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1.
Tunis Med ; 102(2): 100-106, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38567476

RESUMEN

INTRODUCTION: The Toll-like receptor 4 (TLR4), an important member of the host's innate immune response, is coded by a polymorphic gene. This polymorphism could be a predisposing factor for NasoPharyngeal Carcinoma (NPC). AIM: To determine the association between TLR4 gene polymorphisms and the susceptibility to NPC in a cohort of Tunisian affected patients. METHODS: Genomic DNAs from 245 unrelated patients affected by undifferentiated carcinoma type (UCNT) and 264 unrelated healthy controls were genotyped for the five single nucleotides polymorphisms (SNPs) of TLR4 locus (4434 A>G (rs1927914),7263 G>C (rs10759932), 6134 A>G(rs4986790), 8851C>T (rs 4986791), 5272 T>C(rs11536889), +8469 T>C (rs11536891)) by Taqman® 5'-nuclease assay. RESULTS: Among all polymorphisms studied, only the rs4986790 G and rs4986791 T alleles were significantly more prevalent in patients' group than controls (45% vs. 38%; p=0.03; pc=0.06) and increased the risk of the NPC (OR=1.3, 95% CI=1.01-1.69). Also, we found that the frequency of the rs4986790 AA and rs4986791 TT genotypes was significantly higher in controls than in patients (25.7% vs 37%; p=0.006, pc=0.02) and conferred a protector factor in NPC (OR= 0.59, 95% CI= 0.39-0.87). Further, based on the Kaplan-Meier survival curve we observed also the positive effect ofrs1927914 AA genotype on a prognostic of NPC (p=0.006; pc=0.01). CONCLUSION: Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Nasofaríngeas , Humanos , Estudios de Casos y Controles , Genotipo , Carcinoma Nasofaríngeo/epidemiología , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/genética , Receptor Toll-Like 4/genética
2.
Encephale ; 50(2): 178-184, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37718198

RESUMEN

BACKGROUND AND STUDY AIM: Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association between twelve TLR2, TLR4 and TLR9 variants (TLR2: rs4696480T>A, rs3804099T>C, rs3804100T>C; TLR4: rs1927914G>A, rs10759932T>C, rs4986790A>G, rs4986791T>C, rs11536889G>C, rs11536891T>C; TLR9: rs187084A>G, rs352139T>C and rs352140C>T) and SZ susceptibility in a Tunisian population. PATIENTS AND METHODS: This study included 150 patients and 201 healthy controls with no history of psychiatric illness. Genotyping was done using a TaqMan SNP genotyping assay. We also assessed a haplotype analysis for TLR2, TLR4 and TLR9 variants with SZ using Haploview 4.2 Software. RESULTS: We found that the AA genotype of the TLR2 rs4696480T>A variant was significantly associated with an increased risk of SZ (46% vs. 31%, P=4.7×10-3, OR=1.87 and 95% CI [1.18-2.97]). The frequency of the TA genotype was significantly higher in the control group than in SZ patients (27% vs. 43%, P=2.1×10-3) and may be associated with protection against SZ (OR=0.49 and 95% CI [0.30-0.80]). Whereas, the TLR9 rs187084-GG genotype was higher in the control group compared to patients (16% vs. 5%, P=1.6×10-3) and would present protection against SZ (OR=0.28, CI=[0.10-0.68]). The ACT haplotype of the TLR2 and the ACC haplotype of the TLR9 gene were identified as a risk haplotypes for SZ (P=0.04, OR=9.30, 95% CI=[1.11-77.71]; P=3×10-4, OR=6.05, 95% CI=[2.29-15.98], respectively). CONCLUSION: The results indicate that TLR2 and TLR9 genetic diversity may play a role in genetic vulnerability to SZ. However, including more patients and evaluation of TLR2 and TLR9 expression are recommended.


Asunto(s)
Esquizofrenia , Receptor Toll-Like 2 , Humanos , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 9/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Genotipo , Estudios de Casos y Controles
3.
Psychiatr Q ; 92(2): 803-811, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33094434

RESUMEN

Bipolar disorder is a chronic, disabling disease that is characterized by the recurrence of thymic episodes. The role of the immune-inflammatory system in the etiopathogenesis of this affection arouses the interest of research. The aim of this work was to determine the plasma levels of the high sensitivity C reactive protein (hs-CRP) in patients with bipolar disorder in remission phase by comparing them to a control group.A case-control cross-sectional study was conducted from 56 subjects with bipolar disorder in clinical remission, and 56 volunteers and healthy control subjects.Mean plasma hs-CRP was significantly higher in patients with bipolar disorder than control subjects. In bipolar patients, a hs-CRP elevation was significantly associated with the disease severity item mean score.Through this study, bipolar disorder appears to be associated with a state of chronic inflammation. This should lead to randomized controlled trials evaluating the value of anti-inflammatory drugs in the management of bipolar disorder.


Asunto(s)
Trastorno Bipolar/sangre , Trastorno Bipolar/complicaciones , Proteína C-Reactiva/análisis , Inflamación/complicaciones , Adulto , Biomarcadores/sangre , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/inmunología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inflamación/sangre , Masculino , Recurrencia
4.
Int J Immunogenet ; 47(5): 406-413, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32048423

RESUMEN

Identification of candidate genes associated with susceptibility of breast cancer can have a significant impact at a cancer management national healthcare systems level, making genetic testing more affordable and cost-effective. We have previously shown that the major histocompatibility complex class I-related chain A (MICA) was related to breast cancer and plays an important role in modulating immune response mechanisms through NKG2D receptor activation. Compared to our previous study, in this work, we recruited a new cohort composed of 354 unrelated Tunisian women affected by breast cancer and 380 age-matched women as controls, all genotyped for MICA-129 Met/Val (rs 1051792). Subsequently, we exanimated the distribution of this polymorphism in ten families. As a result, an association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 2.5 × 10-15 ; OR = 2.40; p = 6.5 × 10-13 ; OR = 3.03, respectively). Stratified analysis with age and family history of cancer revealed an association between the Val/Val genotype and younger patients <40 years (p = .003; OR = 2.03). Among those patients having a family history of cancer, 68% had a Val/Val genotype (p = .02; OR = 1.82). In the family study, an analyse of pedigrees revealed that the majority of families showed the development of breast cancer at a young age. Moreover, all patients diagnosed with early-onset breast cancer had a Val/Val genotype. Our results lead us to propose that this polymorphism may be an inherited genetic biomarker contributing to an increased breast cancer risk in Tunisian women.


Asunto(s)
Neoplasias de la Mama/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase I/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Túnez/epidemiología , Adulto Joven
5.
Immunol Invest ; 49(5): 498-509, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31814472

RESUMEN

The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A part from its genetic diversity, MICA is characterized by the presence of membrane-bound and soluble isoform (sMICA) and by the propensity to elicit antibody-mediated allogeneicity (MICA Abs). Altogether such properties are important in the cancer setting. Here, we investigated whether MICA polymorphism, serum level of sMICA and MICA antibodies (Abs) may influence nasopharyngeal carcinoma (NPC) risk. 274 NPC naïve of treatment patients and 275 healthy individuals, all originating from Tunisia were included and genotyped. Among them, 160 sera from patients and 51 from controls were analyzed for the sMICA level by ELISA and were tested for the presence of MICA Abs by Luminex assay. The statistical analysis showed that: (1) we extend and confer our previous finding concerning Val/Val association with risk of NPC (p = .02, OR = 1.56; 95%CI [1.12-2.11]). (2) The higher level of sMICA characterized patients advanced stage of the disease. (3) The 18 (78%) of patients having MICA Abs exhibit all a non-advanced stage of the tumor extension at presentation. MICA129 Met /Val, sMICA and MICA Abs could be potential biomarkers of prediction, the diverse staging of NPC and hence prognostic and treatment.


Asunto(s)
Anticuerpos/sangre , Biomarcadores de Tumor/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Estadificación de Neoplasias , Polimorfismo Genético , Pronóstico , Riesgo , Túnez , Adulto Joven
6.
Immunol Invest ; 48(5): 521-532, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30945586

RESUMEN

Human leukocyte antigens G and E (HLA-G and HLA-E) are nonclassical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting natural killer and cytotoxic T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases including tumor. The main objective of the study is to evaluate the impact of three HLA-G 3'UTR potential polymorphisms: +3187 A > G (rs9380142), +3142 G > C (rs1063320), +2960 14-base pair (bp) Insertion/Deletion (Ins/Del) (rs66554220), and the HLA-E*01:01/01:03 A > G (rs1264457) polymorphism in Tunisian breast cancer population. A total of 355 patients and 381 controls were genotyping for HLA-G and HLA-E polymorphisms using a Taq Man assay. +3142 C allele and +3142 C/C genotype were significantly associated with increased risk of breast cancer (p = 0.00002; OR = 1.58; 95% CI = 27-1.97) (49% versus 35%; p = 0.0001; OR = 1.79; 95% CI = 1.32-2.44). In addition, Del allele and the homozygous state for Del/Del genotype confer a risk for breast cancer (52% versus 45%, p = 0.006; OR = 1.33, 95% CI = 1.08-1.64) (28% versus 22%, p = 0.039; OR = 1.43, 95% CI = 0.90-2.25). However, no statistical significant differences were reported for HLA-G + 3187 A > G and HLA-E variations and breast cancer in a Tunisian population. The found results indicate that HLA-G may play an important role in the breast cancer.


Asunto(s)
Regiones no Traducidas 3'/genética , Neoplasias de la Mama/genética , Genotipo , Antígenos HLA-G/genética , Antígenos de Histocompatibilidad Clase I/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Túnez , Adulto Joven , Antígenos HLA-E
7.
Immunol Invest ; 46(6): 603-614, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28742417

RESUMEN

The major histocompatibility complex class I-related chain A (MICA), expressed on cell surface, plays an important role in the elimination of both virus-infected cells and tumor through the activation of the natural killer (NK) receptor NKG2D. A polymorphic change from methionine (Met) to valine (Val) at amino acid position 129 categorizes MICA alleles into strong and weak binders for the NKG2D receptor and has been found in a variety of immune-related disorders. In this study, we investigated the potential interaction between genetic polymorphism of MICA and the development of breast cancer. We recruited 192 unrelated Tunisian women affected by breast cancer and 205 controls age-matched women, all genotyped for MICA-129 Met/Val (rs 1051792). A significant association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 0.002, OR = 1.64, 95% CI = [1.17-2.27]; p = 0.002, OR = 1.88, 95% CI = [1.24-2.87], respectively). After stratification with clinical-pathology parameters, we found that 71% of women aged lower than 40 years had a Val/Val genotype versus 49% (p = 0.014). About 72% of these patients having a family history of cancers had a Val/Val genotype (p = 0.04). These results suggest that tumor escape mechanism because of failure in order to activate NK cells by MICA-129 Val allele may play a role in individual susceptibility for breast cancer development in Tunisian women.


Asunto(s)
Neoplasias de la Mama/genética , Antígenos de Histocompatibilidad Clase I/genética , Adulto , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Metionina/genética , Persona de Mediana Edad , Polimorfismo Genético , Riesgo , Túnez/epidemiología , Valina/genética
8.
J BUON ; 21(3): 732-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27569097

RESUMEN

PURPOSE: To find a possible association between the Mouse Double Minute 2(MDM2) 344T>A, alone and in combination with p53 72 Arg/Pro polymorphism, and resistance to anthracycline-based chemotherapy of breast cancer in Tunisia. METHODS: This study enrolled 542 patients with invasive ductal carcinoma (IDC) treated with anthracycline-based chemotherapy. Genomic DNA was isolated from whole blood, using the phenol chloroform method. Anthracycline response was scored according to the World Health Organization (WHO). MDM2 344T>A polymorphism was genotyped using real time polymerase chain reaction (RT-PCR) with the TaqMan method. Data was statistically analyzed using the x2 test. RESULTS: Response was evaluated in 400 patients, of whom a quarter was found to be resistant to chemotherapy. Genetic data revealed that resistance to anthracycline-based chemotherapy did not seem to be correlated with 344T>A polymorphism in the studied population. Also, no significant association was found between the single nucleotide polymorphism (SNP) 344T>A status and clinicopathologic parameters (p>0.05 for all comparisons). Moreover, analysis of p53 rs1042522 and MDM2 rs1196333 combination showed no significant association between these two genetic variants and anthracycline resistance (p=0.2). CONCLUSIONS: Our findings provide no evidence indicating that SNP 344 T>A may affect response to anthracycline-based chemotherapy. However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.


Asunto(s)
Antraciclinas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-mdm2/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Resistencia a Antineoplásicos , Femenino , Genes p53 , Humanos , Persona de Mediana Edad
9.
Pathol Res Pract ; 212(4): 345-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26896927

RESUMEN

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer, tightly related to Epstein-Barr virus infection and thus to HLA genes. In this study, we aimed to analyze HLA-E polymorphism in NPC advent and prognosis. 130 unrelated patients with CNP and 180 unrelated and healthy controls were included in our study. HLA-E genotyping was performed by PCR/RFLP method; SPSS (13.0) was used for statistical analysis, and survival curbs were established with the "Kaplan-Meier" method (Log Rank<0.05). RESULTS: We found a significant difference within HLA-E*103 variants between patients and controls: E*1031 and E*1032 were associated with CNP (OR=1.613, p=0.013 and OR=1.0809, p=0.055), and E*1033 with controls (OR=0.254, p<10(-4)). CONCLUSION: Our study reveals that HLA-E polymorphism is associated with nasopharyngeal cancer. HLA-E expression studies could be used to understand the implication of E*103 variants.


Asunto(s)
Biomarcadores de Tumor/genética , Predisposición Genética a la Enfermedad/genética , Antígenos de Histocompatibilidad Clase I/genética , Neoplasias Nasofaríngeas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Carcinoma , Niño , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Adulto Joven , Antígenos HLA-E
11.
Bull Cancer ; 102(12): 967-72, 2015 Dec.
Artículo en Francés | MEDLINE | ID: mdl-26582733

RESUMEN

Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors.


Asunto(s)
Alelos , Citocromo P-450 CYP2E1/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético , Adulto , Carcinoma , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Interacción Gen-Ambiente , Genotipo , Humanos , Masculino , Mutación , Carcinoma Nasofaríngeo , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Riesgo , Túnez
12.
Anticancer Res ; 35(3): 1763-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25750340

RESUMEN

BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy. PATIENTS AND METHODS: Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test. RESULTS: Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants. CONCLUSION: We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.


Asunto(s)
Antraciclinas/uso terapéutico , Neoplasias de la Mama/genética , Codón , Resistencia a Antineoplásicos , Polimorfismo de Nucleótido Simple , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Riesgo
13.
Immunobiology ; 220(1): 20-5, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25446398

RESUMEN

Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Polymorphisms of genes encoding nitric oxide synthase (NOS) and antioxidant glutathione-S transferases (GSTs) have been associated with various tumors. We examined the combined role of NOS3, NOS2 and GST polymorphisms in NPC risk in Tunisians. We found that NOS3−786C allele and −786 CC genotype, NOS3+894T allele and +894 GT+TT genotypes, NOS2−277 G allele and −277 GG genotype, and GSTT1 del/del genotype, are more prevalent in NPC patients as compared to healthy controls. Our results suggest that genetically driven dysfunction in red­ox stress pathway could augment the risk in NPC-susceptible individuals.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Nasofaríngeas/genética , Estrés Oxidativo/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Carcinoma , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Glutatión Transferasa/genética , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Adulto Joven
14.
Ann Biol Clin (Paris) ; 72(3): 281-91, 2014.
Artículo en Francés | MEDLINE | ID: mdl-24876139

RESUMEN

Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Genetic predisposition linked to the immune system has been associated with various tumors. This involves genetic diversity of the genes encoding the molecules of the immune response such as inflammation and anti-tumor surveillance. In this work, we examined the impact of the immunogenetic diversity on the risk of the NPC in different populations studied. These data show that the interindividual variability of the genetic regulation of immune processes increases the risk of NPC in individuals previously predisposed due to other risk factors (genetic / environmental). This synthesis, in addition to the predictive aspects, could provide innovative research for the development of new therapeutic approaches.


Asunto(s)
Carcinoma/inmunología , Neoplasias Nasofaríngeas/inmunología , Carcinoma/genética , Interacción Gen-Ambiente , Genes MHC Clase II/genética , Genes MHC Clase II/inmunología , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Variación Genética/inmunología , Humanos , Fenómenos Inmunogenéticos , Vigilancia Inmunológica/genética , Vigilancia Inmunológica/inmunología , Neoplasias Nasofaríngeas/genética
15.
Virol J ; 10: 119, 2013 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-23590857

RESUMEN

BACKGROUND: Because latent Epstein Barr (EBV)-infection is a specific characteristic of malignant nasopharyngeal carcinoma (NPC), various molecules of viral origin are obvious candidate biomarkers in this disease. In a previous study, we could show in a few clinical samples that it was possible to detect a category of EBV microRNAs called miR-BARTs in the plasma of at least a fraction of NPC patients. The first aim of the present study was to investigate the status of circulating miR-BART17-5p (one of the miR-BARTs hereafter called miR-BART17) and EBV DNA in a larger series of NPC plasma samples. The second aim was to determine whether or not circulating miR-BART17 was carried by plasma exosomes. PATIENTS AND METHODS: Plasma samples were collected from 26 NPC patients and 10 control donors, including 9 patients with non-NPC Head and Neck squamous cell carcinoma and one healthy EBV carrier. Concentrations of miR-BART17 and two cellular microRNAs (hsa-miR-16 and -146a) were assessed by real-time quantitative PCR with spike-in normalization and absolute quantification. In addition, for 2 patients, exosome distributions of miR-BART17 and miR-16 were investigated following plasma lipoprotein fractionation by isopycnic density gradient ultrcentrifugation. RESULTS: The miR-BART17 was significantly more abundant in plasma samples from NPC patients compared to non-NPC donors. Above a threshold of 506 copies/mL, detection of miR-BART17 was highly specific for NPC patients (ROC curve analysis: AUC=0.87 with true positive rate = 0.77, false positive rate = 0.10). In this relatively small series, the concentration of plasma miR-BART17 and the plasma EBV DNA load were not correlated. When plasma samples were fractionated, miR-BART17 co-purified with a protein-rich fraction but not with exosomes. CONCLUSIONS: Detection of high concentrations of plasma miR-BART17 is consistent in NPC patients. This parameter is, at least in part, independent of the viral DNA load. Circulating miR-BART17 does not co-purify with exosomes.


Asunto(s)
Biomarcadores/sangre , Herpesvirus Humano 4/genética , MicroARNs/sangre , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Plasma/química , ARN Viral/sangre , Adulto , Anciano , Transporte Biológico , Carcinoma , ADN Viral/sangre , Exosomas/virología , Femenino , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Carcinoma Nasofaríngeo , ARN Viral/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa
16.
Tunis Med ; 91(2): 129-33, 2013 Feb.
Artículo en Francés | MEDLINE | ID: mdl-23526276

RESUMEN

BACKGROUND: The abnormalities of the haemoglobin divide into qualitative abnormalities and quantitative abnormalities. This variant contains polymorphisms often useful as markers of population. At present more than 693 types of abnormal haemoglobin are listed. This hemoglobinopathies can arise at reached subjects of cancerous pathologies. AIM: To bring to report association hémoglobinopathies-cancers. METHODS: Our study was realized to the Institute Salah azaiz (ISA) concerning hémoglobinopathies in carcinologic environment over a period spreading out of May 2004 in February 2008. The phenotypic and biochemical study of haemoglobin revealed the presence of 328 carriers of abnormalities of the haemoglobin on a total of 10550 patients followed to ISA. 7 types of abnormalities of the haemoglobin were identified (HbS, Hb C, Hb O arab, Hb D, Hb G, fast mutant and ß thalassemia. RESULTS: The sickle cell line represents the most wide-spread hémoglobinopathie (51.3 %). 48.2 % of the carrier subjects of abnormalities of the haemoglobin are followed for malignant pathologies. Among these hemoglobinopathies, we revealed the presence of two fast mutants of the haemoglobin corresponding to the haemoglobin Bangkok. This type of rare mutant is described for the first time in Tunisia. According to the genotypic study by these two cases, the haemoglobin Bangkok results from the replacement at the level of the chain ß some aspartic acid by the wisteria, further to a transfer at the level of the codon 56. A phenotypic study family revealed the presence of similar transfers at certain members of the family. CONCLUSION: Our work allowed us to notice a relatively important frequency of rare abnormalities of the haemoglobin at patients presenting varied tumoral processes.


Asunto(s)
Hemoglobinopatías/genética , Neoplasias/epidemiología , Femenino , Humanos , Masculino , Mutación , Fenotipo
17.
Tunis Med ; 90(1): 41-4, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22311447

RESUMEN

AIM: To evaluate the prognostic value of preoperative serum carcino-embryonic antigen (CEA) level in patients with colorectal cancer. METHODS: This retrospective study included 125 colorectal cancer patients aged from 14 to 87 years, surgically treated between January 2001 and December 2006. Preoperative serum CEA was measured by chemiluminescence assay. RESULTS: within the patients, 57 were males and 68 females. They have tumours classified Dukes A in 2 patients, B in 24 patients, C in 53 patients and Dukes D in 46 patients. Median follow-up period was 24 months (range, 4 - 72 months). The relapse-free survival was significantly higher in patients with CEA < 5 ng/ml compared to CEA ³ 5 ng/ml, (p < 0.0001). We observed significant differences in relapse-free survival between patients with CEA < 5 ng/ml and those with CEA ³ 5 ng/ml among patients classified as Dukes stage B (p=0.007) and C (p < 0.0001). However, there was no significant difference in relapse-free survival among those classified as Dukes stage D. Cox multivariate analysis demonstrated that preoperative serum CEA level was a significant independent prognostic factor for relapse-free survival (hazard ratio: 6.49, 95% CI, 3.09 to 13.62, p < 0.0001). CONCLUSION: Preoperative serum CEA is a reliable predictor factor for recurrence in patients with CRC. CEA might be used in staging system and will be useful for therapeutic orientation in patients undergoing curative resection of CRC.


Asunto(s)
Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Recurrencia Local de Neoplasia/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Túnez , Adulto Joven
18.
Tunis Med ; 89(2): 147-50, 2011 Feb.
Artículo en Francés | MEDLINE | ID: mdl-21308622

RESUMEN

AIM: To evaluate and assess disruptions of serum lipids at patients having a colorectal cancer. METHODS: Our prospective study interested 30 patients, from 26 to 93 year old, presenting a colorectal cancer confirmed histologically, examined during the period going from March 2003 to April 2004. Thirty healthy controls were examined in parallel. All patients undergo three blood samples respectively in preoperative, 48h and 6 months after surgical operation. The analyses carried out were determination of a total serum cholesterol, HDL (high density lipoprotéin) and LDL (low density lipoprotein) cholesterol, serum triglyceride and serum apoprotein (AI and B) RESULTS: We noticed a decrease of total serum cholesterol level in 43% of the cases associated to the reduction of the HDL and the LDL cholesterol in respectively 30% and 76% of cases. The mean values of total serum cholesterol, HDL and LDL cholesterol rates were significantly lower for patients compared to those of controls (p respectively : 0.001; 0.04 and 0.001). Moreover, the level of total serum cholesterol varied significantly with tumor localization ( p= 0,02). CONCLUSION: Serum lipid disruptions affect essentially total cholesterol, HDL and LDL cholesterol. It would be therefore interesting to evaluate their rate at the basal state in order to follow their evolution after treatment in colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/sangre , Lípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
19.
Tunis Med ; 88(10): 700-2, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20890814

RESUMEN

BACKGROUND: Glutathione S-transferases (GST) play a vital role in cellular defense against environmentally toxic compounds. These enzymes present a genetic deletion polymorphism, which varies with ethnicity. AIM: To evaluate the frequencies of homozygous deletion of GSTM1 and GSTT1 genes in Tunisian population. METHODS: On the basis of multiplex PCR protocol, the frequency of the deleted genotypes of GSTM1 and GSTT1 genes was evaluated on 145 healthy Tunisian subjects. RESULTS: We found that 34.6% of the individuals had the GSTM1 null genotype, 16.6% had the GSTT1 null genotype and 4.82% had a double deletion of both GSTM1 and GSTT1. CONCLUSION: The distribution of GSTM1 null in Tunisians is rather in the range of black populations and is lower than that reported in Asians, Arabs and Caucasians. However the frequency of GSTT1 null is in the range of several populations studied except Asians. The double deletion frequency seems lower than that described in different populations.


Asunto(s)
Población Negra/genética , Eliminación de Gen , Glutatión Transferasa/genética , Polimorfismo Genético , Adulto , Anciano , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Túnez
20.
Ann Biol Clin (Paris) ; 68(4): 473-9, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20650743

RESUMEN

Helicobacter pylori (HP) chronic gastritis can lead to precursor stages of gastric cancer. New biological markers have been proposed to study the gastric mucosal state. We evaluate biological results in comparison with histological ones in a dyspeptic population. Forty nine dyspeptic patients underwent endoscopy with gastric biopsies for histological examination. Blood samples were obtained to measure levels of gastrin 17 (G17), pepsinogen 1 (PG1), pepsinogen 2 (PG2) and the rate of anti-HP IgG antibodies. Four patients have a healthy gastric mucosa and 45 have a gastritis (32 have a nonatrophic gastritis and 13 an atrophic one). An increase in the level of PG2 and a decrease of the PG1/PG2 ratio were noticed in the group of subjects with a nonatrophic gastritis compared to the healthy mucosa group. The decrease of the PG1/PG2 ratio was more important in the corpus atrophic gastritis group than in the antrum restricted atrophic gastritis one. In conclusion, in front of dyspeptic patients, we advice to practice in first intention the measurement of the serological level of G17, PG1, PG2 and anti-HP IgG antibodies.


Asunto(s)
Gastrinas/sangre , Infecciones por Helicobacter/patología , Helicobacter pylori , Biomarcadores/sangre , Biopsia , Dispepsia/sangre , Dispepsia/microbiología , Gastritis/sangre , Gastritis/patología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/inmunología , Humanos , Inmunoglobulina G/sangre , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Pepsinógeno A/sangre
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