Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.

BACKGROUNDS: Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious. METHODS: A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented. RESULTS: A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group. CONCLUSIONS: A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.

Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system.

Animal fetuses and embryos may have applications in the generation of human organs. Progenitor cells may be an appropriate cell source for regenerative organs because of their safety and availability. However, regenerative organs derived from exogenous lineage progenitors in developing animal fetuses have not yet been obtained. Here, we established a combination system through which donor cells could be precisely injected into the nephrogenic zone and native nephron progenitor cells (NPCs) could be eliminated in a time- and tissue-specific manner. We successfully achieved removal of Six2+ NPCs within the nephrogenic niche and complete replacement of transplanted NPCs with donor cells. These NPCs developed into mature glomeruli and renal tubules, and blood flow was observed following transplantation in vivo. Furthermore, this artificial nephron could be obtained using NPCs from different species. Thus, this technique enables in vivo differentiation from progenitor cells into nephrons, providing insights into nephrogenesis and organ regeneration.

Improvement of gamete quality and its short-term storage: an approach for biotechnology in laboratory fish.

In fish, in vitro fertilization is an important reproductive tool used as first step for application of others biotechniques as chromosome and embryo manipulation. In this study, we aimed to optimize gamete quality and their short-term storage from the yellowtail tetra Astyanax altiparanae, for future application in laboratory studies. Working with sperm, we evaluated the effects of spawning inducers (carp pituitary gland and Ovopel® [(D-Ala6, Pro9-NEt) - mGnRH+metoclopramide]) and the presence of female on sperm motility. Additionally, we developed new procedures for short-term storage of sperm and oocytes. Briefly, sperm motility was higher when male fish were treated with carp pituitary gland (73.1 ± 4.0%) or Ovopel® (79.5 ± 5.5%) when compared with the control group treated with 0.9% NaCl (55.6 ± 27.2%; P=0.1598). Maintenance of male fish with an ovulating female fish also improved sperm motility (74.4 ± 7.4%) when compared with untreated male fish (42.1 ± 26.1%; P=0.0018). Storage of sperm was optimized in modified Ringer solution, in which the sperm was kept motile for 18 days at 2.5°C. The addition of antibiotics or oxygen decreased sperm motility, but partial change of supernatant and the combination of those conditions improve storage ability of sperm. Fertilization ability of oocytes decreased significantly after storage for 30, 60 90 and 120 min at 5, 10, 15 and 20°C when compared with fresh oocytes (P=0.0471), but considering only the stored samples, the optimum temperature was 15°C. Those data describe new approaches to improve semen quality and gametes short-term storage in yellowtail tetra A. altiparanae and open new possibilities in vitro fertilization.

Genomic constitution and atypical reproduction in polyploid and unisexual lineages of the Misgurnus loach, a teleost fish.

The loach (Misgurnus anguillicaudatus) is an excellent animal model to elucidate biological origin and evolutionary significance of genome duplication and unisexual reproduction because artificially induced and naturally occurring polyploids and parthenogenetic (gynogenetic, androgenetic) animals can be compared. First, we summarize the chromosome manipulation techniques to induce triploids and tetraploids by inhibiting meiotic or mitotic divisions of inseminated eggs, respectively, as well as parthenogenetic animals, obtained after fertilization with genetically inactivated gametes. Then, we review the knowledge on natural polyploid and unisexual lineages found in Misgurnus loaches. A natural diploid-tetraploid complex occurs in wild populations in central China, and these diploid and tetraploid loaches reproduce bisexually. Chinese tetraploids are considered autotetraploid, which may have arisen by doubling of the entire genome of an ancestral diploid, based on cytogenetic results from FISH (fluorescence in situ hybridization) karyotypes and meiotic configurations. In contrast, gynogenetically reproducing clonal diploid lineages have been discovered in a few wild populations in Japan, although most wild-type individuals are bisexually reproducing diploids. Such clonal diploid loaches sometimes produce triploid progeny by accidental incorporation of a sperm nucleus into an unreduced diploid egg, and the resulting triploid generates haploid eggs by meiotic hybridogenesis. Unreduced diploid gametes of clonal loaches are generated by a cytological mechanism, premeiotic endomitosis, which likely occurs in the early (gonium stage) germ cells. Initiation of gynogenetic development is related to a failure of decondensation of the male (sperm) pronucleus in unreduced diploid eggs of a clonal loach. Clonal lineages may have arisen from a past hybrid event between genetically divergent groups, but their exact origins are unknown at present. See also the sister article focusing on plants by Hegarty et al. in this themed issue.

Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome.

The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.

Epithelial expression of interleukin-37b in inflammatory bowel disease.

Interleukin (IL)-37 is a member of the IL-1 cytokine family. We investigated IL-37b expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, we analysed IL-37b expression in human colonic epithelial cells. The human colonic epithelial cell line T84 and human colonic subepithelial myofibroblasts (SEMFs) were used. IL-37b expression in the IBD mucosa was evaluated by immunohistochemistry. IL-37b mRNA and protein expression were determined by real time-polymerase chain reaction (PCR) and Western blotting, respectively. IL-37b was not detected in the normal colonic mucosa. In the inflamed mucosa of IBD patients, epithelial IL-37b expression was increased markedly. In ulcerative colitis (UC) and Crohn's disease (CD) patients, IL-37b expression was enhanced in the affected mucosa. In the intestinal epithelial cell line T84, the expression of IL-37b mRNA and protein was enhanced by tumour necrosis factor (TNF)-α. This IL-37b induction by TNF-α was mediated by nuclear factor (NF)-κB and activator protein (AP)-1 activation. Furthermore, IL-37b inhibited TNF-α-induced interferon-γ-inducible protein (IP)-10 expression significantly in human colonic SEMFs. Epithelial IL-37b expression was increased in IBD patients, especially UC patients. IL-37b may be involved in the pathophysiology of IBD as an anti-inflammatory cytokine and an inhibitor of both innate and acquired immune responses.

Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has an essential role in multiple signaling pathways, including cell proliferation and migration, through extracellular ligand binding and subsequent activation of its intracellular tyrosine kinase (TK) domain. The non-small cell lung cancer (NSCLC)-associated EGFR mutants, L858R and G719S, are constitutively active and oncogenic. They display sensitivity to TK inhibitors, including gefitinib and erlotinib. In contrast, the secondary mutation of the gatekeeper residue, T790M, reportedly confers inhibitor resistance on the oncogenic EGFR mutants. In this study, our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant. The G719S/T790M double mutant has enhanced activity and retains high gefitinib-binding affinity. The T790M mutation increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant. Structural analyses of the G719S/T790M double mutant, as well as the wild type and the G719S and L858R mutants, revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR-TK conformation. The Met790 side chain of the G719S/T790M double mutant, in the apo form and gefitinib- and AMPPNP-bound forms, adopts different conformations that explain the accommodation of these ligands. In the L858R mutant structure, the active-site cleft is expanded by the repositioning of Phe723 within the P-loop. Notably, the introduction of the F723A mutation greatly enhanced the gefitinib sensitivity of the wild-type EGFR in vivo, supporting our hypothesis that the expansion of the active-site cleft results in enhanced gefitinib sensitivity. Taken together, our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC-associated EGFR mutations.

Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit.

OBJECTIVE: Radical hysterectomy (RH) is a standard treatment for locally advanced non-squamous cell carcinoma (N-SCC) of the uterine cervix, but there have been no reports on whether neoadjuvant chemotherapy (NAC) followed by radical hysterectomy could improve the outcome of patients with this disease. MATERIALS AND METHODS: This multicenter retrospective study enrolled 77 patients with Stage IB2 to IIB N-SCC of the uterine cervix. Of these, 27 patients were treated with NAC prior to radical hysterectomy (NAC group) and 50 with RH alone (RH group). The two-year recurrence-free survival (RFS) rate, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Clinical parameters such as clinical stage, histological type, and postoperative treatment were also examined between the groups. RESULTS: While the two-year RFS rates were 81.5% and 70.0% in NAC and RH groups, respectively (p = 0.27) and the median PFS was 51 months and 35 months in NAC and RH groups, respectively (p = 0.35), the median OS was 58 months and 48 months in NAC and RH groups, respectively, which was significant (p = 0.0014). The median OS of patients with mucinous adenocarcinoma in NAC group was significantly higher than that in RH group: 58 months versus 37 months (p = 0.03). CONCLUSION: NAC prior to RH may offer the prognostic advantage of patients with locally advanced N-SCC of the uterine cervix, especially mucinous adenocarcinoma.

SU-E-T-106: Evaluation of Sensitivity and Uniformity of New Radiochromic Film with Two Commercial Scanners.

PURPOSE: A newly introduced radiochromic film, the GAFCHROMIC EBT3, has been expected as much useful device for the IMRT dosimetry. The purpose of this study was to investigate the sensitivity and the uniformity of the films between an Epson ES-10000G flatbed scanner and a Vidar DosimetryPRO Advantage (Red) scanner. METHODS: Doses ranging from 1 cGy to 1600 cGy with 15-MV photon beam was irradiated to the film in a solid water phantom, respectively. All of the films were then digitized after irradiation using both two scanners. Sensitivities, local fluctuations of the film with two scanners were evaluated. Local fluctuations were defined as the relative (percent) standard deviation of the film response in ROIs (3 cmx3 cm). RESULTS: As to the Vidar scanner, the sensitivity of the film was higher for low dose range (below <400 cGy). While, as to the Epson scanner, the sensitivity using the red color channel was higher than others for low dose range. At high dose range (above >400 cGy), the green color channel had higher sensitivity than others. The Vidar scanner exhibited the lower local fluctuations than the Epson scanner for all dose ranges. For the Epson scanner, the red color channel had the lower local fluctuations than the green and blue color channel for all dose ranges. CONCLUSIONS: This study shows the characteristics of the new EBT3 films, in conjunction with the Epson ES-10000G flatbed scanner and the Vidar DosimetryPRO Advantage (Red) scanner.

SU-E-J-142: Gafchromic Film Dosimetry in Fluoroscopy for Dynamic Tumor Tracking Irradiation of the Lung Using XR-SP2 Model - A Phantom Study.

PURPOSE: We have recently developed a dynamic tumor tracking irradiation system using Vero4DRT (MHI-Tm2 000). It is needed to create a 4D correlation model between a fiducial marker implanted near a tumor and an external surrogate as a function of time by continuously acquiring both fluoroscopy images and external surrogate signals. The purpose of this study was to propose a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging. METHODS: First, half-value layers (HVLs) were measured using aluminum (Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were irradiated using various milliampere second values on a solid water phantom. The surface air kerma were also measured using the chamber to calculate the surface doses under the same condition. Then, the calibration curve of dose vs. pixel values was calculated. Finally, surface dose by fluoroscopy imaging was measured using several pieces of film taped on the chest phantom. Orthogonal X-ray fluoroscopy imaging was simultaneously performed until completion of data acquisition for creating a 4D correlation model. Those films were scanned after irradiation using a flat-bed scanner and converted to dose by calibration curve. RESULTS: The HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm Al. The calibration curve between surface dose and pixel values was reasonably smooth. The differences between the measured and the calibrated doses were less than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around the area overlapped by both fluoroscopic fields. CONCLUSIONS: We have proposed a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging. This phantom study has demonstrated that it may be feasible to assess surface dose to patients during dynamic tumor tracking irradiation in clinic with ease after further investigation. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovation R&D on Science and Technology (FIRST Program). Research sponsored in part by Mitsubishi Heavy Industries, Ltd.

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors.

PURPOSE: LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. METHODS: Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. RESULTS: LY2181308 was administered to 14 patients, aged 44-73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. CONCLUSIONS: LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.

GST polymorphisms, interaction with smoking and pesticide use, and risk for Parkinson's disease in a Japanese population.

Patients with idiopathic Parkinson's disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms (GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium (D' = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.

The geometric accuracy of frameless stereotactic radiosurgery using a 6D robotic couch system.

The aim of this paper is to assess the overall geometric accuracy of the Novalis system using the Robotic Tilt Module in terms of the uncertainty in frameless stereotactic radiotherapy. We analyzed the following three metrics: (1) the correction accuracy of the robotic couch, (2) the uncertainty of the isocenter position with gantry and couch rotation, and (3) the shift in position between the isocenter and central point detected with the ExacTrac x-ray system. Based on the concept of uncertainty, the overall accuracy was calculated from these values. The accuracy in positional correction with the robotic couch was 0.07 +/- 0.22 mm, the positional shift of the isocenter associated with gantry rotation was 0.35 mm, the positional shift of the isocenter associated with couch rotation was 0.38 mm and the difference in position between the isocenter and the ExacTrac x-ray system was 0.30 mm. The accuracy of intracranial stereotactic radiosurgery with the Novalis system in our clinic was 0.31 +/- 0.77 mm. The overall geometric accuracy based on the concept of uncertainty was 0.31 +/- 0.77 mm, which is within the tolerance given in the American Association of Physicists in Medicine report no. 54.

Tiotropium 5microg via Respimat and 18microg via HandiHaler; efficacy and safety in Japanese COPD patients.

BACKGROUND AND OBJECTIVES: To compare the efficacy and safety of tiotropium inhaled via Respimat Soft Mist Inhaler, a multidose propellant-free inhaler and HandiHaler, a single-dose dry powder inhaler, in a phase 2 study of Japanese COPD patients. METHODS: Patients with FEV(1)10 pack-years received tiotropium once daily via Respimat (5microg) and HandiHaler (18microg) for 4 weeks each in a randomised, double-blind, double-dummy, two-way crossover study. Lung function, adverse events, pharmacokinetics and safety were assessed. RESULTS: Of 184 patients screened, 134 were evaluable. The trough FEV(1) response on Day 29 showed Respimat to be non-inferior to HandiHaler (mean treatment difference, 0.008L; 95% CI, -0.009 to +0.024L; p<0.001). Peak and average FEV(1) and FVC responses on Day 1 and Day 29 were very similar for the two treatments. Tiotropium plasma levels and excretion kinetics showed a similar profile of systemic exposure for the two formulations of tiotropium. Adverse events were reported by similar numbers of patients on each treatment, i.e. 27.9 and 30.6% in the Respimat and HandiHaler groups, respectively. CONCLUSIONS: In Japanese patients with COPD, tiotropium Respimat 5microg and tiotropium HandiHaler 18microg showed a similar profile of efficacy, safety and pharmacokinetics.

The effect of gadodiamide on cancer cell lines.

AIM: Recent literature suggests that some human cancer cell lines possess a calcium cation receptor. Human myeloma cell lines have demonstrated stimulated cell proliferation by the gadolinium cation through this receptor, and osteosarcoma cell lines possess the same cation receptor. Although enhanced MRI is a very useful diagnostic tool for the treatment of sarcoma in the orthopedic area, incorporating the use of MRI contrast agents based on gadolinium raises the possibility of the stimulation of cancer cell growth. METHODS: Human myeloma (RPMI 8226), osteosarcoma (Saos-2) and rat osteosarcoma (UMR-106) cell lines were exposed to various concentrations of common MRI contrast agent gadodiamide Omniscan (5 microM, 50 microM, 500 microM, 5 mM, 50 mM) in a culture medium. The response of the cells was then assessed by measuring cell proliferation and DNA synthesis. RESULTS: Treatment with 5 microM to 5 mM gadodiamide did not stimulate cell proliferation; only cells exposed to 50 mM gadodiamide showed suppressed proliferation rates. CONCLUSIONS: Since intravenously injected gadodiamide is diluted from 500 microM to 1 mM by patient blood flow at enhanced MRI examinations, the results of the present study suggest that gadodiamide has not effect on these types of cancer cells.

Biodistribution of BPA and BSH after single, repeated and simultaneous administrations for neutron-capture therapy of cancer.

The effect of administration mode of L-BPA and BSH on the biodistribution in the melanoma-bearing hamsters was investigated. In single intravenous (i.v.) administration, BSH (100 mg BSH/kg) showed no significant retention of (10)B in all the tissues, including tumors, while long-term retention of (10)B in the tumor, muscle and brain was observed with L-BPA (500 mg BPA/kg). The dose escalation of L-BPA and the simultaneous single administration of L-BPA and BSH were not so effective at increasing boron accumulation in tumor after bolus i.v. injection. The boron concentration in tumor was 41 microg B/g after single bolus i.v. injection even at the dose of 1000 mg BPA/kg. In contrast, two sequential bolus i.v. injections of l-BPA with the dose of 500 mg BPA/kg each was found to be effective at increasing (10)B accumulation in the tumor; the maximum (10)B concentration in the tumor reached 52 microg B/g at 3 h after the second i.v. injection.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.