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10.1186/s12885-015-1474-8 http://scihub22266oqcxt.onion/10.1186/s12885-015-1474-8 C4460948!4460948 !26054341     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26054341 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       BMC+Cancer 2015 ; 15 (ä): 462 Nephropedia Template TP {{tp|p=26054341 |t=2015. Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma |pdf=|usr=}}{{26054341 }} gab.com Text Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma JO: BMC Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26054341 #FOAvip BACKGROUND: Malignant melanoma has an increasing incidence rate and the metastatic disease is notoriously resistant to standard chemotherapy. Loss of cell cycle checkpoints is frequently found in many cancer types and makes the cells reliant on compensatory mechanisms to control progression. This feature may be exploited in therapy, and kinases involved in checkpoint regulation, such as Wee1 and Chk1/2, have thus become attractive therapeutic targets. METHODS: In the present study we combined a Wee1 inhibitor (MK1775) with Chk1/2 inhibitor (AZD7762) in malignant melanoma cell lines grown in vitro (2D and 3D cultures) and in xenografts models. RESULTS: Our in vitro studies showed that combined inhibition of Wee1 and Chk1/2 synergistically decreased viability and increased apoptosis (cleavage of caspase 3 and PARP), which may be explained by accumulation of DNA-damage (increased expression of ?-H2A.X)--and premature mitosis of S-phase cells. Compared to either inhibitor used as single agents, combined treatment reduced spheroid growth and led to greater tumour growth inhibition in melanoma xenografts. CONCLUSIONS: These data provide a rationale for further evaluation of the combination of Wee1 and Chk1/2 inhibitors in malignant melanoma. Twit Text FOAVip Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma ????BMC Cancer http://www.kidney.de/pget.php?&tw=1&pmid=26054341 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26054341 #FOAvip English Wikipedia <ref>{{Cite pmid|26054341 }}</ref> Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma #MMPMID26054341 Magnussen GI ; Emilsen E ; Giller Fleten K ; Engesæter B ; Nähse-Kumpf V ; Fjær R ; Slipicevic A ; Flørenes VA BMC Cancer 2015[Jun]; 15 (ä): 462 PMID26054341 show ga BACKGROUND: Malignant melanoma has an increasing incidence rate and the metastatic disease is notoriously resistant to standard chemotherapy. Loss of cell cycle checkpoints is frequently found in many cancer types and makes the cells reliant on compensatory mechanisms to control progression. This feature may be exploited in therapy, and kinases involved in checkpoint regulation, such as Wee1 and Chk1/2, have thus become attractive therapeutic targets. METHODS: In the present study we combined a Wee1 inhibitor (MK1775) with Chk1/2 inhibitor (AZD7762) in malignant melanoma cell lines grown in vitro (2D and 3D cultures) and in xenografts models. RESULTS: Our in vitro studies showed that combined inhibition of Wee1 and Chk1/2 synergistically decreased viability and increased apoptosis (cleavage of caspase 3 and PARP), which may be explained by accumulation of DNA-damage (increased expression of ?-H2A.X)--and premature mitosis of S-phase cells. Compared to either inhibitor used as single agents, combined treatment reduced spheroid growth and led to greater tumour growth inhibition in melanoma xenografts. CONCLUSIONS: These data provide a rationale for further evaluation of the combination of Wee1 and Chk1/2 inhibitors in malignant melanoma. |*Drug Synergism [MESH] |Animals [MESH] |Antineoplastic Combined Chemotherapy Protocols/administration & dosage [MESH] |Apoptosis/drug effects [MESH] |Cell Cycle Checkpoints/drug effects [MESH] |Cell Cycle Proteins/antagonists & inhibitors/*genetics [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Checkpoint Kinase 2/antagonists & inhibitors/*genetics [MESH] |Humans [MESH] |Melanoma, Cutaneous Malignant [MESH] |Melanoma/*drug therapy/genetics/pathology [MESH] |Mice [MESH] |Nuclear Proteins/antagonists & inhibitors/*genetics [MESH] |Protein Kinase Inhibitors/administration & dosage [MESH] |Protein-Tyrosine Kinases/antagonists & inhibitors/*genetics [MESH] |Pyrazoles/administration & dosage [MESH] |Pyrimidines/administration & dosage [MESH] |Pyrimidinones [MESH] |Skin Neoplasms [MESH] |Thiophenes/administration & dosage [MESH] |Urea/administration & dosage/analogs & derivatives [MESH]Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2(epmc).pdf DeepDyve Pubget Overpricing