Browsing by Author "Burotto, Mauricio"

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    Double hit lymphoma: from biology to therapeutic implications
    (Taylor & Francis Online, 2016) Burotto, Mauricio; Berkovits, Alejandro; Dunleavy, Kieron
    INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a molecularly heterogeneous disease defined by different cellular origins and mechanisms of oncogenic activation. Approximately 10% of DLBCL cases harbor a MYC rearrangement and this has been associated with a more aggressive clinical course following standard therapy. AREAS COVERED: So-called 'double-hit lymphomas' (DHL) or 'triple hit lymphomas' (THL) occur when MYC is concurrently rearranged with BCL2 and/or BCL6. These tumors are characterized by high proliferation rate and a very poor outcome following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin vincristine and prednisone) therapy, in most (though not all) studies that have looked at this. Though there is a paucity of published experience with other chemotherapy regimens, there is emerging evidence that more intensive approaches may improve outcome. Recently, there has been a lot of focus in the literature on 'double-expresser lymphomas' (DEL) with high MYC, BCL2 and/or BCL6 expression but typically without rearrangements of these genes. These DEL cases, have a poor outcome with R-CHOP and there is little consensus on how they should be approached. Expert commentary: This review will focus on the biology and treatment of DHL and DEL, discuss the outcome of these diseases with current standard as well as promising new approaches and conclude with a section on novel agents that are in development for these diseases.
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    MABp1 for the treatment of colorectal cancer
    (Taylor & Francis Online, 2017) O’Sullivan, Geraldine; Burotto, Mauricio
    Inflammation is an established process in colorectal cancer development and a hallmark of progression, and pro-inflammatory cytokines have been implicated in the morbidity and functional compromise associated with malignancy. MABp1, described as a first-in-class true human antibody against interleukin-1α, has undergone clinical trial evaluation in a number of indications, recently completing late phase clinical trial testing under Fast Track designation for cancer anorexia-cachexia syndrome in colorectal cancer patients. To date, MABp1 has been evaluated as a novel therapeutic strategy to ameliorate phenotypic factors associated with poor prognosis in colorectal cancer patients. Areas covered: In this review, the authors discuss the clinical trial data available to date for this antibody in colorectal cancer, including novel clinical trial endpoints utilized to evaluate sarcopenia and inflammation, as well as the proposed role of interleukin-1α antagonism in leading to improved patient outcomes. Expert opinion: There is a multitude of antibodies in therapeutic development in oncology, and MABp1 is a novel class of antibody which has been safely tolerated to date. Clinical studies of this agent suggest a significant improvement in lean body mass, though additional results evaluating the impact of targeting inflammation as a strategy to delay disease progression in this population are awaited.
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    Potential use of n-3 PUFAs to prevent oxidative stress-derived ototoxicity caused by platinum-based chemotherapy
    (2020) Cortés Fuentes, Ignacio A.; Burotto, Mauricio; Retamal, Mauricio A.; Frelinghuysen, Michael; Caglevic, Christian; Gormaz, Juan G.
    Platinum-based compounds are widely used for the treatment of different malignancies due to their high effectiveness. Unfortunately, platinum-based treatment may lead to ototoxicity, an often-irreversible side effect without a known effective treatment and prevention plan. Platinum-based compound-related ototoxicity results mainly from the production of toxic levels of reactive oxygen species (ROS) rather than DNA-adduct formation, which has led to test strategies based on direct ROS scavengers to ameliorate hearing loss. However, favorable clinical results have been associated with several complications, including potential interactions with chemotherapy efficacy. To understand the contribution of the different cytotoxic mechanisms of platinum analogues on malignant cells and auditory cells, the particular susceptibility and response of both kinds of cells to molecules that potentially interfere with these mechanisms, is fundamental to develop innovative strategies to prevent ototoxicity without affecting antineoplastic effects. The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) have been tried in different clinical settings, including with cancer patients. Nevertheless, their use to decrease cisplatin-induced ototoxicity has not been explored to date. In this hypothesis paper, we address the mechanisms of platinum compounds-derived ototoxicity, focusing on the differences between the effects of these compounds in neoplastic versus auditory cells. We discuss the basis for a strategic use of n-3 PUFAs to potentially protect auditory cells from platinum-derived injury without affecting neoplastic cells and chemotherapy efficacy.

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