1,721,101 research outputs found
Oncomirs: From Tumor Biology to Molecularly Targeted Anticancer Strategies
No full textDeregulation of microRNA (miRNA) promotes carcinogenesis, as these molecules can act as oncogenes or tumor suppressor genes. Here we provide an overview of miRNA biology, discuss the most recent findings on miRNA and cancer development/progression, and report on how tumor-related miRNAs (oncomirs) are being used to develop novel cancer specific therapeutic approache
Cancer resistance to type II topoisomerase inhibitors
No full textType II topoisomerases (TOPO2) are ubiquitously expressed enzymes that overcome topological problems in genomic DNA, which can result from DNA replication, transcription and repair. The class of compounds targeting TOPO2 includes some of the most active chemotherapy agents currently available for the treatment of patients with different cancer types. Therefore, understanding of the molecular mechanisms underlying resistance to these drugs is of pivotal importance to improve their efficacy and ultimately increase the life expectancy of cancer patients. The first aim of this review is to summarize the molecular biology of TOPO2 inhibitors, which is the key to understand cancer resistance to them; the second part of this work is dedicated to overview and discuss the available evidence on the mechanisms of resistance to these drugs, with special attention to the strategies that might be useful to circumvent this phenomenon on the clinical ground
Strategies to enhance the anticancer potential of TNF
No full textAlthough tumor necrosis factor (TNF) antitumor activity is evident in several preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Furthermore, due to systemic toxicity, TNF can only be administered via sophisticated drug-delivery systems in patients with solid tumors confined to one extremity or organ. The impossibility to administer TNF systemically does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. Dissecting the cascade of molecular events underlying tumor sensitivity to TNF researchers will allow to further exploit the anticancer potential of this molecule. The rational for the development of strategies aimed at sensitizing malignant cells to TNF is to modulate tumor-specific molecular derangements in order to maximize the selectivity of TNF cytotoxicity towards cancer. This would enhance the anticancer activity of current TNF-based locoregional regimens and would pave the way to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field
Towards the development of tumor necrosis factor (TNF) sensitizers: making TNF work against cancer
No full textAlthough TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field.
In this review we first summarize the molecular biology of TNF and its cancer-related properties then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewe
Peptide-Based Anticancer Vaccines: Recent Advances and Future Perspectives
No full textAnticancer active immunotherapy embodies the ideal antitumor therapy, as it theoretically combines target specificity with long-term disease control. Peptide-based cancer vaccines represent the most specific approach to polarize the immune system against malignant cells, since they are preparations made of single epitopes, the minimal immunogenic region of an antigen. Despite the strong rational, the promising preclinical results and the frequent induction of antigen-specific immune responses, peptide-based cancer vaccines have yielded relatively poor results in the clinical setting, a phenomenon likely due to the immunosuppressive properties of the tumor microenvironment that allow malignant cells to evade both naturally occurring and therapeutically induced immune surveillance. Nevertheless, advances in the engineering of peptides and in our understanding of the molecular mechanisms underlying an effective immune response against tumors have renewed the enthusiasm for peptide-based vaccination regimens in the setting of cancer, and a variety of clinical trials are being conducted based on the use of peptides. This review will describe the most recent insights in the rational design of peptide-based cancer vaccines, as well as the challenges to successful anticancer immunotherapy based on these short amino acid chains
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
Recent advances in conventional and molecular prognostic factors for gastric carcinoma
No full textDespite radical surgery, the prognosis of patients who have gastric carcinoma remains unsatisfactory because of the intrinsic but unpredictable aggressiveness of this malignancy. During the past decade an ever-growing list of molecular prognostic factors has been proposed based on the discovery of the mechanisms underlying gastric cancer aggressiveness. Studies performed in larger and more homogeneous series of patients and adequate statistical analysis are warranted before any of the candidate biomarkers can be implemented in the routine clinical setting for the identification of patients at higher risk and thus for the selection of candidates for adjuvant or more aggressive therapie
Colorectal liver metastasis:towards the integration of conventional and molecularly targeted therapeutic approaches
No full textRadical surgery currently represents the only treatment with curative potential for patients with colorectal cancer (CRC) liver metastases. Unfortunately, only a minority of cases is eligible for hepatic resection and many patients still develop recurrent disease, which underscores the need for more effective adjuvant treatments. In case of unresectable disease, locoregional therapeutic strategies can obtain significant tumor regression/ local disease control rates, but there is no definitive evidence of their effect on patients' survival. In regards to systemic chemotherapy, the conduction of randomized controlled trials has led to a substantial progress in terms of both tumor response and survival rates. Despite these results, most patients ultimately die of their disease due to hepatic and/or extra-hepatic cancer progression. Therefore, novel therapeutic strategies are urgently needed to improve the prognosis of patients with metastatic CRC. The elucidation of CRC biology is paving the way to the development of molecularly targeted strategies, and results from controlled clinical trials have already demonstrated that some agents targeting tumor-specific molecules can significantly improve the therapeutic efficacy of conventional antineoplastic drugs. The dissection of the molecular mechanisms of CRC metastatization and tumor/host interactions will not only accelerate the development of more effective and less toxic anticancer strategies but also will allow for the personalization of the therapeutic regimen according to the molecular features of individual patients and their tumors. Only the broader clinical implementation of these novel molecular oncology findings and the optimal integration of conventional and molecularly targeted therapeutic approaches will enable clinicians to provide patients with a better chance of cure
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