Mean Expression of the X-Chromosome is Associated with Neuronal Density.
; ; et al
in Frontiers in Neuroscience (2012), 6
Background: Neurodegenerative diseases are characterized by key features such as loss of neurons, astrocytosis, and microglial activation/proliferation. These changes cause differences in the density of ... [more ▼]
Background: Neurodegenerative diseases are characterized by key features such as loss of neurons, astrocytosis, and microglial activation/proliferation. These changes cause differences in the density of cell types between control and disease subjects, confounding results from gene expression studies. Chromosome X (ChrX) is known to be specifically important in the brain. We hypothesized the existence of a chromosomal signature of gene expression associated with the X-chromosome for neurological conditions not normally associated with that chromosome. The hypothesis was investigated using publicly available microarray datasets from studies on Parkinson's disease, Alzheimer's disease, and Huntington's disease. Data were analyzed using Chromowave, an analytical tool for detecting spatially extended expression changes along chromosomes. To examine associations with neuronal density and astrocytosis, the expression of cell specific reporter genes was extracted. The association between these genes and the expression patterns extracted by Chromowave was then analyzed. Further analyses of the X:Autosome ratios for laser dissected neurons, microglia cultures and whole tissue were performed to detect cell specific differences. Results: We observed an extended pattern of low expression of ChrX consistent in all the neurodegenerative disease brain datasets. There was a strong correlation between mean ChrX expression and the pattern extracted from the autosomal genes representing neurons, but not with mean autosomal expression. No chromosomal patterns associated with the neuron specific genes were found on other chromosomes. The chromosomal expression pattern was not present in datasets from blood cells. The X:Autosome expression ratio was also higher in neuronal cells than in tissues with a mix of cell types. Conclusions: The results suggest that neurological disorders show as a reduction in mean expression of many genes along ChrX. The most likely explanation for this finding relates to the documented general up-regulation of ChrX in brain tissue which, this work suggests, occurs primarily in neurons. If validated, this cell specific ChrX expression warrants further research as understanding the biological reasons and mechanisms for this expression, may help to elucidate a connection with the development of neurodegenerative disorders. [less ▲]Detailed reference viewed: 4 (2 ULg)
Clinicopathologic and molecular analysis of a choroidal pigmented schwannoma in the context of a PTEN hamartoma tumor syndrome.
; ; DEPREZ, Manuel et al
in Ophthalmology (2012), 119(4), 857-64
PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog ... [more ▼]
PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor. DESIGN: Observational case report. PARTICIPANT: A 10-year-old girl diagnosed with PHTS. METHODS: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing. MAIN OUTCOME MEASURES: Histopathologic and molecular characterization of a choroidal pigmented schwannoma. RESULTS: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor. CONCLUSIONS: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression. [less ▲]Detailed reference viewed: 7 (0 ULg)
Epithelial ingrowth cells after LASIK/ALTK (automated lamellar therapeutic keratoplasty): are they corneal epithelial stem cells?
; ; DEPREZ, Manuel et al
in British Journal of Ophthalmology (2012), 96(7), 1043-6Detailed reference viewed: 2 (0 ULg)
Primary central nervous system lymphoma in a patient treated with Natalizumab.
Phan-Ba, Rémy ; Bisig, Bettina ; Deprez, Manuel et al
in Annals of Neurology (2011), 69(6), 1060-1Detailed reference viewed: 32 (12 ULg)
Radiation-induced malignant peripheral nerve sheat tumors – a report of 2 cases
PHAN BA, Remy ; BELACHEW, Shibeshih ; JEDIDI, Zayd et al
Poster (2011, May)
We discuss the case of two patients who developped delayed malignant peripheral nerve sheath tumor (MPNST) following radiotherapy. Case report: the first patient is a sixty year-old woman with a 2 years ... [more ▼]
We discuss the case of two patients who developped delayed malignant peripheral nerve sheath tumor (MPNST) following radiotherapy. Case report: the first patient is a sixty year-old woman with a 2 years history of right cervicobrachial pain and weakness. The neurological examination depicted severe weakness, atrophy and loss of sensation in the right C5 and C6 territories. A subclavicular hardened and enlarged lymph node was noted. Her past medical history was notable for a Hodgkin’s disease (HD) treated with radiation therapy (>40Gy) 35 years earlier. Brachial plexus MRI revealed a tumoral mass arising from the right brachial plexus. Biopsy of the subclavicular mass revealed a poorly differentiated malignant tumour consisting of spindle cells showing moderate polymorphism and a high mitotic index. Immunohistochemistry showed positivity for the S-100 protein, the CD56 and for the epithelial membrane antigen (EMA) and a diagnosis of MPNST of the brachial plexus was proposed. The second case is a 36 year-old man referred for a history of right sciatic neuralgia that appeared 3 years earlier. The medical history of the patient was notable for a right seminoma, treated by orchidectomy and prophylactic radiotherapy (24 Gy) 5 years earlier. The neurologic examination revealed right L5 and S1 radicular territories involvement, and the CT of the pelvis demonstrated a nodular mass at the level of the greater sciatic foramen. A surgical biopsy was performed and the neuropathological findings were consistent with a diagnosis of low-grade MPSNT. Discussion: MPNSTs are rare tumors accounting for 3 to 10% of all tissues sarcomas. Half of the cases described are sporadic, while the other half tend to appear in patients suffering from tumor prone conditions, such as neurofibromatosis type 1. Although secondary neoplasms are known complications of radiotherapy, descriptions of peripheral nerve sheath tumors (PNST) are scarce. The exact pathophysiology of radiation-induced PNSTs remains unclear but vascular alterations, direct damages to axon or Schwann cell and nerve compression by soft tissue fibrosis are thought to play a role. Although surgical removal sometimes followed by chemotherapy is the mainstay of MPNSTs, they usually carry a poor prognosis. Our 2 cases emphasize that the possibility of radiation-induced MPNST has to be kept in mind when investigating a localized neuropathy in a previously irradiated area. [less ▲]Detailed reference viewed: 21 (0 ULg)
Cancer du sein: importance de la nomenclature anatomo-pathologique
BLETARD, Noëlla ; DETREMBLEUR, Nancy ; SCAGNOL, Irène et al
in Revue Médicale de Liège (2011), 66(5-6), 261-4
The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign ... [more ▼]
The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign or malignant tumours and therefore provides the clinicians with essential information for the therapeutic strategy. In the Pathology laboratory, immunohistochemistry and molecular biology have improved the specificity of the diagnosis and have introduced new prognostic and predictive markers for tumour management. The last edition of the WHO classification, released in 2003, distinguishes 21 varieties of invasive carcinoma and 2 categories of intraepithelial neoplasia based on the morphology and immunohistochemical profile. Other diseases can affect the breast, although much less frequently, such as Paget’s disease of the nipple, phyllode tumours, sarcomas, lymphomas... These diseases will not be reviewed here. [less ▲]Detailed reference viewed: 31 (4 ULg)
Les paralysies du nerf moteur oculaire commun chez l'enfant: a propos d'une observation de tumeur germinale hypophysaire.
; COLLIGNON, Nathalie ; ANDRIS, Cécile et al
in Bulletin de la Société Belge d'Ophtalmologie (2011), (318), 31-6
PURPOSE: Third cranial nerve palsies are unfrequent in childhood and adolescence and are most often congenital. The association of sellar germ cell tumor and ophthalmoplegia is considered as being very ... [more ▼]
PURPOSE: Third cranial nerve palsies are unfrequent in childhood and adolescence and are most often congenital. The association of sellar germ cell tumor and ophthalmoplegia is considered as being very rare at this age. CASE REPORT: A 11-year-old young girl was examined in emergency with a third left cranial nerve partial palsy associated with one- year duration history of hypopituitarism with insipid diabetes and growth retardation. Cerebral IRM revealed a tumor of the pituitary gland. In histopathological examination of pituitary gland biopsies, lesions were compatibles with a sellar germ cell tumor. CONCLUSION: Although they are most often of a congenital nature, third cranial nerve palsies in childhood may be secondary to other causes that should be always taken in mind. When they are secondary to a sellar tumor and according to the clinical presentation and the IRM, the histopahological examination of biopsies is mandatory to have a precise diagnosis. [less ▲]Detailed reference viewed: 20 (1 ULg)
Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection.
Kroonen, Jérôme ; Nassen, Jessica ; et al
in International Journal of Cancer = Journal International du Cancer (2011), 129(3), 574-585
This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs ... [more ▼]
This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs following xenograft in the caudate putamen of immunodeficient mice.In patients with glioblastoma multiforme, recurrence is the rule despite continuous advances in surgery, radiotherapy and chemotherapy. Within these malignant gliomas, glioblastoma stem cells or initiating cells have been recently described and they were shown to be specifically involved in experimental tumorigenesis. In this study, we show that some human glioblastoma cells injected into the striatum of immunodeficient nude mice exhibit a tropism for the subventricular zones. There and similarily to neurogenic stem cells, these subventricular glioblastoma cells were then able to migrate towards the olfactory bulbs. Finally, the glioblastoma cells isolated from the adult mouse subventricular zones and olfactory bulbs display high tumorigenicity when secondary injected in a new mouse brain. Together, these data suggest that neurogenic zones could be a reservoir for particular cancer-initiating cells. [less ▲]Detailed reference viewed: 53 (23 ULg)
Pan-spinal dissemination from a supratentorial primitive neuroectodermal tumor
Pellegrini, Nicolas ; Nguyen Khac, Minh-Tuan ; Racaru, Tudor et al
Poster (2010, March 20)Detailed reference viewed: 27 (10 ULg)
Primary diffuse leptomeningeal gliomatosis: an autopsy case and review of the literature
Somja, Joan ; Boly, Mélanie ; Sadzot, Bernard et al
in Acta Neurologica Belgica (2010), 110(4), 325-33
We report a case of primary diffuse leptomeningeal gliomatosis (PDLG) in a 76-year-old male presenting with confusion, dysarthria, diplopia, lumbal pain and headaches of recent onset. Neurological ... [more ▼]
We report a case of primary diffuse leptomeningeal gliomatosis (PDLG) in a 76-year-old male presenting with confusion, dysarthria, diplopia, lumbal pain and headaches of recent onset. Neurological examination revealed nuchal rigidity and bilateral sixth cranial nerve palsy. The cerebrospinal fluid showed a marked hyperproteinorachia (4711 mg/L) and mild cytorachia (5-10 leucocytes/mm3) with a few atypical lymphoid cells. On admission, brain CT scan and MRI demonstrated diffuse and nodular leptomeningeal contrast enhancement predominant at the skull base and several osteolytic lesions in the right parietal bone. Extensive serological studies for infectious, autoimmune or neoplastic diseases were negative. The work-up diagnosis was neurosarcoidosis or multiple meningeal and osseous metastases of an unknown primary cancer. Surgical biopsy of the right parietal bone lesion showed only fibrous tissue with no evidence of tumour or inflammation. The patient was treated with high dose corticosteroids but its neurological status progressively worsened and he died of aspiration pneumonia 35 days after admission. Post-mortem examination revealed a PDLG, a rare fatal tumour with about 60 cases reported. PDGL is characterized by the diffusion of neoplastic glial cells throughout the leptomeninges without evidence of a primary intra-parenchymal lesion. Recognition of this rare brain tumour is important as recent reports suggest that radiotherapy and chemotherapy can improve patient survival. [less ▲]Detailed reference viewed: 40 (18 ULg)
Fish and chips
DELVENNE, Philippe ; Deprez, Manuel ; BISIG, Bettina et al
in Revue Médicale de Liège (2010), 65 Spec no.
Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In ... [more ▼]
Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In Situ Hybridization) and chips (microarrays,...). The purpose of this article is to describe the principles and the potential applications of these techniques. [less ▲]Detailed reference viewed: 26 (5 ULg)
Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly.
; ; et al
in International Journal of Cancer = Journal International du Cancer (2009), 125(9), 2122-6
Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and ... [more ▼]
Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and acromegaly-associated growth hormone secreting pituitary tumors. Although a good portion of acromegalic patients gets normalized after SSA treatment, strict hormonal control is not achieved in a sizeable proportion of these patients. The reasons for this incomplete response to SSA treatment are unclear. We have found that the tumor suppressor ZAC1 (LOT1/PLAGL1) is essential for the antiproliferative effect of SSA in pituitary tumor cells. The aim of the present retrospective cohort study was to determine whether ZAC1 immunoreactivity in archival somatotrophinoma tissue derived from 45 patients with acromegaly routinely pretreated with SSA before surgery, was associated with response to SSA (normalization of GH, IGF-I and presence of tumor shrinkage). All tumors displayed ZAC1 immunoreactivity [weak (+; n = 15), moderate (++; n = 16) and strong (+++; n = 14)]. A significant positive correlation was found between strong ZAC1 immunoreactivity and IGF-I normalization and presence of tumor shrinkage after SSA treatment, which was not affected by age at diagnosis, gender or duration of SSA treatment. These in vivo data combined with the antiproliferative properties of ZAC1/Zac1 provide evidence of a mechanistic role for this transcription factor on SSA induced tumor shrinkage and hormone normalization. [less ▲]Detailed reference viewed: 18 (7 ULg)
Tumor-like MRS and PET findings in a case of radiation-induced brain necrosis, away from any tumor: an intringuing case report
Nguyen Khac, Minh-Tuan ; Hustinx, Roland ; Deprez, Manuel et al
Conference (2009, March 21)Detailed reference viewed: 28 (6 ULg)
Dural osteomas and chondromas: case reports and review of the litterature
Nguyen Khac, Minh-Tuan ; Martin, Didier ; Deprez, Manuel et al
Poster (2009, March 21)Detailed reference viewed: 17 (2 ULg)
A clinico-pathological report of SCA17 associated with a heterozygote small trinucleotide expansion
Garraux, Gaëtan ; Moonen, Gustave ; Deprez, Manuel
in Movement Disorders : Official Journal of the Movement Disorder Society (2009), 24(Suppl. 1), 12-12Detailed reference viewed: 13 (6 ULg)
Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults.
Robe, Pierre ; Martin, Didier ; Nguyen-Khac, Minh-Tuan et al
in BMC Cancer (2009), 9
BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an ... [more ▼]
BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. RESULTS: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45828668. [less ▲]Detailed reference viewed: 37 (12 ULg)
Contrast-enhanced coded phase-inversion harmonic sonography of knee synovitis correlates with histological vessel density: 2 automated digital quantifications
Kaiser, Marie-Joëlle ; Hauzeur, Jean-Philippe ; Blacher, Silvia et al
in Journal of Rheumatology (2009), 36(7), 1391-400
OBJECTIVE: To use contrast-enhanced coded phase-inversion harmonic B-mode sonography to assess the acoustic enhancement of the synovial area of the knee; and to compare the data with the histological ... [more ▼]
OBJECTIVE: To use contrast-enhanced coded phase-inversion harmonic B-mode sonography to assess the acoustic enhancement of the synovial area of the knee; and to compare the data with the histological vessel density. METHODS: Eleven patients eligible for a knee arthroscopy were studied. Acoustic quantification was carried out by a digital image analysis program that detects the time-dependent increase [intensity (time) = k x time + C] of gray-level intensity in all the pixels of a specific region of interest (ROI) following intravenous injection of the microbubble contrast agent sulfur hexafluoride. Echo-guided synovial biopsies were carried out in the same ROI. Synovial vessel areas were quantified after Factor VIII immunostaining of synovial biopsies using an automated digital image analysis. RESULTS: Significant (p < 0.05) correlations were observed between histological vessel density and percentage of the synovial area with a k value > 0.01 (r = 0.93) and k(max) values (r = 0.79), as well as between the 2 latter parameters (r = 0.72). The histological vessel density and the 2 acoustic parameters were also significantly correlated with the logarithm of erythrocyte sedimentation rate (r = 0.77, r = 0.87, r = 0.67, respectively) and with log C-reactive protein serum concentration (r = 0.69, r = 0.83, r = 0.62, respectively). CONCLUSION: Contrast-enhanced coded phase-inversion harmonic B-mode sonography coupled with an appropriate data analysis method is a new tool to identify and quantify vessel density in knee synovitis. [less ▲]Detailed reference viewed: 45 (6 ULg)
Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature.
Deprez, Manuel ;
in American Journal of Dermatopathology (2009), 31(3), 256-62
Eyelid tumors are the most common neoplasm in daily ophthalmology practice and encompass a wide variety of benign and malignant tumors. In this retrospective study, we report the clinical and histological ... [more ▼]
Eyelid tumors are the most common neoplasm in daily ophthalmology practice and encompass a wide variety of benign and malignant tumors. In this retrospective study, we report the clinical and histological features of 5504 eyelid skin tumors diagnosed at the Laboratory of Ophthalmopathology of the Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland, between January 1989 and December 2007. Benign tumors largely predominated over malignant ones, representing 84% of cases in this series, and the 5 most frequent subtypes were squamous cell papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%), hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and sebaceous carcinoma (3%). For several tumor subtypes, there was a poor correlation between clinical and histological diagnosis, stressing the numerous pitfalls in the diagnosis of eyelid tumors. We further discuss our results with reference to previously published series. [less ▲]Detailed reference viewed: 65 (4 ULg)
The dexamethasone-induced inhibition of proliferation, migration and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors.
Piette, Caroline ; Deprez, Manuel ; et al
in Journal of Biological Chemistry (2009), 284(47), 32483-92
Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema ... [more ▼]
Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy. [less ▲]Detailed reference viewed: 53 (7 ULg)