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Hanan Abu-Tayeh, Keren Weidenfeld, Alisa Zhilin-Roth, Sagi Schif-Zuck, Sonja Thaler, Cristina Cotarelo, Tuan Z Tan, Jean P Thiery, Jeffrey E Green, Geula Klorin, Edmond Sabo, Jonathan P Sleeman, Maty Tzukerman, Dalit Barkan
Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue...
December 1, 2016: Cell Death & Disease
Cui-Juan Qian, Yi-Yi Chen, Xin Zhang, Fu-Qiang Liu, Ting-Ting Yue, Bei Ye, Jun Yao
Overexpression of Notch4 is associated with a variety of tumor types. Only sparse information exists on Notch4 expression in pancreatic cancer (PC). The present study demonstrated that Notch4 expression was significantly upregulated in PC cell lines compared with a non-transformed pancreatic epithelial cell line, HPDE6c-7. To investigate the possible role of Notch4 in PC cells, an RNA interference approach was used to silence Notch4 expression. The results revealed that small interfering RNA (siRNA) targeting Notch4 significantly impeded the viability, migration and invasion abilities of PC cells in vitro...
November 2016: Oncology Letters
Christopher J Cardinale, Dong Li, Lifeng Tian, John J Connolly, Michael E March, Cuiping Hou, Fengxiang Wang, James Snyder, Cecilia E Kim, Rosetta M Chiavacci, Patrick M Sleiman, Jon M Burnham, Hakon Hakonarson
BACKGROUND: Systemic sclerosis (SSc) is a rheumatologic disease with a multifactorial etiology. Genome-wide association studies imply a polygenic, complex mode of inheritance with contributions from variation at the human leukocyte antigen locus and non-coding variation at a locus on chromosome 6p21, among other modestly impactful loci. Here we describe an 8-year-old female proband presenting with diffuse cutaneous SSc/scleroderma and a family history of SSc in a grandfather and maternal aunt...
November 9, 2016: BMC Musculoskeletal Disorders
Maria Oszajca, Guillaume Collet, Grażyna Stochel, Claudine Kieda, Małgorzata Brindell
The antimetastatic ruthenium(III) complex (H2Im)[trans-RuCl4(HIm)(DMSO)] (NAMI-A) as well as its two analogues (H2Ind)[trans-RuCl4(HInd)(DMSO)] (Ru-Ind) and (HIsq)[trans-RuCl4(Isq)(DMSO)] (Ru-Isq) (HIm-imidazole, HInd-indazole, Isq-isoquinoline, DMSO-dimethyl sulfoxide) were tested for their effect on endothelial cell functions in vitro on human skin microvascular endothelial cells (HSkMEC) and human endothelial progenitor cells (HPEC-CB.2) under normoxic (21 % O2) and hypoxic (1 % O2) conditions. All studied complexes showed very low cytotoxicity profiles towards both mature microvascular and precursor endothelial cells (ECs), independently of oxygen concentration...
December 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Wei-Lun Chang, Wu-Wei Lai, I-Ying Kuo, Chien-Yu Lin, Pei-Jung Lu, Bor-Shyang Sheu, Yi-Ching Wang
BACKGROUND: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. METHODS: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients...
September 26, 2016: Journal of Gastroenterology
Jinghai Hu, Fei Ye, Miao Cui, Peng Lee, Chengguo Wei, Yuanyuan Hao, Xiaoqing Wang, Yanbo Wang, Zhihua Lu, Matthew Galsky, Russell McBride, Li Wang, Dongwen Wang, Carlos Cordon-Cardo, Chunxi Wang, David Y Zhang
This study aimed to detect protein changes that can assist to understand the underlying biology of bladder cancer. The data showed forty five proteins were found to be differentially expressed comparing tumors vs non-tumor tissues, of which EGFR and cdc2p34 were correlated with muscle invasion and histological grade. Ten proteins (ß-catenin, HSP70, autotaxin, Notch4, PSTPIP1, DPYD, ODC, cyclinB1, calretinin and EPO) were able to classify muscle invasive BCa (MIBC) into 2 distinct groups, with group 2 associated with poorer survival...
2016: PloS One
Robert Callahan, Barry A Chestnut, Ahmed Raafat
Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment...
January 2017: Experimental Biology and Medicine
Li-Min Long, Jun-Kun Zhan, Hai-Qin Wang, Shuang Li, Yi-Yin Chen, You-Shuo Liu
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits poor prognosis and resistance to chemotherapy. This study was to identify the biomarkers associated with the progression, poor prognosis and chemoresistance of PDAC. METHODS: miR-34a and miR-150 levels in the plasma and tissues from PDAC patients were measured by real-time PCR. Xenograft PDAC tumor models were established in mice by inoculation of CD133+ stem cells isolated from PDAC tumors. Protein expression was measured by Western blot...
2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Luigi Strizzi, Naira V Margaryan, Pedram Gerami, Zahra Haghighat, Paul W Harms, Gabriele Madonna, Gerardo Botti, Paolo A Ascierto, Mary J C Hendrix
The TGF-β associated growth factor Nodal is highly expressed in aggressive metastatic melanoma. Determining the risk for melanomagenesis from Nodal expression in nevi prior to the development of melanoma may be useful for both the screening and prevention of melanoma. Tissue sections of human adult nevi with or without a history of melanoma were stained by immunohistochemistry (IHC) for Nodal, the Nodal co-receptor Cripto-1, and Notch4, which have previously been shown to be associated with Nodal expression in melanoma...
August 2016: Oncology Letters
Rolake O Alabi, Krzysztof Glomski, Coline Haxaire, Gisela Weskamp, Sébastien Monette, Carl P Blobel
RATIONALE: Endothelial Notch signaling is critical for early vascular development and survival. Yet, previously described mice lacking endothelial a disintegrin and metalloproteinase 10 (ADAM10), a key regulator of Notch signaling, survived into adulthood with organ-specific vascular defects. These findings raised questions about whether these vascular defects were related to Notch signaling or other functions of ADAM10. OBJECTIVE: The aims of the study are to determine whether compensatory or redundant functions of ADAM17 in Notch signaling can explain the survival of Adam10ΔEC mice, explore the contribution of different Tie2-Cre transgenes to the differences in survival, and establish whether the Adam10ΔEC vascular phenotypes can be recapitulated by inactivation of Notch receptors in endothelial cells...
August 5, 2016: Circulation Research
Yilin Ping, Feng Lou, Xiao Yang, Ping Zhang
OBJECTIVE: This study aimed to explore the effect of the up-regulation of Notch1 on osteoclastogenesis induced to osteoclasts by receptor activator for nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factors (MCSF) in vitro. METHODS: The bone marrow stem cells (BMSCs) of Rosa(-notch1) mice were cultured and induced to osteoclasts by RANKL and MCSF. The BMSCs were transfected with the Ad-Cre-green fluorescent protein (GFP) virus or Ad-GFP virus...
April 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
Xiao Xiao, Xiong-Jian Luo, Hong Chang, Zichao Liu, Ming Li
Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals...
June 18, 2016: Molecular Neurobiology
Xian Lin, Baocun Sun, Dongwang Zhu, Xiulan Zhao, Ran Sun, Yanhui Zhang, Danfang Zhang, Xueyi Dong, Qiang Gu, Yanlei Li, Fang Liu
Sphere formation in conditioned serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor (tumorospheres) is considered useful for the enrichment of cancer stem-like cells, also known as tumor-initiating cells. We used a gene expression microarray to investigate the gene expression profile of melanoma cancer stem-like cells (MCSLCs). The results showed that MCSLCs highly expressed the following Notch signaling pathway molecules: Notch3 (NM_008716), Notch4 (NM_010929), Dtx4 (NM_172442), and JAG2 (NM_010588)...
August 2016: Cancer Science
Daniel Delev, Anna Pavlova, Alexander Grote, Azize Boström, Anke Höllig, Johannes Schramm, Rolf Fimmers, Johannes Oldenburg, Matthias Simon
OBJECTIVE Arteriovenous malformations (AVMs) of the brain are a frequent and important cause of intracranial hemorrhage in young adults. Little is known about the molecular-genetic pathomechanisms underlying AVM development. Genes of the NOTCH family control the normal development of vessels and proper arteriovenous specification. Transgenic mice with constitutive expression of active NOTCH4 frequently develop AVMs. Here, the authors report a genetic association study investigating possible associations between NOTCH4 gene polymorphisms and formation and clinical presentation of AVMs...
May 27, 2016: Journal of Neurosurgery
Harishankar Mk, Sharon Prince, A Mathan Mohan, K Vinod Krishnan, Arikketh Devi
AIMS: Despite the development of several therapeutic strategies in the past decades, clinicians have failed to improve the survival rate of oral squamous cell carcinoma patients due to the highly metastatic nature of the disease and its high recurrence rate. However, there is accumulating evidence that aberrant Notch4 expression has a critical role in tumorigenesis but its prognostic value and function in OSCC remains uncertain. This study therefore investigates (1) the expression of Notch4 and its downstream target, myelin associated glycoprotein (MAG) in tissue samples representative of different stages of OSCC with varied clinicopathological features and (2) the possible involvement of Notch4 in the proliferation and migration of OSCC cells...
July 1, 2016: Life Sciences
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)
Fernando Ortiz-Martínez, Francisco José Gutiérrez-Aviñó, Elena Sanmartín, Eloy Pomares-Navarro, Cristina Villalba-Riquelme, Araceli García-Martínez, Enrique Lerma, Gloria Peiró
T regulatory cells (Tregs) are a lineage of lymphocytes involved in immune response suppression that are characterized by the expression of the forkhead box P3 (FOXP3) transcription factor. Notch pathway regulates FOXP3 transcription in Tregs, but its role in breast cancer is unknown. We aimed at studying whether Notch pathway regulates FOXP3 expression and Tregs content in breast cancer, and its association with luminal breast carcinomas. We analyzed by quantitative Real-Time PCR the mRNA levels of FOXP3, Notch pathway genes (Notch1, Notch2, Notch4 and Jagged1) and STAT3 in a series of 152 breast carcinomas including hormone receptor-positive and -negative phenotypes (luminal and Triple Negative/Basal-like)...
June 2016: Experimental and Molecular Pathology
Xiaoxia Liu, Qingqing Luo, Yanfang Zheng, Xiaoping Liu, Ying Hu, Weifang Liu, Minglian Luo, Yin Zhao, Li Zou
Preeclampsia is a serious complication of pregnancy and is closely related to endothelial dysfunction, which can be repaired by endothelial progenitor cells (EPCs). The DLL4/NOTCH-EFNB2 (ephrinB2) cascade may be involved in the pathogenesis of preeclampsia by inhibiting the biological activity of EPCs. In addition, both NOTCH1 and NOTCH4, which are specific receptors for DLL4/NOTCH, play critical roles in the various steps of angiogenesis. However, it has not been determined which receptor (NOTCH1, NOTCH4, or both) is specific for the DLL4/NOTCH-EFNB2 cascade...
July 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Micaela Pannella, Cristiana Caliceti, Francesca Fortini, Giorgio Aquila, Francesco Vieceli Dalla Sega, Antonio Pannuti, Cinzia Fortini, Marco Bruno Morelli, Alessandro Fucili, Gloria Francolini, Rebecca Voltan, Paola Secchiero, Giovanni Dinelli, Emanuela Leoncini, Manuela Ferracin, Silvana Hrelia, Lucio Miele, Paola Rizzo
It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4...
December 2016: Journal of Cellular Physiology
Murali Subramani, Ponnalagu Murugeswari, Kamesh Dhamodaran, Priyanka Chevour, Sindhu Gunasekaran, Rajesh S Kumar, Chaitra Jayadev, Rohit Shetty, Nargis Begum, Debashish Das
PURPOSE: Cross-talk between Notch signaling and vascular endothelial growth factor (VEGF) is a major driver of angiogenesis. Here we investigated the temporal effect of bevacizumab (BEV) on Notch signaling and the functional features of cultured primary retinal pigment epithelial (PRPE) cells. METHODS: Human (cadaver) PRPE cells were treated with clinical concentrations of BEV (0.25 mg/mL). Notch signaling pathway receptors, ligands, and downstream target genes were analyzed with quantitative real-time polymerase chain reaction (qRT-PCR)...
March 2016: Investigative Ophthalmology & Visual Science
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