[en] There have been only limited methods for the synthesis of cyclopenta[d][1,2]oxazines and their derivatives. Linn and Sharkey reported the first practical synthesis of cyclopenta[d][1,2]oxazine by use of benzoylated cyclopentadiene. Lloyd and co-workers also reported the synthesis of cyclopenta[d][1,2]oxazine by reaction of diaroylcyclopentadi-enes with hydroxylamine. The reaction of benzonitrile oxide with fulvene was known to yield both 1 : 1 and 2 : 1 adducts. Herein, we report the first example of a facile and convenient synthesis of various cyclopenta[d][1,2]oxazines starting from chlorooxime and fulvene through [6+4] cycloaddition. In an effort to pursue of PTP1B inhibitors, a convenient synthesis of functionalized cyclopenta[d][1,2]-oxazine derivatives was required. Fulvenes were obtained from the reaction of dimethyl sulfate salt of dimethylamides and cyclopentadienyl sodium as cited

[en] We have prepared a series of lithium diisobutyldialkylaminohydroaluminates by reacting DIBAH with lithium dialkylamides. Among them, LDBPA was most effective for partial reduction of esters to aldehydes in moderate to good yields at 0 .deg. C. This reagent proved to be one of effective partial reducing agents for preparation of esters to aldehydes. Therefore, LDBPA is believed to be an alternative reagent for the synthesis of aldehydes from esters instead of DIBAH. Partial reduction of ester to aldehyde is very efficient and reliable procedure in organic synthesis, and a number of reducing agents for this have been reported. Among them, diisobutylaluminium hydride (DIBAH) which is commercially available is used as one of the most popular reducing agent. However, to achieve the partial reduction successfully, this reagent requires very low temperature. Recently, we reported the synthesis of aldehyde from ester with sodium diethylpiperidinohydroaluminate (SDPA) at 0 .deg. C. However, sodium diethyldihydroaluminate which is the precursor for synthesis of SDPA is not commercially available. In the course of our program for developing new selective reducing agent, we found that lithium diisobutyldialkylaminohydroalumonates prepared from DIBAH smoothly reduced esters to aldehydes at 0 .deg. C, although it has been reported that the reduction of esters to aldehydes using aluminium hydride derivatives having n-butyl or alkoxy groups obtained from DIBAH has been not successful

[en] In the periodic repainting of steel bridges, often the steel surface has to be prepared by using power tools to remove surface contaminants, such as deteriorated paint film and rust, and to increase the adhesive strengths of the paint films to be applied newly. Surface preparation by bristle roll-brush grinding, which is a type of power tool, may additionally introduce compressive residual stress and increase the fatigue resistance of welded joints owing to the impact of rotating bristle tips. In this study, fatigue tests were conducted for longitudinally out-of-plane gusset fillet welded joints and transversely butt-welded joints to evaluate the effect of bristle roll-brush grinding prior to repainting on the fatigue resistance of the welded joints. The test results showed that bristle roll-brush grinding introduced compressive residual stress and significantly increased fatigue limits by over 50%.

[en] Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR. Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0—2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m"2, and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile. A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0–57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0–55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm. PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR. The study is registered with ClinicalTrials.gov (NCT01196234). Registration date is 08/09/2010

[en] Purpose: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. Methods and Materials: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m²/day and leucovorin 20 mg/m²/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. Results: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). Conclusions: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

[en] Purpose: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). Methods and Materials: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. Results: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). Conclusion: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated