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Source: Cancer Letters

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Total 56 results found since Jan 2013.

Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib
In this study we systematically screened a library of 306 known anti-cancer drugs for their ability to induce autophagy using a cell-based assay. 114 of the drugs were classified as autophagy inducers; for 16 drugs, the cytotoxicity was potentiated by siRNA-mediated knock-down of Atg7 and Vps34. These drugs were further evaluated in breast cancer cell lines for autophagy induction, and two tyrosine kinase inhibitors, Sunitinib and Erlotinib, were selected for further studies.
Source: Cancer Letters - July 25, 2018 Category: Cancer & Oncology Authors: Matheus Dyczynski, Yasmin Yu, Magdalena Otrocka, Santiago Parpal, Tiago Braga, Aine Brigette Henley, Henric Zazzi, Mikael Lerner, Krister Wennerberg, Jenny Viklund, Jessica Martinsson, Dan Grand ér, Angelo De Milito, Katja Pokrovskaja Tamm Tags: Original Articles Source Type: research

Deficiency of parkin suppresses melanoma tumor development and metastasis through inhibition of MFN2 ubiquitination
Parkin, a critical gene of Parkinson's disease, is involved in the development of numerous cancers. However, the effect of parkin deficiency on melanoma growth and metastasis has not been reported. We showed that the tumor size and number of surface lung metastases, and expression of tumor growth and metastasis marker proteins were significantly lower in parkin-KO mice than those observed in non-transgenic controls. In an in vitro study, we also showed that parkin siRNA inhibited cell growth and migration of B16F10 and SK-Mel-28 cells.
Source: Cancer Letters - July 5, 2018 Category: Cancer & Oncology Authors: Yong Sun Lee, Yu Yeon Jung, Mi Hee Park, In Jun Yeo, Hyung Sik Im, Kyung Tak Nam, Hae Deun Kim, Shin Kook Kang, Ju Koung Song, Yu Ri Kim, Dong-Young Choi, Pil-Hoon Park, Sang Bae Han, Jae Suk Yun, Jin Tae Hong Tags: Original Articles Source Type: research

Hedgehog signaling negatively co-regulates BH3-only protein Noxa and TAp73 in TP53-mutated cells
In the present study, we show that pharmacological repression by the Hedgehog (Hh) pathway inhibitor (HPI) GANT61 induces expression of the proapoptotic protein Noxa in TP53-mutated embryonal pediatric tumor cells driven by Hh signaling (i.e. rhabdomyosarcoma (RMS) and medulloblastoma (MB)). Similarly, genetic silencing of Gli1 by siRNA causes increased Noxa mRNA and protein levels, while overexpression of Gli1 results in decreased Noxa expression. Furthermore, TAp73 mRNA and protein levels are increased upon Gli1 knockdown, while Gli1 overexpression reduces TAp73 mRNA and protein levels.
Source: Cancer Letters - April 24, 2018 Category: Cancer & Oncology Authors: Michael Torsten Meister, Cathinka Boedicker, Thomas Klingebiel, Simone Fulda Tags: Original Articles Source Type: research

RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide
In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA.
Source: Cancer Letters - March 30, 2018 Category: Cancer & Oncology Authors: Bin Lu, Zongqi Wang, Ye Ding, Xuanzhong Wang, Shan Lu, Chongcheng Wang, Chuan He, Meihua Piao, Guangfan Chi, Yinan Luo, Pengfei Ge Tags: Original Articles Source Type: research

ICAM3 mediates inflammatory signaling to promote cancer cell stemness
In this study, we present a medium throughput siRNA screen platform to identify inflammation genes that regulate cancer cell stemness. We identified several novel candidates that decrease OCT4 expression and reduce the ALDH  + subpopulation both of which are characteristic of stemness. Furthermore, one of the novel candidates ICAM3 up-regulates in the ALDH + subpopulation, the side population and the developed spheres. ICAM3 knockdown reduces the side population, sphere formation and chemo-resistance in MDA-MB-231 human breast cancer cells and A549 lung cancer cells.
Source: Cancer Letters - February 22, 2018 Category: Cancer & Oncology Authors: Wenzhi Shen, Junling Xie, Shuangtao Zhao, Renle Du, Xiaohe Luo, Huiwen He, Shan Jiang, Na Hao, Chong Chen, Chunlei Guo, Yanhua Liu, Yanan Chen, Peiqing Sun, Shengyong Yang, Na Luo, Rong Xiang, Yunping Luo Tags: Original Articles Source Type: research

Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells
Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis.
Source: Cancer Letters - September 23, 2017 Category: Cancer & Oncology Authors: Chiara Anania Maria, Elena Cetti, Daniele Lecis, Katia Todoerti, Alessandro Gulino, Giuseppe Mauro, Tiziana Di Marco, Loredana Cleris, Sonia Pagliardini, Giacomo Manenti, Beatrice Belmonte, Claudio Tripodo, Antonino Neri, Angela Greco Source Type: research

Ras Inhibitors Display an Anti-Metastatic Effect by Downregulation of Lysyl Oxidase through Inhibition of the Ras-PI3K-Akt-HIF-1 α Pathway
Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-rasG12Vgene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or an siRNA targeting Ras downregulates the expre...
Source: Cancer Letters - September 23, 2017 Category: Cancer & Oncology Authors: Yoko Yoshikawa, Osamu Takano, Ichiro Kato, Yoshihisa Takahashi, Fumi Shima, Tohru Kataoka Source Type: research

Palbociclib, a selective CDK4/6 inhibitor, enhances the effect of selumetinib in RAS-driven non-small cell lung cancer
In this study, we demonstrated the combination effects of the MEK inhibitor selumetinib and the CDK4/6 inhibitor palbociclib in RAS-driven NSCLC. In vitro, cell lines with CDKN2A mutations were insensitive to selumetinib. We used siRNA and pharmacologic inhibition of CDK4 and found that the combination of selumetinib and palbociclib synergistically inhibited RAS-driven NSCLC cases with CDKN2A mutations but not those with wild type CDKN2A.
Source: Cancer Letters - August 30, 2017 Category: Cancer & Oncology Authors: Jianya Zhou, Shumeng Zhang, Xi Chen, Xianan Zheng, Yinan Yao, Guohua Lu, Jianying Zhou Source Type: research

Silencing of the mRNA-binding protein HuR increases the sensitivity of colorectal cancer cells to ionizing radiation through upregulation of caspase-2
In this study, we investigated whether siRNA-mediated HuR knockdown interferes with cell survival and radiation sensitivity by monitoring apoptosis, DNA repair and three-dimensional (3D) clonogenic survival.
Source: Cancer Letters - February 16, 2017 Category: Cancer & Oncology Authors: Amel Badawi, Stephanie Hehlgans, Josef Pfeilschifter, Franz R ödel, Wolfgang Eberhardt Tags: Original Articles Source Type: research

Rufy3 promotes metastasis through epithelial-mesenchymal transition in colorectal cancer
Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in vitro and in vivo.
Source: Cancer Letters - January 13, 2017 Category: Cancer & Oncology Authors: Ruyi Xie, Jing Wang, Weimei Tang, Yueqiao Li, Ying Peng, Hui Zhang, Guangnan Liu, Xiaoting Huang, Jinjun Zhao, Aimin Li, Wei Gong, Ye Chen, Yuexin Ren, Yadong Wang, Guoxin Li, Side Liu, Jide Wang Tags: Original Articles Source Type: research

Rufy3 promotes metastasis through epithelial –mesenchymal transition in colorectal cancer
Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in  vitro and in vivo.
Source: Cancer Letters - January 13, 2017 Category: Cancer & Oncology Authors: Xie Ruyi, Wang Jing, Tang Weimei, Li Yueqiao, Peng Ying, Zhang Hui, Liu Guangnan, Huang Xiaoting, Zhao Jinjun, Li Aimin, Gong Wei, Chen Ye, Ren Yuexin, Wang Yadong, Li Guoxin, Liu Side, Jide Wang Tags: Original Article Source Type: research

Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in vivo in a mouse xenogtraft model
Multiple myeloma (MM) is an incurable malignancy by the presently known therapies. TRAIL is a promising anticancer agent that virtually not shows any toxicity to normal cells. We have recently carried out clinical trials with a human circularly permuted TRAIL, CPT, against MM saw a partial response in approximate 20 – 30% of patients. In the current study, we investigated the cause of CPT resistance and revealed that the majority of the MM patients express elevated levels of c-FLIP. Knockdown of c-FLIP expression by siRNA alone was sufficient to increase CPT-mediated apoptosis in a CPT-resistant human MM cell line U266.
Source: Cancer Letters - December 17, 2016 Category: Cancer & Oncology Authors: Yin Wu, Marco Giaisi, Rebecca K öhler, Dr. Wen-Ming Chen, Peter H. Krammer, Dr. Min Li-Weber Tags: Original Articles Source Type: research

Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in  vivo in a mouse xenogtraft model
Multiple myeloma (MM) is an incurable malignancy by the presently known therapies. TRAIL is a promising anticancer agent that virtually not shows any toxicity to normal cells. We have recently carried out clinical trials with a human circularly permuted TRAIL, CPT, against MM saw a partial response in approximate 20 –30% of patients. In the current study, we investigated the cause of CPT resistance and revealed that the majority of the MM patients express elevated levels of c-FLIP. Knockdown of c-FLIP expression by siRNA alone was sufficient to increase CPT-mediated apoptosis in a CPT-resistant human MM cell line U266.
Source: Cancer Letters - December 17, 2016 Category: Cancer & Oncology Authors: Yin Wu, Marco Giaisi, Rebecca K öhler, Wen-Ming Chen, Peter H. Krammer, Min Li-Weber Tags: Original Article Source Type: research