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https://www.readbyqxmd.com/read/28821430/nrf2-regulates-cellular-behaviors-and-notch-signaling-in-oral-squamous-cell-carcinoma-cells
#1
Hong Fan, Chorlada Paiboonrungruan, Xinyan Zhang, Justin R Prigge, Edward E Schmidt, Zheng Sun, Xiaoxin Chen
Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC...
August 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28820917/whole-exome-sequencing-of-lacrimal-gland-adenoid-cystic-carcinoma
#2
David W Sant, Wensi Tao, Matthew G Field, Daniel Pelaez, Ke Jin, Anthony Capobianco, Sander R Dubovy, David T Tse, Gaofeng Wang
Purpose: To identify genomic mutations in lacrimal gland adenoid cystic carcinoma (LGACC) samples from patients. Methods: Genomic DNA was extracted from LGACC specimens. Whole exome sequencing (exome-seq) was conducted to screen for mutations. Capillary sequencing was performed to verify mutations in genes shared by multiple samples. Luciferase assays were used to evaluate functional consequences of NOTCH1 mutations. Results: The mutation profile of LGACC was complicated...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#3
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28794168/notch-signaling-in-development-tissue-homeostasis-and-disease
#4
REVIEW
Chris Siebel, Urban Lendahl
Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28791360/classical-vegf-notch-and-ang-signalling-in-cancer-angiogenesis-alternative-approaches-and-future-directions-review
#5
Nunzia Caporarello, Gabriella Lupo, Melania Olivieri, Martina Cristaldi, Maria Teresa Cambria, Mario Salmeri, Carmelina Daniela Anfuso
Angiogenesis is the formation of new vessels starting from pre-existing vasculature. Tumour environment is characterized by 'aberrant angiogenesis', whose main features are tortuous and permeable blood vessels, heterogeneous both in their structure and in efficiency of perfusion and very different from normal vessels. Therapeutic strategies targeting the three pathways chiefly involved in tumour angiogenesis, VEGF, Notch and Ang signalling, have been identified to block the vascular supply to the tumour. However, phenomena of toxicity, development of primary and secondary resistance and hypoxia significantly blunted the effects of anti-angiogenic drugs in several tumour types...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790030/notch-shapes-the-innate-immunophenotype-in-breast-cancer
#6
Qiang Shen, Brenda Cohen, Weiyue Zheng, Ramtin Rahbar, Bernard Martin, Kiichi Murakami, Sara Lamorte, Patrycja Thompson, Hal Berman, Juan Carlos Zúñiga-Pflücker, Pamela S Ohashi, Michael Reedijk
Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment (TME). Here we show that Notch in tumor cells regulates the expression of two powerful pro-inflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAMs). Notch also regulates TGFβ-mediated activation of tumor cells by TAMs, closing a Notch-dependent paracrine signaling loop between these two cell types. We use a novel mouse model in which Notch can be regulated in spontaneous mammary carcinoma to confirm that IL1β and CCL2 production, and macrophage recruitment are Notch-dependent...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28789624/hedgehog-inhibitor-sonidegib-potentiates-177-lu-octreotate-therapy-of-got1-human-small-intestine-neuroendocrine-tumors-in-nude-mice
#7
Johan Spetz, Britta Langen, Nils Rudqvist, Toshima Z Parris, Khalil Helou, Ola Nilsson, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-octreotate can be used to treat somatostatin receptor expressing neuroendocrine tumors. It is highly effective in animal models, but clinical studies have so far only demonstrated low cure rates. Hedgehog inhibitors have shown therapeutic effect as monotherapy in neuroendocrine tumor model systems and might be one option to enhance the efficacy of (177)Lu-octreotate therapy. The aim of this study was to determine the therapeutic effect of combination therapy using (177)Lu-octreotate and the Hedgehog signaling pathway inhibitor sonidegib...
August 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#8
Ken J Kron, Alexander Murison, Stanley Zhou, Vincent Huang, Takafumi N Yamaguchi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Mathieu Lupien
TMPRSS2-ERG (T2E) structural rearrangements typify ∼50% of prostate tumors and result in overexpression of the ERG transcription factor. Using chromatin, genomic and expression data, we show distinct cis-regulatory landscapes between T2E-positive and non-T2E primary prostate tumors, which include clusters of regulatory elements (COREs). This difference is mediated by ERG co-option of HOXB13 and FOXA1, implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression...
August 7, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28777778/kshv-and-the-role-of-notch-receptor-dysregulation-in-disease-progression
#9
REVIEW
Jennifer L DeCotiis, David M Lukac
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of two human cancers, Kaposi's Sarcoma (KS) and primary effusion lymphoma (PEL), and a lymphoproliferation, Multicentric Castleman's Disease (MCD). Progression to tumor development in KS is dependent upon the reactivation of the virus from its latent state. We, and others, have shown that the Replication and transcriptional activator (Rta) protein is the only viral gene product that is necessary and sufficient for viral reactivation. To induce the reactivation and transcription of viral genes, Rta forms a complex with the cellular DNA binding component of the canonical Notch signaling pathway, recombination signal binding protein for Jk (RBP-Jk)...
August 4, 2017: Pathogens
https://www.readbyqxmd.com/read/28776955/antineoplastic-effects-of-histone-deacetylase-inhibitors-in-neuroendocrine-cancer-cells-are-mediated-through-transcriptional-regulation-of-notch1-by-activator-protein-1
#10
Samuel Jang, Haining Jin, Madhuchhanda Roy, Alice L Ma, Shaoqin Gong, Renata Jaskula-Sztul, Herbert Chen
Notch signaling is minimally active in neuroendocrine (NE) cancer cells. While histone deacetylase inhibitors (HDACi) suppress NE cancer growth by inducing Notch, the molecular mechanism underlying this interplay has not yet been defined. NE cancer cell lines BON, H727, and MZ-CRC-1 were treated with known HDACi Thailadepsin-A (TDP-A) and valproic acid (VPA), and Notch1 mRNA expression was measured with RT-PCR. Truncated genomic fragments of the Notch1 promotor region fused with luciferase reporter were used to identify the potential transcription factor (TF) binding site...
August 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28769027/synergistic-effect-of-notch-3-specific-inhibition-and-paclitaxel-in-non-small-cell-lung-cancer-nsclc-cells-via-activation-of-the-intrinsic-apoptosis-pathway
#11
Fenglian He, Ting Du, Qian Jiang, Yanbei Zhang
BACKGROUND Lung cancers are resistant to conventional chemotherapeutic interventions such as paclitaxel. Notch signaling is crucial in the chemoresistance of lung cancer cells. The Notch inhibitor gamma-secretase inhibitor (GSI) inhibits the Notch signaling pathway. MATERIAL AND METHODS Here, we evaluated how Notch-3 inhibition by GSI can enhance the sensitivity of lung cancer cells to paclitaxel. To study how Notch-3-specific inhibition affects non-small cell lung cancer (NSCLC), we compared the cell viability, apoptosis, and colony formation of A549 and H1299 cells treated with Notch-3 siRNA and GSI...
August 3, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28760777/sumoylation-negatively-regulates-angiogenesis-by-targeting-endothelial-notch-signaling
#12
Xiaolong Zhu, Sha Ding, Cong Qiu, Yanna Shi, Lin Song, Yueyue Wang, Yuewen Wang, Jinying Li, Yiran Wang, Yi Sun, Lingfeng Qin, Jun Chen, Michael Simons, Wang Min, Luyang Yu
Rationale: The highly conserved NOTCH signaling pathway functions as a key cell-cell interaction mechanism controlling cell-fate and tissue patterning, while its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls it signal transduction. Our previous study indicated the potential role of post-translational small ubiquitin-like modifier (SUMO) modification (SUMOylation) in vascular disorders...
July 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/28754853/dna-repair-deregulation-in-discrete-prostate-cancer-lesions-identified-on-multi-parametric-mri-and-targeted-by-mri-ultrasound-fusion-guided-biopsy
#13
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...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754458/terfenadine-combined-with-epirubicin-impedes-the-chemo-resistant-human-non-small-cell-lung-cancer-both-in-vitro-and-in-vivo-through-emt-and-notch-reversal
#14
Li An, Dan-Dan Li, Hai-Xiao Chu, Qiao Zhang, Chang-Li Wang, Yan-Hua Fan, Qi Song, Hong-Da Ma, Fan Feng, Qing-Chun Zhao
The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes eventually leads to the recurrence and metastasis of tumours. Thus, the development of therapeutic strategies based on the mechanisms by which cells acquire resistance to prolong their survival rate in chemotherapy drug treatment failure patients are warranted. In this study, we found that the resistant cells acquired increased migratory and invasive capabilities, and this transformation was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway deregulation in the resistant cells...
July 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28754309/retinoic-acid-cyp26-and-drug-resistance-in-the-stem-cell-niche
#15
REVIEW
Salvador Alonso, Richard J Jones, Gabriel Ghiaur
The bone marrow niche is essential for hematopoietic stem cells to maintain lifelong blood production, by balancing their self-renewal and differentiation. Hematologic malignancies have a similar hierarchical organization to their normal counterparts, with rare populations of cancer stem cells that rely on the microenvironment to survive and propagate their differentiated malignant progenitor cells. Cancer cells alter their microenvironment to create a supportive niche where they endure chemotherapy, survive as minimal residual disease, and eventually prevail at relapse...
July 25, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28753789/integrated-phenotypic-genotypic-analysis-of-papillary-renal-cell-carcinoma-subtypes-identification-of-prognostic-markers-cancer-related-pathways-and-implications-for-therapy
#16
Rola M Saleeb, Pamela Plant, Eriny Tawedrous, Adriana Krizova, Fadi Brimo, Andrew J Evans, Samantha Jane Wala, John Bartlett, Qiang Ding, Dina Boles, Fabio Rotando, Mina Farag, George M Yousef
BACKGROUND: Two histologic subtypes are recognized for papillary renal cell carcinoma (PRCC). Studies have shown that the subtypes differ in characteristic genetic alterations and clinical behavior. Clinically, the subtypes are managed similarly. OBJECTIVES: To analyze the biological differences between the two PRCC histological subtypes, in order to further guide their clinical management. DESIGN, SETTING, AND PARTICIPANTS: PRCC cohort consisting of 317 patients from the Cancer Genome Atlas database and our institution...
September 22, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28751447/numb-low-%C3%A2-enriches-a-castration-resistant-prostate-cancer-cell-subpopulation-associated-with-enhanced-notch-and-hedgehog-signaling
#17
Wei-Qiang Gao, Yanjing Guo, Kai Zhang, Chaping Cheng, Zhongzhong Ji, Xue Wang, Minglei Wang, Mingliang Chu, Dean G Tang, Helen He Zhu
To elucidate the role and molecular mechanism of Numb in prostate cancer (PCa) and the functional contribution of Numb(-/low) PCa cells in castration resistance.<br /><br />Experimental Design: The expression of Numb was assessed using multiple Oncomine datasets and PCa tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human PCa cell lines were investigated in vitro and in vivo In addition, we developed a reliable approach to distinguish between PCa cell populations with a high or low endogenous expression of Numb protein using a Numb promoter based lentiviral reporter system...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28745938/inhibition-of-nedd4-inhibits-cell-growth-and-invasion-and-induces-cell-apoptosis-in-bladder-cancer-cells
#18
Wu Wen, Jingying Li, Longwang Wang, Yifei Xing, Xuechao Li, Hailong Ruan, Xiaoqing Xi, Jianhua Xiong, Renrui Kuang
The neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) plays a pivotal oncogenic role in various types of human cancers. However, the function of NEDD4 in bladder cancer has not been fully investigated. In the present study, we aim to explore whether NEDD4 governs cell proliferation, apoptosis, migration, and invasion in bladder cancer cells. Our results showed that downregulation of NEDD4 suppressed cell proliferation in bladder cancer cells. Moreover, we found that inhibition of NEDD4 significantly induced cell apoptosis...
July 26, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28745885/chemical-synthesis-demonstrates-that-dynamic-o-glycosylation-regulates-the-folding-and-functional-conformation-of-a-pivotal-egf12-domain-of-the-human-notch1-receptor
#19
Shun Hayakawa, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro Nishimura
The interaction of the human NOTCH1 receptor and its ligands is a crucial step in initiating the intracellular signal transductions, in which O-glycosylation of the extracellular EGF-like domain strongly affects multiple aspects of cell differentiation, development, and cancer biology. However, consequences of biosynthetic O-glycosylation processes in the endoplasmic reticulum (ER) and Golgi on the folding of EGF domains remain unclear. Synthetic human NOTCH1 EGF12 modules allow for new insight into the crucial roles of O-glycosylation in the folding and conformation of this pivotal domain...
August 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28739265/role-of-adam10-in-intestinal-crypt-homeostasis-and-tumorigenesis
#20
Peter J Dempsey
A disintegrin and metalloproteinases (ADAMs) are a family of mSultidomain, membrane-anchored proteases that regulate diverse cellular functions, including cell adhesion, migration, proteolysis and other cell signaling events. Catalytically-active ADAMs act as ectodomain sheddases that proteolytically cleave type I and type II transmembrane proteins and some GPI-anchored proteins from the cellular surface. ADAMs can also modulate other cellular signaling events through a process known as regulated intramembrane proteolysis (RIP)...
July 22, 2017: Biochimica et Biophysica Acta
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