ognizant Communication Corporation

ONCOLOGY RESEARCH
AN INTERNATIONAL JOURNAL
INCORPORATING ANTI-CANCER DRUG DESIGN

ABSTRACTS
VOLUME 16, NUMBER 4

Oncology Research, Vol. 16, pp. 167-178
0965-0407/06 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2006 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Black Tea Polyphenols Protect Against 7,12-Dimethylbenz[a]anthracene-Induced Hamster Buccal Pouch Carcinogenesis

P. Vidjaya Letchoumy,1 K. V. P. Chandra Mohan,1 R. Kumaraguruparan,1 Y. Hara,2 and S. Nagini1

1Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
2Mitsui Norin Co. Ltd., Shizuoka, Japan

Dietary chemoprevention has emerged as a cost-effective approach for cancer control. We evaluated the chemopreventive effects of black tea polyphenols (Polyphenon-B) administration during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The expression of proliferating cell nuclear antigen (PCNA) in the buccal pouch and the concentration of lipid peroxides, protein carbonyl, and the antioxidant status in the buccal pouch, liver and erythrocytes were used as biomarkers of chemoprevention. All the hamsters painted with DMBA alone for 14 weeks developed buccal pouch carcinomas associated with increased expression of PCNA, diminished lipid and protein oxidation, and enhanced antioxidant status. In the liver and erythrocytes of tumor-bearing animals, enhanced oxidation of lipids and proteins was accompanied by compromised antioxidant defenses. Dietary administration of Polyphenon-B effectively suppressed DMBA-induced HBP carcinogenesis as revealed by decreased incidence of tumours and PCNA expression. In addition, Polyphenon-B modulated lipid and protein oxidation and enhanced the antioxidant status in the pouch, liver, and erythrocytes. We suggest that Polyphenon-B exerts its chemopreventive effects by inhibiting cell proliferation in the target tissue and modulating the oxidant-antioxidant status in the target as well as in host tissues.

Key words: Antioxidants; Black tea polyphenols; Chemoprevention; Hamster buccal pouch carcinogenesis; Lipid peroxidation; Proliferating cell nuclear antigen

Address correspondence to Dr. S. Nagini, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India. Tel: +91-4144-239842; Fax: +91-4144-238145/238080; E-mail: s_nagini@yahoo.com or snlab@sancharnet.in




Oncology Research, Vol. 16, pp. 179-193
0965-0407/06 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2006 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Phosphorylation of ErbB4 on Tyrosine 1056 Is Critical for ErbB4 Coupling to Inhibition of Colony Formation by Human Mammary Cell Lines

Sarah E. Pitfield,* Ianthe Bryant,* Desi J. Penington, Gar Park, and David J. Riese II

School of Pharmacy and Purdue Cancer Research Center, Purdue University, West Lafayette, IN 47907-2064, USA

In many studies, ErbB4 expression in breast tumor samples correlates with a favorable patient prognosis. Similarly, ErbB4 signaling is coupled to cellular differentiation and growth arrest in a variety of model systems. However, in some studies, ErbB4 expression in breast tumor samples correlates with poor outcome. Likewise, studies using some human mammary tumor cell lines suggest that ErbB4 is coupled to malignant phenotypes. Thus, the roles that ErbB4 plays in human breast cancer are still poorly defined. Here we demonstrate that a constitutively active ErbB4 mutant (ErbB4-Q646C) inhibits colony formation on plastic by two human mammary tumor cell lines (SKBR3 and MCF7) and by the MCF10A immortalized human mammary cell line, but does not inhibit colony formation by the MDA-MB-453 and T47D human mammary tumor cell lines. ErbB4 kinase activity is necessary for ErbB4 function and phosphorylation of ErbB4 Tyr1056 is necessary and appears to be sufficient for ErbB4 function. The inhibition of colony formation by MCF10A cells is accompanied by growth arrest but not cell death. These data suggest that ErbB4 behaves as a mammary tumor suppressor and that loss of ErbB4 coupling to growth arrest may be an important event in mammary tumorigenesis.

Key words: ErbB4; Breast cancer; Signal transduction; Tumor suppressor; Receptor tyrosine kinase

Address correspondence to David J. Riese II, HANS 114, 201 S. University Street, Purdue Cancer Research Center, West Lafayette, IN 47907-2064, USA. Tel: 765-494-6091; Fax: 765-496-3601; E-mail: driese@purdue.edu

*Both authors contributed equally to this work.




Oncology Research, Vol. 16, pp. 195-203
0965-0407/06 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2006 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Chemotherapy Influences Inducible Nitric Oxide Synthase (iNOS) and Endothelial Nitric Oxide Synthase (eNOS) Activity on 3D Breast Cancer Cell Line

G. Öktem,1* A. Bilir,2* N. Selvi,3 M. E. Yurtseven,1 S. Vatansever,4 U. Ates,1 A. Uysal,1 and S. B. Omay5

1Department of Histology and Embryology, Ege University School of Medicine, TR-35100 Izmir, Turkey
2Department of Histology and Embryology, Istanbul University School of Medicine, Istanbul, Turkey
3Department of Medical Biology, Ege University School of Medicine, TR-35100 Izmir, Turkey
4Department of Histology and Embryology, Celal Bayar University School of Medicine, TR-45030 Manisa, Turkey
5Department of Hematology, Karadeniz Technical University School of Medicine, Trabzon, Turkey

Multicellular tumor spheroids (MTS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on MTS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the "liquid overlay" technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2´-deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis.

Key words: iNOS; eNOS; Breast cancer; Chemotherapy

Address correspondence to Dr. Gulperi Öktem,  Department of Histology and Embryology, Ege University School of Medicine, TR-35100 Izmir, Turkey. Tel: +90-232-3904091-36; E-mail: goktem@med.ege.edu.tr or goktem@hotmail.com

*These authors contributed equally to this work.




Oncology Research, Vol. 16, pp. 205-209
0965-0407/06 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2006 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Association of Promoter Hypermethylation of the RASSF1A Gene With Prognostic Parameters in Endometrial Cancer

Hoenil Jo,1 Jae Weon Kim,1,2,3 Gyeong Hoon Kang,2,3 Noh-Hyun Park,1,2 Yong-Sang Song,1,2 Soon-Beom Kang,1,2 and Hyo-Pyo Lee1,2

1Department of Obstetrics and Gynecology, Seoul National University, Seoul, Korea
2Cancer Research Institute, Seoul National University, Seoul, Korea
3Human Genome Research Institute, Seoul National University, Seoul, Korea

RASSF1A is a tumor suppressor gene that is frequently hypermethylated in various human cancers. In the present study, we examined RASSF1A methylation status in 70 patients with endometrial cancer to search for correlations between the promoter hypermethylation of RASSF1A and the clinicopathologic parameters. Thirty-six of 70 endometrial cancers demonstrated hypermethylation of the RASSF1A promoter. Advanced stage disease (FIGO stage III, IV), lymph node involvement, and high grade (G3) are more frequent in patients with RASSF1A hypermethylation than in those without. We also observed a higher incidence of recurrences and lower disease-free survival (DFS) in patients with RASSF1A hypermethylation (77.8% and 97.0% at 5 years for methylated and unmethylated patients, respectively, p = 0.039). Our results suggest that RASSF1A hypermethylation might be a useful indicator of tumor aggressiveness in endometrial cancer patients.

Key words: RASSF1A; Hypermethylation; Endometrial cancer; Prognosis; Pathologic parameters

Address correspondence to Jae Weon Kim, M.D., Ph.D., Department of Obstetrics and Gynecology and Cancer Research Institute, Seoul National University, 28 Yeongeon-Dong, Chongno-Gu, Seoul, 110-744, Korea. Tel: +82 2 2072 3511; Fax: +82 2 749 4438; E-mail: kjwksh@snu.ac.kr