ABSTRACT
Background and purpose:It is increasingly focused on that insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 4 (IGFBP-4) effect cell proliferation, differentiation and apoptosis of tumor cells, and pregnancy-associated plasma protein-A (PAPPA) plays an important role in IGF-1-dependent IGFBP-4 protease mechanism that regulats tumor cells' growth. This study aimed to investigate the serum levels and clinical signiifcance of IGF-1, IGFBP-4, and PAPPA in patients with non-small cell lung cancer (NSCLC). Methods:IGF-1, IGFBP-4, and PAPPA plasma levels were measured by enzyme-linked immunosorbent assay from 82 patients with NSCLC and 40 control subjects, then the correlations between variables were assessed by Spearman correlation analysis, and associations between the IGFs variables and lung cancer risk were calculated through the odds ratio (OR) and its 95%conifdence interval (CI) with the use of unconditional logistic regression analysis. Results:Serum levels of IGF-1, IGFBP-4 and PAPPA in NSCLC patients were signiifcantly higher than those in the control group(P<0.05). There was a signiifcant positive correlation between the serum IGF-1 levels and PAPPA levels (r=0.835,P=0.000), and a negative correlation with IGFBP-4 levels (r=-0.612,P=0.000). IGFBP-4 and PAPPA levels were negatively correlated(r=-0.673, P=0.000). High plasma levels of IGF-1(OR=2.28, 95%CI: 1.25-4.36,P=0.008) and PAPPA (OR=1.64, 95%CI: 0.89-3.01,P=0.046)were associated with an increased risk of lung cancer, however high plasma levels of IGFBP-4(OR=0.54, 95%CI:0.30-1.01,P=0.047)were associated with reduced risk of lung cancer. Conclusion:To detect IGF-1, IGFBP-4 and PAPPA in serum in NSCLC patients is meaningful for the clinical auxiliary diagnosis and biology behavior prediction of NSCLC. And further study of signal transduction pathways of IGFs with the occurrence and development of NSCLC is a meaningful research direction.
ABSTRACT
Background Researches have showed that the extraocular muscle injection of insulin-like growth factor(IGF) results in the thickness of extraocular muscle and enhancement of contractility,and lack of IGF probably is associated with pathogenesis of strabismus.If extraocular muscle injection of insulin-like growth factor binding protein 4(IGFBP-4),an inhibitor of IGF,can further ensure the effect of IGF is still under-investigation.Objective The aim of this study was to evaluate the effects of IGFBP-4 on the developing extraocular muscle.Methods IGFBP-4 of 2 μl(1 g/L)was injected into superior rectus muscles via supraorbital margin in the left eyes of 24 postnatal l-day-old chickens once every other day for five times,and the equivalent amount of normal saline solution was used in the same way in the fellow eyes as controls.The animals were sacrificed by overdose of anesthesia 2 days after the final injection and 12 animals were randomly selected for the maximal contractility test of superior rectus muscle.The other 12 pieces of superior rectus muscle of the chickens were obtained for the hematoxylin & eosin staining to evaluate the morphology of superior rectus muscle and calculate the myofiber diameter using imaging system.Results The maximal contractility was (1.602 ± 0.080) mN and(1.815±0.O10)mN in the IGFBP-4 injection group and normal saline solution group respectivily,showing a significant difference between the two groups(t =13.65,P＜0.01).The maximal contraction force in cross-sectional area was (95.500 ± 7.420) mN/cm2 in the IGFBP-4 injection group and it was significantly lower than that of the normal saline solution group(101.510±5.220)mN/cm2(t =28.81,P＜0.01).Histological examination showed that thin myofibers were obvious more in the IGFBP-4 injection group than those with saline injection.The mean diameter was (8.7 ± 0.5) μm in the IGFBP-4 injected group,and that of the normal saline group was(9.1 ±0.4) μm,there was no significant difference between them (t =0.75,P =0.46).However,significant differences were found in the number of different diameters of myofibers between the two groups(all at P＜0.05).Conclusions IGF is one of the key nutrition factors in the development of extraocular musele.The extraocular muscle injection of IGFBP-4 may cause the dysfunction and morphologic abnormality of extraocular muscle.