(5-(2-4-bis((3s)-3-methylmorpholin-4-yl)pyrido(2-3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol and Kidney-Neoplasms

(5-(2-4-bis((3s)-3-methylmorpholin-4-yl)pyrido(2-3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol has been researched along with Kidney-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for (5-(2-4-bis((3s)-3-methylmorpholin-4-yl)pyrido(2-3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol and Kidney-Neoplasms

ArticleYear
The role of stearoyl-coenzyme A desaturase 1 in clear cell renal cell carcinoma.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016, Volume: 37, Issue:1

    This study aimed to investigate the correlations of stearoyl-coenzyme A desaturase 1 (SCD-1) with clear cell renal cell carcinoma (ccRCC) severity and PI3K-AKT-mTOR signaling pathway. From 2004 to 2006, tumor tissue and normal pericarcinomatous tissue from ccRCC samples were collected from ccRCC patients at Renji Hospital of Shanghai Jiaotong University. The expression of SCD-1 in the collected ccRCC samples and four cell lines (A498, 769-P, 786-O, and CAKI) was detected by Western blot. The correlation between SCD-1 expression and ccRCC severity was also analyzed by immunohistochemistry. Stable 786-O and 769-P ccRCC cells expressing SCD-1 short hairpin RNA (shRNA) were constructed, and the expression of proteins in the PI3K-AKT-mTOR signaling pathway was also detected. Finally, the inhibitory effect of PI3K-AKT-mTOR inhibitors (PI103, MK2206, rapamycin, AZD8055, and RAD001) on ccRCC cells stably expressing SCD-1 shRNA was also measured. Higher SCD-1 expression level was observed in ccRCC tissues compared with normal tissues. SCD-1 expression level was the highest in 786-O. SCD-1 expression was positively correlated with the tumor-node-metastasis (TNM) stage, grade of tumor cells, and lymphatic metastasis. There were no changes in the expression of AKT, ERK, PI3K, and PDK1. Significant differences were observed in the expression of p-AKT (at the Ser473 and Thr308 site), p-ERK, and two mTOR downstream molecules (4E-BP1 and p-P70S6K1) in cells stably expressing SCD-1 shRNA. PI103 and AZD8055 could enhance the inhibitory effect of SCD-1 interference on proliferation and migration of 786-O and 769-P cells. AZD8055 is recommended for the combined ccRCC treatment with shRNA interference.

    Topics: Carcinoma, Renal Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Everolimus; Female; Furans; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Heterocyclic Compounds, 3-Ring; Humans; Inhibitory Concentration 50; Kidney Neoplasms; Lymphatic Metastasis; Male; Morpholines; Pyridines; Pyrimidines; RNA Interference; Signal Transduction; Stearoyl-CoA Desaturase

2016
Benchmarking effects of mTOR, PI3K, and dual PI3K/mTOR inhibitors in hepatocellular and renal cell carcinoma models developing resistance to sunitinib and sorafenib.
    Cancer chemotherapy and pharmacology, 2013, Volume: 71, Issue:5

    To evaluate first-generation rapamycin analogs (everolimus, temsirolimus, and rapamycin) and second-generation drugs inhibiting mTOR kinase (AZD-8055), PI3K (BKM-120) or both (BEZ-235 and GDC-0980) in hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) cells characterized for acquired resistance to sorafenib or sunitinib.. Anti-proliferative (MTT assay) and cell signaling (Western blot) effects of rapamycin analogs (1-20 μM) and second-generation drugs (0.03-20.0 μM) were assessed in human HCC SK-HEP1, RCC 786-0, and sorafenib- (SK-Sora) or sunitinib-resistant (786-Suni) cells.. In SK-HEP1 cells displaying high PTEN and Bcl2 expression, rapamycin analogs had poor anti-proliferative effects. However, SK-Sora cells were more sensitive to rapamycin analogs (≥1 μM) than SK-HEP1 cells. In 786-0 cells, lacking PTEN and Bcl2 expression, ≥1 μM rapamycin analogs blocked mTORC1 signaling, transiently activated Akt, and inhibited cell proliferation. Protracted sunitinib exposure in 786-Suni cells yielded an increase in p27 expression and a decreased sensitivity to rapamycin analogs, although mTORC1 function could be inhibited with rapamycin analogs. Second-generation drugs induced more potent growth inhibition than rapamycin analogs at concentrations >0.03 μM in parental cells, SK-Sora, and 786-Suni cells. Growth inhibitory concentrations of these new drugs also blocked mTORC1 downstream targets.. Rapamycin analogs inhibited mTORC1 downstream targets and yielded anti-proliferative effects in HCC and RCC cells. Second-generation drugs also appeared to be potent inhibitors of mTORC1 signaling; however, they appeared to be far more potent in inhibiting cellular proliferation in parental HCC and RCC cells and in cells developing resistance to sorafenib or sunitinib.

    Topics: Aminopyridines; Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Everolimus; Humans; Imidazoles; Indoles; Kidney Neoplasms; Liver Neoplasms; Mechanistic Target of Rapamycin Complex 1; Morpholines; Multiprotein Complexes; Niacinamide; Phenylurea Compounds; Phosphoinositide-3 Kinase Inhibitors; Pyrimidines; Pyrroles; Quinolines; Signal Transduction; Sirolimus; Sorafenib; Sunitinib; TOR Serine-Threonine Kinases

2013