Insulin-like growth factor-binding protein-2 (IGFBP-2) is considered to be a human tumor antigen, and the tumor-specific immunity of IGFBP-2 has been reported in several types of cancer. The purpose of this study was to evaluate whether autoantibodies to IGFBP-2 can be used as diagnostic markers in lung cancer. The results demonstrated that serum anti-IGFBP-2 autoantibody levels were significantly elevated in lung cancer (mean, 1,633.318 ng/ml; median, 1,651.462 ng/ml; range, 342.732–4932.582 ng/ml) compared with benign lung disease (1,210.139, 1,035.900, 547.596–2,331.167 ng/ml) and normal controls (1,303.369, 1,194.800, 528.200–2140.500 ng/ml). The sensitivity and specificity of anti-IGFBP-2 autoantibodies in diagnosing lung cancer was 73.2 and 60.6%, respectively. When serum IGFBP-2 and anti-IGFBP-2 autoantibody were used together in the diagnosis of lung cancer, it can increase the discriminative power for lung cancer with a sensitivity of 85.7% and a specificity of 57.5%. In conclusion, this study demonstrates that circulating anti-IGFBP-2 autoantibodies can be used as a potential biomarker in diagnosing lung cancer.
Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for gastric cancer (GC). However, the occurrence of resistance to 5-FU treatment poses a major problem for its clinical efficacy. In this study, we found that the NFκB-signaling pathway can mediate 5-FU resistance in GC cells. We developed a 5-FU-resistant GC cell line named SGCR/5-FU and found that the 5-FU-induced resistance increased cytosolic IκBα degradation and promoted NFκB nuclear translocation in GC cells. These findings were further confirmed by the activation of the NFκB survival-signaling pathway in clinical specimens. Curcumin, a natural compound, can reverse 5-FU resistance and inhibits proliferation in GC cells by downregulating the NFκB-signaling pathway. Moreover, it can also decrease the expression level of TNFα messenger RNA. Flow cytometry and Western blot analysis results showed that the combination of curcumin and 5-FU caused synergistic inhibition of growth and induction of potent apoptosis in the resistant cancer cell lines in vitro. In conclusion, our results demonstrate that the combination of 5-FU and curcumin could be further developed as a potential therapy for human GC.
Previous studies demonstrated that cancer sera contain antibodies, which react with a unique group of autologous cellular antigens called tumour‐associated antigens (TAAs). This study determines whether a panel of TAAs would enhance antibody detection and be a useful approach in pancreatic cancer (PC) detection and diagnosis. The panel of TAAs was composed of six TAAs including p53, p16, p62, survivin, Koc and IMP1 full‐length recombinant proteins. Enzyme‐linked immunosorbent assay (ELISA) was used to detect antibodies against these six TAAs in 23 sera from patients with PC and also 23 sera from normal individuals. Antibody frequency to any individual TAA in PC was variable and ranged from 14.7% to 30.4%. With the successive addition of TAAs to a final total of six antigens, there was a stepwise increase in positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 87.0% in PC. Positive and negative likelihood ratio were 4.685 and 0.449, respectively. Positive and negative predictive values were, respectively, 82.4% and 69.0%. Agreement rate and Kappa value were 73.9% and 0.478, respectively. The data from this study support our previous hypothesis that using a panel of appropriately selected TAAs can enhance autoantibody detection in immunodiagnosis of PC. In 15 PC sera with carbohydrate antigen 19‐9 (CA19‐9) negative, 6 (40%) were found to have anti‐TAA (anti‐tumour associated antigens) antibodies. When CA19‐9 and anti‐TAAs were used together as markers in PC detection, the diagnostic sensitivity could be raised from 60.9% to 69.6%. Anti‐TAA and CA19‐9 were independent markers, and the simultaneous use of these two markers could raise the sensitivity of PC detection.
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