Sensitivity improvement of infrared imaging video bolometer for divertor plasma measurement.

The sensitivity of an infrared imaging video bolometer (IRVB) was improved for the measurement of relatively low energy plasma radiation from the viewpoint of the metal foil absorber material. The photon energy of the radiation was considered up to 1 keV for the divertor plasma measurement. The thickness of the foil absorber was evaluated not only for conventional heavy elements, e.g., platinum, but also for light elements by the relation between the photon energy and attenuation length and by mechanical strength. A heat-transfer calculation using ANSYS suggested that light elements with practical foil thickness provide a higher temperature rise of the foil absorber compared with heavier elements with practical foil thickness. The maximum of the temperature rise was evaluated using He-Ne laser irradiation onto absorber samples. The material dependence of the temperature rise has a similar tendency between calculations and experiments. Experimentally, the sensitivity of the IRVB improved from 280 to 110 µW/cm2 using titanium with 1 µm thickness compared with conventional platinum with 2.5 µm thickness. Consequently, the signal-to-noise ratio of the IRVB could be improved from 2.8 to 9.1.

Long-term results of concurrent chemoradiotherapy with daily-low-dose continuous infusion of 5-fluorouracil and cisplatin (LDFP) for Stage I-II esophageal carcinoma.

We investigated long-term treatment outcomes and the feasibility of chemoradiotherapy consisting of daily-low-dose 5-fluorouracil and cisplatin (LDFP) chemotherapy plus radiotherapy for Stage I-II squamous cell esophageal cancer. Treatment records from the 2000 through 2008 period were reviewed retrospectively. Fractionated radiotherapy was performed with a total dose of 60 Gy delivered in 2 Gy per fraction. LDFP chemotherapy, as continuous infusion of 200 mg/m2 5-fluorouracil combined with one hour infusion of 4 mg/m2 cisplatin, was administered on the same days as radiotherapy. Survival was calculated by the Kaplan-Meier method. Survival, responses, failure patterns, and toxicities were evaluated. Seventy-six (47 stage I and 29 stage II) patients were analyzed with a median follow-up of 93.6 months. The 8-year overall survival (OS), progression-free survival (PFS) and cause-specific survival (CSS) rates were 63.4%, 49.8%, and 76.7%, respectively. The 8-year OS, PFS, and CSS for stage I and stage II patients were 71.0%/56.1%/82.9% and 45.2%/40.2%/66.6%, respectively. Sixty-eight patients (89.5%) completed the treatment regimen. A complete response (CR) was achieved in 68 patients (89.5%). Twenty-five patients (36.8%) experienced recurrence after CR. The failure patterns were (overlap included): local failure (n = 12), nodal metastasis (n = 12), distant metastasis (n = 3), details unknown (n = 2). Salvage therapy was performed for local failure; endoscopic therapy (n = 7) or surgery (n = 2). Six patients remain alive without relapse after salvage endoscopic therapy. Major Grade 3 or higher acute adverse events were leukopenia (22%), anorexia (17%), and esophagitis (11%). Major late toxicities (Grade 3 or 4) involved pericardial effusion (12%), pleural effusion (4%), and esophageal stenosis (3%). Chemoradiotherapy with LDFP provided favorable long-term survival with acceptable toxicity for Stage I-II squamous cell esophageal cancer. The tumor response was excellent, but close endoscopic follow-up is essential for detecting and treating local recurrence.

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer.

BACKGROUND: Inducible activation of nuclear factor (NF)-κB is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-κB with a novel NF-κB inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy. METHODS: PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-κB activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed. RESULTS: The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-κB activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3σ in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively. CONCLUSION: Blockade of NF-κB activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours.

OBJECTIVE: The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0-1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours. METHODS: Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose-volume histograms (DVHs) were constructed to identify the incidence of RP. RESULTS: The median follow-up period was 12 months (range, 6-45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5-30 Gy (V5-30) and mean lung dose were significant factors differentiating between grade 0-1 and grade 2 RP, and V15-30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0-1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0-1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0-2 RP. CONCLUSIONS: Grade 0-2 RP was dose-volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0-2 RP. However, incidences of V15-30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.

CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function.

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes.

BACKGROUND: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial. METHODS: A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid. RESULTS: Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90). CONCLUSIONS: These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.

Superiority of radioisotope over blue dye for sentinel lymph node detection in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly performed using radioisotopes and/or blue dye. However, it is still undefined which reagent is more suitable for identifying sentinel lymph nodes (SLN). PATIENTS AND METHODS: A consecutive series of 640 breast cancer patients who had undergone SLNB at the Keio University Hospital from 2001 to 2006 was analyzed. The SLN was identified by a combination of technetium-99m tin colloid and isosulfan blue dye. The correlation between clinicopathological factors and the distribution of radioisotopes and blue dye was analyzed. The single metastatic lymph node revealed by axillary lymph node dissection (ALND) is the 'true SLN', and the distribution of radioisotopes and blue dye to the 'true SLN' was also analyzed. RESULTS: Blue-dye- and radioisotope-positive SLN were identified in 79.6 and 94.7% of the patients, respectively. Taken together, SLN were identified in 625 patients (97.7%) by radioisotope and/or blue dye. No significant correlation was observed between clinicopathological features and the distribution of the reagents. ALND found 73 patients with single lymph node metastasis, and 73 'true SLN' were identified by blue dye in 65.7% (48/73), and by radioisotope in 95.9% (70/73) of the cases. CONCLUSION: These data suggest that radioisotopes are superior to blue dye in detecting SLN in breast cancer.

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation.

This study aimed to retrospectively evaluate the incidence of kerato-conjunctivitis in patients receiving TBI followed by high-dose cytarabine, and to clarify how effectively topical corticosteroid eye drops prevent kerato-conjunctivitis in these patients. Fifty-three patients who received cytarabine at a dose of 3 g/m2 every 12 h for 4 days after receiving TBI (12 Gy) as a conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated. For the prophylaxis of kerato-conjunctivitis, all patients received betamethasone sodium phosphate eye drops every 6 h, starting 1 day before the first dose of cytarabine and continuing until 1 day after the last dose of cytarabine or the complete resolution of ocular symptoms. For grading of kerato-conjuncitivitis, the National Cancer Institute-Common Toxicity Criteria were used. Among the 53 patients, the grades of kerato-conjunctivitis were grade 0 in 13 patients, grade 1 in 6 patients (11.3%), grade 2 in 10 patients (18.9%) and grade 3 in 25 patients (47.2%). These results strongly suggest that topical corticosteroid eye drops could not effectively prevent the development of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI. Further investigation into a more effective prophylaxis for cytarabine-induced kerato-conjunctivitis in this setting is required.

First combined electron backscatter diffraction and transmission electron microscopy study of grain boundary structure of deformed quartzite.

The structures of boundaries in a deformed and dynamically recovered and recrystallized quartz polycrystal (mylonite) were characterized by transmission electron microscopy, after the misorientation angles across the same grain boundaries had been analysed using electron backscatter diffraction in a scanning electron microscope. In this new approach, a specific sample area is mapped with electron backscatter diffraction, and the mapped area is then attached to a foil, and by the ion beam thinned for transmission electron microscopy analysis. Dislocations in grain boundaries were recognized as periodic and parallel fringes. The fringes associated with dislocations are observed in boundaries with misorientations less than 9 degrees , whereas such fringes cannot be seen in the boundaries with misorientations larger than 17 degrees . Some boundaries with misorientations between 9 degrees and 17 degrees generally have no structures associated with dislocation. One segment of a boundary with a misorientation of 13.5 degrees has structures associated with dislocations. It is likely that the transition from low-angle to high-angle boundaries occurs at misorientations ranging from approximately 9 degrees to 14 degrees . Change in the grain boundary structure presumably influences the mobility of the boundaries. In the studied deformed quartz vein, a relative dearth of boundaries between misorientation angles of theta = 2 degrees and theta = 15 degrees has previously been reported, and high-angle boundaries form cusps where they intersect low-angle boundaries, suggesting substantial mobility of high-angle boundaries.

Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix.

Patients with cervical cancer are subject to postoperative adjuvant therapy if the histopathologic examination reveals parametrial involvement. This study evaluated the patterns of failure in patients with pathologic parametrial invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and March 1997, 45 patients with pT2b cervical cancer were treated with postoperative pelvic irradiation. The median age was 52 years. Preoperative clinical stages were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had lymph node metastasis. The median total dose of whole pelvic radiation therapy was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the nodal status was examined. None of the 22 patients without lymph node metastasis developed distant metastasis. Among the 23 node-positive patients, 6 developed distant metastasis as an initial failure site. The 5-year overall survival of the entire group was 78%. The actuarial distant metastasis-free rates at 5 years were 73% and 100% for those with and without pelvic lymph node metastasis, respectively (P = 0.016). Results support previous evidence for chemoradiation in patients with pelvic lymph node metastasis. However, it appears that the role of systemic chemotherapy for node-negative pT2b patients is yet to be established.

FR901469, a novel antifungal antibiotic from an unidentified fungus No. 11243. III. Structure determination.

A novel antifungal antibiotic, FR901469, was isolated from an unidentified fungus No. 11243. It is a water-soluble 40-membered macrocyclic lipopeptidolactone, consisting of D-Ala, L-Tyr, L-Val, trans-4OH-L-Pro, trans-3OH-L-Pro, threo-3OH-L-Gln, Gly, L-Orn, L-Thr, three residues of D-alloThr and a (3R)-hydroxypalmitic acid. Its structure, including absolute configurations, was unequivocally determined as 1 based on chemical and spectroscopic evidence.

Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma.

This study was designed to investigate the relationship between Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy and outcome of treatment in patients with non-Hodgkin's lymphoma (NHL). Forty-five patients with NHL were studied with Tc-99m-MIBI before any treatment. Images of the lesions were obtained at 20 min and 2 h after radionuclide administration. Visual semi-quantitative interpretation was performed for Tc-99m-MIBI (grade 0-4) scintigraphy. Patients underwent 3-5 cycles of CHOP chemotherapy with/without involved field radiotherapy for large tumors. Their responses to treatment were evaluated at the end of chemotherapy and during the follow-up period. Forty of 45 patients (89%) showed abnormal uptake of Tc-99m-MIBI. There was no correlation between intensity of MIBI accumulation and response to chemotherapy. However, patients with negative or decreased MIBI activity 2 h after radionuclide administration showed worse response to chemotherapy compared to those with continued MIBI activity. MIBI activity could not predict the development of relapse in the follow-up study. In this study, the number of patients was small and we could not reach definite conclusions. However, we think that MIBI scintigraphy is not valuable for predicting the chemotherapy outcome in patients with NHL.

Breast-conserving therapy for ductal carcinoma in situ.

This retrospective analysis evaluates the treatment results and prognostic factors of 114 patients with ductal carcinoma in situ (DCIS) undergoing breast conserving therapy (BCT) at Keio University Hospital Department of Radiology, between 1988 and 1997. A total of 132 patients with DCIS of the breast came to our hospital between 1988 and 1997, and 114 cases were suitable candidates for BCT. All of the patients were female and ranged in age from 26 to 81 years (median 46). Ninety-one patients were premenopausal, and 23 were postmenopausal. Median clinical tumor size was 2.0 cm (0-8.0 cm). Postoperatively 48 cases received 50 Gy/25 fractions of external irradiation to the whole breast via tangential ports. The follow-up period after treatment ranged from 11 to 162 months (median 46.7). The local relapse-free rate and overall survival rate of the 114 patients were 89.5% and 100%, respectively. Local failure and regional nodal failure occurred in 12 and 1 patient, respectively. Radiotherapy was a significant risk factor for local failure (p=0.05). No postmenopausal patients developed local failure, but the difference did not reach statistical significance (p=0.103). The 12 recurrent cases underwent additional surgery and all remain alive without recurrence, to date, i.e., at least 16 months. Breast-conserving surgery plus irradiation is appropriate treatment for DCIS patients.

Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid in rats.

Extract of Gymnema sylvestre leaves was administered to rats receiving either a high fat diet or normal fat diet for 10 weeks to investigate its influence on plasma and liver lipids and on visceral fat accumulation. In addition, its effect was compared with those of chitosan and the influence of combined use of these two substances was also evaluated. Within the high fat diet groups, the extract suppressed body weight gain and accumulation of liver lipids to the same extent as chitosan and the combined use. In addition, intraperitoneal fat and fat drop vacuoles on the epithelium of renal tubules, noted in the high fat diet group, were scattered by administration of the extract with the same results as for chitosan and combined use. Within the normal fat diet groups, plasma triglyceride levels decreased by administration of the extract, with similar results as chitosan and combined use. Concerning plasma total cholesterol, there was no decreasing effects with the extract, as found with chitosan and combined use. However, the effect of chitosan on plasma total cholesterol tended to be enhanced when used in combination with the extract. In addition, long-term administration of the extract did not show any influence on hematological and blood chemical parameters.

Effect of administration with the extract of Gymnema sylvestre R. Br leaves on lipid metabolism in rats.

Extract of Gymnema sylvestre R. Br leaves (GE) was orally administered once a day to rats fed a high fat diet or normal fat diet for 3 weeks to investigate its influence on lipid metabolism. As a result, GE did not influence body weight gain or feed intake in both diet groups during the experimental period. The apparent fat digestibility was significantly decreased by GE in both diet groups for the last 2 weeks of the experimental period, though not the apparent protein digestibility. In addition, the excretion of neutral sterols and acid steroids into feces was increased by GE in both diet groups. Furthermore, GE decreased the total cholesterol and triglyceride levels in serum. On the other hand, blood lecithin-cholesterol acyltransferase (LCAT) activity was increased by GE. Moreover, it was suggested that GE influenced cecal fermentation and that propionic acid and acetic acid contents in cecum were significantly increased by GE. Consequently, it was suggested that GE improved serum cholesterol and triglyceride levels through influence over a wide range of lipid metabolism in rats.

Effect of combined treatment with radiation and low dose etoposide on cell survival.

BACKGROUND: To improve the radiotherapy results, we evaluated etoposide as an effective radiosensitizer by using cultured cell-lines. MATERIALS AND METHODS: Four cell lines having different doubling times (DT) were used: V79 (Chinese hamster fibroblasts, DT = 9 hours), (1), T24 (human bladder cancer, DT = 19 hours) (2), MDA-MB231 (human breast cancer, DT = 25-30 hours) (3) and RMG1 (human ovarian cancer, DT = 50 hours) (4). Cell survival was determined by colony assay and cell cycle analysis was performed by flow-cytometry. RESULTS: The survival curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and RMG1. Neither 24-hours exposure to etoposide (< or = 0.05 microgram/ml) or 0.5-h exposure (< or = 1.0 microgram/ml) had any cell killing effect on any of the cell lines used. When the cells were irradiated after exposure to 1 microgram/ml of etoposide for 0.5 hours, no radiosensitization was observed in any of the cell lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells (which have a relatively short DT) when they were incubated with 0.05 microgram/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231 or RMG1 cells (which have a relatively long DT). CONCLUSION: It is suggested that a combination of radiation and etoposide may be useful in the treatment of rapidly growing cancer.

Cell killing and mutation induction by heavy ion beams.

Carbon beam radiotherapy for cancer patients was initiated in Japan in June 1994. This study attempts to clarify the radiobiological effects of heavy ion beams. In this study, human cancer cell lines (RMG-1, MDA-MB231) and V79 cells were used. The cell killing was determined by colony forming assay, and mutation induction was determined by counting the number of 6-thioguanine resistant colonies (hprt locus mutation assay). The cell lines were irradiated with carbon (20 or 80 keV/microm) or neon beams (80 keV/microm). Carbon ions with a higher LET value (80 keV/microm) had an enhanced cytotoxic effect compared to those with a lower LET value (20 keV/microm). Carbon beams produced a slightly stronger cytotoxic effect than neon beams when irradiated at the same LET level (80 keV/microm), but the difference was not remarkable. The mutant fraction was significantly higher in all cell lines when they were irradiated with heavy ion beams, compared to the results for X-ray irradiation. The mutant fraction increased when the LET of the carbon beams increased. At equivalent LET values, the mutant fraction was lower for neon beams than for carbon beams. Fractionation of carbon beam irradiation had no effect on survival, but reduced the mutant fraction. Neon beams might be more appropriate for heavy ion therapy, especially when higher doses are being used. In addition, the fractionation of heavy ion beam administration might be appropriate for reducing the mutant fraction.

Microspinosamide, a new HIV-inhibitory cyclic depsipeptide from the marine sponge Sidonops microspinosa.

Microspinosamide (1), a new cyclic depsipeptide incorporating 13 amino acid residues, was isolated from extracts of an Indonesian collection of the marine sponge Sidonops microspinosa. Its structure was elucidated by extensive NMR and mass spectral analyses, and by chemical degradation and derivatization studies. The tridecapeptide 1 incorporates numerous uncommon amino acids, and it is the first naturally occurring peptide to contain a beta-hydroxy-p-bromophenylalanine residue. Microspinosamide (1) inhibited the cytopathic effect of HIV-1 infection in an XTT-based in vitro assay with an EC(50) value of approximately 0.2 microg/mL.

Indications of stereotactic irradiation for brain lesions.

Stereotactic radiosurgery (SRS: single-fraction stereotactic irradiation) was originally developed to treat benign lesions in the brain, and has been adopted for the treatment of small primary or metastatic brain tumours. It has recently been recommended that stereotactic radiotherapy (SRT: fractionated stereotactic irradiation) be applied to the treatment of brain tumours; however, it requires much more time and work than SRS, and sufficient radiobiological evaluations of these techniques have never been carried out. Biologically effective doses were calculated to determine the indications for SRS and SRT, and to decide on an effective SRT schedule, incorporating the factors of 'repair' and 'cell proliferation'. The results suggest that SRS would be recommended for arteriovenous malformations and benign tumours that have distinct margins separating them from surrounding normal tissue and SRT would be recommended for benign or malignant brain tumours without clearly defined boundaries. The recommended SRT schedules would be 7 Gy x 7 fractions every other day for malignant tumours and 3.5 Gy x 12 fractions every other day for benign tumours. However, clinically, these schedules should be modified according to many other factors in individual cases.