RESUMO
Background: Leptin, an adipocytokine functions via the leptin receptor, OB-Rb that contains an intact intracellular domain and activates the JAK/STAT signalling cascade. It stimulates growth, migration and invasion of cancer cells in vitro potentiating angiogenesis. Recently, the involvement of leptin in tumor progression is being explored. Gliomas exhibit poor prognosis, low survival rates demanding for novel therapeutic regimens resulting in discovery of many potential biomarkers and pharmaceutical targets. We analysed the potential role of leptin and OB-Rb in carcinogenesis of malignant gliomas. Methods: Sixty fresh tissue samples of diffuse gliomas were collected after tumor excision. Real time PCR, immunohistochemical (IHC) analysis and western blot analysis were carried out to assess the expression of leptin and its receptor. Results: The present study demonstrates the expression of leptin and LepR and their involvement in tumor progression. Of the 60 cases, 57 cases (95%) and 53 cases (88.3%) showed amplification for leptin and OB-Rb respectively. The expression of these proteins were measured semi-quantitatively and correlated with degree of malignancy (p<0.05). The bands were visualised on western blot. Conclusion: Leptin may be valued as a pharmaceutical target and anti-leptin compounds could be developed as drugs in mono- or combined therapies for these tumors.
Assuntos
Astrocitoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Carcinogênese/metabolismo , Leptina/metabolismo , Oligodendroglioma/metabolismo , Receptores para Leptina/metabolismo , Adulto , Idoso , Astrocitoma/genética , Astrocitoma/patologia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Feminino , Seguimentos , Humanos , Leptina/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Oligodendroglioma/genética , Oligodendroglioma/patologia , Estudos Prospectivos , Receptores para Leptina/genéticaRESUMO
INTRODUCTION: The role of Vascular Endothelial Growth Factor (VEGF) in angiogenesis has been extensively studied in gliomas, such as astrocytoma and oligodendrogliomas, worldwide. However, there is limited information available with regard to the Indian population. AIM: To study, whether VEGF is expressed in the Indian population in a pattern similar to that in other population. MATERIALS AND METHODS: In this prospective study approved by the Institute Ethics Committee for Human Studies at Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER) the patients operated for glioma in 2014 and 2015 (n = 60) were included. Tumours were graded as per the World Health Organization (WHO) grading system. VEGF expression in various grades was analysed using immunohistochemistry. RESULTS: Of the 60 patients included in this study, 15 were Grade II- (diffuse astrocytomas - 12; oligodendrogliomas- 3), 15 were Grade III-(anaplastic astrocytomas- 2; anaplastic oligodendrogliomas - 13) and 30 were Grade IV-glioblastomas. For VEGF antibody staining, two patients (3.33%) showed negative results and 58 patients (96%) showed positive results. VEGF positivity was 100% in Grade II and III, while it was 93.3% (28/30) in Grade IV tumours (p=0.012). CONCLUSION: The expression of VEGF was associated with the grade of tumour, which gradually increased from Grade II to Grade IV. We conclude that VEGF-regulated angiogenesis plays an important role in tumour progression of astrocytomas and oligodendrogliomas in the Indian population as observed worldwide.
