• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10299-10306
• /
• 2015

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8461-8465
• /
• 2016

Gastric cancer (GC) as the fourth most common cause of malignancies shows high rate of morbidity appropriating the second leading cause of cancer-related death worldwide. Developmental pluripotency associated-2 (DPPA2), cancer-testis antigen (CT100), is commonly expressed only in the human germ line and pluripotent embryonic cells but it is also present in a significant subset of malignant tumors. To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to elucidate DPPA2 protein expression in gastric cancer. Fifty five GC tumor and their related margin normal tissues were recruited to evaluate DPPA2 protein expression and its probable associations with different clinicopathological features of the patients. DPPA2 was overexpressed in GC cases compared with normal tissues (P < .005). While DPPA2 expression was detected in all GC samples, its high expression was found in 23 of 55 tumor tissues (41.8%). Interestingly, 50 of 55 normal samples (90.9%) were negative for DPPA2 protein expression and remained 5 samples showed very low expression of DPPA2. DPPA2 protein expression in GC was significantly correlated with lymph node metastasis (p = 0.012). The clinical relevance of DPPA2 in GC illustrated that high level expression of this protein was associated with lymph node metastasis supporting this hypothesis that alteration in DPPA2 was associated with aggressiveness of gastric cancer and may be an early event in progression of the disease. DPPA2 may be introduced as a new marker for invasive and metastatic GCs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8901-8904
• /
• 2014

Background: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. Materials and Methods: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. Results: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT =1.58, 95% CI= 1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. Conclusions: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

• Journal of Gastric Cancer
• /
• v.5 no.3 s.19
• /
• pp.206-212
• /
• 2005

Purpose: Angiogenesis has a critical role in tumor proliferation, invasion, and metastasis. In gastric cancer, tumor-associated macrophages and mast cells produce angiogenic factors such as VEGF, that inhibit the functional maturation of dendritic cells. The aim of this study is to identify tumor-associated macrophages, mast cells, dendritic cell infiltrations, and microvessel densities (MVD) to investigate the relationship between them and the prognosis for gastric-cancer patients. Materials and Methods: The subjects were 79 patients selected from those who had undergone a curative gastric resection for stomach cancer. With them, Immune-histochemical staining was done using CD34 for the MVD, CD68 antigen for macrophages, and S-100 protein for dendritic cells, and toluidine blue staining was done for mast cells. Results: Macrophage infiltration showed a statistically significant positive correlation with histologic differentiation and a negative correlation with invasion depth, nodal metastasis, and stage. S-100 (+) dendritic cells and mast cells had no significant correlations with histologic differentiation, invasion depth, nodal metastasis, distant metastasis, stage, and MVD. As survival, no statistically significant differences were seen between the variables. Conclusion: Tumor-associated macrophages should be evaluated as possible prognostic markers in gastric-cancer patients.

• Journal of Microbiology
• /
• v.45 no.6
• /
• pp.572-577
• /
• 2007

To enhance therapeutic potential of murine monoclonal antibody, humanization by CDR grafting is usually used to reduce immunogenic mouse residues. Most humanized antibodies still have mouse residues critical for antigen binding, but the mouse residues may evoke immune responses in humans. Previously, we constructed a new humanized version (AKA) of mouse CC49 antibody specific for tumor-associated glycoprotein, TAG-72. In this study, to select a completely human antibody light chain against TAG-72, guided selection strategy using phage display was used. The heavy chain variable region (VH) of AKA was used to guide the selection of a human TAG-72-specific light chain variable region (VL) from a human VL repertoire constructed from human PBL. Most of the selected VLs were identified to be originated from the members of the human germline VK1 family, whereas the VL of AKA is more homologous to the VK4 family. Competition binding assay of the selected Fabs with mouse CC49 suggested that the epitopes of the Fabs overlap with that of CC49. In addition, they showed better antigen-binding affinity compared to parental AKA. The selected human VLs may be used to guide the selection of human VHs to get completely human anti-TAG72 antibody.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.4
• /
• pp.547-553
• /
• 2015

The yeast surface-displayed cDNA library has been used to identify unknown antigens. However, when unknown target antigens show moderate-to-low abundance, some modifications are needed in the screening process. In this study, a directional random-primed cDNA library was used to increase the number of candidates for the unknown antigen. To avoid the loss of target yeast clones that express proteins at a low frequency in the cDNA library, a comprehensive monitoring system based on magnetic-activated cell sorting, fluorescence-activated cell sorting, and immunofluorescence was established, and a small number of target yeast cells was successfully enriched. These results showed that our optimized method has potential application for identifying rare unknown antigens of the human monoclonal antibody.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3381-3384
• /
• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• KSBB Journal
• /
• v.24 no.1
• /
• pp.80-88
• /
• 2009

Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

• Journal of Korean Neurosurgical Society
• /
• v.29 no.4
• /
• pp.477-484
• /
• 2000

Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3331-3335
• /
• 2013

Background: The incidence of prostate cancer, one of the most common cancers in elderly men, is increasing annually in Thailand. Matrix metalloproteinase 11 (MMP-11) is a member of the extracellular matrix metalloproteases which has been associated with human tumor progression and clinical outcome. Aim: To quantify MMP-11 expression in prostatic adenocarcinoma tissues and to determine whether its overexpression correlates with survival outcome, and to assess its potential as a new prognostic marker. Materials and Methods: Expression of MMP-11 was analyzed using immunohistochemistry in 103 Thai patients with prostatic adenocarcinoma. Overall survival was analyzed using Kaplan-Meier methods and Cox regression models. Results: Immunoreactivity of MMP-11 was seen in the stroma of prostatic adenocarcinoma tissue samples, high expression being significantly correlated with poor differentiation in Gleason grading, pathologic tumor stage 4 (pT4), and positive-bone metastasis (p<0.05), but not age and prostatic-specific antigen (PSA) level. Patients with high levels of MMP-11 expression demonstrated significantly shorter survival (p<0.001) when compared to those with low levels. Multivariate analysis showed that MMP-11 expression and pT stage were related with survival in prostatic adenocarcinoma [hazard ratio (HR)=0.448, 95% confidence interval (95%CI)=0.212-0.946, HR=0.333, 95%CI=0.15-0.74, respectively]. Conclusions: Expression of MMP-11 is significantly associated with survival in prostatic adenocarcinoma. High levels may potentially be used for prediction of a poor prognosis.