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https://www.readbyqxmd.com/read/29459493/diagnostic-strategy-in-segmentation-defect-of-the-vertebrae-a-retrospective-study-of-73-patients
#1
Mathilde Lefebvre, Anne Dieux-Coeslier, Geneviève Baujat, Elise Schaefer, Saint-Onge Judith, Anne Bazin, Lucile Pinson, Tania Attie-Bitach, Clarisse Baumann, Melanie Fradin, Genevieve Pierquin, Sophie Julia, Chloé Quélin, Bérénice Doray, Sylvie Berg, Catherine Vincent-Delorme, Laetitia Lambert, Nadine Bachmann, Didier Lacombe, Bertrand Isidor, Nicole Laurent, Roume Joelle, Patricia Blanchet, Sylvie Odent, Dominique Kervran, Nathalie Leporrier, Carine Abel, Karine Segers, Fabienne Guiliano, Emmanuelle Ginglinger-Fabre, Angelo Selicorni, Alice Goldenberg, Salima El Chehadeh, Christine Francannet, Benedicte Demeer, Yannis Duffourd, Christel Thauvin-Robinet, Alain Verloes, Valerie Cormier-Daire, Jean Baptiste Riviere, Laurence Faivre, Julien Thevenon
BACKGROUND: Segmentation defects of the vertebrae (SDV) are non-specific features found in various syndromes. The molecular bases of SDV are not fully elucidated due to the wide range of phenotypes and classification issues. The genes involved are in the Notch signalling pathway, which is a key system in somitogenesis. Here we report on mutations identified in a diagnosis cohort of SDV. We focused on spondylocostal dysostosis (SCD) and the phenotype of these patients in order to establish a diagnostic strategy when confronted with SDV...
February 19, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#2
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#3
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#4
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29290251/prevalence-of-delta-like-protein-3-expression-in-patients-with-small-cell-lung-cancer
#5
Kentaro Tanaka, Kumiko Isse, Tomomichi Fujihira, Mitsuhiro Takenoyama, Laura Saunders, Sheila Bheddah, Yoichi Nakanishi, Isamu Okamoto
OBJECTIVES: Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC) positive for this protein. However, the prevalence of DLL3 expression and its association with patient ethnicity and other characteristics have remained unclear. MATERIAIS AND METHODS: Tumor samples from 63 patients with SCLC were subjected to immunohistochemical staining for DLL3...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#6
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29054964/gene-expression-profiling-of-the-notch-ahr-il22-axis-at-homeostasis-and-in-response-to-tissue-injury
#7
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and Interleukin-22 signaling are known to regulate tissue homeostasis and response to injury in humans and mice, and the induction of endogenous arylhydrocarbon receptor ligands through Notch links the two pathways in a hierarchical fashion. However, in adults the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TACE, PSEN1, BSG/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in 10 mature murine and human organs...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28705113/egfl7-participates-in-regulating-biological-behavior-of-growth-hormone-secreting-pituitary-adenomas-via-notch2-dll3-signaling-pathway
#8
Jianpeng Wang, Qian Liu, Hua Gao, Dehong Wan, Chuzhong Li, Zhaojian Li, Yazhuo Zhang
Growth hormone-secreting pituitary adenoma accounts for about 20% of the third most common intracranial neoplasm-pituitary adenomas-which makes up 15% of all intracranial tumors. The growth hormone-secreting pituitary adenoma invasion is a key risk factor associated with the operation results and highly correlated with the clinical prognosis. The epidermal growth factor-like domain multiple 7 protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic angiogenesis and enhance the tumor migration and invasion...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28685608/what-s-new-in-small-cell-lung-cancer-extensive-disease-an-overview-on-advances-of-systemic-treatment-in-2016
#9
Andreas Seeber, Christoph Leitner, Kathrin Philipp-Abbrederis, Gilbert Spizzo, Florian Kocher
Systemic therapy options for small cell lung cancer patients with extensive disease remain poor. After an initial response on first-line therapy, virtually all patients develop disease progression. For those who showed an initial response only few therapy options with low response rates are currently available. Until now, many experimental and targeted agents have failed to yield convincing clinical benefits, and new therapy options are clearly warranted for these patients. In this year's oncological congresses, several new therapy strategies, including checkpoint inhibition, showed promising results in ongoing trials...
July 2017: Future Oncology
https://www.readbyqxmd.com/read/28599454/differential-expression-of-the-notch1-receptor-and-its-ligands-dll1-dll3-and-dll4-in-distinct-human-pituitary-adenoma-subtypes
#10
Jianfu Zhang, Hua Gao, Yazhuo Zhang
Pituitary adenoma (PA) is a common type of benign tumor of the pituitary gland that is characterized by specific signs and symptoms, primarily associated with hypersecretion of pituitary glycoprotein hormones (thyroid-stimulating, growth and adrenocorticotrophic hormones, and prolactin). Surgery is the first-line treatment, although postoperative residual tissues/cells and subsequent recurrence remain notable complications. Gene therapy is an effective approach for treatment, as previous studies have demonstrated that the Notch signaling pathway participates in the pathogenesis of PA...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#11
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
September 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#12
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
July 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28487384/noninvasive-interrogation-of-dll3-expression-in-metastatic-small-cell-lung-cancer
#13
Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D Carlin, Alessandra Piersigilli, Alexander J Bankovich, Eric E Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M Cunanan, Eric B Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M Zeglis, Charles M Rudin, Scott J Dylla, John T Poirier, Jason S Lewis
The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is a first-in-class DLL3-targeted antibody-drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, although orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28482837/selective-gene-expression-analysis-of-the-neuroepithelial-body-microenvironment-in-postnatal-lungs-with-special-interest-for-potential-stem-cell-characteristics
#14
Line Verckist, Robrecht Lembrechts, Sofie Thys, Isabel Pintelon, Jean-Pierre Timmermans, Inge Brouns, Dirk Adriaensen
BACKGROUND: The pulmonary neuroepithelial body (NEB) microenvironment (ME) consists of innervated cell clusters that occur sparsely distributed in the airway epithelium, an organization that has so far hampered reliable selective gene expression analysis. Although the NEB ME has been suggested to be important for airway epithelial repair after ablation, little is known about their potential stem cell characteristics in healthy postnatal lungs. Here we report on a large-scale selective gene expression analysis of the NEB ME...
May 8, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28366784/enhanced-osteogenic-differentiation-of-rat-bone-marrow-mesenchymal-stem-cells-on-titanium-substrates-by-inhibiting-notch3
#15
Huiming Wang, Zhiwei Jiang, Jing Zhang, Zhijian Xie, Ying Wang, Guoli Yang
OBJECTIVE: The role of the Notch pathway has already been identified as a crucial regulator of bone development. However, the Notch signaling pathway has gone largely unexplored during osseointegration. This study aims to investigate the role of Notch signaling on osteogenic differentiation of rat derived bone marrow mesenchymal stem cells (BMSCs) on sandblasted, large-grit, acid-etched (SLA) treated Ti disks. METHODS: The involved target genes in Notch pathways were identified by in vitro microarray and bioinformatics analyses with or without osteogenic induction...
August 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28258914/gene-expression-profiling-of-circulating-cd133-cells-of-hepatocellular-carcinoma-patients-associated-with-hcv-infection
#16
Abdel-Rahman N Zekri, Enas R El-Sisi, Zeinab F Abdallah, Alaa Ismail, Ahmed Barakat Barakat
AIM: Identifying the genetic expression profile of CD133(+) cells from HCC patients compared to CD133(+) cells from healthy volunteers that may contribute in hepatocarcinogenesis process. METHOD: Circulating CD133(+) cells were sorted from the peripheral blood of HCC patients as well as from healthy volunteers using magnetic activated cell sorting. The differential expression profile of stem cell related genes was performed using the Stem Cell PCR profiling assay...
March 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/28158294/deep-proteome-mapping-of-wm-266-4-human-metastatic-melanoma-cells-from-oncogenic-addiction-to-druggable-targets
#17
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
#18
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
#19
(no author information available yet)
Rovalpituzumab tesirine is well tolerated and has single-agent antitumor activity.
February 2017: 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
#20
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
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