1. Therapy for non-muscle invasive bladder cancer: HP-NAP
- Author
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Francesco Pagano, Alessio Filianoti, Fabio Munari, Matteo Fassan, Luca Di Gianfrancesco, Marina de Bernard, Pierfrancesco Bassi, Marco Racioppi, Gaia Codolo, Massimo Rugge, Mario Milco D'Elios, and Daniele D'Agostino
- Subjects
CD4-Positive T-Lymphocytes ,medicine.medical_specialty ,medicine.medical_treatment ,Angiogenesis Inhibitors ,CD8-Positive T-Lymphocytes ,Cystectomy ,Mice ,Lymphocytes, Tumor-Infiltrating ,Immune system ,Adjuvants, Immunologic ,Bacterial Proteins ,Cell Movement ,In vivo ,Bladder Neoplasm ,Animals ,Humans ,Medicine ,Neoplasm ,Neoplasm Invasiveness ,Tumore della Vescica ,Carcinoma, Transitional Cell ,Bladder cancer ,Helicobacter pylori ,Neovascularization, Pathologic ,business.industry ,Settore MED/24 - UROLOGIA ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,Toll-Like Receptor 2 ,Neoplasm Proteins ,Tumor Burden ,Surgery ,Mice, Inbred C57BL ,HP-NAP ,Administration, Intravesical ,Urinary Bladder Neoplasms ,Cancer research ,Tumor necrosis factor alpha ,Immunotherapy ,Lymph Nodes ,business ,CD8 - Abstract
Purpose Patients with non-muscle invasive bladder cancer recurrence after 2 induction courses of BCG are eligible for radical cystectomy. So, in the last years research to discover new drugs for the management of non-muscle invasive bladder cancer recurrence after failure of first and second line therapy is ongoing. In accordance to the results obtained with BCG, whose mechanism depends on the induction of the T helper 1 (TH1) immune response, we investigated the activity of a Toll-like receptor (TLR) 2 ligand, named Helicobacter Pylori Neutrophil Activating Protein (HP-NAP), that we recently demonstrated being able of enhancing the differentiation of Th1 cells, both in vitro and in vivo, because of its ability to create an IL-12 enriched milieu. Materials and Methods We show here, in a mouse model of bladder neoplasm implants, that local administration of HP-NAP decreases tumor growth by inducing tumor necrosis. Results The result is joined up with a massive cluster of both CD4+ and CD8+ IFN-γ+ cells, within neoplasm and regional lymph nodes. It is of note that HP-NAP-treated tumors show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Conclusions The present study suggests that the activity of HP-NAP against urothelial tumor burden warrants subsequent in vivo studies.
- Published
- 2012