Objective
Combination of Doxorubicin (Dox) and the monoclonal antibody trastuzumab (Trz) is being effectively used against breast cancer, but associated with high incidence of cardiotoxicity. The mechanisms of Dox+Trz induced synergic cardiotoxicity are still unclear. Recently the activation of the microRNA 146a has been shown to have a role in the synergistic effect of Dox and Trz cardiotoxicity. MicroRNAs (miRNA) are ~22 nucleotides long non-coding RNAs regulating complex cellular processes. MiRNAs can be detected in the systemic circulation and their levels increase under various stress conditions. Growing body of evidence suggests that circulating miRNAs are actively released and may act as signaling molecules on close or even distant target cells. Mechanism of miRNA secretion is not completely characterized Recent literature suggests a intriguing idea that the nucleolus may play a critical role during miRNA release and reuptake . The short term goal of this proposal is to identify a diagnostic signature of circulating miRNA in response to Dox+Trz treatment. The long term goal is to study the mechanisms of release and reuptake of miRNAs and demonstrate the role of the nucleolus in these processes. Specific tasks will focus on: 1) Analysis of circulating miRNAs from plasma of mice treated with Saline, Dox or Dox+Trz. 2) Identification of secreted miRNAs in response to Dox, Trz , and Dox+Trz in adult human cardiac stromal cells (hCStCs) and cardiac progenitor cells (hCPCs). 3) Study the mechanism/s of release and uptake of miRNAs upon stress. 4) Role of the nucleolar protein nucleophosmin (NPM) on miRNAs export and uptake upon stress. Significance is the delineation of new mechanisms controlling myocardial stress response and identification of molecular interventional targets that mitigate drug-mediated cardiotoxicity and improve myocardial survival.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics nucleotides
- natural sciences biological sciences genetics RNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2011-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
20121 Milano
Italy
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