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| 1 | MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models显示文摘激活 mitogen 的蛋白质 kinase (MAPK ) 的激活小径在癌症是经常的。药发展努力在这条小径集中于 kinases,最尤其是在皇家空军和 MEK 上。我们这里证明 MEK 抑制激活通过 DUSP4 的抑制发信号的 JNK6 月,导致她的受体酷氨酸 Kinases 的激活。这面对药刺激 MAPK 小径,从而弄钝 MEK 抑制的效果。失去了 MAP3K1 或 MAP2K4 的癌症没能因而激活 JNK-JUN. ,在 MAP3K1 或 MAP2K4 的 loss-of-function 变化由在 MEK 抑制之上停用 JNK-JUN-mediated 反馈循环授与敏感到 MEK 抑制。在 168 个耐心的导出的异种皮移植(PDX ) 肿瘤的一块面板, MAP3K1 和 MAP2K4 变化地位是对 MEK 抑制的反应的一个强壮的预言者。我们的调查结果建议在 MAP3K1 或 MAP2K4 有变化的癌症,在胸,前列腺和冒号的肿瘤经常,可以对 MEK 禁止者作出回应。我们的调查结果也建议 MAP3K1 和 MAP2K4 是在有 MEK 禁止者的联合的潜在的药目标,尽管有他们被肿瘤 suppressor 基因编码的事实。 | Zheng Xue Daniel J. Vis Alejandra Bruna Tonci Sustic Sake van Wageningen Ankita Sati Batra Oscar M. Rueda Evert Bosdriesz Carlos Caldas Lodewyk F. A. Wessels Rene Bernardt | 2018 | Cell Research2018，28，7： | 5 |
| 2 | SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer显示文摘 | Andreas I Papadakis Chong Sun Theo A Knijnenburg Yibo Xue Wipawadee Gremrum Michael Holzel Wouter Nijkamp Lodewyk FA Wessels Roderick L Beijersbergen Rene Bernards Sidong Huang | 2015 | Cell Research2015，25，4： | 4 |
| 3 | An expression profile for diagnosis of lymph node metastase from primary heard and neck squamous cell carcinoma显示文摘 | Paul R Lodewyk F W Nienke K | 2005 | Nat Genet2005，37，2： | 1 |
| 4 | Artifacts of Mark- ov blanket filtering based on discretized features in small sample size applications 显示文摘 | Theo A K Marcel J T R Lodewyk F A W | 2006 | Pattern Recognition Letters2006，27，7： | 1 |
| 5 | GABA-B receptor ac- tivation inhibits the in vitro migration of malignant hepatocytes 显示文摘 | Lodewyks C Rodriguez J Yan J | 2011 | Can J Physiol Pharmacol2011，89，： | 1 |
| 6 | GABA-B re- ceptor activation inhibits the in vitro migration of malignant hepatocytes显示文摘 | LODEWYKS C RODRIGUEZ J YAN J et d | 2011 | Canadian Journal of Physiology and Pharmacolo- gy2011，89，6： | 1 |
| 7 | Avoiding false local minima by proper initialization of connections显示文摘 | Lodewyk F A Wessels Etienne Barnard | 1992 | IEEE Transaction on neural networks (S1045-9227)1992，3，6： | 1 |
| 8 | Computational prediction of IH and IaC chemical shifts:a useful tool for natural product, mechanistic,and synthetic organic chemistry 显示文摘 | Lodewyk MW Siebert MR Tantillo DJ | 2012 | Chem Rev2012，112，3： | 1 |
| 9 | Avoiding false local minima by proper initialization of connections 显示文摘 | LODEWYK F A W ETIENNE B | 1992 | IEEE Transactions on Neural Networks1992，3，6： | 1 |
| 10 | Physical literacy for educators显示文摘 | Mandigo J Francis N Lodewyk K | 2012 | Physical Health Education2012，75，： | 1 |
| 11 | Fostering ethicaldevelopment in physical education显示文摘 | LODEWYK K ELCOMBE T | 2010 | Physical & HealthEducation Journal2010，76，3： | 1 |
| 12 | Physical literacy for educators显示文摘 | MANDIGO J FRANCIS N LODEWYK K | 2009 | Physical & HealthEducation Journal2009，75，3： | 1 |
| 13 | Prediction of the structure of nobil- isitine: A using computed NMR chemical shifts 显示文摘 | Lodewyk MW Tantillo DJ | 2011 | J Nat Prod2011，74，5： | 1 |
| 14 | Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial‐to‐mesenchymal transition显示文摘 | Paul Roepman Andreas Schlicker Josep Tabernero Ian Majewski Sun Tian Victor Moreno Mireille H Snel Christine M Chresta Robert Rosenberg Ulrich Nitsche Teresa Macarulla Gabriel Capella Ramon Salazar George Orphanides Lodewyk FA Wessels Rene Bernards Iris M | 2013 | Int. J. Cancer2013，，3： | 1 |
| 15 | Physical litera- cy for educators 显示文摘 | Mandigo J Francis N Lodewyk K | 2012 | Physical Education and Health Journal2012，75，3： | 1 |
| 16 | Avoiding False Local Minima by Proper Initialization of Connections显示文摘 | Lodewyk F A Wessels Etienne Barnard | 1992 | IEEE Transactions on Neural Networks1992，，6： | 1 |
| 17 | The role of ability beliefs and incentives in middle school students' intentions,cardiovascular fitness,and effort显示文摘 | Gao Z Lodewyk K Zhang T | | 0，，： | 1 |
| 18 | Physical lit- eracy for educators显示文摘 | MANDIGO J FRANCIS N LODEWYK K | 2009 | Physi Health Edu J2009，75，3： | 1 |
| 19 | Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial‐to‐mesenchymal transition显示文摘 | Paul Roepman Andreas Schlicker Josep Tabernero Ian Majewski Sun Tian Victor Moreno Mireille H Snel Christine M Chresta Robert Rosenberg Ulrich Nitsche Teresa Macarulla Gabriel Capella Ramon Salazar George Orphanides Lodewyk FA Wessels Rene Bernards Iris M | 2013 | Int J Cancer2013，，3： | 1 |
| 20 | A multilevel pan-cancer map links gene mutations to cancer hallmarks显示文摘Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are manifested.This study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics data.Methods:We created a map that connects genes to cancer hallmarks via signaling pathways.We projected gene mutation and focal copy number data from various cancer types onto this map.We performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this topology.Results:Our analysis showed that although the genetic fingerprint of tumor types could be very different,there were less variations at the level of hallmarks,consistent with the idea that different genetic alterations have similar functional outcomes.Additionally,we showed how the multilevel map could help to clarify the role of infrequently mutated genes,and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways,whereas many co-occurring gene mutations were associated with hallmark characteristics.Conclusions:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks. | Theo A.Knijnenburg Tycho Bismeijer Lodewyk F.A.Wessels llya Shmulevich | 2015 | Chinese Journal of Cancer2015，34，10： | 0 |
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