1,720,988 research outputs found
Bevacizumab in ovarian cancer: Focus on clinical data and future perspectives
No full textThe past five years have yielded substantial developments in the management of advanced ovarian cancer. Initial promise shown by anti-angiogenic agents has translated into positive phase III trials in the front-line and recurrent settings. Nevertheless, several questions remain unanswered, including the most appropriate timing for initiation of anti-angiogenic therapy and patient selection for the various treatment approaches. This review article summarises the key results (including final overall survival data), from five pivotal phase III trials of bevacizumab, highlights emerging data with new maintenance strategies and considers unanswered questions and ongoing research to address uncertainties in treatment duration, re-exposure to bevacizumab in bevacizumab-pretreated patients and the potential integration of anti-angiogenic therapy into neoadjuvant treatment regimens
Predictive value of biological parameters for primary chemotherapy in operable breast cancer
No full textAbstract
Primary chemotherapy represents an ideal model to evaluate the relationships between treatments and the prognostic and predictive parameters provided by the new technologies. First- and second-generation trials have shown that primary chemotherapy significantly improves the rate of breast conservation without increasing the risk of ipsilateral recurrence and while assuring survival rates comparable with those achieved with postoperative chemotherapy. Moreover, patients who exhibited a pathologic complete response (pCR) showed better progression-free survival and overall survival. The third-generation trials were aimed at improving the percentage of pCR, identifying and validating gene and protein biomarkers of chemotherapy sensitivity, and better defining the individual risk of relapse. Several parameters, such as index of proliferation and apoptosis, expression of proteins (eg, p53 and Bcl-2), and hormone receptor and epidermal growth factor family receptors, have been related to response to primary chemotherapy. Negative hormone receptors and greater proliferative activity seem to be the only parameters more consistently associated with greater chemotherapy sensitivity. However, the strength of this association is not sufficient to differentiate patients at different degrees of risk and does not allow for an individualized therapeutic choice. Newer technologies offer the possibility of evaluating thousands of genes and identifying clusters of gene expression associated with significantly different risks of relapse and patterns of sensitivity/resistance to specific drugs. The primary chemotherapy model is the ideal clinical setting in which to validate the relationship between tumor molecular profiling and treatment outcomes and to design tailored therapies based on observed effects on individual tumors
Primary Systemic Therapy in operable breast cancer: clinical data and biological fall-out
No full textAbstract
Primary systemic chemotherapy (PST) was first used in early 1970s for the treatment of locally advanced breast cancer; in this setting primary chemotherapy was administered to allow for radical surgery and the objective response rates were high with a substantial proportion of patients amenable to surgery. On the basis of this activity, PST was subsequently used to treat operable locally advanced or large primary tumors to increase the rate of conservative surgery. First generation clinical trials demonstrated that breast conservation rates were improved, that a proportion of patients experienced a complete pathologic response and that response to PST was a good predictor of long term outcome. Second generation of clinical trials were designed to compare PST to postoperative adjuvant chemotherapy: here again the rate of conservative surgery was significantly improved and the pathologic response rate demonstrated its prognostic value, however no progression free or survival improvement was obtained in comparison with postoperative treatments. Another interesting observation from these trials was that some tumor parameters (histology, grade, hormone receptor status) can predict the likelihood of achieving a pathologic complete response. On the basis of these data, PST can now be considered the standard of care for locally advanced disease, an reasonable option in case of large primary breast tumors not eligible for conservative surgery and an acceptable alternative for all the patients who are candidate to adjuvant treatment. It however clear that PST represents an excellent in vivo model to test new regimens, to evaluate biomarkers with predictive value and to evaluate the treatment induced modifications in tumor biology. Availability of new technologies able to measure the expression of thousands of genes and of new molecularly directed drugs will increase further the interest in this treatment strategy
A computational workflow for the design of irreversible inhibitors of protein kinases
No full textDesign of irreversible inhibitors is an emerging and relatively less explored strategy for the design of protein kinase inhibitors. In this paper, we present a computational approach for the creation of a database of already known reversible inhibitors of protein kinases, the selection of the most promising scaffolds that bind one or more desired kinase templates, the modification of the scaffolds by introduction of chemically reactive groups (suitable cysteine traps) and the final evaluation of the reversible and irreversible protein–ligand. The workflow was tested on a database of known inhibitors of ERK2, a protein kinase possessing a cysteine in the ATP site
Pulmonary strongyloidiasis mimicking cancer symptoms: A case of hyperinfection in a patient with metastatic lung cancer
No full textPulmonary Strongyloidiasis Mimicking Cancer Symptoms A Case of Hyperinfection in a Patient With Metastatic Lung Cance
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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