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Article ; Online: Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans.

Charar, Chayki / Metsuyanim-Cohen, Sally / Bar, Daniel Z

2021 Volume 134, Issue 17

Abstract: Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the ... ...

Abstract	Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream of RAPTOR and S6 kinase β1 (S6K), a key component of and target of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Laminin ; Lamins ; Longevity/genetics ; Mechanistic Target of Rapamycin Complex 1/genetics ; TOR Serine-Threonine Kinases/genetics
Chemical Substances	Caenorhabditis elegans Proteins ; LMN-1 protein, C elegans ; Laminin ; Lamins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.258428
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 14: Show issues

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Article ; Online: Exploring the nuclear lamina in health and pathology using C. elegans.

Charar, Chayki / Metsuyanim-Cohen, Sally / Gruenbaum, Yosef / Bar, Daniel Z

Current topics in developmental biology

2021 Volume 144, Page(s) 91–110

Abstract: The eukaryotic genome inside the nucleus is enveloped by two membranes, the Outer Nuclear Membrane (ONM) and the Inner Nuclear Membrane (INM). Tethered to the INM is the nuclear lamina, a fibrillar network composed of lamins-the nuclear intermediate ... ...

Abstract	The eukaryotic genome inside the nucleus is enveloped by two membranes, the Outer Nuclear Membrane (ONM) and the Inner Nuclear Membrane (INM). Tethered to the INM is the nuclear lamina, a fibrillar network composed of lamins-the nuclear intermediate filaments, and membrane associated proteins. The nuclear lamina interacts with several nuclear structures, including chromatin. As most nuclear functions, including regulation of gene expression, chromosome segregation and duplication as well as nuclear structure, are highly conserved in metazoans, the Caenorhabditis elegans nematode serves as a powerful model organism to study nuclear processes and architecture. This translucent organism can easily be observed under a microscope as a live embryo, larvae and even adult. Here we will review the data on nuclear lamina composition and functions gathered from studies using C. elegans model organisms: We will discuss genome spatial organization and its contribution to gene expression. We will review both the interaction between the cytoplasm and the nucleus and mechanotransduction mechanism. Finally, we will discuss disease causing mutation in nuclear lamins, including the use of this animal model in diseases research.
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Lamins/genetics ; Mechanotransduction, Cellular ; Nuclear Lamina
Chemical Substances	Lamins
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-8933 ; 0070-2153
ISSN (online)	1557-8933
ISSN	0070-2153
DOI	10.1016/bs.ctdb.2020.12.005
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Article ; Online: Molecular evaluation of circulating endothelial progenitor cells in children undergoing hemodialysis and after kidney transplantation.

Metsuyanim, Sally / Levy, Ran / Davidovits, Miriam / Dekel, Benjamin

Pediatric research

2009 Volume 65, Issue 2, Page(s) 221–225

Abstract: Increased risk of cardiovascular disease in end-stage renal disease (ESRD) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPC) may play key roles. Circulating cells with endothelial ... ...

Abstract	Increased risk of cardiovascular disease in end-stage renal disease (ESRD) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPC) may play key roles. Circulating cells with endothelial progenitor phenotype have not been evaluated in children with ESRD. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) approach, we measured endothelial-specific and progenitor-associated genes VE-cadherin (VE-C), CD146, CD31, tyrosine-protein kinase receptor (Tie-2), Flk1, CD133, and growth factors promoting EPC function, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and stromal cell-derived factor-1 (SDF-1) in the blood of pediatric patients undergoing hemodialysis and after transplantation. Patients' metabolic parameters were correlated with EPC marker gene levels. Compared with controls, circulating VE-cadherin, CD146, Flk1, VEGF, and EPO RNA levels were decreased in ESRD and normalized in transplanted patients. Levels of VE-cadherin, which were the most significantly reduced in ESRD (p = 0.001) inversely correlated in all of the patient population with serum urea and creatinine concentration, whereas among the ESRD group showed an inverse correlation with diastolic blood pressure (BP), interventricular septum thickness (IVST), and left ventricular mass index. Pediatric ESRD patients may have lower angiogenic potential and increased cardiovascular morbidity, because of decreased expression of circulating endothelial cell specific transcripts. Prospective studies are required to link this expression pattern and its restoration in transplanted patients to cardiovascular outcome.
MeSH term(s)	Adolescent ; Angiogenic Proteins/blood ; Angiogenic Proteins/genetics ; Biomarkers/blood ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/etiology ; Child ; Endothelial Cells/metabolism ; Female ; Humans ; Kidney Failure, Chronic/blood ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/surgery ; Kidney Failure, Chronic/therapy ; Kidney Transplantation ; Male ; RNA, Messenger/blood ; Renal Dialysis ; Stem Cells/metabolism ; Treatment Outcome ; Young Adult
Chemical Substances	Angiogenic Proteins ; Biomarkers ; RNA, Messenger
Language	English
Publishing date	2009-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1203/PDR.0b013e3181903909
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 373: Show issues

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Article ; Online: BRCA1-dependent Chk1 phosphorylation triggers partial chromatin disassociation of phosphorylated Chk1 and facilitates S-phase cell cycle arrest.

Yarden, Ronit I / Metsuyanim, Sally / Pickholtz, Itay / Shabbeer, Shabana / Tellio, Hadass / Papa, Moshe Z

The international journal of biochemistry & cell biology

2012 Volume 44, Issue 11, Page(s) 1761–1769

Abstract: Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among ... ...

Abstract	Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among several checkpoint mediators that are required for Chk1 activation by ATM and ATR. Previously we showed that BRCA1 is necessary for Chk1 phosphorylation and activation following ionizing radiation. BRCA1 has been implicated in S-phase checkpoint control yet its mechanism of action is not well characterized. Here we report that BRCA1 is critical for Chk1 phosphorylation in response to inhibition of replication by either cisplatin or hydroxyurea. While Chk1 phosphorylation of S317 is fully dependent on BRCA1, additional proteins may mediate S345 phosphorylation at later time points. In addition, we show that a subset of phosphorylated Chk1 is released from the chromatin in a BRCA1-dependent manner which may lead to the phosphorylation of Chk1 substrate, Cdc25C, on S216 and to S-phase checkpoint activation. Inhibition of Chk1 kinase by UCN-01 or expression of Chk1 phosphorylation mutants in which the serine residues were substituted with alanine residues abrogates BRCA1-dependent cell cycle arrest in response replication inhibition. These data reveal that BRCA1 facilitates Chk1 phosphorylation and its partial chromatin dissociation following replication inhibition that is likely to be required for S-phase checkpoint signaling.
MeSH term(s)	BRCA1 Protein/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Checkpoints/radiation effects ; Cell Line, Tumor ; Checkpoint Kinase 1 ; Chromatin/drug effects ; Chromatin/metabolism ; DNA Damage ; DNA Replication/drug effects ; DNA Replication/radiation effects ; Enzyme Activation/drug effects ; Enzyme Activation/radiation effects ; Humans ; Hydroxyurea/pharmacology ; Mutant Proteins/metabolism ; Phosphorylation/drug effects ; Phosphorylation/radiation effects ; Phosphoserine/metabolism ; Protein Kinases/metabolism ; Radiation, Ionizing ; S Phase/drug effects ; S Phase/radiation effects ; Signal Transduction/drug effects ; Signal Transduction/radiation effects ; Stress, Physiological/drug effects ; Stress, Physiological/radiation effects
Chemical Substances	BRCA1 Protein ; Chromatin ; Mutant Proteins ; Phosphoserine (17885-08-4) ; Protein Kinases (EC 2.7.-) ; CHEK1 protein, human (EC 2.7.11.1) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; Hydroxyurea (X6Q56QN5QC)
Language	English
Publishing date	2012-06-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2012.06.026
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Zs.A 431: Show issues

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Article ; Online: Single-nucleotide polymorphisms in the p53 pathway genes modify cancer risk in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

Yarden, Ronit I / Friedman, Eitan / Metsuyanim, Sally / Olender, Tzvia / Ben-Asher, Edna / Papa, Moshe Z

Molecular carcinogenesis

2010 Volume 49, Issue 6, Page(s) 545–555

Abstract: Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of ... ...

Abstract	Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors. Therefore, we assessed whether these genes are modifiers of penetrance. We genotyped Jewish-Ashkenazi women for functional single-nucleotide polymorphisms (SNPs) in the AKT1 (C>T rs3730358) and the PERP (C>T rs2484067) genes that affect p53-mediated apoptosis, as well as two tag-SNPs in the CHEK2 (C>T rs743184) and the ZBRK1/ZNF350 (G>A rs2278414) genes that encode for proteins involved in growth arrest following DNA damage. The study population included 138 healthy women, 148 breast/ovarian cancer BRCA1/2 mutation carriers, 121 asymptomatic BRCA1/2 mutation carriers, and 210 sporadic noncarrier breast cancer patients. Utilizing lambda(2) and Kaplan-Meier analysis revealed a hazard ratio (HR) of 3.23 (95% CI: 1.44-54, P = 0.0184) for the TT genotype of AKT (rs3730358), HR = 2.105 (95% CI: 1.049-7.434, P = 0.039) for CHEK2 CC genotype (rs743184), and HR = 2.4743 (95% CI: 1.205-11.53, P = 0.022) for the AG genotype of ZBRK1/ZNF350 (rs2278414). No significant association between PERP variants and cancer was identified HR = 0.662 (95% CI: 0.289-1.324, P = 0.261). Our results suggest that genes that act upstream of p53, or participate in the DNA damage response, may modify the risk of cancer in women with mutant BRCA1/2 alleles.
MeSH term(s)	Adult ; Breast Neoplasms/ethnology ; Breast Neoplasms/genetics ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genes, p53 ; Genetic Predisposition to Disease ; Humans ; Jews/genetics ; Middle Aged ; Mutation ; Ovarian Neoplasms/ethnology ; Ovarian Neoplasms/genetics ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2010-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.20618
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Zs.A 2664: Show issues

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Article ; Online: Chromatin-modifying agents reactivate embryonic renal stem/progenitor genes in human adult kidney epithelial cells but abrogate dedifferentiation and stemness.

Omer, Dorit / Harari-Steinberg, Orit / Buzhor, Ella / Metsuyanim, Sally / Pleniceanu, Oren / Zundelevich, Adi / Gal-Yam, Einav Nili / Dekel, Benjamin

Cellular reprogramming

2013 Volume 15, Issue 4, Page(s) 281–292

Abstract: Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation and increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been ... ...

Abstract	Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation and increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been shown to promote self-renewal/expansion of hematopoietic stem cells and facilitate the generation of induced pluripotent stem cells (iPSCs). Previously, we observed that downregulation of embryonic renal stem/progenitor genes in the adult kidney was associated, at least in part, with epigenetic silencing. Therefore, we hypothesized that VPA may alter the expression of these genes and reprogram mature human adult kidney epithelial cells (hKEpCs) to a stem/progenitor-like state. Here, using quantitative RT-PCR and flow cytometry [fluorescence-activated cell sorting (FACS)] analysis, we show in VPA-treated primary cultures of human adult and fetal kidney significant reinduction of the renal stem/progenitor markers SIX2, OSR1, SALL1, NCAM, and PSA-NCAM. Robust SIX2 mRNA re-expression was confirmed at the protein level by western blot and was associated with epigenetic changes of the histones at multiple sites of the SIX2 promoter leading to gene activation, significantly increased acetylation of histones H4, and methylation of lysine 4 on H3. Furthermore, we could demonstrate synergistic effects of VPA and Wnt antagonists on SIX2 and also OSR1 reinduction. Nevertheless, VPA resulted in upregulation of E-CADHERIN and reduction in VIMENTIN, preventing the skewing of hKEpCs towards a more replicative mesenchymal state required for clonogenic expansion and acquisition of stem cell characters, altogether inducing cell senescence at early passages. These results demonstrating that chromatin-modifying agents prevent dedifferentiation of hKEpCs have important clinical implications as they may limit ex-vivo self-renewal/expansion and possibly the in vivo renal regenerative capacity initiated by dedifferentiation.
MeSH term(s)	Adult ; Animals ; Cell Dedifferentiation/drug effects ; Cell Dedifferentiation/genetics ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Cells, Cultured ; Chick Embryo ; Chromatin Assembly and Disassembly/drug effects ; Embryonic Stem Cells/drug effects ; Embryonic Stem Cells/physiology ; Epithelial Cells/drug effects ; Epithelial Cells/physiology ; Fetus/cytology ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Kidney/cytology ; Kidney/embryology ; Valproic Acid/pharmacology
Chemical Substances	Histone Deacetylase Inhibitors ; Valproic Acid (614OI1Z5WI)
Language	English
Publishing date	2013-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2542436-1
ISSN	2152-4998 ; 1557-7457 ; 2152-4971
ISSN (online)	2152-4998 ; 1557-7457
ISSN	2152-4971
DOI	10.1089/cell.2012.0087
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Zs.A 5452: Show issues

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Article ; Online: Analysis of circulating hem-endothelial marker RNA levels in preterm infants.

Strauss, Tzipora / Metsuyanim, Sally / Pessach, Itai / Shuchan-Eisen, Irit / Kuint, Jacob / Dekel, Benjamin

BMC pediatrics

2009 Volume 9, Page(s) 42

Abstract: Background: Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating ... ...

Abstract	Background: Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods: Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3-5, 10-15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1) in association with characteristics of prematurity and preterm morbidity. Results: Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion: These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.
MeSH term(s)	AC133 Antigen ; Antigens, CD/blood ; Antigens, CD/genetics ; Basic Helix-Loop-Helix Transcription Factors/blood ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Birth Weight ; Echoencephalography ; Endothelial Cells/cytology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Female ; Gestational Age ; Glycoproteins/blood ; Glycoproteins/genetics ; Hematopoietic Stem Cells/cytology ; Humans ; Infant, Newborn ; Infant, Premature/blood ; Male ; Neovascularization, Physiologic ; Peptides/blood ; Peptides/genetics ; Proto-Oncogene Proteins/blood ; Proto-Oncogene Proteins/genetics ; RNA/blood ; Receptor, TIE-2/blood ; Receptor, TIE-2/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/cytology ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Vascular Endothelial Growth Factor Receptor-2/blood ; Vascular Endothelial Growth Factor Receptor-2/genetics
Chemical Substances	AC133 Antigen ; Antigens, CD ; Basic Helix-Loop-Helix Transcription Factors ; Glycoproteins ; PROM1 protein, human ; Peptides ; Proto-Oncogene Proteins ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; TAL1 protein, human (135471-20-4) ; RNA (63231-63-0) ; Receptor, TIE-2 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2009-06-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/1471-2431-9-42
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Article: MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

Yarden, Ronit I / Friedman, Eitan / Metsuyanim, Sally / Olender, Tsviya / Ben-Asher, Edna / Papa, Moshe Zvi

Breast cancer research and treatment

2008 Volume 111, Issue 3, Page(s) 497–504

Abstract: A functional single nucleotide polymorphism in the promoter of the MDM2 gene, SNP309 (T>G), was recently found to accelerate tumorigenesis in early onset cancer cases. The SNP309 G-allele, introduces an SP1 site in the MDM2 promoter, resulting in ... ...

Abstract	A functional single nucleotide polymorphism in the promoter of the MDM2 gene, SNP309 (T>G), was recently found to accelerate tumorigenesis in early onset cancer cases. The SNP309 G-allele, introduces an SP1 site in the MDM2 promoter, resulting in enhanced MDM2 expression and activity. Thus, the G-allele of MDM2 SNP309 may represent a cancer predisposing allele. In this report, we assessed the role of SNP309 as a modifier of mutant BRCA1/BRCA2 alleles in inherited breast and ovarian cancer cases among Ashkenazi-Jewish (AJ) women. We genotyped several subsets of AJ women: 138 healthy women, 140 affected BRCA1/2 mutation carriers, 120 asymptomatic BRCA1/2 mutation carriers and 187 sporadic breast cancer patients. The frequency of GG genotype of SNP309 was similar among the different groups. Interestingly, we found almost three times higher frequency of the GG genotype among BRCA1/2 carriers diagnosed with breast and/or ovarian cancer at or under the age of 51 years compared with carriers diagnosed with cancer above the age of 51 years (allele frequency, P = 0.019). The GG genotype was significantly associated with breast and ovarian cancer risk among BRCA1/2 carriers diagnosed before 51 years of age (OR, 3.93; 95% CI, 1.41-10.90, P = 0.009). No significant difference in frequency of the GG genotype was observed between early and late onset non-carrier cancer patients and no association with risk, OR, 1.30; 95% CI 0.69-2.47, P = 0.419). These data suggest that MDM2 SNP309 acts as a modifier of mutant BRCA1/2 mutant alleles in AJ and may accelerate breast and ovarian carcinogenesis in genetically predisposed individuals.
MeSH term(s)	Adult ; Age of Onset ; Apoptosis Regulatory Proteins ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/epidemiology ; Breast Neoplasms/ethnology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Case-Control Studies ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Israel/epidemiology ; Jews/genetics ; Middle Aged ; Odds Ratio ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/ethnology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-mdm2/genetics ; Risk Assessment ; Risk Factors
Chemical Substances	Apoptosis Regulatory Proteins ; BLID protein, human ; BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; MDM2 protein, human (EC 2.3.2.27) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27)
Language	English
Publishing date	2008-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-007-9797-z
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Zs.A 1655: Show issues

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Article ; Online: A rapid in vivo assay system for analyzing the organogenetic capacity of human kidney cells.

Noiman, Tsahi / Buzhor, Ella / Metsuyanim, Sally / Harari-Steinberg, Orit / Morgenshtern, Chaya / Dekel, Benjamin / Goldstein, Ronald S

Organogenesis

2011 Volume 7, Issue 2, Page(s) 140–144

Abstract: Transplantation of human kidney-derived cells is a potential therapeutic modality for promoting regeneration of diseased renal tissue. However, assays that determine the ability of candidate populations for renal cell therapy to undergo appropriate ... ...

Abstract	Transplantation of human kidney-derived cells is a potential therapeutic modality for promoting regeneration of diseased renal tissue. However, assays that determine the ability of candidate populations for renal cell therapy to undergo appropriate differentiation and morphogenesis are limited. We report here a rapid and humane assay for characterizing tubulogenic potency utilizing the well-established chorioallantoic membrane CAM) of the chick embryo. Adult human kidney-derived cells expanded in monolayer were suspended in Matrigel and grafted onto the CAM. After a week, grafts were assessed histologically. Strikingly, many of the renal cells self-organized into tubular structures. Host blood vessels penetrated and presumably fed the grafts. Immuno- and histochemical staining revealed that tubular structures were epithelial, but not blood vessels. Some of the cells both within and outside the tubules were dividing. Analysis for markers of proximal and distal renal tubules revealed that grafts contained individual cells of a proximal tubular phenotype and many tubules of distal tubule character. Our results demonstrate that the chick CAM is a useful xenograft system for screening for differentiation and morphogenesis in cells with potential use in renal regenerative medicine.
MeSH term(s)	Adult ; Animals ; Biological Assay/methods ; Chickens ; Chorioallantoic Membrane/metabolism ; HEK293 Cells ; Humans ; Immunohistochemistry ; Kidney/cytology ; Organogenesis ; Stem Cell Transplantation ; Stem Cells/cytology
Language	English
Publishing date	2011-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2159583-5
ISSN	1555-8592 ; 1555-8592
ISSN (online)	1555-8592
ISSN	1555-8592
DOI	10.4161/org.7.2.16457
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Article ; Online: Analysis of circulating hem-endothelial marker RNA levels in preterm infants

Kuint Jacob / Shuchan-Eisen Irit / Pessach Itai / Metsuyanim Sally / Strauss Tzipora / Dekel Benjamin

BMC Pediatrics, Vol 9, Iss 1, p

2009 Volume 42

Abstract: Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of ... ...

Abstract	Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes ( AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1 ) in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.
Keywords	Pediatrics ; RJ1-570 ; Medicine ; R ; DOAJ:Pediatrics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2009-06-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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