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https://www.readbyqxmd.com/read/29050323/histone-deacetylase-inhibitor-thailandepsin-a-activates-notch-signaling-and-suppresses-neuroendocrine-cancer-cell-growth-in-vivo
#1
Samuel Jang, Andrew Janssen, Zviadi Aburjania, Matthew B Robers, April Harrison, Ajitha Dammalapati, Yi-Qiang Cheng, Herbert Chen, Renata Jaskula-Sztul
Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#2
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#3
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29039612/long-non-coding-rna-steroid-receptor-rna-activator-sra-induces-tumor-proliferation-and-invasion-through-the-notch-pathway-in-cervical-cancer-cell-lines
#4
Kyung Jin Eoh, Jiheum Paek, Sang Wun Kim, Hee Jung Kim, Hye Yeon Lee, Sang Kil Lee, Young Tae Kim
Contemporary research has focused on the function of long non-coding RNAs (lncRNAs) in carcinogenesis. However, the involvement of the lncRNA, steroid receptor RNA activator (SRA), in cervical carcinogenesis remains to be elucidated. In the present study, we investigated the bio-functional consequences of lncRNA SRA knockdown in vitro. To verify the role of lncRNA SRA in cell proliferation, migration, and invasion, lncRNA RNA interference was utilized to knock down lncRNA SRA expression in cervical cancer cell lines, resulting in our discovery that lncRNA SRA knockdown inhibited cell proliferation, cell migration and tumor invasion in the cervical cancer cell lines...
October 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29031504/-therapeutic-targeting-of-notch-signaling-in-cancer
#5
REVIEW
Mehdi Brahmi, Olivia Bally, Lauriane Eberst, Philippe Cassier
The Notch pathway plays an essential role during embryonal development and tissue in adults. Notch signaling occurs through transmembrane receptors which undergo several proteolytic cleavages that lead to the release of the Notch intracytoplasmic domain (NICD), which in turn activates the transcription of target genes. Oncogenic alterations of Notch receptors were first identified in T acute lymphoblastic leukemia and subsequently in solid tumors and other hematological malignancies. The important role of Notch signaling in cancer makes it an interesting target for drug development...
October 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29029546/bladder-cancer-stem-cells-clonal-origin-and-therapeutic-perspectives
#6
REVIEW
Yi Li, Kaisu Lin, Zhao Yang, Ning Han, Xiaofang Quan, Xiangyang Guo, Chong Li
In this article, we review the origin and therapeutic perspectives of bladder cancer stem cells (BCSCs), which are integral to the initiation, high recurrence and chemoresistance of bladder cancer. BCSCs are heterogenous and originate from multiple cell types, including urothelial stem cells and differentiated cell types, including basal, intermediate stratum and umbrella cells. Cell surface markers, including CD44, CD67LR, EMA, ALDH1A1 and BCMab1, are used to identify and isolate BCSCs. The Hedgehog, Notch, Wnt and JAK-STAT signaling pathways play key roles in maintaining the stemness, self-renewal and proliferative potential of BCSCs...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029414/targeting-adam17-inhibits-human-colorectal-adenocarcinoma-progression-and-tumor-initiating-cell-frequency
#7
Joseph Dosch, Elizabeth Ziemke, Shanshan Wan, Kathryn Luker, Theodore Welling, Karin Hardiman, Eric Fearon, Suneetha Thomas, Matthew Flynn, Jonathan Rios-Doria, Robert Hollingsworth, Ronald Herbst, Elaine Hurt, Judith Sebolt-Leopold
ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFα converting enzyme) has emerged as a potential therapeutic target in colorectal cancer (CRC) and other cancers, due in part to its role in regulating various tumor cell surface proteins and growth factors and cytokines in the tumor microenvironment. The emergence of MEDI3622, a highly potent and specific antibody-based ADAM17 inhibitor, has allowed testing of the concept that targeting ADAM17 may be an important new therapeutic approach for CRC patients...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027990/il6-blockade-potentiates-the-anti-tumor-effects-of-%C3%AE-secretase-inhibitors-in-notch3-expressing-breast-cancer
#8
Dong Wang, Jiahui Xu, Bingjie Liu, Xueyan He, Lei Zhou, Xin Hu, Feng Qiao, Anli Zhang, Xiaojun Xu, Huafeng Zhang, Max S Wicha, Lixing Zhang, Zhi-Ming Shao, Suling Liu
Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ)...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29025966/notch-signaling-linking-embryonic-lung-development-and-asthmatic-airway-remodeling
#9
Musaddique Hussain, Chengyun Xu, Mashaal Ahmad, Meiping Lu, Xiling Wu, Lanfang Tang, Ximei Wu
Lung development is mediated by assorted signaling proteins, and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development...
October 12, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29023247/mir-449a-a-potential-therapeutic-agent-for-cancer
#10
He Yong-Ming, Ji Ai-Jun, Xu Xiao-Yue, Lu Jian-Wei, Yu Chen, Chen Ye
MicroRNAs (miRNAs) have been reported to be associated with cancer progression and carcinogenesis. They are small, highly conserved, noncoding RNA molecules consisting of 19-25 nucleotides. By binding to complementary binding sites within the 3'-untranslated region of target mRNAs, miRNAs inhibit the translation of mRNAs or promote their degradation. miRNAs play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. Similarly, several studies have shown that miRNAs are involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, signal transduction, and carcinogenesis...
November 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28994095/repression-of-the-notch-pathway-prevents-liver-damage-in-streptozotocin-induced-diabetic-mice
#11
Eda Acikgoz, Huseyin Aktug, Gurkan Yigitturk, Kenan Demir, Ummu Guven, Fahriye Duzagac, Fatih Oltulu, Altug Yavasoglu, Gulperi Oktem
INTRODUCTION: Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathologies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models. MATERIAL AND METHODS: An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice...
October 10, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28981109/dexamethasone-mediates-pancreatic-cancer-progression-by-glucocorticoid-receptor-tgf%C3%AE-and-jnk-ap-1
#12
Li Liu, Ewa Aleksandrowicz, Frank Schönsiegel, Daniel Gröner, Nathalie Bauer, Clifford C Nwaeburu, Zhefu Zhao, Jury Gladkich, Torsten Hoppe-Tichy, Eitan Yefenof, Thilo Hackert, Oliver Strobel, Ingrid Herr
Glucocorticoids such as dexamethasone are widely co-prescribed with cytotoxic therapy because of their proapoptotic effects in lymphoid cancer, reduction of inflammation and edema and additional benefits. Concerns about glucocorticoid-induced therapy resistance, enhanced metastasis and reduced survival of patients are largely not considered. We analyzed dexamethasone-induced tumor progression in three established and one primary human pancreatic ductal adenocarcinoma (PDA) cell lines and in PDA tissue from patients and xenografts by FACS and western blot analysis, immunohistochemistry, MTT and wound assay, colony and spheroid formation, EMSA and in vivo tumor growth and metastasis of tumor xenografts on chicken eggs and mice...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978720/gamma-secretase-inhibition-by-bms-906024-enhances-efficacy-of-paclitaxel-in-lung-adenocarcinoma
#13
Katherine M Morgan, Bruce S Fischer, Francis Y Lee, Jamie J Shah, Joseph R Bertino, Jeffrey Rosenfeld, Amartya Singh, Hossein Khiabanian, Sharon R Pine
Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor (GSI), and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin (mean CI value = 0.54 and 0.85, respectively, P = 0.01). On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI = 0...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978094/dna-repair-deregulation-in-discrete-prostate-cancer-lesions-identified-on-multi-parametric-mri-and-targeted-by-mri-ultrasound-fusion-guided-biopsy
#14
Caleb R Dulaney, Soroush Rais-Bahrami, Debra Della Manna, Jennifer B Gordetsky, Jeffrey W Nix, Eddy S Yang
Prostate cancer is histologically and molecularly heterogeneous. Clinically significant disease is often driven by dominant intra-prostatic lesions (IPLs). Prostate cancers cluster into molecular phenotypes with substantial genetic heterogeneity making pathway-based molecular analysis appealing. MRI/ultrasound fusion biopsy provides a unique opportunity to characterize tumor biology of discrete lesions at diagnosis. This study determined the feasibility of pathway-based gene expression analysis of prostate biopsies and characterized cancer pathway deregulation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977931/inhibition-of-notch-1-pathway-is-involved-in-rottlerin-induced-tumor-suppressive-function-in-nasopharyngeal-carcinoma-cells
#15
Yingying Hou, Shaoyan Feng, Lixia Wang, Zhe Zhao, Jingna Su, Xuyuan Yin, Nana Zheng, Xiuxia Zhou, Jun Xia, Zhiwei Wang
Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977881/microrna-145-induces-apoptosis-of-glioma-cells-by-targeting-bnip3-and-notch-signaling
#16
Yan Du, Juan Li, Tao Xu, Dan-Dan Zhou, Lei Zhang, Xiao Wang
MicroRNAs (miRNAs) are involved in the pathogenesis of various human cancers. Here we show that miR-145 expression is decreased in human glioma samples, rat glioma tissues, and glioma cell lines, while expression of BNIP3 is increased. Over-expression of miR-145 or suppression of BNIP3 induced glioma cell apoptosis. BNIP3 is localized in the nucleus in glioma cells, and miR-145 inhibits BNIP3 expression by binding to the 3' untranslated region of its mRNA. Interestingly, miR-145 and BNIP3 regulate glioma cell apoptosis by modulating Notch signaling...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969912/dysregulation-of-mir-181c-expression-influences-recurrence-of-endometrial-endometrioid-adenocarcinoma-by-modulating-notch2-expression-an-nrg-oncology-gynecologic-oncology-group-study
#17
Eric J Devor, Jeffrey Miecznikowski, Brandon M Schickling, Jesus Gonzalez-Bosquet, Heather A Lankes, Premal Thaker, Peter A Argenta, Michael L Pearl, Susan L Zweizig, Robert S Mannel, Amy Brown, Nilsa C Ramirez, Olga B Ioffe, Kay J Park, William T Creasman, Michael J Birrer, David Mutch, Kimberly K Leslie
OBJECTIVE: Endometrial cancer can be diagnosed early and cured, yet cases that recur portend a very poor prognosis with over 10,000 women succumbing to the disease every year. In this study we addressed the question of how to recognize cases likely to recur early in the course of therapy using dysregulation of tumor microRNAs (miRNAs) as predictors. METHODS: Using the tissue collection from Gynecologic Oncology Group Study-210, we selected and analyzed expression of miRNAs in 54 recurrent and non-recurrent cases...
September 29, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28964793/oncogenic-determination-of-a-broad-spectrum-of-phenotypes-of-hepatocyte-derived-mouse-liver-tumors
#18
Masahiro Yamamoto, Bing Xin, Kenji Watanabe, Takako Ooshio, Kiyonaga Fujii, Xi Chen, Yoko Okada, Hiroaki Abe, Yoshimitsu Taguchi, Naoyuki Miyokawa, Hiroyuki Furukawa, Yuji Nishikawa
Activation of the phosphoinositide 3-kinase-AKT, Yes-associated protein (YAP), and MYC pathways is involved in human liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). However, the nature of the interactions among these pathways has remained poorly understood. Herein, we demonstrate the coordination of these pathways during the formation of mouse liver tumors induced by hepatocyte-specific somatic integration of myristoylated AKT, mutant YAP, Myc, or their combinations. Although the introduction of YAP or Myc alone was inefficient in inducing tumors, these proteins accelerated tumorigenesis induced by AKT...
September 28, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28961379/claudin-5-regulates-blood-brain-barrier-permeability-by-modifying-brain-microvascular-endothelial-cell-proliferation-migration-and-adhesion-to-prevent-lung-cancer-metastasis
#19
Shun-Chang Ma, Qi Li, Jia-Yi Peng, Jian-Long Zhouwen, Jin-Fu Diao, Jian-Xing Niu, Xi Wang, Xiu-Dong Guan, Wang Jia, Wen-Guo Jiang
AIMS: To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis. RESULTS: By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group...
September 29, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28959362/inhibition-of-hes1-enhances-lapatinib-sensitivity-in-gastric-cancer-sphere-forming-cells
#20
Luchun Li, Yan Li, Lulu Wang, Zhijuan Wu, Huiwen Ma, Jianghe Shao, Dairong Li, Huiqing Yu, Weiqi Nian, Donglin Wang
It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere-forming cells were separated from human gastric cancer MKN45 parental cells...
October 2017: Oncology Letters
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