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Biomedical subjects

H Eguchi

Publications and source records attributed to H Eguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers.

The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) beta in human lung. Immunohistochemical staining revealed ERbeta expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas. Adenocarcinomas showed significantly higher expression of ERbeta than squamous cell carcinomas. On the contrary, ERalpha expression was not detected in all cases. The functional integrity of ERbeta such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERbeta, but not ERalpha, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERbeta may play a role in growth and development of adenocarcinomas.

Adenocarcinoma↗
PubMed2001

Apolipoprotein E genotype, serum lipids, and colorectal adenomas in Japanese men.

We examined the relation of serum lipids and apolipoprotein E genotype to colorectal adenomas among 205 cases and 220 controls with normal colonoscopy in Japanese men. With adjustment for body mass index, cigarette smoking, alcohol use, and other covaiates, odds ratios of proximal and distal adenomas associated with the presence of an allele varepsilon4 were 0.59 (95% confidence interval 0.23-1.45) and 0.99 (0.50-1.98), respectively. While serum total and LDL cholesterol were unrelated to both proximal and distal adenomas, serum triglycerides were positively related to distal adenomas. The findings suggest that altered lipid metabolism may be differentially associated with tumorigenesis in the proximal and distal colorectum.

Adenoma↗
PubMed2001

Glutathione S-transferase polymorphisms and risk of colorectal adenomas.

Glutathione S-transferases (GSTs) are a superfamily of detoxification enzymes that may play an important role in human carcinogenesis. While the genetic polymorphisms GSTM1 and GSTT1 have drawn particular interest in relation to cancer susceptibility, previous studies of colorectal cancer are inconsistent regarding their role. We examined the relation between GSTM1 and GSTT1 genotypes combined and colorectal adenomas, and the interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in Japanese men. Neither GSTM1 nor GSTT1 was related to colorectal adenomas, nor were the null genotypes of GSTM1 and GSTT1 combined. The lack of an association with GSTM1 and GSTT1 genotypes combined persisted even when the analysis was done separately for proximal and distal colorectal adenomas. A three- to fivefold significant increase in the odds of colorectal adenomas was observed among men with a high exposure to cigarette smoking across the genotype groups, and a statistically significant increasing trend was noted within each genotype group. The present findings do not support the role for GSTM1 and GSTT1 genotypes in the development of colorectal adenomas.

Adenoma↗
PubMed2001

MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells.

Overexpression of the oncoprotein MDM2, a negative feedback regulator of p53, is often observed in breast cancer tissue and cell lines, particularly in those which express estrogen receptor alpha (ERalpha). In this study, we report a novel function of MDM2, i.e., as a positive regulator of ERalpha. This function does not involve p53. MDM2 overexpressing clones derived from the breast cancer cell line, MCF-7 cells, showed a remarkable growth advantage only in estradiol supplemented conditions, and this profile coincided with increased transcriptional activity of ERalpha in these cells. Though p53 has been reported to be an inhibitor of ERalpha function, p53 protein in MDM2 overexpressing clones was more abundant than in the parental cells. When ERalpha was exogenously expressed in p53-null cells, its activity was enhanced by coexpression of MDM2. Mammalian two-hybrid assays and GST pull-down assays indicated that MDM2 could interact with ERalpha. These results indicate that MDM2 is a direct activator of ERalpha function, and suggest such a role for MDM2 in ERalpha-positive breast cancer.

Blotting, Western↗
PubMed2001

Outcome of acute lymphoblastic leukemia in children with AL90 regimen: impact of response to treatment and sex difference on prognostic factors.

BACKGROUND: In our previous studies, the outcome of high-risk ALL was still poor. In the present study, all children with ALL were classified into three groups and treated with a new regimen (AL90). PATIENTS AND METHODS: Between 1990 and 1996, 220 children with ALL, treated with the AL90 regimen, were classified into three risk groups: low, intermediate, and high: LR, IR, and HR, respectively. The protocol consisted of three- to five-drug induction, consolidation with intermediate-dose methotrexate and/or cytarabine, mercaptopurine and cyclophosphamide, four-drug intensification, and sequential maintenance therapies. Only intrathecal chemotherapy was used for CNS prophylaxis in the LR group, whereas cranial irradiation was added for the IR and HR groups. RESULTS: The number of eligible patients was 91: LR group, 71: IR group, and 58: HR group. Complete remission (CR) was obtained in > 98% of the LR and IR groups, while only 88% achieved CR in the HR group. The 5-year event-free survival (EFS) rate was 67.4% in all patients: 70.4% in the LR group, 71.7% in the IR group, and 57.5% in the HR group. With respect to the previous study, EFS in the HR group who showed positive residual leukemia at 14 days was improved, whereas EFS in boys versus girls was significantly lower (48.8% : 85.7%, P = 0.02). CONCLUSIONS: In high-risk ALL, the rate of induction failure was high and boys had a worse outcome, calling for improvements in induction therapy and a specific approach for boys.

Adolescent↗
PubMed2001

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

Adolescent↗
PubMed2001

Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II genes.

A number of epidemiological and clinical studies have revealed that excess body weight increases the risk of postmenopausal breast cancer and also adversely affects subsequent malignant progression. To elucidate the molecular mechanisms underlying these observations, we examined mRNA expression of various genes in normal (non-cancerous) mammary gland and cancer tissue of Japanese patients with primary breast cancer, in association with their body mass index (BMI). On the basis of analysis of 106 breast cancer patients, we found that mRNA expression of insulin-like growth factor I receptor (IGF-IR) and insulin-like growth factor II (IGF-II) in the normal mammary gland showed a significant and positive association with increased BMI among postmenopausal patients. Furthermore, the positive association of increased BMI with IGF-IR mRNA expression was also found in postmenopausal breast cancer tissue, while this association was not observed among premenopausal patients. In addition, increased mRNA expression of cyclin D1 and bcl-2 was observed in association with increased mRNA levels of IGF-IR among the patients regardless of menopausal status. These findings suggest that the molecular consequence of the increased BMI is the increased expression of IGF-II and IGF-IR, resulting in development of postmenopausal breast cancer and its progression mediated through modulation of the cell cycle and apoptosis.

Adult↗
PubMed2001

Glucose intolerance, plasma insulin levels, and colon adenomas in Japanese men.

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross-sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75-g oral glucose tolerance test, and subjects were classified as normal, impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long-term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer.

Adenoma↗
PubMed2001

Frequent increase of DNA copy number in the 2q24 chromosomal region and its association with a poor clinical outcome in hepatoblastoma: cytogenetic and comparative genomic hybridization analysis.

In a cytogenetic and comparative genomic hybridization (CGH) study of 38 hepatoblastomas, we found gain of 1q in 17 tumors (44.7%), that of 2 / 2q in 14 (36.8%), that of 20 / 20q in 9 (23.7%) and that of 8 / 8q in 8 (21.0%), loss of 4q in 4 (10.5%) and no DNA copy changes with normal karyotype or no mitotic cells in 11 (28.9%). Eleven tumors with 2 / 2q gain detected by CGH had a total chromosome 2 gain, a partial 2q gain, or a total chromosome 2 gain with an augmented partial 2q region; the common region for DNA copy gain was 2q24. Two-color fluorescence in situ hybridization (FISH) analyses using probes covering the centromere of chromosome 2 or HOXD13 (2q31) confirmed the CGH findings, and showed that the common region for gain in 2q was centromeric to HOXD13. Event-free survival (EFS) +/- standard error (SE) at 5 years was lowest in patients with 2q gain [37 +/- 15%], highest in those with no DNA copy changes [82 +/- 12%], and intermediate in those with DNA copy changes other than 2q gain [74 +/- 13%] (P = 0.0549). Multivariate analysis showed that 2q gain was an independent factor predicting a poor outcome. These findings suggest the presence of a growth-promoting gene or an oncogene in the 2q24 chromosome band, and a tumor suppressor gene in terminal 4q, which have important roles in the development and progression of hepatoblastoma.

Antineoplastic Agents↗
PubMed2001

Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner.

In a panel of four human melanoma cell lines, equitoxic doses of cisplatin induced the proapoptotic conformation of the Bcl-2 family protein Bak prior to the execution phase of apoptosis. Because cisplatin-induced modulation of the related Bax protein was seen in only one cell line, a degree of specificity in the signal to Bak is indicated. Little is known about upstream regulation of Bak activity. In this study, we examined whether the apoptosis-specific pathway mediated by a kinase fragment of MEKK1 (DeltaMEKK1) is involved in the observed Bak modulation. We report that expression of a kinase-inactive fragment of MEKK1 (dominant negative MEKK [dnMEKK]) efficiently blocked cisplatin-induced modulation of Bak and cytochrome c release and consequently also reduced DEVDase activation and nuclear fragmentation. Accordingly, expression of a kinase-active MEKK1 fragment (dominant positive MEKK) was sufficient to induce modulation of Bak in three cell lines and to induce apoptosis in two of these. dnMEKK did not block cisplatin-induced c-Jun N-terminal kinase (JNK) activation, in agreement with a specifically proapoptotic role for the DeltaMEKK1 pathway. Finally, we show that reduction of Bak expression by antisense Bak reduced cisplatin-induced loss of mitochondrial integrity and caspase cleavage activity in breast cancer cell lines. In summary, we have identified Bak as a cisplatin-regulated component downstream in a proapoptotic, JNK-independent DeltaMEKK1 pathway.

Antineoplastic Agents↗
PubMed2001

Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample.

OBJECTIVE: Despite a large number of studies, no association of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS: A total of 1,685 subjects (935 women and 750 men, aged 58.7 +/- 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI > or =30 kg/m(2) were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The chi(2) test and analysis of variance were used for the association studies and to assess the differences in the traits' values, respectively. RESULTS: More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84 vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS: Genotype Arg/Arg, but not Trp/Arg, of the beta(3)-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.

Aged↗
PubMed2001

Clinical application of quantitative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR.

In order to detect a hematogenous spread of tumor cells in patients with hepatocellular carcinoma, reverse transcription-polymerase chain reaction assay has been used. In this study, we quantified alpha-fetoprotein (AFP) messenger RNA by real-time PCR approach using LightCyclertrade mark technique. AFP messenger RNA in the blood from 23 hepatocellular carcinoma patients undergoing hepatic resection, 31 healthy volunteers, 10 patients with liver cirrhosis and 5 patients underwent hepatectomy except for hepatocellular carcinoma was quantitated. In the real-time PCR, fluorescence was undetectable in any of the controls. On the contrary, fluorescent signals were detected in 10 out of 39 blood specimens collected from 23 HCC patients. AFP-positive status was significantly associated with the existence of multiple intrahepatic nodules. Out of 8 cases with AFP-positive status, intra- and/or extra-hepatic recurrence has been observed in 3 cases. The quantities of AFP messenger RNA in these 3 cases were relatively high among 8 cases with AFP-positive status. AFP messenger RNA was detectable by newly developed real-time PCR approach with LightCycler and it is suggested that this approach could be applicable in detection of small amounts of tumor cells in the blood of HCC patients.

Biomarkers, Tumor↗
PubMed2000

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy.

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Antibiotics, Antineoplastic↗
PubMed2000

Antagonistic action of novel 1alpha,25-dihydroxyvitamin D(3)-26, 23-lactone analogs on 25-hydroxyvitamin-D(3)-24-hydroxylase gene expression induced by 1alpha,25-dihydroxy-vitamin D(3) in human promyelocytic leukemia (HL-60) cells.

We have demonstrated that 1alpha,25-dihydroxyvitamin D(3)-26, 23-lactone analogs, (23S)- and (23R)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647, TEI-9648, respectively), inhibit HL-60 cell differentiation induced by 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], but not differentiation caused by all-trans retinoic acid (D. Miura et al., 1999, J. Biol. Chem. 274, 16392). To assess whether the antagonistic actions of TEI-9647 and TEI-9648 in HL-60 cells are related to 1alpha,25(OH)(2)D(3) breakdown, we investigated their effects on catabolism of 1alpha,25(OH)(2)D(3). In HL-60 cells, the C-24 but not the C-23 side-chain oxidation pathway of 1alpha,25(OH)(2)D(3) has been reported. Here we demonstrate that 1alpha,25(OH)(2)D(3) was metabolized both to 24,25,26,27-tetranor-1alpha,23-(OH)(2)D(3) and 1alpha,25(OH)(2)D(3)-26,23-lactone; thus HL-60 cells constitutively possess both the 24- and the 23-hydroxylases. Metabolism of 1alpha, 25(OH)(2)D(3) was strongly suppressed by 10(-7) M TEI-9647 or 10(-6) M TEI-9648. 1alpha,25(OH)(2)D(3) alone slightly induced 24-hydroxylase gene expression by 8 h with full enhancement by 24-48 h; this induction was inhibited by 10(-6) M TEI-9647 and 10(-6) M TEI-9648 (86.2 and 31.9%, respectively) 24 h after treatment. However, analogs of TEI-9647 and TEI-9648 without the 25-dehydro functionality induced 24-hydroxylase gene expression. These results indicate that TEI-9647 and TEI-9648 clearly mediate their stereoselective antagonistic actions independent of their actions to block the catabolism of 1alpha,25(OH)(2)D(3). Therefore, TEI-9647 and TEI-9648 appear to be the first antagonists specific for the nuclear 1alpha,25(OH)(2)D(3) receptor-mediated genomic actions of 1alpha,25(OH)(2)D(3) in HL-60 cells.

Calcitriol↗
PubMed2000

Enhanced cytotoxic effect of Ara-C by low intensity ultrasound to HL-60 cells.

A clonogenic assay was tested in order to determine the effects of low intensity ultrasound on HL-60 cells in the presence of cytosine arabinoside (Ara-C). HL-60 cells were exposed to ultrasound at an intensity of 0.3 W/cm2 (48 kHz). Cells were then cultured for 8 days and the number of colonies was statistically analyzed (ANOVA). Ultrasound exposure alone for 120 s resulted in no significant decrease of colonies compared to non-treated cells (P0 = 0.1426). Significant differences (P0 < 0.005) were obtained between ultrasound treated and untreated cells in the presence of various concentrations of Ara-C (2 x 10(-9), 1 x 10(-8), 2 x 10(-8), 5 x 10(-8), 1 x 10(-7) M). Morphological evaluation of ultrasound irradiated cells with scanning electron microscopy showed minor disruption of cell surface and disappearance of microvilli. These observations suggests that low intensity ultrasound altered the cell membrane thus resulting in change in Ara-C uptake into HL-60 cells.

Antimetabolites, Antineoplastic↗
PubMed2000

Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves.

HYPOTHESIS: The clinical significance of hepatectomy for hepatocellular carcinoma (HCC) is still controversial because of frequent intrahepatic recurrence, which results from either recurrence due to residual intrahepatic metastasis (Rim) or recurrence due to metachronous, multicentric liver carcinogenesis (Rmc). DESIGN: Retrospective review. Disease-free survival curves were obtained by the Kaplan-Meier method and the rates of Rim and Rmc were analyzed using 2 regression lines, based on the evidence that Rmc occurs at a constant rate throughout follow-up, whereas Rim occurs only in the early postoperative period. SETTING: University hospital. PATIENTS: From 1980 to 1996, 241 patients with HCC who underwent curative hepatic resection. MAIN OUTCOME MEASURE: Intrahepatic recurrence. RESULTS: Disease-free survival curves for all patients in the early (within 2 years) and late (4 years after surgery) follow-up were approximated by 2 regression lines, which represent both Rim and Rmc (Y(1) = -3.4X + 48) and only Rmc (Y(2) = -23.1X + 98). Using this approximation, the annual incidence of Rim within 2 years (a(1)-a(2)) was calculated as 19.7% and that of Rmc (a(2)) was 3.4%. The ratio of Rim in tumor recurrence (b(1)-b(2)) was 50%, and that of Rmc (b(1)) was 48%. The ratios of Rmc in patients with stages I and II HCC were 60% and 64%, respectively. In contrast, the values could not be calculated in patients with stages III and IVA because all but 2 patients showed recurrence within 4 years after surgery. CONCLUSION: Tumor recurrence is estimated to result from metachronous liver carcinogenesis in 48% of hepatectomized patients with HCC.

Carcinoma, Hepatocellular↗