[show abstract][hide abstract] ABSTRACT: Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.
Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.
The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.
Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.
Current Controlled Trials: ISRCTN45563569.
Journal of Experimental & Clinical Cancer Research 06/2011; 30:65. · 3.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk.
Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study.
No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC.
Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.
Lung Cancer 03/2008; 61(2):152-62. · 3.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.
Annals of Hematology 12/2007; 86(11):815-9. · 2.87 Impact Factor