ABSTRACT
Prostate cancer and diabetes are the two highly prevalent health problems in men worldwide and have a high mortality rates but their association is quite complex and contradictory. This review reported several population based studies which tried to establish a possible association and explains the mechanism by which diabetes exhibits its effect on prostate cancer progression. It also explores the literature around the expression of various receptors and genes which enlightens the possible molecular basis of association and the effect of current antidiabetic drugs like metformin and insulin on the growth and advancement of prostate cancer in diabetic men. Masking of early tumor detection by diabetes might be the possible explanation for the reported inverse association with worse prognosis and shorter survival rate in diabetic prostate cancer patients.
ABSTRACT
Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.
Subject(s)
Carcinoma, Renal Cell , Cell Proliferation , Prognosis , Receptor, IGF Type 1ABSTRACT
The aim of this study was observe differences in the immunological distribution of the placental lactogene and IGF-1 receptor on free-chorionic villi, between studied groups and to relate the neonatal diagnosis of PEG with morphometric and immunohystochemical characteristics of the placenta. A total of, twelve placentas from AEG newborn and twelve from PEG newborn were obtained from the Maternity Ward of Temuco, Chile. H&E, Alcian blue and Masson's trichromic stains, as well as Hematoxilyn-PAS. In the immunoperoxidase technique, were used: 1) placental lactogen (polyclonal, dilution 1:200, NCL-PLP, Novocastra) 2) Insuline-1 like growth factor (monoclonal, dilution 1:200, NCL-GHR, Novocastra). Differences between PEG and AEG placentae in the immnunostaing for placental lactogen and IGF-1 receptor in the sincitial throphoblast were not observed.
El objetivo de este estudio fue observar diferencias en la distribución del lactogeno placentario y receptor del factor de crecimiento similar a la insulina, entre placentas de recién nacidos normales para la edad gestacional AEG y pequeños para la edad gestacional PEG. Un total de 12 placentas de recién nacidos AEG y 12 PEG obtenidas de la maternidad del Hospital de Temuco, Chile fueron procesadas con técnicas histológicas H&E, azul de Alcián y un método de tinción tricrómico. La técnica de inmunoperoxidasa utilizada fue: 1) lactogeno placentario (pohclonal, dilución 1:200, NCL-PLP, Novocastra) 2) Factor de crecimiento similar a la insulina (monoclonal, dilución 1:200, NCL-GHR, Novocastra). No se observaron diferencias en la distribución de lactogeno placentario ni factor de crecimiento similar a la insulina entre las placentas provenientes de recién nacidos pequeños para la edad gestacional y adecuados para la edad gestacional.