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notch cancer

Christine Jungk, Andreas Mock, Janina Exner, Christoph Geisenberger, Rolf Warta, David Capper, Amir Abdollahi, Sara Friauf, Bernd Lahrmann, Niels Grabe, Philipp Beckhove, Andreas von Deimling, Andreas Unterberg, Christel Herold-Mende
BACKGROUND: The spatial relationship of glioblastoma (GBM) to the subventricular zone (SVZ) is associated with inferior patient survival. However, the underlying molecular phenotype is largely unknown. We interrogated an SVZ-dependent transcriptome and potential location-specific prognostic markers. METHODS: mRNA microarray data of a discovery set (n = 36 GBMs) were analyzed for SVZ-dependent gene expression and process networks using the MetaCore™ workflow...
October 26, 2016: BMC Medicine
Joanna Pancewicz-Wojtkiewicz
Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field...
October 21, 2016: Cancer Medicine
Qiang Zhang, Yaqing Zhang, Joshua D Parsels, Ines Lohse, Theodore S Lawrence, Marina Pasca di Magliano, Yi Sun, Meredith A Morgan
Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras(G12D);Fbxw7(fl/fl) (KFC(fl/fl)) compound mice. We found that KFC(fl/fl) mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
A Drouillard, F Puleo, J B Bachet, S Ouazzani, A Calomme, P Demetter, G Verset, J L Van Laethem, R Maréchal
BACKGROUND: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins...
October 18, 2016: British Journal of Cancer
Louise Stone
No abstract text is available yet for this article.
October 18, 2016: Nature Reviews. Urology
Deeksha Pal, Venkatesh Kolluru, Balaji Chanderashekar, Becca V Baby, Mazzy Aman, Suman Suman, Suman Sirimulla, Mary Ann Sanders, Praveen Seshabhatter, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues...
October 18, 2016: Molecular Carcinogenesis
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
Xiaoting Gu, Chunxiao Lu, Dongxu He, Yangfan Lu, Jian Jin, Dequan Liu, Xin Ma
To define the role of the NOTCH signaling pathway in the development of chemoresistance and the associated epithelial-mesenchymal transition (EMT), we investigated the effect of Notch3 on adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM cells). We found that Notch3 was downregulated and involved in the chemoresistance of MCF-7/ADM cells, while forced expression of Notch3 reversed the chemoresistance. Furthermore, fos-related antigen 1 (Fra1) was negatively regulated by Notch3 and was highly expressed in MCF-7/ADM cells...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiuxia Zhou, Jingna Su, Shaoyan Feng, Lixia Wang, Xuyuan Yin, Jingzhe Yan, Zhiwei Wang
Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers...
October 12, 2016: Oncotarget
Jessica C Kling, Antje Blumenthal
Innate lymphoid cells (ILCs) and innate-like lymphocytes have important roles in immune responses in the context of infection, cancer, and autoimmunity. The factors involved in driving the differentiation and function of these cell types remain to be clearly defined. There are several cellular signaling pathways involved in embryogenesis, which continue to function in adult tissue. In particular, the WNT, NOTCH, and Hedgehog signaling pathways are emerging as regulators of hematopoietic cell development and differentiation...
October 12, 2016: Journal of Leukocyte Biology
Platonova Natalia, Lesma Elena, Basile Andrea, Bignotto Monica, Garavelli Silvia, Palano Maria Teresa, Moschini Adriana, Neri Antonino, Colombo Michela, Chiaramonte Raffaella
BACKGROUND: Notch is a multifaceted protein that plays a fundamental role in fetal development and tissue homeostasis by directing many cellular functions, including cell growth and differentiation, cell fate determination and regulation of stem cells maintenance. The Notch family consists of four receptors (Notch 1-4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human tissues. Given the crucial contribution of Notch signaling in many physiological processes, it is not surprising that a variety of human malignancies is characterized by a dysregulation of one or more components of this pathway Methods: In this review, we are going to provide a broad overview on the role of Notch pathway in solid and hematological malignancies and a survey on possible Notch-directed therapeutic strategies...
October 6, 2016: Current Pharmaceutical Design
Yi-Hong Zhou, Yuanjie Hu, Liping Yu, Chao Ke, Christopher Vo, Hao Hsu, Zhenzhi Li, Anne T Di Donato, Abhishek Chaturbedi, Ji Won Hwang, Eric R Siegel, Mark E Linskey
De-regulated EFEMP1 gene expression in solid tumors has been widely reported with conflicting roles. We dissected EFEMP1 to identify domains responsible for its cell context-dependent dual functions, with the goal being to construct an EFEMP1-derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function. Exon/intron boundaries of EFEMP1 were used as boundaries of functional modules in constructing EFEMP1 variants, with removal of various module(s), and/or mutating an amino acid residue to convert a weak integrin binding-site into a strong one...
2016: Oncoscience
Zhenhao Qi, Lisu Wang, Aiqing He, Manling Ma-Edmonds, John Cogswell
AIM: Formalin-fixed, paraffin-embedded (FFPE) clinical tissue samples have the potential to provide valuable gene-expression data for the development of cancer biomarkers. However, FFPE RNA is extensively fragmented, presenting a significant challenge for reliably detecting gene expression using traditional qPCR methods. RESULTS: We evaluated three novel methodologies along with the traditional qPCR method for their ability to detect Notch pathway gene expression in colorectal cancer FFPE tissue RNAs...
October 7, 2016: Bioanalysis
Nameeta P Richard, Raffaella Pippa, Megan M Cleary, Alka Puri, Deanne Tibbitts, Shawn Mahmood, Dale J Christensen, Sophia Jeng, Shannon McWeeney, A Thomas Look, Bill H Chang, Jeffrey W Tyner, Michael P Vitek, María D Odero, Rosalie Sears, Anupriya Agarwal
Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated in T-ALL cell lines and primary samples compared to healthy T cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the activity of PP2A and reduced SET interaction with the PP2A catalytic subunit, resulting in a decrease in cell viability and c-MYC expression in a dose-dependent manner...
October 1, 2016: Oncotarget
M Majidinia, E Alizadeh, B Yousefi, M Akbarzadeh, N Zarghami
Despite remarkable progress in cancer treatment, development of drug resistance is still a big burden to eliminate all tumor cells and a mean cause for tumor recurrence. Recent studies have been revealed the contribution of many signaling pathways in acquisition of resistance to chemotherapy. Because of its potential in maintaining the balance between cell proliferation and apoptosis, Notch signaling pathway has mean relevance to various aspects of cancer biology, from cancer stem cells to tumor immunity to multidrug resistance...
October 4, 2016: Drug Research
Fernanda Silva, Ana Félix, Jacinta Serpa
Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages...
October 2016: Oncology Letters
(no author information available yet)
: Retraction: "Cisplatin-induced antitumor activity is potentiated by the soy isoflavonen genistein in BxPC-3 pancreatic tumor xenografts" by Mohammad RM, Banerjee S, Li Y, Aboukameel A, Kucuk O, Sarkar FH. The above article, published in Wiley Online Library (, has been retracted by agreement amongst the journal Editor in Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and the American Cancer Society following an investigation by Wayne State University into the research activities of the second and last authors...
October 15, 2016: Cancer
(no author information available yet)
: Retraction: "Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells" by Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. The above article, published in Wiley Online Library (, has been retracted by agreement amongst the journal Editor in Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and the American Cancer Society following an investigation by Wayne State University into the research activities of the first and last authors...
October 15, 2016: Cancer
Tanya Stoyanova, Mireille Riedinger, Shu Lin, Claire M Faltermeier, Bryan A Smith, Kelvin X Zhang, Catherine C Going, Andrew S Goldstein, John K Lee, Justin M Drake, Meghan A Rice, En-Chi Hsu, Behdokht Nowroozizadeh, Brandon Castor, Sandra Y Orellana, Steven M Blum, Donghui Cheng, Kenneth J Pienta, Robert E Reiter, Sharon J Pitteri, Jiaoti Huang, Owen N Witte
Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma...
September 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
Kole T Roybal, Jasper Z Williams, Leonardo Morsut, Levi J Rupp, Isabel Kolinko, Joseph H Choe, Whitney J Walker, Krista A McNally, Wendell A Lim
Redirecting T cells to attack cancer using engineered chimeric receptors provides powerful new therapeutic capabilities. However, the effectiveness of therapeutic T cells is constrained by the endogenous T cell response: certain facets of natural response programs can be toxic, whereas other responses, such as the ability to overcome tumor immunosuppression, are absent. Thus, the efficacy and safety of therapeutic cells could be improved if we could custom sculpt immune cell responses. Synthetic Notch (synNotch) receptors induce transcriptional activation in response to recognition of user-specified antigens...
October 6, 2016: Cell
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