LIFE09200604007 Tabish - Homi Bhabha National Institute

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Synopsis Publications: 1. Hussain T, Kotnis A, Sarin R and Mulherkar R. Establishment and characterization of lymphoblastoid cell lines from patients with Multiple Primary Neoplasms in the upper aero-digestive tract and healthy individuals. Indian J Med Res. 2012 Jun; 135(6):820-9. 2. Budrukkar A, Shahid T, Murthy V, Hussain T, Mulherkar R, Vundinti BR, Deshpande M, Sengar M, Laskar SG and Agarwal JP. Squamous cell carcinoma of base of tongue in a patient with Fanconi's anemia treated with radiation therapy: case report and review of literature. Head & Neck, 2010 Oct; 32(10):1422-7. 3. Hussain T and Mulherkar R. Lymphoblastoid cell lines: a continuous in-vitro source to study carcinogen sensitivity and DNA repair. (Review article; International Journal of Cellular and Molecular Medicine, in press). 4. Hussain T, Kotnis A, Sarin R and Mulherkar R. Genetic Susceptibility to Multiple Primary Neoplasms in the Upper Aero-Digestive Tract: Genotype Score and Phenotype Correlation. (communicated to Cancer letters) Poster/oral Presentations: 1. 2008: 13 th Human Genome Meeting “Genomics and the future of medicine”, India (poster presentation). 2. 2010: 29 th Annual Convention of Indian Association for Cancer Research, India (oral presentation). 3. 2010: 6 th Graduate Students Meet, ACTREC, Navi Mumbai, India (Award for best poster presentation). 4. 2011: 30 th Annual Convention of Indian Association for Cancer Research and International Symposium on “Signaling Network and Cancer”, CSIR-IICB, Kolkata India (Award for best poster presentation). 5. 2011: American Association of Cancer Research (AACR) international conference on “New Horizons in Cancer Research: Biology to prevention to Therapy” (poster presentation). 19
Synopsis References: 1. Bobba, R.; Khan, Y., Cancer in India – An Overview. GOR 2003, 5, (4), 93-96. 2. Cancer Incidence, Mortality and Prevalence Worldwide in 2008. GLOBOCAN 2008. 3. Fujita, M.; Rudoltz, M. S.; Canady, D. J.; Patel, P.; Machtay, M.; Pittard, M.Q.; Mohiuddin, M.; Regine, W.F., (1998) Second malignant neoplasia in patients with T1 glottic cancer treated with radiation. Laryngoscope 1998, 108, (11), 1853-55. 4. Khuri, F. R.; Kim, E. S.; Lee, J. J.; Winn, R. J.; Benner, S. E.; Lippman, S. M.; Fu, K. K.; Cooper, J. S.; Vokes, E. E.; Chamberlain, R. M.; Williams, B.; Pajak, T. F.; Goepfert, H.; Hong, W. K., The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 2001, 10, (8), 823-9. 5. Jhavar, S.; Sarin, R.; Mulherkar, R.; Benner, A.; Agarwal, J. P.; Dinshaw, K., Glutathione S transferase M1 or T1 null genotype as a risk factor for developing multiple primary neoplasms in the upper aerodigestive tract, in Indian males using tobacco. Oral Oncol 2004, 40, (1), 84-91. 6. Rydzanicz, M.; Wierzbicka, M.; Gajecka, M.; Szyfter, W.; Szyfter, K., The impact of genetic factors on the incidence of multiple primary tumors (MPT) of the head and neck. Cancer Lett 2005, 224, (2), 263- 78. 7. Kotnis, A.; Namkung, J.; Kannan, S.; Jayakrupakar, N.; Park, T.; Sarin, R.; Mulherkar, R., Multiple pathway-based genetic variations associated with tobacco related multiple primary neoplasms. PLoS One 2012, 7, (1), e30013. 8. Kotnis, A.; Kannan, S.; Sarin, R.; Mulherkar, R., Case-control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk. Br J Cancer 2008, 99, (8), 1340-7. 9. Sie, L.; Loong, S.; Tan, E. K., Utility of lymphoblastoid cell lines. J Neurosci Res 2009, 87, (9), 1953-9. 10. Weinert, T.; Lydall, D., Cell cycle checkpoints, genetic instability and cancer. Semin Cancer Biol 1993, 4, (2), 129-40. 11. Zhao, H.; Spitz, M. R.; Tomlinson, G. E.; Zhang, H.; Minna, J. D.; Wu, X., Gamma-radiation-induced G2 delay, apoptosis, and p53 response as potential susceptibility markers for lung cancer. Cancer Res 2001, 61, (21), 7819-24. 12. Mah, L. J.; El-Osta, A.; Karagiannis, T. C., gammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 2010, 24, (4), 679-86. 13. Wang L.E.; Hu, Z.; Sturgis, E. M.; Spitz, M.R.; Strom, S. S.; Amos, C. I.; Guo, Z.; Qiao, Y; Gillenwater, A. M.; Myers, J. N.; Clayman, g. L.; Weber, R. S.; El-Naggar, a. K.; Mao, L.; Lippman, S.; Hong W. K.; Wei, Q., Reduced DNA repair capacity for removing tobacco carcinogen-induced DNA adducts contributes to risk of head and neck cancer but not tumour characteristics. Clin Cancer Res. 2010, 16, (7) 764-74. 14. Wang, L. E.; Cheng, L.; Spitz, M. R.; Wei, Q., Fas A670G polymorphism, apoptotic capacity in lymphocyte cultures, and risk of lung cancer. Lung Cancer 2003, 42, (1), 1-8. 15. Hong, W. K.; Lippman, S. M.; Itri, L. M.; Karp, D. D.; Lee, J. S.; Byers, R. M.; Schantz, S. P.; Kramer, A. M.; Lotan, R.; Peters, L. J.; et al., Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 1990, 323, (12), 795-801. 16. Lin, J.; Swan, G. E.; Shields, P. G.; Benowitz, N. L.; Gu, J.; Amos, C. I.; de Andrade, M.; Spitz, M. R.; Wu, X., Mutagen sensitivity and genetic variants in nucleotide excision repair pathway: genotypephenotype correlation. Cancer Epidemiol Biomarkers Prev 2007, 16, (10), 2065-71. 17. Kaufmann, W. K.; Paules, R. S., DNA damage and cell cycle checkpoints. FASEB J 1996, 10, (2), 238- 47. 18. Wu, X.; Zhao, H.; Amos, C. I.; Shete, S.; Makan, N.; Hong, W. K.; Kadlubar, F. F.; Spitz, M. R., p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and Ethnicity. J Natl Cancer Inst 2002, 94, (9), 681-90. 20
Page 1: Genotype-Molecular Phenotype Correl
Page 7 and 8: CONTENTS Page No Synopsis 1 List of
Page 9 and 10: Synopsis
Page 11 and 12: Synopsis Genotype-Molecular Phenoty
Page 13 and 14: Synopsis Materials and Methods: 1.
Page 15 and 16: Synopsis loading control. PCR produ
Page 17 and 18: Synopsis 7.1 Percent cell death aft
Page 19 and 20: Synopsis slides were then dried and
Page 21 and 22: Synopsis range 41.77% - 90.95% at 5
Page 23 and 24: Synopsis 5. Genotyping of genes: Ge
Page 25 and 26: Synopsis G2/M arrest and delaying e
Page 27: Synopsis may have an important bear
Page 31 and 32: Abbreviations MOPS : 3-(N-morpholin
Page 33 and 34: List of Figures Fig. 28: Percent re
Page 35 and 36: Chapter 1 Introduction
Page 37 and 38: Introduction In previous studies fr
Page 39 and 40: Introduction important carcinogenes
Page 41 and 42: Review of Literature The yet undeci
Page 43 and 44: Review of Literature Fig. 2: Incide
Page 45 and 46: Review of Literature sustained angi
Page 47 and 48: Review of Literature 2.6 Genotype p
Page 49 and 50: Review of Literature 2.7.2 Biologic
Page 51 and 52: Review of Literature Table 1: Steps
Page 53 and 54: Review of Literature future analysi
Page 55 and 56: Review of Literature Inefficient ce
Page 57 and 58: Review of Literature XRCC1 (X-ray r
Page 59 and 60: Review of Literature 2.9.2 Gene inv
Page 61 and 62: Review of Literature MPO gene polym
Page 63 and 64: Review of Literature important role
Page 65 and 66: Materials and Methods Source of che
Page 67 and 68: Materials and Methods Method: EBV-t
Page 69 and 70: Materials and Methods Immunophenoty
Page 71 and 72: Materials and Methods with 500 μl
Page 73 and 74: Materials and Methods cDNA it can b
Page 75 and 76: Materials and Methods Cobalt-60 iso
Page 77 and 78: Materials and Methods specific bind
Page 79 and 80:
Materials and Methods h half of the
Page 81 and 82:
Materials and Methods phenol and th
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Materials and Methods 7. Filter ste
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Materials and Methods viz. EXO-SAP
Page 88 and 89:
Materials and Methods Table 2: List
Page 90 and 91:
Materials and Methods SMAD6 AREG HM
Page 92 and 93:
Materials and Methods 3.9 Effect of
Page 94 and 95:
Materials and Methods fresh eppendo
Page 96 and 97:
Materials and Methods Power SYBR Gr
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Results Objective 1 To generate EBV
Page 100 and 101:
Results Fig. 8: Frequency of second
Page 102 and 103:
Results Table 6: Demographics of he
Page 104 and 105:
Results Fig. 10: Cell population do
Page 106 and 107:
Results Fig. 12: Cell surface marke
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Results 4.1.5 Expression of ATM gen
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Results Objective 2 To compare the
Page 112 and 113:
Results Fig. 17: Standardization of
Page 114 and 115:
Results Fig. 19: Standardisation of
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Results The cells were incubated fu
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Results 4.2.3.1 Percent G2 delay af
Page 120 and 121:
Results 4.2.3.2 Effect of BPDE expo
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Results Fig. 29: Comparison of perc
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Results Fig. 31: Percent cell death
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Results normalization with baseline
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Results 4.2.5.2 Real time PCR valid
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Results homozygous wild-type, heter
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Results Fig. 36b: Electrophoresis o
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Results Fig. 37a: Representative el
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Results Table 13: Consolidated geno
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Results LCL Genes NAT2(1) NAT2(2) N
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Results Fig. 38: Distribution of Ge
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Results Fig. 39: Various combinatio
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Results Table 14: Genotype-phenotyp
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Discussion Introduction Squamous ce
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Discussion stimulated lymphocytes w
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Discussion H2AX is currently the mo
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Discussion or G2/M phase arrest. As
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Discussion differential expression
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Discussion DNA repair genes and MPN
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Chapter 6 Summary and Conclusions
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Summary and Conclusions Statistical
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Bibliography 1. Dikshit, R.; Gupta,
Page 164 and 165:
Bibliography 43. Lei, D.; Sturgis,
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Bibliography 76. Fry, R. C.; Svenss
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Bibliography 115. Kote-Jarai, Z.; M
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Bibliography 149. Hashibe, M.; Bren
Page 172 and 173:
Bibliography 183. Bergamaschi, D.;
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Bibliography 216. Bondy, M. L.; Wan
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Indian J Med Res 135, June 2012, pp
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822 INDIAN J MED RES, JUNE 2012 mar
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824 INDIAN J MED RES, JUNE 2012 (h)
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826 INDIAN J MED RES, JUNE 2012 Tab
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828 INDIAN J MED RES, JUNE 2012 lik
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CASE REPORT Eben L. Rosenthal, MD,
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FIGURE 2. Chromosomal breakage anal
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FA along with ataxia telangiectasia
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