Aldo-keto reductases tighten coenzyme binding by forming a hydrogen bond across the pyrophosphate group of NAD(P)(H). Mutation of the hydrogen bonding anchor Lys24 in Candida tenuis xylose reductase prevents fastening of the "safety belt" around NAD(H). The loosened NAD(H) binding leads to increased turnover numbers (k(cat)) for reductions of bulky-bulky ketones at constant substrate and coenzy...

OPINION STATEMENT Stage III, locally advanced NSCLC, represents an incredibly heterogeneous group of patients. Optimal therapy for this group is controversial and the role of surgery is not clearly defined. There have been several randomized trials over the past three decades that have helped to guide our decision-making. In patients with T3N1 tumors, surgery is the primary treatment and there ...

Gallbladder cancer has a reputation for being aggressive and incurable. Single institution series, however, have defined successful management strategies in which the extent of resection is based on the stage of the tumor at presentation. Careful ultrasound screening for abnormalities in the gallbladder wall, and CA19-9 serum determination prior to routine cholecystectomy may heighten awareness...

Soft tissue sarcomas are a heterogenous group of rare tumors arising from embryonic mesoderm. Almost 15% of such sarcomas arise in the retroperitoneum. Rhabdomyosarcoma and fibrosarcoma are the two most common histologic variants in the retroperitoneum. The prognosis for patients with retroperitoneal sarcomas (RPS) is relatively poor characterized by late locoregional recurrence as principal ca...

PURPOSE We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in p...

The use of the commercially available, bifunctional phosphine 1,3,5-triaza-7-phosphaadamantane (abbreviated as PN3) in conjunction with a series of Zn(salphen) complexes leads to sterically encumbered phosphine ligands as a result of (reversible) coordinative Zn-N interactions. The solid state and solution phase behaviour of these supramolecular ligand systems have been investigated in detail a...

A series of bulky monodentate phosphoramidite ligands were synthesized from chiral 3,3'-diaryl substituted BINOL derivatives and achiral or dendritic amines in good yields. Asymmetric hydrosilylation of styrenes with trichlorosilane in the presence of palladium complexes of these bulky ligands gave chiral silanes in high yields with excellent activity and productivity. Oxidation of these chiral...

We determined the crystal structure of an inactive Ser70Gly mutant of CTX-M-9 in complex with the bulky penicillin piperacillin at precovalent and posthydrolytic stages in the catalytic process. The structures obtained at high resolution were compared with the corresponding structures for the small penicillin benzylpenicillin and the bulky cephalosporin cefotaxime. The findings highlight the ke...

Cycloxygenase-2 (COX-2) is an attractive target for molecular imaging because it is an inducible enzyme that is expressed in response to inflammatory and proliferative stimuli. Recently, we reported that conjugation of indomethacin with carboxy-X-rhodamine dyes results in the formation of effective, targeted, optical imaging agents able to detect COX-2 in inflammatory tissues and premalignant a...