Airports at Risk: The Impact of Information Sources on Security Decisions

Security decisions in high risk organizations such as airports involve obtaining ongoing and frequent information about potential threats. Utilizing questionnaire survey data from a sample of airport employees in European Airports across the continent, we analyzed how both formal and informal sources of security information affect employee's decisions to comply with the security rules and directives. This led us to trace information network flows to assess its impact on the degree employees making security decisions comply or deviate with the prescribed security rules. The results of the multivariate analysis showed that security information obtained through formal and informal networks differentially determine if employee will comply or not with the rules. Information sources emanating from the informal network tends to encourage employees to be more flexible in their security decisions while formal sources lead to be more rigid with complying with rules and protocols. These results suggest that alongside the formal administrative structure of airports, there exists a diverse and pervasiveness set of informal communications networks that are a potent factor in determining airport security levels

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m−2) and cyclophosphamide (2 g m−2) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m−2 and thiotepa 200 mg m−2. At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m−2 cyclophosphamide and 400 mg m−2 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity

Neurotensin Receptor 1 Is Expressed in Gastrointestinal Stromal Tumors but Not in Interstitial Cells of Cajal

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present in the majority of GIST, leading to ligand-independent activation of the intracellular signal transduction pathways. We previously investigated the gene expression profile in the murine KitK641E GIST model and identified Ntsr1 mRNA, encoding the Neurotensin receptor 1, amongst the upregulated genes. Here we characterized Ntsr1 mRNA and protein expression in the murine KitK641E GIST model and in tissue microarrays of human GIST. Ntsr1 mRNA upregulation in KitK641E animals was confirmed by quantitative PCR. Ntsr1 immunoreactivity was not detected in the Kit positive ICC of WT mice, but was present in the Kit positive hyperplasia of KitK641E mice. In the normal human gut, NTSR1 immunoreactivity was detected in myenteric neurons but not in KIT positive ICC. Two independent tissue microarrays, including a total of 97 GIST, revealed NTSR1 immunoreactivity in all specimens, including the KIT negative GIST with PDGFRA mutation. NTSR1 immunoreactivity exhibited nuclear, cytoplasmic or mixed patterns, which might relate to variable levels of NTSR1 activation. As studies using radio-labeled NTSR1 ligand analogues for whole body tumor imaging and for targeted therapeutic interventions have already been reported, this study opens new perspectives for similar approaches in GIST

Targeting Signal Transduction Pathways in Metastatic Breast Cancer: A Comprehensive Review

This review summarizes some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for the treatment of metastatic breast cancer patients

CD40L induces multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways

BACKGROUND: CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown. METHODS: The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated. RESULTS: Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89%) the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways. CONCLUSION: These results indicate that CD40L expressed on adjacent non tumoral cells induces multidrug resistance to cytotoxic agents and ceramides in both breast carcinoma and non Hodgkin's lymphoma cell lines, albeit through a caspase independent and dependent pathway respectively

High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Metastatic Rhabdomyosarcoma—A Systematic Review

INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials