Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction.

BACKGROUND: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers. METHODS: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways. RESULTS: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%). CONCLUSION: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.

Biomaterial effects in articular cartilage tissue engineering using polyglycolic acid, a novel marine origin biomaterial, IGF-I, and TGF-beta 1.

Bovine articular chondrocytes were seeded on either polyglycolic acid (PGA) non-woven mesh scaffolds or a biomatrix from the species Porites lutea (POR). These constructs were cultured for 6 weeks in the presence of insulin-like growth factor (IGF)-I (10 ng/ml or 100 ng/ml) or transforming growth factor (TGF)-beta 1 (5 ng/ml or 30 ng/ml) to determine the in-vitro articular cartilage regeneration capacity of each. Histology, deoxyribonucleic acid content, collagen I and II (immunohistochemistry and enzyme-linked immunosorbent assay), and glycosaminoglycan (GAG) contents were measured at 0 weeks, 2 weeks, and 6 weeks to assess the characteristics of chondrogenesis. Both scaffolds supported the maintenance of the chondrocytic phenotype, as evidenced by the predominance of collagen II and the presence of rounded chondrocytes embedded in lacunae. Regardless of growth factor treatment, cells cultured on PGA scaffolds produced more collagen type II than those cultured on POR. Conversely, by 6 weeks, cells cultured on POR scaffolds produced more GAG than those cultured on PGA scaffolds, again regardless of the growth factor used. Across the two groups, 100 ng/ml of IGF-I had the greatest overall effect in GAG content. This work indicates that PGA and the POR scaffolds are both effective growth matrices for articular cartilage, with each scaffold exhibiting different yet desirable profiles of articular cartilage growth.

A unique perspective on advanced practice nursing.

This article presents a working definition of the advanced practice registered nurse (APRN). The types of nurses that could be included in this definition and the benefits of broadening the category are discussed, as well as possible reasons for the less inclusive, previous definition of this category. Strategies are proposed for resolving concerns about broadening the category.

Effects of intra-PVN injections of d- and l-norephedrine on feeding in rats.

Phenylpropanolamine (PPA) is thought to inhibit feeding by activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). Systemic injections of the PPA component enantiomers, d- and l-norephedrine (NEP), result in differential suppression of feeding (l-NEP more potent than d-NEP). Whether the norephedrine racemates induce differential anorexia subsequent to injection into the PVN is unknown. In the present study, adult male rats received intra-PVN injections of the d- and l-norephedrine enantiomers (0, 80, 160, and 240 nmol). Significantly greater anorexia was obtained for l-NEP relative to d-NEP. These results document a stereospecific effect of the norephedrine enantiomers within the PVN in inhibiting food intake and suggest that the interaction of these enantiomers with PVN alpha 1-adrenoceptors may mediate the similar difference in potency noted for systemic injections of d- and l-norephedrine.

Microinjection of the alpha 1-agonist methoxamine into the paraventricular hypothalamus induces anorexia in rats.

Adrenergic receptors within the paraventricular hypothalamus (PVN) play a prominent role in the control of food intake: stimulation of alpha 2-adrenoceptors induces food intake whereas stimulation of alpha 1-adrenoceptors suppresses food intake. This study further examines the role of PVN alpha 1-adrenoceptors by examining the effects on food and water intake of the alpha 1-adrenergic agonist methoxamine (100, 200, 400 nMol) microinjected into the rat paraventricular hypothalamus. Methoxamine suppressed food intake but not water intake. Doses of 100, 200, and 400 nMol methoxamine suppressed food intake by 47%, 64%, and 96%, respectively. These results further confirm the hypothesis that administration of alpha 1-agonists into the PVN acts to significantly suppress food intake; an action that is in opposition to the facilitory effects of alpha 2-adrenergic agonists on food intake.