Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients

BACKGROUND: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. PATIENTS AND METHODS: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P=0.03), lymph nodal involvement (P=0.002), and PML expression (P=0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P=0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P=0.003) and the only statically significant prognostic factor for OS (P=0.009). CONCLUSIONS: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients

PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients

PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. EXPERIMENTAL DESIGN: 74 metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. RESULTS: PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P\u2009=\u20090.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P\u2009<\u20090.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months respectively, P\u2009=\u20090.003). The impact of PML down-regulation on TTP and OS was statistically significant also in a multivariate model. CONCLUSIONS: This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine-based first line therapy

Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27–79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m−2, followed by weekly infusions of 250 mg m−2. Irinotecan was administered weekly at the dose of 90 mg m−2. All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7–39.6%); 38.2% (95 CI: 18.6–39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4–70.6%). The median time to progression was 4.7 months (95% CI: 2.5–7.1 months) and the median survival time was 9.8 months (95% CI: 3.9–10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3–4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens

A Matter of Time. Digital-Financial Consumers' Vulnerability in the Retail Payments Market

This Article aims to conceptualize the figure of the digital-financial payment consumer, which combines two separate - and ex se relevant - sources of vulnerability: digital vulnerability and financial vulnerability

Reliability of short-term follow-up for assessing bioprosthetic heart valve performancE

[No abstract available

Assessing and promoting psychological wellbeing among healthcare employees

This thesis presents two studies conducted over several years in the field of psychological wellbeing within the National Health System in Malta. The thesis is entitled' Assessing and promoting psychological wellbeing among healthcare employees'. The first study in this project aimed at assessing the psychological wellbeing of all the healthcare employees working within the NHS in Malta while the second study aimed at promoting psychological wellbeing with a small group of physiotherapists working within an NHS Outpatients Clinic in Malta. A further aim of this thesis was to learn more about the possibility of emancipatory change through empowerment, drawing from a Participatory Action Research (PAR) design. Incorporating the two studies exemplified the values in Counselling Psychology, in taking a detailed assessment of the context and the lived experience of the people being studied and then helping in bringing about a change in the situation for the better through co-participation and empowerment of the research participants. The experience of conducting this research has 'enabled the researcher to further develop the value of pragmatism as a way of appreciating the use of both quantitative and qualitative research methodologies. Pragmatism also allowed the researcher to embrace methods that were appropriate and is thus resonant with the value system of the researcher to be driven by the aims of the research. Empowerment was a recurring theme within the two studies. Together, the two studies can be seen as a research endeavour with three aims: 1. To assess and explore the psychological wellbeing of the employees working within the Maltese National Health System. 2. To translate and examine the factor structure of the Maltese version of the GHQ-28. 3. An attempt to enhance the current situation in a way that could potentially lead to further positive changes in the future through the empowerment of the participants themselves and the insights they gain during this process. Study 1 assessed the wellbeing of employees from different occupational groups who filled in the General Health Questionnaire -28 (N=1 13 1). Furthermore, in this study five focus groups were conducted with two directors, five physiotherapists, five nurses, nine nursing officers and four health inspectors. The use of a mixed methods research design provided more depth to the analysis as the qualitative data complemented the quantitative data. This provided the basis for Study 2 in which a Participatory Action Research design was utilized with a small group of five physiotherapists. The outcome of this research benefited other employees within the organization, and can be further applied with other occupational groups. The relative lack of empirical research about the psychological wellbeing of health care employees in Malta to date highlights the significance of this thesis. The findings from this thesis will contribute to the understanding of the significance of utilizing PAR as an intervention designed to promote psychological wellbeing within organizations. Furthermore, the experience of the participants in working within this particular organization may be generalized to other related settings. This thesis can be an inspiration to those who aspire to empower others within the organization.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A mediator-based approach for integrating heterogeneous multimedia sources

In many applications, the information required by the user cannot be found in just one source, but has to be retrieved from many varying sources. This is true not only of formatted data in database management systems, but also of textual documents and multimedia data, such as images and videos. We propose a mediator system that provides the end-user with a single query interface to an integrated view of multiple heterogeneous data sources. We exploit the capabilities of the MOMIS integration system and the MILOS multimedia data management system. Each multimedia source is managed by an instance of MILOS, in which a collection of multimedia records is made accessible by means of similarity searches employing the query-by-example paradigm. MOMIS provides an integrated virtual view of the underlying multimedia sources, thus offering unified multimedia access services. Two features are that MILOS is flexible—it is not tied to any particular similarity function—and the MOMIS’s mediator query processor only exploits the ranks of the local answers