RESUMO
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.
Assuntos
Esquizofrenia , Receptor 2 Toll-Like , Humanos , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Genótipo , Estudos de Casos e ControlesRESUMO
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.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/complicações , Proteína C-Reativa/análise , Inflamação/complicações , Adulto , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/imunologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Masculino , RecidivaRESUMO
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.
Assuntos
Anticorpos/sangue , Biomarcadores Tumorais/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Estadiamento de Neoplasias , Polimorfismo Genético , Prognóstico , Risco , Tunísia , Adulto JovemRESUMO
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.
Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Tunísia/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
Regiões 3' não Traduzidas/genética , Neoplasias da Mama/genética , Genótipo , Antígenos HLA-G/genética , Antígenos de Histocompatibilidade Classe I/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Tunísia , Adulto Jovem , Antígenos HLA-ERESUMO
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.
Assuntos
Neoplasias da Mama/genética , Antígenos de Histocompatibilidade Classe I/genética , Adulto , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Metionina/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Risco , Tunísia/epidemiologia , Valina/genéticaRESUMO
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.
Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Genes p53 , Humanos , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Predisposição Genética para Doença , Neoplasias Nasofaríngeas , Humanos , Estudos de Casos e Controles , Genótipo , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/genética , Receptor 4 Toll-Like/genéticaRESUMO
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.
Assuntos
Biomarcadores/sangue , Herpesvirus Humano 4/genética , MicroRNAs/sangue , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Plasma/química , RNA Viral/sangue , Adulto , Idoso , Transporte Biológico , Carcinoma , DNA Viral/sangue , Exossomos/virologia , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
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.
Assuntos
Hemoglobinopatias/genética , Neoplasias/epidemiologia , Feminino , Humanos , Masculino , Mutação , FenótipoRESUMO
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.
Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Recidiva Local de Neoplasia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Tunísia , Adulto JovemRESUMO
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is the third most frequent virus-associated human malignancy. How this tumor escapes immune recognition despite the expression of several viral antigens has remained poorly understood. Our previous in vitro studies have shown that NPC cells release exosomes containing high amounts of galectin-9, a ligand of the membrane receptor Tim-3, which is able to induce apoptosis in mature Th1 lymphocytes. Here, we sought to determine whether galectin-9-carrying exosomes were produced in NPC patients and whether such exosomes might play a role in the immune evasion of NPC cells. We report that galectin-9-containing exosomes are selectively detected in plasma samples from NPC patients and mice xenografted with NPC tumors. The incorporation into exosomes protects galectin-9 against proteolytic cleavage but retains its Tim-3-binding capacity. Importantly, NPC exosomes induce massive apoptosis in EBV-specific CD4(+) cells used as a model of target T cells. This effect is inhibited by both anti-Tim-3 and antigalectin-9 blocking antibodies. These results indicate that blocking galectin-9/Tim-3 interaction in vivo might alleviate the Th1-suppressive effect of NPC exosomes and sustain antitumoral T-cell responses and thereby improve clinical efficacy of immunotherapeutic approaches against NPC.
Assuntos
Carcinoma/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Exossomos/metabolismo , Galectinas/metabolismo , Neoplasias Nasofaríngeas/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Evasão Tumoral , Animais , Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Vasos Sanguíneos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Carcinoma/sangue , Carcinoma/complicações , Carcinoma/metabolismo , Linhagem Celular Tumoral , Difusão , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/metabolismo , Exossomos/patologia , Galectinas/antagonistas & inibidores , Galectinas/sangue , Galectinas/imunologia , Células HeLa , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Camundongos , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/metabolismo , Ligação Proteica/efeitos dos fármacos , Receptores Virais/antagonistas & inibidores , Receptores Virais/imunologia , Receptores Virais/metabolismo , Linfócitos T Auxiliares-Indutores/patologia , Transplante Heterólogo , Evasão Tumoral/imunologiaRESUMO
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.
Assuntos
Neoplasias Colorretais/sangue , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
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.
Assuntos
Gastrinas/sangue , Infecções por Helicobacter/patologia , Helicobacter pylori , Biomarcadores/sangue , Biópsia , Dispepsia/sangue , Dispepsia/microbiologia , Gastrite/sangue , Gastrite/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/imunologia , Humanos , Imunoglobulina G/sangue , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Pepsinogênio A/sangueRESUMO
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.
Assuntos
População Negra/genética , Deleção de Genes , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , TunísiaAssuntos
Doença de Hodgkin/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Antineoplásicos Fitogênicos/uso terapêutico , Progressão da Doença , Etoposídeo/uso terapêutico , Evolução Fatal , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
AIM: Evaluate and show the importance of CRP, ACE and LDH in colorectal cancer. METHODS: Our prospective study interested 30 patients, from 26 to 93 years old and present a colorectal cancer, confirmed histologically, during the period going from March 2003 to April 2004, and 30 healthy controls. A blood sample was collected from each patient respectively in preoperative, 48 hours before any treatment, and 6 months after surgical operation to measure serum LDH, CRP, and ACE. RESULTS: The mean serum of LDH, CRP and ACE values were significant higher in patients than those in controls (p respectively: 0,01; 0,04 et 0,01). Moreover, the level of three parameters varied significantly with stages of tumor. After follow up, we have noticed e normalisation of the mean of the level of LDH, CRP and ACE with favorable evolution. Analysis of survival at 2 years showers that survival is better in patients with normal value of CRP, ACE and LDH. CONCLUSION: CRP, LDH and ACE values have a great importance during follows up after colorectal cancer surgery.
Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , L-Lactato Desidrogenase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Major histocompatibility complex (MHC) class I chain-related A (MICA) molecules mediate natural killer (NK) cell activation and T lymphocyte co-stimulation. A polymorphic methionine (met) to valine (val) variation at amino acid position 129 of the alpha2 heavy chain domain is in linkage disequilibrium with other allelic changes and seems to categorize MICA alleles into strong and weak binder of NKG2D receptor and thereby to influence effector cell function. We investigated here whether MICA-129 dimorphism is associated with susceptibility to/or resistance against developing nasopharyngeal cancer (NPC). DNA from 130 NPC patients and 180 healthy individuals from Tunisia were genotyped for MICA-129 variation. We found a higher frequency of MICA-129 val/val genotype in patients than in controls (corrected p value = 0.02) that could suggest a tumor escape mechanism because of failure to activate NK cells by MICA-129 val allele or absence of NK cell activation because of absence of MICA-129 met allele in individuals otherwise predisposed to viral/environmental factors.
Assuntos
Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético , Adulto , Idoso , Substituição de Aminoácidos , Estudos de Coortes , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Risco , TunísiaRESUMO
Seric tumour markers (STM) are molecules that theoretically indicate the presence of malignancy, and used for monitoring response to therapy and early detection of relapse. This article describes the use and limitations of common SMT in patient with solid tumors. Excepting prostate specific antigen (PSA) and thyroglobulin, STM are not poorly sensitive or specific for screening and diagnosis of cancers. Alpha foetoprotein (AFP) is however used to screen hepatocellular carcinoma in high risk patients with suspect masses. Beta subunit of human chorionic gonadotrophin (beta-HCG) is frequently used for the diagnosis and management of gestational trophoblastic disease, while combined AFP and beta-HCG dosage is a good adjunct in the evaluation and treatment of non seminomatous germ cell tumors. PSA is used for screening and follow up of prostate cancer. Ca 125 is useful for evaluating pelvic masses in postmenopausal women and monitoring response to therapy in women with ovarian cancer, while Ca 15 3 is used to follow response to therapy in patients with breast cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Antígeno Ca-125/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Mucina-1/sangue , Neoplasias/terapia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Sensibilidade e Especificidade , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Soluble interleukin-2 receptor alpha (slL-2Ralpha) is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma. METHODS: Our prospective study interested 45 patients (35M/10F) with a mean age of 49 years (15 to 78), presenting a nasopharyngeal carcinoma histologically confirmed and 61 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure sIL-2Ralpha by immunoenzymatic assay. According to the disease status after a period of follow-up ranging from three to 22 months (median 12 months), patients were divided into two groups: The remission group (n=28) represented those with favourable evolution and a second group of 15 patients with unfavourable evolution (2 death, 4 cases of persistent primary disease and 9 patients with distance metastasis). 2 patients were lost to follow-up. RESULTS: serum sIL-2Ralpha levels were significantly higher in patients vs healthy controls (p < 0.0001). The serum levels correlated with the stage T of NPC (p = 0.01). Patients having a favourable evolution have lower sIL-2Ralpha levels before treatment vs those with unfavourable evolution without statistical difference. CONCLUSION: Measurement of serum sIL-2Ralpha provides a good estimation of the nasopharyngeal tumor burden. The usefulness of this marker as a parameter to predict prognosis in NPC should be examined further.