The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry / 亚洲男科学杂志(英文版)

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

Detection and identification of specific serum biomarkers in papillary thyroid cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect and identify the potential specific serum biomarkers for diagnosis of papillary thyroid cancer.</p><p><b>METHODS</b>Samples of 35 patients with papillary thyroid carcinoma, 40 patients with benign thyroid nodule and 34 healthy individuals were analyzed using the SELDI-TOF ProteinChip System and bioinfomation technology to find the differential peaks which were separated by HPLC and then further analyzed by LC-MS/MS. The protein sequences were analyzed by SEQUEST software and searched in Bioworks database.</p><p><b>RESULTS</b>The top six mass-to-charge ratio (M/Z) peaks with the smallest P value were 6651, 6452, 7653, 7932, 15 106 and 15 848 Da, respectively. The 6651 and 6452 Da proteins were weakly expressed in papillary thyroid carcinoma but highly expressed in benign thyroid nodules and healthy individuals. The differences had statistical significance (P < 0.01). The 7653, 7932, 15 106, 15 848 Da proteins were highly expressed in papillary thyroid carcinoma but weakly expressed in benign thyroid nodules and healthy individuals. The differences were statistically significant (P < 0.01). Combination of these six proteins, using the method of leave-one-out to make crossing detection, the specificity of discriminating papillary thyroid carcinoma and non-cancer was 88.0%, and its sensitivity was 92.5%. The 6651 and 6452 Da proteins were identified as apolipoprotein C-I and apolipoprotein C-III, respectively. The 7653 and 15 106 Da proteins were identified as the same protein-alpha-globin, and the 7932 and 15,848 Da proteins were identified as the same protein-beta-globin.</p><p><b>CONCLUSION</b>The detection of differentially expressed apolipoprotein C-I, apolipoprotein C-III, alpha-globin, and beta-globin may have utility for diagnosis of papillary thyroid carcinoma and are worthy of further investigation.</p>

Expression of apoC1 and FTL Genes in Human with Carotid Atherosclerosis

PURPOSE: The pathogenesis of carotid atherosclerosis (CA) is known to involve several pathologic processes, such as lipid disturbances, thrombosis, oxidative stress and apoptosis. However, the genetic factors contributing to the development of CA, are, poorly understood. Thus, this study was performed to clarify the genes that are related with CA by comparing the expression patterns of mRNA in the arteries of a control group and in the arteries of a CA patients group. MATHODS: The total RNAs in the arteries of both groups were obtained from the abdominal aorta of 5 brain death donors and also the carotid arteries of 10 CA patents, and the DNAs were then reversely transcribed into complementary DNA (cDNA). The annealing control primer (ACP) method was applied to identify the differentially expressed messenger RNAs (mRNAs). RESULTS: The prominently expressed genes in the CA group compared with the control group were those of apolipoprotein C1 (apoC1) and ferritin light chain (FTL). There was a difference in the gene and protein expressions in the development of vascular disease between the coronary and carotid arteries, i.e., the transcriptional pathway for the FTL expression in CA patient arteries, and the posttranscriptional pathway in the coronary artery disease. The ApoC1 gene was another prominently expressed gene in the current study, and it has been reported to promote apoptosis in the cultured smooth muscle cells of human aorta. CONCLUSION: The increased expression of the apoC1 and FTL genes in the carotid artery might increase the possibility of CA via the apoptosis and oxidation of the increased LDL and VLDL.

The apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate associations between the apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease (CAD).</p><p><b>METHODS</b>apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the polymorphisms of both apoCI and apoCII genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 203 cases of CAD and 365 controls. Pairwise linkage disequilibrium coefficients (D, D') were estimated by the LINKAGE program.</p><p><b>RESULTS</b>The frequencies of apoE E3/4 genotype (0.259) and epsilon4 (0.139) in CAD group were significantly higher than that in control group (0.125, 0.069), (P<0.05). The significant difference was also found for the apoCI locus, the frequencies of H2 allele were 0. 205 in the CAD and 0.113 in the control. Linkage disequilibrium coefficient D' was 0.672 (P<0.01) between apoE and apoCI genes. Significant differences for a deficit of epsilon3-H1-T1 and excess of epsilon4-H2-T1 were found in the CAD by estimation of the haplotype frequencies. After adjustment for possible confounding factors, the multivariate Logistic analysis showed a significant interaction among epsilon4, H2 and smoking, OR value was 18.3 (95%CI:2.35-150.81, P<0.05), attributable proportions of interaction (API) was 57.3%, it was a multiplicative model. An additive model was shown among epsilon4, H2 and bibulosity; the odds ratio (OR) (95%CI) and API of their interaction were 12.7(2.8-58.6, P<0.05) and 43.5%, respectively.</p><p><b>CONCLUSION</b>The results suggested that both apoE and apoCI on chromosome 19 were the susceptibility loci for CAD, their linkage disequilibrium should be responsible for the development of CAD. Smoking and bibulosity can significantly increase the risk of CAD.</p>