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https://www.readbyqxmd.com/read/27909729/self-renewal-molecular-mechanisms-of-colorectal-cancer-stem-cells
#1
Tianhui Pan, Jinghong Xu, Yongliang Zhu
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal...
November 30, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#2
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#3
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27906684/phase-i-study-of-the-gamma-secretase-inhibitor-pf-03084014-in-combination-with-docetaxel-in-patients-with-advanced-triple-negative-breast-cancer
#4
Marzia A Locatelli, Philippe Aftimos, E Claire Dees, Patricia M LoRusso, Mark D Pegram, Ahmad Awada, Bo Huang, Rossano Cesari, Yuqiu Jiang, M Naveed Shaik, Kenneth A Kern, Giuseppe Curigliano
BACKGROUND: The NOTCH signaling pathway may be involved in the survival of stem cell-like tumor-initiating cells and contribute to tumor growth. In this phase Ib, open-label, multicenter study (NCT01876251), we evaluated PF-03084014, a selective gamma-secretase inhibitor in patients with advanced triple-negative breast cancer. METHODS: The dose-finding part was based on a 2×3 matrix design using the modified toxicity probability interval method. Oral PF-03084014 was administered twice daily continuously in combination with intravenous docetaxel given on day 1 of each 21-day cycle...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904763/microrna-133a-3p-exerts-inhibitory-effects-on-gallbladder-carcinoma-via-targeting-rbpj
#5
Yuan Huang, Yaoshi Wu, Jiahong Dong, Dongdong Han, Shiwei Yang, Lin Jiang
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27902974/na-h-exchanger-1-has-tumor-suppressive-activity-and-prognostic-value-in-esophageal-squamous-cell-carcinoma
#6
Yosuke Ariyoshi, Atsushi Shiozaki, Daisuke Ichikawa, Hiroki Shimizu, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Yoshinori Marunaka, Eigo Otsuji
Na+/H+ exchanger 1 (NHE1) is a plasma membrane transporter that controls intracellular pH and regulates apoptosis and invasion in various cancer cells. However, the function of NHE1 in esophageal squamous cell carcinoma (ESCC) cells and the relationship between the expression of NHE1 and prognosis of ESCC remain unclear. We found that the knockdown of NHE1 in ESCC cells inhibited apoptosis and promoted cell proliferation, migration, and invasion and showed increases in Snail, β-catenin, and activation of PI3K-AKT signaling, which was consistent with the results obtained from microarrays...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900056/inhibition-of-cell-proliferation-and-tumor-growth-of-colorectal-cancer-by-inhibitors-of-wnt-and-notch-signaling-pathways
#7
Yuliang Xiao, Xiaojing Yang, Yinglei Miao, Xikun He, Ming Wang, Weihong Sha
Understanding the role and mechanism of signaling pathways including Notch and Wnt in colorectal carcinogenesis is critical to the development of novel therapeutics. In the present study, we analyzed the cell proliferation, migration, G2/M percentage and the expression of molecules of signaling pathways in HCT-116 cells through the inhibition of Wnt and Notch pathways, and also investigated the effect of inhibitors of Wnt and Notch pathways on tumor growth in a transplantation tumor model. We observed that rDDK-1 (an inhibitor of the Wnt signaling pathway) and LY374973 (an inhibitor of the Notch signaling pathway) synergistically inhibited the proliferation, migration and G2/M percentage of HCT-116 cell lines, and could further synergistically inhibit the tumor volume and weight in the transplantation tumor model...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#8
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27891816/dll4-overexpression-increases-gastric-cancer-stem-progenitor-cell-self-renewal-ability-and-correlates-with-poor-clinical-outcome-via-notch-1-signaling-pathway-activation
#9
Zhi-Feng Miao, Hao Xu, Hui-Mian Xu, Zhen-Ning Wang, Ting-Ting Zhao, Yong-Xi Song, Ying-Ying Xu
Gastric cancer is one of the most common malignant diseases, and poses a serious threat to the quality of human life. Gastric cancer stem/progenitor cells (GCSPCs) have critical effects on tumor formation, affecting specific features of self-renewal and differentiation and playing a critical role in metastasis. The Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27888801/common-profiles-of-notch-signaling-differentiate-disease-free-survival-in-luminal-type-a-and-triple-negative-breast-cancer
#10
Magdalena Orzechowska, Dorota Jędroszka, Andrzej K Bednarek
Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27882186/erratum-oncogenic-role-of-the-notch-pathway-in-primary-liver-cancer-review
#11
Jie Lu, Yujing Xia, Kan Chen, Yuanyuan Zheng, Jianrong Wang, Wenxia Lu, Qin Yin, Fan Wang, Yingqun Zhou, Chuanyong Guo
[This corrects the article DOI: 10.3892/ol.2016.4609.].
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27880939/inhibition-of-the-transcriptional-repressor-complex-bcl-6-bcor-induces-endothelial-sprouting-but-does-not-promote-tumor-growth
#12
Elisabeth Buchberger, Dietmar Payrhuber, Miriam El Harchi, Branislav Zagrapan, Katharina Scheuba, Anna Zommer, Edina Bugyik, Balazs Dome, Julia Barbara Kral, Waltraud Cornelia Schrottmaier, Gernot Schabbauer, Peter Petzelbauer, Marion Gröger, Martin Bilban, Christine Brostjan
The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma 6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6 inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6 interacting co-repressor) to be regulated in human microvascular endothelium by colorectal cancer cells, we investigated their function in sprouting angiogenesis which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found that the transcriptional repressor complex in fact constitutes an endogenous inhibitor of vascular sprouting by supporting the stalk cell phenotype: control of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and B1)...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878283/hes5-promotes-cellular-proliferation-of-non-small-cell-lung-cancer-through-stat3-signaling
#13
Shudong Gu, Rui Zhang, Jun Gu, Xia Li, Liting Lv, Jingting Jiang, Zhen Xu, Shuo Wang, Cui Shi, Dan Ping Wang, Changping Wu
HES5 is a transcription factor activated downstream of the Notch pathway and regulates cell differentiation in multiple tissues. Disruption of its normal expression has been associated with developmental diseases and cancer. But its role in non-small cell lung cancer (NSCLC) remains elusive. Western blot analysis and immunohistochemistry assays demonstrated that HES5 expression was frequently increased in NSCLC tumor tissues and cell lines. Moreover, immunohistochemistry analysis revealed that upregulation of HES5 expression was positively correlated with a more invasive tumor phenotype and poor prognosis...
November 22, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27878243/different-functions-of-akt1-and-akt2-in-molecular-pathways-cell-migration-and-metabolism-in-colon-cancer-cells
#14
Sara Häggblad Sahlberg, Anja C Mortensen, Jakob Haglöf, Mikael K R Engskog, Torbjörn Arvidsson, Curt Pettersson, Bengt Glimelius, Bo Stenerlöw, Marika Nestor
AKT is a central protein in many cellular pathways such as cell survival, proliferation, glucose uptake, metabolism, angiogenesis, as well as radiation and drug response. The three isoforms of AKT (AKT1, AKT2 and AKT3) are proposed to have different physiological functions, properties and expression patterns in a cell type-dependent manner. As of yet, not much is known about the influence of the different AKT isoforms in the genome and their effects in the metabolism of colorectal cancer cells. In the present study, DLD-1 isogenic AKT1, AKT2 and AKT1/2 knockout colon cancer cell lines were used as a model system in conjunction with the parental cell line in order to further elucidate the differences between the AKT isoforms and how they are involved in various cellular pathways...
November 18, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27878242/esc-3-induces-apoptosis-of-human-ovarian-carcinomas-through-wnt-%C3%AE-catenin-and-notch-signaling-in-vitro-and-in-vivo
#15
Qi-Rui Fu, Wei Song, Yi-Tao Deng, Hua-Liang Li, Xiao-Mei Mao, Chen-Lu Lin, Ya-Hui Zheng, Shu-Ming Chen, Qiong-Hua Chen, Qing-Xi Chen
Apoptosis, programmed cell death under physiological or pathological conditions, plays a critical role in the tissue homeostasis of eukaryotes. It is desirable to prevent the occurrence and metastasis of cancer through inducing apoptosis. Our previous study demonstrated that apoptosis could be induced by extract from crocodile in human cholangiocarcinoma. ESC-3, a novel cytotoxic compound isolated from the extract induced apoptosis in Mz-ChA-1 cells via the mitochondria-dependent pathway in a dose-dependent manner...
November 18, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27876309/vertical-breast-measurement-in-east-asian-women-a-guide-for-mastopexy-and-reduction-to-form-nonptotic-breasts-in-unilateral-prosthetic-breast-reconstruction
#16
Takashi Fujiwara, Kenji Yano, Yoshio Tanji, Masaya Nomura
BACKGROUND: Following unilateral breast cancer surgery, mastopexy and reduction of the unaffected breast are often performed to obtain symmetrical breasts. The use of implants in breast reconstruction results in a nonptotic breast. To achieve symmetry following the procedure, the unaffected side should be nonptotic too. However, no study has yet reported any indices for the design of mastopexy and reduction in this direction. We present a new method of preoperative design that uses vertical breast measurements to form nonptotic breasts according to individual breast shapes...
October 26, 2016: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
https://www.readbyqxmd.com/read/27875990/inverse-relationship-between-alzheimer-s-disease-and-cancer-and-other-factors-contributing-to-alzheimer-s-disease-a-systematic-review
#17
Ovais Shafi
BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease...
November 22, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27870831/asymmetric-division-coordinates-collective-cell-migration-in-angiogenesis
#18
Guilherme Costa, Kyle I Harrington, Holly E Lovegrove, Donna J Page, Shilpa Chakravartula, Katie Bentley, Shane P Herbert
The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27861750/notch3-expression-correlates-with-thyroid-cancer-differentiation-induces-apoptosis-and-predicts-disease-prognosis
#19
Yash R Somnay, Xiao-Min Yu, Ricardo V Lloyd, Glen Leverson, Zviadi Aburjania, Samuel Jang, Renata Jaskula-Sztul, Herbert Chen
BACKGROUND: Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact. METHODS: Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27861232/safety-and-efficacy-of-magnetic-resonance-guided-vacuum-assisted-large-volume-breast-biopsy-mr-guided-valb
#20
Simone Schrading, Kevin Strobel, Annika Keulers, Timm Dirrichs, Christiane K Kuhl
OBJECTIVE: Magnetic resonance (MR)-guided vacuum-biopsy is technically demanding and may fail depending on target-lesion size or breast size, and location of lesions within the breast. We developed an MR-guided vacuum-assisted biopsy protocol that collects larger amounts of tissue, aiming at an at least partial or complete ablation of the target-lesion, just as it is intended during surgical (excisional) biopsy. Rationale is to avoid biopsy failures (false-negative results due to undersampling) by collecting larger amounts of tissue...
November 17, 2016: Investigative Radiology
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