| Grant number: | 99/01229-2 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Start date: | June 01, 2000 |
| End date: | March 31, 2004 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Raul Cavalcante Maranhao |
| Grantee: | Raul Cavalcante Maranhao |
| Host Institution: | Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
Abstract
In a recently concluded project (FAPESP, proc. 1995/0591), we showed the usefulness of two lipidic emulsion systems that mimick the metabolic behavior of chylomicrons (referred as artificial chylomicrons) and LDL (artificial LDL or LDE). Using the artificial chylomicrons we unraveled pronounced alterations of chylomicron metabolism in conditions with increased incidence of atherogenesis, such as Systemic Lupus Eritematosus and patients submitted to heart transplantation. Regarding LDE, we showed in clinical studies that this emulsion can be useful as vehicle for chemotherapeutic agents in cancer treatment. This allows the possibilite of drug targeting with doses much higher and reduced side effects as compared to conventional chemotherapy. The present project aims to continue those studies, by means of two distinct subprojects. In the first, entitled "Artificial lipoproteins in atherogenesis" the artificial chylomicron will be used to verify whether there are metabolic defects related to chylomicrons in post-menopausal patients with coronary artery disease (CAD), in type II diabetes with CAD and in patients with systemic arterial hypertension. In the second subproject, entitled "Use of LDE in cancer treatment", basic studies (physical-chemical, in vitro experiments with neoplastic cell lines and animal experiments) already initiated in the previous project will be pursued aiming to enlarge the understanding of the chemotherapeutic agent carmustine associated to LDE. A Phase I study of carmustine complexed with LDE will be also completed, as well as a Phase II study. In this subproject basic studies as well as phase I and phase II studies of the complex of LDE with two other chemotherapeutic agents, LDE-Etoposide and LDE-Paclitaxel (Taxol) will be pursued. In the first subproject with aim to describe chylomicron metabolism in diseases that bear increased atherogenesis and to clarify whether LDL plasma kinetics is also disturbed in those diseases. In the second subproject we aim to offer three new weapons to cancer therapeutics, namely the LDE-Carmustine, LDE-Etoposide and LDE-Paclitaxel. According to the experience so far accumulated by our group regarding LDE-Carmustine, we can foresee that the LDE method, by concentrating those drugs in the neoplastic tissues and by diminishing their flux to the normal tissues will lead to the use of much higher doses and decrease the devastating side-effects of those drugs. We then hope that the way will be paved for a real upgrade in the treatment of cancer. (AU)
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