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Effect of acetylsalicylic acid solution on colorectal tumors - in vitro study of cytological and genetic alterations in normal and tumor fragments

Grant number: 07/08611-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2008
Effective date (End): October 31, 2008
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Rogério Saad Hossne
Grantee:Enrico Salomão Ioriatti
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Effect of acetylsalicylic solution on colorectal tumors - Study of cytologic and genetic alterations in normal and tumor in vitroAbstractIn Brazil, data provided by the Ministry of Health show that malignant neoplasias is, respectively, the second and third most frequent cause of death among individuals over 40 years and individuals of all ages. Among malignant neoplasias, colorectal cancer accounts for the highest incidence and mortality rates, being the third most incident neoplasia in 2005, with approximately 26,000 new cases and an increasing mortality rate.The main prognostic and recurrence factors in neoplasia are local recurrence, staging, presence of metastasis and lymphonode involvement. Local recurrence is one of the principal factors involved in colorectal cancer survival, and is most frequently caused by the implantation of tumor cells in anastomosis, which may occur in 16% of the cases.Several authors have demonstrated the presence of viable neoplastic cells in the intestinal lumen in patients with colorectal cancer. These free tumor cells are responsible for the tumor implantation in the anastomosis through local recurrence. In this sense, some prophylacatic procedures have been aimed at avoiding both the implantation of cells in the anastomosis and local recurrence. One of these procedures is chemical lavage of the intestinal lumen, whose effects on free tumor cells viability have been largely investigated. Chemical lavage of the intestinal lumen is believed to decrease the frequency of tumor implantation in the anastomosis from 10-16% to 2-3%, through mechanical and chemical action. Prospective studied demonstrate that mere lavage with saline solution effectively reduces the viability of neoplastic cells in the intestinal lumen. Besides, saline solution, several other substances have been used for this purpose, such as povidone iodine, chlorhexidine, water, sodium hypochlorite, among others. The most commonly used, povidone iodine and chlorhexidine, have cytolytic and anti-tumoral effects proven in vitro. However, the same effectiveness has not been demonstrated in vivo.These difficulties, and the characteristics of free tumor cells implantation in the intestinal lumen in patients with colorectal cancer, warrant the development of new substances. Based on previous investigations conducted at the Experimental Surgery Laboratory of Botucatu Medical School, in which we were able to study the effects of several substances of cytolytic and histolytic effects, the idea of assessing the effect of aspirin on human tumor tissue came up.In pursuance to this line of research, we carried out, supported by Fapesp (scientific initiation scholarship), another study to evaluate the effects of intestinal lumen lavage (instillation) with the solution of aspirin in rat or rabbit normal colonic mucosa. A total of 100 animals were studied at 10, 30 and 60 minutes of exposure. Sacrifice occurred after 24, 48 and 72 hours. The following conclusions were drawn:1.Aspirin solution causes no change in the colonic mucosa of rats and rabbits.2.Due to its antitumoral and cytolytic activity, as well as low toxicity, aspirin solution may exert a potent action on the reduction free tumor cells viability in the colonic lumen.Thus, to continue following this research line, we propose to study the effect of aspirin on normal mucosa and colonic tumors in humans, to provide a foundation for the clinical application of the colon preparation in patients with colorectal tumors. ObjectiveTo assess the cytologic and genetic effects of bicarbonated acetylsalcylic acid solution, in vitro, using fragments of normal colonic mucosa and neoplastic tumor tissue from humans.