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Biomedical subjects

Hiroshi Tsuji

Publications and source records attributed to Hiroshi Tsuji.

At least 19 recordsLinked to original sources
PubMed2007

Immunologic effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides in Japanese infants.

Effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides on lymphocyte subsets were investigated in the peripheral blood from 101 Japanese infants with approximately 10 months of age. Perinatal exposure to these organochlorine compounds were estimated by their contamination levels in the breast milk of the mothers. Lymphocyte subsets such as CD16+, HLA-DR+, CD4+, CD4+8+, CD8+, CD3+ and CD20+ cells in peripheral venous blood were assessed in a subgroup of 92 infants. Greater exposures to HCE, chlordane and dioxins were significantly associated with the increase in the percentages of CD8+ and CD3+ T lymphocytes and CD4+/CD8+ T cell ratios, respectively. In addition, higher HCH exposure was also associated with a decrease in the percentage of HLA-DR+ T lymphocytes. Furthermore effects of dioxins, DDT and PCBs on the percentage of CD16+ T lymphocyte were more pronounced by the combined exposure of dioxins and PCBs or by the combined exposure of DDT and PCBs. Effects of HCE on the percentages of CD8+ T lymphocyte were also more pronounced by the combined exposure of HCE and chlordane. In conclusion, our study suggests that greater exposures to dioxins, PCBs and organochlorine pesticides determined in this study (except dieldrin) influence the immune system of Japanese infant, although the clinical significance of these changes is uncertain.

Breast Feeding↗
PubMed2006

Decrease of cholesterol in mouse melanoma causes secretion of lysosomal enzymes.

We examined the change in the subcellular distribution of a lysosomal enzyme, beta-glucuronidase (beta-G), caused by decreased cholesterol levels in mouse melanoma cells using an HMG-CoA reductase inhibitor, lovastatin and lipoprotein-deficient serum (LDS). There was a decrease in the cholesterol content of the cells and increased secretion of the mature form of beta-G located in lysosomes, as documented by Percoll density gradient fractionation, digitonin permeabilization and immunoprecipitation. Furthermore, another lysosomal enzyme, cathepsin H, was found to be released in the medium from cells treated with lovastatin. Both the precursor and mature forms of cathepsin H were detected in the medium of treated cells. Next, when cells were treated with LDS without lovastatin, concomitantly with the decrease in the levels of cholesterol and beta-G activity in the cells, beta-G activity in the medium increased. Also, the ratio of beta-G (3.2-fold) released in the medium from cells treated with Dulbecco's modified Eagle medium (D-MEM) containing lovastatin and LDS was higher than that (2.3-fold) on treatment with D-MEM containing LDS without lovastatin. From these results, it was suggested that the exocytosis of mature enzymes from lysosomes into the medium or mis-sorting of the lysosomal precursor forms to the medium was caused by the lovastatin- and/or LDS-induced decrease in the cholesterol content of the cells, although the mechanism of secretion by lysosomal enzymes differed somewhat.

Animals↗
PubMed2006

Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: a Phase I/II dose-escalation study.

PURPOSE: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. RESULTS: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. CONCLUSION: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

Adult↗
PubMed2006

Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis.

PURPOSE: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. METHODS AND MATERIALS: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). RESULTS: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 +/- 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50IC (volume irradiated > or =50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50IC > or =0.127 mL and those with V50IC <0.127 mL were 71.4 +/- 8.5% and 11.5 +/- 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 +/- 10.4% and 28.4 +/- 8.0%, respectively. CONCLUSION: Dose-volume histogram analysis with computed tomography indicated that V50IC and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.

Adult↗
PubMed2006

Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer.

PURPOSE: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. METHODS AND MATERIALS: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. RESULTS: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 +/- 5.6% with toxicity; 11.4 +/- 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. CONCLUSIONS: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.

Aged↗
PubMed2006

Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study.

BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April 2000 and November 2003, 175 patients received C-ion RT using a recommended dose fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT alone was performed for 33 patients constituting a low-risk group (Stage < or =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk patients received an additional androgen deprivation therapy (ADT). RESULTS: The 4-year overall survival and bNED rates were 91% and 87%, respectively. Local control was achieved in all but one patient. The 4-year bNED rates were 87% in the low-risk group and 88% in the high-risk group. In very advanced diseases (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was significant difference in the bNED rate according to period of ADT administration (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities developed in 4 patients (2%) for the rectum and 9 patients (5%) for the genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS: The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based on these results, new study of a C-ion RT modified for the administration strategy of ADT according to the patient risk has been started by dividing patients into 3 groups, high-risk, intermediate-risk, and low-risk.

Adenocarcinoma↗
PubMed2006

Monotherapy with carbon ion radiation for localized prostate cancer.

BACKGROUND: Radiation treatment for localized prostate cancer has become a prominent choice of monotherapy, and carbon ion beam is a powerful means for this purpose. METHODS: In total, 37 patients with localized prostate cancer were treated by monotherapy with carbon ion radiation and the outcome, more than 4 years later, was followed. RESULTS: PSA relapse-free survival was overall 85%, 5 years after radiation, and 96% in low-risk patients. Local control was mostly achieved, and no cancer-specific death was obtained. Except in cases of relapse, 1.0 ng/ml or less of PSA was shown in 78%, 3 years after radiation. Half of biopsy specimens out of 12 cases revealed non-viable or no cancer cells after a rather short time from treatment. CONCLUSION: Monotherapy with carbon ion radiation may be an excellent treatment for localized prostate cancer with low risk.

Aged↗
PubMed2006

Basic fibroblast growth factor promotes nerve regeneration in a C- -ion-implanted silicon chamber.

We reported previously that a silicone tube whose inner surface has been implanted with negatively charged carbon ions (C-) enables a nerve to regenerate across a 15-mm inter-stump gap. In this study, we investigated whether a C- -ion-implanted tube pretreated with basic fibroblast growth factor promotes peripheral nerve regeneration. The C- -ion-implanted tube significantly accelerated nerve regeneration, and this effect was enhanced by basic fibroblast growth factor.

Action Potentials↗
PubMed2006

Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix.

PURPOSE: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. METHODS AND MATERIALS: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). RESULTS: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were > or =60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with > or =62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors > or =6.0 cm (64%). CONCLUSIONS: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy.

Adenocarcinoma↗
PubMed2006

Effect of benzo[a]pyrene on P-glycoprotein-mediated transport in Caco-2 cell monolayer.

The main exposure pathway of benzo[a]pyrene (Bap) for humans is considered to be via the daily diet. The purpose of this study was to investigate the effect of BaP on the intestinal transport of chemicals mediated by P-glycoprotein (P-gp). The intestinal epithelial membrane transport of rhodamine-123 (Rho-123), a substrate of P-gp, was examined using a monolayer of the human Caco-2 cell line grown in transwells. In the monolayer exposed to Bap for 72 h before transport experiments, the ratio of the apparent permeability coefficients (P(app)) of Rho-123 efflux increased compared to that of the control. The permeability of rhodamine-B (Rho-B), not a substrate of P-gp, showed no difference between the monolayers. Treatment with quinidine or cyclosporine A, which are P-gp inhibitors, decreased the P(app) of Rho-123 to the same degree in both monolayers. The transport of Rho-123 was not influenced by the presence of Bap. Thus, Bap seemed not to act directly on the efflux activity of P-gp and be a binding site competitor of Rho-123. In the Caco-2 cells that enhanced the efflux of Rho-123 by the treatment with Bap, an increase in mRNA expression of MDR 1 (P-gp) was confirmed compared to that of control by RT-PCR. Furthermore, Western blot analysis using a monoclonal antibody, C219, demonstrated the increase of P-gp in Caco-2 cells exposed to Bap, compared with controls. It was inferred that Bap exposure induced the expression of P-gp, which led to the observed increase in efflux transport of Rho-123. The possibility was suggested that Bap might affect the disposition of medicines by increasing P-gp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Examination of GyE system for HIMAC carbon therapy.

PURPOSE: A retrospective analysis was made to examine appropriateness in the estimation of the biologic effectiveness of carbon-ion radiotherapy using resultant data from clinical trials at the heavy-ion medical accelerator complex (HIMAC) at the National Institute of Radiological Sciences in Chiba, Japan. METHODS AND MATERIALS: At HIMAC, relative biologic effectiveness (RBE) values of therapeutic carbon beams were determined based on experimental results of cell responses, on values expected with the linear-quadratic model, and based on experiences with neutron therapy. We use fixed RBE values independent of dose levels, although this apparently contradicts radiobiologic observations. Our RBE system depends only on LET of the heavy-ion radiation fields. With this RBE system, over 2,000 patients have been treated by carbon beams. With data from these patients, the local control rate of non-small-cell lung cancer was analyzed to verify the clinical RBE of the carbon beam. The local control rate was compared with rates published by groups from Gunma University and Massachusetts General Hospital. Using a simplified tumor control probability (TCP) model, clinical RBE values were obtained for different levels of TCP. RESULTS: For the 50% level of the clinical TCP, the RBE values nearly coincide with those for in vitro human salivary gland cell survival at 10%. For the higher levels of clinical TCP, the RBE values approach closer to those adapted in clinical trials at HIMAC.

Algorithms↗
PubMed2006

Urinary yttrium excretion and effects of yttrium chloride on renal function in rats.

Evaluation of yttrium exposure in biological samples has not been fully examined. To evaluate yttrium nephrotoxicity, yttrium chloride was orally administered to male Wistar rats and the urine volume (UV) and N-acetyl-beta-D-glucosaminidase (NAG) and creatinine excretion (Crt) were measured in 24-h urine samples. The urinary yttrium concentration and excretion rate were determined by inductively coupled plasma-argon emission spectrometry (ICP-AES). Large significant decreases of UV (>30%) and Crt (>10%) were observed at yttrium doses of 58.3-116.7 mg per rat, but no significant NAG changes was observed. This response pattern shows that a high yttrium dosage alters glomerular function rather than the proximal convoluted tubules. A urinary yttrium excretion rate of 0.216% and good dose-dependent urinary excretion (r=0.77) were confirmed. These results suggest that urinary yttrium is a suitable indicator of occupational and environmental exposure to this element, an increasingly important health issue because recent technological advances present significant potential risks of exposure to rare earth elements. We propose that the ICP-AES analytical method and animal experimental model described in this study will be a valuable tool for future research on the toxicology of rare earth elements.

Acetylglucosaminidase↗
PubMed2006

[Clinical experience of carbon ion radiotherapy for malignant tumors].

The carbon ion (C-ion) beams provide unique advantageous biological and physical properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high relative biological effectiveness (RBE) resulting from the high linear energy transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a spread-out Bragg peak (SOBP) and make for a better dose distribution of the target volume by specified beam modulations. Between June 1994 and August 2005, a total of 2,371 patients with malignant tumors were registered in phase I/II dose-escalation studies and clinical phase II trials using C-ion beams generated at Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation studies, grade 3 or more late rectal complications had developed in some patients. However, the adverse effects were resolved because of the use of appropriate dose levels and modification of the radiation technique. C-ion beams can carry out hypofractionated radiotherapy with a large fraction dose and reduce the overall treatment times compared with conventional radiotherapy. They can also achieve better local tumor control even for radio-resistant tumors such as malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas with minimal morbidity to the normal surrounding tissues.

Bone Neoplasms↗
PubMed2005

DNA repair capacity measured by high throughput alkaline comet assays in EBV-transformed cell lines and peripheral blood cells from cancer patients and healthy volunteers.

We collected peripheral blood (PB) from 556 patients with various types of cancer who had undergone radiotherapy and from 81 healthy volunteers. We exposed whole PB and Epstein-Barr virus-transformed lymphoblastoid cell lines (EBLs) derived from the PB mononucleocytes to X-irradiation (5 Gy). Using the alkaline comet assay, we measured the immediate DNA damage and, at 15 min, the % residual damage. In PB, the immediate damage was similar in patients and healthy volunteers while the % residual damage (mean+/-S.D.) was significantly higher in patients with breast (54.3+/-A23.9), cervical (54.7+/-A23.9), head/neck (56.8+/-A24.4), lung (60.1+/-23.5), or esophageal cancers (59.5+/-A33.7) than in healthy donors (42.9+/-19.6) (P<0.05). We did not observe such differences in the EBV-transformed cell lines. Thus, radiation sensitivity of fresh PB cells measured by the alkaline comet assay was related to cancer status.

Blood Donors↗
PubMed2005

Hypofractionated radiotherapy with carbon ion beams for prostate cancer.

PURPOSE: Analysis of the results of hypofractionated conformal carbon ion radiotherapy for localized prostate cancer was performed, with special regard to normal tissue morbidity and biochemical relapse-free rate (bNED). METHODS AND MATERIALS: Analysis was performed for 201 patients treated with the dose fractionation regimen established during three clinical trials performed between June 1995 and February 2004. Outcomes were measured in terms of toxicity, survival, freedom from local recurrence, and bNED. RESULTS: No Grade 3 or higher toxicities were observed in either the rectum or genitourinary system, and the incidences of Grade 2 rectum or genitourinary morbidity were only 1.0% and 6.0%, respectively. The overall 5-year biochemical relapse-free survival was 83.2% without any local recurrence. Gleason score, initial PSA, and T stage were all significant prognostic factors for bNED, which was 97.1% in patients with Gleason score < or =7 and initial PSA <20 ng/mL. CONCLUSION: Hypofractionated carbon ion radiotherapy with the established dose fractionation regimen yielded satisfactory bNED without local recurrence and with minimal morbidity. Long-term results are necessary to confirm the utility of carbon ion radiotherapy in the treatment of localized prostate cancer.

Adenocarcinoma↗
PubMed2005

Concentrations of dioxins and related compounds in the blood of Fukuoka residents.

Blood samples of 152 residents (male 75 and female 77) aged 20-60 years in Fukuoka, Japan, were analyzed for dioxin toxic compounds of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) as well as 35 PCB congeners and 12 chlorinated pesticides by high-resolution gas chromatography/high-resolution mass spectrometry. Average concentrations of dioxin toxic equivalents (TEQ) from PCDDs, PCDFs, non-ortho PCBs, mono-ortho PCBs and their total in the blood of 152 residents were 10.28, 5.56, 7.75, 4.57 and 28.15 ppt in lipid, respectively. These total TEQ levels were comparable to the blood TEQ levels of normal Japanese (n=735). Lipid basis total TEQ levels progressively increased in the males from 17.1 ppt at age 20s to 47.5 ppt at age 50s and in the females from 19.5 ppt at age 20s to 54.5 ppt at age 50s. Dioxin toxic contribution of PCBs to total TEQ was increased from 31% at age 20s to 55% at age 50s. Average concentrations of total 35 PCBs and total 12 pesticides in the blood of 151 residents were 386 and 1079 ppb in lipid, respectively. Average concentrations (ppb in lipid) of total PCBs and total pesticides also progressively increased in the males from 213 and 444 at age 20s to 868 and 2140 at age 50s, respectively, and in the females from 199 and 588 at age 20s to 550 and 1977 at age 50s, respectively. The levels of TEQ, PCBs, hexachlorobenzene, beta-hexachlorocyclohexane, dieldrin, p,p'-dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyltrichloroethane, trans-nonachlor and cis-nonachlor were positively correlated with each other in most of the combinations, and the highest correlations (r>0.8) were observed between total TEQ and PCBs in both sexes.

Adult↗
PubMed2005

Disruptive effect of chloroquine on lysosomes in cultured rat hepatocytes.

Chloroquine has been used as an anti-malarial drug and is known as a lysosomotropic amine as well. The effects of chloroquine on lysosomal integrity in cultured rat hepatocytes were studied by measuring lysosomal enzyme beta-glucuronidase (beta-G) or lysosomal membrane glycoprotein (lamp-1) in Percoll density gradient fractions, in the cytosolic fraction obtained from cells permeabilized by digitonin or in the cytosolic fraction obtained by conventional cell fractionation. The distribution of beta-G on a Percoll density gradient in chloroquine-treated cells was approximately similar to that of a cytosolic protein, mevalonate pyrophosphate decarboxylase, in nontreated cells. Lamp-1 was decreased in the lysosomal fractions on a Percoll density gradient in chloroquine-treated cells, and was increased in the plasma membrane fraction, as compared with the levels in nontreated cells. Furthermore, after cells were cultured in the presence and absence of chloroquine, the proportions of beta-G activity in the cytosolic fraction obtained from the digitonin-permeabilized cells were 19% and 4%, while those in the cytosolic fraction obtained by conventional cell fractionation were 54% and 26%, respectively. From these findings, we infer that chloroquine caused the disruption of lysosomes in the living cells, and that lysosomes treated with chloroquine were easily disrupted by homogenization or centrifugation during cell fractionation.

Animals↗