1,721,208 research outputs found
Predictive modeling in colorectal cancer: time to move beyond consensus molecular subtypes
No full textDuration of oxaliplatin-based adjuvant chemotherapy in patients with Stage III or high-risk Stage II resected colon cancer
No full textClinical applications of bevacizumab in the treatment of colorectal and ovarian cancer
No full textThe development of biological drugs, which began in the 1980s, has revolutionized the treatment of numerous oncological diseases and severely disabling autoimmune diseases, with widely demonstrated evidence of benefit. Today, biological drugs represent an important and continuously developing category and are used both as a support therapy in onco-hematology and as molecules with their own therapeutic activity, such as monoclonal antibodies. Among these, bevacizumab represents a drug of relevant clinical value, used as antiangiogenic therapy in numerous cancers, in particular colorectal and ovarian cancers. The expiry of the patent period of monoclonal antibodies, including bevacizumab, has opened up to the development of biosimilar drugs, represented by structurally similar molecules with pharmacokinetic, pharmacodynamic and clinical characteristics equivalent to a biological drug already present in clinical use (originator biologic). The development process of these drugs is contained in the guidelines of the major regulatory bodies (FDA/EMA) and is faster than that provided for the originator biologic. Since biosimilars have a lower cost than reference drugs, their use represents a possibility of containing health care costs and of satifying the growing demand in terms of efficacy and personalization of pharmacological therapies. Considering the particular severity of the diseases treated, including colorectal and ovarian cancers, biosimilar drugs must be used with full awareness, in terms of efficacy and safety, since their approval is based on a rigorous analytical process, as well as preclinical and clinical evaluation
Advanced nanotechnology for enhancing immune checkpoint blockade therapy
Full text linkImmune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell‐to‐cell connection that represses T‐lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long‐lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems
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
Clinical experience with encorafenib and cetuximab in patients with BRAFV600E-mutant metastatic colorectal cancer after early relapse following adjuvant chemotherapy
No full textMetastatic colorectal cancer (mCRC) is constituted of several biological subgroups characterized by molecular alterations activating specific proliferative pathways. These alterations have, for a long time, lacked targeted therapies capable of inactivating these signalling pathways and eventually modifying the course of the disease. This scenario has rapidly been evolving in recent years, thanks to a better understanding of mCRC biology and advances in drug development, that have turned these alternations into "actionable" targets. BRAFV600E is a landmark example of this process. Conceived for roughly a decade as a negative prognostic factor of outcome and as a predictor of resistance to anti-EGFRs, today it is also a predictor of response to the combination of the anti-BRAF encorafenib and of the anti-EGFR cetuximab, and a standard of care in patients with BRAFV600E-mutated mCRC, after failure of previous systemic therapy. In this work, we report three clinical scenarios where encorafenib and cetuximab are used in label as first-line of treatment, at the diagnosis of mCRC, after early relapse occurring at the end of adjuvant chemotherapy
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