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  1. Article ; Online ; Conference proceedings: How Regenerative Medicine Stakeholders Adapt to Ever-Changing Technology and Regulatory Challenges? Snapshots from the World TERMIS Industry Symposium (September 10, 2015, Boston).

    Bayon, Yves / Van Dyke, Mark / Buelher, Robert / Tubo, Ross / Bertram, Tim / Malfroy-Camine, Bernard / Rathman, Michelle / Ronfard, Vincent

    Tissue engineering. Part B, Reviews

    2017  Volume 23, Issue 2, Page(s) 159–162

    Abstract: Regenerative medicine (RM) is a fascinating area of research and innovation. The huge potential of the field has been fairly underexploited so far. Both TERMIS-AM and TERMIS-EU Industry Committees are committed to mentoring and training young ... ...

    Abstract Regenerative medicine (RM) is a fascinating area of research and innovation. The huge potential of the field has been fairly underexploited so far. Both TERMIS-AM and TERMIS-EU Industry Committees are committed to mentoring and training young entrepreneurs for more successful commercial translation of upstream research. With this objective in mind, the two entities jointly organized an industry symposium during the past TERMIS World Congress (Boston, September 8-11, 2015) and invited senior managers of the RM industry for lectures and panel discussions. One of the two sessions of the symposium-How to overcome obstacles encountered when bringing products to the commercial phase?-aimed to share the inside, real experiences of leaders from TEI Biosciences (an Integra Company), Vericel (formerly Aastrom; acquirer of Genzyme Regenerative Medicine assets), RegenMedTX (formerly Tengion), Mindset Rx, ViThera Pharmaceuticals, and L'Oreal Research & Innovation. The symposium provided practical recommendations for RM product development, for remaining critical and objective when reviewing progress, for keeping solutions simple, and for remaining relevant and persistent.
    MeSH term(s) Genetic Therapy/legislation & jurisprudence ; Humans ; Intellectual Property ; Regenerative Medicine/legislation & jurisprudence ; Regenerative Medicine/methods ; Social Control, Formal ; Tissue Engineering/legislation & jurisprudence
    Language English
    Publishing date 2017-04
    Publishing country United States
    Document type Congresses
    ZDB-ID 2420584-9
    ISSN 1937-3376 ; 1937-3368
    ISSN (online) 1937-3376
    ISSN 1937-3368
    DOI 10.1089/ten.TEB.2016.0292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study.

    Rayner, Fiona / Anderson, Amy E / Baker, Kenneth F / Buckley, Christopher D / Dyke, Bernard / Fenton, Sally / Filer, Andrew / Goodyear, Carl S / Hilkens, Catharien M U / Hiu, Shaun / Kerrigan, Sean / Kurowska-Stolarska, Mariola / Matthews, Fiona / McInnes, Iain / Ng, Wan-Fai / Pratt, Arthur G / Prichard, Jonathan / Raza, Karim / Siebert, Stefan /
    Stocken, Deborah / Teare, M Dawn / Young, Stephen / Isaacs, John D

    BMC rheumatology

    2021  Volume 5, Issue 1, Page(s) 22

    Abstract: Background: Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from ... ...

    Abstract Background: Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism.
    Methods: The BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data.
    Discussion: This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need.
    Trial registration: The study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380 .
    Language English
    Publishing date 2021-07-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2918121-5
    ISSN 2520-1026 ; 2520-1026
    ISSN (online) 2520-1026
    ISSN 2520-1026
    DOI 10.1186/s41927-021-00194-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis.

    Juarez, Maria / Bang, Holger / Hammar, Friederike / Reimer, Ulf / Dyke, Bernard / Sahbudin, Ilfita / Buckley, Christopher D / Fisher, Benjamin / Filer, Andrew / Raza, Karim

    Annals of the rheumatic diseases

    2015  Volume 75, Issue 6, Page(s) 1099–1107

    Abstract: Objective: To investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis.: Methods: A panel of PTMPs was developed. Microtitre plates were coated with ...

    Abstract Objective: To investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis.
    Methods: A panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)-either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms ≤3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis).
    Results: Antibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly higher in the RA group than in the other groups. Anti cyclic citrullinated peptide (CCP)-positive patients with RA had higher numbers of peptides recognised and higher levels of antibodies against those peptides, representing a distinct profile compared with the other groups.
    Conclusions: We show for the first time that antibodies against acetylated vimentin are present in the sera of patients with early RA and confirm and extend previous observations regarding anticitrullinated and anticarbamylated antibodies.
    MeSH term(s) Adult ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; Case-Control Studies ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Peptides, Cyclic/immunology ; Protein Processing, Post-Translational ; Vimentin/immunology
    Chemical Substances Autoantibodies ; Peptides, Cyclic ; Vimentin ; cyclic citrullinated peptide
    Language English
    Publishing date 2015-07-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2014-206785
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Tumor-specific cooperation of retinoblastoma protein family and Snf5 inactivation.

    Chai, Jingjing / Lu, Xiangdong / Godfrey, Virginia / Fletcher, Christopher / Roberts, Charles W M / Van Dyke, Terry / Weissman, Bernard E

    Cancer research

    2007  Volume 67, Issue 7, Page(s) 3002–3009

    Abstract: Malignant rhabdoid tumors (MRT) are rare aggressive cancers that occur in young children. Seventy-five percent of sporadic MRTs harbor inactivating SNF5 mutations, and mice heterozygous for an Snf5-null allele develop MRTs with partial penetrance. The ... ...

    Abstract Malignant rhabdoid tumors (MRT) are rare aggressive cancers that occur in young children. Seventy-five percent of sporadic MRTs harbor inactivating SNF5 mutations, and mice heterozygous for an Snf5-null allele develop MRTs with partial penetrance. The diagnosis of choroid plexus carcinomas (CPC) in addition to MRTs in families with a single mutant SNF5 allele prompted us to assess the role of SNF5 loss in CPC in genetically engineered mice. With high frequency, TgT(121) mice develop CPCs that are initiated by inactivation of retinoblastoma protein (pRb) and related proteins p107 and p130. However, CPC penetrance and latency were not significantly affected by Snf5 heterozygosity, consistent with recent evidence that CPCs in SNF5 families were, in many cases, misdiagnosed MRTs. Surprisingly, although the CPC phenotype was unaffected, TgT(121);Snf5(+/-) mice developed MRTs with increased penetrance and decreased latency compared with TgT(121);Snf5(+/+) littermates. MRTs expressed the T(121) protein with a concomitant increase in mitotic activity. The predominant appearance of TgT(121);Snf5(+/-) MRTs in the spinal cord led to the discovery that these tumors likely arose from a subset of spinal cord neural progenitor cells expressing T(121) rather than from transdifferentiation of CPC. Significantly, the target cell type(s) for MRT is unknown. Hence, this study not only shows that pRb(f) and SNF5 inactivation cooperate to induce MRTs but also provides new insight into the MRT target population.
    MeSH term(s) Animals ; Choroid Plexus Neoplasms/genetics ; Chromosomal Proteins, Non-Histone/genetics ; DNA, Neoplasm/genetics ; DNA, Neoplasm/isolation & purification ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Loss of Heterozygosity ; Male ; Mice ; Mice, Inbred C57BL ; Retinoblastoma Protein/genetics ; Rhabdoid Tumor/genetics ; SMARCB1 Protein
    Chemical Substances Chromosomal Proteins, Non-Histone ; DNA, Neoplasm ; Retinoblastoma Protein ; SMARCB1 Protein ; Smarcb1 protein, mouse
    Language English
    Publishing date 2007-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-06-4207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inactivation of SNF5 cooperates with p53 loss to accelerate tumor formation in Snf5(+/-);p53(+/-) mice.

    DelBove, Jessica / Kuwahara, Yasumichi / Mora-Blanco, E Lorena / Godfrey, Virginia / Funkhouser, William K / Fletcher, Christopher D M / Van Dyke, Terry / Roberts, Charles W M / Weissman, Bernard E

    Molecular carcinogenesis

    2009  Volume 48, Issue 12, Page(s) 1139–1148

    Abstract: Malignant rhabdoid tumors (MRTs) are poorly differentiated pediatric cancers that arise in various anatomical locations and have a very poor outcome. The large majority of these malignancies are caused by loss of function of the SNF5/INI1 component of ... ...

    Abstract Malignant rhabdoid tumors (MRTs) are poorly differentiated pediatric cancers that arise in various anatomical locations and have a very poor outcome. The large majority of these malignancies are caused by loss of function of the SNF5/INI1 component of the SWI/SNF chromatin remodeling complex. However, the mechanism of tumor development associated with SNF5 loss remains unclear. Multiple studies have demonstrated a role for SNF5 in the regulation of cyclin D1, p16(INK4A), and pRb(f) activities suggesting it functions through the SWI/SNF complex to affect transcription of genes involved in cell cycle control. Previous studies in genetically engineered mouse models (GEMM) have shown that loss of SNF5 on a p53-null background significantly accelerates tumor development. Here, we use established GEMM to further define the relationship between the SNF5 and p53 tumor suppressor pathways. Combined haploinsufficiency of p53 and Snf5 leads to decreased latency for MRTs arising in alternate anatomical locations but not for the standard facial MRTs. We also observed acceleration in the appearance of T-cell lymphomas in the p53(+/-);Snf5(+/-) mice. Our studies suggest that loss of SNF5 activity does not bestow a selective advantage on the p53 spectrum of tumors in the p53(+/-);Snf5(+/-) mice. However, reduced p53 expression specifically accelerated the growth of a subset of MRTs in these mice.
    MeSH term(s) Animals ; Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/physiology ; Female ; Lymphoma, T-Cell/genetics ; Lymphoma, T-Cell/pathology ; Male ; Mice ; Mice, Knockout ; Osteosarcoma/genetics ; Osteosarcoma/pathology ; Rhabdoid Tumor/genetics ; Rhabdoid Tumor/pathology ; SMARCB1 Protein ; Survival Rate ; Tumor Suppressor Protein p53/physiology
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; SMARCB1 Protein ; Smarcb1 protein, mouse ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2009-07-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.20568
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Outcomes following pre-operative clopidogrel administration in patients with acute coronary syndromes undergoing coronary artery bypass surgery: the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.

    Ebrahimi, Ramin / Dyke, Cornelius / Mehran, Roxana / Manoukian, Steven V / Feit, Frederick / Cox, David A / Gersh, Bernard J / Ohman, E Magnus / White, Harvey D / Moses, Jeffrey W / Ware, James H / Lincoff, A Michael / Stone, Gregg W

    Journal of the American College of Cardiology

    2009  Volume 53, Issue 21, Page(s) 1965–1972

    Abstract: Objectives: This study sought to evaluate the impact of upstream clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent ...

    Abstract Objectives: This study sought to evaluate the impact of upstream clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.
    Background: Despite benefits of clopidogrel in patients with NSTE-ACS undergoing percutaneous coronary intervention, this agent is often not administered upstream (before angiography) as recommended by the American College of Cardiology/American Heart Association guidelines because of potential bleeding in the minority of patients who require CABG.
    Methods: The ACUITY trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management. The timing of clopidogrel initiation was per investigator discretion. A 5-day washout period before CABG was recommended for patients having received clopidogrel.
    Results: Of 13,819 patients enrolled, 1,539 (11.1%) underwent CABG before discharge. Clopidogrel-exposed patients had a longer median duration of hospitalization (12.0 days vs. 8.9 days, p < 0.0001), but fewer adverse composite ischemic events (death, myocardial infarction, or unplanned revascularization) at 30 days; 12.7% vs. 17.3%, p = 0.01), with nonsignificantly different rates of non-CABG-related major bleeding (3.4% vs. 3.2%, p = 0.87) and post-CABG major bleeding (50.3% vs. 50.9%, p = 0.83) compared with those patients not administered clopidogrel. By multivariable analysis, clopidogrel use before CABG was an independent predictor of reduced 30-day composite ischemia (odds ratio: 0.67, 95% confidence interval: 0.48 to 0.92, p = 0.001) but not of increased post-CABG major bleeding (odds ratio: 0.98, 95% confidence interval: 0.80 to 1.19, p = 0.80).
    Conclusions: Clopidogrel administration before catheterization in patients with NSTE-ACS requiring CABG is associated with significantly fewer 30-day adverse ischemic events without significantly increasing major bleeding, compared to withholding clopidogrel until after angiography. These findings support the American College of Cardiology/American Heart Association guidelines for upstream clopidogrel administration in all NSTE-ACS patients, including those who subsequently undergo CABG. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).
    MeSH term(s) Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/drug therapy ; Acute Coronary Syndrome/surgery ; Adult ; Aged ; Aged, 80 and over ; Cardiac Catheterization/methods ; Coronary Angiography ; Coronary Artery Bypass/methods ; Coronary Care Units ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/administration & dosage ; Preoperative Care/methods ; Prospective Studies ; Ticlopidine/administration & dosage ; Ticlopidine/analogs & derivatives ; Time Factors ; Treatment Outcome ; Triage
    Chemical Substances Platelet Aggregation Inhibitors ; clopidogrel (A74586SNO7) ; Ticlopidine (OM90ZUW7M1)
    Language English
    Publishing date 2009-05-26
    Publishing country United States
    Document type Comment ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2009.03.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Rapid HIV-1 testing during labor: a multicenter study.

    Bulterys, Marc / Jamieson, Denise J / O'Sullivan, Mary Jo / Cohen, Mardge H / Maupin, Robert / Nesheim, Steven / Webber, Mayris P / Van Dyke, Russell / Wiener, Jeffrey / Branson, Bernard M

    JAMA

    2004  Volume 292, Issue 2, Page(s) 219–223

    Abstract: Context: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis.: Objectives: To determine the feasibility and acceptance of rapid HIV testing among ... ...

    Abstract Context: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis.
    Objectives: To determine the feasibility and acceptance of rapid HIV testing among women in labor and to assess rapid HIV assay performance.
    Design, setting, and patients: The Mother-Infant Rapid Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and voluntary rapid HIV testing for women in labor at 16 US hospitals from November 16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood was used.
    Main outcome measures: Acceptance of HIV testing; sensitivity, specificity, and predictive value of the rapid test; time from blood collection to patient notification of results.
    Results: There were 91,707 visits to the labor and delivery units in the study, 7381 of which were by eligible women without documentation of HIV testing. Of these, 5744 (78%) women were approached for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test were 100% and 99.9%, respectively; positive predictive value was 90% compared with 76% for enzyme immunoassay (EIA). Factors independently associated with higher test acceptance included younger age, being black or Hispanic, gestational age less than 32 weeks, and having had no prenatal care. Lower acceptance was associated with being admitted between 4 pm and midnight, particularly on Friday nights, but this may be explained in part by fewer available personnel. Median time from blood collection to patient notification of result was 66 minutes (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001).
    Conclusions: Rapid HIV testing is feasible and delivers accurate and timely test results for women in labor. It provides HIV-positive women prompt access to intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal HIV transmission, and may be particularly applicable to higher-risk populations.
    MeSH term(s) AIDS Serodiagnosis/methods ; Adult ; Antibodies, Viral/blood ; Delivery, Obstetric ; Female ; HIV Infections/diagnosis ; HIV-1/immunology ; Humans ; Labor, Obstetric ; Predictive Value of Tests ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis ; Sensitivity and Specificity
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2004-07-14
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.292.2.219
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  8. Article ; Online: Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

    Herschkowitz, Jason I / Simin, Karl / Weigman, Victor J / Mikaelian, Igor / Usary, Jerry / Hu, Zhiyuan / Rasmussen, Karen E / Jones, Laundette P / Assefnia, Shahin / Chandrasekharan, Subhashini / Backlund, Michael G / Yin, Yuzhi / Khramtsov, Andrey I / Bastein, Roy / Quackenbush, John / Glazer, Robert I / Brown, Powel H / Green, Jeffrey E / Kopelovich, Levy /
    Furth, Priscilla A / Palazzo, Juan P / Olopade, Olufunmilayo I / Bernard, Philip S / Churchill, Gary A / Van Dyke, Terry / Perou, Charles M

    Genome biology

    2007  Volume 8, Issue 5, Page(s) R76

    Abstract: Background: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene ... ...

    Abstract Background: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.
    Results: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors.
    Conclusion: Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.
    MeSH term(s) Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cluster Analysis ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mice ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Species Specificity
    Chemical Substances Neoplasm Proteins
    Language English
    Publishing date 2007
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2007-8-5-r76
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  9. Article: Simultaneous measurements of cytoplasmic Ca2+ responses and intracellular pH in neutrophils of localized aggressive periodontitis (LAP) patients.

    Herrmann, Jens Martin / Kantarci, Alpdogan / Long, Heidi / Bernardo, John / Hasturk, Hatice / Wray, Lewis V / Simons, Elizabeth R / Van Dyke, Thomas E

    Journal of leukocyte biology

    2005  Volume 78, Issue 3, Page(s) 612–619

    Abstract: In view of the reports that polymorphonuclear leukocytes (PMN) of patients with localized aggressive periodontitis (LAP) exhibit hyper-responsiveness to stimulation, it has been suggested that such abnormalities could lead to PMN-mediated tissue damage ... ...

    Abstract In view of the reports that polymorphonuclear leukocytes (PMN) of patients with localized aggressive periodontitis (LAP) exhibit hyper-responsiveness to stimulation, it has been suggested that such abnormalities could lead to PMN-mediated tissue damage during inflammation. To determine whether these abnormalities include signal transduction, we compared cytoplasmic calcium concentration (Delta[Ca2+](i)) and cytoplasmic pH (DeltapH(i)) changes, early stimulus responses to chemotactic agents, of LAP versus control (C)-PMN and explored whether these could be modulated by sensitizing cytokines or calcium channel-blocking agents. PMN responses of LAP patients were compared with age- and gender-matched controls. Delta[Ca2+](i) and DeltapH(i) were measured fluorimetrically using 1H-indole-6-carboxylic acid, 2-[4-[bis[2-[(acetyloxy)methoxy]-2-oxoethyl]amino]-3-[2-[2-[bis[2-[(acetyloxy)methoxy]-2-oxoethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-1 and 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein as respective probes. Not only was the maximal calcium response to chemoattractants higher in LAP-PMN, but also their subsequent intracellular calcium redistribution was significantly slower. The slower calcium redistribution of LAP-PMN, but not their higher maximal calcium response, was successfully mimicked in C-PMN treated with Nifedipine or 1-[b-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole-HCl, both known to be inhibitors of membrane-associated calcium influx, but this redistribution was not affected when inhibitors of other calcium influx mechanisms, Diltiazem or Verapamil, were used. Taken together, our findings indicate that certain early stimulus responses are aberrant in LAP-PMN, that internal redistribution of cytoplasmic-free calcium is compromised, and, additionally, that a membrane-associated Ca2+ transport defect may be present.
    MeSH term(s) Aggressive Periodontitis/diagnosis ; Aggressive Periodontitis/metabolism ; Calcium/analysis ; Calcium/metabolism ; Cytokines/pharmacology ; Cytoplasm/chemistry ; Cytoplasm/metabolism ; Diltiazem/pharmacology ; Dose-Response Relationship, Drug ; Humans ; Hydrogen-Ion Concentration ; Imidazoles/pharmacology ; Interleukin-8/pharmacology ; Intracellular Fluid/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/drug effects ; Neutrophils/immunology ; Neutrophils/physiology ; Nifedipine/pharmacology ; Substance P/pharmacology ; Time Factors ; Verapamil/pharmacology
    Chemical Substances Cytokines ; Imidazoles ; Interleukin-8 ; Substance P (33507-63-0) ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6) ; Verapamil (CJ0O37KU29) ; Diltiazem (EE92BBP03H) ; 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole (I61V87164A) ; Nifedipine (I9ZF7L6G2L) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2005-09
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.0105023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors

    Herschkowitz, Jason I / Andrey I Khramtsov / Charles M Perou / Gary A Churchill / Igor Mikaelian / Jeffrey E Green / Jerry Usary / John Quackenbush / Juan P Palazzo / Karen E Rasmussen / Karl Simin / Laundette P Jones / Levy Kopelovich / Michael G Backlund / Olufunmilayo I Olopade / Philip S Bernard / Powel H Brown / Priscilla A Furth / Robert I Glazer /
    Roy Bastein / Shahin Assefnia / Subhashini Chandrasekharan / Terry Van Dyke / Victor J Weigman / Yuzhi Yin / Zhiyuan Hu

    Genome biology. 2007 May, v. 8, no. 5

    2007  

    Abstract: BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression ...

    Abstract BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T ₁₂₁ , TgMMTV-Wnt1, Brca1 Cᵒ/Cᵒ ;TgMMTV-Cre;p53⁺/⁻and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors. CONCLUSION: Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.
    Keywords animal models ; breast neoplasms ; carcinoma ; cluster analysis ; DNA microarrays ; estrogen receptors ; gene expression ; genes ; humans ; mammary neoplasms (animal) ; mice ; phenotype ; tumor suppressor proteins
    Language English
    Dates of publication 2007-05
    Size p. 1558.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2007-8-5-r76
    Database NAL-Catalogue (AGRICOLA)

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