Publications (30) View all
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Article: MicroRNA Expression and JAK2 Allele Burden in Bone Marrow Trephine Biopsies of Polycythemia Vera, Essential Thrombocythemia and Early Primary Myelofibrosis.
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ABSTRACT: Background/Aims: MicroRNAs (miRNAs) play an important role in cellular differentiation and cancer pathogenesis. However, their role in promoting the malignant phenotype of myeloproliferative diseases and their importance for differential diagnosis of early-stage chronic myeloproliferative diseases (CMPDs) remains widely obscure. Methods: In this study, we systematically evaluated the differential expression of miRNAs previously described to be associated with myelopoiesis and myeloproliferative pathogenesis by quantitative RT-PCR in polycythemia vera, essential thrombocythemia, early primary myelofibrosis (PMF) and normal hematopoiesis. Our goal was to establish certain miRNAs as potential markers for CMPDs to facilitate the differentiation between these diseases and to further investigate molecular differences between the subtypes of myeloproliferative neoplasia. Results: An aberrant expression of miRNAs 10a and 150 could be demonstrated for essential thrombocythemia and PMF as well as for polycythemia vera and PMF, respectively. The expression of miR-150 could further be shown to correlate with both JAK2 allele burden and peripheral blood counts. Conclusion: Thus, the miRNAs investigated in this study seem to be potential marker oncomiRs in the differential diagnosis of CMPDs and possibly hold potential for the elucidation of a JAK2-independent mechanism of pathogenesis.Acta Haematologica 01/2013; 129(4):251-256. · 1.35 Impact Factor -
Article: The effect of adjuvant dimethylenastron, a mitotic Kinesin Eg5 inhibitor, in experimental glaucoma filtration surgery.
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ABSTRACT: The aim of the study was to analyze the effect of Dimethylenaston, a mitotic kinesin 5 (Eg5) inhibitor, in an experimental setting of glaucoma filtration surgery. On 37 chinchilla rabbits (ChBBCH), glaucoma filtration surgery similar to clinical practice, was performed. The animals received either no adjuvant, one unilateral subconjunctival injection of Dimethylenastron (1.0 µmol, 3.0 µmol), or the vehicle alone at baseline and in two further groups additionally at days 3 and 7 thereafter (1.0 µmol, 3.0 µmol). The evaluation of antifibrotic efficacy was performed by clinical response, histological examination, and immunohistochemical staining for smooth muscle actin (SMA) and CD 31. The animals were sacrificed on day 14, and the eyes processed for histology. The vehicle was well tolerated. Except for two cases of transient fibrinous reaction after the injection of 3.0 µmol Dimethylenastron, no adverse effects, such as inflammation or blurring of the optical media, were observed. A bleb scarring occurred in the group that received surgery only, adjuvant DMSO, or Dimethylenastron 3.0 µmol. Dimethylenastron (1.0 µmol) induced a milder scarring compared with the control group but the length of bleb survival was not significantly prolonged (p = 0.053, Kaplan-Meier log rank test). In all groups, the intraocular pressure correlated with the fibrotic process and reached normal levels within 14 days after surgery. Those groups injected with 1.0 µmol Dimethylenastron revealed a significantly reduced ratio of intraocular pressure and a milder, but not sufficiently reduced, subconjunctival fibrotic reaction according to the histological and immunohistochemical analysis. The subconjunctival administration of Dimethylenastron 1.0 µmol induced a milder conjunctival scarring. The applied concentrations of Dimethylenastron did not improve the surgical outcome of glaucoma filtration treatments in rabbits sufficiently.Current eye research 10/2010; 35(12):1090-8. · 1.51 Impact Factor -
Article: Interleukin-9 (IL-9) and NPM-ALK each generate mast cell hyperplasia as single 'hit' and cooperate in producing a mastocytosis-like disease in mice.
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ABSTRACT: Mast cell neoplasms are characterized by abnormal growth and focal accumulation of mast cells (MC) in one or more organs. Although several cytokines, including stem cell factor (SCF) and interleukin-9 (IL-9) have been implicated in growth of normal MC, little is known about pro-oncogenic molecules and conditions triggering differentiation and growth of MC far enough to lead to the histopathological picture of overt mastocytosis. The anaplastic lymphoma kinase (ALK) has recently been implicated in growth of neoplastic cells in malignant lymphomas. Here, we describe that transplantation of NPM-ALK-transplanted mouse bone marrow progenitors into lethally irradiated IL-9 transgenic mice not only results in lymphoma-formation, but also in the development of a neoplastic disease exhibiting histopathological features of systemic mastocytosis, including multifocal dense MC-infiltrates, occasionally with devastating growth in visceral organs. Transplantation of NPM-ALK-transduced progenitors into normal mice or maintenance of IL-9-transgenic mice without NPM-ALK each resulted in MC hyperplasia, but not in mastocytosis. Neoplastic MC in mice not only displayed IL-9, but also the IL-9 receptor, and the same was found to hold true for human neoplastic MC. Together, our data show that neoplastic MC express IL-9 receptors, that IL-9 and NPM-ALK upregulate MC-production in vivo, and that both'hits' act in concert to induce a mastocytosis-like disease in mice. These data may have pathogenetic and clinical implications and fit well with the observation that neoplastic MC in advanced SM strongly express NPM and multiple "lymphoid" antigens including CD25 and CD30.Oncotarget 06/2010; 1(2):104-19. · 4.78 Impact Factor -
Article: Giant thymoma in the anterior-inferior mediastinum.
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ABSTRACT: Thymomas are usually found in the superior mediastinum and sternotomy is the standard approach for resection. We report a case of a male patient with a giant left-sided thymoma, nearly fulfilling the whole hemithorax. Due to the sheer size of the tumor and its location in the anterior-inferior mediastinum, we performed a lateral approach for thymectomy. On resection the specimen measured 18 x 16 x 12 cm. Histology revealed a mixed stage I thymoma. The patient is doing well 36 months after resection and has no signs of recurrence. In literature, a significant increase in the risk of recurrence for thymomas >8 cm is reported.Interactive cardiovascular and thoracic surgery 03/2010; 10(3):451-3. -
Article: BCL6-translocations affect the phenotype of follicular lymphomas only in the absence of t(14;18)IgH/BCL2.
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ABSTRACT: The translocation t(14;18)IgH/BCL2 is the molecular hallmark of follicular lymphomas (FL). A subset of cases harbours translocations involving the BCL6-gene locus. This study aimed to determine the frequency of BCL2- and BCL6-translocations in FL and to identify morphological and immuno-histochemical features with respect to the presence of BCL2- and BCL6-translocations. Fluorescence-in-situ-hybridisation (FISH) was used to determine the BCL2- and BCL6-translocation status of 102 FL and these were compared to morphological and immunohistochemical parameters. Lymphomas with BCL6- and BCL2-translocations were very similar to t(14;18)-positive lymphomas without BCL6-translocations. In contrast, t(14;18)-negative lymphomas with BCL6-translocations were amongst others of higher grade, less often CD10-positive, involved the bone marrow less frequently and did not infiltrate the lymph node capsule. BCL2- and BCL6-translocations correlate with particular phenotypes of follicular lymphomas. BCL6-translocations seem to affect the phenotype only when they are not accompanied by BCL2-translocations.Anticancer research 11/2009; 29(11):4649-55. · 1.73 Impact Factor
