ognizant Communication Corporation

ONCOLOGY RESEARCH
Featuring PRECLINICAL AND CLINICAL CANCER THERAPEUTICS

ABSTRACTS
VOLUME 17, NUMBER 4

Oncology Research, Vol. 17, pp. 151-157
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Aberrant Promoter CpG Islands Methylation of Tumor Suppressor Genes in Cholangiocarcinoma

Kyung-Ok Uhm,1 Eun Soo Lee,1 Yun Mi Lee,1 Hyeon Soo Kim,1 Young-Nyun Park,2 and Sun-Hwa Park1

1Institute of Human Genetics, Department of Anatomy, Brain Korea 21 Biomedical Sciences, Korea University College of Medicine, Seoul, 136-705, Korea
2Department of Pathology, Yonsei University College of Medicine, Seoul, 120-752, Korea

Aberrant DNA methylation of 5´-CpG islands located within gene promoters has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. To ascertain the mechanism of gene promoter hypermethylation in cholangiocarcinoma (CC), we investigated promoter methylation status of the candidate genes ID4, DLC-1, and SFRP1 in 41 CCs, 19 adjacent nontumor tissues, and 15 normal liver tissues using methylation-specific PCR (MSP). The frequencies of DNA methylation were: 57.5% (23 of 40) for ID4, 14.3% (5 of 35) for DLC-1, and 63.4% (26 of 41) for SFRP1, respectively. In contrast, a low frequency of methylation was detected in nontumor tissues. In addition, hypermethylated status of these genes was detected in three kinds of CC cell lines. Moreover, the downregulated expression of these genes in these cells was restored by treatment with 5-aza-2´-deoxycytidine, a DNA methyltransferase inhibitor. Taken together, these results suggest that aberrant DNA methylation may contribute to the tumorigenesis of cholangiocarcinoma.

Key words: Cholangiocarcinoma; Hypermethylation; Methylation-specific PCR; Tumor suppressor gene

Address correspondence to Sun-Hwa Park, Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, 126-1, Anam-Dong 5-Ka, Sungbuk-Ku, Seoul, 136-705, Korea. Tel: 82-2-920-6152; Fax: 82-2-929-5696; E-mail: parksh@korea.ac.kr




Oncology Research, Vol. 17, pp. 159-166
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Association of Interleukin-18 Gene Promoter Polymorphism on the Risk of Cervix Carcinogenesis in North Indian Population

Ranbir Chander Sobti,1 Mohammad Shekari,1 Dor Mohammad Kordi Tamandani,1 Keyanoosh Malekzadeh,1 and Vanita Suri2

1Department of Biotechnology, Punjab University, Chandigarh, India
2Department of Obstetrics & Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases. Considering the fact that IL-18 plays an important role in the interactions among T cells, NK cells, and macrophages and induces IFN-gproduction, efforts should be made to understand the clinical impact of IL-18 cytokine in patients with solid malignancies, as not much study has been conducted in cervix carcinoma. In this study, we have observed in GC genotype statistically significant marginal increased risk of developing of cervical cancer (OR 1.8, 95% CI 1.17-2.76, p = 0.006). Similarly, when the GC with CC genotypes were combined results were once more statistically significant with borderline risk of developing cervix cancer (OR 1.6,95% CI 1.09-2.50, p = 0.01). Likewise, we found statistically significant increased risk between cases and controls in GC genotype and passive smokers with risk of cervical cancer (OR 4.3, 95%CI 2.13-8.99, p = 0.00001). Our investigation suggests that IL-18 gene -137 in different genotypes, as also in passive smokers, may increase risk of cervix carcinogenesis in north Indian women.

Key words: Cervical cancer; Polymorphism; Interleukin-18; PCR-SSP

Address correspondence to Ranbir Chander Sobti or Mohammad Shekari, Department of Biotechnology, Punjab University, Chandigarh, India. E-mail: rcsobti@pu.ac.in or mshekari_ch@yahoo.com




Oncology Research, Vol. 17, pp. 167-174
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Interaction of EGFR 497Arg>Lys With EGF +61A>G Polymorphism: Modulation of Risk in Esophageal Cancer

Rohit Upadhyay,1 Meenu Jain,1 Shaleen Kumar,2 Uday Chand Ghoshal,3 and Balraj Mittal1

1Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India
2Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India
3Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India

Genetic polymorphisms in EGFR 497Arg>Lys and EGF +61A>G genes influence cell cycle progression, apoptosis, angiogenesis, and metastasis. Therefore, we assessed association of esophageal cancer (EC), its clinical characteristics, and environmental interactions with these polymorphisms in 174 patients with EC and 196 controls. No association of EGFR 497Arg/Arg genotype was observed (OR 1.48, p = 0.067) but EGF +61A/A genotype was significantly associated with risk of EC (OR 1.65, p = 0.025), particularly in males (OR 1.76, p = 0.031). Patients with EGF +61A/A genotype were at risk for squamous cell carcinoma (SCC) (OR 1.70, p = 0.021) and tumor at upper anatomical location (OR 3.11, p = 0.009). Interaction of EGF or EGFR genotypes with environmental exposure did not modulate EC risk. However, in gene-gene interaction, EGFR 497Arg/Arg*EGF +61A/A showed significant risk for EC (OR 2.47, p = 0.011). In conclusion, EGF +61A>G gene polymorphisms influenced EC susceptibility and its clinical characteristics. Gene-gene interaction of EGFR 497Arg>Lys and EGF +61A>G polymorphisms enhanced risk for EC, indicating additive effects.

Key words: EGF-EGFR interactions; Cancer risk; Esophageal cancer; Cancer susceptibility

Address correspondence to Prof. Balraj Mittal, Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow-226014, India. Tel: +91-522-2668973, 004-8, ext. 2322; Fax: +91-522-2668017, 2668074; E-mail: balraj@sgpgi.ac.in or bml_pgi@yahoo.com




Oncology Research, Vol. 17, pp. 175-182
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Retinoic Acid and Sodium Butyrate as Cell Cycle Regulators in the Treatment of Oral Squamous Carcinoma Cells

Anxun Wang,1 Rongsheng Zeng,2 and Hongzhang Huang2

1Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. China
2Department of Oral and Maxillofacial Surgery, Guanghua College of Stomatology, Sun Yat-Sen University, Guangzhou,
510055, P. R. China

All-trans retinoic acid (ATRA) and sodium butyrate (SB) have shown growth-inhibitory and differentiation-inducing properties to tumor cells when used as single agents or in combination, but the exact molecular mechanism still remains to be determined. In order to determine the mechanism of the synergy in treatment with RA and SB, we evaluated the growth inhibition capability of ATRA and SB, alone or in combination, in human oral squamous carcinoma cell lines SCC-1 and SCC-9, and identified the expression of cell cycle-related genes. ATRA and SB inhibited cell growth and induced cell cycle G1 arrest. The inhibition effect was more pronounced with SB than with ATRA (p = 0.000). There were interactions between ATRA and SB (p = 0.000). Consistent with the inhibition effect and G1 arrest, ATRA and SB, alone or in combination, induced the expression of G1 phase markers cyclin-dependent kinase (CDK) 6, p21, and p27; inhibited the expression of S-G2 phase proteins CDK2; and decreased Rb phosphorylation. Cyclin D1 expression was increased in the SB- and ATRA +SB-treated groups, but inhibited in the ATRA-treated group. Cyclin B1 and cyclin E expression was slightly decreased in the SB- and ATRA +SB-treated groups, but did not change in the ATRA-treated group. These results indicate that the growth inhibition and G1 arrest of oral squamous carcinoma cells in response to ATRA and/or SB correlates with the induction of G1 phase cell cycle regulatory proteins CDK6, p21, and p27 and the inhibition of S-G2 phase cell cycle regulatory protein CDK2.

Key words: All-trans retinoic acid; Sodium butyrate; Human oral squamous cell carcinoma (OSCC); Cell cycle

Address correspondence to Rongsheng Zeng, Department of Oral and Maxillofacial Surgery, Guanghua College of Stomatology, Sun-Yat-Sen University, 56 Lingyuanxi Road, Guangzhou, 510055, P. R. China. Tel: +86-0-13802513663; E-mail: rongsheng_zeng@yahoo.com.cn




Oncology Research, Vol. 17, pp. 183-189
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Expression of Heparanase in Hepatocellular Carcinoma Has Prognostic Significance: A Tissue Microarray Study

Gang Chen, Yi-Wu Dang, Dian-Zhong Luo, Zhen-Bo Feng, and Xiao-Ling Tang

Department of Pathology, Guangxi Medical University, Nanning 530021 ,Guangxi Zhuang Autonomous Region, China

Heparanase plays an important role in invasion and metastasis of tumor cells. In this study, we explored the expression and clinicopathological significance of heparanase protein in hepatocellular carcinogenesis to investigate their roles in invasion and the relationship between biological behavior and prognosis of hepatocellular carcinoma (HCC) in tissue microarrays (TMAs). Heparanase expression was examined by immunohistochemistry in TMAs comprising 120 cases of HCC, 48 cases of adjacent tumor liver, 62 cases of cirrhosis, and 23 cases of normal liver tissues. Statistical analyses were determined to access the correlation between heparanase expression and the clinicopathological features of HCC. The results showed a positive level of heparanase in HCC tissues that was significantly higher than that in adjacent tumor liver, cirrhosis, and normal liver tissue. Heparanase was expressed lower in clinical TNM stages I and II than in III and IV. Moreover, the expression of heparanase in cases without metastasis within 20 months was statistically lower than in those with metastasis. Furthermore, heparanase expression in groups of /gk/a-fetoprotein (AFP) >400 mg/L, portal vein tumor emboli, multiple tumor nodes, and tumor diameter >=5 cm were significantly higher than those of corresponding groups, while it was not associated with patients' age, sex, histological classification, cirrhosis, or tumor capsular infiltration. In conclusion, TMA is a powerful tool for the rapid identification of molecular alterations in HCC. The overexpression of heparanase may play an important role in hepatocarcinogenesis, progression, and metastases of HCC. It could serve as a determining factor for clinical prognosis and curative effect.

Key words: Heparanase; Hepatocellular carcinoma; Immunohistochemistry; Tissue microarray

Address correspondence to Prof. Dr. Dian-Zhong Luo, Department of Pathology, Guangxi Medical University, Shuangyong Road 530021, Guangxi Zhuang Autonomous Region, China. Tel: +0086-771-5356534; Fax: +0086-771-5358943; E-mail: luodianzhong@yahoo.com.cn