RESUMO
BACKGROUND: Colorectal carcinoma (CRC) is one of the common carcinomas with a rising incidence of metastasis due to its advanced stage of presentation. The existing biomarkers such as CEA (Carcinoembryonic antigen) etc., for prognosis, have low sensitivity and specificity. Hence a need for a newer definitive biomarker. Obesity is the leading cause of CRC. Leptin and adiponectin secreted by adipose tissue have been studied as potential biomarkers in the field of CRC. The present study helps to understand the association of leptin and adiponectin receptors with clinicopathological parameters. OBJECTIVE: To correlate the various clinicopathological parameters with the tissue expression of leptin and adiponectin receptors in CRC. METHODS: It is a cross-sectional prospective study conducted at a tertiary care hospital. Formalin fixed paraffin blocks of all radical resection CRC cases were collected and immunohistochemistry (IHC)was carried out on tumor tissue for leptin and adiponectin receptor. Tumor characteristics and clinical parameters were collected from the hospital medical records. Pearson's correlation coefficient test was used. RESULTS: Immunohistochemistry was performed on 60 cases of CRC. Significant positive correlation of leptin was observed with size, lymph node metastasis, advanced stage, and grade of tumor (P<0.05). A significant correlation between adiponectin receptor and CRC was observed concerning age, stage, lymph node metastasis, distant metastasis and grade of tumor. CONCLUSION: Positive expression of leptin and negative expression of adiponectin receptors in CRC helps to predict the risk of metastasis.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Imuno-Histoquímica , Leptina , Estadiamento de Neoplasias , Receptores de Adiponectina , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Estudos Transversais , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Leptina/metabolismo , Leptina/análise , Receptores de Adiponectina/análise , Receptores de Adiponectina/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Adulto , Receptores para Leptina/metabolismo , Receptores para Leptina/análise , Gradação de Tumores , Metástase LinfáticaRESUMO
PURPOSE: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. METHODS: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. RESULTS: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). CONCLUSION: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.
Assuntos
Calcitriol/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Triglicerídeos/sangue , Animais , Glicemia/análise , Western Blotting , Peso Corporal , Diabetes Mellitus Tipo 2/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Lipase Lipoproteica/análise , Lipase Lipoproteica/efeitos dos fármacos , Masculino , Ratos Wistar , Receptores de Adiponectina/análise , Receptores de Adiponectina/efeitos dos fármacos , Valores de Referência , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacosRESUMO
Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.
Assuntos
Animais , Masculino , Triglicerídeos/sangue , Calcitriol/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Valores de Referência , Glicemia/análise , Peso Corporal , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Regulação para Cima , Western Blotting , Reprodutibilidade dos Testes , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Receptores de Adiponectina/análise , Receptores de Adiponectina/efeitos dos fármacos , Lipase Lipoproteica/análise , Lipase Lipoproteica/efeitos dos fármacosRESUMO
Hyperandrogenemia, hyperinsulinemia, and obesity affect 60-70% of patients with Polycystic Ovarian Syndrome (PCOS), who exhibit an altered endometrial insulin signaling. The aim of the study was to evaluate whether hyperandrogenism, hyperinsulinism, and obesity present in PCOS patients impair the endometrial adiponectin signaling pathway. The ex vivo study was conducted on 27 samples from lean (n=9), obese (n=9), and obese-PCOS (n=9) patients. The in vitro assays were performed in immortalized human endometrial stromal cells stimulated with testosterone, insulin, or testosterone plus insulin. Serum steroid-hormones, adiponectin, glucose, and insulin; body mass index, free androgen index, ISI-Composite, and HOMA were evaluated in the 3 groups. Ex vivo and in vitro gene expression and protein content of adiponectin, AdipoR1, AdipoR2, and APPL1 were determined. Adiponectin serum levels were decreased in obese-PCOS patients compared to lean (78%) and obese (54%) controls (p<0.05). AdipoR1 protein and gene expression were increased in obese group vs. obese-PCOS and lean groups (2-fold, p<0.05). In turn, AdipoR2 protein and mRNA content was similar between the 3 groups. APPL1 protein levels were reduced in endometria from both obese groups, compared to lean group (6-fold, p<0.05). Testosterone plus insulin stimulation of T-HESC and St-T1b leads to a reduction of adiponectin, AdipoR1, AdipoR2, and APPL1 protein content in both endometrial cell lines (p<0.05), whereas, in the presence of testosterone or insulin alone, protein levels were similar to basal. Therefore, endometrial adiponectin-signaling pathway is impaired in hyperandrogenemic and hyperinsulinemic obese-PCOS patients, corroborated in the in vitro model, which could affect endometrial function and potentially the implantation process.