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Background The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. Methods CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). Results The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher. Conclusions CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

Recently, there have been many developments on power devices to improve their functions. Especially, the junction temperature of power modules that equip SiC (Silicon Carbide) chips will be higher than 200 °C as current densities are too high, and new electronic packaging technologies shall be developed to meet higher temperature and higher power cycle durability requirements. In order to meet these requirements, in the present study, we propose Cu wire, Cu ribbon and Cu connector between Cu wirings of the substrates and investigate their feasibilities, including electrical resistances, footprints of bonding area, and bonding reliability under accelerated stress test, respectively.

接ぎ木キュウリ苗の奇形葉発生要因の究明を目的として，接ぎ木法，台木品種およびホウ素処理が奇形葉発生に及ぼす影響を明らかにした．キュウリの接ぎ木苗に発生する奇形葉は，断根挿し接ぎ，割り接ぎ，挿し接ぎで発生し，呼び接ぎでは発生しなかった．呼び接ぎでは，穂木および台木胚軸の切断の有無にかかわらず，全く発生しなかった．奇形葉の発生は台木品種によっても異なり，台木として‘改良新土佐1号’など，セイヨウカボチャ × ニホンカボチャのF1品種を使用すると多かった．接ぎ木直後にホウ砂0.05～0.1％溶液を葉面散布すると，奇形葉の発生が抑制された．接ぎ木前の2日間ホウ素の供給を断つと，奇形葉が多発した．ホウ素処理は，台木の発根および接ぎ木後の活着に強い影響を及ぼした．

Decabromodiphenyl ether (decaBDE) is a brominated flame retardant used in many commercial products such as televisions, computers, and textiles. Recent reports indicate that decaBDE adversely affects male reproductive organs in mice, but the underlying molecular mechanisms remain unknown. We hypothesized that decaBDE affects mouse testes by altering the expression and phosphorylation level of cortactin (CTTN), an F-actin-binding protein that is similar to flutamide, and we performed western blot analyses on testicular samples from mice subcutaneously injected with decaBDE (0.025, 0.25, and 2.5 mg/kg body weight/day) on postnatal days 1 to 5. Mice treated with low-dose decaBDE (0.025 mg/kg) showed reduced testicular weight, sperm count, elongated spermatid and Sertoli cell numbers, as well as induced Tyr phosphorylation of CTTN and reduced the expression level of p60 Src tyrosine kinase (SRC). Further, 0.25 and 2.5 mg/kg decaBDE-exposed groups produced an decrease the expression level of CTTN. High-dose decaBDE (2.5 mg/kg) showed increased abnormal germ cells, as well as induced Ser phosphorylation of CTTN and activated extracellular signal-regulated kinase (ERK1/2); however, high-dose decaBDE did not affect testicular weight and sperm count. These findings suggest that postnatal exposure to low-dose decaBDE inhibits mouse testicular development by increasing Tyr phosphorylation of CTTN, although different mechanisms may be involved depending on the dose of decaBDE.

A sensitive high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for measuring vinorelbine was developed. A 100 µL aliquot of plasma was spiked with deuterium-labeled internal standard and subjected to solid-phase extraction using an Oasis HLB μ-elution plate. Two microliters of the extracted samples was directly injected into LC/MS/MS. Chromatographic separation was achieved on a Capcell Pak C18 UG column (2 × 75 mm) with a gradient elution of methanol (mobile phase B) against 0.05% formic acid in aqueous 10 mm ammonium formate (mobile phase A). The LC flow rate was set to 0.28 mL/min and the gradient (solvent B concentration) was processed from 40 to 90%. In mass spectrometric detection, observation of the reaction from a double-charged precursor ion [M + 2H]2+ (m/z 390) to product ion m/z 122 provided very high sensitivity. The method was validated with a lower limit of detection of 0.2 ng/mL with 0.1 mL of plasma, and the method was used to determine the plasma pharmacokinetics of vinorelbine in dogs. Copyright © 2010 John Wiley & Sons, Ltd.

高温・高湿度管理を行うキュウリの促成栽培における作業の快適化を目的として，温度管理が室内の温熱環境，作業者の労働負担およびキュウリの生育，果実収量，果実品質，病害の発生に及ぼす影響を明らかにした．収穫作業を行う9時30分～11時30分までの換気温度を25℃にすると，慣行栽培である29℃に対してWBGTが低下し，作業者の心拍数の上昇は抑制され，施設内での労働負担が軽減された．また，11時30分～13時30分までを38℃にするとキュウリの上物収量が低下し，曲がり果の発生が増加し，果皮色は淡くなったが，33℃では慣行の温度管理と同等の収量・品質を維持することができた．さらに，33℃変温区は慣行区の29℃に比べてうどんこ病やべと病の発生が少なく，薬剤散布の労力やコストの削減につながるものと考えられた．

At Chiba University, gross anatomy laboratory sessions (“laboratories”) are required for physical therapy students. Though most physical therapy schools require their students to participate in laboratories so that they will better understand the structure of the human body, few data exist on the value of these laboratories specifically for physical therapy students. We administered questionnaires to physical therapy undergraduate students both before and after they participated in laboratories. Questionnaire items focused on student attitudes toward the laboratories and on human life and dignity. Data from 83 students were analyzed, with the following results: (1) 74.7% of students had a positive attitude about attending laboratories before doing so; (2) with few exceptions, students' attitudes about upcoming laboratories grew more positive after experiencing the laboratory work (P < 0.001); (3) laboratories caused students to contemplate the topics of human life and dignity; and (4) 83.1% of students hoped to participate in laboratories at least four times. These results indicate that laboratories reinforce physical therapy students' positive attitudes about laboratory learning and promote student reflection on human life and dignity. This study provides support for the implementation of multiple laboratory sessions using cadavers into a uniform curriculum for physical therapy students in Japan. Anat Sci Educ 2: 273–279, 2009. © 2009 American Association of Anatomists.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants to prevent combustion in consumer products, such as electronics, construction materials, and textiles and, therefore, have become important commercial substances. PBDEs were also detected in maternal blood, breast milk, umbilical cord blood, and cord tissue, thereby indicating that fetuses were also exposed to PBDEs. The purpose of this study is to identify the effect of PBDEs on human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were exposed to a commercial mixture of penta-BDE (DE71), octa-BDE (DE79), and deca-BDE (DE83). Each gene expression that was altered in DNA microarray was confirmed by real-time reverse transcription—polymerase chain reaction and Western blotting analysis. The results indicated that gene expressions concerning antioxidant system, i.e., thioredoxin family, 24-dehydrocholesterol reductase (DHCR24), and tumor suppressor protein p53, were altered by PBDEs exposure in HUVECs. Moreover, it was demonstrated that thioredoxin-interacting protein (TXNIP) was a target gene in exposure to DE71 and DE79 in HUVECs, by drastically decreasing time-dependent TXNIP expression in HUVECs.

Applicability of atmospheric pressure photoionization mass spectrometry (APPI-MS) to the analysis of hydrophilic drugs was investigated. Model compounds with moderate to high hydrophilicity was tested, and most compounds showed good signal response with APPI-MS, but some compounds with high molecular polarity like folic acid derivatives, glycoside and some nucleic acid derivatives showed very weak signal responses. By observing relationship between the compounds' physicochemical properties and APPI response, compounds with higher lipophilicity and less polar surface area were considered to be advantageous for APPI-MS. To provide information for applying APPI-MS to the analysis of hydrophilic drugs, approximate lower limit of calculated octanol-water partition coefficient and the higher limit of the number of oxygen and nitrogen atoms were determined to be -0.95 and 6, respectively. These APPI-applicable model compounds could be analyzed by reversed-phase high performance liquid chromatography-APPI-tandem mass spectrometry.

キュウリの促成栽培において，ガラス室内の二酸化炭素濃度500 ppm長時間施用と同1,000 ppm短時間施用が，果実収量に及ぼす影響を明らかにするととともに，その経済性評価を行った．二酸化炭素施用により上物収量は無施用より39～55％増加した．二酸化炭素施用に伴う経費を差し引いた収益は，無施用に比べ，1 a当たり5.8～9.6万円増加した．500 ppm長時間施用は，1,000 ppm短時間施用に比べて増収効果が高いとともに，二酸化炭素施用量が少なかった．

In this study, 60 solder compositions were examined in an effort to improve the integrity against impact loads of the solder joints on an electroless Ni–P/Au surface finish. The Ag, Cu, and Ni contents in the Sn-based solder varied from 0 to 4.5 wt%, 0 to 2.0 wt%, and 0 to 0.05 wt%, respectively. Impact shear tests were performed to investigate solder joint integrity after solder ball reflowing, after reflow soldering twice more, after storage at room temperature for 168 hours, and after storage at 150°C for 1,000 hours. According to the results, the Ag content should be as low as possible, the Cu content should be from 0.5 to 0.7 wt%, and the Ni content should be as high as possible. The Ag and Ni contents should be determined in consideration of the wettability and the board-level reliability of the solder joints.

The kinetically controlled synthesis of N-benzyloxycarbonyl (Z)-dipeptides was investigated by the use of free amino acids as nucleophiles and a cysteine protease papain as catalyst. The coupling efficiency was significantly improved by the combined use of the carbamoylmethyl (Cam) ester of a Z-amino acid as acyl donor and frozen aqueous solution (ice, −16 or −24 °C) as reaction medium. The yield of peptide synthesis became high when both P1- and P ′ 1 -positions were occupied by small non-polar amino acids (Z-Gly-Gly-OH, 76%; Z-Gly-Ala-OH, 75%; Z-Ala-Ala-OH, 72%). Similar results were observed by the use of ficin as catalyst instead of papain. Furthermore, this strategy was applied to the papain-catalyzed incorporation of a d -configured amino acid such as d -alanine into the resulting peptides. Although the coupling in aqueous solution (30 °C) afforded the desired Z-dipeptides in low yields, the freezing of reaction medium reduced significantly unfavorable hydrolysis of the acyl donors, resulting in improvement of the coupling efficiency (Z-Gly- d -Ala-OH, 80%; Z-Ala- d -Ala-OH, 45%; Z- d -Ala-Ala-OH, 22%).

Porcine pancreatic lipase (PPL)-catalyzed enantioselective hydrolysis of N-benzyloxycarbonyl-dl-amino acid esters (Z-dl-AA-ORs) was studied for the optical resolution of a variety of non-protein amino acids. The ester moiety (R) of the substrate affected the rate of hydrolysis significantly. The glyceryl (Gl) and carbamoylmethyl (Cam) esters were found to be highly reactive substrates. The hydrolysis of the Gl esters (Z-dl-AA-OGls) of both aliphatic and aromatic amino acids was examined in acetonitrile containing 70% (v/v) of 0.02 M phosphate buffer (pH 7.0) at 30°C. With all amino acids tested, the corresponding l-enantiomers were hydrolyzed preferentially. PPL favored aromatic amino acids, such as phenylalanine and p-chlorophenylalanine, leading to completion of the hydrolysis within 20 min with excellent enantioselectivities (E>100). The PPL-catalyzed hydrolysis of the corresponding Cam esters (Z-dl-AA-OCams) was also examined under the same reaction conditions. Although the hydrolysis of the Cam ester...

Brominated flame retardants (BFRs) are used to prevent combustion in consumer products. Examples of BFRs are polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA), and tribromophenol (TBP). These compounds are reported to have adverse effects on human health and endocrine disrupting effects. The purpose of this study was to identify the Japanese perinatal exposure to PBDEs, hydroxylated PBDE metabolites (OH-PBDEs), TBBPA, and TBP compared with polychlorinated biphenyls (PCBs) and hydroxylated PCB metabolites (OH-PCBs). We investigated the concentrations of these compounds in maternal blood, maternal milk, cord blood, and umbilical cords from 16 Japanese mother-infant pairs by HRGC/HRMS. PBDEs were detected in all samples of maternal blood (mean+/-SD; median=25+/-23 pg/g; 18 pg/g wet weight), maternal milk (140+/-220 pg/g; 59 pg/g wet weight), cord blood (4.8+/-6.5 pg/g; 1.6 pg/g wet weight), and umbilical cords (3.1+/-3.1 pg/g; 2.1 pg/g wet weight). The mothers were divided into two groups, a high-concentration group and a low-concentration group. The percentage of BDE-47 showed the greatest difference between the two groups. 6-OH-BDE-47, TBBPA, and TBP were detected in all umbilical cord samples (mean+/-SD; median=8.4+/-8.1 pg/g; 8.0 pg/g, 16+/-5.5 pg/g; 15 pg/g, and 33+/-8.2 pg/g; 32 pg/g wet weight respectively), but not in all maternal blood or cord blood samples. These results indicate that OH-PBDEs, TBBPA, and TBP, in addition to PBDEs, PCBs, and OH-PCBs, pass through the blood-placenta barrier and are retained in the umbilical cord.

Background Heart failure (HF) represents a major public health issue in an aging population. Although HF is a leading cause of morbidity and mortality in developed countries, the clinical features of HF in Japan remain unclear. Methods and Results This observational cohort study analyzed data from the Heart Institute of Japan - Department of Cardiology (HIJC)-HF Registry, which is based on a nationwide survey by the HIJC, Tokyo Women's Medical University and its affiliated hospitals. Of 3,578 consecutive patients (average age, 69.8 years; females 40.7%) hospitalized for HF between January 2001 and December 2002, 95.0% were followed up until the end of 2005 (median, 2.8 years). The 1- and 3-year mortality rates were 11.3% and 29.2%, respectively. Multivariate analysis revealed that advanced age (hazard ratio 1.71 [95% confidence interval 1.38-2.12]; p

A kinetically controlled peptide synthesis catalyzed by α-chymotrypsin was performed in frozen aqueous solution (ice, −24 °C). The yield of the peptide was significantly improved by the use of the carbamoylmethyl (Cam) ester as the acyl donor instead of the conventional ethyl ester. The peptide yield increased up to ca. 90% when N-benzyloxycarbonyl (CBZ)-Phe-OCam and H-Phe-NH2 were used as the acyl donor and nucleophile, respectively. Such an improvement of the peptide yield in ice was also observed in the coupling of other CBZ-amino acid Cam esters as acyl donors. Furthermore, this approach was applied to the synthesis of peptides containing d -amino acids. The peptides such as CBZ- d -Phe-Phe-NH2, CBZ-Phe- d -Phe-NH2 and CBZ- d -Phe- d -Phe-NH2 were also obtained in excellent to moderate yields in ice. A high diastereoselectivity towards the l – l peptide was observed when the racemic amino acid Cam ester was used as the acyl donor in ice.

Alpha-chymotrypsin-catalyzed peptide synthesis was carried out between an N-protected D-amino acid ester and an L-amino acid amide (acyl donor, 10 mM; acyl acceptor, 50 mM; enzyme, 2 mg ml(-1); pH 8). By using a highly reactive carbamoylmethyl (Cam) ester as acyl donor, the D-amino acid was incorporated into the N-terminus of the resulting dipeptide amide. N-Protected dipeptide amides bearing D-amino acids such as D-Phe, D-Leu and D-Ala at their N-terminus were synthesized in high yields (up to 80%) in 1-3 h.

In order to prepare calcium hydroxyapatite (CaHAp) containing a component with photo-catalytic activities such as Ti4+, two preparation procedures, coprecipitation and surface treatment, were investigated since it was recently reported that CaHAp containing Ti4+ species possessed rather greater activities than the corresponding oxide. The solid produced from the coprecipitation of Ca2+, Ti4+ and PO43− in aqueous phase was not homogeneous due to the precipitation of Ti-species in the solution during the preparation, indicating that a particle of the Ti-species was present in the bulk phase of the hydroxyapatite. Since it is sufficient that the Ti-species is present on the surface of CaHAp in respect to the employment as a photo-catalyst, the surface treatment of CaHAp with Ti4+ was examined under the dilution conditions of TiSO4 in acidic solution to avoid the precipitation of the Ti-species. The employment of pH = 1.1 was rather unfavorable due to the conversion of CaHAp to CaHPO4 while the conversion was suppressed by using the solution of pH = 1.7. When CaHAp was added to the homogeneous solution containing Ti4+ by the atomic ratio Ti4+/Ca2+ = 1/10, in which the former and latter were corresponded to molar number of Ca2+ in CaHAp added and that of Ti4+ in the solution, Ti4+ was completely immobilized within 30 mim. Similar immobilization behaviors were also observed in the immobilization of aqueous Zr4+ with CaHAp. It was pointed out that the surface of CaHAp treated with Ti4+ and Zr4+ was covered with Ca2+ species since re-precipitation of Ca2+ species occurred after the immobilization of those tetravalent cations.

ABRとDPOAE検査を同時期に施行した1歳未満の症例53例106耳について検討した。ABRとDPOAEの結果の解離は19例28耳 (26.4%) に認められた。ABR:pass・DPOAE:refbr の例は滲出性中耳炎や外耳道狭窄によるものが多かったが, 聴力型が結果不一致の原因と考えられた症例もあった。ABR:refbr・DPOAE:pass の例については, 4例7耳が auditory neuropathy と考えられた。ABR・DPOAE ともに利点と限界があるので, 新生児・乳幼児の精密聴力検査ではBOA・CORなどの行動検査を含め, 検査法を組み合わせて評価を行うべきものと考えられた。

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems. CYP1A2 and CYP1A2Gln478His did not show any differences in 7-ethoxyresorufin O-deethylase activity. CYP2A6 and CYP2A6Glu419Asp metabolized coumarin to form 7-hydroxycoumarin in a similar manner, whereas CYP2A6Ile471Thr showed low activity compared to the wild-type CYP2A6. CYP2B6, CYP2B6Pro167Ala and CYP2B6Arg487Cys showed the same activity for 7-ethoxy-4-triflouromethyl-coumarin O-deethylation. However, CYP2B6Gln172His was roughly twice as active as CYP2B6 and the other CYP2B6 variants for 7-ethoxy-4-triflouromethylcoumarin O-deethylation activity. Although higher inter- and intra-laboratory variations were observed for the calculated Km and V(max) values because the studies were conducted in several different laboratories, the degree of variations was reduced by the increased number of analyses and the adoption of a simple analysis system.

The dissolution–precipitation mechanism has been suggested for the immobilization of aqueous lead cation with calcium hydroxyapatite (Ca10(PO4)6(OH)2; CaHAp). Here Na2HPO4, K2HPO4, MgHPO4 and CaHPO4 were employed for CaHAp. These hydrogenphosphates could favorably remove Pb2+, Cd2+, Co2+ and Cu2+ from aqueous solution for 0.5 h at 293 K. The removability of those hydrogenphosphates was evidently greater than that of CaHAp and seemed to be dependent on solubility of those hydrogenphosphates and the hydration enthalpy of those heavy metal cations. The structures of phosphates recovered after immobilization of Pb2+, Cd2+, and Co2+ were strongly influenced by the pH in the aqueous solution, while the structures after immobilization of Cu2+ for 0.5 and 12 h were amorphous compound and Cu2(PO4)(OH), respectively. The employment of solid state 31P MAS NMR and XRD revealed that the amorphous compound was also Cu2(PO4)(OH). The removability found with those hydrogenphosphates was also observed in the immobilizatio...

A phage-displayed library selection was performed to obtain metal ion-chelating peptides. A dodecamer (12-mer) random peptide library was displayed on the surface of filamentous bacterial phage and subjected to an affinity selection. Four rounds of the selection gave fourteen Zn2+-positive phage clones. Enzyme-linked immunosorbent assay showed that the selected clones specifically bound to Zn2+ and Ni2+, but not to Cu2+ and Fe3+. Deduced amino acid sequences of the clones had histidine-rich consensus motifs. These chelating peptides should be applied to designing for metal ion-trapping biomaterials.

小児の声門部異物1例および声門下異物2例を経験したので，文献的考察を含め報告する。1例目は9カ月男児，プラスチック片の声門部異物で，発症当日に摘出された。2例目は1歳1カ月の女児で突然の咳嗽のため他院で仮性クループとして治療を施されたが，発症翌日喘鳴が増悪してきたため当科受診した。エビの尻尾が声門下に嵌頓しているのを認めたため摘出した。3例目は2歳8カ月の女児，ピスタチオナッツの殼による声門下異物を認め摘出したが，喘鳴が続くため喘息の診断のもと7カ月間治療を行った。その後の再精査の結果，殼の一部が残存していたことが判明し，摘出したところ喘鳴は消失した。小児では十分な問診が行えず，診察の協力も得られないため，喉頭異物の発見が遅れることがある。したがって小児の喘鳴，嗄声，咳嗽では異物の可能性を念頭に置き，喉頭ファイバーと頸部単純X線写真による異物の検索は必須である。また，異物摘出後も喘鳴が持続する場合は異物残存の可能性を考慮し，再検索する必要がある。

Thymidine phosphorylase (TP) has diverse functions within cells, including increasing the sensitivity of cancer cells to cytotoxic drugs including 5-fluorouracil (5-FU) and methotrexate. However, the regulators of TP still remains largely unknown. In this study, we examined whether tamoxifen has specific effects on TP expression in the T47D breast cancer cell line. We studied the TP expression in the T47D cell line before and after tamoxifen treatment using Western blot analysis and ELISA. We found that TP expression is significantly up-regulated in tamoxifen-treated cells compared with control. Our findings suggest that tamoxifen may increase chemotherapy sensitivity through TP up-regulation for treatment regimens including doxifluridine, capecitabine, and or methotrexate.

The most common form of nasal obstruction in neonates is soft tissue edema, but congenital bony nasal anomalies are recognized as an important cause of newborn airway obstruction. We reviewed 20 cases of congenital bony nasal abnormalties such as choanal atresia and nasal stenosis referred to National Children's Hospital between 1996 and 2001. Of the 20, 8 involved choanal atresia (6 bilateral and 2 unilateral) and 12 nasal stenosis (5 nasal cavity stenosis, 2 pyriform aperture stenosis and 5 unknown). Six cases of bilateral choanal atresia and 5 of 12 cases of the nasal stenosis presented severe airway distress. Most cases in respiratory distress required immediate surgical enlargement of nasal cavity and stenting with an endotracheal tube for 4 to 8 weeks. Of 12 with nasal stenosis, 5 with mild nasal obstruction were treated with nasal drops and 3 with mild airway distress required no treatment. Five of 7 (71%) with choanal atresia and 1 of 4 with nasal stenosis (25%) required restenosis of the nasal cavity after stent removal. Restenosis occurred more often in choanal atresia than in nasal atresia. Two of 5 with nasal restenosis required stenting for 1 to 2 months again and 1 of those was followed by stenting for more 4 months. Longer stenting did not prevent choanal from restenosis, however, no standard stenting protocol exists for neonates, highlighting the need for further study.

OBJECTIVE: \nPancreatic cancer is a difficult to treat disease with a persistently high mortality rate. We evaluated dose distribution simulation with respiratory-gated carbon-ion pencil beam scanning (C-PBS) with a simultaneous integrated boost (SIB) to increase tumour dose, sparing organs at risk (OARs). \nMETHODS: \nUsing four-dimensional CT data of 12 patients, we delineated gross tumour volume and two clinical target volumes (CTVs). To consider beam range intrafractional uncertainty, we calculated field-specific target volumes, from which two planning target volumes (PTVs) were generated. PTV1 would receive a planned dose of 55.2 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] in 12 fractions, and PTV2 would receive an SIB dose up to 67.2 Gy (RBE). Dose assessments were conducted with regard to the targets and OARs. \nRESULTS: \nCTV2 dose covering 95% of the volume (D95%) increased from 50.3 ± 5.1 Gy (RBE) to 62.5 ± 3.5 Gy (RBE) for a planned dose from 55.2 Gy (RBE) to 67.2 Gy (RBE). For 4 of 12 patients with a distance of ≥5 mm between the tumour and the gastrointestinal tract, CTV2 D95% was ≥95% of planned dose at all dose levels. \nCONCLUSION: \nWe quantified dose escalation with respiratory-gated C-PBS using SIB for pancreatic cancer and revealed that OAR dose was not affected to the same degree as the tumour dose. Advances in knowledge: A simulation study on respiratory-gated C-PBS with SIB for pancreatic cancer was performed. The results indicated the feasibility of dose escalation for pancreatic cancer, which should be confirmed in clinical trials.

Toremifene (TOR) and Tamoxifen (TAM) are widely used as endocrine therapy for estrogen receptor positive breast cancer. Poor metabolizers of TAM are likely to have worse clinical outcomes than patients who exhibit normal TAM metabolism due to lower plasma level of its active metabolite, 4-hydroxy-N-desmethyl (4OH-NDM) tamoxifen (endoxifen). In this study, we examined the role of individual cytochrome P450 (CYP) isoforms in the metabolism of TOR to N-desmethyl (NDM), 4-hydroxy (4OH) and 4OH-NDM metabolites in comparison with TAM using human liver microsomes (HLMs) with selective chemical inhibitors for each CYP isoform and recombinant CYP proteins. Similar levels of NDM metabolites were formed for both TOR and TAM, and N-demethylation of both compounds was primarily carried out by CYP3A4. We found that the formation of 4OH-NDM-TOR was catalyzed both by CYP2C9 and CYP2D6, whereas the formation of 4OH-TAM and endoxifen was specifically catalyzed by CYP2D6 in HLMs. Our results suggest that the potential contribution of CYP2D6 in the bioactivation pathway of TOR may be lower compared to TAM, and may have a different impact on clinical outcome than CYP2D6 polymorphisms.

This research focuses on the formation and growth behavior of Cu/Al intermetallic compounds (IMCs). In order to investigate IMC growth after 30, 60 and 120 min of aging at 270, 300 and 330 °C, cross-section of Al, Cu and Cu/Al IMCs were examined by scanning electron microscopy (SEM). The results showed that the consumption of the Al layer is more rapid than that of Cu layer, and that after 120 min at 330 °C the Al layer is entirely consumed. The formation of three distinct Cu/Al IMC layers was observed. Scanning transmission electron microscopy (STEM)/energy-dispersive X-ray spectroscopy (EDS) was used to identify the three IMC layers formed at the interface. These were CuAl, Cu 3 Al 2 and Cu 9 Al 4 . Also, the activation energies of Cu/Al IMC growth were obtained from an Arrhenius plot.