1,721,000 research outputs found

    New therapies in soft tissue sarcoma

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    Importance of the field: Soft tissue sarcomas are rare mesenchymal tumors accounting for < 1% of all adult neoplasia. In the last decade, locally advanced and metastatic soft tissue sarcoma have been managed only through surgery, radiotherapy and standard chemotherapy (mainly based on anthracycline and ifosfamide). Despite the efforts, overall 5-year survival rate in patients with soft tissue sarcomas of all stages remains only 50 - 60%. Areas covered in this review: In the present article, all the main new molecules under clinical evaluation for the treatment of soft tissue sarcoma are revised by describing the mechanism of action, the biological rationale of their use in sarcoma and by reporting the available data about safety and efficacy, up to 2009. What the reader will gain: A brief summary of the standard treatments available at the moment and a complete analysis of the state of art about the development of new target therapies in the management of soft tissue sarcoma. Take home message: The identification of new biological therapies that target soft tissue sarcoma tumorigenesis key points seems to offer a real opportunity of improving the prognosis of this often aggressive disease. In this sense, the best management for soft tissue sarcoma patients is in a clinical trial and participation in clinical trials should be encouraged

    Target therapy in gastrointestinal tract sarcoma: What is new?

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    Soft tissue sarcoma are rare tumors arising mostly from embryonic mesoderm, that can affect almost any part of the human body, including the gastrointestinal tract. The prognosis associated with soft tissue sarcoma is still poor, mainly because of the low efficacy of traditional approaches based on surgery and chemotherapy. As a result of genetic and molecular analysis, several new target therapies have been developed, leading to a significant improvement in the survival of patients affected by advanced disease. In this review we aim to explore the therapeutic potential and benefit of target therapy in the management of gastrointestinal soft tissue sarcoma and the possible complications or pitfalls of such an approach. (C) 2010 Baishideng. All rights reserved

    Docetaxel induced pericardial effusion

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    Docetaxel is a complex diterpene obtained from Taxus Brevifolia, and it is one of the most widely used anticancer agents. The main mechanism of citotoxic action depends on stabilization of microtubules leading to cell mitotic arrest. Independently from the schedule, the primary dose limiting toxicity of docetaxel using is neutropenia. The most common acute side effects related with docetaxel are hypersensivity reactions and dermatitis. There are also other toxicities that may be cumulative in both onset and severity; an important dose limiting side effect in patients who receive multiple cycles of the drug is fluid retention. In previous clinical trials docetaxel resulted often associated with fluid retention, even if phisiopatology of this effect is still unknown. In the majority of cases its manifestations are edema or pleural effusion. We report two cases of patients who developed repeated episodes of pericardial effusion after docetaxel infusion

    Targeted therapy in sarcomas: mammalian target of rapamycin inhibitors from bench to bedside

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    Introduction: Sarcomas are rare heterogeneous malignancies of mesenchymal origin relatively common during childhood. Disruption of the mammalian target of rapamycin (mTOR) pathway is a very common event during the tumorigenesis of several types of cancer. In particular, strong preclinical evidences suggest pivotal roles of this pathway during the sarcomagenesis. Therefore, the inhibition of mTOR via rapamycin, rapamycin analogs (rapalogs) and ATP-competitive inhibitors seems to be a promising path to follow for a fully tailored therapy. Areas covered: The aim of the present review is to summarize the available data about the mechanisms of mTOR pathway, its biological implications and its possible role in the pathogenesis of soft tissue sarcoma. Moreover, preclinical and clinical evidences of different mTOR inhibitors in the treatment of sarcomas are reported. Expert opinion: Early studies with mTOR inhibitors have demonstrated promising antitumor activity in patients with metastatic sarcoma who have failed standard treatments: that is why mTOR inhibitors represents today a promising chance to improve the prognosis of those patients affected by these rare disease, which is today still extremely poor

    The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retrospective analysis in patients affected by resected colorectal cancer treated with adjuvant FOLFOX regimen

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    BACKGROUND: Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage. PATIENTS AND METHODS: A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded. RESULTS: Aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p < 0.0001) and dose reduction (p = 0.031). CONCLUSIONS: The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen

    Wide-spectrum characterization of trabectedin: biology, clinical activity and future perspectives

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    Ecteinascidin-743 (trabectedin, Yondelis (R); PharmaMar, Madrid, Spain), a 25-year-old antineoplastic alkylating agent, has recently shown unexpected and interesting mechanisms of action. Trabectedin causes perturbation in the transcription of inducible genes (e.g., the multidrug resistance gene MDR1) and interaction with DNA repair mechanisms (e.g., the nucleotide excision repair pathway) owing to drug-related DNA double strand breaks and adduct formation. Trabectedin was the first antineoplastic agent from a marine source (namely, the Caribbean tunicate Ecteinascidia turbinata) to receive marketing authorization. This article summarizes the mechanisms of action, the complex metabolism, the main toxicities, the preclinical and clinical evidences of its antineoplastic effects in different types of cancer and, finally, the future perspectives of this promising drug
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