Jaberipour M.,Shiraz Institute for Cancer Research |
Habibagahi M.,Immunotherapy Laboratory |
Hosseini A.,Shiraz Institute for Cancer Research |
Abbasi M.,Shiraz Institute for Cancer Research |
And 4 more authors.
Indian Journal of Cancer | Year: 2010
Background: Proteins encoded by FAS, BCL-2 and TP53 genes are major regulators of cellular survival and apoptosis. Results of recent investigations show remarkable biological features of these factors, which propose their role in the course of cancer. Therefore, it is plausible to test whether transcripts of these genes could be detected in the peripheral blood cells of patients with breast cancer. Materials and Methods: Real-time polymerase chain reaction assay was performed to detect FAS, BCL-2, and TP53 gene transcripts in the peripheral blood samples of 50 women with histologically confirmed infiltrative ductal carcinoma of the breast. Gene expression of patients was compared with 40 healthy women without history of malignancies or autoimmune disorders. Results: The relative overexpression of BCL-2 in the blood cells from patients of early stages (I and II), nonmetastatic and low-grade tumors compared with healthy individuals, was shown by measuring the gene transcript. Similarly, 3-4-fold higher expression of FAS was found in those patients. The measurement of TP53 transcripts also showed higher levels of gene expression in patients compared with healthy controls. BCL-2 gene expression showed a significant correlation with FAS, while such a correlation was not observed between BCL-2 and TP53. Conclusion: It seems tumor cells overexpress BCL-2 to inhibit apoptosis and guarantee their cell survival. As a physiologic response, FAS and TP53 could be upregulated to suppress tumors. However, these pathways at early stages of disease may be inadequate and cause progressive malignancy. Source
Leusen J.H.W.,Immunotherapy Laboratory
Molecular Immunology | Year: 2015
This review is focused on the promises of IgA as a new therapeutic antibody. For more than 30 years IgG molecules have been used in the clinic in the fields of oncology, hematology, auto immune diseases and infections. However, IgA might be a good alternative, since it recruits different effector cells, i.e. polymorphonuclear cells or neutrophils, but can also activate monocytes and macrophages. The present knowledge, but also future direction for IgA- based drugs are discussed. © 2015 Elsevier Ltd. Source
Orengo A.M.,Istituto Nazionale per la Ricerca sul Cancro |
Fabbi M.,Istituto Nazionale per la Ricerca sul Cancro |
Miglietta L.,Istituto Nazionale per la Ricerca sul Cancro |
Andreani C.,Istituto Nazionale per la Ricerca sul Cancro |
And 13 more authors.
International Journal of Cancer | Year: 2011
Interleukin (IL)-18 is a proinflammatory and immune-enhancing cytokine, which exerts antitumor effects in vivo, mediated by the induction of interferon (IFN)γ. We previously reported that IL-18 processing is defective in epithelial ovarian carcinoma (EOC) cells, which secrete an inactive precursor (pro-IL-18) in vitro. In addition, IL-18 was reported as a potential biomarker of EOC. Here, we further investigated its role as a serological marker in human EOC and addressed its possible biological activity in vivo. Our data indicate that immunoreactive IL-18 is increased in EOC patients' sera at diagnosis as compared with age-matched healthy women. IL-18 levels were higher in the ascitic fluids than in sera, suggesting a local production in the peritoneal cavity. Indeed, immunohistochemical analysis of tumors showed IL-18 expression in cytokeratine-positive neoplastic cells, although also scattered histiocytes and some lymphoid cells stained for IL-18. The detection of human IL-18 in sera and ascitic fluids of immunodeficient mice, orthotopically implanted with human EOC cells, further suggested that circulating IL-18 is tumor-derived. However, IL-18 is not an EOC specific biomarker, as increased serum levels were found also in some endometrial cancer patients. By means of a new monoclonal antibody, we characterized IL-18 present in the ascitic fluid as pro-IL-18, which is biologically inactive. Accordingly, IFNγ was not increased in EOC patients' sera and ascitic fluids and showed no correlation with IL-18 levels. Altogether these data indicate that IL-18 in EOC fluids is predominantly tumor-derived and that its lack of biological activity may represent a mechanism of tumor-escape. Copyright © 2011 UICC. Source
Raaz-Schrauder D.,University Hospital |
Ekici A.B.,University Hospital |
Munoz L.E.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Klinghammer L.,University Hospital |
And 8 more authors.
Autoimmunity | Year: 2012
Patients with Systemic Lupus Erythematosus (SLE) carry an increased risk for the development of coronary artery disease (CAD). The R131 allele of the Fc gamma receptor IIa (FcγRIIa) is associated with SLE incidence and disease severity but also with CAD. Compared to stable angina pectoris (SAP) the unstable angina (UAP), as a manifestation of destabilizing CAD, is associated with increased risk of persistent instability, myocardial infarction, and death. Identification of clinically relevant determinants for unstable angina promises reduction of UAP-associated mortality in patients with SLE. We conducted a clinical study among 553 consecutive patients with stable angina pectoris (n 330) and unstable angina pectoris (n 223). All patients were genotyped for a frequent functional variant at position 131 of the mature FcγRIIa. UAP, but not SAP was significantly associated with the R/R131 genotype (P < 0.001). In troponin-negative patients with angina carrying the R/R131 genotype the odds ratio for suffering from UAP was 4.02 (95% confidence interval, 2.526.41) compared to those with non-R/R131 genotypes. In a multivariable analysis, the R/R131 genotype independently predicted the risk for development of UAP in a model adjusted for classical atherogenic risk factors. Our data imply that risk stratification of SLE- and other high risk patients with troponin-negative angina could be significantly improved by FcγRIIa genotyping. © Informa UK, Ltd. Source
Otten M.A.,Immunotherapy Laboratory |
Bakema J.E.,VUmc |
Tuk C.W.,VUmc |
Glennie M.J.,Tenovus Research Laboratory |
And 5 more authors.
European Journal of Immunology | Year: 2012
Neutrophils potently kill tumour cells in the presence of anti-tumour antibodies in vitro. However, for in vivo targeting, the neutrophils need to extravasate from the circulation by passing through endothelial barriers. To study neutrophil migration in the presence of endothelial cells in vitro, we established a three-dimensional collagen culture in which SK-BR-3 tumour colonies were grown in the presence or absence of an endothelial barrier. We demonstrated that - in contrast to targeting FcγR on neutrophils with mAbs - targeting the immunoglobulin A Fc receptor (FcαRI) instead triggered neutrophil migration and degranulation leading to tumour destruction, which coincided with release of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α. Interestingly, neutrophil migration was enhanced in the presence of endothelial cells, which coincided with production of significant levels of the neutrophil chemokine IL-8. This supports the idea that stimulation of neutrophil FcαRI, but not FcγR, initiates cross-talk between neutrophils and endothelial cells, leading to enhanced neutrophil migration towards tumour colonies and subsequent tumour killing. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source