29 results on '"Libbrecht, Louis"'
Search Results
2. Le sarcome intimal cardiaque : tumeur rare illustrée par un cas de présentation histopathologique inhabituelle
- Author
-
Nassereddine, Hussein, Sciot, Raf, Debiec-Rychter, Maria, Aydin, Selda, and Libbrecht, Louis
- Abstract
Les sarcomes cardiaques primitifs sont extrêmement rares et de pronostic sombre. L’existence du sarcome intimal, tumeur mésenchymateuse maligne affectant principalement l’artère pulmonaire et l’aorte, est rapportée au niveau du cœur mais reste encore débattue. Nous rapportons le cas d’un sarcome intimal développé chez une patiente de 70 ans, avec ses caractéristiques macroscopiques, microscopiques et moléculaires.
- Published
- 2019
- Full Text
- View/download PDF
3. Para-anal lipoma as a rare consequence to perineal trauma. Case-report and review of the literature
- Author
-
Uscilowska, Ewelina, Abbes Orabi, Nora, Léonard, Daniel, Mourin-Jouret, Anne, Libbrecht, Louis, Trefois, Pierre, Denis, Marie-Armelle, Bachmann, Radu, Remue, Christophe, and Kartheuser, Alex
- Abstract
AbstractIntroduction:Lipomas are the most common benign mesenchymal tumors which can be found in any part of the body. Nevertheless, their etiology and pathogenesis remain unknown. It is hypothesized that some of these lesions could result from an acute or chronic trauma.Patients and methods:We report a case of a 54-year-old man presenting a perineal lipoma which volume grew rapidly after he fell on his buttock, in the context of inaugural epileptic seizure. Pelvic MRI showed a voluminous fatty mass, measuring 6.6 × 5 × 9 cm without any signs of local invasion. Furthermore, we review the latest research on lipomas originating from traumatic lesion.Results:The mass was completely excised in one block under general anesthaesia, using an elliptical incision and a deep dissection. We did not close the skin incision in view of the cutaneous defect. Post-operative recovery was uneventful and the patient was discharged from hospital two days after the operation. Histopathology indicated a reorganised lipoma with no evidence of malignancy.Conclusion:Perineal lipomas are extremely rare, pathological examination of imaging guided biopsies are needed to exclude malignancy especially a well-differentiated liposarcoma. MRI remains the first option and radical surgical excision is the gold standard treatment.
- Published
- 2019
- Full Text
- View/download PDF
4. Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis
- Author
-
Dachy, Guillaume, de Krijger, Ronald R., Fraitag, Sylvie, Théate, Ivan, Brichard, Bénédicte, Hoffman, Suma B., Libbrecht, Louis, Arts, Florence A., Brouillard, Pascal, Vikkula, Miikka, Limaye, Nisha, and Demoulin, Jean-Baptiste
- Abstract
IMPORTANCE: Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease. OBJECTIVE: To determine the frequency, spectrum, and clinical implications of mutations in the PDGFRB receptor tyrosine kinase found in sporadic myofibroma and myofibromatosis. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study of 69 patients with sporadic myofibroma or myofibromatosis, 85 tumor samples were obtained and analyzed by targeted deep sequencing of PDGFRB. Mutations were confirmed by an alternative method of sequencing and were experimentally characterized to confirm gain of function and sensitivity to the tyrosine kinase inhibitor imatinib. MAIN OUTCOMES AND MEASURES: Frequency of gain-of-function PDGFRB mutations in sporadic myofibroma and myofibromatosis. Sensitivity to imatinib, as assessed experimentally. RESULTS: Of the 69 patients with tumor samples (mean [SD] age, 7.8 [12.7] years), 60 were children (87%; 29 girls [48%]) and 9 were adults (13%; 4 women [44%]). Gain-of-function PDGFRB mutations were found in samples from 25 children, with no mutation found in samples from adults. Mutations were particularly associated with severe multicentric disease (13 of 19 myofibromatosis cases [68%]). Although patients had no familial history, 3 of 25 mutations (12%) were likely to be germline, suggesting de novo heritable alterations. All of the PDGFRB mutations were associated with ligand-independent receptor activation, and all but one were sensitive to imatinib at clinically relevant concentrations. CONCLUSIONS AND RELEVANCE: Gain-of-function mutations of PDGFRB in myofibromas may affect only children and be more frequent in the multicentric form of disease, albeit present in solitary pediatric myofibromas. These alterations may be sensitive to tyrosine kinase inhibitors. The PDGFRB sequencing appears to have a high value for diagnosis, prognosis, and therapy of soft-tissue tumors in children.
- Published
- 2019
- Full Text
- View/download PDF
5. Elevated ΔNp63α Levels Facilitate Epidermal and Biliary Oncogenic Transformation
- Author
-
Devos, Michael, Gilbert, Barbara, Denecker, Geertrui, Leurs, Kirsten, Mc Guire, Conor, Lemeire, Kelly, Hochepied, Tino, Vuylsteke, Marnik, Lambert, Jo, Van Den Broecke, Caroline, Libbrecht, Louis, Haigh, Jody, Berx, Geert, Lippens, Saskia, Vandenabeele, Peter, and Declercq, Wim
- Abstract
Unlike its family member p53, TP63is rarely mutated in human cancer. However, ΔNp63α protein levels are often elevated in tumors of epithelial origin, such as squamous cell carcinoma and cholangiocarcinoma. To study the oncogenic properties of ΔNp63α in vivo, we generated transgenic mice overexpressing ΔNp63α from the Rosa26locus promoter controlled by keratin 5-Cre. We found that these mice spontaneously develop epidermal cysts and ectopic ΔNp63α expression in the bile duct epithelium that leads to dilatation of the intrahepatic biliary ducts, to hepatic cyst formation and bile duct adenoma. Moreover, when subjected to models of 7,12-dimethylbenz[a]anthracene-based carcinogenesis, tumor initiation was increased in ΔNp63α transgenic mice in a gene dosage-dependent manner although ΔNp63α overexpression did not alter the sensitivity to 7,12-dimethylbenz[a]anthracene-induced cytotoxicity in vivo. However, keratinocytes isolated from ΔNp63α transgenic mice displayed increased survival and delayed cellular senescence compared with wild-type keratinocytes, marked by decreased p16Ink4aand p19Arfexpression. Taken together, we show that increased ΔNp63α protein levels facilitate oncogenic transformation in the epidermis as well as in the bile duct.
- Published
- 2017
- Full Text
- View/download PDF
6. A Global Risk Score (GRS) to Simultaneously Predict Early and Late Tumor Recurrence Risk after Resection of Hepatocellular Carcinoma
- Author
-
Dekervel, Jeroen, Popovic, Dusan, van Malenstein, Hannah, Windmolders, Petra, Heylen, Line, Libbrecht, Louis, Bulle, Ashenafi, De Moor, Bart, Van Cutsem, Eric, Nevens, Frederik, Verslype, Chris, and van Pelt, Jos
- Abstract
OBJECTIVES:Recurrence of hepatocellular carcinoma can arise from the primary tumor (“early recurrence”) or de novofrom tumor formation in a cirrhotic environment (“late recurrence”). We aimed to develop one simple gene expression score applicable in both the tumor and the surrounding liver that can predict the recurrence risk. METHODS:We determined differentially expressed genes in a cell model of cancer aggressiveness. These genes were first validated in three large published data sets of hepatocellular carcinoma from which we developed a seven-gene risk score. RESULTS:The gene score was applied on two independent large patient cohorts. In the first cohort, with only tumor data available, it could predict the recurrence risk at 3 years after resection (68 ± 10% vs 35 ± 7%, P= .03). In the second cohort, when applied on the tumor, this gene score predicted early recurrence (62 ± 5% vs 37 ± 4%, P< .001), and when applied on the surrounding liver tissue, the same genes also correlated with late recurrence. Four patient classes with each different time patterns and rates of recurrence could be identified based on combining tumor and liver scores. In a multivariate Cox regression analysis, our gene score remained significantly associated with recurrence, independent from other important cofactors such as disease stage (P= .007). CONCLUSIONS:We developed a Global Risk Score that is able to simultaneously predict the risk of early recurrence when applied on the tumor itself, as well as the risk of late recurrence when applied on the surrounding liver tissue.
- Published
- 2016
- Full Text
- View/download PDF
7. Impact of surgical margins on overall and recurrence-free survival in parenchymal-sparing laparoscopic liver resections of colorectal metastases
- Author
-
Montalti, Roberto, Tomassini, Federico, Laurent, Stéphanie, Smeets, Peter, Man, Marc, Geboes, Karen, Libbrecht, Louis, and Troisi, Roberto
- Abstract
The relationship between the width of surgical margins and local and distant recurrence of colorectal liver metastases (CRLM) remain controversial. We analyzed the impact of surgical margins in laparoscopic liver resections (LLR) for CRLM, using the parenchymal-sparing approach on overall (OS) and recurrence-free survival (RFS). From January 2005 to October 2012, 114 first LLR for CRLM were performed and retrospectively analyzed. The ultrasonic aspirator was used for parenchyma division. R1 margins were defined when the tissue width was <1 mm. After a mean follow-up of 30.9 ± 1.71 months, OS was 97.1–73.9–58.9 % and the RFS 64.2–35.2–31 % at 1–3–5 years, respectively. The major resection rate was 7 %. The median margin width was 3 (0–40) mm, and R1 resection was recorded in 14 (12.3 %) cases. Twenty-two patients (33.3 %) with hepatic recurrence underwent a repeat hepatectomy. R1 margins were significantly related to lower RFS survival (p= 0.038) but did not affect OS. Multivariate analysis showed that lesions located in postero-superior segments (HR = 2.4, 95 % CI 1.24–4.61, p= 0.009) as well as blood loss (HR = 3.2, 95 % CI 1.23–7.99, p= 0.012) were independent risk factors for tumor recurrence. The carcinoembryonic antigen level >10 mcg/L affected OS (HR = 4.2 95 % CI 2.02–16.9, p= 0.001), and the resection of more than two tumors was significantly associated with R1 margins (HR = 9.32, 95 % CI 1.14–32.5, p= 0.037). Laparoscopic parenchymal-sparing surgery of CRLM does not compromise the oncological outcome, allowing a higher percentage of repeat hepatectomy. R1 margins are a risk factor for tumor recurrence but not for overall survival. The presence of multiple lesions is the only independent risk factor of R1 margins and also the major disadvantage of this technique.
- Published
- 2015
- Full Text
- View/download PDF
8. Detection of MDM2CDK4 Amplification in Lipomatous Soft Tissue Tumors From Formalin-fixed, Paraffin-embedded Tissue
- Author
-
Creytens, David, van Gorp, Joost, Ferdinande, Liesbeth, Speel, Ernst-Jan, and Libbrecht, Louis
- Abstract
In this study, the detection of MDM2and CDK4amplification was evaluated in lipomatous soft tissue tumors using multiplex ligation-dependent probe amplification (MLPA), a PCR-based technique, in comparison with fluorescence in situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 atypical lipomatous tumorswell-differentiated liposarcomas, 18 dedifferentiated liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio of >2, 3671 samples (22 atypical lipomatous tumorswell-differentiated liposarcomas, and 14 dedifferentiated liposarcomas) showed MDM2and CDK4amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90 (3640) and a specificity of 100 (3131) in detecting amplification of MDM2 and CDK4 in lipomatous soft tissue tumors. In case of high-level amplification (MDM2-CDK4CEP12 ratio >5), concordance was 100. Four cases of atypical lipomatous tumorwell-differentiated liposarcoma (426, 15) with a low MDM2and CDK4amplification level (MDM2-CDK4CEP12 ratio ranging between 2 and 2.5) detected by FISH showed no amplification by MLPA, although gain of MDM2and CDK4(ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, there was a very high concordance between the ratios obtained by FISH and MLPA. In conclusion, MLPA proves to be an appropriate and straightforward technique for screening MDM2CDK4amplification in lipomatous tumors, especially when a correct cut-off value and reference samples are chosen, and could be considered a good alternative to FISH to determine MDM2and CDK4amplification in liposarcomas. Moreover, because MLPA, as a multiplex technique, allows simultaneous detection of multiple chromosomal changes of interest, it could be in the future a very reliable and fast molecular analysis on paraffin-embedded material to test for other diagnostically, prognostically, or therapeutically relevant genomic mutations in lipomatous tumors.
- Published
- 2015
- Full Text
- View/download PDF
9. Agreement of Gleason Score on Prostate Biopsy and Radical Prostatectomy Specimen: Is There Improvement With Increased Number of Biopsy Cylinders and the 2005 Revised Gleason Scoring?
- Author
-
Van Praet, Charles, Libbrecht, Louis, D'Hondt, Frederiek, Decaestecker, Karel, Fonteyne, Valérie, Verschuere, Stephanie, Rottey, Sylvie, Praet, Marleen, De Visschere, Pieter, and Lumen, Nicolaas
- Abstract
For prostate cancer diagnoses we simultaneously incorporated the 2005 modified Gleason score (GS) and increased the standard number of biopsy cylinders to 8 to 12. This provided better Gleason score concordance between biopsy and radical prostatectomy (RP) specimens (n = 193) than before this change of practice (n = 135), although concordance rate (54%) remained rather poor. More tumors are labeled intermediate-/high-grade using the modified Gleason score.
- Published
- 2014
- Full Text
- View/download PDF
10. On the Concept of Tumor Homogeneity
- Author
-
Libbrecht, Louis
- Published
- 2020
- Full Text
- View/download PDF
11. Molecular Diagnostic Approach to Liver Tissue as an Ancillary Tool for Liver Histopathology
- Author
-
Libbrecht, Louis and Roskams, Tania
- Abstract
Diagnostic liver histopathology is currently based on the microscopic assessment of morphological and immunohistochemical features in a biopsy. In other fields of diagnostic pathology, it has been shown that the diagnostic process can be improved by the incorporation of ancillary molecular techniques and this will most likely also occur in liver pathology in the future. This article gives an overview of several liver diseases for which the diagnosis could be improved by the addition of a molecular technique to the classical histopathologic working method. For each of these diseases, the most promising molecular techniques are discussed. It is very likely that ancillary molecular techniques will be applied in routine practice to improve diagnosis and prognostication of liver tumors in the foreseeable future.
- Published
- 2006
12. Molecular Diagnostic Approach to Liver Tissue as an Ancillary Tool for Liver Histopathology
- Author
-
Libbrecht, Louis and Roskams, Tania
- Published
- 2006
- Full Text
- View/download PDF
13. Neuroregulation of the neuroendocrine compartment of the liver
- Author
-
Roskams, Tania, Cassiman, David, De Vos, Rita, and Libbrecht, Louis
- Abstract
Liver progenitor cells as well as hepatic stellate cells have neuroendocrine features. Progenitor cells express chromogranin-A and neural cell adhesion molecule, parathyroid hormone-related peptide, S-100 protein, neurotrophins, and neurotrophin receptors, while hepatic stellate cells express synaptophysin, glial fibrillary acidic protein, neural cell adhesion molecule, nestin, neurotrophins, and their receptors. This phenotype suggests that these cell types form a neuroendocrine compartment of the liver, which could be under the control of the central nervous system. We recently showed that the parasympathetic nervous system promotes progenitor cell expansion after liver injury, since selective vagotomy reduces the number of progenitor cells after chemical injury in the rat. Similarly, after transplantation, which surgically denervates the liver, human livers that develop hepatitis have fewer progenitor cells than native, fully innervated livers with similar degrees of liver injury. There is also accumulating experimental evidence linking the autonomic system, in particular the sympathetic nervous system (SNS), with the pathogenesis of cirrhosis and its complications. Recently, it has been shown that hepatic stellate cells themselves respond to neurotransmitters. Moreover, inhibition of the SNS reduced fibrosis in carbon tetrachloride-induced liver injury. In view of the denervated state of transplanted livers, it is very important to unravel the neural control mechanisms of regeneration and fibrogenesis. Moreover, since there is a shortage of donor organs, a better understanding of the mechanisms of regeneration could have therapeutic possibilities, which could even obviate the need for orthotopic liver transplantation. © 2004 Wiley-Liss, Inc.
- Published
- 2004
- Full Text
- View/download PDF
14. Liver pathology and hepatocarcinogenesis in a long‐term mouse model of erythropoietic protoporphyria
- Author
-
Libbrecht, Louis, Meerman, Leo, Kuipers, Folkert, Roskams, Tania, Desmet, Valeer, and Jansen, Peter
- Abstract
Erythropoietic protoporphyria (EPP) is an inherited disease of haem synthesis caused by a mutation in one of the alleles of the enzyme ferrochelatase. This mutation leads to partial deficiency of the enzyme, resulting in increased concentrations of protoporphyrin (PP) in blood, liver, and faeces. Five to ten per cent of patients with EPP develop severe liver disease characterized by the presence of PP deposits. This study used histochemistry and immunohistochemistry to investigate the histopathological features present in the livers of 44 mice with a heterozygous or homozygous point mutation in the ferrochelatase gene (fch/+ and fch/fch mice, respectively). Some fch/+ mouse livers showed mixed steatosis and large cell dysplasia. The livers of fch/fch mice showed periportal or septal fibrosis accompanied by an atypical ductular reaction. These findings suggest that the obstruction and damage of a proportion of large and small bile ducts by PP deposits cause an accumulation of PP in the parenchyma, which leads to damage and loss of hepatocytes due to the toxic effects of PP. The classical stages of hepatocarcinogenesis were observed and hepatic progenitor cells appear to be involved in this process. PP acts as the promoting agent and is probably also the initiating agent. Copyright © 2002 John Wiley & Sons, Ltd.
- Published
- 2003
- Full Text
- View/download PDF
15. Progenitor Cells in Diseased Human Liver
- Author
-
Roskams, Tania A., Libbrecht, Louis, and Desmet, Valeer J.
- Published
- 2003
- Full Text
- View/download PDF
16. The Vagal Nerve Stimulates Activation of the Hepatic Progenitor Cell Compartment via Muscarinic Acetylcholine Receptor Type 3
- Author
-
Cassiman, David, Libbrecht, Louis, Sinelli, Nicoletta, Desmet, Valeer, Denef, Carl, and Roskams, Tania
- Abstract
In the rat the hepatic branch of the nervus vagus stimulates proliferation of hepatocytes after partial hepatectomy and growth of bile duct epithelial cells after bile duct ligation. We studied the effect of hepatic vagotomy on the activation of the hepatic progenitor cell compartment in human and rat liver. The number of hepatic progenitor cells and atypical reactive ductular cells in transplanted (denervated) human livers with hepatitis was significantly lower than in innervated matched control livers and the number of oval cells in vagotomized rat livers with galactosamine hepatitis was significantly lower than in livers of sham-operated rats with galactosamine hepatitis. The expression of muscarinic acetylcholine receptors (M1-M5 receptor) was studied by immunohistochemistry and reverse transcriptase-polymerase chain reaction. In human liver, immunoreactivity for M3 receptor was observed in hepatic progenitor cells, atypical reactive ductules, intermediate hepatocyte-like cells, and bile duct epithelial cells. mRNA for the M1-M3 and the M5 receptor, but not the M4 receptor, was detected in human liver homogenates. In conclusion, the hepatic vagus branch stimulates activation of the hepatic progenitor cell compartment in diseased liver, most likely through binding of acetylcholine to the M3 receptor expressed on these cells. These findings may be of clinical importance for patients with a transplant liver.
- Published
- 2002
- Full Text
- View/download PDF
17. Expression of neurotrophins and their receptors in pigment cell lesions of the skin
- Author
-
Innominato, Pasquale F., Libbrecht, Louis, and van den Oord, Joost J.
- Abstract
The neurotrophins (NTs) are a group of growth factors involved in the development of the nervous system and presumed to play a role in neural crest‐derived tumours. The expression of three NTs (NGF, BDNF, and NT‐3) and their receptors (NTRs; i.e. low‐affinity pan‐NT receptor p75, Trk‐B, and Trk‐C) was studied in frozen sections of benign and malignant cutaneous pigment cell lesions, using immunohistochemistry. In order to understand the possible role of these growth factors and their receptors in the progression of primary cutaneous malignant melanomas (PCMMs), their distribution in the radial (RGP) and vertical (VGP) growth phases was particularly studied. While most of the common acquired naevi were unreactive, Spitz and blue naevi showed scattered immunoreactive cells, especially for the p75 NTR. Dysplastic naevi, but not common naevi, expressed NT‐3 in their junctional component. PCMM and melanoma metastases often showed a diffuse pattern of immunostaining. NT‐3 was significantly more frequently expressed in the RGP of PCMMs than in the junctional component of benign naevi, whereas more extensive immunoreactivity for NGF was found in the VGP of PCMMs, compared with the RGP; metastases more frequently expressed NGF, BDNF, and Trk‐B than PCMMs. Interestingly, neurotropic melanoma expressed all NTs/NTRs except Trk‐B. These immuunohistochemical data confirm suggestions from previous in vitrostudies that autocrine loops of certain NTs and their respective receptors may be involved in melanoma progression; in addition, NT‐3 may be involved in the junctional growth of dysplastic naevi. The precise role of these growth factors in melanoma, however, will await further functional studies. Copyright © 2001 John Wiley & Sons, Ltd.
- Published
- 2001
- Full Text
- View/download PDF
18. Deep intralobular extension of human hepatic progenitor cells correlates with parenchymal inflammation in chronic viral hepatitis: can progenitor cells migrate?
- Author
-
Libbrecht, Louis, Desmet, Valeer, Damme, Boudewijn Van, and Roskams, Tania
- Abstract
Ductular reaction and putative progenitor cells (or progenitor cells), which are presumed to be the human counterpart of the oval cells in rat liver, have been discerned in various human liver diseases, including chronic viral hepatitis. Since in experimental models of chronic hepatitis the activation of oval cells is correlated with the inflammatory infiltrate, this study investigated whether there is a correlation in chronic viral hepatitis between the number of progenitor cells extending into the lobule and the severity of parenchymal inflammation, on the one hand, and the extent of ductular reaction and the severity of interface hepatitis, on the other hand. Liver biopsies of 55 patients with chronic hepatitis B and/or C were used. The severity of parenchymal inflammation and of interface hepatitis was semiquantitatively graded on a haematoxylin and eosin-stained paraffin section, while the number of progenitor cells and the extent of the ductular reaction were assessed on a serial section stained for cytokeratin (CK) 7. In addition, more extensive phenotyping of progenitor cells was performed on sections from frozen material from five patients, using antibodies against CK7, CK8, CK18, CK19, chromogranin-A, and the rat oval cell marker OV-6. The number of more centrally located progenitor cells correlated significantly with the severity of the parenchymal inflammation, while the extent of the ductular reaction correlated significantly with the severity of interface hepatitis. These findings suggest that in chronic viral hepatitis, inflammation plays a role in progenitor cell activation and its topography. In cases with moderate and severe lobular inflammation, progenitor cells were strikingly scattered throughout the parenchyma and surrounded by intermediate hepatocyte-like cells, suggesting their migration into the parenchyma and their differentiation towards the hepatocytic lineage. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
19. Deep intralobular extension of human hepatic ‘progenitor cells’ correlates with parenchymal inflammation in chronic viral hepatitis: can ‘progenitor cells’ migrate?
- Author
-
Libbrecht, Louis, Desmet, Valeer, Van Damme, Boudewijn, and Roskams, Tania
- Abstract
Ductular reaction and putative progenitor cells (or ‘progenitor cells’), which are presumed to be the human counterpart of the oval cells in rat liver, have been discerned in various human liver diseases, including chronic viral hepatitis. Since in experimental models of chronic hepatitis the activation of oval cells is correlated with the inflammatory infiltrate, this study investigated whether there is a correlation in chronic viral hepatitis between the number of ‘progenitor cells’ extending into the lobule and the severity of parenchymal inflammation, on the one hand, and the extent of ductular reaction and the severity of interface hepatitis, on the other hand. Liver biopsies of 55 patients with chronic hepatitis B and/or C were used. The severity of parenchymal inflammation and of interface hepatitis was semiquantitatively graded on a haematoxylin and eosin‐stained paraffin section, while the number of ‘progenitor cells’ and the extent of the ductular reaction were assessed on a serial section stained for cytokeratin (CK) 7. In addition, more extensive phenotyping of ‘progenitor cells’ was performed on sections from frozen material from five patients, using antibodies against CK7, CK8, CK18, CK19, chromogranin‐A, and the rat oval cell marker OV‐6. The number of more centrally located ‘progenitor cells’ correlated significantly with the severity of the parenchymal inflammation, while the extent of the ductular reaction correlated significantly with the severity of interface hepatitis. These findings suggest that in chronic viral hepatitis, inflammation plays a role in ‘progenitor cell’ activation and its topography. In cases with moderate and severe lobular inflammation, ‘progenitor cells’ were strikingly scattered throughout the parenchyma and surrounded by intermediate hepatocyte‐like cells, suggesting their migration into the parenchyma and their differentiation towards the hepatocytic lineage. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
- Full Text
- View/download PDF
20. Fas and Fas ligand: strong co-expression in human hepatocytes surrounding hepatocellular carcinoma; can cancer induce suicide in peritumoural cells?
- Author
-
Roskams, Tania, Libbrecht, Louis, Damme, Boudewijn Van, and Desmet, Valeer
- Abstract
Fas (Apo-1, CD95), a member of the nerve growth factor/tumour necrosis factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (Fas-L) binding. Fas has been shown to be present on hepatocyte membranes in normal liver and in chronic hepatitis C. At the present time, very limited data are available on the expression of Fas-L. This paper describes a study of 20 cases of active chronic hepatitis of different aetiologies, 20 hepatocellular carcinomas (HCCs) and the adjacent non-tumoural liver parenchyma, and five normal livers. The immunohistochemical expression of Fas and Fas-L was determined using specific monoclonal antibodies. In normal liver, Fas was faintly expressed on membranes of hepatocytes and bile duct cells, while Fas-L was negative. In active chronic hepatitis, Fas expression in hepatocytes was enhanced, resulting in a diffuse honeycomb pattern. Fas-L showed cytoplasmic positivity in hepatocytes in areas of interface hepatitis. Strong expression of Fas as well as Fas-L in the hepatocytes immediately adjacent to HCC was a constant finding. Within the HCCs, Fas-L expression was variable, but present only in a minority of cells. Fas varied from a diffuse honeycomb pattern to focal positivity in occasional cells. There was no correlation between Fas and Fas-L expression in the tumours. In conclusion, hepatocytes can co-express Fas and Fas-L in areas of interface hepatitis and adjacent to HCC, suggesting that they have the ability to induce apoptosis in an autocrine or paracrine way. Within the tumour, the FasFas-L apoptosis pathway seems to be little involved. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
21. Fas and Fas ligand: strong co‐expression in human hepatocytes surrounding hepatocellular carcinoma; can cancer induce suicide in peritumoural cells?
- Author
-
Roskams, Tania, Libbrecht, Louis, Van Damme, Boudewijn, and Desmet, Valeer
- Abstract
Fas (Apo‐1, CD95), a member of the nerve growth factor/tumour necrosis factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (Fas‐L) binding. Fas has been shown to be present on hepatocyte membranes in normal liver and in chronic hepatitis C. At the present time, very limited data are available on the expression of Fas‐L. This paper describes a study of 20 cases of active chronic hepatitis of different aetiologies, 20 hepatocellular carcinomas (HCCs) and the adjacent non‐tumoural liver parenchyma, and five normal livers. The immunohistochemical expression of Fas and Fas‐L was determined using specific monoclonal antibodies. In normal liver, Fas was faintly expressed on membranes of hepatocytes and bile duct cells, while Fas‐L was negative. In active chronic hepatitis, Fas expression in hepatocytes was enhanced, resulting in a diffuse honeycomb pattern. Fas‐L showed cytoplasmic positivity in hepatocytes in areas of interface hepatitis. Strong expression of Fas as well as Fas‐L in the hepatocytes immediately adjacent to HCC was a constant finding. Within the HCCs, Fas‐L expression was variable, but present only in a minority of cells. Fas varied from a diffuse honeycomb pattern to focal positivity in occasional cells. There was no correlation between Fas and Fas‐L expression in the tumours. In conclusion, hepatocytes can co‐express Fas and Fas‐L in areas of interface hepatitis and adjacent to HCC, suggesting that they have the ability to induce apoptosis in an autocrine or paracrine way. Within the tumour, the Fas–Fas‐L apoptosis pathway seems to be little involved. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
- Full Text
- View/download PDF
22. Gemcitabine Recruits M2-Type Tumor-Associated Macrophages into the Stroma of Pancreatic Cancer
- Author
-
Bulle, Ashenafi, Dekervel, Jeroen, Deschuttere, Lise, Nittner, David, Libbrecht, Louis, Janky, Rekin's, Plaisance, Stéphane, Topal, Baki, Coosemans, An, Lambrechts, Diether, Van Cutsem, Eric, Verslype, Chris, and van Pelt, Jos
- Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease that can develop therapy resistance over time. The dense stroma in PDAC plays a critical role in tumor progression and resistance. How this stroma interacts with the tumor cells and how this is influenced by chemotherapy remain poorly understood. METHODS: The backbone of this study is the parallel transcriptome analysis of human tumor and mouse stroma in two molecular and clinical representative patient-derived tumor xenografts models. Mice (8 animals per group) were treated for 4 weeks with gemcitabine or control. We studied tumor growth, RNA expression in the stroma, tumor-associated macrophages (TAMs) with immunofluorescence, and cytokines in the serum. RESULTS: A method for parallel transcriptome analysis was optimized. We found that the tumor (differentiation, gene expression) determines the infiltration of macrophages into the stroma. In aggressive PDAC (epithelial-to-mesenchymal transition high), we find more M2 polarized TAMs and the activation of cytokines and growth factors (TNFα, TGFβ1, and IL6). There are increased stromal glycolysis, reduced fatty acid oxidation, and reduced mitochondrial oxidation (tricarboxylic acid cycle and oxidative phosphorylation). Treatment with gemcitabine results in a shift of innate immune cells, especially additional infiltration of protumoral M2 TAMs (P< .001) and metabolic reprogramming. CONCLUSIONS: Gemcitabine treatment of PDAC xenografts stimulates a protumoral macrophage phenotype, and this, in combination with a shift of the tumor cells to a mesenchymal phenotype that we reported previously, contributes to tumor progression and therapeutic resistance. Targeting M2-polarized TAMs may benefit PDAC patients at risk to become refractory to current anticancer regimens.
- Published
- 2020
- Full Text
- View/download PDF
23. Evaluation of the correlation between KRASmutated allele frequency and pathologist tumorous nuclei percentage assessment in colorectal cancer suggests a role for zygosity status
- Author
-
Libbrecht, Louis, Baldin, Pamela, Dekairelle, Anne-France, and Jouret-Mourin, Anne
- Abstract
Evaluation of molecular tumour heterogeneity relies on the tumorous nuclei percentage (TNP) assessment by a pathologist, which has been criticised for being inaccurate and suffering from interobserver variability. Based on the ‘Big Bang theory’ which states that KRASmutation in colorectal cancer is mostly homogeneous, we investigated this issue by performing a critical analysis of the correlation of the KRASmutant allele fraction with the TNP in 99 colorectal tumour samples with a positive KRASmutation status as determined by next-generation sequencing. Our results yield indirect evidence that the KRAS zygosity status influences the correlation between these parameters and we show that a well-trained pathologist is indeed capable of accurately assessing TNP. Our findings indicate that tumour zygosity, a feature which has largely been neglected until now, should be taken into account in future studies on (colorectal) molecular tumour heterogeneity.
- Published
- 2018
- Full Text
- View/download PDF
24. Case Report of Gastrointestinal Bleeding in an Adult with Chronic Visceral Acid Sphingomyelinase Deficiency
- Author
-
Cassiman, David, Libbrecht, Louis, Meersseman, Wouter, and Wilmer, Alexander
- Abstract
Introduction. Acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick Type A and Type B disease) is a rare, inherited metabolic disorder. Liver-related issues, including cirrhosis and variceal haemorrhage, are a leading cause of early mortality in individuals with chronic forms of ASMD. Due to the rarity of this lysosomal storage disorder, there can be a lack of awareness that adults with chronic ASMD disease are at significant risk of cirrhosis, portal hypertension, and variceal bleeding. This case highlights an unusual presentation of recurrent variceal bleeding in an adult with cirrhosis and portal hypertension due to chronic visceral ASMD. Case Presentation. A patient with severe splenomegaly was diagnosed with ASMD at age of 25. At age 64 they had multiple hospital admissions for hematochezia (originally diagnosed as ischemic colitis) accompanied by hypotension (blood pressure 91/45 mmHg), anemia (hemoglobin 8.5g/dL, ref 12-16; INR 1.4, ref ≤1.2), and mild renal insufficiency (creatinine 1.33mg/dL, ref 0.51-0.95). Colonoscopy did not reveal a source of bleeding. Computerized tomography scanning imaging showed diffuse venous collaterals and ascites. Arteriographies during subsequent episodes of bleeding were negative for active arterial intestinal bleeding. Recurrent gastrointestinal bleeding was found to originate from a varicose vein cluster connected to the right iliac vein and the superior mesenteric vein, located in the submucosa of a small intestinal loop. Multiple varices were secondary to portal hypertension in the context of cirrhosis. The patient died from recurrent variceal bleeding that exacerbated liver failure worsened by pneumonia and hypovolemic and septic shock. Conclusions. The variceal bleeding in this patient was atypical in that it originated from venous collaterals bleeding into the small intestine rather than the more typical gastroesophageal varices observed in ASMD. With long standing liver dysfunction and gradual development of portal hypertension, intestinal varices rather than occult intestinal bleeding due to ischemia should be considered in ASMD patients presenting with either hematochezia or hematemesis.
- Published
- 2019
- Full Text
- View/download PDF
25. Phenotype of Hepatocellular Neoplasms Associated With Androgen Use
- Author
-
Libbrecht, Louis and Colle, Isabelle
- Published
- 2016
- Full Text
- View/download PDF
26. Nuclear Expression of STAT6 in Dedifferentiated Liposarcomas With a Solitary Fibrous Tumor-like Morphology
- Author
-
Creytens, David, Libbrecht, Louis, and Ferdinande, Liesbeth
- Published
- 2015
- Full Text
- View/download PDF
27. Fibroblast-induced matrix remodeling paves the path for invasion
- Author
-
Van Bockstal, Mieke, Libbrecht, Louis, and De Wever, Olivier
- Published
- 2015
- Full Text
- View/download PDF
28. On the Pathogenesis of Central Liver Nodules in Alagille Syndrome
- Author
-
Libbrecht, Louis and Cassiman, David
- Published
- 2017
- Full Text
- View/download PDF
29. On the Pathogenesis of Central Liver Nodules in Alagille Syndrome
- Author
-
Libbrecht, Louis and Cassiman, David
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.