From conventional chemotherapy to targeted therapy: use of monoclonal antibodies (moAbs) in gastrointestinal (GI) tumors.

In recent years, significant progress has been made in the diagnosis and treatment of gastrointestinal cancers. Researches and clinicians however are still faced with challenges, not the least is the detection and management of tumors with varied gene mutation status. Clarification of the molecular pathology of gastrointestinal cancers may improve treatment options as well as quality of life and the long-term survival of this patient class. Therefore, molecular-targeted therapies have emerged as clinically useful drugs for gastrointestinal cancers cure, and predictive biomarkers have been heralded as the way to develop the right drug for the right patient. Moving from such appealing molecular background, we wrote an overview of the main targeted therapies, with particular interest to monoclonal antibodies that have already been approved in clinical practice or are being tested in gastrointestinal cancers treatment.

Variations of neck structures after supracricoid partial laryngectomy: a multislice computed tomography evaluation.

BACKGROUND: Surgery of laryngeal cancer used to profoundly alter the anatomy of the cervical region. Accurate anatomo-embryologic studies and repeated surgical trials allowed recognition of the cricoarytenoid complex as the smallest anatomofunctional unit able to maintain all the laryngeal functions. OBJECTIVES: The aim of this study was to determine whether significant variations of neck anatomical parameters exist after partial laryngectomy, and to analyze whether some of these parameters are associated with a positive functional outcome. METHODS: Out of 48 patients treated with a surgical technique according to Mayer-Piquet (cricohyoidoepiglottopexy, CHEP) over a 6-year period, 18 patients were enrolled in the study. Patients were all males with a mean age of 60 years. Cervical structures and their relationships were measured by computed tomography, and the measurements before and after surgery were compared. RESULTS: Our data showed that hyoid bone is modified, both in morphology and position during CHEP. More specifically the relation of the hyoid bone to other neck structures (identified by the alpha-angle) is modified. The neolarynx and trachea undergo a caudocranial shift. All diameters of the cricoid cartilage remain unchanged after surgery. The position of the epiglottis after CHEP, in particular its relation with the arytenoid cartilage, is closely related to swallowing function outcome and recovery time. CONCLUSIONS: Our study showed that these structures, and more specifically the relations among them, undergo significant variations after CHEP. Our results identify some parameters, i.e. the alpha-angle, width of the hyoid bone and position of the epiglottis, that may predispose to a positive functional outcome after surgery.

Carbohydrate natural products as a scaffolding for the preparation of potential neuraminidase inhibitors.

Compound 10b, 6-acetamido-6,8-dideoxy-D-erythro-beta-D- galacto-octopyranosyl-1-oxyacetic acid sodium salt, was synthesised by hydrazinolysis of Lincomycin, acetylation of methylthiolincosaminide (MTL) 9a, and by subsequent glycosylation of acetate 9b with methyl glycolate under mild conditions (NIS/TfOH). The methyl ester 10a was hydrolysed by treatment with Amberlite Ira-4OO (OH-) resin and aqueous sodium hydroxide, followed by neutralisation with Dowex-50 W x 8 (H+) resin and lyophilisation to give 10b. This carboxylate may represent the first derivative in a novel series of sialidase inhibitors utilising carbohydrate natural products. The phosphonate 11c, prepared under the same experimental conditions with dibenzyl(hydroxymethyl)phosphonate as acceptor, also displays an inhibitory activity towards Clostridium perfringens sialidase (Ki in mM range as with Neu5Ac).