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  • 1
    Keywords: CANCER ; EXPRESSION ; miRNAs ; MICRORNA SIGNATURES
    Abstract: In a multicenter study, we determined the expression profiles of 863 microRNAs by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and validated this 'miRNome' by quantitative real-time PCR. We detected consistently deregulated profiles for all tested diseases; pathway analysis confirmed disease association of the respective microRNAs. We observed significant correlations (P = 0.004) between the genomic location of disease-associated genetic variants and deregulated microRNAs
    Type of Publication: Journal article published
    PubMed ID: 21892151
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  • 2
    Keywords: IN-VIVO ; GENES ; DIFFERENTIATION ; TRANSPLANTATION ; STATES ; EX-VIVO EXPANSION ; POLYCOMB ; EZH2 ; EPIGENOMIC LANDSCAPES ; TRICHOSTATIN
    Abstract: Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.
    Type of Publication: Journal article published
    PubMed ID: 26198814
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  • 3
    Abstract: BACKGROUND: Ovarian cancer (OvCA) tissues show abundant expression of the ectonucleotidases CD39 and CD73 which generate immunomodulatory adenosine, thereby inhibiting cytotoxic lymphocytes. Little, however, is known about the effect of adenosine on myeloid cells. Considering that tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) constitute up to 20 % of OvCA tissue, we investigated the effect of adenosine on myeloid cells and explored a possible contribution of myeloid cells to adenosine generation in vitro and ex vivo. METHODS: Monocytes were used as human blood-derived myeloid cells. After co-incubation with SK-OV-3 or OAW-42 OvCA cells, monocyte migration was determined in transwell assays. For conversion into M2-polarized "TAM-like" macrophages, monocytes were co-incubated with OAW-42 cells. Ex vivo TAMs were obtained from OvCA ascites. Macrophage phenotypes were investigated by intracellular staining for IL-10 and IL-12. CD39 and CD73 expression were assessed by FACS analysis both on in vitro-induced TAM-like macrophages and on ascites-derived ex situ-TAMs. Myeloid cells in solid tumor tissue were analyzed by immunohistochemistry. Generation of biologically active adenosine by TAM-like macrophages was measured in luciferase-based reporter assays. Functional effects of adenosine were investigated in proliferation-experiments with CD4(+) T cells and specific inhibitors. RESULTS: When CD39 or CD73 activity on OvCA cells were blocked, the migration of monocytes towards OvCA cells was significantly decreased. In vivo, myeloid cells in solid ovarian cancer tissue were found to express CD39 whereas CD73 was mainly detected on stromal fibroblasts. Ex situ-TAMs and in vitro differentiated TAM-like cells, however, upregulated the expression of CD39 and CD73 compared to monocytes or M1 macrophages. Expression of ectonucleotidases also translated into increased levels of biologically active adenosine. Accordingly, co-incubation with these TAMs suppressed CD4(+) T cell proliferation which could be rescued via blockade of CD39 or CD73. CONCLUSION: Adenosine generated by OvCA cells likely contributes to the recruitment of TAMs which further amplify adenosine-dependent immunosuppression via additional ectonucleotidase activity. In solid ovarian cancer tissue, TAMs express CD39 while CD73 is found on stromal fibroblasts. Accordingly, small molecule inhibitors of CD39 or CD73 could improve immune responses in ovarian cancer.
    Type of Publication: Journal article published
    PubMed ID: 27532024
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  GMS German Medical Science; VOL: 3; DOC08 /20050913/
    Publication Date: 2005-09-14
    Description: Aims, results, advantages and possible disadvantages of preoperative chemotherapy (pCHT) for breast cancer are discussed in this review. Established chemotherapeutic regimens are described with respect to new drugs that are added to combinations now and in the future. Illustrating the potential of new components, trastuzumab and cytotoxic chemotherapy, were combined in neoadjuvant trials for the first time. This approach yielded impressing and unprecedented high pathological response rates. An overview regarding current neoadjuvant cytostatic and immunotherapy trials is given.Established prognostic factors like axillary lymph-nodal status are altered during pCHT, which causes the need for new prognostic markers. The consequences of these changes for clinical decision making are demonstrated. It seems possible that the advances of gene array and protein expression profile technologies will lead to improved prognostic and predictive statements. Tumor tissue can be analyzed before during and after treatment in this regard recent studies investigating the response to specific, chemotherapeutics in correlation to molecular markers are reviewed. These approaches might enable us to identify chemoresistance of specific tumors. Furthermore pCHT allows testing of chemosensitivity in vivo in an early stage, which might lead to a more individualized cancer therapy.We discuss radiotherapy after neoadjuvant therapy and the risk of local relapse after breast conserving surgery, which was made feasible by pCHT. It is shown how the evaluation of efficacy of new cancer drugs, using the neoadjuvant situation, can be done more rapidly than in the metastatic and adjuvant setting.
    Description: Diese Übersichtsarbeit beschäftigt sich mit Zielen, Resultaten, Vorteilen, Kontraindikationen und möglichen Nachteilen der präoperativen Chemotherapie (pCHT) des Mammakarzinoms. Etablierte chemotherapeutische Kombinationen werden mit neuen Pharmaka verglichen, welche momentan und zukünftig in neoadjuvante Regime integriert werden. Das Potential neuerer Komponenten illustrieren erstmals unternommene neoadjuvante Studien, in welchen Trastuzumab und konventionelle Chemotherapeutika kombiniert wurden. Die Raten an pathohistologischen Ansprechraten waren beeindruckend und unerwartet hoch. Ein Überblick über aktuelle präoperative chemotherapeutische und immunotherapeutische klinische Studien wird in dieser Übersichtsarbeit vermittelt. Aufgezeigt werden die therapeutisch bedingten Veränderungen etablierter Prognosefaktoren wie der des axillären Lymphknotenstatus während der pCHT, die sich daraus ergebende Notwendigkeit neue Prognosemarker zu finden und die hieraus erwachsenden Konsequenzen für die klinische Entscheidungsfindung. Es erscheint möglich, dass die Fortschritte der Gene Array und Protein Expressionsprofil Technologie verbesserte prognostische and prädiktive Aussagen ermöglichen. Tumorgewebe kann vor, während und nach der Therapie analysiert werden. Diesbezüglich werden aktuelle Arbeiten, die das Ansprechen der Tumoren auf bestimmte Chemotherapeutika mit molekularen Markern korrelieren, diskutiert. Diese Ansätze könnten uns die frühzeitige Identifikation chemoresistenter Tumoren ermöglichen. Darüber hinaus handelt es sich bei der pCHT um einen in vivo Chemosensitivitätstest, der in Zukunft zu einer individualisierteren und maßgeschneiderteren Krebsbehandlung führen könnte. Wir diskutieren die Strahlentherapie nach neoadjuvanter Therapie und das Risiko eines Lokalrezidivs nach brusterhaltender Chirurgie, welche erst durch die präoperative Applikation der Chemotherapie ermöglicht wurde.Es wird aufgezeigt, wie die Evaluation und Zulassung neuerer Krebstherapeutika im Rahmen von präoperativen Behandlungskonzepten viel schneller als in der metastasierten oder adjuvanten Situation erfolgen kann.
    Keywords: ANTINEOPLASTIC AGENTS, HORMONAL/administration & dosage ; BREAST NEOPLASMS/* ; BREAST NEOPLASMS/*drug therapy ; BREAST NEOPLASMS/pathology ; BREAST NEOPLASMS/surgery ; ANTINEOPLASTIC AGENTS, COMBINED/* ; ANTINEOPLASTIC AGENTS, COMBINED/*therapeutic use ; NEOADJUVANT THERAPY/* ; FEMALE ; HUMANS ; PROGNOSIS ; ANTINEOPLASTIKA, HORMONELLE/Verabreichung & Dosierung ; MAMMATUMOREN, MENSCH/* ; MAMMATUMOREN, MENSCH/*Arzneimitteltherapie ; MAMMATUMOREN, MENSCH/Pathologie ; MAMMATUMOREN, MENSCH/Chirurgie ; ANTINEOPLASTISCHE KOMBINATIONSCHEMOTHERAPIE-PROTOKOLLE/* ; ANTINEOPLASTISCHE KOMBINATIONSCHEMOTHERAPIE-PROTOKOLLE/*therapeutische Anwendung ; NEOADJUVANTE THERAPIE/* ; WEIBLICH ; MENSCH ; PROGNOSE ; preoperative/neoadjuvant chemotherapy ; breast cancer ; local recurrence ; prognostic factors ; cancer biology ; ddc: 610
    Language: English
    Type: article
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  • 5
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0306-4565
    Keywords: Vertebrates ; fish ; heat-hardening ; proteinbiosynthesis ; temperature ; tissue-cultures
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2307
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Häufigkeit nichtrupturierter Tubargraviditäten hat weltweit zugenommen und damit auch die Möglichkeit, die befallene Tube zu erhalten. Nach organerhaltenden Operationen treten im Vergleich zur Salpingektomie häufiger intrauterine Schwangerschaften auf. Die Rate erneuter Extrauteringraviditäten (EUG) ist kaum erhöht. Bei entsprechender Übung bietet die laparoskopische Operation wegen des kleineren Eingriffes Vorteile. Die medikamentöse Behandlung der EUG mit Methotrexat, Prostaglandinen oder Antiprogesteron sollte derzeit noch Studien vorbehalten werden. Bei abgestorbener, nichtrupturierter EUG mit abfallenden HCG-Werten ist das Abwarten der spontanen Rückbildung möglich. Nach organerhaltender Behandlung ist die Kontrolle des HCG bis zur Normalisierung obligat.
    Notes: Summary Worldwide, the incidence of nonruptured tubal pregnancy has increased, and so has the feasibility of conservative management of this condition. Following conservative surgery the rate of intrauterine pregnancy is significantly higher than after salpingectomy. The rate of ectopic pregnancy has not (or hardly) increased. For a surgeon skilled in this technique, the laparoscopic approach has advantages because it avoids laparotomy. For the time being, medical treatment of ectopic pregnancy with methotrexate, prostaglandins, and antiprogesterone should be confined to clinical studies. For nonviable, nonruptured tubal pregnancy with decreasing HCG titers expectant management seems possible; following conservative treatment, monitoring of HCG until it becomes undertectable is mandatory.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 245 (1989), S. 866-868 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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