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H Tsujii

Publications and source records attributed to H Tsujii.

At least 19 recordsLinked to original sources

X-rays vs. carbon-ion tumor therapy: cytogenetic damage in lymphocytes.

PURPOSE: To measure chromosomal aberrations in peripheral blood lymphocytes from cancer patients treated with X-rays or carbon ions (C-ions). METHODS AND MATERIALS: Blood samples from patients diagnosed for esophageal or uterine cervical cancer were obtained before, during, and at the end of the radiation treatment. The novel technique of interphase chromosome painting was used to detect aberrations in prematurely condensed chromosomes 2 and 4. The fraction of aberrant lymphocytes was measured as a function of the dose to the tumor volume. For comparison, blood samples were also exposed in vitro to X-rays or to carbon ions accelerated at the HIMAC. RESULTS: C-ions were more efficient than X-rays in the induction of chromosomal aberrations in vitro. In patients with similar pathologies, tumor positions, and radiation field sizes, however, C-ions induced a lower fraction of aberrant lymphocytes than X-rays during the treatment. The initial slope of the dose-response curve for the induction of chromosomal aberrations during the treatment was correlated to the relative decrease in the number of white blood cells and lymphocytes during the treatment. CONCLUSION: C-ions induce a lower level of cytogenetic damage in lymphocytes than X-rays, reducing the risk of bone marrow morbidity.

Aged↗

Complex-type chromosomal exchanges in blood lymphocytes during radiation therapy correlate with acute toxicity.

The new method of chemical-induced premature chromosome condensation combined with fluorescence in situ hybridization was used to analyze chromosomal damage in peripheral blood mononuclear lymphocytes of patients undergoing radiation treatment for esophageal cancer with high-energy X-rays or accelerated carbon ions at the National Institute of Radiological Sciences (Chiba, Japan). Total number of aberrant cells correlated with radiation field size, but no correlation was found with acute toxicity. A high frequency of complex-type exchanges were also recorded. This aberration type presented a high individual variability, and correlated well with the acute morbidity. Cytogenetic analysis by interphase chromosome painting is proposed as a useful tool for monitoring normal tissue effects during radiotherapy.

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MR imaging of radiation osteitis in the sacroiliac joints.

The purpose of this study was to analyze magnetic resonance (MR) images of radiation osteitis of sacroiliac joints, retrospectively. Seven patients with radiation osteitis, which was diagnosed by pelvic plain radiographs and CT images, underwent MRI. T(1)-weighted spin echo images and T(2)-weighted fast spin echo images were obtained in all patients. Four patients were examined after gadolinium injection. Major signal changes of radiation osteitis were distributed on the iliac side. T(1)-weighted images showed diffuse low intensity both in sacral and iliac sides. T(2)-weighted images showed very low intensity adjacent to sacroiliac joints, but mixed intensity was illustrated apart from joints, and high intensity in the peripheral areas. Radiation osteitis showed slight to mild, but irregular enhancement in four patients after gadolinium administration. MRI can illustrate abnormal bone change distribution and is useful for diagnosing this entity by characteristic intensity patterns on T(1)-weighted images with and without gadolinium and T(2)-weighted image. However, the diagnosis of accompanied insufficiency fractures in the area of radiation osteitis is occasionally difficult with conventional MRI.

Aged↗

Usefulness of PET with 11C-methionine for the detection of hilar and mediastinal lymph node metastasis in lung cancer.

UNLABELLED: We retrospectively evaluated the usefulness of PET with 11C-methionine (methionine PET) for the diagnosis of lymph node metastases in patients with lung cancer. METHODS: Methionine PET and CT were performed before surgical intervention in 41 patients with primary lung cancer. We evaluated individual lymph nodes by methionine PET along with corresponding CT images. The 11C-methionine accumulation of lymph nodes was assessed semiquantitatively by analysis of the tumor-to-muscle ratio (TMR) and was compared with CT and histological diagnoses. RESULTS: A total of 126 lymph nodes, 36 of which were histologically diagnosed as metastatic, were assessed by CT and methionine PET. The TMR in metastatic lymph nodes (n = 36) was 5.15+/-1.69, whereas that of nonmetastatic lymph nodes (n = 90) was 2.91+/-0.76; this difference was significant (P < 0.0001). The most adequate TMR cutoff value for diagnosis of metastasis based on the results of receiver operating characteristic curve analysis was 4.1. The positive and negative predictive values, sensitivity, specificity, and accuracy of methionine PET were 79.5%, 94.3%, 86.1%, 91.1%, and 89.7%, respectively, and were superior to those of CT (57.6%, P = 0.04; 81.7%, P = 0.008; 52.8%, P = 0.002; 84.4%, NS; and 75.4%, P = 0.002, respectively). All positive nodes that were shown to be true-positive by CT, and 12 of 17 false-negatives on CT were correctly diagnosed by PET. Ten of 14 lymph nodes that were false-positive on CT were also correctly diagnosed by PET. CONCLUSION: Methionine PET appears to be superior to CT for the diagnosis of lymph node metastasis in lung cancer patients. The high negative predictive value of methionine PET suggests that cases in which lymph nodes are enlarged on CT with negative PET analysis may be diagnosed as negative for metastasis.

Carbon Radioisotopes↗

Relationship between p21/WAF-1/CIP-1 and apoptosis in cervical cancer during radiation therapy.

PURPOSE: P21/WAF-1/CIP-1 was not considered to be involved in the regulation of apoptosis, an important indicator of radiosensitivity. However, it has been reported recently that apoptosis was suppressed when p21 expressed. The purpose of this study was to clarify the relationship between p21 and apoptosis and to evaluate the role of p21 in cervical cancer during radiation therapy (RT). METHODS AND MATERIALS: Twenty-one patients with cervical cancer were treated by RT. Tissue samples were obtained from cervical tumors of all patients before RT, and 6 hours after the fifth dose of 1.8 Gy (5th Dose). Samples were subjected to nick end labeling for apoptosis and immunohistochemical staining for p21 and p53 antigen expression. RESULTS: The mean apoptotic index, p21 labeling index and p53 labeling index were 0.27%, 9.24% and 6.60%, respectively, before RT and increased significantly to 1.20%, 17.5% and 13.9%, respectively, after 5th Dose. The apoptotic index at 5th Dose was inversely correlated with the p21 labeling index (r = -0.50, p = 0.025). Furthermore, a positive correlation was observed between the p21 and p53 labeling indices both before RT and at 5th Dose (r = 0.52, p = 0. 02; r = 0.63, p < 0.01, respectively). CONCLUSION: Our results demonstrate that apoptosis and expression of p21 and p53 were induced in cervical cancer during RT. p21 expression was dependent on p53 expression and moreover, it is suggested-that p21 might be a potential suppressor of radiation-induced apoptosis in cervical cancer during RT.

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Early detection of radiation-induced liver injury in rat by superparamagnetic iron oxide-enhanced MR imaging.

The detectability of early liver injury induced by irradiation was studied using magnetic resonance (MR) imaging enhanced with superparamagnetic iron oxide (SPIO), a tissue-specific contrast agent against the reticuloendothelial system (RES). In rat, 3 days after focal irradiation (0-10 Gy), MR imaging was performed and specimens were obtained to observe the phagocytic function of RES. The irradiated portion of the liver was visualized with a clear demarcation from the nonirradiated part by SPIO-enhanced MR images as a decrease in negative enhancement reflecting the function of RES (P < 0.05), whereas this was impossible with nonenhanced MR images. Significant regression was observed as a dose-related change of the signal intensity in the irradiated portion on SPIO-enhanced MR images (R = 0.867, P < 0.0001). SPIO-enhanced MR imaging was reliable for detecting the range and extent of liver injury a few days after low-dose irradiation, and it may be a useful procedure for verifying the target area in clinical cases of radiation therapy.

Animals↗

Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome.

BACKGROUND & AIMS: The Dubin-Johnson syndrome is characterized by conjugated hyperbilirubinemia and by impaired secretion of anionic conjugates from hepatocytes into bile. Absence of the multidrug-resistance protein 2 (MRP2; symbol ABCC2), an adenosine triphosphate-dependent conjugate export pump, from the hepatocyte canalicular membrane is the molecular basis of this syndrome. The aim of this study was the elucidation of all exon-intron boundaries of the MRP2 gene as a prerequisite for the analysis of mutations in patients with Dubin-Johnson syndrome. METHODS: Exon-intron boundaries of MRP2 were determined, and the amplified exons were screened for mutations. Immunofluorescence microscopy served to localize the MRP2 protein in human liver. RESULTS: The human MRP2 gene is approximately 45 kilobases long; it contains 32 exons and a high proportion of class 0 introns. In 2 patients with Dubin-Johnson syndrome, we detected a nonsense mutation at codon 1066 and a 6-nucleotide deletion mutation affecting codons 1392-1394. The MRP2 protein was absent from the canalicular membrane of both patients. CONCLUSIONS: The mutations detected so far show that various mutations in the MRP2 gene can lead to the Dubin-Johnson syndrome. The exon-intron boundaries established in this article will facilitate the analysis of additional mutations in the MRP2 gene.

ATP Binding Cassette Transporter, Subfamily B↗

A horizontal CT system dedicated to heavy-ion beam treatment.

A horizontal helical CT system to be used for 3-D treatment planning and for positioning verification of patients in seated position was installed in the treatment room with a fixed horizontal heavy-ion beam line. The system achieved the expected mechanical consistency and reliability.

Humans↗

Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods.

Estimates of equivalent whole-body dose following partial body exposure can be performed using different biophysical models. Calculations should be compared with biodosimetry data, but measurements are complicated by mitotic selection induced in target cells after localized irradiation. In this paper we measured chromosomal aberrations in peripheral blood lymphocytes during radiotherapy, and estimated the equivalent whole-body dose absorbed, by using the novel technique of interphase chromosome painting. Premature chromosome condensation was induced in stimulated lymphocytes by incubation in calyculin A, and slides were hybridized in situ with whole-chromosome DNA probes specific for human chromosomes 2 and 4. Reciprocal exchanges were used to estimate the equivalent whole-body dose, based on individual pre-treatment in vitro calibration curves. Equivalent whole-body dose increased as a function of the number of fractions, and reached a plateau at high fraction numbers. Chromosomal aberration yields were dependent on field size, tumour position and concurrent chemotherapy. Results suggest that interphase chromosome painting is a simple technique able to give a reliable estimate of the equivalent whole-body dose absorbed during therapeutic partial-body irradiation.

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Bax protein expression correlates with radiation-induced apoptosis in radiation therapy for cervical carcinoma.

BACKGROUND: Bax protein serves as a positive regulator of apoptosis by forming heterodimers with bcl-2 protein, thereby promoting cell survival. It is unclear whether the regulation of apoptosis reported in many studies is applicable to the apoptotic phenomenon observed in conventional fractionated radiation therapy for cervical carcinoma. METHODS: The authors assessed the relation between apoptosis and the expression of Bax and bcl-2 protein in fractionated radiation therapy for cervical carcinoma by using in situ nick end labeling (ISEL) and immunohistochemical methods. RESULTS: Specimens were excised from the cervical tumors of 20 patients before and after administration of a total irradiation dose of 9 gray (Gy). The apoptotic cell index (AI) in tumor cells was 0.22% before irradiation and 1.20% after the administration of the 9 Gy, which represented a significant increase (P=0.0004). The positive rate of Bax protein increased from 15% (in 3 of 20 patients) before irradiation to 60% (in 12 of 20 patients) after the 9 Gy was administered, a statistically significant change (P=0.0126). In addition, there was a significant correlation between Bax protein expression and apoptosis positivity after the 9 Gy was administered (P=0.018). CONCLUSIONS: These results suggest that Bax protein is associated with apoptosis induced by fractionated radiation therapy.

Apoptosis↗

[Clinical evaluation of heavy-particle radiotherapy using dose volume histogram (DVH)].

Radiotherapy with heavy particles such as proton and heavy-charged particles is a promising modality for treatment of localized malignant tumors because of the good dose distribution. A dose calculation and radiotherapy planning system which is essential for this kind of treatment has been developed in recent years. It has the capability to compute the dose volume histogram (DVH) which contains dose-volume information for the target volume and other interesting volumes. Recently, DVH is commonly used to evaluate and compare dose distributions in radiotherapy with both photon and heavy particles, and it shows that a superior dose distribution is obtained in heavy particle radiotherapy. DVH is also utilized for the evaluation of dose distribution related to clinical outcomes. Besides models such as normal tissue complication probability (NTCP) and tumor control probability (TCP), which can be calculated from DVH are proposed by several authors, they are applied to evaluate dose distributions themselves and to evaluate them in relation to clinical results. DVH is now a useful and important tool, but further studies are needed to use DVH and these models practically for clinical evaluation of heavy-particle radiotherapy.

Elementary Particles↗

Radiation tolerance of cirrhotic livers in relation to the preserved functional capacity: analysis of patients with hepatocellular carcinoma treated by focused proton beam radiotherapy.

PURPOSE: To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy. MATERIALS AND METHODS: We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12-27 months after proton beam radiotherapy. Tumors were treated with focused proton beams with target doses of 140-186 TDF (time, dose, and fractionation). We measured the degree of hypertrophy of the untreated liver volume by measuring the total liver volume and the treated liver volume which was radiologically identified on contrast-enhanced CT scans. The risk of radiation-induced liver failure was estimated using the prediction score (PS) originally used for estimating posthepatectomy liver failure, substituting the planned treated liver volume for the resection liver volume. RESULTS: The degree of hypertrophy ranged from -19% to 51%, and was significantly positively correlated with the ratio of the planned treated liver volume to the functional liver volume. The PS agreed well with observed radiation tolerance in 21 patients, but underestimated the tolerance in 5. This underestimation was diminished when the PS was recalculated using the identified untreated liver volume in lieu of the planned untreated liver volume. CONCLUSION: As in surgical treatment, radiation tolerance of the cirrhotic liver after focused treatment is closely related to the preserved functional capacity of the identified untreated liver volume, which shows compensatory hypertrophy following radiotherapy.

Aged↗

Comparison between magnetization transfer contrast and fast spin-echo MR imaging of degenerative disease of the cervical spine at 0.3 T.

We compared magnetization transfer contrast (MTC) with gradient recalled echo (GRE) magnetic resonance imaging (MRI) and fast spin-echo (FSE) MRI of the degenerative cervical spine at 0.3 T. Fifty patients with suspected degenerative disease of the cervical spine were prospectively evaluated. Multislice sagittal and axial images of the cervical spine were obtained using MTC GRE sequence [repetition time (TR)/echo time (TE)/flip angle = 750/23/25 degrees] and FSE sequence with peripheral gating (TR/effective TE = 2000-4000/120). Quantitatively, FSE showed higher signal-to-noise ratio and superior disk contrast between normal and degenerative disks, while MTC images showed superior contrast-to-noise ratio for the cerebrospinal fluid (CSF) versus cord and superior CSF homogeneity. In qualitative analysis, similar results were obtained. In conclusion, FSE and MTC GRE sequences are MRI techniques of imaging the cervical spine that have different characteristics and supplement each other in the diagnostic imaging of degenerative disease of the cervical spine.

Adult↗

[Clinical evaluation and perspective of charged particle therapy].

In cancer radiotherapy, protons and heavy-ions share the same beneficial property of superior dose localization. In addition, heavy-ions are high-LET radiations and have increased biological effectiveness when compared with photons or protons. The potential indications for them are those diseases which are usually hard to cure with conventional radiations. At present there are 17 operating facilities world-wide for proton therapy, which in Japan is being conducted at the National Institute of Radiological Sciences (NIRS) and Tsukuba University (PMRC). Currently, Massachusetts General Hospital (MGH) in USA and the National Cancer Institute East Hospital in Japan are building a hospital-based proton facility, both of them will have a fixed energy cyclotron (230MeV). New plans for commencing proton therapy are also proposed by many other institutions in the world. As with heavy-ion therapy, clinical trials have been carried out since 1994 using carbon-ions generated by HIMAC (Heavy-ion medical accelerator in Chiba) at NIRS. The HIMAC is the world's only heavy-ion accelerator complex dedicated to medical use in a hospital environment. The Hyogo prefecture has just decided to build a similar ion therapy facility. As of February 1997, a total of 230 patients were treated in carbon-ion Phase I/II studies at NIRS. So far, carbon-ions appear to be effective in such cases as locally advanced tumors and non-squamous tumors.

Carbon↗

[Metabolic imaging of human brain tumors: H-1 chemical shift imaging and PET].

Positron Emission Tomography(PET) and Proton Chemical Shift Imaging(1H-CSI) has provided a cerebral metabolism. The glucose analog fluorine-18 fluorodeoxy-glucose(FDG) and amino acid analog 11C-L-methionine is the most commonly used PET tumor tracer. This time we compare with 1H-CSI and PET in gliomas and metastatic brain tumor with computer-assisted fusion images. We experienced some cases of the brain tumor. One case is metastatic brain tumor after radiation therapy, localized in right parietal hemisphere, with hemorrhage, and slightly accumulated Gd-DTPA in tumors. 11C-methionine PET demonstrates defects in tumors, but slight accumulated surrounding tumors. Accumulation of PET lesion is not elevated choline in CSI, but lactate is accumulated in tumors. Choline signal elevation seen in brain neoprasms, associated with increased cellular proliferation. Accumulation of PET and another accumulation of lactate in tumor are not demonstrate recurrence. Fusion image of PET and CSI is useful in understanding metabolism of brain tumor.

Aspartic Acid↗

Clearance of parenchymal tumors following radiotherapy: analysis of hepatocellular carcinomas treated by proton beams.

Clearance of a parenchymal tumor following radiotherapy was determined by using follow-up CT scans of 18 hepatocellular carcinoma tumors treated with focused proton beams. Regression analysis of the daily decrement (DD) and the diameter (D) of a tumor mass in each CT observation interval, DD = a*Db, showed that the exponent b was 3.0 or larger in early periods and 2.0 or smaller in late periods. This suggests that the clearance depends initially on the tumor volume, subsequently on the tumor surface area, and then it becomes much more moderate, possibly due to radiation damage to the parenchymal tissues.

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