Modulation of tumor perfusion as a strategy to improve the distribution of chemotherapeutic drugs in a melanoma model

• Grant number: 13/06120-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2013
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Roger Chammas
• Grantee: Roger Chammas
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

A critical issue in the treatment of cancer patients is the accessibility of chemotherapeutic drugs to tumors after its systemic administration. The high tumor interstitial pressure, a result of the high permeability of tumor vessels and of the low tumor lymphatic irrigation, hinders the intratumoral infusion of molecules circulating throughout the bloodstream, which characterizes an obstacle to the therapeutic efficacy.The use of hypertonic solutions seems to be an interesting approach to increase the colloidosmotic and hydrostatic pressures in the plasma and, thus, reduces the differences between blood vessel and tumor interstitium pressures, resulting in an improved transcapillary transport.Based on this, we propose in this project to evaluate if transient changes in the hydrostatic blood pressure through the use of hypertonic solutions favor the perfusion and the distribution of agents with therapeutic potential in an experimental melanoma model. To achieve this objective, we will use cisplatin, a low-molecular-weight cytotoxic chemotherapeutic drug, and a monoclonal antibody specific for fibroblast growth factor 2 (FGF-2), a critical factor for melanoma angiogenesis and metastasis. We will use non-invasive in vivo imaging methods, such as SPECT and ultrasound, as well as histological and molecular approaches to access the tumor uptake of these agents when administered in hypertonic solutions and the tumor response behind this uptake. The results to be obtained will help us to improve the way we manage chemotherapeutic drugs in order to achieve a better antitumor efficacy. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SAITO, RENATA DE FREITAS; TORTELLI, JR., THARCISIO CITRANGULO; JACOMASSI, MAYARA D'AURIA; OTAKE, ANDREIA HANADA; CHAMMAS, ROGER. Emerging targets for combination therapy in melanomas. FEBS Letters, v. 589, n. 22, SI, p. 3438-3448, NOV 14 2015. (13/06120-8)

SAITO, RENATA DE FREITAS; TORTELLI, THARCISIO CITRANGULO, JR.; JACOMASSI, MAYARA D'AURIA; OTAKE, ANDREIA HANADA; CHAMMAS, ROGER. Emerging targets for combination therapy in melanomas. FEBS Letters, v. 589, n. 22, p. 11-pg., 2015-11-14. (13/06120-8)

FERREIRA CARDOSO, ANA CAROLINA; DE SOUSA ANDRADE, LUCIANA NOGUEIRA; BUSTOS, SILVINA ODETE; CHAMMAS, ROGER. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments. FRONTIERS IN ONCOLOGY, v. 6, MAY 23 2016. (13/06120-8)

CARNACHO, XIMENA; MACHADO, CAMILA LONGO; GARCIA, MARIA FERNANDA; GAMBINI, JUAN PABLO; BANCHERO, AGUSTINA; FERNANDEZ, MARCELO; ODDONE, NATALIA; ZANATTA, DANIELA BERTOLINI; ROSAL, CAROLINA; BUCHPIGUEL, CARLOS ALBERTO; et al. Technetium-99m-or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma. ONCOLOGY, v. 92, n. 4, p. 229-242, 2017. (13/06120-8)

DE AGUIAR, RODRIGO BARBOSA; PARISE, CAROLINA BELLINI; TEIXEIRA SOUZA, CAROLINA ROSAL; BRAGGION, CAMILA; QUINTILIO, WAGNER; MORO, ANA MARIA; NAVARRO MARQUES, FABIO LUIZ; BUCHPIGUEL, CARLOS ALBERTO; CHAMMAS, ROGER; DE MORAES, JANE ZVEITER. Blocking FGF2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings. Cancer Letters, v. 371, n. 2, p. 151-160, 2016. (09/18631-1, 98/14247-6, 13/06120-8)

PATINO, ANGELICA M.; JUNQUEIRA, MARA S.; ZHANG, XIAOMENG; BAILEY, KATE; IBRAHIM-HASHIM, ARIG; GILLIES, ROBERT J.; CHAMMAS, ROGER. Transient increase of tumor perfusion using hypertonic saline. MOLECULAR CANCER THERAPEUTICS, v. 17, n. 1, p. 2-pg., 2018-01-01. (13/06120-8, 15/22814-5)