Molecular and Circulating Biomarkers in Patients with Glioblastoma.

Glioblastoma is the most aggressive malignant tumor of the central nervous system with a low survival rate. The difficulty of obtaining this tumor material represents a major limitation, making the real-time monitoring of tumor progression difficult, especially in the events of recurrence or resistance to treatment. The identification of characteristic biomarkers is indispensable for an accurate diagnosis, the rigorous follow-up of patients, and the development of new personalized treatments. Liquid biopsy, as a minimally invasive procedure, holds promise in this regard. The purpose of this paper is to summarize the current literature regarding the identification of molecular and circulating glioblastoma biomarkers and the importance of their integration as a valuable tool to improve patient care.

Molecular identification and antibiotic resistance of bacteriocinogenic lactic acid bacteria isolated from table olives.

In the present study, lactic acid bacteria were isolated from table olive in Morocco. Random Amplified Polymorphic DNA fingerprinting with (GTG)'(5) primer revealed a remarquable variability within isolates. According to the molecular identification, Enterococcus faecium was the most dominant species isolated with 32 strains (84.21%), followed by 4 strains of Weissella paramesenteroides (10.52%), 1 strain of Leuconostoc mesenteroides (2.63%) and Lactobacillus plantarum (2.63%). All of the strains that were identified showed occurrence of more than one bacteriocin-encoding gene. Based on the results obtained, L. plantarum 11 showed a mosaic of loci coding for nine bacteriocins (pln A, pln D, pln K, pln G, pln B, pln C, pln N, pln J, ent P). A phenotypic and genotypic antibiotic resistance was also examined. L. plantarum 11, L. mesenteroides 62, W. paramesenteroides 9 and W. paramesenteroides 36 as well as all the strains of E. faecium were susceptible to ampicillin, clindamycin and teicoplanin; however, isolates showed a resistance profile against tetracycline and erythromycin. Except E. faecium 114, E. faecium 130 and L. plantarum 11, no antibiotic resistance genes were detected in all of the strains, which might be due to resistances resulting from non-transferable or non-acquired resistance determinants (intrinsic mechanism).

Marinobacter maroccanus sp. nov., a moderately halophilic bacterium isolated from a saline soil.

During the taxonomic investigation of exopolymer-producing halophilic bacteria, a rod-shaped, motile, Gram-stain-negative, halophilic bacterium, designated strain N4T, was isolated from a saline soil located in northern Morocco. Optimal growth of the isolate was at 30-37 ºC and at pH 7.0-8.0, in the presence of 5-7 % (w/v) NaCl. Useful characteristics for the phenotypic differentiation of strain N4T from other Marinobacter species included α-chymotrypsin and α-glucosidase activities and the carbohydrate assimilation profile. The major fatty acids detected in strain N4T were C16:0 and C18:1ω9c and the predominant respiratory quinone was ubiquinone-9. Sequence analysis of the 16S rRNA gene indicated that strain N4T belonged to the genus Marinobacter and was closely related to the type strains of Marinobacter adhaerens (99.04 % similarity), Marinobacter salsuginis (98.97 %) and Marinobacter flavimaris (98.36 %). Phylogenetic analysis of the rpoD gene sequence also showed that the nearest neighbours of strain N4T were M. salsuginis (91.49 % similarity), M. adhaerens and M. flavimaris (90.63 %). Strain N4T showed 87.98 % average nucleotide identity with M. flavimaris and M. salsuginis, and 87.47 % with M. adhaerens. Regarding in-silico genome-to-genome distance, strain N4T showed DNA-DNA hybridization values of 33.30 % with M. adhaerens, 34.60 % with M. flavimaris and 34.70 % with M. salsuginis. The DNA G+C content of strain N4T was 57.3 mol%. Based on the results of phenotypic characterization, phylogenetic analysis and genome comparison, strain N4T represents a novel species of the genus Marinobacter, for which the name Marinobacter maroccanus sp. nov. is proposed. The type strain is N4T (=CECT 9525T=LMG 30466T).

The Contribution of Carotenoids, Phenolic Compounds, and Flavonoids to the Antioxidative Properties of Marine Microalgae Isolated from Mediterranean Morocco.

This study aimed to investigate the potential of four sea water microalgae, isolated and cultivated at M'diq Bay in Morocco, as a new source of natural antioxidants. These microalgae belong to different classes, including Phaedactylium tricornitum (Bacillariophyceae), Nannochloropsis gaditana (Eustigmatophyceae), Nannochloris sp (Trebouxiophyceae), and Tetraselmis suecica (Chlorodendrophycea). The antioxidant properties were screened by the use of in vitro assays, namely 2,2-difenil-1-picrylhydrazyl, Ferric reducing antioxidant power, and Ferrous ions chelating activity, and compoundidentification was carried out in methanol and acetone extracts of both dried and fresh microalgae biomass by HPLC-PDA-MS analysis. Among the investigated microalgae, Phaedactylium tricornutum was the richest one regarding its carotenoid (especially all-E-fucoxanthin) and phenolic (especially protocatechuic acid) contents, as well as antioxidant activity (65.5%), followed by Nannochloris sp, Tetraselmis suicica, and Nannochloropsis gaditana, with antioxidant activity of 56.8%, 54.9%, and 51.1%, respectively.

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.

Prognostic Value of ATRX and p53 Status in High-Grade Glioma Patients in Morocco.

INTRODUCTION: Glioblastoma and astrocytoma, grade 4, are the most common and aggressive brain tumors. Several biomarkers, such as the isocitrate dehydrogenase mutation (IDH-1), alpha-thalassemia/mental retardation, and the X-linked mutation (ATRX), enable more accurate glioma classification and facilitate patient management. This study aimed to determine the prognostic value of clinical and molecular factors (IDH, TP53, and ATRX mutations). We also studied the relationship between these molecular markers and the overall survival (OS) of 126 patients with grade 4 glioblastoma/astrocytoma. METHODS: The immunohistochemical study was conducted using antibodies namely, IDH1, R132H, p53, and ATRX. Statistical tests were used to investigate factors that might influence overall survival using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY). RESULTS: The median age at diagnosis was 51.5 years. Patients with a Karnofsky performance score (KPS) <70 presented less favorable survival outcomes compared to those with a KPS ≥70. The median OS for patients was found to be 11.17 months. Expression of IDH1 R132H was found in 13.5% of patients, p53 overexpression was identified in 55.6% of cases, and loss of ATRX expression was detected in 11.9%. The group of patients with IDH mutant/ATRX mutant/p53 wild-type had the best prognosis (OS = 27.393 months; p = 0.015). Our results were in line with previous studies. CONCLUSION: The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.

Mathematical modeling of Escherichia coli O157:H7 growth in carrot juice influenced by Thymbra capitata essential oil, heat treatment, and storage temperature.

The aim of this study was to develop a mathematical model describing the survival of Escherichia coli O157:H7 in carrot juice treated with Thymbra capitata essential oil combined with mild heat treatment and stored at different temperatures. The viable count method was used to investigate the effect of the treatment on bacterial survival, and the response surface methodology was used to develop a statistical model fitting the data. The results showed that the variance of bacterial growth is explained by storage temperature (37 %) and heat treatment (35 %), these are followed by Thymbra capitata essential oil (18 %) and their interaction (9 %). Positive multiplicative interaction was obtained for any pair of the studied treatments and cooperative effect synergy was observed over a large domain of these factors. A mathematical model was successfully developed to describe Escherichia coli O157:H7 response to the selected factors, within the study limits, and to estimate the risk of juice contamination and shelf-life. Based on our results, the use of Thymbra capitata essential oil combined with heat treatment may control Escherichia coli O157:H7 growth in carrot juice stored at low temperature.

New Biomarkers and Treatment Advances in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer lacking hormone receptor expression and HER2 gene amplification. TNBC represents a heterogeneous subtype of breast cancer, characterized by poor prognosis, high invasiveness, high metastatic potential, and a tendency to relapse. In this review, the specific molecular subtypes and pathological aspects of triple-negative breast cancer are illustrated, with particular attention to the biomarker characteristics of TNBC, namely: regulators of cell proliferation and migration and angiogenesis, apoptosis-regulating proteins, regulators of DNA damage response, immune checkpoints, and epigenetic modifications. This paper also focuses on omics approaches to exploring TNBC, such as genomics to identify cancer-specific mutations, epigenomics to identify altered epigenetic landscapes in cancer cells, and transcriptomics to explore differential mRNA and protein expression. Moreover, updated neoadjuvant treatments for TNBC are also mentioned, underlining the role of immunotherapy and novel and targeted agents in the treatment of TNBC.

Prevalence and antimicrobial profiling of Campylobacter spp. isolated from meats, animal, and human feces in Northern of Morocco.

The present work was carried out to understand the occurrence and antimicrobial susceptibility of Campylobacter spp., in various samples in Northern of Morocco. For this purpose, a random sampling was undertaken from butcher shops, traditional markets, and slaughterhouse. First, the research of Campylobacter was performed according to the Moroccan standard NM ISO: 10272-1 (2008). Second, the isolates were identified by biochemical tests and real time PCR. After the biochemical and molecular identification of suspected colonies, a disk diffusion method was executed to determine the sensitivity of Campylobacter spp. against 18 antibiotics. The results showed a moderate prevalence of Campylobacter species (130/466) recovered mainly on the Campylobacter blood base agar, where C. coli (108/130) were more prevalent comparable to C. jejuni (22/130) in poultry and cattle meat, raw milk, cloacal and surface swabs, and stool of patient suffering from diarrhea. The findings supported also the sensitivity of multiplex qPCR to detect Campylobacter strains compared to Moroccan standard NM ISO: 10272-1 (2008). Among our isolates, C. jejuni were the most susceptible strain toward colistin, florfenicol, gentamicin, streptomycin, and erythromycin. Nonetheless, the presence of multidrug Campylobacter resistant strains was highly observed in C. jejuni isolated, particularly, from broiler chickens toward the antibiotic classes of cephalosporin, penicillin, monobactam, quinolone, fluoroquinolone, sulfamide, as well as tetracycline. This may be due to common use of these drugs in veterinary medicine and farms as growth factor, which limits the usefulness of these molecules. Hence, the study highlights the importance of resistance profile monitoring of these pathogens in Northern of Morocco, in order to develop appropriate control measures and to reduce the emergence of multidrug-resistant strains.

Isolation of Microalgae from Mediterranean Seawater and Production of Lipids in the Cultivated Species.

Isolation and identification of novel microalgae strains with high lipid productivity is one of the most important research topics to have emerged recently. However, practical production processes will probably require the use of local strains adapted to commanding climatic conditions. The present manuscript describes the isolation of 96 microalgae strains from seawater located in Bay M'diq, Morocco. Four strains were identified using the 18S rDNA and morphological identification through microscopic examination. The biomass and lipid productivity were compared and showed good results for Nannochloris sp., (15.93 mg/L/day). The lipid content in the four species, namely Nannochloropsis gaditana, Nannochloris sp., Phaedactylum tricornutum and Tetraselmis suecica, was carried out by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS )highlighting the identification of up to 77 compounds.

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."

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

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.

Prevalence, serotype distribution, and antimicrobial resistance of Salmonella isolated from food products in Morocco.

INTRODUCTION: Salmonellosis is one of the most common foodborne diseases worldwide. The irrational use of antibiotics in medicine and in animal feed has greatly promoted the emergence and spread of resistant strains of non-typhoidal Salmonella. METHODOLOGY: A total of 464 food products were collected in Tetouan from January 2010 to December 2012. The isolation and identification of Salmonella were performed according to Moroccan standard 08.0.116. All isolates were serotyped and were then tested for antibiotic resistance using the disk diffusion method. RESULTS: The microbiological analysis showed that 10.3% of food samples were contaminated with Salmonella. Eleven serotypes were identified: Kentucky 22.9% (11/48), Agona 16.7% (8/48), Reading 12.5% (6/48), Corvallis 8.3% (4/48), Saintpaul 8.3% (4/48), Typhimurium 6.2% (3/48), Montevideo 6.2% (3/48), Enteritidis 4.2% (2/48), and 2% (1/48) for each of Israel, Hadar, and Branderup. Drug susceptibility testing showed that 39.6% of Salmonella were resistant to at least one antibiotic and 60.4% were susceptible to all tested antibiotics. The highest percentage of resistance was found to the following antimicrobial agents: nalidixic acid (27.1%), sulfonamides (25%), amoxicillin (12.5%), amoxicillin/clavulanic acid 12.5%, trimethoprim (10.4%), cephalothin (4.2%), and chloramphenicol (2.1%). CONCLUSIONS: This study revealed a relatively high prevalence of Salmonella in food products in Tetouan and a large percentage of drug-resistant strains. Hygienic measures should be rigorously implemented, and monitoring resistance of Salmonella is required to reduce the risks related to the emergence of multi-resistant bacteria.

EGFR Amplification and IDH Mutations in Glioblastoma Patients of the Northeast of Morocco.

Glioblastomas are the most frequent and aggressive primary brain tumors which are expressing various evolutions, aggressiveness, and prognosis. Thus, the 2007 World Health Organization classification based solely on the histological criteria is no longer sufficient. It should be complemented by molecular analysis for a true histomolecular classification. The new 2016 WHO classification of tumors of the central nervous system uses molecular parameters in addition to histology to reclassify these tumors and reduce the interobserver variability. The aim of this study is to determine the prevalence of IDH mutations and EGFR amplifications in the population of the northeast region of Morocco and then to compare the results with other studies. Methods. IDH1 codon 132 and IDH2 codon 172 were directly sequenced and the amplification of exon 20 of EGFR gene was investigated by qPCR in 65 glioblastoma tumors diagnosed at the University Hospital of Fez between 2010 and 2014. Results. The R132H IDH1 mutation was observed in 8 of 65 tumor samples (12.31%). No mutation of IDH2 was detected. EGFR amplification was identified in 17 cases (26.15%). Conclusion. A systematic search of both histological and molecular markers should be requisite for a good diagnosis and a better management of glioblastomas.

Prevalence of IDH1/2 Mutations in Different Subtypes of Glioma in the North-East Population of Morocco.

BACKGROUND: Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. MATERIALS AND METHODS: IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. RESULTS: The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. CONCLUSIONS: Our results confirmed other studies published earlier for other populations with some small discrepancies.