1,721,097 research outputs found
Identificazione di markers prognostici in pazienti con carcinoma colo-rettale metastatico trattati con Regorafenib
No full textRegorafenib è un farmaco anti-angiogenico approvato nel trattamento dei pazienti con carcinoma
del colon-retto metastatico, dopo trattamento chemioterapico con tutti i farmaci attualmente
disponibili. Le frequenti tossicità e l'assenza di indicatori di risposta hanno limitato l'utilizzo di tale
risorsa terapeutica.
Lo scopo dello studio è di valutare il ruolo prognostico di fattori quali il risultato degli esami di
laboratorio e dei polimorfismi della via neoangiogenica VEGF-mediata nel trattamento di pazienti
con tumore del colon-retto metastatico trattati con Regorafenib.
Lo studio è del tipo osservazionale multicentrico retrospettivo. Tutti i pazienti hanno ricevuto una
monoterapia con Regorafenib e sono stati inclusi nell'analisi da Agosto 2013-Luglio 2014. In tutti i
pazienti sono stati raccolti i dati relativi all'andamento clinico ed il risultato degli esami di
laboratorio. E' stato conservato il materiale biologico (sangue o tessuto istologico) per la
determinazioni dei polimorfismi di VEGF-VEGFR.
Sono stati inclusi nell'analisi 138 pazienti. La mediana di sopravvivenza è stata di 7.3 mesi, con
una sopravvivenza libera da progressione di 1.9 mesi. Si è evidenziato il valore prognostico dell'alto
valore di LDH, di un performance status elevato, di un alta conta piastrinica, di un alto rapporto
neutrofili/linfociti e dell'assenza di un polimorfismo favorente (rs2010963 di VEGF-A CC
omozigote recessivo) come fattori in grado di influire negativamente sulla prognosi. In presenza di
al più 1 di tali fattori si è osservata una sopravvivenza mediana di 14.76 mesi rispetto ai 3.09 mesi
dei pazienti che presentavano almeno 4 fattori positivi (p<0.0001).
E' stato dimostrato un possibile ruolo dei fattori evidenziati come determinanti una diversa prognosi
in pazienti trattati con Regorafenib. E' auspicabile che questi vengano inclusi in successive analisi
di sopravvivenza riguardanti il farmaco, in maniera prospettica ed in una casistica più ampia
Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase
No full textFluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (Clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy
Role and mechanisms of resistance of epidermal growth factor receptor antagonists in the treatment of colorectal cancer
No full textIntroduction: Although epidermal growth factor receptor (EGFR) inhibitors have progressively become a relevant therapeutic arm in the treatment of patients with advanced colorectal cancer, the responses achieved are not durable and resistance invariably occurs. The advances in sequencing technology have allowed not only a more profound molecular tumor characterization but also the identification of the different molecular pathways involved in drug resistance and disease progression. These biological improvements have encouraged researchers to design clinical studies testing novel target therapies.Areas covered: After discussing the results of key Phase III randomized trials and providing commentary on the most promising novel agents (Sym004, MM-151, GA201 and MEHD7945A), the authors present the future steps ahead toward a real tailored treatment.Expert opinion: EGFR inhibitors are highly effective in the advanced disease setting. Although the negative predictive role of RAS and possibly BRAF mutations has already been established, more comprehensive efforts are needed to optimize the use of these drugs. At the same time, understanding the underlying biology will help basic scientists to develop new compounds able to overcome both primary and acquired resistance and help clinical researchers to test novel drugs within adequately designed trials whose results eventually are expected to reshape the overall treatment strategy
Panitumumab for the treatment of metastatic colorectal cancer: A review
No full textIn recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth. Its use has been approved by randomized clinical trials as monotherapy in chemorefractory patients or combined with chemotherapy in the treatment of RAS wild-type mCRC, where it demonstrated a significant improvement in survival and response rate. The purpose of this review is to analyze the use and efficacy profile of panitumumab, particularly focusing on recently reported data on its use, and future perspectives in patients with mCRC
State of the Art and Future Perspectives for the Use of Insulin-like Growth Factor Receptor 1 (IGF-1R) Targeted Treatment Strategies in Solid Tumors
No full textDalotuzumab, a recombinant humanized mAb targeted against IGFR1 for the treatment of cancer.
No full textDalotuzumab (MK-0646; h7C10), being developed by Merck & Co Inc under license from Pierre Fabre SA, is a recombinant humanized IgG1 mAb against the IGFR1 for the potential intravenous treatment of cancer. Preclinical studies have demonstrated that dalotuzumab acts by inhibiting IGF-1- and IGF-2-mediated tumor cell proliferation, IGFR1 autophosphorylation and Akt phosphorylation. In multiple cancer cell lines and in mouse xenograft models, dalotuzumab displayed significant antitumor activity, in particular against NSCLC and breast cancer. In addition, coadministration of dalotuzumab with other anticancer agents, such as taxanes, enhanced the in vitro and in vivo antitumor activity of dalotuzumab. Preliminary data from phase I clinical trials suggest that dalotuzumab is safe, well tolerated and significantly inhibits tumor proliferation. At the time of publication, several clinical trials evaluating dalotuzumab, alone and in combination with other anticancer agents, were ongoing in patients with various types of solid tumor and in patients with multiple myeloma. Although preliminary results appear promising, only future clinical and translational data will clarify the best clinical setting and treatment combinations for the optimal use of dalotuzumab in clinical practice
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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