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Hideaki Shimada

Publications and source records attributed to Hideaki Shimada.

At least 73 records · Page 4Linked to original sources
PubMed2003

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.

Adult↗
PubMed2003

Treatment response and prognosis of patients after recurrence of esophageal cancer.

BACKGROUND: Although radical operation and adjuvant chemoradiotherapy improve survival in patients with advanced esophageal cancer, more than half of these patients have recurrence. The aim of this study was to explore treatment responses and prognostic factors in patients with recurrent esophageal cancer. METHODS: The operative specimens from 258 patients undergoing radical esophagectomy with extended lymphadenectomy for esophageal squamous cell carcinoma between 1990 and 1999 were analyzed. Depth of tumor invasion, and the extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month examinations of tumor markers, 6-month examinations of ultrasonography, and annual computed tomography. Of 258 patients, 95 had recurrence by the end of 2000 (mean follow-up was 22 months, range, 2-113). Of those 95 patients, 76 received nonsurgical treatment, 7 received operative intervention, and 12 received no treatment. Clinicopathologic features of recurrent tumors were analyzed to determine prognostic values. Serum anti-p53 antibodies (S-p53-Abs), serum C-reactive protein concentration (S-CRP), and albumin concentration were also analyzed. RESULTS: The main recurrent patterns were nodal (n = 45) and organ (n = 35). Of the nonsurgical treatment group, 47 patients received chemoradiotherapy; 17, chemotherapy; and 12, radiotherapy. Overall clinical response was observed in 26 of 76 patients (34%). Treatment response was significantly associated with the type of recurrence, history of perioperative adjuvant therapy, time of recurrence, number of recurrent tumors, albumin concentration, S-CRP, and S-p53-Abs. Multivariate analysis suggested that S-p53-Abs and S-CRP were independent prognostic factors. CONCLUSION: The status of S-p53-Abs and S-CRP may predict response and outcome of patients with recurrence of esophageal cancer after radical operation.

Adult↗
PubMed2003

Inactivation of rabbit liver carbonyl reductase by phenylglyoxal and 2,3,4-trinitrobenzenesulfonate sodium.

The chemical modifications of rabbit liver carbonyl reductase (RLCR) with phenylglyoxal (PGO) and 2,3,4-trinitrobenzenesulfonate sodium (TNBS), which are respective chemical modifiers of arginine and lysine residues, were examined. RLCR was rapidly inactivated by these modifiers. Kinetic data for the inactivation demonstrated that each one of arginine and lysine residues is essential for catalytic activity of the enzyme. Furthermore, based on the protective effects of NADP+, NAD+ and their constituents against the inactivation of RLCR by PGO and TNBS, we propose the possibility that the functional arginine and lysine residues are located in the coenzyme-binding domain of RLCR and interact with the 2'-phosphate group of NADPH.

Alcohol Oxidoreductases↗
PubMed2003

Transcriptional activity of the tandem repeat polymorphism in the 5'-flanking region of the human CYP2E1 gene.

BACKGROUND: There are remarkable interindividual differences in the expression of cytochrome P-4502E1(CYP2E1), which in turn may alter susceptibility to alcohol-related diseases and various cancers. We recently characterized the tandem repeat polymorphism in the 5'-flanking region of the human CYP2E1 gene and found that subjects with the homozygous mutant-type (A4/A4) may be at higher risk of developing esophageal cancer. In this study, we determined how this tandem repeat polymorphism alters transcriptional activities of the human CYP2E1 gene by transfection studies. METHODS: The 5'-flanking region (-2,562 base pair to +9 base pair) of the CYP2E1 gene from three individuals of different genotypes (A2/A2, A2/A4, A4/A4) was amplified by polymerase chain reaction. The polymerase chain reaction products placed in front of a luciferase reporter gene were transfected into human hepatoblastoma cells, human esophageal cancer cells, and human uterus cancer cells. Transcriptional activities were determined by the dual-luciferase assay. When indicated, ethanol (50 mM) was included in the culture medium. CYP2E1 messenger RNA levels in peripheral lymphocytes were measured by the real-time reverse transcription-polymerase chain reaction using the LightCycler system. RESULTS: The construct including the tandem repeat region exhibited luciferase activities in both A2 and A4 type. It was of note that the activity produced by the A4 allele was significantly greater than that by A2 allele in HeLa cells (p < 0.001). CYP2E1 messenger RNA levels in peripheral blood lymphocytes were comparable between the two genotypes. CONCLUSION: Transcriptional activity of the mutant allele of the tandem repeat polymorphism in the 5'-flanking region of the CYP2E1 gene is greater than that of the wild type.

5' Flanking Region↗
PubMed2003

Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.

High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 +/- 342 pg/ml vs. 154 +/- 76 pg/ml, P < 0.001). Using 300 pg/ml as the cut-off value (representing the mean + 2 standard deviations of the S-MK of healthy controls), 61% of patients with esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK (>/= 300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival.

Adult↗
PubMed2003

[Automatic activation of addition and multiplication facts: an examination of effects of SOA, problem size, and presentation of operator symbol].

The purpose of this study was to examine boundary conditions and time course in automatic activation of addition and multiplication facts. Utilizing a number-matching task in which subjects were required to verify whether a target had been presented in a previously viewed number pair, the stimulus onset asynchrony (SOA), problem size, and operator symbol were manipulated. As a result, products were rejected more slowly than unrelated numbers in all problem size conditions, but sums were rejected more slowly than unrelated numbers only in small size condition, and this effect was not related to SOA and operator symbol. These results suggest that (a) automatic activation is restricted to small facts in addition, but not restricted in multiplication, (b) operator symbols have no effect on automatic activation, and (c) time course in automatic activation of addition facts does not differ from that of multiplication facts.

Adult↗
PubMed2002

Prognostic significance of serum thymidine phosphorylase concentration in esophageal squamous cell carcinoma.

BACKGROUND: Thymidine phosphorylase (dThdPase), which also is referred to as platelet-derived endothelial cell growth factor, is a potent inducer of angiogenesis in malignant tumors. Increased dThdPase expression and activity have been found to be associated with poor prognosis in various solid tumor tissues. Because very little was known about the significance of serum dThdPase concentration (S-dThdPase), the objective of this study was to analyze the clinicopathologic significance of S-dThdPase in the patients with esophageal squamous cell carcinoma. METHODS: The S-dThdPase was measured by enzyme-linked immunosorbent assay in 77 healthy controls and 153 patients with primary esophageal squamous cell carcinoma. A total of 80 patients underwent surgery alone; 46 patients received chemoradiotherapy alone; 17 patients received chemoradiotherapy followed by surgery; and 10 patients did not receive any treatment. Thymidine phosphorylase expression in esophageal carcinoma tissues was examined by immunohistochemistry. The clinicopathologic value and prognostic value of S-dThdPase was determined in 80 patients treated by surgery alone. RESULTS: The S-dThdPase is significantly higher in patients with esophageal carcinoma than in healthy controls (30.8 +/- 31.8 ng/mL vs. 13.8 +/- 7.6 ng/mL; P < 0.001). Statistically significant differences in S-dThdPases were observed depending on tumor size (P < 0.01) and tumor depth (P < 0.01). A S-dThdPase of more than 29.0 ng/mL (which represented the mean plus 2 standard deviation of the concentration in healthy controls) was associated with dThdPase expression (P = 0.022), poor response (P = 0.022), and poor survival (P < 0.01). Because S-dThdPase was associated with tumor depth, S-dThdPase was not an independent prognostic factor (P = 0.095). CONCLUSIONS: A high S-dThdPase is associated with depth of tumor invasion and poor response to treatment.

Adult↗
PubMed2002

Alteration of integrin expression relates to malignant progression of human papillomavirus-immortalized esophageal keratinocytes.

To investigate cellular changes related to the malignant progression of keratinocytes, we studied the serum-resistant clones from CHEK-1, a human papillomavirus type 16 E6/E7-immortalized esophageal cell line cultured in a serum-free medium. Established clones exhibited morphologic variety. Slow growing clones presented in cuboidal shapes with tight cellular adhesion and highly expressed alpha2 and alpha6beta4 integrins. Moderately proliferating clones showed loose intercellular adhesion and reduced expression of alpha2 integrin. Spindle-shaped, rapidly proliferating clones with prominent actin stress fibers demonstrated reduced alpha6 and alpha4 integrin expression in addition to alpha2 integrin and showed anchorage-independent growth. Reduced expression of alpha2 integrin was observed between 50 and 100 population doubling lengths (PDLs) during the immortalization of CHEK-1. These results suggest that the reductions of alpha2 and alpha6beta4 integrins are related to changes seen during immortalization and malignant progression.

Actins↗
PubMed2002

Serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as a prognostic tumor marker in patients with esophageal squamous cell carcinoma.

BACKGROUND: Serum cross-linked carboxyterminal telopeptide of Type I collagen (ICTP) is a metabolite of Type I collagen and has been reported to serve not only as a marker of bone metastasis but also as an indicator of treatment response and prognosis in several malignant tumors. The objective of this work was to evaluate the value of serum ICTP as a tumor marker in patients with esophageal squamous cell carcinoma (SCC). METHODS: In this study, pretreatment serum ICTP concentrations were measured by double-antibody radioimmunoassay in 50 patients undergoing tumor resection, chemoradiotherapy, or palliation for newly diagnosed esophageal SCC. The cutoff value for positive ICTP levels was defined as 4.50 ng/mL. As a comparison, serum concentrations of SCC antigen, carcinoembryonic antigen, cytokeratin-19 fragment, alkaline phosphatase, and lactate dehydrogenase were simultaneously evaluated. The results were categorized according to several clinicopathologic variables. RESULTS: Among the markers tested, ICTP showed the highest sensitivity (58.0%) in esophageal SCC sera. Positive ICTP levels were significantly correlated with tumor progression variables, such as tumor depth > or = T2, regional lymph node metastasis (N1), distant metastasis (M1), TNM stage > or = II, and maximal tumor length greater than 50 mm. Survival analyses of 29 patients who underwent curative resection demonstrated that patients who were positive for ICTP had significantly worse outcomes in terms of overall, disease specific, and disease free survival than those who were negative. Multivariate analyses confirmed that serum ICTP levels provided an independent prognostic indicator of overall and disease specific survival. However, serum ICTP values did not correlate with prognosis or treatment response in 17 unresectable cases treated by chemoradiotherapy. CONCLUSIONS: Our results indicated that serum ICTP concentrations might be a novel prognostic tumor marker for assessing the progression of esophageal SCC.

Adult↗
PubMed2002

Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells.

To investigate the effect of p33(ING1) on wild-type p53 gene therapy, T.Tn human esophageal carcinoma cells were stably transfected with p33(ING1) cDNA. Infection with Ad-p53 (recombinant adenovirus containing wild-type p53) into p33-transfected cells reduced cell viability, while infection with empty vector had little effect. This reduced viability was shown to be due to apoptotic cell death by the TUNEL (terminal deoxynucleotidyl transferase-mediated nick end-labeling) assay. Following infection with Ad-p53, levels of p53 were similar in p33-expressing cells and in the parental line. However, levels of p21 and Mdm2 were elevated in p33-transfected cells. Nonetheless, this enhanced expression of Mdm2 appeared to be ineffective in downregulating p53. Transient transfection with mutant Mdm2 prior to Ad-p53 infection provided a significant protection as compared with cells transfected with wild-type Mdm2. These results imply a synergistic effect between p33 and p53 in the induction of apoptosis of human esophageal carcinoma cells. A role for Mdm2 in this synergism is suggested.

Adenoviridae↗
PubMed2002

Involvement of active transport systems in the mobilization of cadmium by dithiocarbamates in vivo.

Previously, we reported that the action of cadmium (Cd) complexing dithiocarbamates, such as N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), in removing Cd from the kidney involves a probenecid-sensitive organic anion transport system. However, other mechanisms responsible for Cd mobilizing effects of BGD and HBGD are still unclear. Therefore, in the present study we examined the effects of phloretin (an inhibitor of plasma membrane glucose carrier), phloridzin (an inhibitor of Na(+)-dependent active hexose transport) and alpha-aminoisobutyric acid (AIB, an inhibitor of amino acid transport) on the excretion and distribution of the chelating agents and Cd in mice. Phloretin pretreatment markedly decreased the biliary and urinary excretions of BGD and HBGD. Phloridzin pretreatment also decreased the biliary and urinary excretions of HBGD, but had no effect on the BGD. AIB pretreatment had no effect on the excretions of either BGD or HBGD. Phloretin pretreatment increased the hepatic and renal contents of BGD and HBGD. Contrary to this, phloridzin pretreatment decreased the hepatic content of BGD and hepatic and renal contents of HBGD, while AIB pretreatment decreased the renal contents of BGD and HBGD. The mobilizing effects of BGD and HBGD on the hepatic and renal Cd was also investigated using Cd-exposed mice. Phloretin or phloridzin pretreatment decreased the mobilizing effect of BGD and HBGD on the hepatic Cd, but had no effect on the renal Cd. These results suggest that BGD and HBGD are taken up into the liver and kidney by phloridzin- and phloretin-sensitive transport system, respectively; that Cd-BGD and Cd-HBGD complexes formed in the hepatic cells are secreted to the bile by phloridzin- and phloretin-sensitive transport systems; and that free BGD and HBGD secreted from these organ to the bile and urine might have occurred, at least in part, by different mechanisms.

Amino Acid Transport Systems↗
PubMed2002

p53 gene therapy for esophageal cancer.

Despite improvement of surgical treatment and application of multimodality therapies to advanced esophageal cancer, the prognosis is extremely poor for patients with unresectable tumors. Based on the genetic background of esophageal cancer, we have developed various gene therapy strategies against human esophageal cancer. In this article, we review molecular events of esophageal cancer and p53 gene therapy approaches for its treatment. First, we analyzed p53 genetic alterations and angiogenesis in esophageal cancer. Second, we tested a p53 recombinant adenoviral vector (Ad5CMV-p53). Significant growth suppression was observed following infection with Ad5CMV-p53 in human esophageal cancer cell lines. This observation suggests that Ad5CMV-p53 may be a potentially effective therapeutic agent for locally advanced esophageal cancer. Promising avenues for investigation include double gene therapy and adjuvant use of gene therapy with radiation therapy. Third, based on recent reports of clinical trials of p53 gene therapy for lung cancer and head and neck cancer, we developed a clinical protocol for p53 gene therapy for unresectable advanced esophageal cancer. This clinical trial was planned to evaluate vector tolerability and efficacy. Up to December 1, 2001, four patients were enrolled in this phase I/II trial. No serious adverse events related to Ad5CMV-p53 have occurred so far in these patients, and the trial has been safely conducted.

Animals↗
PubMed2002

Analysis of experimental liver metastasis from tumors inoculated in the mouse stomach cavity.

PURPOSE: This study was conducted to develop a patient-like hematogenous metastatic model of gastric-cancer in order to gain an understanding of the tumor biology and to search for new methods of treatment. METHODS: We established a natural and easily reproducible liver metastasis model by orthotopic gastric inoculation in Balb/c mice, using the syngeneic tumor, colon 26. RESULTS: This model allowed us to evaluate the effect of partial gastric resection with excision of tumor nodules on the formation of experimental liver metastases from the stomach cavity. Mice given partial gastrectomy showed less metastatic ability than control mice. In these experimental groups, liver metastasis was observed in the only group of mice that died of local tumor regrowth due to incomplete resection of the primary tumor. It is suggested that a period of at least 10 days is required for the formation of liver metastases after tumor inoculation into the stomach cavity. There was no significant increase in the number of liver metastases following splenectomy, or after the administration of anti-asialo GM1 antibody or silica. CONCLUSION: This experimental model of liver metastases will provide a useful means of understanding tumor biology and the regulation of liver metastases by host immunocompetent cells, and for assessing new therapeutic agents.

Animals↗
PubMed2002

Acutely exaggerated hepatitis B induced by the withdrawal of immunosuppressants in a seroconverted renal transplant recipient: report of a case.

The long-term reciprocal impact of renal transplantation on infection by hepatitis B virus (HBV) is still a matter of intense debate, and the topic remains controversial. We herein report the case of a 50-year-old male asymptomatic HBV carrier who had seroconverted to positive anti-HBe antibody (Ab) and received a kidney transplantation from a cadaver donor (HB surface(s) antigen (Ag)-negative). Nine months later, his kidney function deteriorated due to chronic rejection, and hemodialysis was temporarily required. Triple drug therapy (cyclosporine, prednisolone, azathioprine) for immunosuppression was changed to two-drug therapy (cyclosporine and prednisolone) at a reduced dosage because of this episode. After that episode, severe hepatitis with HBV antigenemia developed without any change in the serological state. The levels of DNA polymerase in a potential recipient from a cadaveric donor should be checked before transplantation to predict the occurrence of hepatitis when the recipient is an asymptomatic carrier of HBV, especially in cases of serologically HBeAg-negative, and anti-HBeAb-positive carriers.

Acute Disease↗
PubMed2002

Structure-effect relationship in the mobilization of cadmium in mice by several dithiocarbamates.

The structural characteristics of several dithiocarbamates (DTCs) [N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD)] that induce in vivo mobilization of cadmium (Cd) were examined in mice. The renal and hepatic contents of Cd were lower in the treatments with Cd-DTC combinations than in that with Cd alone. Probenecid pretreatment decreased the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, but it increased the renal content of Cd and decreased the urinary excretion of the metal in Cd-HBGD and Cd-CBGD treated mice. Furthermore, although ureter-ligation did not affect the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, it increased the renal content of Cd in Cd-HBGD and Cd-CBGD treated mice. These findings suggest that Cd-MBGD and Cd-BGD complexes are taken up into the tubular cells by an organic anion transport system through the basolateral membrane, whereas Cd-HBGD and Cd-CBGD complexes are secreted to the tubular lumen by an organic anion transport system through the brush border membrane. The results of probenecid pretreatment also led us to assume that the hepatic transport of these four Cd-DTC complexes is regulated, at least in part, by a probenecid-sensitive organic anion transport system.

Animals↗
PubMed2002

Sex-dependent pharmacokinetics of S(-)-hydroxyhexamide, a pharmacologically active metabolite of acetohexamide, in rats.

The pharmacokinetic profile of S(-)-hydroxyhexamide (S-HH), a pharmacologically active metabolite of acetohexamide, was examined in male and female rats. S-HH was eliminated more rapidly from plasma in the males than in the females. A significant sex difference was observed in the pharmacokinetic parameters of S-HH in rats. Testectomy caused significant alteration in these parameters of S-HH in male rats, whereas ovariectomy did not in the females. The co-administration of sulfamethazine significantly decreased the plasma clearance (CL(p)) of S-HH in male rats, but had no effect in the females. The plasma concentrations of acetohexamide generated from S-HH showed no sex-related difference. Furthermore, there was no difference in the accumulation of S-HH by renal cortical slices from male and female rats. We propose the possibility that the sex-dependent pharmacokinetics of S-HH in rats is mediated through the male-specific hydroxylation of the cyclohexyl ring catalyzed by a major cytochrome p450 (CYP) isoform (CYP2C11), although the detailed mechanism remains to be elucidated.

Acetohexamide↗
PubMed2002

Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma.

BACKGROUND: The p53 protein overexpression that usually results from genetic alterations has been reported to induce serum antibodies against p53. There is little information about the clinicopathologic and prognostic significance of preoperative serum p53 antibody in patients with esophageal cancer. METHODS: A highly specific enzyme-linked immunosorbent assay was used to analyze serum p53 antibodies in 105 patients with esophageal squamous cell carcinoma. The cutoff level of 1.3 U/mL was used to indicate seropositive patients, and the cutoff level of 10 U/mL was used to identify high titer patients. At 3 months after surgery, seropositive patients were examined again. RESULTS: A total of 28 patients (26.7%) were positive for serum p53 antibodies. The patients who remained seropositive were more likely to develop tumor recurrence (P =.025). Seropositive patients had worse outcome than seronegative patients. The high titer group had significant association with advanced tumor stages and worse outcomes than the low titer group. High serum p53 antibody titer was an independent prognostic factor (P <.001). CONCLUSIONS: We found that serum p53 antibody was useful to detect esophageal cancer and to identify those with a high risk of tumor recurrence and a poor prognosis.

Adult↗