Inflammation, a key factor in cancer ambush

Inflammatory condition is the consequence of defensive mechanism of immune system against viral and bacterial infection, tissue injury, UV radiation, stress and etc. Persistently acute inflammation leads to chronic phase which is characterized by production of pro-inflammatory mediators from T cells. These molecules [e.g. IL-6, TNF-alpha, IL-1beta and IL-17] are mostly pleiotropic cytokines involved in multiple signaling cascades. NF-kappaB, STAT3, and HIF-1alpha are the major engaged pathways directing to several downstream targets associating with tumorigenesis and inflammation. Carcinogenesis processes such as DNA mutation/damage, proliferation, angiogenesis, apoptosis, and invasion are implicated to inflammation. Clearly there is a closely association between cancer and inflammation reported as "Seven Hallmark of Cancer". The elucidation of relationship between inflammation and cancer and their interaction may result in effective therapy and prevention. Gastric cancer is one of the main cancer involved in complex correlation of inflammation and cancer. Inflammation in gastric epithelium could trigger cellular transformation and promote invasion by inducing immune responses and utilizing signaling cascades. Gastric tumor microenvironment has inverse association by providing cytokines and inflammatory mediators. This closely relationship facilitates gastric tumor development and the induction of chronic inflammation in tumor microenvironment. The current review will focus on describing the possible and critical ways in which inflammation and cancer are linked together with specific view to gastric cancer and inflammation. Finally, it introduces some putative treatment generally used in this way in order to direct more attention for further exploration

Genetic profile variation in vaccine strains and clinical isolates of bordetella pertussis recovered from Iranian patients

Re-emergence of pertussis has been reported in Iran despite a high rate of vaccination coverage. Low efficacy of the vaccine might be due to the genetic divergence between Clinical versus vaccine strains. In the current study, the genetic profiles of Clinical isolates and vaccine strains of Bordetella pertussis [B. pertussis] were assessed by using Pulsed Field Gel Electrophoresis [PFGE]. Following phenotypic and molecular identification of isolates, XbaIdigested genomic DNA of 5 Clinical isolates, 2 vaccine strains and a Tohama I strain were analyzed by PFGE along with B. parapertussis as a control. Seven distinct PFGE profiles were found among all examined isolates/strains. In 5 Clinical isolates, 4 profiles were identified whereas the vaccine strains displayed 2 distinct profiles. The reference strain, Tohama I had a distinct profile. Vaccine and Clinical profiles had low similarity, with relatedness of approximately 40%. The genetic profiles of B. pertussis were different between circulating isolates and vaccine strains used in the national vaccination programs. Since new genetic profiles of B. pertussis can be disseminated periodically, the profiles of isolates circulating in the population should be monitored over the course of the re-emergence

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9+/-32.5 microg/mL vs 219.8+/-59.0 microg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

Expression, purification and characterization of three overlapping immunodominant recombinant fragments from Bordetella pertussis filamentous hemagglutinin

Filamentous hemagglutinin [FHA] is one of the most important immunoprotective antigens of Bordetella pertussis [B. pertussis] and a major component of the acellular pertussis vaccine. In the present study, three overlapping recombinant fragments from the immunodominant region of FHA were produced and their immunogenicity was investigated. Three overlapping coding sequences of FHA antigen were amplified from B. pertussis genomic DNA by PCR. Amplified fragments were expressed in Escherichia coli [E. coli] BL21[DE3] strain and purified through His-tag using Nickel-based chromatography. Purified fragments were characterized by SDS-PAGE and Western blotting techniques. In vitro peripheral blood mononuclear cells [PBMC] proliferation and IFN- gamma production were assessed in a limited number of healthy adults vaccinated with a commercial acellular pertussis vaccine in response to all purified FHA fragments by H3-Thymidine incorporation and ELISA, respectively. Recombinant FHA segments were successfully cloned and produced at high levels in E. coli BL21[DE3]. SDS-PAGE and Western blot analyses confirmed their purity and reactivity. All three recombinant fragments together with a commercial native FHA were able to induce in vitro PBMC proliferation and IFN- gamma production. Our preliminary results suggest that these overlapping recombinant FHA fragments are immunogenic and may prove to be immunoprotective

Differential WNT gene expression in various subtypes of acute lymphoblastic leukemia

Dysregulation of WNT signaling has been reported in many malignancies. This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into B-ALL [76%], T-ALL [22.6%] and mixed lineage [1.4%] and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results. Among the WNT genes, WNT-7B [p=0.026], WNT-9A [p=0.020] and WNT-16B [p=0.023] were significantly over-expressed, whereas WNT-2B [p=0.033], WNT-5A [p=0.016], WNT-7A [p<0.0001] and WNT-10A [p<0.0001] were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes. Our results suggest contribution of the WNT genes in leukemogenesis of ALL

Comparative expression profile of orphan receptor tyrosine kinase ROR1 in Iranian patients with lymphoid and myeloid leukemias

It has recently been shown that ROR1, a member of the receptor tyrosine kinase family, is overexpressed in leukemic B cells of Chronic Lymphocytic Leukemia [CLL] and a subset of Acute Lymphoblastic Leukemia [ALL]. In this comparative study the expression profile of ROR1 mRNA was investigated in Iranian patients with CLL and Acute Myelogenous Leukemia [AML] and the results were compared with those previously reported in our Iranian ALL patients. RT-PCR was performed on bone marrow and/or peripheral blood samples of 84 CLL and 12 AML patients. CLL samples were classified into immunoglobulin heavy chain variable region [IGHV] gene mutated [n=55] and unmutated [n=29] and also indolent [n=42] and progressive [n=39] subtypes. ROR1 expression was identified in 94% of our CLL patients, but none of the AML patients expressed ROR1. No significant differences were observed between different CLL subtypes for ROR1 expression. Taken together the present data and our previous results on ROR1 expression in ALL, our findings propose ROR1 as a tumor-associated antigen overexpressed in a large proportion of lymphoid [CLL and ALL], but not myeloid [AML] leukemias. Expression of ROR1 seems to be associated to lineage and differentiation stages of leukemic cells with a potential implication for immunotherapy

B-cell lineage study in patients with juvenile idiopathic arthritis

Juvenile idiopathic arthritis [JIA] is the most common rheumatic disease in children. The exact causes of disease are still poorly understood. It seems that B cells have several functions in JIA, including production of autoantibodies, antigen presentation, production of cytokines, and activation of T cells. Here, we aimed to evaluate B-cell lineage and its precursors in the bone marrow of patients with JIA Twenty consecutive patients with JIA were enrolled in this study. JIA is subdivided into three groups of Pauciarticular, Polyarticular, and Systemic JIA. Bone marrow mononuclear cells were separated. Then we analyzed the immunophenotype of the JIA patients by flow cytometry. After separation, the mononuclear cells were stained specific for B cell lineage [CD10, CD19 and CD20], T cell lineage [CD3] and non specific lineage [CD34, HLA-DR and TdT]. Flow cytometric study of bone marrow showed that JIA patients had low level of CD10, CD19, and CD20.Polyarticular patients had lower level of D10, CD19, and CD20 than pauciarticular JIA patients and systemic onset JIA patients had lower levels than both of them. Decreasing of B cell precursor in bone marrow is one of mechanisms for pathogenesis of JIA and the more decreased B cell precursors in bone marrow are, the worst severity of the disease is. Significant differences in CD10 content of bone marrow were detected between the polyarticular and pauciarticular groups. So, it seems that polyarticular JIA patients had lower percentage of pre B cell stage

Immunophenotypic subtyping of leukemic cells from Iranian patients with acute lymphoblastic leukaemia: association to disease outcome

Immunophenotypic characterization of the leukemic cells has been widely used as a tool for diagnosis, classification, stratification and prognosis of leukaemia. To investigate the immunophenotypic subtype profiles of Iranian patients with acute lymphoblastic leukemia [ALL] and its association to disease outcome. In this study, a total of 60 Iranian patients with ALL were immunophenotyped by flow cytometry using a panel of monoclonal antibodies specific for CD2, CD3, CD5, CD10, CD13, CD14, CD19, CD20, CD33, CD34, CD45, HLA-DR and TdT molecules. The samples were initially categorized into T-ALL [n=9], B-ALL [n=50] and mixed lineage [n=1] based on the expression patterns of CD3 and CD19 molecules. B-ALL patients could further be classified into four subtypes, including Pro-B [n=7, 11.7%], Pre-B I [n=28, 46.7%], Pre-B II [n=13, 21.7%] and immature/mature B cells [n=2, 3.3%] on the basis of expression of CD10, CD19, CD20, HLA-DR and TdT. Clinical manifestations and laboratory findings of the patients did not reveal association with immunophenotypic sub-types of ALL, with the exception of mediastinal mass and WBC count at the time of diagnosis which were found to be significantly higher in patients with T-ALL compared with B-ALL [p=0.001 and 0.014], respectively. Our results indicate that overall the immunophenotypic profile of Iranian ALL patients is similar to previous reports and it might be used for monitoring of minimal residual disease and prognosis

CD40 ligand expression on stimulated t-helper lymphocytes in patients with common variable immunodeficiency

Common variable immunodeficiency [CVID] is the most common symptomatic primary antibody deficiency, characterized by reduced serum immunoglobulins levels and increased susceptibility to recurrent pyogenic infections. In this study, we evaluated CD40 ligand expression on stimulated versus unstimulated T-helper lymphocytes of nine Common variable immunodeficient patients in comparison with fifteen normal controls. Phorbol myristate acetate [PMA] and Ionomycin were used to stimulate cells in vitro. After six hours stimulation, the cells were subjected to surface staining with three-color staining procedure. Events were analyzed by flow cytometer, using FloMax software. Results were reported as the percentage of lymphocytes expressing CD markers. We did not find any significant statistical difference in CD40 ligand expression between patients and controls [p>0.05], despite having stimulation documented by CD69 expression as activation marker in each run. The results of this study are in agreement with some other studies, indicating that CD40 ligand expression on stimulated T-helper lymphocytes of Common variable immunodeficiency patients is similar to normal controls