RESUMO
Chemokines have been proposed to contribute to tumour growth and metastatic spread of several cancer entities. Here, we examined the relative levels of CXCL12/CXCR4 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as colorectal liver metastases (CRLM). CXCL12/CXCR4 mRNA and protein expression profiles were assessed by quantitative real-time PCR, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry in resection specimens from patients with ulcerative colitis (UC; n = 15), colorectal adenoma (CRA; n = 15), colorectal adenocarcinoma (CRC; n = 47) and CRLM (n = 16). Corresponding non-affected tissues served as control. In contrast to UC tissues, CXCL12 showed a distinct down-regulation in CRA, CRC and CRLM specimens, whereas the corresponding receptor CXCR4 demonstrated a significant up-regulation in CRC and CRLM related to corresponding non-affected tissues (p < 0.05, respectively). Our results strongly suggest an association between CXCL12/CXCR4 expression and the induction of CRA, CRC and the development of CRLM. Therefore, CXCR4 may be a potential target for specific therapeutic interventions.
Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores CXCR4/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Quimiocina CXCL12/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Receptores CXCR4/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Immunosuppressive therapy is essential for patients after renal transplantation, but it may have mutagenic side effects. The frequency of micronuclei (MN) assessed by the cytokinesis block assay is well established in the diagnosis of DNA damage. METHODS: We examined 79 patients before and after renal transplantation with the cytokinesis block assay. For MN evaluation, the criteria of the Human Micron Nucleus (HUMN) project were used. RESULTS: Age and sex had no influence on the number of MN before transplantation. Patients with a shorter time on dialysis had fewer MN than patients with a longer time on dialysis. After 3 weeks of immunosuppressive therapy, the ability of cells to proliferate was reduced; therefore, only 36 patients could be analyzed. In these patients, MN frequency rose significantly. There was no linear relationship between MN after transplantation and age, sex, time on dialysis or graft function. The majority of patients (79%) were treated with cyclosporine A, mycophenolate mofetil and methylprednisolone when leaving the hospital. There was no difference between the different therapeutic schemes with regard to MN frequency after transplantation, but patients with mycophenolate mofetil showed less cellular proliferation. The function of the transplanted organ or the occurrence of rejection had no effect on MN frequency after transplantation. CONCLUSION: In patients with renal transplantation, immunosuppressive therapy intensifies the genotoxic damage of the preceding chronic renal failure.