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Apotherapy: Research Activities

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Research Activities Content : Dissemination of Knowledge
Posted by admin on Friday, October 03 @ 12:27:33 EEST (3976 reads)

Eliopoulos AG: "Make and Brake" in Cell Signaling. Science 2008, 321: 648-649.
Moschonas A, Kouraki M, Knox PG, Thymiakou E, Kardassis D & Eliopoulos AG: CD40 Induces antigen transporter and immunoproteasome gene expression in carcinomas via the coordinated action of NF-kappaB and of NF-kappaB-mediated de novo synthesis of IRF-1. Mol. Cell. Biol. 2008, 28: 6208-6222.
Loskog A and Eliopoulos AG: CD40 Ligand-based Cancer Therapy. In: New Gene Therapy & Cancer Research, 2008, pp 1-7. Ed. WB Gustaffsson, Nova Publishing Group.
Bauerschmitz GJ, Kangasniemi L, Pesonen S, Eriksson M, Porten M, Herrmann I, Virkkunen P, Tarkkanen M, Ranki T, Hakkarainen T, Kanerva A, Rein D & Hemminki A. Tissue specific promoter controlled oncolytic adenoviruses for killing of CD44+CD24-/low breast cancer cells. Cancer Res. 2008; 68: 5533-9.
Sala G, Dituri F, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M: Phospholipase C gamma1 is required for metastasis development and progression. Cancer Res. 2008; 68: 10187-10196.
Sarkioja M, Pesonen S, Raki M, Hakkarainen T, Salo J, Kanerva A & Hemminki A. Changing the adenovirus fiber for retaining gene delivery efficacy in the presence of neutralizing antibodies. Gene Ther. 2008;15: 921-9.
Krcova Z, Ehrmann J, Krejci V, Eliopoulos A, Kolar Z. Tpl-2/cot and cox-2 in breast cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008; 152: 21-5.
Sarkioja M, Eriksson M, Ristimäki A, Desmond RA, Hakkarainen T, Kanerva A, Hemminki A. The cyclo-oxygenase 2 promoter is induced in non-target cells following adenovirus infection, but an AU-rich 3' UTR destabilization element can increase specificity. J Gene Med. 2008; 10:744-53.
Raki M, Sarkioja M, Desmond RA, Chen D-T, Hemminki A and Kanerva A. Oncolytic adenovirus Ad5/3-?24 and chemotherapy for treatment of orthotopic ovarian cancer. Gynecol Oncol, 2008;108:166-72.
Ribacka C and Hemminki A. Virotherapy as an approach against cancer stem cells. Curr Gene Ther. 2008;8:88-96.
 
CD40, cancer, therapy, PI3 kinase, immunotherapy, gene therapy, signaling, European Commission Program, FP6, Virtual Medical Lab, Faculty of Medicine, University of Crete
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Research Activities Content : Summary
Posted by admin on Monday, May 07 @ 17:09:17 EEST (2809 reads)

Apotherapy: CD40 ligand-based modalities for the treatment of cancer.

Project Summary

Cancer is a major disease which is responsible for approximately 23% of all deaths in the European Union. Epithelial tumours, such as those of the ovary, lung and oesophagus, have particularly poor prognosis, with only a minority of patients achieving a 5 year survival. Conventional treatments, including chemotherapy and radiotherapy, have limited efficacy and frequently cause severe side effects in the patients.

The Apotherapy project brings together expertise from academic and biotechnology sectors across 7 European countries with the aim to develop and validate novel anti-cancer agents with wide therapeutic index and minimal side-effects. The focal point of our research is the utilisation of combined approaches which attack the tumour cell at multiple levels, achieving maximal apoptosis while limiting the risk of drug resistance. These approaches involve the efficient delivery of a pro-apoptotic molecule to cancer cells in combination with inhibitors of anti-apoptotic signal transduction pathways.

Specifically, the project will formulate therapeutic strategies which exploit the ability of CD40 ligand (CD40L), a TNF family member, to reduce proliferation, promote apoptosis and activate anti-tumor immune responses selectively in cancer cells. Apotherapy will develop state-of-the-art vehicles for the efficient delivery of CD40L to cancer cells, such as CD40L-encapsulated liposome formulations and recombinant adenoviruses expressing CD40L and examine their in vitro and in vivo effects on tumour cell growth and metastasis.

Apoptosis induced by CD40 engagement is dramatically augmented in the presence of inhibitors of the phosphoinositide 3-kinase (PI3 kinase) pathway which is frequently found activated in human tumours. The Apotherapy project will expand on the development of novel PI3 kinase antagonists and evaluate their in vitro and in vivo capacity to kill tumour cells and to amplify the CD40L-mediated effects on carcinoma cell growth, angiogenesis and metastasis.

The Apotherapy project is expected to lead to the development of novel anti-cancer strategies which will be directly applicable to the clinic for the benefit of cancer sufferers. The strong focus on translational research will translate R&D results into tangible benefits for health, science and economy in Europe.
CD40, cancer, therapy, PI3 kinase, immunotherapy, gene therapy, signaling, European Commission Program, FP6, Virtual Medical Lab, Faculty of Medicine, University of Crete
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