1,721,015 research outputs found
The new era in the treatment of advanced colorectal cancer patients: the role of monoclonal antibodies
No full textColorectal cancer (CRC) represents a major health problem in the Western world. Approximately 60% of patients with CRC require systemic therapy for metastatic disease, either at diagnosis or at disease recurrence. Until recently, classic chemotherapeutic agents have been combined in the treatment of advanced CRC. The recent considerable development of novel monoclonal antibodies that target key components of biological pathways has expanded the options to treat advanced CRC patients. These newer agents more specifically target unique features of the cancer cell and its surroundings and so attempt to exploit the progress that has been made in the understanding of basic cell biology. Two targets in particular--the process of new blood vessel development, or angiogenesis, and the EGF receptor and its signalling pathway--are exploited by the newest monoclonal antibodies available for use in this setting. This clinical review focuses on the defining role of the two most clinically advanced novel agents, bevacizumab and cetuximab in metastatic colorectal cancer
Antiangiogenic properties of metronomic chemotherapy in breast cancer
No full textChemotherapeutic agents cause DNA damage and disrupt DNA replication in proliferating cells. Drug regimens have been designed to kill as many tumor cells as possible with the use of the maximum-tolerated doses of these cytotoxic agents. Damage in proliferating tissues (the bone marrow, gut and skin) and healthy tissues place serious constraints on the use of chemotherapy. To balance toxicity with efficacy, cytotoxic agents are administered in a pulsed manner with breaks between cycles to allow for the recovery of normal tissues. Many chemotherapy regimens are initially efficacious, determining tumor regression or stabilization and prolonged survival. However, responses are generally short-lived, with relapses often marked by aggressive cancers that are resistant to the cytotoxic drug. Cytotoxic chemotherapy remains an important part of optimal therapy for patients in all stages of disease, but its use is limited by toxicity, nonspecificity and the inevitable development of resistance, with serious consequences on the patients quality of life. For these reasons, clinical research is moving to improve our understanding of the altered molecular events in cancer cells and find new targets to be inhibited in order to optimize cytotoxicity and overcome resistance mechanisms. This review aims to explain the rationale behind metronomic and targeted therapies in breast cancer and to examine the main preclinical and clinical (neoadjuvant, adjuvant and advanced settings) studies conducted
The biological properties of cetuximab
No full textCetuximab is a recombinant chimeric human murine immunoglobulin G1 antibody that binds to the extra-cellular domain of epidermal growth factor receptor with a higher affinity than either endogenous ligand. This binding inhibits receptor phosphorylation and activation and it leads to receptor internalization and degradation. Several studies have shown that cetuximab is able to inhibit growth of epidermal growth factor receptor (EGFR)-expressing tumour cells in vitro. Moreover, treatment with cetuximab results in a marked inhibition of tumour growth in nude mice bearing xenografts of human cancer cell lines. These results are linked to cetuximab biological effects as inhibition of cell cycle, tumour progression, neo-angiogenesis, invasion and metastatization, as well as increase and activation of pro-apoptotic molecules. Additionally, cetuximab potentiates, in combination, the effects of chemotherapy and radiation therapy in eradicating well-established tumours in nude mice and it may even reverse the resistance to some cytotoxic agents in these xenografts. Moreover, numerous clinical trials demonstrated cetuximab efficacy in different tumour types. It has been approved by Food and Drugs Administration in the treatment of metastatic colorectal cancer as single agent or in combination with chemotherapy, in locally and regionally advanced head and neck squamous cell carcinoma in combination with radiation, and as monotherapy for recurrent and metastatic head and neck squamous cell carcinoma after failing platinum-based chemotherapy. This paper will overview all the experimental and pre-clinical data on the biological properties of cetuximab. (C) 2008 Elsevier Ireland Ltd. All rights reserved
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Stevens-Johnson syndrome associated with reduced tear production complicating the use of cetuximab and panitunumab
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