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https://www.readbyqxmd.com/read/28158294/deep-proteome-mapping-of-wm-266-4-human-metastatic-melanoma-cells-from-oncogenic-addiction-to-druggable-targets
#1
Eumorphia G Konstantakou, Athanassios D Velentzas, Athanasios K Anagnostopoulos, Zoi I Litou, Ourania A Konstandi, Aikaterini F Giannopoulou, Ema Anastasiadou, Gerassimos E Voutsinas, George Th Tsangaris, Dimitrios J Stravopodis
Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma's heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28007595/the-notch-ligand-delta-like-3-promotes-tumor-growth-and-inhibits-notch-signaling-in-lung-cancer-cells-in-mice
#2
San-Ming Deng, Xian-Chun Yan, Liang Liang, Li Wang, Yuan Liu, Juan-Li Duan, Zi-Yan Yang, Tian-Fang Chang, Bai Ruan, Qi-Jun Zheng, Hua Han
Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27986711/rovalpituzumab-tesirine-is-active-in-patients-with-dll3-positive-tumors
#3
(no author information available yet)
Rovalpituzumab tesirine is well tolerated and has single-agent antitumor activity.
December 16, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27969444/oral02-01-safety-and-efficacy-of-single-agent-rovalpituzumab-tesirine-a-dll3-targeted-adc-in-recurrent-or%C3%A2-refractory-sclc-topic-medical-oncology
#4
Todd M Bauer, David Spigel, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Howard Burris, Francisco Robert, Donald K Strickland, Maria C Pietanza, Ramaswamy Govindan, Scott J Dylla, Stanford Peng, Charles Rudin
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27932068/rovalpituzumab-tesirine-a-dll3-targeted-antibody-drug-conjugate-in-recurrent-small-cell-lung-cancer-a-first-in-human-first-in-class-open-label-phase-1-study
#5
Charles M Rudin, M Catherine Pietanza, Todd M Bauer, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Melissa L Johnson, Howard A Burris, Francisco Robert, Tae H Han, Sheila Bheddah, Noah Theiss, Sky Watson, Deepan Mathur, Bharathi Vennapusa, Hany Zayed, Satwant Lally, Donald K Strickland, Ramaswamy Govindan, Scott J Dylla, Stanford L Peng, David R Spigel
BACKGROUND: Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in more than 80% of patients with small-cell lung cancer. We aimed to assess the safety and activity of rovalpituzumab tesirine in patients who progressed after one or more previous regimen. METHODS: We conducted a phase 1 open-label study at ten cancer centres in the USA...
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27932065/rovalpituzumab-tesirine-and-dll3-a-new-challenge-for-small-cell-lung-cancer
#6
Antonio Rossi
No abstract text is available yet for this article.
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27929540/inflammation-and-notch-signaling-a-crosstalk-with-opposite-effects-on-tumorigenesis
#7
REVIEW
Chiara Fazio, Luigi Ricciardiello
The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1-4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, DLL3 or DLL4) or non-canonically (through various molecules shared by other pathways). In the context of tumor biology, the deregulation of Notch signaling is found to be crucial, but it is still not clear if the activation of this pathway exerts a tumor-promoting or a tumor suppressing function in different cancer settings...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#8
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27894818/supt20-is-required-for-development-of-the-axial-skeleton
#9
Sunita Warrier, Samer Nuwayhid, Julia A Sabatino, Kelsey F Sugrue, Irene E Zohn
Somitogenesis and subsequent axial skeletal development is regulated by the interaction of pathways that determine the periodicity of somite formation, rostrocaudal somite polarity and segment identity. Here we use a hypomorphic mutant mouse line to demonstrate that Supt20 (Suppressor of Ty20) is required for development of the axial skeleton. Supt20 hypomorphs display fusions of the ribs and vertebrae at lower thoracic levels along with anterior homeotic transformation of L1 to T14. These defects are preceded by reduction of the rostral somite and posterior shifts in Hox gene expression...
January 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/27882195/design-and-synthesis-of-tesirine-a-clinical-antibody-drug-conjugate-pyrrolobenzodiazepine-dimer-payload
#10
Arnaud C Tiberghien, Jean-Noel Levy, Luke A Masterson, Neki V Patel, Lauren R Adams, Simon Corbett, David G Williams, John A Hartley, Philip W Howard
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. One of the reactive imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust synthetic route was developed to allow the production of tesirine on clinical scale, employing a flexible, convergent strategy...
November 10, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27782828/spatial-transcriptome-analysis-reveals-notch-pathway-associated-prognostic-markers-in-idh1-wild-type-glioblastoma-involving-the-subventricular-zone
#11
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
https://www.readbyqxmd.com/read/27520484/chemotherapy-enhances-tumor-vascularization-via-notch-signaling-mediated-formation-of-tumor-derived-endothelium-in-breast-cancer
#12
Peng Zhang, Dongxu He, Zhen Chen, Qiongxi Pan, Fangfang Du, Xian Zang, Yan Wang, Chunlei Tang, Hong Li, He Lu, Xiaoqiang Yao, Jian Jin, Xin Ma
It is believed that tumor cells can give rise to endothelial cells and tumor endothelium has a neoplastic origin. Yet, the stimuli and underlying mechanism remain unclear. Here, we demonstrate that adriamycin or paclitaxel, first-line chemotherapy agent, induced breast cancer cells to generate morphological, phenotypical and functional features of endothelial cells in vitro. In xenografts models, challenges from adriamycin or paclitaxel induced cancer cells to generate the majority of microvessels. Importantly, in breast cancer specimens from patients with neoadjuvant anthracycline-based or taxane-based chemotherapy, tumor-derived endothelial microvessels, lined by EGFR-amplified or/and TP53(+)-CD31(+) endothelial cells, was significantly higher in patients with progressive or stable disease (PD/SD) than in those with a partial or complete response (PR/CR)...
October 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27472720/five-known-tagging-dll3-snps-are-not-associated-with-congenital-scoliosis-a-case-control-association-study-in-a-chinese-han-population
#13
Yong Yang, Bing-Qiang Wang, Zhi-Hong Wu, Hai-Yan Zhang, Gui-Xing Qiu, Jian-Xiong Shen, Jian-Guo Zhang, Yu Zhao, Yi-Peng Wang, Qi Fei
Genetic etiology hypothesis is widely accepted in the development of congenital scoliosis (CS). The delta-like 3 (DLL3) gene, a member of the Notch signaling pathway, was implicated to contribute to human CS. In this study, a case-control association study was conducted to determine the association of single nucleotide polymorphism (SNP) in the DLL3 gene with CS in a Chinese Han Population. Five known tagging SNPs of the DLL3 gene were genotyped among 270 Chinese Han subjects (128 nonsyndromic CS patients and 142 matched controls)...
July 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27452466/ascl1-and-neurod1-reveal-heterogeneity-in-pulmonary-neuroendocrine-tumors-and-regulate-distinct-genetic-programs
#14
Mark D Borromeo, Trisha K Savage, Rahul K Kollipara, Min He, Alexander Augustyn, Jihan K Osborne, Luc Girard, John D Minna, Adi F Gazdar, Melanie H Cobb, Jane E Johnson
Small cell lung carcinoma (SCLC) is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC...
August 2, 2016: Cell Reports
https://www.readbyqxmd.com/read/27308627/toppling-high-grade-pulmonary-neuroendocrine-tumors-with-a-dll3-targeted-trojan-horse
#15
Scott J Dylla
Delta-like protein 3 (DLL3) is a novel and tractable tumor-initiating cell-associated target for the antibody-drug conjugate SC16LD6.5 in high-grade pulmonary neuroendocrine tumors. Elevated expression of DLL3, an inhibitor of Notch pathway activation, marks the second recent observation that impairment of Notch receptor signaling may play a critical role in neuroendocrine tumorigenesis.
March 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27196489/notch-signaling-components-diverging-prognostic-indicators-in-lung-adenocarcinoma
#16
Zhi-Yan Liu, Tao Wu, Qing Li, Min-Cong Wang, Li Jing, Zhi-Ping Ruan, Yu Yao, Ke-Jun Nan, Hui Guo
Non-small-cell lung cancer (NSCLC) is a lethal and aggressive malignancy. Currently, the identities of prognostic and predictive makers of NSCLC have not been fully established. Dysregulated Notch signaling has been implicated in many human malignancies, including NSCLC. However, the prognostic value of measuring Notch signaling and the utility of developing Notch-targeted therapies in NSCLC remain inconclusive. The present study investigated the association of individual Notch receptor and ligand levels with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) prognosis using the Kaplan-Meier plotte database...
May 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/26911688/lhx2-is-an-essential-factor-for-retinal-gliogenesis-and-notch-signaling
#17
Jimmy de Melo, Cristina Zibetti, Brian S Clark, Woochang Hwang, Ana L Miranda-Angulo, Jiang Qian, Seth Blackshaw
Müller glia (MG) are the only glial cell type produced by the neuroepithelial progenitor cells that generate the vertebrate retina. MG are required to maintain retinal homeostasis and support the survival of retinal neurons. Furthermore, in certain vertebrate classes, MG function as adult stem cells, mediating retinal regeneration in response to injury. However, the mechanisms that regulate MG development are poorly understood because there is considerable overlap in gene expression between retinal progenitor cells and differentiated MG...
February 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26673007/quinomycin-a-targets-notch-signaling-pathway-in-pancreatic-cancer-stem-cells
#18
Sivapriya Ponnurangam, Prasad R Dandawate, Animesh Dhar, Ossama W Tawfik, Rajashri R Parab, Prabhu Dutt Mishra, Prafull Ranadive, Rajiv Sharma, Girish Mahajan, Shahid Umar, Scott J Weir, Aravind Sugumar, Roy A Jensen, Subhash B Padhye, Arun Balakrishnan, Shrikant Anant, Dharmalingam Subramaniam
Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notch signaling pathway. Quinomycin treatment resulted in significant inhibition of proliferation and colony formation in pancreatic cancer cell lines, but not in normal pancreatic epithelial cells...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26662803/aberrant-expression-of-notch1-hes1-and-dtx1-genes-in-glioblastoma-formalin-fixed-paraffin-embedded-tissues
#19
Rajeswari Narayanappa, Pritilata Rout, Madhuri G S Aithal, Ashis Kumar Chand
Glioblastoma is the most common malignant brain tumor accounting for more than 54 % of all gliomas. Despite aggressive treatments, median survival remains less than 1 year. This might be due to the unavailability of effective molecular diagnostic markers and targeted therapy. Thus, it is essential to discover molecular mechanisms underlying disease by identifying dysregulated pathways involved in tumorigenesis. Notch signaling is one such pathway which plays an important role in determining cell fates. Since it is found to play a critical role in many cancers, we investigated the role of Notch genes in glioblastoma with an aim to identify biomarkers that can improve diagnosis...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26637806/molecular-heterogeneity-of-glioblastomas-does-location-matter
#20
Emilie Denicolaï, Emeline Tabouret, Carole Colin, Philippe Metellus, Isabelle Nanni, Celine Boucard, Aurélie Tchoghandjian, David Meyronet, Nathalie Baeza-Kallee, Olivier Chinot, Dominique Figarella-Branger
Glioblastomas in adults are highly heterogeneous tumors that can develop throughout the brain. To date no predictive-location marker has been identified. We previously derived two glioblastoma cell lines from cortical and periventricular locations and demonstrated distinct transcriptomic profiles. Based on these preliminary results, the aim of this study was to correlate glioblastoma locations with the expression of ten selected genes (VEGFC, FLT4, MET, HGF, CHI3L1, PROM1, NOTCH1, DLL3, PDGFRA, BCAN). Fifty nine patients with newly diagnosed glioblastomas were retrospectively included...
January 5, 2016: Oncotarget
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