMed2002

Heterogeneous hepatic enhancement on CT angiography in idiopathic portal hypertension.

BACKGROUND: Idiopathic portal hypertension is an uncommon condition characterized by presinusoidal portal perfusion disturbance without known causes. METHODS: In the present study, portal and arterial perfusion dynamics were evaluated in two cases with idiopathic portal hypertension using computed tomography during arterial portography and hepatic arteriography. Ten cases with liver cirrhosis were also studied as a reference. RESULTS: In cases with idiopathic portal hypertension, portal perfusion was conspicuously heterogeneous and decreased especially at the periphery of the liver where arterial perfusion was reciprocally increased. When the spatial heterogeneity of an enhancement of the liver was quantified using a densitometric analysis of computed tomography during hepatic arteriography images, the densities at the periphery were higher and varied more than those of the inner areas in cases with idiopathic portal hypertension. In contrast, the densities did not vary between the periphery and the inner areas at the cases with liver cirrhosis. CONCLUSIONS: The heterogeneous increase of arterial perfusion in periphery of the liver may be an important feature of idiopathic portal hypertension.

Adult↗