Low Expression of Bax Predicts Poor Prognosis in Resected Non-small Cell Lung Cancer Patients with Non-squamous Histology†

doi:10.1093/jjco/hyn089 Objective: The present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection. Methods: We investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) i

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 μg ml−1. This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated

Reliability of doming and toe flexion testing to quantify foot muscle strength

Abstract Background Quantifying the strength of the intrinsic foot muscles has been a challenge for clinicians and researchers. The reliable measurement of this strength is important in order to assess weakness, which may contribute to a variety of functional issues in the foot and lower leg, including plantar fasciitis and hallux valgus. This study reports 3 novel methods for measuring foot strength – doming (previously unmeasured), hallux flexion, and flexion of the lesser toes. Methods Twenty-one healthy volunteers performed the strength tests during two testing sessions which occurred one to five days apart. Each participant performed each series of strength tests (doming, hallux flexion, and lesser toe flexion) four times during the first testing session (twice with each of two raters) and two times during the second testing session (once with each rater). Intra-class correlation coefficients were calculated to test for reliability for the following comparisons: between raters during the same testing session on the same day (inter-rater, intra-day, intra-session), between raters on different days (inter-rater, inter-day, inter-session), between days for the same rater (intra-rater, inter-day, inter-session), and between sessions on the same day by the same rater (intra-rater, intra-day, inter-session). Results ICCs showed good to excellent reliability for all tests between days, raters, and sessions. Average doming strength was 99.96 ± 47.04 N. Average hallux flexion strength was 65.66 ± 24.5 N. Average lateral toe flexion was 50.96 ± 22.54 N. Conclusions These simple tests using relatively low cost equipment can be used for research or clinical purposes. If repeated testing will be conducted on the same participant, it is suggested that the same researcher or clinician perform the testing each time for optimal reliability

Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours

Contains fulltext : 89775.pdf (publisher's version ) (Closed access)AIM: Cediranib is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR) signalling. Preclinical and clinical data suggest that inhibition of the VEGFR and epidermal growth factor receptor (EGFR) pathways may be synergistic. Combination treatment with cediranib and gefitinib, an EGFR signalling inhibitor, was evaluated in patients with advanced solid tumours. PATIENTS AND METHODS: Ninety patients received treatment in this four-part, open-label study (NCT00502060). The patients received once-daily oral doses of cediranib (20-45mg) and gefitinib 250mg (part A1; n=16) or 500mg (part B1; n=44). A cohort expansion phase investigated the potential pharmacokinetic interaction of cediranib 30mg with gefitinib 250mg (part A2; n=15) or 500mg (part B2; n=15). The primary objective was to assess the safety and tolerability of cediranib with gefitinib. Secondary assessments included pharmacokinetics, efficacy and pharmacodynamics. RESULTS: Combination treatment was generally well tolerated; the protocol-defined maximum-tolerated dose of cediranib was 30mg/day with gefitinib 250mg/day (part A1) and cediranib 45mg/day was the maximum dose investigated with gefitinib 500mg/day (part B1). The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) and fatigue (60 [67%]). Cediranib pharmacokinetic parameters were not substantially different when given alone or in combination with gefitinib. Gefitinib pharmacokinetic parameters were similar to those seen previously with gefitinib monotherapy. Efficacy results included eight (9%) confirmed partial responses (6 renal; 1 lung; 1 osteosarcoma) and 38 (42%) patients with stable disease. Pharmacodynamic assessments demonstrated changes in levels of VEGF and soluble VEGFR-2 following treatment. CONCLUSIONS: Combination treatment was generally well tolerated and showed encouraging antitumour activity in patients with advanced solid tumours. These results merit further exploration.1 maart 201