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Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T-cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T-cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T-cell-derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility-associated proteins were regarded, T-cell-derived cHL cell lines showed the highest similarity to ALK− ALCL cell lines. In contrast, T-cell-derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T-cell-derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T-cell-derived cHL. In summary, our cell line-derived data suggest that based on proteomics and migration behaviour, T-cell-derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted.
Background The differential diagnosis between follicular thyroid adenoma and minimal invasive follicular thyroid carcinoma is often difficult for several reasons. One major aspect is the lack of typical cytological criteria in well differentiated specimens. New marker molecules, shown by poly- or monoclonal antibodies proved helpful. Methods We performed global gene expression analysis of 12 follicular thyroid tumours (4 follicular adenomas, 4 minimal invasive follicular carcinomas and 4 widely invasive follicular carcinomas), followed by immunohistochemical staining of 149 cases. The specificity of the antibody was validated by western blot analysis Results In gene expression analysis QPRT was detected as differently expressed between follicular thyroid adenoma and follicular thyroid carcinoma. QPRT protein could be detected by immunohistochemistry in 65% of follicular thyroid carcinomas including minimal invasive variant and only 22% of follicular adenomas. Conclusion Consequently, QPRT is a potential new marker for the immunohistochemical screening of follicular thyroid nodules.
Meeting Abstract : Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008 Einleitung: Beim follikulären Schilddrüsenkarzinom ist die prae- und intraoperative Diagnose nur eingeschränkkt möglich. Immunhistochemische und immuncytologische Marker können hier hilfreich sein. Bei Patienten mit follikulären Karzinomen ist auf mRNA-Ebene eine up-Regulation für qprt (quinolinate-phosphoribosyltransferase) zu beobachten. Material und Methoden: Seit Januar 2004 werden bei Patienten mit prae- und intraoperativem Verdacht auf Schilddrüsenkarzinom, Frischgewebeproben zur Genexpressions-Analyse asserviert. Die so gewonnen Ergebnisse wurden an prospektiv und retrospektiv gewonnenen Präparaten von follikulären Adenomen und follikulären Karzinomen überprüft [Gruppe A]. Bei 20 prospektiven Punktionscytologien mit follikulärer Neoplasie werden aktuell zusätzliche immuncytologische Färbungen auf qprt durchgeführt und mit den nachfolgenden histologischen und immunhistochemischen Ergebnissen der Operationspräparate verglichen. Ergebnisse: Gruppe A (151 Patienten): bei 79 follikulären Adenomen und 72 follikulären Karzinomen wurden immunhistochemische Färbungen auf qprt durchgeführt. Hier zeigten sich 60 der 79 Adenome richtig negativ (76%) und 47 der 72 Karzinome richtig positiv (66%). Dies ergab eine Treffsicherheit zwischen Adenom und Karzinom von 71%. Gruppe B (20 Patienten): Die Ergebnisse der Korrelation zwischen präoperativer Immuncytochemie und postoperativer Diagnose und Immunhistochemie stehen derzeit noch aus. Schlussfolgerung: qprt ist ein immunhistochemischer Marker für follikuläre Schilddrüsenkarzinome mit einer befriedigenden Trennschärfe zwischen Adenom und Karzinom. Zusätzlich stellt qprt möglicherweise einen aussagekräftigen präoperativen immuncytochemischen Marker mit Auswirkung auf OP-Zeitpunkt, OP-Verfahren und OP-Taktik dar.
The human immune system is determined by the functionality of the human lymph node. With the use of high-throughput techniques in clinical diagnostics, a large number of data is currently collected. The new data on the spatiotemporal organization of cells offers new possibilities to build a mathematical model of the human lymph node - a virtual lymph node. The virtual lymph node can be applied to simulate drug responses and may be used in clinical diagnosis. Here, we review mathematical models of the human lymph node from the viewpoint of cellular processes. Starting with classical methods, such as systems of differential equations, we discuss the values of different levels of abstraction and methods in the range from artificial intelligence techniques formalism.
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.