References of "de Leval, Laurence"
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See detailBm-573, an original thromboxane receptor antagonist, reduces development of atherosclerosis in apoe–deficient (apo e-/-) mice
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

Poster (2007, October 11)

To test the efficacy of BM-573 in atherogenesis, the effect of 10 weeks of treatment with BM573 (10 mg/l) on early aortic atherosclerotic lesions of apo E deficient mice was assessed. These mice were fed ... [more ▼]

To test the efficacy of BM-573 in atherogenesis, the effect of 10 weeks of treatment with BM573 (10 mg/l) on early aortic atherosclerotic lesions of apo E deficient mice was assessed. These mice were fed with chow diet, with spontaneous increase of total plasma cholesterol and triglycerides. In this experiment, while BM-573 did not affect body weight, it significantly decreases early atherogenesis lesions confirmed by macroscopic, microscopic and biochemical analysis. These results confirm that selective antagonism of TP receptor is effective in reducing atherosclerotic lesion in apo E deficient mice. Consequently, BM-573 could be a potential drug for prevention of atherosclerosis [less ▲]

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See detailHigh frequency of JAZF1-JJAZ1 gene fusion in endometrial stromal tumors with smooth muscle differentiation by interphase FISH detection
Oliva, E.; de Leval, Laurence ULg; Soslow, R. A. et al

in American Journal of Surgical Pathology (2007), 31(8), 1277-1284

The most common cytogenetic alteration observed in low-grade endometrial stromal tumors (EST) is the t(7;17)(p15.-q21) translocation, resulting in the fusion of the JAZF1 and JJAZ1 genes. By reverse ... [more ▼]

The most common cytogenetic alteration observed in low-grade endometrial stromal tumors (EST) is the t(7;17)(p15.-q21) translocation, resulting in the fusion of the JAZF1 and JJAZ1 genes. By reverse-transcription polymerase chain reaction, the translocation has been detected overall in one-third of ESTs. but only rarely in its variants. The purpose of this study was to develop a fluorescence in situ hybridization assay for detection of this translocation using archival paraffin-embedded samples of ESTs with smooth muscle differentiation and to assess the nature of the smooth Muscle component of these tumors. Representative paraffin blocks of 9 endometrial stromal nodules and I low-grade endometrial stromal sarcoma were collected for the study. In I case, the block selected also contained areas of sex cordlike differentiation. A fluorescence in situ hybridization probe set was designed to detect the t(7;17)(p15;q12) on tissue sections. Six Out of 10 collected ESTs were assessable. Fusion signals were detected in 3 out of 6 cases (50%) in both the conventional endometrial stromal and the smooth muscle components of the tumors. The tumor sample with sex cordlike differentiation harbored the fusion signal in all the 3 components. Out-results Support the contention that the endometrial stromal and smooth muscle components of these tumors have the same ori.-in, either from a common precursor cell with pluripotential differentiation or from endometrial stromal cells that have undergone smooth muscle metaplasia. Our results indicate that the detection of this chromosomal abnormality can be used to diagnose ESTs with smooth muscle differentiation when the smooth muscle component is predominant. [less ▲]

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See detailEarly inflammation in the airways of a cystic fibrosis foetus
Verhaeghe, C.; Delbecque, Katty ULg; de Leval, Laurence ULg et al

in Journal of Cystic Fibrosis (2007), 6(4), 304-308

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic ... [more ▼]

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic fibrosis foetus compared to the lungs of two normal foetuses. Our findings suggest therefore the existence of an early intrinsic pro-inflammatory state in cystic fibrosis airways. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailBm-573, a thromboxane receptor antagonist, reduces development of atherosclerosis in apoe–deficient mice
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

Poster (2007, June 22)

Atherosclerotic cardiovascular disease, according to World Health Organization, is the primary cause of heart disease and stroke. Atherosclerosis is a chronic vascular disease whose development is ... [more ▼]

Atherosclerotic cardiovascular disease, according to World Health Organization, is the primary cause of heart disease and stroke. Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators. Among them, the action of eicosanoïds such as thromboxane A2 and 8-iso-PGF2a have recently received a lot of attention. The aim of our study was the evaluation of benefits of original molecules, synthesised in our lab, targeting the thromboxane receptor (TP) in an apo E deficient mouse. We previously demonstrated in several in vitro and in vivo pharmacological experiments that our original sulfonylurea derivate, BM-573 was a potent combined inhibitor of the thromboxane synthase and antagonist of TP. Since TP is implied in atherosclerosis development, such antagonist could have a great therapeutic impact in atherogenesis.To test the efficacy of BM-573 in atherogenesis, the effect of 10 weeks of treatment with BM573 (10 mg/kg) on early aortic atherosclerotic lesions of apo E deficient mice was assessed. These mice were fed with chow diet, with spontaneous increase of total plasma cholesterol and triglycerides. In this experiment, while BM-573 did not affect body weight, it significantly decreased early atherogenesis lesions confirmed by macroscopic, microscopic and biochemical analysis. These results confirm that selective antagonism of TP receptor is effective in reducing atherosclerotic lesion in apo E deficient mice. Consequently, BM-573 could be a potential drug for prevention of atherosclerosis. [less ▲]

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See detailThe gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells
de Leval, Laurence ULg; Rickman, David; Thielen, Caroline ULg et al

in Blood (2007), 109(11), 4952-4963

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ... [more ▼]

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T-FH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T-FH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T-FH genes was validated by immunohistochemistry in AITLs. A few cases with molecular T-FH-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL. [less ▲]

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See detailLe bm-573, un antagoniste original de récepteur au thromboxane a2, réduit le développement des lesions atheromateuses chez des souris deficientes en apolipoproteine e (apo e-/-)
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

Poster (2007, May 10)

Afin d’examiner l'efficacité du BM-573 dans l'athérogenèse, des souris apo E-/- ont été traitées durant 10 semaines avec le BM573 (10mg/kg). Au cours de cette expérience, le traitement des animaux par le ... [more ▼]

Afin d’examiner l'efficacité du BM-573 dans l'athérogenèse, des souris apo E-/- ont été traitées durant 10 semaines avec le BM573 (10mg/kg). Au cours de cette expérience, le traitement des animaux par le BM-573, a eu pour effet de diminuer les lésions athéromateuses précoces de manière significative. Ces données ont été confirmées par des analyses histopathologiques et biochimiques. Ces résultats confirment que l'antagonisme sélectif des récepteurs TP associé à une inhibition de la thromboxane synthase réduit significativement les lésions athéromateuses chez les souris apoE-/-.. Le BM-573 est, par conséquent, un agent thérapeutique potentiel pour la prévention de l'athérosclérose [less ▲]

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See detailNK CELLS AND NKG2D LIGANDS IN HPV-ASSOCIATED CERVICAL CANCER
Jacobs, Nathalie ULg; Renoux, Virginie ULg; Dortu, Estelle ULg et al

Poster (2007, April 12)

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See detailIdentification of specific reachable molecular targets in human breast cancer using a versatile ex vivo proteomic method
Castronovo, Vincenzo ULg; Kischel, Philippe ULg; Guillonneau, Francois et al

in Proteomics (2007), 7(8), 1188-1196

Targeting of tumoral tissues is one of the most promising approaches to improve both the efficacy and safety of anticancer treatments. The identification of valid targets, including proteins specifically ... [more ▼]

Targeting of tumoral tissues is one of the most promising approaches to improve both the efficacy and safety of anticancer treatments. The identification of valid targets, including proteins specifically and abundantly expressed in cancer lesions, is of utmost importance. Despite state-of-the-art technologies, the discovery of cancer-associated target proteins still faces the limitation, in human tissues, of antigen accessibility to suitable high-affinity ligands such as human mAb bound to bioactive molecules. Terminal perfusion of tumor-bearing mice or ex vivo perfusion of human cancer-bearing organs with a reactive biotin ester solution has successfully led to the identification of novel accessible biomarkers. This methodology is however restricted to perfusable organs, and excludes most of the tissues of interest to targeted therapies, e.g. primary breast cancer and metastases. Herein, we report on the development of a new chemical proteomic method that bypasses the perfusion step and thus offers the potential to identify accessible molecular targets in virtually all types of animal and human tissues. We have validated our new procedure by identifying biomarkers selectively expressed in human breast carcinoma. Overall, this powerful technology may lay the ground not only for custom-made therapies in cancer, but also for the development of therapies that need to be selectively delivered in a specific tissue. [less ▲]

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See detailThe A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protei n-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits
Boudry, Christel ULg; Markine-Goriaynoff, Nicolas ULg; Delforge, Cédric ULg et al

in Journal of General Virology (2007), 88(Pt 12), 3224-3233

Many gammaherpesviruses encode G-protein-coupled receptors (GPCRs). Several in vivo studies have revealed that gammaherpesvirus GPCRs are important for viral replication and for virus-induced pathogenesis ... [more ▼]

Many gammaherpesviruses encode G-protein-coupled receptors (GPCRs). Several in vivo studies have revealed that gammaherpesvirus GPCRs are important for viral replication and for virus-induced pathogenesis. The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) is carried asymptomatically by wildebeest, but causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species. The A5 ORF of the AlHV-1 genome encodes a putative GPCR. In the present study, we investigated whether A5 encodes a functional GPCR and addressed its role in viral replication and in the pathogenesis of MCF. In silico analysis supported the hypothesis that A5 could encode a functional GPCR as its expression product contained several hallmark features of GPCRs. Expression of A5 as tagged proteins in various cell lines revealed that A5 localizes in cell membranes, including the plasma membrane. Using [35S]GTPgammaS and reporter gene assays, we found that A5 is able to constitutively couple to alpha i-type G-proteins in transfected cells, and that this interaction is able to inhibit forskolin-triggered cAMP response element-binding protein (CREB) activation. Finally, using an AlHV-1 BAC clone, we produced a strain deleted for A5 and a revertant strain. Interestingly, the strain deleted for A5 replicated comparably to the wild-type parental strain and induced MCF in rabbits that was indistinguishable from that of the parental strain. The present study is the first to investigate the role of an individual gene of AlHV-1 in MCF pathogenesis. [less ▲]

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See detailAssociation between Epstein-Barr virus and Hodgkin's lymphoma in Belgium: A pathological and virological study
Trimeche, M.; Bonnet, Christophe ULg; Korbi, S. et al

in Leukemia & Lymphoma (2007), 48(7), 1323-1331

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of ... [more ▼]

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of 111 cHL cases diagnosed in Belgium. The overall prevalence of EBV infection detected by in situ hybridization in Reed-Sternberg cells was 33%. EBV positivity correlated with older age at diagnosis (454 years; p = 0.01), mixed cellularity subtype (p = 0.000001), male gender (p = 0.004) and tended to be associated with higher clinical stage (III/IV; p = 0.02). The molecular features of the virus in EBV-positive cHL were studied by comparison with a series of reactive tonsils. A 30-bp deletion within the LMP-1 gene was in 15/28 (53.6%) EBV-positive cHL cases, and in 41.7% of reactive tonsil samples. This variant did not correlate with any clinical or pathological feature. The EBV strain was type A in all cHL and reactive samples. [less ▲]

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See detailEndocardite infectieuse tricuspidienne comme cause d'une fievre d'origine indeterminee.
Schrouff, I.; Valdes-Socin, H.; Frippiat, Frédéric ULg et al

in Revue Médicale de Liège (2007), 62(11), 654-8

Isolated tricuspid valve endocarditis is the least common endocarditis with an incidence of 5 to 10% in the literature. It is usually described in drug abusers and as a complication of nosocomial ... [more ▼]

Isolated tricuspid valve endocarditis is the least common endocarditis with an incidence of 5 to 10% in the literature. It is usually described in drug abusers and as a complication of nosocomial infections (catheter, post-surgery...). We present the case of a 70 year-old patient admitted for a fever of unknown origin lasting for 2 months. He had an isolated tricuspid endocarditis with Enterococcus faecalis. We review the diagnostic criterias predisposing factors and treatment of right-sided valvular endocarditis, particularly the endocarditis produced by Enterococcus faecalis, a rare etiopathogenic agent of tricuspid endocarditis. [less ▲]

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See detailConfrontation anatomo-clinique: duplication caecale
Scagnol, Irène ULg; Detry, Olivier ULg; de Leval, Laurence ULg et al

in Revue Médicale de Liège (2007), 62(2), 118-21

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical ... [more ▼]

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical diseases. A surgical management is the treatment of choice. The diagnosis can then be made or confirmed by histopathologic analysis. [less ▲]

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See detailA thromboxane receptor antagonist, reduces development of atherosclerosis in apoE-deficient mice.
Cherdon, Céline ULg; Rolin, S.; Hanson, S. et al

in Journal of Molecular and Cellular Cardiology (2007), 42

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See detailBM-573, a thromboxane receptor antagonist, reduces development of atherosclerosis in apoE–deficient mice
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

in Journal of Molecular and Cellular Cardiology (2007), 42(suppl 1.), 33-34

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See detailDevelopment of urine-based DNA methylation assay for prostate cancer screening
Vener, T. I.; Derecho, C.; Varde, S. et al

Poster (2007)

Introduction: The best outcome for patients with prostate cancer (PCa) is seen for those treated at an early stage of the disease. A digital rectal examination (DRE) and the measurement of serum prostate ... [more ▼]

Introduction: The best outcome for patients with prostate cancer (PCa) is seen for those treated at an early stage of the disease. A digital rectal examination (DRE) and the measurement of serum prostate specific antigen (PSA) levels are the current standards for PCa early detection. However, serum PSA testing lacks both sensitivity and specificity, and core biopsies frequently fail to identify small foci of PCa. The availability of non-invasive diagnostic molecular tests that could allow for a more precise identification of malignant prostate cells in asymptomatic men would be of great clinical value to improve PCa diagnosis. Study design: 114 men scheduled to undergo a prostate biopsy were enrolled in the study. The biopsies were triggered either by an abnormally high PSA value or by suspicious findings on DRE. Patients with other known or suspected urinary malignancy were excluded from the study. Morning, post-prostate massage and post-biopsy urine samples were collected from all individuals. The main goals of this study were a) to determine if prostate massage can improve the prostate DNA quantity compared to urine collected in the morning or after biopsy, and b) to evaluate the methylation status of a gene panel in urine samples from subjects with cancer found in prostate biopsy tissue cores versus subjects without cancer. Methods: Gene promoter methylation is associated with prostate cancer and has been successfully used for the molecular detection of neoplasia in urine. We have developed real-time methylation specific PCR assays to define the methylation status of several genes. Results: Median age of the patients was 65 years (range 48-85). PCa was found in 51% of the patients. Histological diagnosis of the biopsies was compared to methylation results in urine from 102 samples (89% success rate due low DNA yields for 12 samples). The comparison between different urine sampling techniques showed that prostate massage is needed. The best results were obtained in post massage urine samples with a combination of GSTP1, p14, p16, RARβ2 and RASSF1A resulting in a sensitivity of 74% and a specificity of 75%. Future: A multiplex assay using the Cepheid SmartCycler™ II platform is under development. Further studies are in progress to validate the assay across multiple centers. [less ▲]

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See detailActivation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage
Dassesse, Thibaut; de Leval, Xavier; de Leval, Laurence ULg et al

in European Urology (2006), 50(5), 1021-311031

OBJECTIVE: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa). METHODS: Expression of cyclooxygenase-2 (COX-2), TXA(2) synthase (TXS), and ... [more ▼]

OBJECTIVE: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa). METHODS: Expression of cyclooxygenase-2 (COX-2), TXA(2) synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the TXA(2) pathway, was analyzed on serial tissue sections from 46 human PCa specimens. RESULTS: The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells. Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands. COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections. Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages. CONCLUSIONS: Proteins specifically involved in the TXA(2) pathway are up-regulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation. Our study is the first to examine simultaneously all key proteins involved in this pathway including TXA(2) receptors and results suggest that the TXA(2) pathway may be a potential target for PCa prevention/therapy. [less ▲]

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See detailEstablishment and characterisation of two novel human KSHV- and EBV-negative Burkitt cell lines, GAL-01 and GAL-02, from a primary lymphomatous effusion
Thielen, Caroline ULg; Herens, Christian ULg; Fassotte, Marie-France ULg et al

in European Journal of Haematology (2006), 77(4), 318-326

Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to ... [more ▼]

Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to investigate the biology of lymphoid neoplasia. In this study, we succeeded in establishing two human cell lines, GAL-01 and GAL-02, from a HIV-negative patient with Epstein-Barr virus (EBV) -negative sporadic BL presenting as an effusion. GAL-01 and GAL-02 were established at diagnosis and after one course of polychemotherapy, respectively. The in vivo effusion occurred in a very peculiar clinical setting; the patient having a previous history of intestinal diffuse large B-cell lymphoma. Methods: The morphologic, immunophenotypic and molecular genetic features of GAL cell lines are reported and compared with those of the parental tumour. The findings clearly demonstrated that the Burkitt effusion did not represent disease progression of the intestinal tumour, but represented a second primary haematological malignancy. The in vivo tumorigenic properties of the cells were tested by subcutaneous injection to NOD/SCID mice. Results: Both cell lines were composed of medium-sized lymphoid cells with clumped chromatin, multiple medium-sized nucleoli and moderate amounts of vacuolated cytoplasm. GAL cells display the phenotype and genotype of a B-cell lineage (positive for CD20, CD79a and clonal rearrangement of Ig heavy chain), carry the c-MYC rearrangement by t(8;22)(q24;q11) translocation and are characterised by the expression of the germinal centre-associated antigens CD10, BCL6, CD38 and absent to low BCL2 expression. EBV and HHV8 were not identified within parental tumour or in cultured cells. Subcutaneous injection of both cell lines to NOD/SCID mice induced tumour formation. Conclusions: GAL-01 and GAL-02, two novel EBV-negative human BL cell lines represent a potentially useful experimental model to study the biology of BL possibly including the resistance to chemotherapy. [less ▲]

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See detailReport of two cases of gastric cancer after bariatric surgery: Lymphoma of the bypassed stomach after Roux-en-Y gastric bypass and gastrointestinal stromal tumor (GIST) after vertical banded gastroplasty
De Roover, Arnaud ULg; Detry, Olivier ULg; de Leval, Laurence ULg et al

in Obesity Surgery (2006), 16(7), 928-931

We report two new cases of gastric cancer diagnosed after a bariatric operation. The first case is a 66-year-old male who 3 years after gastric bypass suffered from a perforation of the fundus that was ... [more ▼]

We report two new cases of gastric cancer diagnosed after a bariatric operation. The first case is a 66-year-old male who 3 years after gastric bypass suffered from a perforation of the fundus that was found to be secondary to a diffuse large B-cell lymphoma of the distal stomach. The second case is a 47-year-old woman who presented 12 years after a vertical banded gastroplasty with a gastric pouch outlet obstruction caused by a gastrointestinal stromal tumor (GIST). Based on the few reports of cancer in the literature, analysis of these cases suggests that the main risk of gastric cancer after bariatric surgery comes from the delayed diagnosis of malignancy. [less ▲]

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See detailT-cell/histiocyte-rich large B-cell lymphoma associated with a near-tetraploid karyotype and complex genetic abnormalities
de Leval, Laurence ULg; Harris, N. L.; Lampertz, S. et al

in APMIS : Acta Pathologica, Microbiologica, et Immunologica Scandinavica (2006), 114(6), 474-478

Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations ... [more ▼]

Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). [less ▲]

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