Overexpression and elevated plasma level of tumor-associated antigen 90K/Mac-2 binding protein in colorectal carcinoma

The cancer cell secretome may contain potentially useful biomarkers. Previously, we have analyzed the colorectal carcinoma (CRC) cell secretome. In this study, tumor‐associated antigen 90K (TAA90K)/Mac‐2 binding protein (Mac‐2BP), one of the CRC cell secreted proteins, was chosen for evaluation as a potential CRC biomarker because its mRNA level was also found to be significantly elevated in CRC tissues and in a more metastatic CRC cell line from the analysis of two public domain array‐based datasets. Immunohistochemical analysis of 241 CRC specimens showed that TAA90K/Mac‐2BP was positively detected in 52.7% of the tumors, but weakly or not detected in over 95% of the adjacent nontumor epithelial cells. The plasma TAA90K/Mac‐2BP levels were significantly higher in CRC patients (N = 280) versus healthy controls (N = 147) (7.77 ± 3.49 vs. 5.72 ± 2.67 μg/mL, p<0.001). Moreover, combination of TAA90K/Mac‐2BP and carcinoembryonic antigen (CEA) could outperform CEA alone in discriminating CRC patients from healthy persons in this case‐control study. Our results collectively indicate that analysis of cancer cell secretome is a feasible strategy for identifying cancer biomarker candidates, and the TAA90K/Mac‐2BP may be a potential CRC biomarker.     

Identification of nasopharyngeal carcinoma antigens that induce humoral immune response by proteomic analysis

A proteomics-based approach has been used to identify proteins that commonly elicit a humoral immune response in nasopharyngeal carcinoma (NPC). Sera from 19 newly diagnosed NPC patients and 19 healthy individuals were analyzed for IgG autoantibodies against NPC proteins resolved by 2-DE. Protein spots that exhibited selective reactivity with sera from NPC patients were identified by MS. Among nine identified proteins, cytokeratin 19 (CK19), Erb3 binding protein (EBP1), and Rho GDP dissociation inhibitor-beta (Rho-GDI-2) induced autoantibodies in more than 36.8% of NPC patients but not in healthy individuals. Furthermore, Western blot analysis and immunohistochemical staining were performed to determine the expression and localization of CK19, EBP1, and Rho-GDI-2 in NPC and normal nasopharyngeal mucosal tissues. Up-regulated CK19 and EBP1, but not Rho-GDI-2, were observed in NPC vs. normal tissue. Subcellular localization of the three proteins in NPC tissue was same as that in the normal tissue. Thus, overexpression of CK19 and EBP1 may be one of the mechanisms for their autoantibody development in NPC. To validate the findings of a proteomic analysis, occurrence of autoantibodies against these three proteins was detected by immunoprecipitation and Western blot analysis in additional 30 NPC patients, 23 other types of cancer patients and 20 healthy individuals. Results showed that frequency of autoantibodies against CK19, EBP1 and Rho-GDI-2 in NPC patients was significantly higher than that in other types of cancer patients and healthy individuals. We conclude that CK19, EBP1 and Rho-GDI-2 may have utility in NPC screening and diagnosis.     

Contribution of laser microdissection-based technology to proteomic analysis in hepatocellular carcinoma developing on cirrhosis

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.     

99Tcm(V)-DMSA与99Tcm-MIBI亲肿瘤显像在诊断甲状腺髓样癌中的对比

对62例甲状腺髓样癌(MTC)患者手术前行SPECT亲肿瘤显像,其中99Tcm(V)-DMSA显像组32例,99Tcm-MIBI显像组30例;并对两组患者早期和延迟影像的定性和半定量分析结果进行比较.结果显示两种显像方法对MTC原发灶诊断的阳性率无显著性差异(P＞0.05),但半定量分析结果显示99Tcm(V)-DMSA对原发灶显像的早期摄取比、延迟摄取比、滞留指数明显高于99Tcm-MIBI显像,差异有显著性(P＜0.001),提示99Tcm(V)-DMSA显像更具有优越性.     

HSP70基因在人胃癌、宫颈癌中高表达和癌变关系的研究

采用人的HSP70基因探针P17与人的胃癌、宫颈癌的癌组织中提取的RNA进行northern杂交，结果均出现了比正常组织较强的杂交信号。表明HSP70基因在癌变组织中呈现高表达，与组织的癌变程度表现出了很强的相关性，为进一步了解细胞的癌变机理和对癌症的预防及基因治疗提供了可靠的实验依据。     

DISCRETE WAVELET TRANSFORM FOR DENOISING RAMAN SPECTRA OF HUMAN SKIN TISSUES USED IN A DISCRIMINANT DIAGNOSTIC ALGORITHM

In this work, we applied the discrete wavelet transform (DWT) method as a denoising tool for dispersive Raman spectra of skin samples, and we compared the results obtained with the low-order polynomial fitting in a discriminating model based on principal components analysis (PCA). We used a set of 50 Raman spectra of skin tissue fragments diagnosed as normal (N) (25 spectra) and basocellular cell carcinoma (BCC) (25 spectra). A denoising procedure using DWT and its inverse was employed, and the resulting spectra were compared to denoising using low-order polynomial fitting and adjacent averaging smoothing. The tissue spectral profile showed changes in the intensity of bands below 1400 cm^?1 for DWT compared to the denoising by polynomial and smoothing. By applying PCA and Mahalanobis distance in both groups processed, we verified that the filtering method does not alter significantly the discrimination of N and BCC tissues. However, the DWT denoising presented an interesting result, which showed the main components after decomposition of the Raman signal used in the reconstruction.     

A nano- and micro- integrated protein chip based on quantum dot probes and a microfluidic network

A novel nano- and micro-integrated protein chip (NMIPC) that can detect proteins with ultrahigh sensitivity has been fabricated. A microfluidic network (μFN) was used to construct the protein chips, which allowed facile patterning of proteins and subsequent biomolecular recognition. Aqueous phase-synthesized, water-soluble fluorescent CdTe/CdS core-shell quantum dots (aqQDs), having high quantum yield and high photostability, were used as the signaling probe. Importantly, it was found that aqQDs were compatible with microfluidic format assays, which afforded highly sensitive protein chips for cancer biomarker assays. Electronic Supplementary Material  Supplementary material is available for this article at and is accessible for authorized users.     

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.     

32P-玻璃微球介入治疗肝细胞肝癌的临床初步应用

采用Ｓｅｌｄｉｎｇｅｒｓ穿刺法,导管超选择至肝固有动脉以远,灌注＾３２Ｐ－玻璃微球（＾３２Ｐ－ＧＭＳ）,对９７例肝细胞肝癌（ＨＣＣ）实施了９９次内照射介入治疗。结果表明,Ａ方案半年及１、２、３年生存率分别为１００％、９６．７％、５６．７％和４３．３％;Ｂ方案分别为９７．９％、９１．８％、６１．２％和５１．０％。经治后的中位生存时间为５８５天。多因素分析显示：肝功能、肿瘤大小、临床类型及＾３２Ｐ－Ｇ