ognizant Communication Corporation

ONCOLOGY RESEARCH
Featuring PRECLINICAL AND CLINICAL CANCER THERAPEUTICS

ABSTRACTS
VOLUME 17, NUMBER 2

Oncology Research, Vol. 17, pp. 51-58
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Natriuretic Peptides: Biochemical Markers of Anthracycline Cardiac Toxicity?

D. Urbanova,1 L. Urban,2 K. Danova,2 and I. Simkova2

1Institute of Pathophysiology, Comenius University Medical School, Bratislava, Slovakia
2National Institute of Cardiovascular Diseases, Bratislava, Slovakia

Patients with cancer are often treated with potentially cardiotoxic chemotherapeutics. Cardiotoxicity ranges from relatively benign arrhythmias to serious conditions such as myocardial ischemia/infarction, congestive heart failure, and cardiomyopathy. In spite of different diagnostic methods, with echocardiography as a gold standard, there is an intensive search for new diagnostic tools for the early detection of myocardial abnormalities. Available data suggest that the levels of circulating cardiomarkers can monitor the extent and severity of the myocardial damage. The role of routinely used cardiomarkers is controversial and limited in this setting. Natriuretic peptides have shown promising results in assessment and monitoring of both acute and late clinical and subclinical damage of the myocardium in association with chemotherapy. This article reviews clinical studies evaluating the role of natriuretic peptides in the early diagnosis of anthracycline cardiotoxicity, and their use in the management of cancer survivors.

Key words: Cardiotoxicity; Anthracyclines; Natriuretic peptides

Address correspondence to Dagmar Urbanova, M.D., Institute of Pathophysiology, Comenius University Medical School, Sasinkova 4, 811 08 Bratislava, Slovakia. Tel: +421 911 609646; Fax: +421 2 59320513; E-mail: dagmar.urbanova@fmed.uniba.sk




Oncology Research, Vol. 17, pp. 59-68
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

aPKC Inhibitors Might be the Sensitizer of Chemotherapy and Adoptive Immunotherapy in the Treatment of hASIPa-Overexpressed Breast Cancer

Yi-ting Jin,1* Xue-xiang Ying,1* Yi-hong Hu,2 Qiang Zou,1 Hong-ying Wang,1 and Yong-hua Xu2

1Department of Surgery, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200040, China
2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

The atypical protein kinase C (aPKC) plays an important role in cell growth through the interaction with its substracts, including human ASIP (hASIP), which contains an aPKC phosphorylation site encoded by exon 17b of the gene. hASIP is expressed as numerous alternative splicing isoforms in the cells. Our results showed that hASIPa, an exon 17b-containing isoform of hASIP, is overexpressed in human breast cancer (HBC) MDA-MB-231, SK-BR-3, and MCF-7 cell lines and HBC specimens. The anticancer effects of 5-FU chemotherapy or adoptive immunotherapy and the synergic action of aPKC inhibitor against hASIPa-overexpressed HBC cells were tested. The results indicated that HBC MDA-MB-231 and SK-BR-3 cells were sensitive to 5-FU treatment in vitro. The combined treatment of aPKC inhibitor and 5-FU raised the anticancer activities against hASIPa-overexpressed HBC cells. The coculture of cytokine-induced killer (CIK) cells and autologous dendritic cells (DCs) with or without Her-2 peptide GP2 pulse created two new populations of effective immune-active T-cell populations called DC-modulated and cytokine-induced killer (DCIK) cells and peptide-DC-modulated and cytokine-induced killer (DCIK-P) cells. The DCIK cells showed cytotoxic activities on MDA-MB-231, SK-BR-3, and MCF-7 cells in MHC unrestricted manner. The DCIK-P cells possessed extra-enhanced cytotoxic activities against HLA-A2+/Her-2+ MDA-MB-231 cells in MHC restricted manner, but not for HLA-A2±/Her-2+ SK-BR-3 cells and HLA-A2+/Her-2± MCF-7 cells. The data suggested specific cytotoxic T-lymphocyte (CTL) activity of DCIK-P cells on MDA-MB-231 cells. The combined treatment of aPKC inhibitor with DCIK/DCIK-P cells further raised the anticancer activities against hASIPa-overexpressed HBC cells. The results demonstrated that the hASIPa/aPKC signaling pathway functions as an important regulator in the growth of HBC cells and aPKC inhibitor treatment showed the synergic activities on 5-FU or DCIK/DCIK-P cells adoptive immunotherapy against hASIPa-overexpressed HBC cells.

Key words: Human breast cancer; hASIP; aPKC inhibitor; 5-FU; DCIK/DCIK-P cells

Address correspondence to Prof. Qiang Zou, Department of Surgery, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200040, China. Tel: 86-21-6248-9999, ext. 4355; E-mail: zouqiang003@yahoo.com.cn

*Authors contributed equally to this work.




Oncology Research, Vol. 17, pp. 69-74
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

RNASET2 as a Tumor Antagonizing Gene in a Melanoma Cancer Model

Laura Monti,1 Monica Rodolfo,2 Girieca Lo Russo,3 Douglas Noonan,3 Francesco Acquati,1 and Roberto Taramelli1

1Department of Biotechnology and Molecular Sciences, University of Insubria, Varese, Italy
2Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy
3Department of Biological and Clinical Sciences, University of Insubria, Varese, Italy

The RNASET2 gene, mapped in 6q27, was previously found to exert control of tumorigenesis in an ovarian cancer system. We present here results indicating a similar control in a melanoma cancer model. Thus, this gene is most likely involved in a common general pathway of tumorigenesis. Moreover, its antitumorigenic activity is manifested in vivo but not in vitro, suggesting that this gene belongs to the growing category of tumor antagonizing/malignancy suppressor genes. A possible role of RNASET2 in the activation of a senescence program, whose responsible locus was mapped in the same chromosomal 6q27 region, seems to be inconsistent with our data.

Key words: Melanoma model; RNASET2; Antitumorigenic activity Tumor suppressor gene

Address correspondence to Francesco Acquati, Department of Biotechnology and Molecular Sciences, via JH Dunant 3, 21100 Varese, Italy. Tel: +39-0332-421512; Fax: +39-0332-421500; E-mail: francesco.acquati@uninsubria.it




Oncology Research, Vol. 17, pp. 75-85
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

P. Vidjaya Letchoumy,1 K. V. P. Chandra Mohan,1 J. J. Stegeman,2 H. V. Gelboin,3 Y. Hara,4 and S. Nagini1

1Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
2Woods Hole Oceanographic Institution, Woods Hole, MA, USA
3National Cancer Institute, Bethesda, MD, USA
4Mitsui Norin Co., Ltd, Shizuoka, Japan

The objective of this study was to evaluate the chemopreventive potential of the black tea polyphenols Polyphenon-B and BTF-35 during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into six groups. Animals in groups 2 and 3 received diet containing Polyphenon-B and BTF-35, respectively, 4 weeks before carcinogen administration when they were 6 weeks of age and continued until the final exposure to carcinogen. At 10 weeks of age, animals in groups 1, 2, and 3 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 4 and 5 were given Polyphenon-B and BTF-35 alone, respectively, as in groups 2 and 3. Animals in group 6 served as control. All the animals were sacrificed after an experimental period of 18 weeks. Phase I and phase II xenobiotic-metabolizing enzymes and 8-hydroxy-deoxyguanosine (8-OHdG) in the buccal pouch and liver were used as biomarkers of chemoprevention. Hamsters painted with DMBA showed increased expression of 8-OH-dG and enhanced activities of phase I (CYP450; total as well as CYP1A1, 1A2, and 2B isoforms and cytochrome b5) and phase II (GST and quinone reductase) xenobiotic-metabolizing enzymes with increased immunohistochemical expression of CYP1A1, and CYP1B1 isoforms in the buccal pouch. This was accompanied by increased phase I and decreased phase II enzyme activities in the liver. Administration of Polyphenon-B and BTF-35 significantly decreased tumor incidence, oxidative DNA damage, phase I enzyme activities as well as expression of CYP1A1 and CYP1B1 isoforms, while enhancing phase II enzyme activities in the buccal pouch and liver. Our results provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. Furthermore, the greater efficacy of BTF-35 in chemoprevention of HBP carcinomas via inhibition of oxidative DNA damage and modulation of xenobiotic-metabolizing enzymes may have a major impact in human oral cancer prevention.

Key words: Black tea polyphenols; Chemoprevention; DMBA; Hamster buccal pouch carcinogenesis; Xenobiotic-metabolizing enzymes; 8-OH-dG

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 snlabau@gmail.com




Oncology Research, Vol. 17, pp. 87-91
0965-0407/08 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2008 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

CCR5-D32 Polymorphism and Susceptibility to Cervical Cancer: Association With Early Stage of Cervical Cancer

Hariom Singh,1 Rekha Sachan,2 Meenu Jain,1 and Balraj Mittal1

1Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India
2Department of Obstetrics and Gynecology, Chatarapati Sahuji Maharaj Medical University, Lucknow, India

Inflammation plays a major role in the pathogenesis of cervical cancer. Chemokines are involved in inflammation, cancer, and infectious diseases. Therefore, we evaluated the association of the chemokine receptor gene polymorphism CCR5 D32 with risk of cervical cancer. A total of 150 histopathologically confirmed patients with cervical cancer and 162 age and ethnically matched cervical cytology negative healthy controls were genotyped for CCR5 D32 polymorphisms using PCR. Association of CCR5 D32 genotypes with risk of cervical cancer, clinical stages, and tobacco exposure was analyzed using chi-square statistical tests. The frequency of the mutant allele CCR5 D32 was higher in patients with cervical carcinoma (2.3%) but there was no statistically significant difference (OR = 1.51; p = 0.685;). Association of CCR5 genotypes with clinical phenotypes showed significant risk with stage IB patients due to CCR5+/D32 genotype (OR = 4.43; p = 0.021). Furthermore, patients with CCR5+/D32 genotype and tobacco usage were at risk of cervical cancer (OR = 1.73, 95% CI = 0.27-1.28). In summary, CCR5 heterozygous genotype (+/D32) may significantly influence the early stage of cervical cancer development. However, the cervical cancer risk due to tobacco usage was not significantly modulated after interaction with CCR5+/D32 genotype.

Key words: Cervical cancer; Chemokine receptor; Genetic polymorphism; Genetic susceptibility

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