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The naturally occurring compound 3[beta],16[beta],17[alpha]-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-[beta]-D-xylopyranosyi)-(1[right arrow]3)-(2-O-acetyl-[alpha]-L-arabinopyranoside) (OSW-1) is found in the bulbs of Ornithogalum saudersiae and is highly cytotoxic against tumor cell lines. Using various human cancer and nonmalignant cell lines, we investigated the anticancer activity and selectivity of OSW-1 and its underlying mechanisms of action. OSW-1 exhibited extremely potent cytotoxic activity against cancer cells in vitro. Nonmalignant cells were statistically significantly less sensitive to OSW-1 than cancer cells, with concentrations that cause a 50% loss of cell viability 40-150-fold greater than those observed in malignant cells. Electron microscopy and biochemical analyses revealed that OSW-I damaged the mitochondrial membrane and cristae in both human leukemia and pancreatic cancer cells, leading to the loss of transmembrane potential, increase of cytosolic calcium, and activation of calcium-dependent apoptosis. Clones of leukemia cells with mitochondrial DNA defects and respiration deficiency that had adapted the ability to survive in culture without mitochondrial respiration also were resistant to OSW-1. In vitro analysis revealed that OSW-1 effectively killed primary leukemia cells from chronic lymphocytic leukemia patients with disease refractory to fludarabine. The promising anticancer activity of OSW-1 and its unique mechanism of action make this compound worthy of further investigation for its potential to overcome drug resistance. [J Natl Cancer Inst 2005;97:1781-5]

Background: For esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosa (T1a-MM) or upper submucosa (T1b-SM1, up to 200 µm), the curative effectiveness of endoscopic submucosal dissection (ESD) and additional therapeutic strategies remain controversial. The present study aims to investigate the effectiveness of ESD followed by different therapeutic strategies in treating such patients. Methods: A total of 242 patients with T1a-MM/T1b-SM1 ESCCs were involved. Data on therapeutic outcomes and long-term survivals were collected for analysis. Propensity score-matched analysis was performed to compensate for selection bias between patients with no additional therapy (NAT group) and those with additional therapy (AT group). Results: R0 resection rate was 83.1% and curative resection rate was 78.5%. After a mean follow-up period of 57.8 ± 27.3 months, the cumulative recurrence rate was 7.9%. The 5-year overall survival (OS) and cause-specific survival (CSS) rate was 91.1% and 94.0%. In a matched cohort of 24 pairs, the 5-year OS and CSS rates showed no significant difference between NAT group (82.0% and 87.1%) and AT group (86.0% and 89.9%) (P> 0.05). In the subgroup of patients with noncurative ESD (n= 52), the 5-year OS and CSS rates were significantly higher in surgery group (90.2% and 95.2%) than that in NAT group (50.1% and 59.5%) and chemoradiotherapy group (51.4% and 60.0%) (P< 0.05). Conclusions: ESD with no additional therapy could achieve favorable long-term outcomes in treating T1a-MM/T1b-SM1 ESCCs. For patients with noncurative ESD, surgery ranks a prime recommendation over CRT.

Supplemental Digital Content is available in the text.

Purpose: The purpose of our study is to propose a preoperative computer-aided diagnosis system based on a radiomics method to differentiate gastrointestinal stromal tumors (GISTs) of the higher-risk group (HRG) from those of the lower-risk group (LRG) on endoscopic ultrasound (EUS) images. Materials and method: Gastro-EUS (G-EUS) images of four different risk level GISTs were collected from 19 hospitals. The datasheet included 168 case HRG GISTs and 747 case LRG GISTs. A radiomics method with image segmentation, feature extraction, feature selection and classification was developed. Here 439 radiomics features were firstly extracted, and then, the least absolute shrinkage selection operator (lasso) model with a tenfold cross-validation and 31 bootstraps was used to reduce the dimension of feature sets. Finally, random forest was applied to establish the classification model. Results: The proposed model differentiated 32 case HRG GISTs from 149 case LRG GISTs. Result for the testing set achieved the area under the receiver operating characteristic curve of 0.839, the accuracy of 0.823, the sensitivity of 0.813 and the specificity of 0.826. Conclusion: The model could increase preoperative diagnostic accuracy and provide a valuable reference for the doctors.

Methods for the stereocontrolled construction of 1,1′‐disaccharides, 2‐deoxy glycosides, and orthoesters are reported. Specifically, a tin‐acetal moiety was utilized to fix the anomeric stereochemistry of a carbohydrate acceptor leading to an efficient and stereoselective synthesis of 1,1′‐disaccharides, while a newly discovered 1,2‐phenylseleno migration reaction in carbohydrates opened entries to 2‐deoxy glycosides and orthoesters. Thus, reaction of 2‐hydroxy phenylselenoglycosides with DAST led to 2‐phenylselenoglycosyl fluorides which reacted with carbohydrate acceptors to afford, stereoselectively, 2‐phenylselenoglycosides. The latter compounds could be reductively deselenated to 2‐deoxy glycosides or oxidatively converted to orthoesters via the corresponding ketene acetals.

New Wadsworth-Emmons reagents, bis(2,2,2-trifluoroethyl)-(2-oxopropyl)phosphonate 6and bis(2,2,2-trifluoroethyl)-(1-methyl-2-oxopropyl)-phosphonate 7were prepared and their reactions with aldehydes yielded disubstituted and trisubstituted (Z)-α,β-unsaturated ketones.

Tertiary allylic sulfones which bear a secondary aminopropyl moiety undergo smooth palladium [0]-mediated spirocyclization. The reaction proceeds via a π-allyl intermediate and the resultant azabicyclic product is formed with net retention of sulfone stereochemistry. The use of tetramethylguanidine as companion base is required for high yielding reactions.

Using phosphazene base, P 4-t-Bu or basic phase-transfer catalyst conditions, vinyl sulfones were regiospecifically alkylated at the α-position. No β-elimination products were observed in a system capable of undergoing anion-promoted β-elimination. The scope and limitations of these reactions were studied.

Observations made during the synthesis of the anticancer agent homoharringtonine 37 have resulted in the development of several new synthetic methods based upon the alkylation and conjugate-addition chemistry of γ-methoxy allylsulfonyl anions. Enones, dienyl ketones, and trienyl ketones are readily constructed. Sultinium ion intermediates facilitate the sulfone to olefin transformation.

Human serum albumin (HSA) acts as a carrier for testosterone, other sex hormones, fatty acids, and drugs. However, the dynamics of testosterone’s binding to HSA and the structure of its binding sites remain incompletely understood. Here, we characterize the dynamics of testosterone’s binding to HSA and the stoichiometry and structural location of the binding sites using 2-dimensional nuclear magnetic resonance (2D NMR), fluorescence spectroscopy, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid dipotassium salt partitioning, and equilibrium dialysis, complemented by molecular modeling.2D NMR studies showed that testosterone competitively displaced 18-[13C]-oleic acid from at least 3 known fatty acid binding sites on HSA that also bind many drugs. Binding isotherms of testosterone’s binding to HSA generated using fluorescence spectroscopy and equilibrium dialysis were nonlinear and the apparent dissociation constant varied with different concentrations of testosterone and HSA. The binding isotherms neither conformed to a linear binding model with 1:1 stoichiometry nor to 2 independent binding sites; the binding isotherms were most consistent with 2 or more allosterically coupled binding sites. Molecular dynamics studies revealed that testosterone’s binding to fatty acid binding site 3 on HSA was associated with conformational changes at site 6, indicating that residues in in these 2 distinct binding sites are allosterically coupled.There are multiple, allosterically coupled binding sites for testosterone on HSA. Testosterone shares these binding sites on HSA with free fatty acids, which could displace testosterone from HSA under various physiological states or disease conditions, affecting its bioavailability.

Treatment of vinyl sulfones with 0.1–0.2 eq of Phosphazene base, P 2-Et in THF at 25°C affords the corresponding allyl sulfones in high yield. P 2-Et has shown clear superiority to both DBU and KO-t-Bu in these reactions.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.