Biomedical subjects

Jian-Ying Zhang

Publications and source records attributed to Jian-Ying Zhang.

16 recordsLinked to original sources

PubMed2007

Association of interleukin-1 gene polymorphisms with gastric cancer: a meta-analysis.

Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the risk of the original studies. Thirty-nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta-analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL-1B-511T, -31C, +3954T and IL-1RN*2 was 1.26 (95% confidence interval (CI): 1.03-1.55), 1.00 (95% CI: 0.82-1.22), 1.37 (95% CI: 0.94-2.00) and 1.20 (95% CI: 1.01-1.41), respectively. A stratified analysis showed that IL-1B-511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12-2.57). Moreover, IL-1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09-1.54). In conclusion, IL-1B-511 and IL-1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.

DNA, Neoplasm↗

PubMed2006

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma.

BACKGROUND/AIMS: Previous studies have demonstrated that during transition from chronic liver disease to hepatocellular carcinoma (HCC), autoantibodies can appear which are not detected in the prior pre-malignant conditions. These antibody responses may be stimulated by cellular proteins involved in carcinogenesis. This study determines the prevalence of antibodies to a selected panel of eight tumor-associated antigens (TAAs) in sera from patients with chronic hepatitis, liver cirrhosis and HCC, and considers the possibility and usefulness of antibodies to such a panel of TAAs in differentiating between these conditions. The panel of eight TAAs includes Imp1, p62, Koc, p53, c-myc, cyclin B1, survivin and p16 full-length recombinant proteins. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against eight selected TAAs in 30 sera from chronic hepatitis, 30 from liver cirrhosis, and 142 from HCC. Positive results were also confirmed by slot blot, Western blotting and immunoprecipitation assay. RESULTS: Antibody frequency to any individual TAA in HCC varied from 9.9% to 21.8%. With the successive addition of TAAs to a final total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a frequency of 59.8% with whole cohort of HCC patients. This was significantly higher than the frequency of antibodies in chronic hepatitis (20%), liver cirrhosis (30%) and normal individuals (12.2%). CONCLUSIONS: This study demonstrates that malignant transition to HCC is associated with increased autoantibody responses to certain cellular proteins which might have a role in tumorigenesis, and shows that a mini-array of eight TAAs enhanced antibody detection for diagnosis of HCC. More studies in patients with HCC and precursor conditions such as chronic hepatitis, alcoholic hepatitis and liver cirrhosis using enlarged TAA mini-array panels might further improve the sensitivity and specificity of this mode of cancer immunodiagnosis. Its additional usefulness might be in the early detection of cancer in some patients with predisposing conditions.

Adult↗

PubMed2006

QSPR/QSAR models for prediction of the physicochemical properties and biological activity of polybrominated diphenyl ethers.

Polybrominated diphenyl ethers (PBDEs) are a group of important persistent organic pollutants. In the present study, geometrical optimization and electrostatic potential calculations have been performed for all 209 PBDE congeners at the HF/6-31G level of theory. A number of statistically-based parameters have been obtained. Linear relationships between gas-chromatographic relative retention time (RRT), n-octanol/air partition coefficient (lgK(OA)), 298 K supercooled liquid vapour pressures (lgp(L)), Henry's law constant (lgH) and Ah receptor binding affinity (-lgRBA) of PBDEs and the structural descriptors have been established by multiple regression method. The result shows that the quantities derived from electrostatic potential V(s,max),V(s,min),Pi, Sigma V+(S), V-(S) , nu, sigma 2(tot), and N-(v), together with the molecular volume (Vmc) can be well used to express the quantitative structure-property relationships of PBDEs, which proves the general applicability of this parameter set to a great extent. Good predictive capabilities have also been demonstrated. Based on these equations, the predicted values have been presented for those PBDE congeners whose experimentally determined physicochemical properties are unavailable. The QSAR model for the Ah receptor binding affinity is relatively poor, which can be ascribed to the complexity of factors which affect biological activity and the limitations of the present parameter set in describing steric characters of the molecule.

Algorithms↗

PubMed2006

Humoral immune response to p16, a cyclin-dependent kinase inhibitor in human malignancies.

The p16 protein is a cyclin-dependent kinase (CDK) inhibitor, which plays an important role in the regulation of the cell cycle by inactivating the cyclin-dependent kinase (CDK) that phosphorylates the retinoblastoma (Rb) protein. Overexpression of p16 protein has been found in many types of human malignancy. Autoantibody response to p16 in cancer has not been reported. This study determined the extent and frequency of autoantibodies to p16 in diverse malignancies. p16 recombinant protein was expressed in E. Coli BL21 (DE3) cells, and purified using GST fusion protein purification system. In further studies, p16 recombinant proteins were used as antigens in enzyme-linked immunoassay (ELISA) and Western blotting. Sera from 479 cancer patients and 82 normal individuals were analyzed. Autoantibodies to p16 were found in 11.7% in cancer, with significant difference from the normal individuals (p<0.05). The results in this study also showed that the frequency of antibodies to p16 is relatively higher in nasopharyngeal cancer (28.6%), breast cancer (17.1%) and hepatocellular carcinoma (HCC, 21.4%). Of the 56 ELISA positive sera with the anti-p16 antibodies, 85.7% (48/56) had positive reactions in Western blotting. The antigen-antibody absorption experiment was also performed to confirm the specificity of the anti-p16 antibody. In order to increase the frequency of antibody detection in cancer, a combination of three tumor-associated antigens (TAAs) p16, p53 and c-myc were used. Increased frequencies at p<0.01 were found for antibodies to p16 in breast, esophageal, and nasopharyngeal cancer as well as HCC. For antibodies to c-myc, increased frequencies at p<0.01 were found in breast, cervical, colorectal and lung cancer. For antibodies to p53, increased frequencies at p<0.01 were only found in breast cancer. With the successive addition of three TAAs, there was a stepwise increase of positive anti-body reaction up to 44% in breast cancer and 43% in nasopharyngeal cancer. In summary, the results in this study suggest that the combination of antibodies might acquire higher sensitivity for early cancer diagnosis. It is conceivable that auto-antibody profiles involving different panels or arrays of TAAs might be developed in the future and the results could be useful for cancer diagnosis.

Antibodies, Neoplasm↗

PubMed2005

Preferential humoral immune response in prostate cancer to cellular proteins p90 and p62 in a panel of tumor-associated antigens.

BACKGROUND: Cytoplasmic p90 autoantigen was recently cloned from a cDNA expression library using serum antibody from a cancer patient. The humoral immune response to p90 in prostate cancer and benign prostatic hyperplasia (BPH) was examined. METHODS: An antigenic fragment of recombinant p90 protein and several other tumor-associated antigens (TAAs) were used in ELISA and Western blotting to detect antibodies in sera from patients with prostate cancer, BPH, and other controls. RESULTS: Autoantibodies to p90 were detected in 30.8% of 133 prostate cancer patients versus 1.5% in 68 BPH patients. When a selected panel of six TAAs including p90 were used for immunoscreening, the cumulative positive reactions in prostate cancer sera reached 92.5%, significantly higher than in BPH and other control sera. Antibodies to p90 showed the highest frequency in prostate cancer (30.8%), followed by antibodies to p62 (22.6%). CONCLUSIONS: A panel of six selected TAAs was shown to have high sensitivity and specificity as immunodiagnostic markers in prostate cancer.

Antigens, Neoplasm↗

PubMed2005

A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus.

PURPOSE: To evaluate the potential role of external beam radiation therapy (EBRT) in the treatment of patients with hepatocellular carcinoma (HCC) who have portal vein (PV) and/or inferior vena cava (IVC) tumor thrombi. METHODS AND MATERIALS: One hundred fifty-eight patients with HCC who had PV and/or IVC tumor thrombus were reviewed and analyzed by Kaplan-Meier and Cox regression analysis. Forty-four patients with HCC who received local limited EBRT (in addition to other treatment modalities) were classified as the EBRT group. The total radiation dose was 36-60 Gy (median, 50 Gy) and was focused on the tumor thrombi. One hundred fourteen patients with HCC who did not receive EBRT were selected from hospitalized patients with HCC who had PV and/or IVC thrombi during the same period; these were classified as the non-EBRT group, and their intrahepatic tumors were treated with transarterial chemoembolization or resection, on the basis of the patients' status. Parameters observed included survival rates and the tumor thrombus response to EBRT as seen on CT scan or MRI. RESULTS: Of the 44 patients who received EBRT, 15 (34.1%) showed complete disappearance of tumor thrombi, 5 (11.4%) were in partial remission, 23 (52.3%) were stable in their tumor thrombi, and 1 (2.3%) showed disease progression at the end of the study period. The median survival was 8 months, and the 1-year survival rate was 34.8% in the EBRT group. In the non-EBRT group, the median survival and 1-year survival rates were 4 months and 11.4%, respectively. In stepwise multivariate analysis, EBRT showed a strongly protective value (relative risk = 0.324, p < 0.001). Survival was not related to intrahepatic tumor status in the non-EBRT patients. However, in the EBRT group, poorer prognosis was significantly related to intrahepatic multifocal or diffusion lesions, and the most common reason for death was liver failure caused by uncontrolled intrahepatic disease. CONCLUSION: Although EBRT is palliative in intent, it is preferred for prolonging survival in the treatment of tumor thrombi.

Adolescent↗

PubMed2005

Autoimmune response to anti-apoptotic protein survivin and its association with antibodies to p53 and c-myc in cancer detection.

Survivin, an inhibitor of apoptotic protein, is over-expressed in many cancers but not in normal differentiated adult tissues. Recently, antibodies to survivin have been demonstrated in patients with lung and colorectal cancer. Whether antibodies to survivin can be used as a marker for the diagnosis of cancer, and how antibody to survivin is related to antibodies against tumor suppressor protein p53 and oncoprotein c-myc remains to be evaluated. In the present study, the full-length recombinant proteins survivin, p53 and c-myc, were expressed and used as antigens in enzyme-linked immunosorbent assay (ELISA) and Western blot for the detection of antibodies to these three proteins. Sera from 1137 patients with 11 different types of cancer were analyzed. Antibodies to survivin were detected in 8.4% (96/1137), with a significant difference from the control groups consisting of normal individuals and autoimmune disease patients (p<0.05). Of 1137 cancer sera, 546 were also tested for the presence of antibodies to p53 and c-myc. Frequencies of antibodies to p53 and c-myc were 11.5 and 12.3%, respectively. Although antibodies to either one of three antigens do not reach levels of sensitivity, which could become routinely useful in diagnosis, it appears that there are different patterns of antibody frequency in individual cancer type. The results also indicated that when the presence of antibody to any one of these three antigens was considered, the cumulative frequency was increased to 27.3% (149/546) for the total group of cancer patients. It became apparent from our data that the combination of antibodies might acquire higher sensitivity.

Antibodies, Neoplasm↗

PubMed2005

Radiation therapy for adrenal gland metastases from hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from hepatocellular carcinoma. However, it has been the subject of few studies, and the optimal treatment remains unclear. Methods previously tried for the management of adrenal gland metastasis of hepatocellular carcinoma included surgical resection, transarterial chemoembolization or percutaneous ethanol injection, on the basis of case reports. External beam radiation therapy has seldom been applied for patients with adrenal gland metastases. METHODS: We retrospectively studied 22 patients with adrenal metastases from hepatocellular carcinoma who were treated with limited-field external beam radiation therapy. The radiation dose to the adrenal lesion ranged from 36 to 54 (median 50) Gy, while the intrahepatic lesions were treated with either surgical resection or transarterial chemoembolization. RESULTS: Among the 14 patients who had pain related to adrenal metastases, 11 (78.6%) had complete pain relief without medication that lasted until death. Two (14.3%) patients had marked pain relief, but still required analgesics. Partial responses were observed in 73% of the patients. The median survival period for all patients was 10 months. No patient died from complications related to adrenal metastasis. Adverse effects were mild. CONCLUSION: Adrenal metastases from hepatocellular carcinoma are sensitive to radiation treatment. Radiation therapy with 50 Gy for adrenal gland metastases is a good palliative therapy with reasonable safety.

Adrenal Gland Neoplasms↗

PubMed2005

Significance of autoantibodies against insulin-like growth factor II mRNA-binding proteins in patients with hepatocellular carcinoma.

Autoantibodies against insulin-like growth factor II mRNA-binding proteins (IMPs) were analyzed in patients with hepatocellular carcinoma (HCC) to elucidate the significance of these autoantibodies. Five of 86 (5.8%) HCC patients had one or more of these autoantibodies. Serum alpha-fetoprotein (AFP) levels ranged within normal limits in HCC patients seropositive for anti-IMPs except for one case. One of HCC patients had anti-IMP1 and anti-IMP3 before the diagnosis of HCC. On the other hand, overexpressions of IMP1 and IMP2 in the tumor tissues were observed in 2 (28.6%) and 3 (42.9%) of 7 HCC tissues, respectively. One HCC patient with IMP1/2-overexpression in the tumor tissue had anti-IMP1/2, while the other HCC patients with overexpressions of IMP1/2 in the tumors did not have anti-IMP1/2. These findings may suggest that autoantibodies against IMPs are produced in an antigen-driven immune system and that anti-IMPs seem to be supplementary serological markers for the diagnosis of HCC in AFP-negative cases or predictive markers of HCC.

Animals↗

PubMed2005

Analyses of autoantibodies against tumor-associated antigens in patients with hepatocellular carcinoma.

Autoantibodies against tumor-associated antigens (TAAs) such as insulin-like growth factor II mRNA-binding proteins (IMPs), p53, c-myc, and survivin were analyzed in patients with hepatocellular carcinoma (HCC), using recombinant proteins of these antigens. Eight of 86 (9.3%) HCC patients had one or more of these autoantibodies. However, serum alpha-fetoprotein (AFP) levels ranged within normal limits in HCC patients with anti-TAAs except for one case with anti-IMP1. One of the HCC patients had autoantibodies against IMP1, IMP3 and p53 before the diagnosis of HCC. These findings may indicate that anti-TAAs seem to be supplementary serological markers for the diagnosis of HCC in AFP-negative cases and that autoantibodies against IMP1, IMP3 and p53 are candidates for predictive markers of HCC development.

Antigens, Neoplasm↗

PubMed2004

Tumor-associated antigen arrays to enhance antibody detection for cancer diagnosis.

Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). Cancer has long been recognized as a multi-step process which involves not only genetic changes conferring growth advantage but also factors which disrupt regulation of growth and differentiation. It is possible that some of these factors could be identified and their functions evaluated with the aid of autoantibodies arising during tumorigenesis. The multi-factorial and multi-step nature in the molecular pathogenesis of human cancers must be taken into account in both the design and interpretation of studies to identify biomarkers which will be useful for early detection of cancer. Our recent studies suggest that the combination of antibodies against a group of TAAs might acquire higher sensitivity for diagnosis of cancer. It is conceivable that autoantibody profiles involving different panels or arrays of TAAs might be developed in the future and the results could be useful for cancer diagnosis.

Antibodies, Neoplasm↗

PubMed2003

Recursive partitioning as an approach to selection of immune markers for tumor diagnosis.

PURPOSE AND EXPERIMENTAL DESIGN: Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs), but the low frequency of positive reactions against any individual antigen has precluded use of autoantibodies as useful diagnostic markers. With enzyme immunoassay, we examined antibody frequencies to a panel of seven TAAs, c-myc, cyclin B1, IMP1, Koc, p53, p62, and survivin, in 527 cancer patients (64 breast cancer patients, 45 colorectal cancers, 91 gastric cancers, 65 hepatocellular carcinomas, 56 lung cancers, and 206 prostate cancers), and 346 normals. We used recursive partitioning to assess whether we could accurately classify individuals as either cancer patients or normals on the basis of the profile of antibody reactivity to the seven TAAs for each individual. RESULTS: Recursive partitioning resulted in the selection of subsets of the seven-panel TAA, which differentiated between tumors and controls, and these subsets were unique to each cancer cohort. The classification trees had sensitivities ranging from 0.77 to 0.92 and specificities ranging from 0.85 to 0.91 in the cancer cohorts when normal means +2 SDs were used as standard cutoffs for immunoassay positivity. Antibody to cyclin B1 was the initial discriminating node for gastric and lung cancers, and for hepatocellular carcinoma, and was a subsequent discriminating node in all of the other cancer cohorts. c-myc was the initial discriminating node in breast cancer, p62 in prostate cancer, and IMP1 in colon cancer. Recursive partitioning demonstrated that no more than three of the seven TAAs were needed for any cancer cohort to arrive at these levels of sensitivity and specificity. CONCLUSIONS: This initial study shows that multiple antigen miniarrays can provide accurate and valuable tools for cancer detection and diagnosis. Performance of the miniarrays might be enhanced by other combinations of TAAs appropriately selected for different cancer cohorts.

Antibodies, Neoplasm↗

PubMed2003

Three-dimensional biocompatible ascorbic acid-containing scaffold for bone tissue engineering.

A biodegradable, biocompatible, ascorbic acid-containing three-dimensional polyurethane matrix was developed for bone tissue-engineering scaffolds. This matrix was synthesized with lysine-di-isocyanate (LDI), ascorbic acid (AA), glycerol, and polyethylene glycol (PEG). LDI-glycerol-PEG-AA prepolymer when reacted with water foamed with the liberation of CO(2) to provide a pliable, spongy urethane polymer with pore diameters of 100 to 500 microm. The LDI-glycerol-PEG-AA matrix degraded in aqueous solution and yielded lysine, glycerol, PEG, and ascorbic acid as breakdown products. The degradation products did not significantly affect the solution pH. The LDI-glycerol-PEG-AA matrix can be fabricated into diverse scaffold dimensions and the physicochemical properties of the polymer network supported in vitro cell growth. Green fluorescent protein-transgenic mouse bone marrow cells (GFP-MBMCs) attached to the polymer matrix and remained viable, and the cells became confluent cultures. Furthermore, ascorbic acid released from LDI-glycerol-PEG-AA matrix stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis in vitro. Cells grown on LDI-glycerol-PEG-AA matrix did not differ phenotypically from cells grown on tissue culture polystyrene plates as assessed by cell growth, expression of mRNA for collagen type I, and transforming growth factor beta(1). These observations suggest that AA-containing polyurethane may be useful in bone tissue-engineering applications.

Absorbable Implants↗

PubMed2003

Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens.

Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). This study determines whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach to cancer detection and diagnosis. The mini-array of TAAs comprised full-length recombinant proteins expressed from cDNAs encoding c-myc, p53, cyclin B1, p62, Koc, IMP1, and survivin. Enzyme immunoassay was used to detect antibodies in 527 sera from six different types of cancer. Antibody frequency to any individual TAA was variable but rarely exceeded 15-20%. With the successive addition of TAAs to a final total of seven antigens, there was a stepwise increase of positive antibody reactions up to a range of 44-68%. Breast, lung, and prostate cancer patients showed separate and distinct profiles of reactivity, suggesting that uniquely constituted antigen mini-arrays might be developed to distinguish between some types of cancer. Distinct antibody profiles were not observed in gastric, colorectal, and hepatocellular carcinomas with this set of seven TAAs. Detection of autoantibodies in cancer can be enhanced by using a mini-array of several TAAs as target antigens. Additional studies in early cancer patients and high-risk individuals and the design of unique antigen panels for different cancers would help to determine whether multiple antigen mini-arrays for the detection of autoantibodies might contribute a clinically useful noninvasive approach to cancer detection and diagnosis.

Antibodies, Neoplasm↗

PubMed2002

Autoantibody responses in Chinese hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in Henan, China. The objective of this study was to analyze the frequency and specificity of autoantibodies associated with HCC in Henan. In the present study, 137 sera from HCC patients, 77 sera from other liver diseases, and 30 sera from normal human individuals were examined for autoantibodies using immunohistochemistry, Western blotting, and immunoprecipitation assays. Autoantibodies were detected in 80 of 137 (58.4%) HCC sera. Antinucleolar antibodies were seen more frequently in HCC compared to other liver diseases (9.5% vs. 1.3%, P < 0.05). Two nucleolar proteins-fibrillarin and NOR-90/ hUBF-were identified as autoantigens. The frequency of autoantibodies in HCC sera with known hepatitis C virus (HCV) infection was significantly higher than that in sera without HCV infection (84.2% vs. 57.7%, P < 0.01). Another interesting finding was that autoantibodies to a 90-kDa cytoplasmic antigen were found in 21% of HCC patients. This is the first report on the frequency and specificity of autoantibodies in sera from Chinese patients with HCC. The data support that autoimmune responses to certain cellular proteins may be a by-product in the transformation to HCC, and further studies of novel targeted autoantigens in Chinese HCC may provide insights into how these proteins might be involved in malignancy.

Autoantibodies↗

PubMed2002

Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers.

The success of a tissue-engineering application depends on the use of suitable biomaterials that degrade in a timely manner and induce the least immunogenicity in the host. With this purpose in mind, we have attempted to synthesize a novel nontoxic biodegradable lysine diisocyanate (LDI)- and glucose-based polymer via polymerization of highly purified LDI with glucose and its subsequent hydration to form a spongy matrix. The LDI-glucose polymer was degradable in aqueous solutions at 37, 22, and 4 degrees C, and yielded lysine and glucose as breakdown products. The degradation products of the LDI-glucose polymer did not significantly affect the pH of the solution. The physical properties of the polymer were found to be adequate for supporting cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSCs) attached to the polymer matrix, remained viable on its surface, and formed multilayered confluent cultures with retention of their phenotype over a period of 2 to 4 weeks. These observations suggest that the LDI-glucose polymer and its degradation products were nontoxic in vitro. Further examination in vivo over 8 weeks revealed that subcutaneous implantation of hydrated matrix degraded in vivo three times faster than in vitro. The implanted polymer was not immunogenic and did not induce antibody responses in the host. Histological analysis of the implanted polymer showed that LDI-glucose polymer induced a minimal foreign body reaction, with formation of a capsule around the degrading polymer. The results suggest that biodegradable peptide-based polymers can be synthesized, and may potentially find their way into biomedical applications because of their biodegradability and biocompatibility.

Biocompatible Materials↗