PCN20 MAINTENANCE ERLOTINIB VERSUS PEMETREXED FOR THE TREATMENT OF NON-SMALL CELL LUNG CANCER: INDIRECT COMPARISON APPLYING REAL-LIFE OUTCOMES

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The Immune Response to Tumors as a Tool toward Immunotherapy

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes

Right ventricular dysfunction parallels left ventricular functional involvement in women with breast cancer experiencing subclinical cardiotoxicity

Abstract Funding Acknowledgements Type of funding sources: None. Background Cancer therapy related cardiac toxicity disease (CRCTD) of the left ventricle (LV)can influence the outcome of oncologic patients. Little is known on CRCTD related right ventricular (RV)dysfunction even though RV involvement has been proven to be a remarkable prognosticator in heart failure. Purpose To analyse parallel changes in LV and RV function occurring during the course of cancer therapy in women affected by breast cancer by using both standard and speckle tracking echocardiography. Methods Fifty Her-2 positive breast cancer women (age = 53.6 ± 11.7 years) underwent sequential cancer therapy protocol including anthracycline (ANT) epirubicine + cyclophosphamide (4 cycles) followed by a total amount of 18 cycles with trastuzumab (TRZ) + paclitaxel. A complete echo-Doppler exam, including LV and RV global longitudinal strain (GLS)as well as RV septal and free wall longitudinal strain (SLS and FWLS respectively) assessment, was performed at baseline, after ANT end and after TRZ completion. Patients with overt heart failure and LV ejection fraction < 50%, coronary artery disease,atrial fibrillation, hemodinamically significant valve disease and inadequate echo were excluded. Overt CRCTD was defined according guidelines and both subclinical LV and RV CRCTD as a LV and RV GLS drop from baseline >15%. Results None of the patients experienced overt CTCRD but 6 patients (14%) showed subclinical LV dysfunction and 33 (66%) had a significant drop of RV longitudinal function.The comparison of standard echo-Doppler exam at baseline and after ANT and TRZ completion did not show significant changes of LV and RV systolic and diastolic parameters. Conversely, a progressive significant reduction of RV GLS (p < 0.002 after TRZ), SLS and FWLS and, with a lower extent, of LV GLS (p < 0.02 after TRZ) was observed after ANT and TRZ completion (Figure). Percentage reduction in RV GLS (DRV GLS) from baseline to ANT end correlated with LV GLS both at EC end (r=-0.40, p = 0.006) and after TRZ completion (r=-0.62, p < 0.0001). Conclusions Detrimental cardiac effects of cancer therapy involve both LV and RV systolic longitudinal function. Progressive RV dysfunction is evident through ANT and TRZ treatment. Early RV dysfunction parallels LV involvement and predicts subsequent LV subclinical dysfunction. A comprehensive LV and RV longitudinal function assessment might better predict the onset of CRCTD in breast cancer patients. Abstract Figure

Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison

Background: Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. Methods: Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. Results: Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. Conclusions: The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments

Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis

The Lantern Vol. 54, No. 1, Fall 1987

• Darkside • Reflections on a Subway Ride • Demand for Love • Music Man • Something Wild • The Nice Guy\u27s Story • The Picnic • Internalize • Days When You Feel Like Wonder Bread • II • A Tear • In Pursuit of Beauty • A Walk Down Sycamore Lane • A Wish • Sins of Omission • Pessimism • And the Sky Cracked • The Clock Strikes • Invinciblehttps://digitalcommons.ursinus.edu/lantern/1131/thumbnail.jp

Atrophin proteins: an overview of a new class of nuclear receptor corepressors

The normal development and physiological functions of multicellular organisms are regulated by complex gene transcriptional networks that include myriad transcription factors, their associating coregulators, and multiple chromatin-modifying factors. Aberrant gene transcriptional regulation resulting from mutations among these elements often leads to developmental defects and diseases. This review article concentrates on the Atrophin family proteins, including vertebrate Atrophin-1 (ATN1), vertebrate arginine-glutamic acid dipeptide repeats protein (RERE), and Drosophila Atrophin (Atro), which we recently identified as nuclear receptor corepressors. Disruption of Atrophin-mediated pathways causes multiple developmental defects in mouse, zebrafish, and Drosophila, while an aberrant form of ATN1 and altered expression levels of RERE are associated with neurodegenerative disease and cancer in humans, respectively. We here provide an overview of current knowledge about these Atrophin proteins. We hope that this information on Atrophin proteins may help stimulate fresh ideas about how this newly identified class of nuclear receptor corepressors aids specific nuclear receptors and other transcriptional factors in regulating gene transcription, manifesting physiological effects, and causing diseases

Inhibition of the Nicotinic Acetylcholine Receptors by Cobra Venom α-Neurotoxins: Is There a Perspective in Lung Cancer Treatment?

Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs) and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated

Moving Towards Accountability for Reasonableness – A Systematic Exploration of the Features of Legitimate Healthcare Coverage Decision-Making Processes Using Rare Diseases and Regenerative Therapies as a Case Study

Background: The accountability for reasonableness (A4R) framework defines 4 conditions for legitimate healthcare coverage decision processes: Relevance, Publicity, Appeals, and Enforcement. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide decision-making towards legitimacy. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer therefore a useful case study. Methods: Features operationalizing each A4R condition as well as three different approaches to address these features (cost-per-QALY-focused and multicriteria-based) were defined and organized into a matrix. Seven experts explored these features during a panel run under the Chatham House Rule and provided general and RDRT-specific recommendations. Responses were analyzed to identify converging and diverging recommendations. Results: Regarding Relevance, recommendations included supporting deliberation, stakeholder participation and grounding coverage decision criteria in normative and societal objectives. Thirteen of 17 proposed decision criteria were recommended by a majority of panelists. The usefulness of universal cost-effectiveness thresholds to inform allocative efficiency was challenged, particularly in the RDRT context. RDRTs raise specific issues that need to be considered; however, rarity should be viewed in relation to other aspects, such as disease severity and budget impact. Regarding Publicity, panelists recommended transparency about the values underlying a decision and value judgements used in selecting evidence. For Appeals, recommendations included a life-cycle approach with clear provisions for re-evaluations. For Enforcement, external quality reviews of decisions were recommended. Conclusion: Moving coverage decision-making processes towards enhanced legitimacy in general and in the RDRT context involves designing and refining approaches to support participation and deliberation, enhancing transparency, and allowing explicit consideration of multiple decision criteria that reflect normative and societal objectives