Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse

Psychometric properties and factorial analysis of invariance of the Satisfaction with Life Scale (SWLS) in cancer patients

Purpose The purpose of this study was to assess the psychometric properties of the Satisfaction with Life Scale (SWLS), evaluate the measurement invariance with respect to sex, age, and tumor location, as well as analyze associations between life satisfaction and socio-demographic and clinical variables among individuals with resected, non-advanced cancer. Methods A confirmatory factor analysis was conducted to explore the dimensionality of the scale and test invariance across gender, age, and tumor localization in a prospective, multicenter cohort of 713 patients who completed the following scales: SWLS, Health-related Quality of Life Questionnaire (EORTC QLQ-C30), Brief Symptom Inventory (BSI-18). Results Confirmatory factor analysis results indicated that the SWLS is an essentially unidimensional instrument, providing accurate scores: both McDonald's omega and Cronbach's alpha estimates were 0.91. Strong measurement invariance was found to hold across gender, age, and tumor localization. Low satisfaction with life was associated with psychological symptoms (anxiety, depression, and somatization), and decreased quality of life (malfunction, symptoms, poor global QoL). Conclusion The SWLS is a reliable, valid satisfaction with life measurement among people with cancer and should be recommended as an indicator of psychological adjustment in oncological patients

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma (OPSCC):Hypoxia biomarkers from 64Cu-ATSM PET/CT imaging

Background: Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT. Methods: 64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived. Results: Hypoxic volume was significantly associated with a reported hypoxia gene signature (rho=0.57, P=0.045), but SUVmax and TMR were not. Immunohistochemical staining with the hypoxia marker carbonic anhydrase 9 (CA9) was associated with a gene expression hypoxia response (rho=0.63, P=0.01). Sixteen genes were positively and five genes negatively associated with hypoxic volume (adjusted P<0.1; eight genes had adjusted P<0.05; HVS). This signature was associated with inferior 3-year progression-free survival (HR=1.5 (1.0–2.2), P=0.047) in an independent patient cohort. Conclusions: 64Cu-ATSM-defined hypoxic volume was associated with underlying hypoxia gene expression response. A 21-gene signature derived from hypoxic volume from patients with OPSCCs in our study may be linked to progression-free survival

Quality in Emergency Departments: a study on 3,285,440 admissions

INTRODUCTION: A multi-centre study has been conducted, during 2005, by means of a questionnaire posted on the Italian Society of Emergency Medicine (SIMEU) web page. Our intention was to carry out an organisational and functional analysis of Italian Emergency Departments (ED) in order to pick out some macro-indicators of the activities performed. Participation was good, in that 69 ED (3,285,440 admissions to emergency services) responded to the questionnaire. METHODS: The study was based on 18 questions: 3 regarding the personnel of the ED, 2 regarding organisational and functional aspects, 5 on the activity of the ED, 7 on triage and 1 on the assessment of the quality perceived by the users of the ED. RESULTS AND CONCLUSION: The replies revealed that 91.30% of the ED were equipped with data-processing software, which, in 96.83% of cases, tracked the entire itinerary of the patient. About 48,000 patients/year used the ED: 76.72% were discharged and 18.31% were hospitalised. Observation Units were active in 81.16% of the ED examined. Triage programmes were in place in 92.75% of ED: in 75.81% of these, triage was performed throughout the entire itinerary of the patient; in 16.13% it was performed only symptom-based, and in 8.06% only on-call. Of the patients arriving at the ED, 24.19% were assigned a non-urgent triage code, 60.01% a urgent code, 14.30% a emergent code and 1.49% a life-threatening code. Waiting times were: 52.39 min for non-urgent patients, 40.26 min for urgent, 12.08 for emergent, and 1.19 for life-threatening patients

Chemical Linkage to Injected Tissues Is a Distinctive Property of Oxidized Avidin

We recently reported that the oxidized avidin, named AvidinOX®, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation

Development of a Novel Anti-CD19 Chimeric Antigen Receptor : A Paradigm for an Affordable CAR T Cell Production at Academic Institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients