Search

We introduce a novel dynamic water range shifter (DWRS) that enables range shifting of a mono-energetic proton beam for the purpose of obtaining a water equivalent path length (WEPL). A scintillation screen and a charge-coupled device (CCD) camera were assembled with a mirror for a detecting system. We acquired two sets of proton radiographs with and without the scanned object, and calculated 2D distribution of the WEPL. We first optimized measurement conditions, i.e., the sampling interval and the nearest sampling point from the surface. Then we evaluated the performance of the proton radiography system by use of the step phantoms and a patient-specific range compensator. The step phantom measurement was designed to evaluate WEPL accuracy and standard deviation, and the patient-specific compensator was utilized to evaluate image quality dependency on the shifting motions of the DWRS. Based on the optimization and evaluation in the radiographic setting, a cylindrical phantom having multiple insert holes was used to obtain proton CT and the image contrasts of the holes were evaluated. This study successfully demonstrates the feasibility of using the DWRS for proton radiography and CT.

The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.

Bepotastine salts (nicotinate and salicylate) were investigated for their physicochemical properties to develop novel salt forms of bepotastine, bioequivalent to the bepotastine besilate-loaded tablet (Talion). These bepotastine salts of either nicotinate- or salicylate-loaded tablets were prepared by conventional wet granulation method, and dissolution profiles and pharmacokinetics in beagle dogs were compared to those of Talion. A novel bepotastine nicotinate has a higher solubility at varying pH levels (1.2, 4, or 6.8) than salicylate-loaded or besilate-loaded salt. In addition, those bepostastine salt forms (nicotinate and salicylate) are stable in heat, light, and water. Further, the novel nicotinate- and salicylate-loaded tablets showed similar dissolution rates to Talion in several selected dissolution media and were bioequivalent to Talion in beagle dogs in terms of area under the concentration-time curve (AUC) and maximum observed concentration (Cmax). A pharmacokinetic study performed in beagle dogs demonstrated that test and reference products were found to be bioequivalent in terms of safety, efficacy, and pharmacokinetic properties. These results suggest that bepostastine nicotinate and salicylate formulations are considered applicable candidates and are well tolerated versus the conventional bepostastine besilate formulation.

In order to investigate the potential application of blood biomarkers as surrogate indicators of carcinogen-adduct formation in target-specific tissues, temporal formation of benzo[a]pyrene (BaP)-associated DNA adducts, protein adducts, or lipid damage in target tissues such as lung, liver, and kidney was compared with globin adduct formation or plasma lipid damage in blood after continuous intraperitoneal (ip) injection of [(3)H]BaP into female ICR mice for 7 d. Following treatment with [(3)H]BaP, formation of [(3)H]BaP-DNA or -protein adducts in lung, liver, and kidney increased linearly, and persisted thereafter. This finding was similar to the observed effects on globin adduct formation and plasma lipid damage in blood. The lungs contained a higher level of DNA adducts than liver or kidneys during the treatment period. Further, the rate of cumulative adduct formation in lung was markedly greater than that in liver. Treatment with a single dose of [(3)H]BaP indicated that BaP-globin adduct formation and BaP-lipid damage in blood reached a peak 48 h after treatment. Overall, globin adduct formation and lipid damage in blood were significantly correlated with DNA adduct formation in the target tissues. These data suggest that peripheral blood biomarkers, such as BaP-globin adduct formation or BaP-lipid damage, may be useful for prediction of target tissue-specific DNA adduct formation, and for risk assessment after exposure.

In the present study, we addressed the question of whether the up-regulation of laminin expression represents the astroglio-vascular responses to status epilepticus (SE) in the rat brain to better understand the role of vasogenic edema in epileptogenic insult. In the hippocampus, vasogenic edema was observed in the hippocampus 12h after SE when astroglial degeneration was undetected. Vasogenic edema in the hippocampus was more severe in the CA1 region where astroglial loss was absent than in the dentate gyrus showing astroglial degeneration. In the piriform cortex (PC), vasogenic edema was accompanied by appearance of astroglial degeneration 12h after SE. Laminin expression in the hippocampus and the PC was increased 3 days and 4 days after SE, respectively. Laminin expression was up-regulated in the hippocampus and the PC with concomitant reduction of SMI-71 (the endothelial barrier antigen) expression. Four weeks after SE, laminin expression was reduced in vessels showing strong SMI-71 expression within vasogenic edema lesion. Inhibition of SE-induced vasogenic edema formation by BQ788 effectively prevented laminin over-expression. Therefore, our findings indicate that laminin over-expression may be one of consequences from vasogenic edema rather than astroglial loss, and that laminin over-expression may promote migration of astrocytes to damaged or newly generated vessels to repair brain-blood barrier (BBB) disruption accompanied by the reconstruction of endothelial barrier.

The name of the 14th author was incorrect in the original publication. It is correct in this erratum (Young-Shin Ra).

The aim of this work was to evaluate the clinical efficacy and safety of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in patients with inoperable hepatocellular carcinoma (HCC).A total of 53 patients with inoperable HCC underwent SIB-IMRT using two dose-fractionation schemes, depending on the proximity of gastrointestinal structures. The 41 patients in the low dose-fractionation (LD) group, with internal target volume (ITV)1 cm from gastrointestinal structures, received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 (PTV1) and 2 (PTV2), respectively. The 12 patients in the high dose-fractionation (HD) group, with ITV ≥ 1 cm from gastrointestinal structures, received total doses of 66 and 55 Gy in 22 fractions to the PTV1 and PTV2, respectively.Overall, treatment was well tolerated, with no grade3 toxicity. The LD group had larger sized tumors (median: 6 vs. 3.4 cm) and greater frequencies of vascular invasion (80.6 vs. 16.7 %) than patients in the HD group (p 0.05 each). The median overall survival (OS) was 25.1 mKonzept ist machbar und sicheronths and the actuarial 2-year local progression-free survival (LPFS), relapse-free survival (RFS), and OS rates were 67.3, 14.7, and 54.7 %, respectively. The HD group tended to show better tumor response (100 vs. 62.2 %, p = 0.039) and 2-year LPFS (85.7 vs. 59 %, p = 0.119), RFS (38.1 vs. 7.3 %, p = 0.063), and OS (83.3 vs. 44.3 %, p = 0.037) rates than the LD group. Multivariate analysis showed that tumor response was significantly associated with OS.SIB-IMRT is feasible and safe for patients with inoperable HCC.

The use of molybdate as a new anionic dopant that replaces phosphate in LiFePO4 was studied. When a small amount of molybdate (0.5 mol%) was used as a dopant, the olivine structure was maintained, while the lattice volume increased by 0.4%. The expanded volume facilitates ionic transfer, because of which the capacity of doped LiFePO4 at high current discharge rates is higher than that of pure LiFePO4. The discharge value increased by 25.2% at a charge rate of 5 C when the material was doped with 0.5 mol% molybdate ions. The slight expansion of the lattice volume in the olivine structure facilitates a fast redox reaction by lowering the charge transfer resistance. The current values from cyclic voltammetry indicate that the oxidation (charge) process of the cathode material is more improved than the corresponding reduction (discharge) process. Increasing the level of doping beyond 0.5 mol% had no effect on the results. At some discharge rates, the discharge capacity became worse. Because molybdate is divalent while phosphate is trivalent, a large number of molybdate ions in the lattice can exert considerable stress on the structure.

Exposure to the wide variety of chemicals used for manufacturing consumer products commonly occurs daily and the consequences to health are beneficial. However, some of these products are hazardous and exert deleterious effects on humans and the ecosystem. To protect consumers from exposure to hazardous chemicals, appropriate risk management systems are needed. Developed countries such as the United States and Canada have developed their own risk management systems for regulating hazardous agents. However, the risk management systems prepared by developed countries may not be readily applicable to developing or underdeveloped countries because of certain economic, political, cultural, or social factors in each country. In general, a risk management framework includes evaluation components of risk assessment, risk confrontation, risk intervention, risk communication, and risk management, but these may differ in specifics. The European Commission (EC) requires a socioeconomic analysis for formulating restrictions suggested by the European Chemicals Agency (ECHA). The EC has an early warning system for safety management termed the Rapid Alert System (RAPEX). Korea, Australia, and Japan also developed integrated network systems for risk management of consumer products. Monitoring entails the collection of information and evaluation. The risk assessment process includes scientific evaluation of potential adverse health effects. Risk communication tasks are to (1) identify stakeholders, (2) develop stakeholder analysis, (3) assess stakeholder acceptability, (4) consult with stakeholders, (5) inform stakeholders about their options, (6) evaluate control options, and (7) monitor changing issues. The risk management process involves weighing policy options and selecting regulatory options. The decision-making step is related to the determination of governmental or voluntary actions. This review examines the critical points of risk management system in Korea to effectively control hazardous agents for human safety and compliance with global harmonization.

Background Although capecitabine has theoretical advantages in the pharmacokinetics, such as higher intratumoral and lower systemic concentration, relative to bolus 5-fluorouracil (5-FU), outcomes of chemoradiotherapy (CRT) with capecitabine or bolus 5-FU have not been directly compared in patients with locally advanced pancreatic cancer. Therefore, we retrospectively compared the outcomes, including toxicity, tumor response, and overall survival, of oral capecitabine plus radiotherapy (RT) with bolus 5-FU plus RT, in patients with locally advanced pancreatic cancer. Methods Between August 2006 and January 2012, 98 patients with locally advanced pancreatic cancer received CRT, with 52 receiving concurrent oral capecitabine and 46 receiving bolus injection of 5-FU. Primary tumor and overall response after CRT were evaluated radiologically, and toxicity, tumor response, and overall survival (OS) were compared in the two groups. Results Baseline clinical parameters of the two groups were similar. The rates of ≥ Grade 3 hematologic (0% vs. 8.7%, p = 0.045) and non-hematologic (0% vs. 8.7%, p = 0.045) toxicities were significantly lower in the capecitabine group than in the 5-FU group. Primary tumor (30.7% vs. 28.2%, p = 0.658) and overall (13.7% vs. 15.2%, p = 0.273) response rates and median OS time (12.5 months vs. 11.6 months, p = 0.655) were similar in the two groups. Conclusions Capecitabine plus RT may be a safe and feasible regimen for patients with locally advanced pancreatic cancer, with similar efficacy and low rates of toxicities compared with bolus 5-FU plus RT.

Background and purpose Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS). Materials and methods Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days. Results All patients completed PB-APBI. The median follow-up time was 59months (range: 43–70months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2months that was not observed beyond 6months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2months, respectively, and decreased to 69% at 3years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period ( p =0.02); however, it did not increase in patients treated with two-field PB-APBI ( p =0.3). Conclusions PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.

Background. Hypofractionated radiotherapy potentially offers therapeutic gain for prostate cancer. we investigated the feasibility of hypofractionated proton therapy (PT). Material and methods. Eighty-two patients with biopsy-proven T1-3N0m0 prostate adenocarcinoma and no history of androgen deprivation therapy were randomly assigned to five different dose schedules: arm 1, 60 CGE (cobalt gray equivalent  proton dose in Gy  1.1)/20 fractions/5 weeks; arm 2, 54 CGE/15 fractions/5 weeks; arm 3, 47 CGE/10 fractions/5 weeks; arm 4, 35 CGE/5 fractions/2.5 weeks; or arm 5, 35 CGE/5 fractions/5 weeks. Results. The median follow-up duration was 42 months (11–52 months). The acute GI and Gu grade  2 toxicity rates were 0 and 5%, respectively. The late GI and Gu grade  2 toxicity rates were 16% and 7%, respectively. The best arm for acute Gu toxicity was arm 3, while that for late GI toxicity was arm 2 in which none had grade  2 toxicity. The four-year american Society for Therapeutic Radiology and oncology and Nadir  2ng/ml BCF free survival (BCFFS) rates were 85% and 86%, respectively. Conclusions. Hypofractionated PT for patients with prostate adenocarcinoma as used in this study is feasible with an acceptable toxicity profile. as the BCFFS rates do not seem to be inferior to those produced using conventional fractionation, the application of hypofractionated PT may save patients time and money.

Purpose We assessed the value of dose-volumetric parameters predicting rectosigmoid mucosal changes (RMC) and late rectosigmoid complications (LRC). Methods Between January 2004 and February 2006, 77 patients with stage IB-IIIB cervical cancer underwent external beam radiotherapy and computed tomography (CT)-based intracavitary irradiation. Total dose to the rectal point and several dose-volumetric parameters for rectosigmoid colon (D20cc, D15cc, D10cc, D5cc, D2cc, D1cc, and D0.1cc , defined as the minimal doses received by the highest irradiated volumes of 20, 15, 10, 5, 2, 1, and 0.1 cc, respectively), were calculated using the equivalent dose in 2 Gy fractions (α/β = 3, Gy3). The RMC and LRC were graded by rectosigmoidoscopy and Radiation Therapy Oncology Group criteria every 6 months, respectively. Results Of 77 patients, 27 (35.1%) patients developed RMC ≥ score 3 and 22 (28.6 %) patients developed LRC ≥ grade 2. There was a positive correlation between RMC score and LRC grade (r = 0.728, p 5cc, among the dose-volumetric parameters, was significant parameter for the risks of RMC ≥ score 3 and LRC ≥ grade 2 (p < 0.05). Conclusions D5cc may be a more reliable estimate than other dose-volumetric parameters for predicting the risk of RMC ≥ score 3 and LRC ≥ grade 2 in CT-based brachytherapy.

We retrospectively compared accelerated hypofractionation (AHF) with conventional fractionation (CF) in the radiation therapy (RT) for early-stage breast cancer patients. Three hundred seventy-nine early-stage (pT1–2 and pN0–1a) breast cancer patients who received RT with AHF after breast-conserving surgery (BCS) were included. These patients were matched with 379 corresponding patients who received BCS and RT with CF at a different center with respect to the year BCS was performed, patient age (±3 years), and cancer stage. The AHF regimen consisted of 39 Gy in 13 fractions to the whole breast and a consecutive boost of 9 to 12 Gy in 3 to 4 fractions to the tumor bed. CF comprised whole-breast irradiation up to 50.4 Gy in 28 fractions and a boost of 9 to 14 Gy in 5 to 7 fractions to the tumor bed. The median follow-up period was 75 months (range, 3.8–110.8 months). There was no statistically significant difference between the AHF and CF groups in terms of age distribution, T and N stage, resection margin, and histologic grade. There were 5 ipsilateral breast tumor relapse (IBTR) cases in the AHF group compared with 7 cases in the CF group. Seven and eight locoregional relapse (LRR) cases were observed in the AHF and CF groups, respectively. The 7-year rates of IBTR-free survival, LRR-free survival, and disease-free survival were 98.9%, 98.4%, and 97.1% in the AHF group and 98.1%, 97.9%, and 96.0% in the CF group, respectively (P > 0.05). The incident rates of grade 3 edema, hyperpigmentation, or wet desquamation at the end of RT were higher in the CF group than in the AHF group (16.4% vs 0.2%, respectively; P

Ji Hyeon Joo, Yeon Joo Kim, Young Seok Kim, Young Pil Cho, Ho Yeon Lee, Chang Young Jeong, Jungwon Kwak, Byung Chul Cho Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Background: The authors conducted this prospective study to analyze the amount of interfractional prostate bed motion (PBM) and quantify its components with the use of an endorectal balloon (ERB).Methods: A total of 1,348 cone beam computed tomography images from 46 patients who underwent postprostatectomy radiotherapy were analyzed. For the pilot image, electronic portal imaging, guided by skin marks was performed to ensure proper positioning and inflation of the ERB. Then, for bone matching, manual or automatic registration of the planning and each cone beam computed tomography was performed, based on the bony anatomy of the pelvis. Shifts (bony misalignment [BM]) in three directions were recorded at each treatment session. For prostate bed matching, manual matching was conducted based on the anterior rectal wall and the shift (PBM) was recorded. Total setup error was defined as the shift from the skin mark to the prostate bed matching, based on anterior rectal wall stretched by the ERB. PBM was defined as the difference between the total setup error and BM.Results: Systematic errors for the total setup error were 1.0, 1.3, and 1.0 mm in the right–left, anterior–posterior, and superior–inferior directions, with random errors of 1.9, 2.4, and 1.9 mm, respectively. Systematic errors were 1.6, 1.6, and 0.3 mm for BM and 0.8, 1.1, and0.9mm for PBM, with random errors of 2.4, 2.5, and 1.1 mm for BM and 1.8, 2.2, and 1.9 mm for PBM.Conclusion: The BM was the main component of the total setup error, suggesting that interfractional PBM was well controlled by the ERB device. Planning target volume margins of

We analyzed the treatment outcomes of intracranial ependymomas in Korean children aged

We report herein a case of intestinal amyloidosis with grave prognosis that caused intractable diarrhea and intestinal pseudo-obstruction, alternately in spite of intensive conservative treatment. A 44-year-old woman was admitted for fever, diarrhea, and crampy abdominal pain which had been continuned during 6 months. Abdomen CT scan showed edematous wall thickening of the small bowel and right colon, and colonoscopic biopsy revealed amyloid deposition in the mucosa. Monoclonal light chains in serum and/or urine were not detected and highly elevated serum amyloid A was shown. In spite of intensive treatment including oral prednisolone and colchicine, diarrhea and intestinal pseudo-obstruction developed alternately, general status rapidly got worsened and died after two months.

The purpose of this study was to evaluate whether bulky lymphadenopathy located in the abdominopelvic cavity in cervical cancer can be controlled without severe toxicity by increasing radiation dose using helical tomotherapy. From January 2007 to December 2010, 26 patients with cervical cancer with metastatic lymph nodes (LNs) having at least one short diameter > 1.5 cm were treated with helical tomotherapy. A total of 58 LN sites were treated and the largest LN of each site was evaluated for response. Median follow-up time was 28 months (4–50 months). Median short diameter of the LNs was 1.7 cm (0.7–4.2 cm) with median radiation dose of 62.6 Gy10 in 2 Gy equivalent dose (53.3–77.9 Gy10). Initial LN response was evaluated on imaging obtained within 4 months after radiotherapy. Initial complete response (CR), partial response (PR), and stable disease (SD) were observed in 54, 2 and 2 lesions, respectively. Recurrence occurred in two with CR and progression in one with PR. Therefore, final CR, PR, SD, and progression of disease were observed in 52, 1, 2, and 3, respectively. Actuarial 3-year LN progression-free survival and overall survival (OS) were 63% and 65%, respectively. Multivariate analysis revealed final LN response (CR vs. non-CR) as a strong prognostic factor for OS (p = 0.016). Radiation Therapy Oncology Group grade 2 or more acute and late toxicity was observed in 8 and 1 patients, respectively. The treatment of bulky lymphadenopathy using helical tomotherapy in advanced cervical cancer is highly effective and has acceptable toxicity.

A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg−1 per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P

Purpose To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg(-1) per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P 0.05), whereas the levels of 3-indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2-oxoglutarate (×2.3) increased significantly (P 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3-indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3-indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation.

Lymph node (LN) metastasis is a well-known prognostic factor of the cervical cancer. In the current study, the size of metastatic LN was evaluated for its significance in the patients treated with definitive radiotherapy.LN metastasis was evaluated for the 268 consecutive patients. The short-axis diameters of the largest LN were measured on magnetic resonance images for the 155 patients with LN metastasis. All the patients were classified into three groups: the negative lymphadenopathy (group N), the small (15mm) lymphadenopathy (group SP), and the large (≥15mm) lymphadenopathy (group LP).Patients in the group LP showed significantly lower survival rates than the groups N and SP (5-year overall survival rates of 89%, 82%, and 58%, for groups N, SP, and LP, respectively, P0.001; 5-year disease-free survival rates of 80%, 67%, and 50%, respectively, P0.001). Regarding the pattern of failure, patients in the group LP showed inferior regional control rates and higher distant metastasis.The current study shows that the patients with large metastatic LNs are at increased risk of dying from early distant metastasis with substantial number of combined regional failures. Adoption of more effective systemic treatment as well as high radiotherapy dose for LNs may improve cure rates for these patients.

Purpose TIMP-2 has been studied as an attractive cancer therapeutic candidate, and a TIMP-2 fusion protein (HSA/TIMP-2) displayed effective anticancer activity, despite a lack of information about its pharmacokinetics (PK) and biodistribution. The purpose of this work was to assess the PK and biodistribution of HSA/TIMP-2 as well as to quantify accumulated HSA/TIMP-2 in tumors. Methods Cy5.5 near-infrared (NIR) fluorescence was conjugated to the HSA/TIMP-2 protein (Cy5.5–HSA/TIMP-2) for monitoring spatio-temporal changes in vivo. For PK and biodistribution analysis, 0.2 μg/g body weight of Cy5.5–HSA/TIMP-2 was injected into MAT-LyLu prostate tumor xenografts, which were then imaged using an IVIS-200 optical imaging system. To quantify the accumulated HSA/TIMP-2 in tumors, we introduced a standard curve with depth-corrected fluorescence measurement. Results In the vascular tube formation assay with human umbilical vein endothelial cells (HUVECs), Cy5.5–HSA/TIMP-2 showed an antiangiogenic effect. In prostate cancer xenografts, Cy5.5–HSA/TIMP-2 exhibited a prolongation of blood half-life to 19.6 h and relatively preferential distribution to the tumor. The amount of tumor-accumulated Cy5.5–HSA/TIMP-2 was calculated to be 4.5 ± 0.5 ng/g body weight at 2 days, representing 2.25 ± 0.25% of the initial dose. Conclusions We evaluated the pharmacokinetic profile and biodistribution of HSA/TIMP-2 with favorable results, providing new information for more effective approaches to cancer therapeutics using HSA/TIMP-2. Additionally, real-time in vivo fluorescence imaging analysis using a depth-corrected standard curve may serve as a platform to quantify biodistributed drug in anticancer therapeutic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Background Although serum carcinoembryonic antigen (CEA) levels reflect tumor volume in rectal cancer patients intrapersonally, it is unclear interpersonally. We determined the correlation between pretreatment serum CEA levels and tumor volume. Methods A total of 489 patients with locally advanced primary rectal cancer who underwent preoperative chemoradiotherapy followed by surgery between October 2001 and April 2007 were retrospectively evaluated. CEA levels were measured by chemiluminescent microparticle immunoassay, and magnetic resonance (MR) volumetry was performed using MR data. The correlation between CEA levels and tumor volume was assessed using linear regression analysis and one-way analysis of variance. The prognostic values of CEA levels and tumor volume for survival were evaluated. Results There was no significant correlation between CEA levels and tumor volume. The five-year overall survival and disease-free survival were 89.0%, 80.6% and 82.9%, and 72.0%, 70.0% and 60.3% in patients with CEA levels of ≤ 3 ng/ml, > 3–10 ng/ml, and > 10 ng/ml, respectively. Tumor volume had no prognostic value for either overall survival or disease-free survival Conclusions Pretreatment serum CEA levels were not correlated with tumor volume. While there was no correlation between tumor volume and survival, there was a positive correlation between CEA levels and survival.

Background The aim of this study was to investigate the profile of antibodies against several antigens of Plasmodium vivax and Plasmodium falciparum in Mandalay, Myanmar. Methods Malaria parasites were identified by microscopic examination. To test the antibodies against P. vivax and P. falciparum in sera, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood parasite antigens. An enzyme-linked immunosorbent assay (ELISA) was performed with circumsporozoite protein (CSP), Pvs25 and Pvs28 recombinant proteins of transmission-blocking vaccine candidates for P. vivax, and liver stage specific antigen-1 and -3 (PfLSA-1, PfLSA-3) for P. falciparum. Results Fourteen patients among 112 were found to be infected with P. vivax and 26 with P. falciparum by thick smear examination. Twenty-three patients were found to be infected with P. vivax, 19 with P. falciparum and five with both by thin smear examination. Blood samples were divided into two groups: Group I consisted of patients who were positive for infection by microscopic examination, and Group II consisted of those who showed symptoms, but were negative in microscopic examination. In P. falciparum, IgG against the blood stage antigen in Group I (80.8%) was higher than in Group II (70.0%). In P. vivax, IgG against the blood stage antigen in Group I (53.8%) was higher than in Group II (41.7%). However, the positivity rate of the PvCSP VK210 subtype in Group II (40.0%) was higher than in Group I (23.1%). Similarly for the PvCSP VK247 subtype, Group II (21.7%) was higher than that for Group I (9.6%). A similar pattern was observed in the ELISA using Pvs25 and Pvs28: positive rates of Group II were higher than those for Group I. However, those differences were not shown significant in statistics. Conclusions The positive rates for blood stage antigens of P. falciparum were higher in Group I than in Group II, but the positive rates for antigens of other stages (PfLSA-1 and -3) showed opposite results. Similar to P. falciparum, the positive rate of pre-blood stage (CSP VK210 and 247 subtype) and post-blood stage (Pvs25 and 28) antigens of P. vivax were higher in Group II than in Group I. Therefore, sero-diagnosis is not helpful to discriminate between malaria patients and symptomatic individuals during the epidemic season in Myanmar.

A series of resorcinarene host–amphiphilic guest complexes have been developed where guest orientation in the host is drastically influenced by pH. Guests appended with a trimethylammonium and a tert-butyl group switch orientation by 180° in response to a buildup of negative charge in the cavitand host.

In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5K alpha) that is responsible for production of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) regulates many important cell functions at the cell surface. Here, we have examined whether PIP5K alpha is associated with astrocyte inflammatory responses. Gangliosides are releasable from damaged cell membranes of neurons and capable of inducing inflammatory responses. We found that treatment of primary cultured astrocytes with gangliosides significantly enhanced PIP5K alpha mRNA and protein expression levels. PI(4,5)P2 imaging using a fluorescent tubby (R332H) expression as a PI(4,5)P2-specific probe showed that ganglioside treatment increased PI(4,5)P2 level. Interestingly, microRNA-based PIP5K alpha knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1 beta and TNFalpha. PIP5K alpha knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-kappaB and the degradation of I kappaB-alpha, indicating that PIP5K alpha knockdown interfered with the ganglioside-activated NF-kappaB signaling. Together, these results suggest that PIP5K alpha is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-kappaB activation in ganglioside-stimulated astrocytes.

A family of calcium-dependent protein kinases (CDPKs) is a unique enzyme which plays crucial roles in intra- cellular calcium signaling in plants, algae, and protozoa. CDPKs of malaria parasites are known to be key regulators for stage-specific cellular responses to calcium, a widespread secondary messenger that controls the progression of the pa- rasite. In our study, we identified a gene encoding Plasmodium vivax CDPK4 (PvCDPK4) and characterized its molecular property and cellular localization. PvCDPK4 was a typical CDPK which had well-conserved N-terminal kinase domain and C-terminal calmodulin-like structure with 4-EF hand motifs for calcium-binding. The recombinant protein of EF hand domain of PvCDPK4 was expressed in Echerichia coli and a 34 kDa product was obtained. Immunofluorescence assay by confo- cal laser microscopy revealed that the protein was expressed at the mature schizont of P. vivax. The expression of Pv- CDPK4-EF in schizont suggests that it may participate in the proliferation or egress process in the life cycle of this parasite.

Background We evaluated the predictive significance of 14 reported markers using immunohistochemical study in nasopharyngeal carcinoma. Methods Immunohistochemical stainings were done in 38 patients for Met, cyclooxygenase-2 (COX-2), nm23-H1, epidermal growth factor receptor (EGFR), p63, early growth response factor 1 (Egr1), chromosome segregation 1-like (CSE1L), cathepsin-D (aspartyl protease), C-erbB2, p53, signal transducers and activators of transcription (STAT3/STAT5), CD138 (Syndecan-1), and LIN28 with the usual methods. Results The median follow-up time was 30 months (11–83 months). High Met and CD138 expression were statistically significant negative prognostic factors on survival. The expression of Egr1 had a positive prognostic effect on survival. The combined score of these 3 markers, Met plus CD138 minus Egr1, was a strong prognostic factor. The median survival curve was distinctly separated in accord with this combined score. No prognostic value was revealed in COX-2, nm23-H1, EGFR, p63, CSE1L, cathepsin-D, C-erbB2, p53, STAT3, STAT5, and LIN28. Conclusions The combined score of these markers could be used to stratify biomolecular risk groups. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

Reemerged Plasmodium vivax malaria in South Korea has not yet been eradicated despite continuous governmental efforts. It has rather become an endemic disease. Our study aimed to determine the genetic diversity in P. vivax merozoite surface protein-1 (PvMSP-1) and circumsporozoite protein (PvCSP) genes over an extended period after its reemergence to its current status. Sequence analysis of PvMSP-1 gene sequences from the 632 P. vivax isolates during 1996-2007 indicates that most isolates recently obtained were different from isolates obtained in the initial reemergence period. There was initially only one subtype (recombinant) present but its subtypes have varied since 2000; six MSP-1 subtypes were recently found. A similar variation was observed by CSP gene analysis; a new CSP subtype was found. Understanding genetic variation patterns of the parasite may help to analyze trends and assess extent of endemic malaria in South Korea.

To evaluate the efficacy of an activin receptor-like kinase (ALK) 5 inhibitor, IN-1233, for the prevention of neointimal hyperplasia after bare stent placement in a rat common iliac artery (CIA) model.All experiments were approved by the committee of animal research. A self-expanding metallic bare stent (2 mm × 6 mm) was inserted into the left CIA of 26 Sprague-Dawley male rats (300-360 g) under fluoroscopic guidance. IN-1233 was injected via the intraperitoneal route daily in 13 rats for 8 weeks after stent placement (group A); the other 13 rats underwent stent placement only (group B). Angiography was performed immediately and 4 weeks and 8 weeks after stent placement. Rats were sacrificed at 8 weeks after stent placement, and histologic findings were obtained. The neointimal area (NA), percentage of neointimal hyperplasia (%NH), and neointimal-to-medial area ratio (N/M) were assessed and compared between the two groups.Stent placement was technically successful. In 25 rats, arteries with stent placement were angiographically patent, whereas 1 rat in group B had an occlusion. The NA (0.31 mm(2) ± 0.09 vs 0.56 mm(2) ± 0.17; P.001), the %NH (26.16% ± 8.75 vs 44.71% ± 17.75; P.001) and the N/M (1.93 ± 0.77 vs 4.77 ± 2.26; P.001) were significantly decreased in group A compared with group B.IN-1233 was shown in this study to be effective for the prevention of neointimal hyperplasia after bare metallic stent placement in a rat CIA model.

The Republic of Korea (ROK) Army instituted a vivax malaria chemoprophylaxis program (hydroxychloroquine [HCQ] 400 mg per week) in 1997 that was expanded to nearly 200,000 soldiers by 2007, raising concerns for the emergence of drug-resistant vivax malaria. Therefore, a study of whole blood HCQ concentrations for all malaria patients admitted to four ROK Army hospitals was conducted from June through September 2007. For all 142 vivax malaria patients enrolled, fevers returned to normal by Day 3 post-treatment and all thin blood films were negative for parasites by Day 7. Pre-treatment whole blood concentrations of HCQ for 14 patients were > 100 ng/mL. Eight of the patients were enrolled in the ROK Army chemoprophylaxis program that reported taking HCQ as directed, with the last pill taken > or = 4 days before diagnosis. Although there was no evidence of clinical resistance, chemoprophylaxis data indicates the biological resistance or tolerance to HCQ in ROK.

Metabonomic investigation of doxorubicin (adriamycin) was carried out in male Sprague-Dawley rats using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistics. Urine samples (d -1 to 7) from rats treated with doxorubicin at two dose levels (5 or 15 mg/kg body weight) were collected at each time point and doxorubicin-induced biomarkers were examined. Of metabolites, early elevated biochemical changes were observed in trimethylamine N-oxide (TMAO) levels suggesting renal dysfunction. Perturbation in TMAO was maximal in the low-dose group at 48 h post dose (p.d.) and returned to control at 168 h p.d., indicating recovery from renal toxicity induced by doxorubicin. After doxorubicin administration, the high-dose group was divided into low and high responders at 48 h and further divided into high, moderate, and no recovery animals at 96 h, indicating individual susceptible response to drug-induced toxicity. Urinary increases in glucose, lactate, alanine, and valine suggested progression of renal damage resulting in glycosuria, lactic aciduria, and aminoaciduria up to 168 h in the high-dose group. Urinary elevation of creatine and phenylacetylglycine (PAG) together with reduction of N-methylnicotinic acid (NMNA) and hippurate levels was suggestive of liver injury in the high-dose group. Impairment of energy metabolism was also indicated by decreased levels of tricarboxylic acid cycle intermediates in urine of rats treated with high-dose doxorubicin. This study highlights the applicability of NMR-based metabonomics with multivariate statistics for monitoring biomarkers produced by doxorubicin treatments.

The aim of the present study was to evaluate the clinical characteristics, prognoses and predictors of mortality of patients with pulmonary tuberculosis (TB) with acute respiratory failure (ARF), and to investigate the adjunctive use of corticosteroids in such cases. TB patients with ARF requiring mechanical ventilation (n = 90) were enrolled retrospectively during 1989-2006. The patients were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB (MTB; n = 24). The TBP patients were older than the MTB patients (mean age 68.0 versus 54.5 yrs), and the mean+/-SD interval from hospital admission to start of anti-TB treatment was longer for the TBP than for the MTB group (5.0+/-7.0 versus 2.8+/-2.5 days). However, there was no difference in in-hospital mortality rate between the two groups (68.2 versus 58.3%). In the TBP patients, multivariate analysis showed that advanced age and shock unrelated to sepsis were associated with poor outcomes. Even though corticosteroid use was a predictor of survival in TBP patients, it was difficult to conclusively determine the efficacy of corticosteroids in TBP with ARF because of the retrospective study design. The present study reveals the need for randomised controlled trials to clarify the role of corticosteroids as adjunctive therapy in the management of tuberculous pneumonia with acute respiratory failure.

In this paper, a channel allocation scheme for mediating UHF RFID bands is proposed. This scheme is designed for delivering a less-invasive channel area, a system capability enhancement, and intuitive data offering for overall strict the channel use and standardization UHF band (860 MHz-to-960 MHz). Several critical factors shall be discussed and simulated; thus, we can show the validity of this channel allocation proposal. Mostly, we focused on reducing collision effects among different types of UHF RFID reader systems within a single channel area and this shall be extended through some calculation and simulation works. Based on those works, we could obtain the appropriate solution for allocating each channel at less-invasion levels. This also will be discussed, presented and concluded with simulation results.

Generalized subcutaneous edema is an uncommon manifestation of inflammatory myopathy. We report a 48-year-old female patient who presented with severe generalized edema, an erythematous skin rash, dysphagia and proximal muscle weakness. She was diagnosed with dermatomyositis from the clinical signs, increased muscle enzymes, electromyographic findings and a muscle biopsy. Magnetic resonance imaging revealed increased signal intensity in the muscular and subcutaneous layers. The conditions causing generalized edema were excluded. It was concluded that the generalized edema was secondary to dermatomyositis. Aggressive treatments with high-dose glucocorticoids and immunosuppressive agents were used to control the severe subcutaneous edema.

Materials and Methods: We evaluated 335 consecutive patients with clinical stage II-III breast cancer with known hormone receptor (HR), HER2, and Ki-67 who received NAC plus BCT from 2002 to 2009. Patients were classified into six molecular subtypes: luminal A (HR+/HER2-/Ki-67

Background/Aims Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. Methods Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. Results Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. Conclusions Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.

Purpose: The thulium laser is the most recently introduced technology for the surgical treatment of benign prostatic hyperplasia (BPH). Until recently, most thulium laser enucleation of the prostate (ThuLEP) was performed by use of the three-lobe technique. We introduce a novel one-lobe enucleation technique for ThuLEP called the “All-in-One” technique. We report our initial experiences here. Materials and Methods: From June 2013 to May 2014, a total of 47 patients underwent the All-in-One technique of ThuLEP for symptomatic BPH performed by a single surgeon. All patients were assessed with the International Prostate Symptom Score (IPSS), transrectal ultrasonography, serum prostate-specific antigen (PSA), maximal urine flow rate (Qmax), and postvoid residual urine volume (PVR) before and 1 month after surgery. We reassessed IPSS, Qmax, and PVR 3 months after surgery. To assess the efficacy of the All-in-One technique, we checked the PSA reduction ratio, transitional zone volume reduction ratio, and enucleation failure rate. Results: The mean operative time was 82.1±33.3 minutes. The mean enucleation time and morcellation time were 52.7±21.7 minutes and 8.2±7.0 minutes, respectively. The mean resected tissue weight and decrease in hemoglobin were 36.9±24.6 g and 0.4±0.8 g/dL, respectively. All perioperative parameters showed significant improvement (p