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6. Site-specific topoisomerase I-mediated DNA cleavage induced by nogalamycin: a potential role of ligand-induced DNA bending at a distal site

Author

Sim, Sai-Peng, Pilch, Daniel S., and Liu, Leroy

Subjects
Cytochemistry -- Research, Binding sites (Biochemistry) -- Physiological aspects, DNA binding proteins -- Physiological aspects, Daunorubicin -- Physiological aspects, Enzymes -- Physiological aspects, DNA topoisomerase I -- Physiological aspects, DNA-ligand interactions -- Physiological aspects, Eukaryotic cells -- Physiological aspects, Biological sciences, Chemistry
Abstract

Nogalamycin was used as a model to study the mechanism of ligand-induced topoisomerase I-mediated DNA cleavage. The nogalamycin binding site responsible for topoisomerase I cleavage is upstream of the site of cleavage. When the site was replaced with the DNA bending sequence A(sub.5) stimulation of topoisomerase I-mediated DNA cleavage at the same site was seen in the absence of nogalamycin. A DNA bending sequence can substitute for the nogalamycin-DNA complex in stimulating topoisomerase I-mediated DNA cleavage.

Published
2000

7. Differential poisoning of topoisomerases by menogaril and nogalamycin dictated by the minor groove-binding nogalose sugar

Author

Sim, Sai-Peng, Gatto, Barbara, Yu, Chiang, Liu, Angela A., Li, Tsai-Kun, Pilch, Daniel S., LaVoie, Edmond J., and Liu, Leroy F.

Subjects
DNA topoisomerase I -- Analysis, DNA topoisomerase II -- Analysis, Daunorubicin -- Research, DNA-ligand interactions -- Research, Biological sciences, Chemistry
Abstract

A study was conducted on the effect of DNA binding on poisoning of human DNA TOP1 using a pair of related anthracyclines. The findings indicate that the nogalose sugar ring of nogalamycin plays a key role in affecting topoisomerase-specific poisoning. Menogaril was found to poison topoisomerase II but not topoisomerase I while nogalamycin poisons topoisomerase I but not topoisomerase II. Moreover, nogalamycin may act as a TOP1 cleavage stimulant by binding to a site distal to the site of cleavage.

Published
1997

14. High cell density and latent membrane protein 1 expression induce cleavage of the mixed lineage leukemia gene at 11q23 in nasopharyngeal carcinoma cell line

Author

Sim Sai-Peng and Yee Peter

Subjects
Medicine
Abstract

Abstract Background Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes. Methods In this study, cells were seeded at various densities to induce apoptosis. Genomic DNA extracted was processed for Southern hybridization. In order to investigate the role of EBV, especially the latent membrane protein 1 (LMP1), LMP1 gene was overexpressed in NPC cells and chromosome breaks were analyzed by inverse polymerase chain (IPCR) reaction. Results Southern analysis revealed that high cell density resulted in cleavage of the mixed lineage leukemia (MLL) gene within the breakpoint cluster region (bcr). This high cell density-induced cleavage was significantly reduced by caspase inhibitor, Z-DEVD-FMK. Similarly, IPCR analysis showed that LMP1 expression enhanced cleavage of the MLL bcr. Breakpoint analysis revealed that these breaks occurred within the matrix attachment region/scaffold attachment region (MAR/SAR). Conclusions Since MLL locates at 11q23, a common deletion site in NPC, our results suggest a possibility of stress- or virus-induced apoptosis in the initiation of chromosome rearrangements at 11q23. The breakpoint analysis results also support the role of chromatin structure in defining the site of chromosome rearrangement.

Published
2010
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24. Proceedings of the 7th Biannual International Symposium on Nasopharyngeal Carcinoma 2015

Author

Tan, IB, Chang, Ellen T., Chen, Chien-Jen, Hsu, Wan-Lun, Chien, Yin-Chu, Hildesheim, Allan, McKay, James D., Gaborieau, Valerie, Kaderi, Mohamed Arifin Bin, Purnomosari, Dewajani, Voegele, Catherine, LeCalvez-Kelm, Florence, Byrnes, Graham, Brennan, Paul, Devi, Beena, Li, L., Zhang, Y., Fan, Y., Sun, K., Du, Z., Sun, H., Chan, A. T., Tsao, S. W., Zeng, Y. X., Tao, Q., Busson, Pierre, Lhuillier, Claire, Morales, Olivier, Mrizak, Dhafer, Gelin, Aurore, Kapetanakis, Nikiforos, Delhem, Nadira, Mansouri, Sheila, Cao, Jennifer, Vaidya, Anup, Frappier, Lori, Wai, Lo Kwok, Chen, Sui-Hong, Du, Jin-lin, Ji, Ming-Fang, Huang, Qi-Hong, Liu, Qing, Cao, Su-Mei, Doolan, Denise L., Coghill, Anna, Mulvenna, Jason, Proietti, Carla, Lekieffre, Lea, Bethony, Jeffrey, Hildesheim, and Allan, Fles, Renske, Indrasari, Sagung Rai, Herdini, Camelia, Martini, Santi, Isfandiari, Atoillah, Rhomdoni, Achmad, Adham, Marlinda, Mayangsari, Ika, van Werkhoven, Erik, Wildeman, Maarten, Hariwiyanto, Bambang, Hermani, Bambang, Kentjono, Widodo Ario, Haryana, Sofia Mubarika, Schmidt, Marjanka, O’Sullivan, Brian, Ozyar, Enis, Lee, Anne W. M., Zeng, Mu-Sheng, Gao, Xiaojiang, Tang, Minzhong, Martin, Pat, Zeng, Yi, Carrington, Mary, Coghill, Anna E., Bu, Wei, Nguyen, Hanh, Yu, Kelly J., Lou, Pei-Jen, Wang, Cheng-Ping, Cohen, Jeffrey I., King, Ann D., Chen, Tseng-Cheng, Lin, Ching-Yuan, Tsou, Yung-An, Leu, Yi-Shing, Laio, Li-Jen, Chang, Yen-Liang, Hua, Chun-Hun, Wu, Ming-Shiang, Hsiao, Chu-Hsing Kate, Lee, Jehn-Chuan, Tsai, Ming-Hsui, Cheng, Skye Hung-Chun, Liao, Li-Jen, Yang, Tsung-Lin, Ko, Jenq-Yuh, Ko, Josephine Mun Yee, Dai, Wei, Kwong, Dora, Ng, Wai Tong, Lee, Anne, Ngan, Roger Kai Cheong, Yau, Chun Chung, Tung, Stewart, Lung, Maria Li, Ji, Mingfang, Sheng, Wei, Ng, Mun Hon, Cheng, Weimin, Yu, Xia, Wu, Biaohua, Wei, Kuangrong, Zhan, Jun, Zeng, Yi Xin, Cao, Su Mei, Xia, Ningshao, Yuan, Yong, Cui, Qian, Xu, Miao, Bei, Jin-Xin, Zeng, Yi-Xin, Şahin, B, Dizman, A, Esassolak, M, İkizler, A Saran, Yıldırım, HC, Çaloğlu, M, Atalar, B, Akman, F, Demiroz, C, Atasoy, BM, Canyilmaz, E, Igdem, S, Ugurluer, G, Kütük, T, Akmansoy, M, Ozyar, E, Sommat, Kiattisa, Wang, Fu Qiang, Kwok, Li-Lian, Tan, Terence, Fong, Kam Weng, Soong, Yoke Lim, Cheah, Shie Lee, Wee, Joseph, Casanova, M, Özyar, E, Patte, C, Orbach, D, Ferrari, A, Cristine, VF, Errihani, H, Pan, J, Zhang, L, Liji, S, Grzegorzewski, K, Gore, L, Varan, A, Hutajulu, Susanna Hilda, Khuzairi, Guntara, Kusumo, Henry, Hardianti, Mardiah Suci, Taroeno-Hariadi, Kartika Widayati, Purwanto, Ibnu, Kurnianda, Johan, Messick, Troy E., Malecka, Kimberly, Tolvinski, Lois, Soldan, Samantha, Deakyne, Julianna, Song, Hui, van den Heuvel, Antonio, Gu, Baiwei, Cassel, Joel, McDonnell, Mark, Smith, Garry R., Velvadapu, Venkata, Bian, Haiyan, Zhang, Yan, Carlsen, Marianne, Chen, Shuai, Donald, Alastair, Lemmen, Christian, Reitz, Allen B., Lieberman, Paul M., Chan, King Chi, Chan, Lai Sheung, Lo, Kwok Wai, Yip, Timothy Tak Chun, Kahn, Michael, Mak, Nai Ki, Liu, Fei-Fei, Khaali, Wafa, Thariat, Juliette, Fantin, Laurence, Spirito, Flavia, Khyatti, Meriem, Driss, El Khalil Ben, Olivero, Sylvain, Maryanski, Janet, Doglio, Alain, Xia, Mengxue, Xia, Yunfei, Chang, Hui, Shaw, Rachel, Rahaju, Pudji, Wisesa, Sindhu, Taroeno-Harijadi, Kartika Widayati, Dhamiyati, Wigati, Tan, Sang-Nee, Sim, Sai-Peng, Yusuf, Muhtarum, Romdhoni, Ahmad C., K, Widodo Ario, Rantam, Fedik Abdul, Sugiyanto, Aryati, Lina, Adi-Kusumo, Fajar, Bintoro, SY, Oktriani, R., Herawati, C., Surono, A., Haryana, Sofia M., Zhong, L., Ma, B. B., Kalra, M., Ngo, M., Perna, S., Leen, A., Lapteva, N., Rooney, C. M., Gottschalk, S., Mustikaningtyas, Elida, Herawati, Sri, Romdhoni, Achmad C., Xu, Yarui, Ge, Shengxiang, Li, Fugui, Ng, M. H., Tan, Louise SY, Wong, Benjamin, Lim, C. M., Rantam, Fedik A., Madani, Deasy Z., Akbar, Nur, Permana, Agung Dinasti, Fachiroh, Jajah, Hartati, Dwi, Rahayudjati, T. Baning, Darwis, Iswandi, Anwar, Khoirul, Dwidanarti, Sri Retna, Pramana, Dominicus Wendhy, Safitri, Diah Ari, Danarti, Sri Retna Dwi, Taroeno, Suryo A, Wijaya, I., Oehadian, A., Prasetya, D., Yu, Kelly J, Rahman, Sukri, Budiman, Bestari J., Novialdi, Rahmadona, Lestari, Dewi Yuri, Yin, C., Foussadier, A., Blein, E., Chen, C., Ammour, N. Bournet, Khiatti, M., Cao, S., Marzaini, Dewi Syafriyetti Soeis, Rahayujati, Baning, Gunawan, L., Mubarika Haryana, S., Hartono, Michael, Intansari, Umi, Paramita, Dewi Kartikawati, Akbar, Akmal, Hermawan, Benny, Paramita, Dewi K., Argy, Gabriella, Sihotang, Theodora Caroline, Wahyono, Daniel Joko, Soeharso, Purnomo, Suryandari, Dwi Anita, Lisnawati, Musa, Zanil, Daker, Maelinda, Tzen, Yeo Jiun, Bakar, Norhasimah, Rahman, Asma’ Saiyidatina Aishah Abdul, Ahmad, Munirah, Chia, Yeo Tiong, Beng, Alan Khoo Soo, Sasikirana, Widyandani, Wardana, Tirta, Radifar, Muhammad, Herawati, Cita, Surono, Agus, and Çocuk Sağlığı ve Hastalıkları

Subjects
Meeting Abstracts
Abstract

A1 Hope and despair in the current treatment of nasopharyngeal cancer, IB Tan, I1 NPC international incidence and risk factors, Ellen T Chang, I2 Familial nasopharyngeal carcinoma and the use of biomarkers, Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien, I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings, Allan Hildesheim, I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia, James D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena Devi, I6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylation, Li L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao Q, I7 Tumor exosomes and translational research in NPC, Pierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira Delhem, I8 Host manipulations of the Epstein-Barr virus EBNA1 protein, Sheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori Frappier, I9 Somatic genetic changes in EBV-associated nasopharyngeal carcinoma, Lo Kwok Wai, I10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern China, Sui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei Cao, I11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disorders, Denise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan Hildesheim, I12 The nasopharyngeal carcinoma awareness program in Indonesia, Renske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB Tan, I13 Current advances and future direction in nasopharyngeal cancer management, Brian O’Sullivan, I14 Management of juvenile nasopharyngeal cancer, Enis Ozyar, I15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapy, Anne WM Lee, I16 The predictive/prognostic biomarker for nasopharyngeal carcinoma, Mu-Sheng Zeng, I17 Effect of HLA and KIR polymorphism on NPC risk, Xiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary Carrington, I18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal Carcinoma, Anna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I Cohen, I19 Advances in MR imaging in NPC, Ann D King, O1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Yin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, O2 Familial tendency and environmental co-factors of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Kelly J Yu, Yin-Chu Chien, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang, Tsung-Lin Yang, Chun-Hun Hua, Ming-ShiangWu, Chu-Hsing Kate Hsiao, Jehn-ChuanLee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Jenq-Yuh Ko, Allan Hildesheim, Chien-Jen Chen, O3 The genetic susceptibility and prognostic role of TERT-CLPTM1L and genes in DNA damage pathways in NPC, Josephine Mun Yee Ko, Wei Dai, Dora Kwong, Wai Tong Ng, Anne Lee, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Maria Li Lung, O4 Long term effects of NPC screening, Mingfang Ji, Wei Sheng, Mun Hon Ng, Weimin Cheng, Xia Yu, Biaohua Wu, Kuangrong Wei, Jun Zhan, Yi Xin Zeng, Su Mei Cao, Ningshao Xia, Yong Yuan, O5 Risk prediction of nasopharyngeal carcinoma by detecting host genetic and Epstein-Barr virus variation in saliva, Qian Cui, Miao Xu, Jin-Xin Bei, Yi-Xin Zeng, O6 Patterns of care study in Turkish nasopharyngeal cancer patients (NAZOTURK): A Turkish Radiation Oncology Association Head and Neck Cancer Working Group Study, B Şahin, A Dizman, M Esassolak, A Saran İkizler, HC Yıldırım, M Çaloğlu, B Atalar, F Akman, C Demiroz, BM Atasoy, E Canyilmaz, S Igdem, G Ugurluer, T Kütük, M Akmansoy, E Ozyar, O7 Long term outcome of intensity modulated radiotherapy in nasopharyngeal carcinoma in National Cancer Centre Singapore, Kiattisa Sommat, Fu Qiang Wang, Li-Lian Kwok, Terence Tan, Kam Weng Fong, Yoke Lim Soong, Shie Lee Cheah, Joseph Wee, O8 International phase II randomized study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents, M Casanova, E Özyar, C Patte, D Orbach, A Ferrari, VF Cristine, H Errihani, J Pan, L Zhang, S Liji, K Grzegorzewski, L Gore, A Varan, O9 Prognostic impact of metastatic status in patients with nasopharyngeal carcinoma, Susanna Hilda Hutajulu, Guntara Khuzairi, Camelia Herdini, Henry Kusumo, Mardiah Suci Hardianti, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Johan Kurnianda, O10 Development of small molecule inhibitors of latent Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma, Troy E. Messick, Kimberly Malecka, Lois Tolvinski, Samantha Soldan, Julianna Deakyne, Hui Song, Antonio van den Heuvel, Baiwei Gu, Joel Cassel, Mark McDonnell, Garry R Smith, Venkata Velvadapu, Haiyan Bian, Yan Zhang, Marianne Carlsen, Shuai Chen, Alastair Donald, Christian Lemmen, Allen B Reitz, Paul M Lieberman, O11 Therapeutic targeting of cancer stem-like cells using a Wnt modulator, ICG-001, enhances the treatment outcome of EBV-positive nasopharyngeal carcinoma, King Chi Chan, Lai Sheung Chan, Kwok Wai Lo, Timothy Tak Chun Yip, Roger Kai Cheong Ngan, Michael Kahn, Maria Li Lung, Nai Ki Mak, O12 Role of micro-RNA in NPC biology, Fei-Fei Liu, O13 Expansion of EBNA1- and LMP2-specific effector T lymphocytes from patients with nasopharyngeal carcinoma without enhancement of regulatory T cells, Wafa Khaali; Juliette Thariat; Laurence Fantin; Flavia Spirito; Meriem Khyatti; El Khalil Ben Driss; Sylvain Olivero; Janet Maryanski; Alain Doglio, O14 The experience of patients’ life after amifostine radiotherapy treatment (ART) for nasopharyngeal carcinoma (NPC), Mengxue Xia, Yunfei Xia, Hui Chang, Rachel Shaw, O15 Analysis of mitochondrial DNA mutation in latent membrane protein-1 positive nasopharyngeal carcinoma, Pudji Rahaju, O16 Factors influencing treatment adherence of nasopharyngeal cancer and the clinical outcomes: a hospital-based study, Mardiah Suci Hardianti, Sindhu Wisesa, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, O17 Chromosomal breaks mediated by bile acid-induced apoptosis in nasopharyngeal epithelial cells: in relation to matrix association region/scaffold attachment region, Sang-Nee Tan, Sai-Peng Sim, O18 Expression of p53 (wild type) on nasopharyngeal carcinoma stem cell that resistant to radiotherapy, Muhtarum Yusuf, Ahmad C Romdhoni, Widodo Ario K, Fedik Abdul Rantam, O19 Mathematical model of nasopharyngeal carcinoma in cellular level, Sugiyanto, Lina Aryati, Fajar Adi-Kusumo, Mardiah Suci Hardianti, O20 Differential expression of microRNA-21 on nasopharyngeal carcinoma plasma patient, SY Bintoro, R Oktriani, C. Herawati, A Surono, Sofia M. Haryana, O21 Therapeutic targeting of an oncogenic fibroblast growth factor-FGF19, which promotes proliferation and induces EMT of carcinoma cells through activating ERK and AKT signaling, L. Zhong, L. Li, B. B. Ma, A. T. Chan, Q. Tao, O22 Resist nasopharyngeal carcinoma (NPC): next generation T cells for the adoptive immunotherapy of NPC, M. Kalra, M. Ngo, S. Perna, A. Leen, N. Lapteva, C. M. Rooney, S. Gottschalk, O23 The correlation of heat shock protein 70 expressions and staging of nasopharyngeal carcinoma, Elida Mustikaningtyas, Sri Herawati, Achmad C Romdhoni, O24 Epstein-Barr virus serological profiles of nasopharyngeal carcinoma - A tribute to Werner Henle, Mingfang Ji, YaruiXu, Weimin Cheng, ShengxiangGe, Fugui Li, M. H. Ng, O25 Targeting the apoptosis pathway using combination TLR3 agonist with anti-survivin molecule (YM-155) in nasopharyngeal carcinoma, Louise SY Tan, Benjamin Wong, CM Lim, O26 The resistance mechanism of nasopharyngeal cancer stem cells to cisplatin through expression of CD44, Hsp70, p53 (wild type), Oct-4, and ß-catenin encoded-genes, Achmad C Romdhoni, Fedik A. Rantam, Widodo Ario Kentjono, P1 Prevalence of nasopharyngeal carcinoma patients at Departement of Otorhinolaringology-Head and Neck Surgery, Dr. Hasan Sadikin general hospital, Bandung, Indonesia in 2010-2014, Deasy Z Madani, Nur Akbar, Agung Dinasti Permana, P2 Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito Hospital, Yogyakarta, Camelia Herdini, Sagung Rai Indrasari, Jajah Fachiroh, Dwi Hartati, T. Baning Rahayudjati, P3 Report on loco regionally advanced nasopharyngeal cancer patients treated with induction chemotherapy followed by concurrent chemo-radiation therapy, Iswandi Darwis, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P4 Sex and age differences in the survival of patients with nasopharyngeal carcinoma, Sindhu Wisesa, Mardiah Suci Hardianti, Susanna Hilda Hutajulu, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Camelia Herdini, Wigati Dhamiyati, Johan Kurnianda, P5 Impact of delayed diagnosis and delayed therapy in the treatment outcome of patients with nasopharyngeal carcinoma, Khoirul Anwar, Susanna Hilda Hutajulu, Sagung Rai Indrasari, Sri Retna Dwidanarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P6 Anaysis of pretreatment anemia in nasopharyngeal cancer patients undergoing neoadjuvant therapy, Dominicus Wendhy Pramana, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P7 Results of treatment with neoadjuvant cisplatin-5FU in locally advanced nasopharyngeal carcinoma: a local experience, Diah Ari Safitri, Susanna Hilda Hutajulu, Camelia Herdini, Sri Retna Dwi Danarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P8 Geriatrics with nasopharyngeal cancer, Suryo A Taroeno, Sindhu Wisesa, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, P9 Correlation of lymphocyte to monocyte and neutrophil to lymphocyte ratio to the response of cisplatin chemoradiotheraphy in locally advance nasopharyngeal carcinoma, I. Wijaya, A. Oehadian, D. Prasetya, P10 Prediction of nasopharyngeal carcinoma risk by Epstein-Barr virus seromarkers and environmental co-factors: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Yin-Chu Chien, Kelly J Yu, Cheng-Ping Wang, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang191,192, Jenq-Yuh Ko, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, P11 Non-viral risk factors for nasopharyngeal carcinoma in West Sumatra, Indonesia, Sukri Rahman, Bestari J. Budiman, Novialdi, Rahmadona, Dewi Yuri Lestari, P12 New prototype Vidas EBV IgA quick: performance on Chinese and Moroccan populations, C. Yin, A. Foussadier, E. Blein, C. Chen, N. Bournet Ammour, M. Khiatti, S. Cao, P13 The expression of EBV-LMP1 and VEGF as predictors and plasma EBV-DNA levels as early marker of distant metastasis after therapy in nasopharyngeal cancer, Dewi Syafriyetti Soeis Marzaini, P14 Characteristics and factors influencing subjects refusal for blood samples retrieval: lesson from NPC case control study in Yogyakarta – Indonesia, Dwi Hartati, Baning Rahayujati, Camelia Herdini, Jajah Fachiroh, P15 Expression of microRNA BART-7-3p and mRNA PTEN on blood plasma of patients with nasopharyngeal carcinoma, L. Gunawan, S. Mubarika Haryana, A. Surono, C. Herawati, P16 IgA response to native early antigen (IgA-EAext) of Epstein-Barr virus (EBV) in healthy population and nasopharyngeal carcinoma (NPC) patients: the potential for diagnosis and screening tools, Michael Hartono, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P17 IgA responses against Epstein-Barr Virus Early Antigen (EBV-EA) peptides as potential candidates of nasopharyngeal carcinoma detection marker, Akmal Akbar, Jajah Fachiroh, Dewi Kartikawati Paramita, P18 Association between smoking habit and IgA-EBV titer among healthy individuals in Yogyakarta, Indonesia, Benny Hermawan, T Baning Rahayudjati, Dewi K Paramita, Jajah Fachiroh, P19 Epstein-Barr virus IgA titer comparison of healthy non-family individuals and healthy first degree family of NPV patients, Gabriella Argy, Jajah Fachiroh, Dewi Kartikawati Paramita, Susanna Hilda Hutajulu, P20 Identification of EBV Early Antigen (EA) derived peptides for NPC diagnosis, Theodora Caroline Sihotang, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P21 Host-pathogen study: relative expression of mRNA BRLF1 Epstein-Barr virus as a potential biomarker for tumor progressivity and polymorphisms of TCRBC and TCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma, Daniel Joko Wahyono, Purnomo Soeharso, Dwi Anita Suryandari, Lisnawati, Zanil Musa, Bambang Hermani, P22 In vitro efficacy of silvestrol and episilvestrol, isolated from Borneo, on nasopharyngeal carcinoma, a major cancer in Borneo, Maelinda Daker, Yeo Jiun Tzen, Norhasimah Bakar, Asma’ Saiyidatina Aishah Abdul Rahman, Munirah Ahmad, Yeo Tiong Chia, Alan Khoo Soo Beng, P23 The expression of mir-141 in patients with nasopharyngeal cancer, Widyandani Sasikirana, Tirta Wardana, Muhammad Radifar, Cita Herawati, Agus Surono, Sofia Mubarika Haryana

Published
2016

27. Oxidative stress-induced chromosome breaks within the ABLgene: a model for chromosome rearrangement in nasopharyngeal carcinoma

Author

Tan, Sang-Nee, Sim, Sai-Peng, and Khoo, Alan Soo-Beng

Abstract

The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. During apoptosis, chromatin cleavage and DNA fragmentation occur. However, cells may undergo DNA repair and survive apoptosis. Non-homologous end joining (NHEJ) pathway has been known as the primary DNA repair system in human cells. The NHEJ process may repair DNA ends without any homology, although region of microhomology (a few nucleotides) is usually utilised by this DNA repair system. Cells that evade apoptosis via erroneous DNA repair may carry chromosomal aberration. Apoptotic nuclease was found to be associated with nuclear matrix during apoptosis. Matrix association region/scaffold attachment region (MAR/SAR) is the binding site of the chromosomal DNA loop structure to the nuclear matrix. When apoptotic nuclease is associated with nuclear matrix during apoptosis, it potentially cleaves at MAR/SAR. Cells that survive apoptosis via compromised DNA repair may carry chromosome rearrangement contributing to NPC tumourigenesis. The Abelson murine leukaemia (ABL)gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This study aimed to identify the chromosome breakages and/or rearrangements in the ABLgene in cells undergoing oxidative stress-induced apoptosis. In the present study, in silico prediction of MAR/SAR was performed in the ABLgene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABLBCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ. Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed.

Published
2018
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35. Oxidative stress-induced chromosome breaks within the <italic>ABL</italic> gene: a model for chromosome rearrangement in nasopharyngeal carcinoma.

Author

Tan, Sang-Nee, Sim, Sai-Peng, and Khoo, Alan Soo-Beng

Abstract

Background: The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. During apoptosis, chromatin cleavage and DNA fragmentation occur. However, cells may undergo DNA repair and survive apoptosis. Non-homologous end joining (NHEJ) pathway has been known as the primary DNA repair system in human cells. The NHEJ process may repair DNA ends without any homology, although region of microhomology (a few nucleotides) is usually utilised by this DNA repair system. Cells that evade apoptosis via erroneous DNA repair may carry chromosomal aberration. Apoptotic nuclease was found to be associated with nuclear matrix during apoptosis. Matrix association region/scaffold attachment region (MAR/SAR) is the binding site of the chromosomal DNA loop structure to the nuclear matrix. When apoptotic nuclease is associated with nuclear matrix during apoptosis, it potentially cleaves at MAR/SAR. Cells that survive apoptosis via compromised DNA repair may carry chromosome rearrangement contributing to NPC tumourigenesis. The Abelson murine leukaemia (ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress-induced apoptosis. Results: In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ. Conclusions: Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed. [ABSTRACT FROM AUTHOR]

Published
2018
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