705 research outputs found

    Supplemental material for Successful conception in a 34-year-old lupus patient following spontaneous pregnancy after autotransplantation of cryopreserved ovarian tissue

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    Supplemental Material for Successful conception in a 34-year-old lupus patient following spontaneous pregnancy after autotransplantation of cryopreserved ovarian tissue by G Chehab, J Krüssel, T Fehm, R Fischer-Betz, M Schneider, A Germeyer, MB Suerdieck, V Kreuzer and J Liebenthron in Lupus</p

    Comparison of a new RT-PCR-based detection of disseminated tumor cells in breast cancer patients with immunocytochemistry

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    Tumorzelldissemination ist ein wichtiger Schritt im komplexen Prozess der Metastasierung. Die klinische Relevanz der disseminierten Tumorzellen im Knochenmark sowie ihr Einfluss auf die Prognose von Mammakarzinompatientinnen wurden in zahlreichen Studien und einer Metaanalyse demonstriert (Level-1-Evidenz). Die Ziele der vorliegenden Studie waren einerseits die Evaluation einer neu etablierten RT-PCR-basierten Methode zum Nachweis der Tumorzelldissemination in der klinischen Routine und andererseits ihr Vergleich mit dem antikörperbasierten Goldstandard (Immunzytochemie). Die von uns verwendete real-time „One-Step” RT-PCR basierte auf der Hybridisierungssonden-Technologie und amplifizierte die in epithelialen Zellen üblicherweise vorhandene Zytokeratin 19-mRNA. Knochenmarkaspirate von 405 Mammakarzinompatientinnen wurden mittels Immunzytochemie (ICC) und RT-PCR untersucht. Immunzytochemisch ließen sich bei 34% aller Patientinnen disseminierte Tumorzellen nachweisen. Die höchste Positivitätsrate (58%) wurde in der Subgruppe der Patientinnen mit Rezidiv / Metastasierung beobachtet. Hingegen blieben 20% der Patientinnen ohne Hinweis auf Reaktivierung der Erkrankung (Kontrollpunktionen) positiv. 142 von 405 (35%) Knochenmarkaspiraten wurden mittels qualitativer RT-PCR als positiv beurteilt. Die höchste Positivitätsrate ergab sich im Kollektiv der neoadjuvant vorbehandelten Patientinnen (48%), gefolgt von Patientinnen mit Rezidiv/Metastase (42%) und primär operierten Patientinnen (37%). Die niedrigste Positivitätsrate wurde in der Subgruppe der Patientinnen mit Kontrollpunktion beobachtet (15%). 48% der Aspirate wurden mit mindestens einer Methode als positiv diagnostiziert. Bei 294 (73%) Knochenmarkaspiraten lieferten beide Methoden das gleiche Ergebnis (p<0,001). Zwischen dem ICC- bzw. RT-PCR-basierten Tumorzellnachweis wurde keine direkte Korrelation mit Patientencharakteristika oder klinisch-pathologischen Faktoren gefunden, wodurch die DTZ als eine Erweiterung der bisher vorhandenen Diagnostik anzusehen ist. In dieser Arbeit wurde eine neu etablierte molekularbiologische Methode zum Nachweis disseminierter Tumorzellen anhand eines großen Patientenkollektivs evaluiert. Immunzytochemie, die Standardmethode zur DTZ-Detektion, ist ein preiswertes, robustes Verfahren, verfügt über eine hohe Sensitivität und wurde bis dato in zahlreichen Studien evaluiert. Die in unserer Arbeitsgruppe etablierte real-time RT-PCR zum Nachweis von Tumorzellen bietet alle Vorteile einer konventionellen PCR, nämlich Schnelligkeit, hohe Sensitivität und Reproduzierbarkeit und stellt somit eine Alternative zur Diagnostik der Tumorzelldissemination dar. Ziel künftiger Studie muss sein, die prognostische Relevanz beider Verfahren zu evaluieren. Möglicherweise kann die RT-PCR die Diagnostik der Tumorzelldissemination und ihre Relevanz hinsichtlich der Prognose ergänzen.Haematogenous spread of disseminated tumour cells (DTCs) is considered to be the cause of systemic disease progression. Numerous studies have shown that the presence of DTCs in the bone marrow (BM) of breast cancer (BC) patients is associated with unfavourable clinical outcome (Level I evidence). The gold standard for the detection of DTCs is immunocytochemistry (ICC). In the meantime molecular-based assays were developed, such as RT-PCR. The purpose of our investigation was to evaluate our newly established RT-PCR-based assay and compare to ICC with respect to sensitivity on the basis of 405 bone marrow aspirates from breast cancer patients. Altogether, in 48% of the aspirates at least one method detected disseminated tumor cells. Concordance rate of 73% between ICC and RT-PCR was observed. On the contrary, in 111 patients discordant results were found. The positivity rates of ICC and RT-PCR were 34% and 35%, respectively. Immunocytochemistry is the current gold standard with well-known correlation to the prognosis. However, it is observer-dependent and labor intensive. RT-PCR is time-efficient and may increase the sensitivity but it lacks a standard protocol. We conclude that RT-PCR-based assays have a potential to improve diagnostics in this field

    Dormancy in breast cancer

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    Malgorzata Banys,1,2 Andreas D Hartkopf,1 Natalia Krawczyk,1 Tatjana Kaiser,1 Franziska Meier-Stiegen,1 Tanja Fehm,1 Hans Neubauer11Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany; 2Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg, GermanyAbstract: Tumor dormancy describes a prolonged quiescent state in which tumor cells are present, but disease progression is not yet clinically apparent. Breast cancer is especially known for long asymptomatic periods, up to 25 years, with no evidence of the disease, followed by a relapse. Factors that determine the cell&amp;#39;s decision to enter a dormant state and that control its duration remain unclear. In recent years, considerable progress has been made in understanding how tumor cells circulating in the blood interact and extravasate into secondary sites and which factors might determine whether these cells survive, remain dormant, or become macrometastases. The mechanisms of tumor cell dormancy are still not clear. Two different hypotheses are currently discussed: tumor cells persist either by completely withdrawing from the cell cycle or by continuing to proliferate at a slow rate that is counterbalanced by cell death. Because dormant disseminated tumor cells may be the founders of metastasis, one hypothesis is that dormant tumor cells, or at least a fraction of them, share stem cell-like characteristics that may be responsible for their long half-lives and their suggested resistance to standard chemotherapy. Therefore, knowledge of the biology of tumor cell dormancy may be the basis from which to develop innovative targeted therapies to control or eliminate this tumor cell fraction. In this review, we discuss biological mechanisms and clinical implications of tumor dormancy in breast cancer patients.Keywords: tumor dormancy, disseminated tumor cell, circulating tumor cell, targeted therap

    Existential ∅-Definability of Henselian Valuation Rings

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    In [1], Anscombe and Koenigsmann give an existential ∅-definition of the ring of formal power series F[[t]] in its quotient field in the case where F is finite. We extend their method in several directions to give general definability results for henselian valued fields with finite or pseudo-algebraically closed residue fields.publishe

    Sums of two squares in short intervals in polynomial rings over finite fields

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    Landau's theorem asserts that the asymptotic density of sums of two squares in the interval 1 n x is K=p log x, where K is the Landau-Ramanujan constant. It is an old problem in number theory whether the asymptotic density remains the same in intervals jn &amp;#x100000; xj x for a xed and x ! 1. This work resolves a function eld analogue of this problem, in the limit of a large niteeld. More precisely, consider monic f0 2 Fq[T] of degree n and take with 1 &gt; 2n. Then the asymptotic density of polynomials f in the `interval' deg(f &amp;#x100000; f0) n that are of the form f = A2+TB2, A;B 2 Fq[T] is 1 4n &amp;#x100000;2n n as q ! 1. This density agrees with the asymptotic density of such monic f's of degree n as q ! 1, as was shown by the second author, Smilanski, and Wolf. A key point in the proof is the calculation of the Galois group of f(&amp;#x100000;T2), where f is a polynomial of degree n with a few variable coecients: The Galois group is the hyperoctahedral group of order 2nn!
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