ognizant Communication Corporation

ONCOLOGY RESEARCH
Featuring PRECLINICAL AND CLINICAL CANCER THERAPEUTICS

ABSTRACTS
VOLUME 18, NUMBER 1

Oncology Research, Vol. 18, pp. 1-8
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

The Anticancer Effects of Sodium Selenite and Selenomethionine on Human Colorectal Carcinoma Cell Lines in Nude Mice

Yang Yang, Fang Huang, Yun Ren, Lu Xing, Ying Wu, Zhushi Li, Huazhen Pan, and Caimin Xu

National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China

The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.

Key words: Sodium selenite; Selenomethionine; Apoptosis; GSH and GPX; Apoptotic-related proteins; SW480

Address correspondence to Caimin Xu, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Dong Dan San Tiao 5, Beijing 100005, P.R. China. Tel: +86-0-65296445; Fax: +86-0-65296445; E-mail: caiminxu@yahoo.com.cn




Oncology Research, Vol. 18, pp. 9-15
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Dexamethasone Downregulates BCRP mRNA and Protein Expression in Breast Cancer Cell Lines

Fatemeh Elahian,1,2 Fatemeh Kalalinia,1,2 and Javad Behravan1,2

1Biotechnology Laboratory, Biotechnology Research Centre, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

It is hypothesized that anti-inflammatory drugs regulate breast cancer resistance protein (BCRP) expression. Hence, we examined the effects of indomethacin and dexamethasone on BCRP expression in MCF cells. For evaluation of BCRP mRNA expression, relative quantitative PCR and comparative Ct method was exploited. BCRP protein expression was measured flow cytometrically with the monoclonal antibody (mAb) BXP-21. Dexamethasone showed a dose-independent and a time-dependent effect on decreasing the mRNA level of BCRP gene in comparison with control in MCF-7 and MCF-7/MX breast cancer cell lines, whereas no changes were noted in the presence of indomethacin. The level of BCRP protein, expressed as a ratio of the corresponding control, was decreased in dexamethasone-treated MCF-7/MX cells. These results could be of great importance when combination therapy protocols with cytotoxic agents and dexamethasone regimens are considered in breast cancer patients.

Key words: Breast cancer; BCRP; Dexamethasone; Multidrug resistance; Glucocorticoids; Indomethacin

Address correspondence to Professor Javad Behravan, Department of Pharmaceutical Biotechnology, School of Pharmacy, P.O. Box 91775-1365, Mashhad, Iran. Tel: +98-511-8823255; Fax: +98-511-8823251; E-mail: behravanj@mums.ac.ir




Oncology Research, Vol. 18, pp. 17-23
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Membrane Fluidity and Surface Changes During Initiation of 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis: Protection by Zinc

Vijayta Dani Chadha and D. K. Dhawan

Department of Biophysics, Panjab University, Chandigarh 160 014, India

The present study evaluated the modulatory effects of zinc on colonic membrane fluidity and surface abnormalities following 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum, for the entire duration of the study. Brush border membranes (BBM) were isolated from the colon of rats and the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. The results demonstrated a significant increase in the polarization and anisotropy, accompanied by an increase in order parameter in the membrane preparations from the colon of DMH-injected rats. Further, studies with pyrene fluorophore indicated a marked decrease in membrane microviscosity following DMH treatment. However, the alterations in membrane fluorescence polarization and the fluidity parameters were completely restored following zinc treatment. Drastic alterations in colon surface were noticed after 8 weeks of DMH treatment. However, zinc treatment to DMH-treated rats greatly restored normalcy in the colonic surface. The study concludes that zinc has a strong membrane stabilizing effect and thus has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.

Key words: Dimethylhydrazine; Membrane dynamics; Zinc

Address correspondence to D. K. Dhawan, Ph.D., Department of Biophysics, Panjab University, Chandigarh-160014, India. Tel: +91-172-2534121; Fax: +91-172-2534118; E-mail: dhawan@pu.ac.in




Oncology Research, Vol. 18, pp. 25-30
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

TP53 Codon 72 Polymorphism and Breast Cancer in Northern Iran

Masood Kazemi,1 Zivar Salehi,1 and Roohi Jamal Chakosari2

1Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
2Guilan Medical Sciences University, Rasht, Iran

The p53 gene is one of the most extensively studied human genes because of its role as a tumor suppressor gene. Its diverse functions include DNA binding, cell cycle control, DNA repair, differentiation, genomic plasticity, and apoptosis. A common polymorphism of the p53 gene at codon 72 has been associated with human cancer susceptibility and prognosis. In this study, we investigated p53 codon 72 polymorphism in 42 breast cancer cases and 60 healthy individual in northern Iran. Genomic DNA was extracted from fresh tumor tissues of patients and blood samples of healthy individuals. AS-PCR method was applied for determination of codon 72 polymorphism. The distribution of genotypes in breast cancer cases and controls were different (p = 0.001). Pro allele was significantly associated with the presence of breast cancer (odds ratio = 1.5 and 95% confidence interval = 0.85-2.63). Pro/Pro genotype was overrepresented in breast cancer. Based on these data, it is suggested that Pro allele may modify the risk of breast cancer in northern Iranian women.

Key words: p53; Codon 72; Polymorphism; Breast cancer

Address correspondence to Dr. Zivar Salehi, Department of Biology, Faculty of sciences, PO Box 1914, University of Guilan, Rasht, Iran. Tel: 0098-9113337003; Fax: 0098-131-3233647; E-mail: geneticzs@yahoo.co.uk




Oncology Research, Vol. 18, pp. 31-39
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Fas Expression in Metastatic Osteosarcoma Cells Is Not Regulated by CpG Island Methylation

Gangxiong Huang, Nadezhda V. Koshkina, and Eugenie S. Kleinerman

Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

Fas expression in osteosarcoma (OS) cells is inversely correlated with the metastatic potential of OS to the lung. The purpose of this study was to determine whether loss of Fas expression in metastatic OS cells is secondary to DNA methylation of CpG islands in the Fas gene. SAOS-2 cells have high levels of Fas expression and do not form lung metastases when injected intravenously, whereas LM7 cells have low levels of Fas expression and do produce lung metastases. Using the endonucleases HpaII and MspI and a polymerase chain reaction-based methylation assay, we found that all four CpG sites in the CCGG sequence in the Fas promoter region were unmethylated in both SAOS-2 and LM7 cells. We performed detailed analysis of the 28 and 46 CpG sites in the Fas promoter and first intron region, respectively, using bisulfite-modified genomic DNA sequencing. More than 99.8% of the examined CpG sites were unmethylated and there was no difference of CpG methylation in SAOS-2 and LM7 cells as well as LM7 metastatic lung tumor tissue samples. Treatment of LM7 cells and another OS cell line, DLM8 with low levels of Fas expression, with demethylation agent, 5-azadeoxycitidine (AzadC), did not change the Fas expression and did not increase sensitivity of AzadC-treated cells to Fas ligand (FasL) treatment. In conclusion, our data indicate that decreased Fas expression in OS cells is not secondary to DNA methylation of CpG islands in the Fas gene and that Fas expression cannot be increased by using demethylation agents.

Key words: Fas gene; Osteosarcoma; CpG methylation

Address correspondence to Eugenie S. Kleinerman, Division of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel: 713-792-8110; Fax: 713-794-5042; E-mail: ekleiner@mdanderson.org




Oncology Research, Vol. 18, pp. 41-45
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Role of TGF-b1 (-509C>T) Promoter Polymorphism in Susceptibility to Cervical Cancer

Hariom Singh, Meenu Jain, and Balraj Mittal

Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India

Transforming growth factor-b (TGF-b) family members are multifunctional cytokines that play a key role in cellular growth, proliferation, and differentiation. The aim of study was to evaluate the association of TGF-b1 -509 C>T gene polymorphism with risk of cervical cancer. The study was carried out in 150 histopathology confirmed patients with cervical cancer and 162 cervical-cytology negative females. Polymorphisms for TGF-b1 -509C>T gene was genotyped by polymerase chain reaction and restriction enzyme digestion. Frequencies of individuals with -509TT genotype and T allele of TGF-b1 gene polymorphisms did not differ significantly in patients with cervical cancer and controls (p = 0.328, OR = 1.37 and p = 0.605, OR = 1.09). Cervical cancer patients with -509TT had marginal low risk for stage I (p = 0.04, OR = 0.95, 95% CI = 0.91-0.99) but -509TT genotype of TGF-b1 was associated with increased risk of stage II of cancer (p = 0.07, OR = 3.13, 95% CI = 0.87-11.14). In gene-environment interaction, carriers of TGF-b1 -509TT genotype with tobacco usage were at higher risk of cervical cancer (OR = 3.67, 95% CI = 0.38-35.1). In conclusion, our data suggest that TGF-b1 -509T allele confers marginal protection for early stage 1B but risk for stage II of cervical cancer.

Key words: Cytokine; Cervical cancer; Polymorphism; Transforming growth factor

Address correspondence to Dr. B. Mittal, Professor, Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India. Fax: 91-522-2668017/2668973; Email: balraj@sgpgi.ac.in or bml_pgi@yahoo.com