1,720,999 research outputs found
Current trends in prostate cancer treatment and drug resistance
No full textProstate cancer is the second most common cancer in men with approximately 256,000 deaths reported worldwide. Active surveillance which involves careful monitoring of the tumour over time is often considered in patients with low risk and slow progressing tumours. Surgery and radiation therapy are also used to treat patients with localised tumours. However, for patients with aggressive tumours or patients who fail localised treatment androgen-deprivation therapy (ADT) is the mainstay of treatment. Despite initial tumour regression and prostate-specific antigen (PSA) decline in about 90% of patients treated with ADT, relapse occurs in many patients after a mean of 2 to 3 years leading to the development of more aggressive castration-resistant prostate cancer (CRPC). CRPC is often metastatic, associated with poor prognosis, and patients die within 2 years. Currently available chemotherapeutics to treat metastatic tumours extend the life span of patients by only a few months. Majority of prostate cancer drugs target either androgen signalling or cell division in prostate cancer cells. Novel immunotherapeutic and natural compound approaches are currently being tested to treat prostate cancer. However, resistance to therapy continues to be one of the major hurdles for the successful treatment of CRPC. To overcome drug resistance multiple approaches have been employed. For example, prostate cancer cells depend on androgens and its cognate receptor androgen-receptor (AR) for their growth and survival. Therefore, targeting androgen synthesis and AR provides a main avenue for drug discovery research. Drugs that target tumour cell survival also offer therapeutic benefit and are used either alone or in combination therapy
Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?
No full textLimited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed
Multi-drug Resistance in Cancer and New Approaches for Its Overcoming
No full textResistance to chemotherapy is the main obstacle to efficient cancer treatment. The problem of multi-drug resistance (MDR) has been intensively studied for the last three decades. Classically defined as resistance to structurally and/or functionally unrelated drugs, MDR is connected with aggressive, untreatable cancers. There are two types of MDR: inherent (intrinsic) and acquired. Selection pressures within the tumor microenvironment favor the development of intrinsic MDR, while the ordinary dose and schedule chemotherapy practices induce acquired MDR. In recent years, patient-to-patient variability within each type of cancer has arisen as an unsolved problem. Even more, heterogeneous populations of cancer cells within one patient must be considered as a cause of chemotherapy impediment.
Several genes and pathways have been found to contribute to the MDR. Tentatively, MDR phenotype could develop from point mutations, gene amplification or other genetic or epigenetic changes that affect biological functions. Therefore, MDR is driven by similar mechanisms as cancerogenesis. This is also supported by the fact that important characteristics of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and an elevated apoptotic threshold. Understanding these mechanisms and developing agents to target them are important steps in the design of new therapies.
Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect due to the interaction with intracellular target molecules. Decreased activity of membrane-embedded drug uptake as well as increased activity of efflux pumps reduce the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells prompted the efforts in overcoming drug resistance by inhibition of P-gp.
The search for nontoxic anti-cancer agents able to overcome MDR has been an imperative in the field of drug design and discovery for many years. Two main approaches in combating the problem of MDR in cancer include (i) development of agents able to preserve cytotoxic activity toward MDR cancer cells; (ii) development of compounds able to restore the cytotoxicity of classic anti-cancer drugs.
In this chapter, we discuss the new findings regarding MDR reversal strategies, the alterations obtained in our artificially developed MDR models and advantages of our different approaches in overcoming MDR.Morais C, editor. Advances in Drug Resistance Research. New York: Nova Science Publishers, Inc. 2014. p. 39-100
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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