Highly enantioselective synthesis of cyclopropylamine derivatives via Ru(II)-pheox-catalyzed direct asymmetric cyclopropanation of vinylcarbamates.

The Ru(II)-Pheox-catalyzed asymmetric cyclopropanation of vinylcarbamates with diazoesters resulted in the corresponding cyclopropylamine derivatives in high yield and excellent diastereoselectivity (up to 96:4) and enantioselectivity (up to 99% ee).

Lack of association of proteinuria and clinical outcome in patients treated with bevacizumab for metastatic colorectal cancer.

Background: Although bevacizumab-related hypertension has been reported as a predictive marker of therapy efficacy, an association between proteinuria and efficacy has not been reported.

Patients And Methods: Eighty-two consecutive patients with metastatic colorectal cancer treated with bevacizumab as first-line treatment between July 2007 and April 2009 were examined.

Results: Seventy-one patients were included in the analysis set.

Fluorimetric assay for D-amino acid oxidase activity in rat brain homogenate by using D-kynurenine as a substrate.

An easy fluorimetric assay for measuring D-amino acid oxidase (DAAO) activity by using one of the D-amino acids--D-kynurenine (D-KYN)--as a substrate was applied to assess DAAO activity in the cerebrum, cerebellum, and brainstem of Sprague-Dawley (SD) male rats. In this assay, DAAO produces kynurenic acid (KYNA) from D-KYN, and the fluorescence originating from KYNA can then be used to evaluate DAAO activity. Here, pellet fractions obtained by centrifugation of brain homogenates were allowed to react enzymatically with D-KYN.

Successful rechallenge for oxaliplatin hypersensitivity reactions in patients with metastatic colorectal cancer.

Background: Discontinuation of oxaliplatin-containing regimens is sometimes necessary due to hypersensitivity reactions for which effective countermeasures have not yet been identified.

Patients And Methods: We retrospectively reviewed cases in which hypersensitivity reactions developed in 623 patients treated with oxaliplatin for colorectal cancer. Clinical outcomes of patients who underwent oxaliplatin rechallenge with rechallenge protocol (STEP 1: hydrocortisone, chlorpheniramine, and/or ranitidine; STEP 2: hydrocortisone with an escalating dose to 500 mg, and/or prolonged administration time of oxaliplatin; and STEP 3: STEP 2 plus a subcutaneous injection of epinephrine) were examined.

Development of immunoassay based on monoclonal antibody reacted with the neonicotinoid insecticides clothianidin and dinotefuran.

Enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody (MoAb) was developed for the neonicotinoid insecticide clothianidin. A new clothianidin hapten (3-[5-(3-methyl-2-nitroguanidinomethyl)-1,3-thiazol-2-ylthio] propionic acid) was synthesized and conjugated to keyhole limpet hemocyanin, and was used for monoclonal antibody preparation. The resulting MoAb CTN-16A3-13 was characterized by a direct competitive ELISA (dc-ELISA).

A double-blind, placebo-controlled study of the safety and efficacy of vitamin K1 ointment for the treatment of patients with cetuximab-induced acneiform eruption.

A double-blind, placebo-controlled study evaluating the efficacy and safety of vitamin K1 ointment for the treatment of patients with cetuximab-induced acneiform eruption has started. Vitamin K1 ointment and placebo are applied twice daily for 8 consecutive weeks after the development of acneiform eruptions. Vitamin K1 ointment is applied in the middle of one side (face, neck or chest) and placebo is applied to the other side.

Long-term results of a phase II study of S-1 plus irinotecan in metastatic colorectal cancer.

Aim: The current study aimed to assess the long-term efficacy of combination therapy with oral S-1, a fluoropyrimidine prodrug, plus irinotecan in previously untreated patients with metastatic colorectal cancer.

Patients And Methods: Between April 2004 and February 2005, 41 patients with previously untreated advanced or recurrent colorectal cancer were enrolled in the study. Chemotherapy consisted of oral administration in S-1 at 40 mg/m(2) twice daily on days 1 to 14 and intravenous infusion of irinotecan at 150 mg/m(2) on day 1 in a 21-day cycle.

Multicenter feasibility study of combination therapy with fluorouracil, leucovorin and paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake.

Objective: Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy in such patients.

Methods: In the first phase of the study, we investigated the maximum tolerated dose and recommended dose in Cycle 1 of fluorouracil, l-leucovorin and paclitaxel, at two dose levels [Level 1 (n = 6): 5-fluorouracil/l-leucovorin/paclitaxel = 500/250/60 mg/m(2); Level 2 (n = 6): 600/250/80 mg/m(2) on Days 1, 8 and 15, every 28 days].

Highly stereoselective Ru(II)-Pheox catalyzed asymmetric cyclopropanation of terminal olefins with succinimidyl diazoacetate.

The Ru(II)-Pheox complex is an efficient catalyst for the intermolecular cyclopropanation of various terminal olefins with succinimidyl diazoacetate. This catalytic system can perform under mild conditions, and the desired cyclopropane products are obtained in high yields with excellent diastereoselectivity and enantioselectivity.

Practical synthesis of 4,4,4-trifluorocrotonaldehyde: a versatile precursor for the enantioselective formation of trifluoromethylated stereogenic centers via organocatalytic 1,4-additions.

The practical synthesis of 4,4,4-trifluorocrotonaldehyde (1) and its application to enantioselective 1,4-additions are described. The organocatalytic 1,4-addition of 1 with several nucleophiles such as heteroaromatics, alkylthiols and aldoximes afforded the corresponding products, each bearing a trifluoromethylated stereogenic center with high optical purity. A resulting product was converted into an MAO-A inhibitor, befloxatone.

Highly enantioselective chlorination of β-keto esters and subsequent S(N)2 displacement of tertiary chlorides: a flexible method for the construction of quaternary stereogenic centers.

Highly enantioselective chlorination of β-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of β-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired α-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as α-amino, α-alkylthio, and α-fluoro esters, without loss of enantiopurity.

Transtricuspid approach in redo surgery for post-infarction ventricular septal rupture.

A 59-year-old man, who had been treated using the infarction exclusion technique for inferior post-infarction ventricular septal rupture (VSR) 4 months previously, was readmitted because of deterioration of mitral valve regurgitation, residual shunt, and progression of pulmonary hypertension. We performed mitral valve replacement via the transseptal approach, patch closure of the defect via the transtricuspid approach, and tricuspid valve annuloplasty. The post-operative course was uneventful.

Risk factors for infantile atopic dermatitis and recurrent wheezing.

Background: The pathogenic mechanisms of atopic dermatitis (AD) and recurrent wheezing (RW) during infancy are not fully understood.

Objective: We evaluated immunological markers associated with AD and RW during infancy.

Methods: We followed a cohort (n = 314) from birth to 14 months of age.

Reasons for avoidance of bevacizumab with first-line FOLFOX for advanced colorectal cancer.

Background: The addition of bevacizumab to standard chemotherapy has significant clinical benefits in metastatic colorectal cancer. However, its use is often avoided due to patient condition or disease status.

Methods: Of 228 consecutive patients receiving first-line FOLFOX-based regimens from June 2007 to June 2009, 96 patients (42 %) received FOLFOX alone without bevacizumab.

Light exposure at night, sleep duration and sex hormone levels in pregnant Japanese women.

The association between light exposure at night and sex hormone levels in utero has scarcely reported. We assessed the associations between sleep duration or being awake in the late evening hours, which can be as indicator of light exposure at night, and the maternal and umbilical blood hormone levels during pregnancy and at delivery among Japanese women. The data for 236 women and their newborns who visited a maternal clinic in Gifu, Japan, between May 2000 and October 2001 were analyzed.

Development of an enzyme-linked immunosorbent assay (ELISA) for residue analysis of the fungicide azoxystrobin in agricultural products.

A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) was developed for residue analysis of azoxystrobin in garden crops, for which the maximum residue limits (MRLs) are 0.5-50 mg/kg in Japan. For hapten synthesis, an ethyl carboxyl group was introduced to the 4-position of the 2-cyanophenoxy group in azoxystrobin, and its cyano group was changed to a methyl group.

Phase II study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel as first-line therapy for advanced gastric cancer.

Objective: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients.

Methods: Patients with untreated stage IV GC received paclitaxel 80 mg/m(2) as a 1-hour infusion, followed by 5-FU 600 mg/m(2) as a bolus infusion and L-leucovorin 250 mg/m(2) as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days.

A Diels-Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers.

Highly enantioselective Diels-Alder reactions of β-fluoromethylacrylates were carried out in the presence of a Lewis acid activated chiral oxazaborolidine catalyst. These reactions yielded fluoromethylated cyclohexenes, including trifluoromethyl-, difluoromethyl-, and monofluoromethyl cyclohexenes, as nearly pure enantiomers. The resulting fluoromethyl cyclohexenes were converted into potential synthetic intermediates for bioactive compounds.

Inhibition of D-amino acid oxidase activity by antipsychotic drugs evaluated by a fluorometric assay using D-kynurenine as substrate.

A facile fluorometric assay using D-kynurenine as a substrate was utilized for evaluating the inhibition of D-amino acid oxidase (DAAO), which is one of the products of a susceptibility gene for schizophrenia, by commercial antipsychotic drugs, namely, chlorpromazine (CPZ), carbamazepine, sulpiride, quetiapine, and imipramine. CPZ inhibited DAAO (65.8 ± 13.

First-line fluorouracil-based chemotherapy for patients with severe peritoneal disseminated gastric cancer.

Background: Treatment with an oral fluoropyrimidine plus cisplatin is widely used for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate such treatment, due to inadequate oral intake or massive ascites. The aim of this study was to assess the efficacy and safety of systemic chemotherapy for advanced gastric cancer with severe peritoneal metastasis.

Methods: The cases of 92 patients with advanced gastric cancer and severe peritoneal metastasis who received first-line chemotherapy at our hospital between May 2001 and February 2007 were retrospectively analyzed.

Enantioselective gem-chlorofluorination of active methylene compounds using a chiral spiro oxazoline ligand.

Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity.

Transcatheter arterial infusion chemotherapy with a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

Objective: The aim of this study was to assess the safety and efficacy of transcatheter arterial infusion chemotherapy using a fine-powder formulation of cisplatin for patients with advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

Methods: We retrospectively examined the data of 84 consecutive patients with transcatheter arterial chemoembolization-refractory hepatocellular carcinoma who underwent transcatheter arterial infusion chemotherapy with a fine-powder formulation of cisplatin. Cisplatin was administered at the dose of 65 mg/m(2) into the feeding artery of the hepatocellular carcinoma.