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WG3: Gianni Sava (Italy) - New targets for metal-based drugs: beyond DNA

Novel Bifunctional anti-Cancer Metallodrugs - Synthesis and Pharmacological Evaluation

Callerio Foundation Onlus has gained a leadership role in the study of the pharmacological properties of metal-based compounds, active against metastases of solid malignant tumours (e.g. carcinomas).

These studies, initially done in collaboration with researchers of the Departments of Chemical Sciences and of Biomedical Sciences of the University of Trieste were subsequently extended to the collaboration to research groups of other Universities such as Bari, Florence, Padua and Sassari. Such collaborations allowed to point out a common strategy for these studies. The main goal was that of understanding the potential offered by metals, in order to “build-up” drugs oriented to prevent and treat metastases of solid malignant tumours. In this context, a relevant role has been taken by LINFA, the specialised laboratory opened within Callerio Foundation in the late 1999. Such laboratory, with the determinant financial support of CRTrieste Foundation, alowed to establish a Research Network that, besides the research groups mentioned above, includes researchers from the Universities of Seville (Spain), Vienna (Austria), Leiden (The Netherlands), Athens (Greece), Brno (Czech Republic), Lousanne (Switzerland) and Dublin (Ireland).

Aim of the present Research Project is, therefore, to open a new road in the pharmacological approach to tumour treatment. Our proposal is to study new molecules, based on metals of the VIII group, such as ruthenium, that can be effective in order to control the post-transcriptional functions of proteins involved in tumour malignancy.
The results expected from the activation of the present Project of Research are the following:

a) acquiring more knowledge in the field of tumour pharmacology;
b) starting of an innovative research field;
c) training of young scientific Researchers in a field that can be considered very important for the amelioration of the quality of life and human health.

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Proposed Start Date: May 2001

This study is aimed at three major goals.
First, to examine a number of complexes of ruthenium and of other transition metals belonging to VIII group in order to set up a sequence of experimental in vitro assays with the purpose of predicting their selective antimetastatic activity in vivo.
Second, to identify the nature and the biological relevance for the interaction of ruthenium complexes with the components of the extracellular matrix.
Third, to ascertain the existence of a cell membrane receptor for ruthenium complexes, responsible for the non cytotoxic effects on solid tumour metastases.
The ultimate goal of this study is the identification of a chemical structure and a biological target for the selective treatment of solid tumour metastases by interfering with the mechanism that sustains the malignant growth. The group of laboratories involved in this study represent a wide and integrated competence on inorganic compounds which may allow the identification of a new strategy for the study of novel metal-based drugs in cancer chemotherapy.

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2001-2003

NAMI-A is a new antitumour ruthenium-based complex, conceived and developed entirely in Trieste, capable of inhibiting the occurrence and the growth of lung metastatic tumours in metastatic carcinoma study models.
The NAMI-A action is not based on letal interaction with cellular components, but rather on interference with the mechanism sustaining the metastatic tumour growth, thus reducing its malignancy. NAMI-A acts upon metastases released by solid tumours, that cannot be easily removed, and thus lead the patient to death.
NAMI-A can be the first of a new generation of innovative anti-tumour drugs featuring selective activity and low toxicity.
This project main goal is to proof that NAMI-A can modify the genectic structure of tumour metastatic cells by maintaining silent the genes sustaining the malignancy and neoplastic immortality, and activating the normal cellular growth and death.

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1998-1999

The project has the main goal of using lysozyme in aquiculture in order to enhance the immunization response of oral vaccine subministration with the purpose of reducing the disease treatement cost and the environmental impact of drugs treatment.

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