ognizant Communication Corporation

ONCOLOGY RESEARCH
Featuring PRECLINICAL AND CLINICAL CANCER THERAPEUTICS

ABSTRACTS
VOLUME 17, NUMBER 9

Oncology Research, Vol. 17, pp. 387-396
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Evaluation of Fluoren-NU as a Novel Antitumor Agent

Asama Mukherjee,1 Sushanta Dutta,1 Gousia Chashoo,2 Madhulika Bhagat,2 Ajit Kumar Saxena,2 and Utpal Sanyal1

1Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Kolkata 700026, India
2Pharmacology Division, Indian Institute of Integrative Medicine, Jammu-Tawi 180001, India

A new nitrososourea derivative, namely fluoren-NU, 3-[2-{3-(2-chloroethyl)-3-nitrosouriedo}ethyl]-spiro[5,9´-fluorenyl]imidazolidine-2,4-dione (compound 2e), was synthesized from 3-(2-bromoethyl)-spiro[5,9´-fluorenyl]imidazolidine-2,4-dione via a four-step synthetic procedure. Its chemical alkylating activity was assessed by coupling with 4-(4-nitrobenzyl)pyridine. In vitro screening in six human tumor cell lines, namely SK-N-SH CNS, IMR-32 neuroblastoma, A549 lung, DU-145 prostate, HL-60 leukemia, and U-937 lymphoma, revealed its significant cytotoxicity in SK-N-SH. Its in vivo antitumoral potency was assessed in murine ascites tumors Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice. Results revealed significant tumor regression effects in both of these tumors. Life span of mice bearing advanced tumor for 5 days before the drug challenge was also considerably increased. In vivo toxicological assay at its optimum dose of 40 mg/kg for days 1-7 treatment schedule was conducted sequentially on day 9, 14, and 19 in normal and EAC-bearing mice. Results revealed that it did not adversely affect hematopoiesis or exhibit drug-induced hepatotoxicity and nephrotoxicity. It has shown minimal cytotoxic effect on human peripheral blood mononuclear cells (PBMC) having a high IC50 value of 792 mM. Compared to Mitonafide and CCNU used as standards it also significantly inhibited DNA and RNA synthesis in EAC tumor cells in vitro at 8 mM concentration.

Key words: New nitrosourea; Antitumor agent; Tumor cells; Cytotoxicity; In vivo assay; Toxicological assay

Address correspondence to Dr. Utpal Sanyal, Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Kolkata 700026, India. Tel: +91-33-24765101, ext. 329; Fax: +91-33-24757606; E-mail: utpalsanyal@yahoo.co.in




Oncology Research, Vol. 17, pp. 397-402
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Prevalence of CYP1A1 and GST Polymorphisms in the Population of Northeastern India and Susceptibility of Oral Cancer

Sumana Chatterjee,1 Sila Chakrabarti,1 Bani Sengupta,1 Sandeep Poddar,1 Debolina Biswas,2 Sarthak Sengupta,2 and Geeta Talukder1

1Thalassaemia Research Unit, Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan, West Bengal, India
2Department of Anthropology, Dibrugarh University, Dibrugarh, Assam, India

Individual cancer susceptibility is the result of several host factors, including differences in lifestyle habits and genetic susceptibility. There is a correlation between CYP1A1 polymorphism (MspI) and oral cancer susceptibility. Individuals carrying the deletions of GSTM1 and GSTT1 are at high risk of developing oral cancers. In the present study on healthy tribal and nontribal individuals of Assam, we found that the genetic variation of GSST polymorphisms is evident (p = 0.20) with differential dose of toxic exposure. Prevalence of different polymorphic alleles of CYP1A1 also proves the same result. A mini-case-control study with very small sample size showed no marked increase in the risk of developing oral cancer as the frequencies of the studied GST genotypes did not show any statistical significance. But GSTT1-null genotypes were found to have higher risk of developing leukoplakia (OR 1.94, 95% CI 2.61-18.54). CYP1A1 genotype m2 allele was also not found to be associated with the risk of developing leukoplakias in the population.

Key words: Oral cancer; Gene polymorphism; Mutation; Population; Tobacco

Address correspondence to Sumana Chatterjee, Thalassaemia Research Unit, Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan, 99, Sarat Bose Road, Kolkata 700 026, West Bengal, India. Tle: 9103324753636; E-mail: chatterjeesumana@yahoo.com




Oncology Research, Vol. 17, pp. 405-411
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Vascular Endothelial Growth Factor C and Microvessel Density in Gastric Carcinoma: Correlation With Clinicopathological Factors. Our Experience and Review of the Literature

Paolo Aurello,1 Simone Rossi Del Monte,1 Francesco D'Angelo,1 Claudia Cicchini,1 Antonio Ciardi,2 Riccardo Bellagamba,1 Matteo Ravaioli,1 and Giovanni Ramacciato1

1Surgery Unit D, Second Faculty of Medicine, Sant'Andrea Hospital, University of Rome La Sapienza, Rome, Italy
2Department of Pathology, Second Faculty of Medicine, Sant'Andrea Hospital, University of Rome La Sapienza, Rome, Italy

Vascular endothelial growth factor (VEGF) has been reported to promote lymphangiogenesis and its overexpression may be related to lymph node metastasis in gastric carcinoma. Microvessel density (MVD) has been investigated as a promoting factor for angiogenesis with conflicting results about its relation to survival. The study aims to investigate the expression of one subtype of VEGF, vascular endothelial growth factor C (VEGF-C), and MVD in gastric carcinoma specimens and their relation with clinicopathological factors. Specimens from 72 patients who underwent gastric resection for gastric carcinoma were analyzed by immunohistochemistry for the VEGF-C study and by monoclonal antibodies for the study of MVD. The VEGFC and MVD expressions were related to clinicopathological features. High MVD was significantly related to the T stage (p = 0.036); VEGF-C expression was significantly higher in N positive patients (p = 0.047). No relation was found between MVD and VEGF-C expression. An extensive review of the literature was made and data were compared to ours. VEGF-C and MVD resulted to have significant relation with clinicopathological features. Further studies are required to determine whether these factors may be used in clinical practice in order to define the relationship with prognosis and to better characterize the biologic features of gastric carcinoma.

Key words: Gastric carcinoma; Vascular endothelial growth factor (VEGF); VEGF-C; Microvessel density (MVD)

Address correspondence to Paolo Aurello, c/o Ospedale Sant'Andrea, Chirurgia D, Via di Grottarossa 1035, 00189, Roma, Italy. Tel: +390633775693; Fax: +390633775322; E-mail: paolo_aurello@yahoo.it




Oncology Research, Vol. 17, pp. 413-423
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Transcriptional Activation of hTERT in Breast Carcinomas by the Her2-ER81-Related Pathway

Dimitra Vageli, Maria G. Ioannou, and George K. Koukoulis

Department of Pathology, University Hospital of Larissa, Medical School of Thessaly, Larissa, Greece

Her2 and ER81 (a member of ETS family) have been suggested to cause a synergistic increase in the transcriptional activation of hTERT. Our study aimed to offer further confirmation in clinical material. We determined the mRNA levels of Her2, ER81, and hTERT, by QRT-PCR, in 43 breast carcinomas. In the specimens showing hTERT transcriptional activation, Her2 and ER81 were increased in statistically significant tumor subgroups (61% and 79% correspondingly). The 86% of specimens with both Her2 and ER81 increased expression showed hTERT transcriptional activation. Synchronous transcriptional activation of hTERT, Her2, and ER81 elevated expression was noted in 42% of the samples. In conclusion, we agree with a previous study that Her2 overexpression may increase the hTERT transcriptional activation. Our data indicate that the mechanism may involve Her2-ER81 interaction(s) and that the activation of hTERT could be mainly mediated by transcriptional activation of ER81.

Key words: hTERT; Her2; ER81; Q-RT real-time PCR

Address correspondence to Dr. Dimitra Vageli, Molecular Histopathology Lab, Department of Pathology, University Hospital of Larissa, 41110, Larissa, Thessaly, Greece. E-mail: vagelidim@yahoo.gr or vagelidim@med.uth.gr




Oncology Research, Vol. 17, pp. 425-435
0965-0407/09 $90.00 + .00
E-ISSN 1555-3906
Copyright © 2009 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

In Vitro Expression and Redistribution of Nucleolar Proteins Following the Treatment With cis-Dichloro-1,2-propylenediamine-N,N,N´,N´-tetraacetato Ruthenium (III) (RAP)

Fatima Azzahra Delmani,1 José Torreblanca,1 Javier Moreno,1 Gregorio García-Herdugo,1 Rosario Vilaplana,2 and Francisco González-Víltchez2

1Departamento de Biología Celular, Facultad de Biología, Campus Reina Mercedes, Universidad de Sevilla, 41012 Sevilla, Spain
2Departamento de Química Inorgínica, Laboratorio de Qímica Bioinorgánica, Facultad de Química, Universidad de Sevilla, 41071 Sevilla, Spain

In this study, we used a newly synthesized antitumor complex [RuLCl2]H.4H2O (RAP), having the same antitumor effects as cisplatin but showing lower cytotoxicity. We found that RAP-DNA adducts induce a high expression of proteins with high molecular weight and a low expression of proteins with low molecular weight. We choose two proteins: the upstream binding factor (UBF), an RNA polymerase I-specific transcription factor that recognizes the ribosomal RNA gene promoter and initiates transcription; and fibrillarin, which is involved in many posttranscriptional processes including pre-rRNA processing, pre-rRNA methylation, and ribosome assembly. Our results showed that UBF was present in high quantities in TG cell extracts treated with RAP with a major abundance of UBF1 more than UBF2, which was explained by a high affinity of UBF1 for DNA modified by RAP than UBF2; while fibrillarin was present in low quantities in protein extracts treated with RAP. Also, following treatment with RAP, there was a similar redistribution of UBF along the nucleus of TG cells as in the controls but with the presence of higher quantities of this factor in the nucleoplasm, which could be explained by an increase of the UBF affinity for the no nucleolar chromatin as a consequence of the modifications induced by RAP. Fibrillarin was found in low quantities in the fibrillar centers and in the nucleoplasm after treatment with RAP.

Key words: Antitumor drugs; RAP; UBF; Fibrillarin; Whole protein extracts

Address correspondence to Dr. Fatima Azzahra Delmani, Departamento de Biología Celular, Facultad de Biología, Campus Reina Mercedes, Universidad de Sevilla, 41012 Sevilla, Spain. Tel: +962 795977540; E-mail: delmanisa@yahoo.com