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Functional analysis of genes involved in carcinogenesis and development of penile cancer

Grant number: 09/11203-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2010
Effective date (End): November 30, 2013
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Paula Rahal
Grantee:Marilia de Freitas Calmon Saiki
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
Associated research grant:09/52088-3 - Cancer of the penis, a real Brazilian problem: from morphology to molecular etiopathogenesis, AP.TEM

Abstract

In the USA, the incidence for the penile cancer is 0.2/100.000 inhabitants and it is nearly zero in Israeli. However, it is a considerable health problem in developmental countries and may constitute almost 10% of the total malignances in men in some countries of Africa and South America. In Brazil, this type of tumor represents 2% out of all cases in men and it is more frequent in the north and northeast than in the south and southeast. In regions of high incidence, the cancer of the penis surpasses the cases of prostate cancer and bladder cancer. Although the squamous cell carcinoma of the penis can occur in any age, the majority of the cases affect men with advanced age and its peak of incidence is about 60 years old. Among the risk factors for this type of cancer are poor conditions of hygiene in non- circuncised men, the accumulation of the smegma on the skin of the foreskin, the fimosis, preexisting diseases like HIV and HPV infections, cigarette consumption and extended exposition to UV radiation. The cancer of the penis has, in the majority, squamous epithelial origin and includes carcinomas in situ, that are restricted to the epithelium and they don't infiltrate the inferior layer of the derma and invasive carcinomas, represented by squamous cell carcinomas and its variant of low degree well differentiated, the verrucous carcinoma. The clinic presentation of the penile carcinoma is varied from a small excrescence, pustule or warty growth to extensive carcinoma with desquamation. The progression of the cancer of the penis occurs in a locoregional, with sequential involvement of inguinal and pelvic lymphonodus before the development of distant metastasis. The common sites for the metastasis include lung, brain and bone. The recurrence of the tumor can develop inside of the lymphatic system with discrete nodules or in distant sites as has been established. The death of the individuals occurs frequently in consequence of starvation and sepsis or of bleeding as a result of the eruption of femoral vessels caused by ulceration of inguinal metastasis. The knowledge about pathogenic changes that occur in the cancer of the penis is still very limited mainly because of a small number of samples and scarcity of pathologic tissues for pre clinic research. The researches in the pre clinic or clinic level have been focused in viral associations, though genetic and molecular factors also play an important role in the carcinogenesis of the penis being that many of these factors are independent of the HPV infection. The cancer of the penis is a rare disease and there are few studies about the molecular alterations in this type of cancer. So, it is fundamental to study the genetic changes that occur in the cancer of the penis and the role of the genes for the carcinogenesis and development of the penile cancer. Functional studies has demonstrated an immense efficiency in providing new data about how certain genes can influence in the imbalance of the cellular homeostasis and the possible consequences in the carcinogenesis. Thus, the functional analysis of the specific genes can reveal how they act in the control of the growth and cellular differentiation, cellular metabolism, apoptosis and tumor genesis, helping in the identification of molecular markers for an early diagnostic, identification of prognostic markers and in the design of the disease treatment. For these reasons, the aim of this project is analyzing the mechanisms of action of the selected genes by several functional studies, trying with this, to identify in which pathways they are inserted. (AU)

Scientific publications
(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)
CALMON, MARILIA FREITAS; SICHERO, LAURA; BOCCARDO, ENRIQUE; VILLA, LUISA LINA; RAHAL, PAULA. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines. VIROLOGY, v. 496, p. 35-41, SEP 2016. Web of Science Citations: 3.
CALMON, MARILIA FREITAS; DE OLIVEIRA MOTA, MANLIO TASSO; BABETO, ERICA; CANDIDO, NATALIA MARIA; GIROL, ANA PAULA; MENDIBURU, CARLOS FABIAN; BONILHA, JANE LOPES; DUARTE SILVESTRE, RODRIGO VELLASCO; ROSA, BRUNO MIZIARA; THOME, JORGE ALBERTO; AMERICO MEDEIROS, GUSTAVO HERNANDEZ; SOARES, FERNANDO AUGUSTO; GUIMARAES, GUSTAVO CARDOSO; FERRAZ DE ARRUDA, JOSE GERMANO; OLIANI, SONIA MARIA; VILLA, LUISA LINA; VASSALLO, JOSE; RAHAL, PAULA. Overexpression of ANXA1 in Penile Carcinomas Positive for High-Risk HPVs. PLoS One, v. 8, n. 1 JAN 14 2013. Web of Science Citations: 13.
CALMON, MARILIA FREITAS; DE SOUZA, ARYANE TOFANELLO; CANDIDO, NATALIA MARIA; BARTOLOMEU RAPOSO, MARIA IRENE; TABOGA, SEBASTIAO; RAHAL, PAULA; NERY, JOSE G. A systematic study of transfection efficiency and cytotoxicity in HeLa cells using iron oxide nanoparticles prepared with organic and inorganic bases. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 100, p. 177-184, DEC 1 2012. Web of Science Citations: 21.

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