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Investigation of the expression and activity of kallikreins during HCMV infection in tumoral cells

Abstract

Kallikreins (KLKs) are serine-proteases with tryspsin-like or chymotrypsin-like specificity. The KLK family is composed of 15 members, named as KLK1 to KLK15 comprising the largest protease genes cluster, with structural homology of approximately 40%. The KLKs are related with diverse physiological functions, such as regulatory mechanisms of skin desquamation, formation of tooth enamel, renal function, semen liquefaction, neural synaptic plasticity and bran function. In the Central Nervous System (CNS), KLK6 is the predominantly expressed, and its deregulation seems to be involved with Alzheimer's disease, Parkinson's disease, multiple sclerosis, as well as to demyelination processes. In addition, aberrant expression of KLK6 appears to be related to cell resistance to chemotherapy and radiotherapy treatments. The KLK8 is also expressed in the CNS, in areas of the limbic system, and it deregulation is related to development of schizophrenia. Recent studies demonstrated that play a role replication of Human Papillomavirus and Influenza virus. The Human Cytomegalovirus is a high prevalent viral agent worldwide. In immunocompetent individuals, the virus remains in a persistent or a latent state, characterized by absence of viral replication. However, in immunosuppressed patients such as solid-organs transplant recipients, AIDS and Cancer patients and neonates, the virus can be reactivated, leading to diverse pathologies. The presence of HCMV in tumors has been shown in diverse studies and an oncomodulatory role, augmenting cell malignancy is proposed. Gliomas are the most common CNS tumors and are classified as astrocytomas (Grade I to IV) and Olidendrogliomas (Grade II and III). Glioblastoma multiforme (GBM) or grade IV astrocytoma is the most malignant and infiltrative type of glioma with a low rate of survival. We and others reported the presence of HCMV and gliomas, especially in GBM and various ongoing studies are investigating the possible molecular mechanism related with the virus and tumoral progression. The goal of this study is to evaluate the expression and activity of calicreínas during HCMV infection in tumoral and non tumoral cells and their possible roles in viral replication and oncogenesis. (AU)

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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)
DOS SANTOS, CLAUDIA JANUARIO; FERREIRA CASTRO, FABIANE LUCY; DE AGUIAR, RODRIGO BARBOSA; MENEZES, ISABELA GODOY; SANTOS, ANA CAROLINA; PAULUS, CHRISTINA; NEYELS, MICHAEL; CALLAN DA SILVA, MARIA CRISTINA. Impact of human cytomegalovirus on glioblastoma cell viability and chemotherapy treatment. JOURNAL OF GENERAL VIROLOGY, v. 99, n. 9, p. 1274-1285, . (16/19925-2)

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