Characterisation, expression and ontogeny of interleukin-6 and its receptors in zebrafish (Danio rerio)

10 páginas, 8 figuras, 2 tablasInterleukin-6 (IL-6) is one of the most pleiotropic cytokines due to its importance in both innate and adaptive immune responses and other physiological processes. In this study, we identified the zebrafish (Danio rerio) IL-6 homologue by investigating the synteny between the human (Homo sapiens), the fugu (Takifugu rubripes) and the zebrafish genome. Although zebrafish IL-6 showed a low sequence homology with other IL-6 sequences in other species, it presented a high structural similarity to human IL-6. We also analysed IL-6 expression in several different tissues, along with analysis of the expression of the genes that form the IL-6 receptor complex, IL-6R and gp130. After treatment with bacterial or viral stimuli, zebrafish IL-6 expression was modulated in a manner similar to that of other proinflammatory molecules, such as IL-1β and TNF-α. The expression of IL-6, IL-6R and gp130 was also studied during the ontogeny of zebrafish larvae using quantitative PCR and in situ hybridisation. Our results indicated that the transcripts were detected very early, increased during the first week of life and were predominantly expressed in the head, epidermis and neuromasts of the anterior and posterior lateral line system, suggesting their involvement in the normal development of these tissues.We want to thank the funding from the project CSD2007-00002 “Aquagenomics” of the program Consolider-Ingenio 2010 from the Spanish Ministerio de Ciencia e Innovación. M. Varela gratefully acknowledges the JAE Program, co financed by CSIC and European Social Funds, for a predoctoral grant.Peer reviewe

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms

Quality of Life in the PACT-Programme (Patient's Anastrozole Compliance to Therapy Programme): Influence of a Standardized Information Service on Patient Satisfaction and Health Related Quality of Life in Postmenopausal Women with Early Breast Cancer (EBC)

Abstract Introduction: In recent years, patient reported outcomes have become increasingly a focus in clinical investigations. Health related quality of life (HRQoL) is now regularly evaluated in clinical trials, yet data on HRQoL in postmenopausal women receiving adjuvant aromatase inhibitor treatment for early breast cancer (EBC) is limited. Here, we present the 12 months results on HRQoL and patient satisfaction from PACT, a program which aims to increase awareness, motivation and adherence to adjuvant anastrozole therapy in routine clinical practice by adding regular standardized information (brochures and motivational letters) to standard clinical care. Methods: PACT is a prospective, randomised, two-arm parallel-group study with 60 months follow-up (NCT00555867, sponsored by AstraZeneca Germany). Postmenopausal women on anastrozole for hormone-receptor positive (HR+) EBC were randomized to routine clinical care alone or additional regular standardized information (educational arm) for the first year of adjuvant endocrine therapy. Primary endpoint was the compliance rate in the educational vs. routine arm after 12 months. Secondary endpoints include HRQoL and patient satisfaction, evaluated via EORTC IN-PATSAT32, QLQ-C30, and QLQ-BR23. The present analysis focuses on differences in HRQoL and patient satisfaction between the standard and educational arm and between compliant and non-compliant patients at 12 months after treatment initiation. Results: 4,923 patients were enrolled into PACT by Nov. 2008. Of these, 2,707 were evaluable for analysis of the primary endpoint compliance and the secondary endpoints patient satisfaction and HRQoL. Analysis of HRQoL and patient satisfaction scores showed no differences between the standard and the educational arm at 12 months. When comparing compliant vs. non-compliant patients, however, compliant patients reached significantly higher (=better) patient satisfaction scores in all domains. In addition, compliant patients achieved significantly higher (=better) scores in the HRQoL domains of physical functioning (p=0.04), emotional functioning (p=0.018), cognitive functioning (p=0.004), social functioning (p=0.005), and sexual enjoyment (p=0.047), as well as lower (=better) scores in the domains of fatigue (p=0.01), systemic therapy (p=0.003), and arm symptoms (p=0.03). After correction for multiple testing, statistically significant differences favouring compliant patients were retained in the areas of information provision and availability (p=0.0008 and p=0.0005, respectively). Conclusion: In postmenopausal patients with HR+ EBC assigned to adjuvant endocrine treatment with an aromatase inhibitor (anastrozole), HRQoL and patient satisfaction were not affected by the intervention. However, analysis of compliant vs. non-compliant patients revealed improved scores for patient satisfaction in multivariate analysis favouring compliant patients at 12 months after treatment initiation. PACT represents an important project in health outcomes research regarding adjuvant endocrine therapy in postmenopausal patients with HR+ EBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-12.</jats:p

Influence of Demographic and Histopathological Characteristics on Compliance and Persistence in 4.923 Postmenopausal Women with Early Breast Cancer (EBC) - Results of the Patient's Anastrozole Compliance to Therapy Programme (PACT)

Abstract Introduction: According to recent retrospective studies, compliance to adjuvant endocrine therapy for early breast cancer (EBC) may drop below 70% after one year and to as low as 50% by year 4. The PACT-study aims investigate the effect of standardized information materials (brochures and motivational letters) to standard clinical care. Here we present the results for the primary endpoints compliance and persistence rates at 12 months as well as the influence of demographic and histopathological characteristics on compliance and persistence. Methods: PACT is a prospective, randomised, parallel-group study with 60 months of follow-up (NCT00555867, sponsored by AstraZeneca Germany). Postmenopausal women on anastrozole (ANA) for hormone-receptor positive (HR+) EBC were randomized to routine clinical care alone or additional standardized information (educational arm) for the first 12 months of adjuvant therapy. Primary endpoints are compliance and persistence rates in the educational versus routine arm after 12 months. Secondary endpoints include influence of baseline demographic and histopathol. characteristics on compliance and persistence as well as influence of compliance on clinical outcome parameters (DFS, OS). Compliance is evaluated via patient questionnaires, prescription data and physician recall and was defined as intake of at least 80% of the total medication (292 ANA tablets in 12 months). Persistence is defined as“duration of time from initiation to discontinuation of therapy” (Cramer 2007). A patient was defined as persistent if the documentation supported the intake of ANA during the full first 12-months. Results: PACT enrolled 4,923 patients at 109 breast centres and 1,361 registered specialist practices from Germany. 4,397 patients were evaluable for baseline characteristics. 2,707 patients had a visit documented at 12 months (≥9 to 18 months) and were evaluable for the primary endpoint. No difference in compliance could be shown between the standard (88.2%) and educational arm (88.3%) at 12 months (p=0.95, Fisher's exact test). In a modified analysis classifying patients not attending for a follow-up visit after 12 months as non-compliant, the compliance rate in both arms was sign. lower with 53.9% in the standard and 55.1% in the educational arm, yet no significant intergroup difference (p=0.43). Persistence rates were 40.3% for the standard and 43.0% for the educational arm (p=0.17). Influence of baseline demographic and histopathological characteristics on compliance and persistence are currently under review and will be presented at the meeting. Conclusion: The addition of standardized information materials to standard clinical care did not lead to increased compliance or persistence rates at 12 months. Data on the influence of baseline demographic and histopathological characteristics on compliance and persistence will be presented. PACT represents the largest prospective study to evaluate the influence of educational materials and baseline demographic and histopathol. characteristics on compliance and persistence to adjuvant endocrine therapy in postmenopausal patients with HR+ EBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-05.</jats:p