1,721,075 research outputs found
New Understanding of the Role of Anthracyclines in Early-Stage Breast Cancer: Patient Selection Considerations
No full textIn the past decade, a considerable effort has been made to Identify molecular markers that predict anthracycline activity. A number of retrospective studies that evaluated the clinical activity of anthracyclines according to HER2 status suggested that the additional benefit of these agents, as compared with non-anthracycline-based chemotherapy, is confined to HER2-positive tumors. More recently, 2 meta-analyses, based on abstracted data, have reinforced this concept, challenging the use of adjuvant anthracyclines in patients with HER2-negative tumors. Additional data suggested that patients who derive the largest clinical benefit from anthracycline-based chemotherapy have TOP2A gene-amplified tumors. The last hypothesis is based on the fact that topoisomerase Il alpha protein is the molecular target of Topo II inhibitors such as anthracyclines. The TOP2A gene is located on chromosome 17q12-17q21, next to the HER2/neu gene. TOP2A gene aberrations (amplifications or deletions) are more frequent in HER2/neu-amplified than in HER2/neu-nonamplified tumors. Approximately 35% and 25% of HER2/neu-amplified tumors carry TOP2A gene amplifications and deletions, respectively; however, although TOP2A gene aberrations are detected most frequently in HER2-amplified tumors, topoisomerase Il alpha protein overexpression (largely regulated by proliferation signals) and DNA repair dysfunctions are observed in different breast cancer subtypes, independent of HER2 status. This finding suggests that hypersensitivity to anthracyclines might not be confined to HER2-positive tumors, and as a consequence, some patients with HER2-negative disease also could derive clinically relevant benefit from these compounds
Annual Hazard Rates of Recurrence for early breast cancer. What has changed in the last 10 years? Results from the NORA study.
No full textTrastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients
No full textHurvitz SA, Dirix L, Kocsis J et al. Phase II randomised study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J. Clin. Oncol. 31(9), 1157-1163 (2013). The introduction of trastuzumab in the treatment of HER-2-positive metastatic breast cancer patients favorably changed the natural history of this disease. First-line treatment with trastuzumab and taxanes demonstrated a significant improvement in overall survival and progression-free survival compared with taxane alone. Despite such a major advance, HER-2-positive metastatic breast cancer will eventually progress in most patients. Moreover chemotherapy-associated toxicities, such as myelosuppression (docetaxel) and neurotoxicity (paclitaxel), may hamper the possibility to adequately treat metastatic breast cancer and may have a negative effect on patients' quality of life. The need for more effective and better-tolerated therapy for HER-2-positive metastatic breast cancer led to the development of new anti-HER-2 agents. Pertuzumab and trastuzumab emtansine are two of the new agents that will change the approach to the treatment of HER-2-positive metastatic breast cancer. Pertuzumab is a humanized monoclonal antibody that binds HER-2 at a different epitope of the HER-2 extracellular domain (subdomain II) than that at which trastuzumab binds. Trastuzumab emtansine is a HER-2-targeted antibody-drug conjugate, composed of the cytotoxic microtubule polymerization inhibitor DM1 that is conjugated to the monoclonal antibody trastuzumab, able to selectively deliver a cytotoxic agent to HER-2-positive tumor cells. TDM-1 is superior and less toxic than lapatinib plus capecitabine in metastatic breast cancer patients previously treated with trastuzumab and taxanes, and its role as a first-line therapy is currently under investigation
Skin toxicities difference between erlotinib and gefitinib in the treatment of advanced non-small-cell lung cancer (NSCLC)
No full textLuteinising hormone releasing hormone agonists (LH-RHa) in premenopausal early breast cancer patients: current role and future perspectives
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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