centro biotecnologie avanzate

LABORATORY OF : Vascular Biology
CONTACT PERSON: Prof. Adriana Albini (Multimedica)
Phone +39 0105737565 - 566 E-mail: adriana.albini@multimedica.it

Description of Laboratory and Expertise:

Prof. A. Albini is an expert in angiogenesis, vascular biology, inflammation and chemoprevention. She has extensive experience in oncology research, developing and utilizing “in vitro” and “in vivo” assays for the study of potential inhibitors of tumor invasion and angiogenesis.In 1987 she established the matrigel invasion assay ("chemoinvasion") the most widely used assay for testing the invasiveness of malignant cells and screening of antimetastatic drugs.She has also contributed to the development of the technique of tumor xenografting with the aid of matrigel, a reconstituted basement membrane derived from a murine sarcoma.Recently she has developed the concept of the chemoprevention in anti-angiogenesis, i.e. "angioprevention".

Abstract of Activities:

Biological mechanisms that regulate angiogenesis, formation of new blood vessels and its regulation. Physiopathology of endothelial cells towards the development of new molecular strategies for the prevention of tumors and other chronic degenerative diseases: cardiovascular, diabetes, obesity; identification of common risk factors; biological factors responsible for the promotion or inhibition of angiogenesis. Control of the microenvironment’s health. Development of therapeutic and preventive strategies. Role of endothelial progenitors in the pathogenesis and therapy of tumors and parallels with their role in coronary diseases; research of genomic and postgenomic differences responsible for pathologies correlated with inappropriate angiogenesis.
In progress we are developing a project of nanotechnology in vascular biology.

Detailed Research Activities:

Angiogenesis is necessary for solid tumor growth and dissemination and it is increasingly clear that inflammation is a key component in tumor insurgence, also involved in promoting tumor angiogenesis. We found that angiogenesis is a common and key target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in pre-malignant tumors, a concept we termed "Angioprevention”
In the last years increased evidences have underlined that microenvironment has a key role in the tumor development and progression. Inflammatory cells release several cytokines, chemokines and growth factors that play a pivotal role in the carcinogenesis. This supports our idea that the future tumor therapies should target not only the malignant cells but also the components that surround them.
In our laboratory we are studying new chemopreventive and anti-angiogenic agents that are able to modify tumor microenvironment interfering with different molecular pathways such as Akt and NF-kB. NF-kB is a crucial molecular hub during the inflammatory process and it is often hyperactivated in tumor cells; leading to an increased resistance of these cells to the apoptosis. We have shown that several chemopreventive agents are able to inhibit the NF-kB pathway, reducing its nuclear translocation and resulting in an increased susceptibility of tumor cells to apoptosis.
Furthermore we have shown that various molecules, such as flavonoids, antioxidants and retinoids, act in the tumor micro-environment inhibiting the recruitment and/or activation of endothelial cells and phagocytes of the innate immunity.
Tumor microenvironment contributes to tumor angiogenesis. All these cues released by stromal cells are potential activators of endothelial cells.Our in vivo model for angiogenesis allowed us to identify and study the cellular infiltrate that acts during tumor angiogensis.
Further, we have set up an in vivo tumor model for angiogenesis. We use KS-Imm cells derived from human Kaposi Sarcoma that is recognised to be a highly angiogenic tumor. We evaluate the ability of our angiopreventive agents to inhibit the KS-Imm growth and vascularisation.
These experimental sets allowed us to identify novel antiangiogenic compounds and to identify the molecular pathways involved in their activity.
We are now using nanotechnologies to address the endothelial cell.

Applications and Developments:

Identification of signal transduction molecules involved in the regulation of neoangiogenesis and in its inhibition. Identification of genes involved in neovascularization in “in vitro” and animal angiogenesis models. Identification of natural and synthetic chemopreventive molecules and diet factors that can prevent chronic degenerative diseases.
New diagnostic and therapeutic tools.

Managed core facilities:

Angiogenesis battery of assays.

Ongoing collaborations:

IRCCS Multimedica, Milano, Italy
University of Insubria, Varese, Italy
University of Padova, Italy
University of Torino, Italy

Most recent and significant publications:

Pfeffer U., Ferrari N., Dell’Eva R., Indraccolo S., Morini M., Noonan D.M., Albini A.

Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.

Ferrari N., Pfeffer U., Dell’Eva R., Ambrosiani C., Noonan D.M., Albini A.
The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide. Clin Cancer Res. 2005 Jun 15;11(12).

Albini A., Tosetti F., Benelli R., Noonan D.M. Tumor inflammatory angiogenesis and its chemoprevention. Cancer Res. 2005 Dec 1;65(23):10637-41.

Benelli R., Loruso G., Albini A., Noonan M.D. Cytokines and chemokines as regulators of angiogenesis in health and disease. Curr Pharm Des. 2006;12(24):3101-15.

Venè R., Arena G., Pogi A., D’Arrigo C., MorminoM., Noonan D.M., Albini A., Tosetti F.

Novel cell death pathways induced by N-(4-hydroxyphenyl)retinamide: therapeutic implications. Mol Cancer Ther. 2007 Jan;6(1):286-98.

Dell’Eva R., Ambrosini C., Vannini N., Piaggio G., Albini A., Ferrari N. AKT/NF-kappaB inhibitor xanthohumol targets cell growth and angiogenesis in hematologic malignancies. Cancer. 2007 Nov 1;110(9):2007-11.

Albini A., Mirisola V., Pfeffer U. Metastasis signatures: genes regulating tumor-microenvironment interactions predict metastatic behavior. Cancer Metastasis Rev. 2008 Mar;27(1):75-83.

Dell’Eva R., Ambrosini C., Minghelli S., Noonan D.M., Albini A., Ferrari N. The Akt inhibitor deguelin, is an angiopreventive agent also acting on the NF-kappaB pathway. Carcinogenesis. 2007 Feb;28(2):404-13.

Larghero P., Venè R., Minghelli S., Travaini G., Morini M., FerrariN., Pfefer U., Noonan D.M., Albini A., Benelli R. Biological assays and genomic analysis reveal lipoic acid modulation of endothelial cell behavior and gene expression. Carcinogenesis. 2007 May;28(5):1008-20.

Albini A., Fascina G., Nicolò M., Dell’Eva R., Venè R., Cammarota R., Barberis M., Noonan D.M. Inhibition of a vascular ocular tumor growth by IL-12 gene transfer. Clin Exp Metastasis. 2007;24(7):485-93.

Patents:

1996 "HCG (gonadotropina corionica) come inibitore della collagenasi"- Brevetto per Inventore Industriale a nome Ares Serono Holding N.V.

1997 "Composizione farmaceutica atta a inibire la formazione di metastasi tumorali"- brevetto Italiano a nome Zambon Group S.p.A

2000 "Peptidi ad attivita' chemiotattica e anti- HIV (3 sottobrevetti) - Brevetto a nome A. Albini

2004 "Sostanze ad attivit‡ antinfiammatoria"- Brevetto USA

2005 Attività antineoplastica di una molecola polimerica isolata da un porifero marino mediterraneo

2006 "Peptidi di angiostatina e suoi impieghi terapeutici" brevetto esteso al estero

2006 "Peptide antiangiogenico e suoi impieghi terapeutici" - brevetto in fase id estensone al estero

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