Treatment decisions, clinical outcomes, and pharmacoeconomics in the treatment of patients with EGFR mutated stage III/IV NSCLC in Germany: an observational study.

Background: We evaluated treatment decisions and outcomes in a cohort of predominately Caucasian patients with EGFR mutation-positive (EGFR Mut+) non-small-cell lung cancer (NSCLC).

Methods: REASON (NCT00997230) was a non-interventional study in German patients with stage IIIB/IV NSCLC. Secondary endpoints for EGFR Mut + NSCLC included progression-free survival (PFS), overall survival (OS), adverse event (AE) management, and pharmacoeconomic outcomes.

Generation of a conditionally transformed murine embryonic fibroblast cell line using doxycycline-dependent IGF-1R overexpression.

The insulin-like growth factor I receptor (IGF1-R) system has long been implicated in cancer and is a promising target for tumor therapy. Besides in vitro screening assays, the discovery of specific inhibitors against IGF-1R requires relevant cellular models, ideally applicable to both in vitro and in vivo studies. With this aim in mind, the authors generated an inducible cell line using the tetracycline-responsive gene expression system to mimic the effects of therapeutic inhibition of the IGF-1R both in vitro and on established tumors in vivo.

The Crataegus extract WS 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-beta.

Objective: Effective systemic drugs against restenosis upon percutaneous transluminal coronary angioplasty (PTCA) are largely lacking. Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Hawthorn (Crataegus spp.

Plasma sE-selectin in premature infants: a possible surrogate marker of retinopathy of prematurity.

PURPOSE. To prospectively study plasma levels of soluble E-selectin (sE-selectin) in premature infants and to identify their relationship to retinopathy of prematurity (ROP) on the background of known clinical risk factors. METHODS.

Antitumor and antiangiogenic activity of cediranib in a preclinical model of renal cell carcinoma.

Cediranib is a highly potent and selective vascular endothelial growth factor (VEGF) signaling inhibitor with activity against all three VEGF receptors (VEGFRs) that inhibits angiogenesis and growth of human tumor xenografts in vivo. The present study evaluated the antitumor and antiangiogenic activity of cediranib in the clinically relevant, murine renal cell carcinoma (RENCA) model and its biological response using VEGF and sVEGFR-2 as biomarkers. Mice were treated with cediranib (5 mg/kg/d p.

Anti-tumor effects of AMT in the renal cell carcinoma model.

Auron-Misheil-Therapy (AMT) is a defined but unique combination of approved pharmaceuticals. It consists of insulin, chlorpheniramine and an aqueous camomile extract, and it has been successfully applied clinically in late-stage cancer patients. The purpose of this study was to elucidate the anti-tumor efficacy of AMT in a validated murine renal cell carcinoma animal model (RENCA).

Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization.

Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.

An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia.

VEGFR and c-Kit signaling pathways may contribute to the pathophysiology of acute myeloid leukemia (AML). Thirty-five patients with AML received cediranib (RECENTIN), an oral, highly potent VEGF signaling inhibitor with c-Kit activity, at doses of < or =30 mg/day. The most common adverse events were diarrhea, hypertension and fatigue.

Bioactive metabolites from the endophytic fungus Stemphylium globuliferum isolated from Mentha pulegium.

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10).

Antitumoral and antiangiogenic efficacy of bisphosphonates in vitro and in a murine RENCA model.

Background: Bisphosphonates have shown direct antitumoral activity in vitro, in vivo and even in clinical studies, but the exact mechanism for this has not yet been elucidated. In this study the antiangiogenic potency of zoledronic acid and clodronate were evaluated.

Materials And Methods: The effects of zoledronic acid and clodronate on the proliferation of endothelial cells and different tumor cells, and on the activity of protein kinases were investigated.

Cytotoxic metabolites from the fungal endophyte Alternaria sp. and their subsequent detection in its host plant Polygonum senegalense.

From the Egyptian medicinal plant Polygonum senegalense the fungal endophyte Alternaria sp. was isolated. Extracts of the fungus grown either in liquid culture or on solid rice media exhibited cytotoxic activity when tested in vitro against L5178Y cells.

Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors.

Purpose: AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling. This phase I study was designed to evaluate the safety and tolerability of increasing doses of AZD2171, with additional assessments of pharmacokinetics, pharmacodynamics, and efficacy.

Patients And Methods: In part A, 36 patients with solid tumors and liver metastases refractory to standard therapies received once-daily oral AZD2171 (0.

Plasma vascular endothelial growth factor and serum soluble angiopoietin receptor sTIE-2 in patients with dural arteriovenous fistulas: a pilot study.

Our aim was to correlate concentrations of circulating vascular endothelial growth factor (VEGF) and serum soluble angiopoietin receptor (sTIE-2) before and after endovascular treatment with the grading in human dural arteriovenous fistulas (DAVFs). In ten patients with DAVFs undergoing diagnostic cerebral angiography and endovascular intervention, pre-treatment and post-treatment levels of plasma VEGF and serum TIE-2 were examined in a prospective study design. A total of 32 plasma samples and 19 serum samples was collected from the cubital vein, the arterial sheath before and--if applicable--after intervention.

ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3.

Our recent studies have shown that extracellular-regulated protein kinase (ERK) promotes cell death in cerebellar granule neurons (CGN) cultured in low potassium. Here we report that the "death" phenotypes of CGN after potassium withdrawal are heterogeneous, allowing the distinction between plasma membrane (PM)-, DNA-, and PM/DNA-damaged populations. These damaged neurons display nuclear condensation that precedes PM or DNA damage.

Neuronal MEK is important for normal fear conditioning in mice.

The extracellular signal-regulated kinase (ERK) cascade has received much attention for its possible role in neuronal synaptic plasticity. Although ERK activation has been linked to learning behaviors and activity-dependent neuronal function, much of the acquired data has relied upon pharmacological agents that suppress ERK function in both neurons and nonneuronal cells. To determine the function of neuronal ERK activity in learning, a new line of transgenic mice was generated wherein dominant-negative MEK1, the upstream obligate activator of ERK1/2, was expressed by using a neuronal-specific and pan-neuronal Talpha1 alpha-tubulin promoter element.