Infarctus de l´os fémoral révélant une drépanocytose composite SC chez un patient marocain

La double hétérozygotie SC est considérée comme un syndrome drépanocytaire majeur; en effet, son évolution peut être marquée par des complications sévegrave;res voire irréversibles, tel que l´infarctus osseux. Notre observation rapporte la découverte d´une hétérozygotie composite SC chez un patient de 17 ans à la suite de gonalgies intenses et met ainsi en exergue le retard diagnostic de cette maladie, et soulegrave;ve la nécessité de mise en place d´une politique de dépistage précoce afin d´améliorer la prise en charge et le pronostic des sujets atteints

Anémie de fanconi au CHU Hassan II Fès: à propos de 6 observations

L'anémie de Fanconi est une maladie récessive associée à une instabilité chromosomique, elle est marquée par une hétérogénéité phénotypique qui inclut une insuffisance médullaire, un syndrome malformatif variable, une prédisposition à développer des leucémies aiguës myéloïdes (LAM) et une hypersensibilité cellulaire aux agents pontant l'ADN. Le diagnostic est basé sur l'augmentation anormale du taux de cassures chromosomiques spontanées mais surtout, et de manière spécifique, sur une augmentation nette de ces cassures chromosomiques en présence d'agents alkylants bifonctionnels, ce qui est le cas pour nos six patients. Le conseil génétique rejoint celui des maladies autosomiques récessives. Nous rapportons nos premières observations au CHU Hassan II Fès, confirmées par la mise en évidence d'une grande instabilité chromosomique après culture sous Mitomycine C en comparaison avec un témoin normal. Le but de cet article est la mise à jour de nos connaissances sur la génétique de l'Anémie de Fanconi et à travers ces six observations nous illustrons le rôle de la cytogénétique dans le diagnostic et le conseil génétique pour une meilleure prise en charge aussi bien des enfants atteints que de leurs familles

Syndromes microdélétionnels (syndrome de Williams et syndrome de la délétion 22q11) au CHU Hassan II de Fès: à propos de 3 observations

Les syndromes microdélétionnels sont définis par la présence d’une anomalie chromosomique de taille mineure (inférieure à 5 mégabases) ou aneusomie segmentaire, décelable par cytogénétique moléculaire (FISH : Fluorescent in Situ Hybridization). Les syndromes microdélétionnels représentent des syndromes cliniques avec des phénotypes suffisamment caractéristiques pour être reconnus cliniquement. Actuellement la FISH est la technique de choix pour rechercher ces syndromes. Plusieurs syndromes microdélétionnels peuvent être confirmés aisément, les plus recherchés sont Le syndrome de Williams (microdélétion en 7q11.23) et le syndrome de la délétion 22q11 (microdélétion en 22q11.2). Le syndrome de Williams est caractérisé par une anomalie du développement qui associe un retard psycho-moteur, une dysmorphie du visage évocatrice et un profil cognitif et comportemental spécifique, une sténose aortique supravalvulaire -SASV- le plus souvent. Le Syndrome de la délétion 22q11 se caractérise par l’association de plusieurs malformations d’expression variable: une cardiopathie congénitale de type conotroncal, une dysmorphie faciale discrète mais caractéristique et une hypoplasie du thymus et des parathyroïdes. Nous rapportons nos premières observations au CHU Hassan II confirmées par FISH : Syndrome de la délétion 22q11 (n:2) et un syndrome de Williams. Le but de cet article est la mise à jour de nos connaissances sur ces deux syndromes et la mise en valeur du rôle de la cytogénétique moléculaire dans le diagnostic et le conseil génétique des syndromes microdélétionnels

Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez)

<p>Abstract</p> <p>Introduction</p> <p>Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).</p> <p>The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer.</p> <p>Methods</p> <p>This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome.</p> <p>Results</p> <p>A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.</p> <p>The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS).</p> <p>Conclusion</p> <p>TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.</p

EWSR1 Rearrangement and CD99 Expression as Diagnostic Biomarkers for Ewing/PNET Sarcomas in a Moroccan Population

Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) are a group of round cell tumors. Malignant round cell tumors form a large and diverse group that includes rhabdomyosarcoma, synovial sarcoma, non-Hodgkin’s lymphoma, neuroblastoma, hepatoblastoma, Wilm’s tumor, desmoplastic small round cell tumor, and other morphologically similar entities. Differential diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) is difficult. In addition to morphology and immunohistochemistry (IHC), differential diagnosis of these tumors is based on molecular analysis of the EWSR1 gene rearrangement using fluorescent in situ hybridization (FISH) technique. We investigated the diagnostic value of combined CD99 immunostaining and EWSR1 t(22q12) alteration using a dual-color, break-apart rearrangement probe in forty-one formalin-fixed paraffin-embedded (FFPE) tissue samples from pediatric and adult patients diagnosed with EPS. IHC was performed in all cases using the CD99 antibody and showed a positivity of 92.7% in the enrolled cases (38/41) followed by FISH analysis where 48.8% of the cases (20/41) were rearranged. Sensitivity and specificity for IHC assays were 88% and 58%, respectively. Notably, FISH had a sensitivity of 100% and a specificity of 87%. In addition, CD99 positivity was found to correlate with EWSR1 rearrangement (p<0.05). This report shows that FISH has better sensitivity and specificity than IHC in the Moroccan population, and supports its combination with CD99 immunostaining as diagnostic biomarkers for this rare malignant entity.

Differential over-expression ofmdr1 genes in multidrug-resistant rat glioblastoma cell lines selected with doxorubicin or vincristine

International audienceWe have compared the pharmacological and molecular characteristics of 2 cell lines derived from the C6 rat glioblastoma, and selected for resistance either to doxorubicin (C6 0.5 line) or to vincristine (C6 IV line). Each line displays a preferential 400-fold resistance towards the drug used for selection, the C6 IV line being especially weakly resistant to doxorubicin (13-fold). Verapamil completely restored doxorubicin sensitivity in the C6 IV line as well as vincristine resistance in the C6 0.5 line, but could not completely reverse doxorubicin resistance in the C6 0.5 line or vincristine resistance in the C6 IV line. This suggests that specific mechanisms of resistance against each drug were added to a common P-glycoprotein-mediated multidrug-resistance mechanism. Doxorubicin efflux was total within 2 hr in the C6 IV line, whereas it remained 8 to 10% of drug in the C6 0.5 line 4 hr after drug removal, despite a more rapid efflux of the drug in the first 30 min. This 2-compartment behavior could be related to a special sub-cellular distribution of doxorubicin in C6 0.5 cells. Northern and Western blot analysis of the mdrI gene and of the P-glycoprotein expressed by the 2 resistant cell lines made it possible to quantify their degree of over-expression; when compared with the C6 wild strain, the C6 0.5 line over-expressed both the mdrI gene and the P-glycoprotein to a slightly higher level than the C6 IV line. Northern and Western blot analysis also suggested that C6 0.5 cell preferentially over-expressed the mdrIa gene, whereas the C6 IV cells preferentially over-expressed the mdrIb gene. This differential over-expression was confirmed after polymerase-chain-reaction amplification of the cDNA sequences transcribed from total RNA extracted from the 2 lines. It can be concluded therefore that the mdrIa gene product is more efficient than the mdrIb gene product in extruding anti-cancer drugs from the cells; and that the mdrIb gene product might preferentially extrude vincristine rather than doxorubicin

Clinical Evidence of Circulating Tumor DNA Application in Aggressive Breast Cancer

Breast cancer is clinically and biologically heterogeneous and is classified into different subtypes according to the molecular landscape of the tumor. Triple-negative breast cancer is a subtype associated with higher tumor aggressiveness, poor prognosis, and poor response to treatment. In metastatic breast cancer, approximately 6% to 10% of new breast cancer cases are initially staged IV (de novo metastatic disease). The number of metastatic recurrences is estimated to be 20–30% of all existing breast tumor cases, whereby the need to develop specific genetic markers to improve the prognosis of patients suffering from these deadly forms of breast cancer. As an alternative, liquid biopsy methods can minutely identify the molecular architecture of breast cancer, including aggressive forms, which provides new perspectives for more precise diagnosis and more effective therapeutics. This review aimed to summarize the current clinical evidence for the application of circulating tumor DNA in managing breast cancer by detailing the increased usefulness of this biomarker as a diagnostic, prognostic, monitoring, and surveillance marker for breast cancer

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas

Astroblastoma – a rare and challenging tumor: a case report and review of the literature

Abstract Background Astroblastoma is a controversial and an extremely rare central nervous system neoplasm. Although its histogenesis has been clarified recently, controversies exist regarding its cellular origin and validity as a distinct entity. Because of its extreme rarity and because its common features are shared with other glial neoplasms, this tumor is prone to misdiagnosis and remains challenging not only in terms of diagnosis and classification but also in the subsequent management. This case report describes a new case of astroblastoma. It discusses clinical, radiologic, pathological, and therapeutic features and differential diagnosis of this rare neoplasm, with a review of the recent literature. Case presentation We report the case of an 8-year-old Moroccan girl who presented with a 1-year history of epileptic seizure, headache, and decreased visual acuity. Cranial magnetic resonance imaging revealed a right occipito-temporal mass. A tumor resection was performed and histological examination combined with immunohistochemical study confirmed the diagnosis of low-grade astroblastoma. Conclusions Astroblastoma is a very rare primary brain tumor. Its diagnosis is often challenging because of the astroblastic aspects that can be found in astrocytic tumors, in ependymomas, and in non-neuroepithelial tumors. Considerable confusion surrounds its histogenesis and classification. The low incidence rate makes it difficult to conduct studies to examine tumor characteristics