S100A12 and RAGE expression in human bladder transitional cell carcinoma: a role for the ligand/RAGE axis in tumor progression?

BACKGROUND: Transitional cell carcinoma (TCC) and prostate cancer are the most frequent cancers in the male genitourinary tract. Measurement of biological biomarkers may facilitate clinical monitoring and aid early diagnosis of TCC. The aim of the present investigation was to detect the mRNA levels of S100A12 and RAGE (receptor for advanced glycation end products) in patients suffering from bladder TCC. MATERIALS AND METHODS: To explore the involvement of S100A12 and RAGE genes, total RNA was harvested from cancer tissues and samples obtained from normal non-tumorized urothelium of the same patients. Quantitative PCR (qPCR) was subsequently employed to determine the mRNA levels of S100A12 and RAGE. RESULTS: The results showed that mRNA expression of S100A12 and RAGE was significantly up-regulated in the cancer tissue. CONCLUSIONS: According to the results presented in the current study, mRNA expression of S100A12 and RAGE might be as a useful biomarker for TCC. Therefore, this ligand-receptor axis possibly plays important roles in the development of TCC and may serve either as an early diagnostic marker or as a key factor in monitoring of response to treatment. More research is required concerning inhibition of the S100A12-RAGE axis in different cancer models.

The Intricate Expression of CC Chemokines in Glial Tumors: Evidence for Involvement of CCL2 and CCL5 but Not CCL11.

Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 and CCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, the CCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment.

Lack of Correlation Between the CCR5-Δ32 Mutation and Acute Myeloid Leukemia in Iranian Patients.

Chemokines and their receptors are crucially important in the pathogenesis of acute myeloblastic leukemia (AML). The CC chemokine receptor 5 (CCR5) is a specific chemokine receptor for CC chemokine ligand 3 (CCL3), CCL4 and CCL5 which all play key roles in identifying cancer properties and localization of leukemia cells. It has been demonstrated that the known mutation in CCR5 gene (CCR5-Δ32) leads to mal-expression of the receptor and affect its function. The aim of this study was to determine the rate of CCR5-Δ32 mutation within Iranian AML patients. In this study, blood samples were obtained from 60 AML patients and 300 healthy controls. The CCR5-Δ32 mutation was evaluated using Gap-PCR technique. Our results showed that CCR5-Δ32 mutation was not found in the patients, while three out of the controls had hetrozygotic form of this mutation. The rest of studied samples had the wild form of the gene. According to these findings, it can probably be concluded that the CCR5-Δ32 is not associated with susceptibility to AML in Iranian patients.

Overproduction of CXC chemokines CXCL1, CXCL9, CXCL10 and CXCL12 in ß-thalassemia major or patients.

BACKGROUNDS AND OBJECTIVES: B-thalassemia major is one of the most frequent hematological genetic disorders, worldwide. Chemokines are the main components of the immune system and play fundamental roles in pathogenesis of inflammatory disorders. Therefore, the present study aimed to examine whether serum CXC chemokines are altered in b-thalassemia major patients. DESIGN AND SETTINGS: We enrolled 63 b-thalassemia patients and 80 controls in this cross-sectional study, which was performed during 2012-2013 in Kerman, Iran. METHODS: We enrolled 63 b-thalassemia patients and 80 controls in the present study. Patients were selected from referrals to Samenolhojaj clinic for thalassemia, Kerman, Iran. The circulating levels of CXCL1, CXCL9, CXCL10, and CXCL12 were detected by enzyme-linked immunosorbent assay in thalassemia patients and healthy controls immediately after blood collection. Data were analyzed by c2, t-test, and analysis of variance statistical methods and using SPSS, version 13 (SPSS Inc., Chicago, IL). RESULTS: The results of the study demonstrated a significant elevation of CXCL1, CXCL9, CXCL10, and CXCL12 in thalassemia patients than in control. These results also demonstrated that serum chemokine levels are related to transfusion duration and post-transfusion viral infections. CONCLUSION: According to the results obtained, it can probably be concluded that chemokines are also involved in the pathogenesis of b-thalassemia major and its clinical complications in addition to several other parameters.

The SDF-1 3'A genetic variation is correlated with elevated intra-tumor tissue and circulating concentration of CXCL12 in glial tumors: a study on Iranian anaplastic astrocytoma and glioblastoma multiforme patients.

Immunological factors are important in pathogenesis of various malignancies, including neural cancers. The CXC chemokine CXCL12 is involved in the immune responses. Therefore, the aim of the present study was to investigate the association between tumor tissue and circulating concentrations of CXCL12 as well as its genetic variation at position +801 known as(the SDF-1 3'A), in Iranian patients suffering from malignant glial tumors. In this study, stereotactic tumor biopsy specimens in parallel with peripheral blood samples were collected from 123 patients and 189 healthy controls. The serum level of CXCL12 was measured by ELISA and tumor tissues were subjected to Western blotting for intra-tumor CXCL12 detection; we also employed PCR-RFLP to detect the SDF-1 3'A polymorphism. Demographic data were collected by a researcher-designed questionnaire. These results demonstrated a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of CXCL12. We also indicated elevated levels of CXCL12 in circulation and tumor tissue obtained from in patients suffering from malignant glial tumors. Based upon the results of this investigation, we propose that CXCL12 and its SDF-1 3'A polymorphism play a fundamental part in the pathogenesis of malignant glial tumors. It is also noteworthy that CXCL12 could probably be utilized as a beneficial biological marker in the diagnosis of these tumors.