ABSTRACT
Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that contribute to tumor initiation and therapeutic resistance. The aim of this research was to estimate and compare the effectiveness ratio (α/ß) of stem-like cells and differentiated glioma cells derived from the U87MG glioblastoma cell line. Cell survival experiments were obtained in a dose range of 0-20â¯Gy (13.52 ± 0.09â¯Gy/h) as a hyperfractionationated accelerated radiotherapy scheme. Biochemical characterization of the post-irradiated cells was performed by flow cytometry analysis and the percentage of stem-like cells that resisted irradiation was determined by the CD133 expression. Results showed that U87MG stem-like cells are highly proliferative and more radioresistant than the U87MG adherent group (with a lesser stem-like character), this in association with the calculated α/ß ratio of 17 and 14.1, respectively.
Subject(s)
Brain Neoplasms/radiotherapy , Glioblastoma/radiotherapy , AC133 Antigen/metabolism , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cell Differentiation , Cell Line, Tumor , Cell Proliferation/radiation effects , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Glioblastoma/immunology , Glioblastoma/pathology , Humans , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/radiation effects , Radiation Tolerance , Spheroids, Cellular/pathology , Spheroids, Cellular/radiation effects , Tumor Microenvironment/radiation effectsABSTRACT
BACKGROUND: Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics. METHODS: This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported. RESULTS: Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up. CONCLUSIONS: The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics.
Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Colistin/adverse effects , Colistin/therapeutic use , Cross Infection/drug therapy , Gram-Negative Bacterial Infections/drug therapy , Adult , Aged , Cohort Studies , Cross Infection/mortality , Drug Resistance, Multiple, Bacterial , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/mortality , Humans , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Hypertension and tachycardia are common during fiber-optic bronchoscopy (FOB), and this may lead to cardiac ischemia. The prophylactic addition of a beta-adrenergic anatagonist might mask this response and prevent the deleterious cardiovascular effects of FOB. METHODS: We performed a randomized double-blind placebo-controlled trial of labetalol 10mg iv given with midazolam-alfentanil sedation. We monitored heart rate (HR) and systolic/diastolic blood pressure (SBP/DBP) throughout the bronchoscopy and calculated the rate-pressure product (RPP=(HRxSBP)/100). One-hundred twenty patients were enrolled. RESULTS: In the placebo group, there was no rise in HR, SBP, DBP or RPP, and there was no difference between the placebo and labetalol groups. Adverse events during bronchoscopy were similar in both groups. In a subgroup of patients undergoing interventional bronchoscopy, there was a trend towards lower SBP (p=0.06). CONCLUSIONS: Patients undergoing FOB under adequate midazolam-alfentanil sedation do not develop excessive sympathetic drive that may lead to cardiac stress. The addition of labetalol did not confer additional benefit or risk to the patients. (ClinicalTrials.gov number, NCT00394537).
