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241 results on '"Reinhard, Christoph"'

1. Mutational landscape of gastric adenocarcinoma in Chinese: Implications for prognosis and therapy

Author

Chen, Kexin, Yang, Da, Li, Xiangchun, Sun, Baocun, Song, Fengju, Cao, Wenfeng, Brat, Daniel J, Gao, Zhibo, Li, Haixin, Liang, Han, Zhao, Yanrui, Zheng, Hong, Li, Miao, Buckner, Jan, Patterson, Scott D, Ye, Xiang, Reinhard, Christoph, Bhathena, Anahita, Joshi, Deepa, Mischel, Paul S, Croce, Carlo M, Wang, Yi Michael, Raghavakaimal, Sreekumar, Li, Hui, Lu, Xin, Pan, Yang, Chang, Han, Ba, Sujuan, Luo, Longhai, Cavenee, Webster K, Zhang, Wei, and Hao, Xishan

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Biotechnology, Cancer, Breast Cancer, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adenocarcinoma, Age Factors, Asian People, Case-Control Studies, China, DNA Mutational Analysis, Databases, Nucleic Acid, Disease-Free Survival, Female, Genome-Wide Association Study, Homologous Recombination, Humans, Male, Mutation, Neoplasm Proteins, Stomach Neoplasms, Survival Rate, clonality, exome sequencing, mutation, ERBB, BRCA2
Abstract

Gastric cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with three primary tumors and two matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC). The HiC subtype of intratumoral heterogeneity was associated with older age, TP53 (tumor protein P53) mutation, enriched C > G transition, and significantly shorter survival, whereas the LoC subtype was associated with younger age, ARID1A (AT rich interactive domain 1A) mutation, and significantly longer survival. Phylogenetic tree analysis of whole-genome sequencing data from multiple samples of two patients supported the clonal evolution of GC metastasis and revealed the accumulation of genetic defects that necessitate combination therapeutics. The most recurrently mutated genes, which were validated in a separate cohort of 216 cases by targeted sequencing, were members of the homologous recombination DNA repair, Wnt, and PI3K-ERBB pathways. Notably, the drugable NRG1 (neuregulin-1) and ERBB4 (V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 4) ligand-receptor pair were mutated in 10% of GC cases. Mutations of the BRCA2 (breast cancer 2, early onset) gene, found in 8% of our cohort and validated in The Cancer Genome Atlas GC cohort, were associated with significantly longer survivals. These data define distinct clinicogenetic forms of GC in the Chinese population that are characterized by specific mutation sets that can be investigated for efficacy of single and combination therapies.

Published
2015

3. Influence of eukaryotic translation initiation factor 6 on non–small cell lung cancer development and progression

Author

Gantenbein, Nadine, Bernhart, Eva, Anders, Ines, Golob-Schwarzl, Nicole, Krassnig, Stefanie, Wodlej, Christina, Brcic, Luka, Lindenmann, Joerg, Fink-Neuboeck, Nicole, Gollowitsch, Franz, Stacher-Priehse, Elvira, Asslaber, Martin, Gogg-Kamerer, Margit, Rolff, Jana, Hoffmann, Jens, Silvestri, Alessandra, Regenbrecht, Christian, Reinhard, Christoph, Pehserl, Anna-Maria, Pichler, Martin, Sokolova, Olga, Naumann, Michael, Mitterer, Valentin, Pertschy, Brigitte, Bergler, Helmut, Popper, Helmut, Sattler, Wolfgang, and Haybaeck, Johannes

Published
2018
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4. Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma

Author

Peille, Anne-Lise, Vuaroqueaux, Vincent, Wong, Swee-Seong, Ting, Jason, Klingner, Kerstin, Zeitouni, Bruno, Landesfeind, Manuel, Kim, Woo Ho, Lee, Hyuk-Joon, Kong, Seong-Ho, Wulur, Isabella, Bray, Steven, Bronsert, Peter, Zanella, Nina, Donoho, Greg, Yang, Han-Kwang, Fiebig, Heinz-Herbert, Reinhard, Christoph, and Aggarwal, Amit

Published
2020
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5. Author Correction: Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma

Author

Peille, Anne-Lise, Vuaroqueaux, Vincent, Wong, Swee-Seong, Ting, Jason, Klingner, Kerstin, Zeitouni, Bruno, Landesfeind, Manuel, Kim, Woo Ho, Lee, Hyuk-Joon, Kong, Seong-Ho, Wulur, Isabella, Bray, Steven, Bronsert, Peter, Zanella, Nina, Donoho, Greg, Yang, Han-Kwang, Fiebig, Heinz-Herbert, Reinhard, Christoph, and Aggarwal, Amit

Published
2020
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6. A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Author

Kendzia, Sandra, primary, Franke, Susanne, additional, Kröhler, Tarek, additional, Golob-Schwarzl, Nicole, additional, Schweiger, Caroline, additional, Toeglhofer, Anna M., additional, Skofler, Christina, additional, Uranitsch, Stefan, additional, El-Heliebi, Amin, additional, Fuchs, Julia, additional, Punschart, Andreas, additional, Stiegler, Philipp, additional, Keil, Marlen, additional, Hoffmann, Jens, additional, Henderson, David, additional, Lehrach, Hans, additional, Yaspo, Marie-Laure, additional, Reinhard, Christoph, additional, Schäfer, Reinhold, additional, Keilholz, Ulrich, additional, Regenbrecht, Christian, additional, Schicho, Rudolf, additional, Fickert, Peter, additional, Lax, Sigurd F., additional, Erdmann, Frank, additional, Schulz, Marcel H., additional, Kiemer, Alexandra K., additional, Haybaeck, Johannes, additional, and Kessler, Sonja M., additional

Published
2023
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8. Molecular dissection of CRC primary tumors and their matched liver metastases reveals critical role of immune microenvironment, EMT and angiogenesis in cancer metastasis

Author

Liu, Jiangang, Cho, Yong Beom, Hong, Hye Kyung, Wu, Song, Ebert, Philip J., Bray, Steven M., Wong, Swee Seong, Ting, Jason C., Calley, John N., Whittington, Catherine F., Bhagwat, Shripad V., Reinhard, Christoph, Wild, Robert, Nam, Do-Hyun, Aggarwal, Amit, Lee, Woo Yong, and Peng, Sheng-Bin

Published
2020
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11. A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Author

Kendzia, Sandra, Franke, Susanne Lieselotte, Kröhler, Tarek, Golob-Schwarzl, Nicole, Schweiger, Caroline, Toeglhofer, Anna M., Skofler, Christina, Uranitsch, Stefan, El-Heliebi, Amin, Fuchs, Julia, Punschart, Andreas, Stiegler, Philipp, Keil, Marlen, Hoffmann, Jens, Henderson, David, Lehrach, Hans, Yaspo, Marie-Laure, Reinhard, Christoph, Schäfer, Reinhold, Keilholz, Ulrich, Regenbrecht, Christian René Alexander, Schicho, Rudolf, Fickert, Peter, Lax, Sigurd F., Erdmann, Frank, Schulz, Marcel Holger, Kiemer, Alexandra Kathrin, Haybäck, Johannes, and Keßler, Sonja

Subjects
Drug resistance, Neoplasm, RNA-binding proteins, Colorectal neoplasms
Abstract

Aim: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. Methods: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. Results: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. Conclusions: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.

Published
2023
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14. Abstract 187: Let’s get physiological! Impact of media conditions on drug response to targeted therapies in CRC organoids

Author

Loskutov, Jürgen, primary, Erdmann, Gerrit, additional, Arndt, Anja, additional, Adelmann, Quirin Graf, additional, Dudys, Przemyslaw, additional, Flechner, Marie, additional, Nadolny, Madeleine, additional, Osman, Katja, additional, Pfohl, Ulrike, additional, Reinhard, Christoph, additional, Templin, Markus, additional, Uhlig, Katja, additional, Wedeken, Lena, additional, and Regenbrecht, Christian, additional

Published
2023
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15. Data from Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Author

Du, Jian, primary, Yan, Lei, primary, Torres, Raquel, primary, Gong, Xueqian, primary, Bian, Huimin, primary, Marugán, Carlos, primary, Boehnke, Karsten, primary, Baquero, Carmen, primary, Hui, Yu-Hua, primary, Chapman, Sonya C., primary, Yang, Yanzhu, primary, Zeng, Yi, primary, Bogner, Sarah M., primary, Foreman, Robert T., primary, Capen, Andrew, primary, Donoho, Gregory P., primary, Van Horn, Robert D., primary, Barnard, Darlene S., primary, Dempsey, Jack A., primary, Beckmann, Richard P., primary, Marshall, Mark S., primary, Chio, Li-Chun, primary, Qian, Yuewei, primary, Webster, Yue W., primary, Aggarwal, Amit, primary, Chu, Shaoyou, primary, Bhattachar, Shobha, primary, Stancato, Louis F., primary, Dowless, Michele S., primary, Iversen, Phillip W., primary, Manro, Jason R., primary, Walgren, Jennie L., primary, Halstead, Bartley W., primary, Dieter, Matthew Z., primary, Martinez, Ricardo, primary, Bhagwat, Shripad V., primary, Kreklau, Emiko L., primary, Lallena, Maria Jose, primary, Ye, Xiang S., primary, Patel, Bharvin K.R., primary, Reinhard, Christoph, primary, Plowman, Gregory D., primary, Barda, David A., primary, Henry, James R., primary, Buchanan, Sean G., primary, and Campbell, Robert M., primary

Published
2023
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16. Supplementary Figures S1-S15 from Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene

Author

Gong, Xueqian, primary, Du, Jian, primary, Parsons, Stephen H., primary, Merzoug, Farhana F., primary, Webster, Yue, primary, Iversen, Philip W., primary, Chio, Li-Chun, primary, Van Horn, Robert D., primary, Lin, Xi, primary, Blosser, Wayne, primary, Han, Bomie, primary, Jin, Shaoling, primary, Yao, Sufang, primary, Bian, Huimin, primary, Ficklin, Chris, primary, Fan, Li, primary, Kapoor, Avnish, primary, Antonysamy, Stephen, primary, Mc Nulty, Ann M., primary, Froning, Karen, primary, Manglicmot, Danalyn, primary, Pustilnik, Anna, primary, Weichert, Kenneth, primary, Wasserman, Stephen R., primary, Dowless, Michele, primary, Marugán, Carlos, primary, Baquero, Carmen, primary, Lallena, María José, primary, Eastman, Scott W., primary, Hui, Yu-Hua, primary, Dieter, Matthew Z., primary, Doman, Thompson, primary, Chu, Shaoyou, primary, Qian, Hui-Rong, primary, Ye, Xiang S., primary, Barda, David A., primary, Plowman, Gregory D., primary, Reinhard, Christoph, primary, Campbell, Robert M., primary, Henry, James R., primary, and Buchanan, Sean G., primary

Published
2023
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17. Data from Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene

Author

Gong, Xueqian, primary, Du, Jian, primary, Parsons, Stephen H., primary, Merzoug, Farhana F., primary, Webster, Yue, primary, Iversen, Philip W., primary, Chio, Li-Chun, primary, Van Horn, Robert D., primary, Lin, Xi, primary, Blosser, Wayne, primary, Han, Bomie, primary, Jin, Shaoling, primary, Yao, Sufang, primary, Bian, Huimin, primary, Ficklin, Chris, primary, Fan, Li, primary, Kapoor, Avnish, primary, Antonysamy, Stephen, primary, Mc Nulty, Ann M., primary, Froning, Karen, primary, Manglicmot, Danalyn, primary, Pustilnik, Anna, primary, Weichert, Kenneth, primary, Wasserman, Stephen R., primary, Dowless, Michele, primary, Marugán, Carlos, primary, Baquero, Carmen, primary, Lallena, María José, primary, Eastman, Scott W., primary, Hui, Yu-Hua, primary, Dieter, Matthew Z., primary, Doman, Thompson, primary, Chu, Shaoyou, primary, Qian, Hui-Rong, primary, Ye, Xiang S., primary, Barda, David A., primary, Plowman, Gregory D., primary, Reinhard, Christoph, primary, Campbell, Robert M., primary, Henry, James R., primary, and Buchanan, Sean G., primary

Published
2023
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18. Supplementary Materials and Methods from Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Author

Du, Jian, primary, Yan, Lei, primary, Torres, Raquel, primary, Gong, Xueqian, primary, Bian, Huimin, primary, Marugán, Carlos, primary, Boehnke, Karsten, primary, Baquero, Carmen, primary, Hui, Yu-Hua, primary, Chapman, Sonya C., primary, Yang, Yanzhu, primary, Zeng, Yi, primary, Bogner, Sarah M., primary, Foreman, Robert T., primary, Capen, Andrew, primary, Donoho, Gregory P., primary, Van Horn, Robert D., primary, Barnard, Darlene S., primary, Dempsey, Jack A., primary, Beckmann, Richard P., primary, Marshall, Mark S., primary, Chio, Li-Chun, primary, Qian, Yuewei, primary, Webster, Yue W., primary, Aggarwal, Amit, primary, Chu, Shaoyou, primary, Bhattachar, Shobha, primary, Stancato, Louis F., primary, Dowless, Michele S., primary, Iversen, Phillip W., primary, Manro, Jason R., primary, Walgren, Jennie L., primary, Halstead, Bartley W., primary, Dieter, Matthew Z., primary, Martinez, Ricardo, primary, Bhagwat, Shripad V., primary, Kreklau, Emiko L., primary, Lallena, Maria Jose, primary, Ye, Xiang S., primary, Patel, Bharvin K.R., primary, Reinhard, Christoph, primary, Plowman, Gregory D., primary, Barda, David A., primary, Henry, James R., primary, Buchanan, Sean G., primary, and Campbell, Robert M., primary

Published
2023
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19. Table S2 from Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene

Author

Gong, Xueqian, primary, Du, Jian, primary, Parsons, Stephen H., primary, Merzoug, Farhana F., primary, Webster, Yue, primary, Iversen, Philip W., primary, Chio, Li-Chun, primary, Van Horn, Robert D., primary, Lin, Xi, primary, Blosser, Wayne, primary, Han, Bomie, primary, Jin, Shaoling, primary, Yao, Sufang, primary, Bian, Huimin, primary, Ficklin, Chris, primary, Fan, Li, primary, Kapoor, Avnish, primary, Antonysamy, Stephen, primary, Mc Nulty, Ann M., primary, Froning, Karen, primary, Manglicmot, Danalyn, primary, Pustilnik, Anna, primary, Weichert, Kenneth, primary, Wasserman, Stephen R., primary, Dowless, Michele, primary, Marugán, Carlos, primary, Baquero, Carmen, primary, Lallena, María José, primary, Eastman, Scott W., primary, Hui, Yu-Hua, primary, Dieter, Matthew Z., primary, Doman, Thompson, primary, Chu, Shaoyou, primary, Qian, Hui-Rong, primary, Ye, Xiang S., primary, Barda, David A., primary, Plowman, Gregory D., primary, Reinhard, Christoph, primary, Campbell, Robert M., primary, Henry, James R., primary, and Buchanan, Sean G., primary

Published
2023
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20. Supplementary Figures from Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Author

Du, Jian, primary, Yan, Lei, primary, Torres, Raquel, primary, Gong, Xueqian, primary, Bian, Huimin, primary, Marugán, Carlos, primary, Boehnke, Karsten, primary, Baquero, Carmen, primary, Hui, Yu-Hua, primary, Chapman, Sonya C., primary, Yang, Yanzhu, primary, Zeng, Yi, primary, Bogner, Sarah M., primary, Foreman, Robert T., primary, Capen, Andrew, primary, Donoho, Gregory P., primary, Van Horn, Robert D., primary, Barnard, Darlene S., primary, Dempsey, Jack A., primary, Beckmann, Richard P., primary, Marshall, Mark S., primary, Chio, Li-Chun, primary, Qian, Yuewei, primary, Webster, Yue W., primary, Aggarwal, Amit, primary, Chu, Shaoyou, primary, Bhattachar, Shobha, primary, Stancato, Louis F., primary, Dowless, Michele S., primary, Iversen, Phillip W., primary, Manro, Jason R., primary, Walgren, Jennie L., primary, Halstead, Bartley W., primary, Dieter, Matthew Z., primary, Martinez, Ricardo, primary, Bhagwat, Shripad V., primary, Kreklau, Emiko L., primary, Lallena, Maria Jose, primary, Ye, Xiang S., primary, Patel, Bharvin K.R., primary, Reinhard, Christoph, primary, Plowman, Gregory D., primary, Barda, David A., primary, Henry, James R., primary, Buchanan, Sean G., primary, and Campbell, Robert M., primary

Published
2023
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21. Supplementary Tables from Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Author

Du, Jian, primary, Yan, Lei, primary, Torres, Raquel, primary, Gong, Xueqian, primary, Bian, Huimin, primary, Marugán, Carlos, primary, Boehnke, Karsten, primary, Baquero, Carmen, primary, Hui, Yu-Hua, primary, Chapman, Sonya C., primary, Yang, Yanzhu, primary, Zeng, Yi, primary, Bogner, Sarah M., primary, Foreman, Robert T., primary, Capen, Andrew, primary, Donoho, Gregory P., primary, Van Horn, Robert D., primary, Barnard, Darlene S., primary, Dempsey, Jack A., primary, Beckmann, Richard P., primary, Marshall, Mark S., primary, Chio, Li-Chun, primary, Qian, Yuewei, primary, Webster, Yue W., primary, Aggarwal, Amit, primary, Chu, Shaoyou, primary, Bhattachar, Shobha, primary, Stancato, Louis F., primary, Dowless, Michele S., primary, Iversen, Phillip W., primary, Manro, Jason R., primary, Walgren, Jennie L., primary, Halstead, Bartley W., primary, Dieter, Matthew Z., primary, Martinez, Ricardo, primary, Bhagwat, Shripad V., primary, Kreklau, Emiko L., primary, Lallena, Maria Jose, primary, Ye, Xiang S., primary, Patel, Bharvin K.R., primary, Reinhard, Christoph, primary, Plowman, Gregory D., primary, Barda, David A., primary, Henry, James R., primary, Buchanan, Sean G., primary, and Campbell, Robert M., primary

Published
2023
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22. Supplementary Information from Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene

Author

Gong, Xueqian, primary, Du, Jian, primary, Parsons, Stephen H., primary, Merzoug, Farhana F., primary, Webster, Yue, primary, Iversen, Philip W., primary, Chio, Li-Chun, primary, Van Horn, Robert D., primary, Lin, Xi, primary, Blosser, Wayne, primary, Han, Bomie, primary, Jin, Shaoling, primary, Yao, Sufang, primary, Bian, Huimin, primary, Ficklin, Chris, primary, Fan, Li, primary, Kapoor, Avnish, primary, Antonysamy, Stephen, primary, Mc Nulty, Ann M., primary, Froning, Karen, primary, Manglicmot, Danalyn, primary, Pustilnik, Anna, primary, Weichert, Kenneth, primary, Wasserman, Stephen R., primary, Dowless, Michele, primary, Marugán, Carlos, primary, Baquero, Carmen, primary, Lallena, María José, primary, Eastman, Scott W., primary, Hui, Yu-Hua, primary, Dieter, Matthew Z., primary, Doman, Thompson, primary, Chu, Shaoyou, primary, Qian, Hui-Rong, primary, Ye, Xiang S., primary, Barda, David A., primary, Plowman, Gregory D., primary, Reinhard, Christoph, primary, Campbell, Robert M., primary, Henry, James R., primary, and Buchanan, Sean G., primary

Published
2023
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23. Supplementary Tables S1-S7 from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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24. Supplementary Figure Legends from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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25. Supplementary Figure S2 from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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26. Data from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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29. Genomic characterization of intrinsic and acquired resistance to cetuximab in colorectal cancer patients

Author

Bray, Steven M., Lee, Jeeyun, Kim, Seung Tae, Hur, Joon Young, Ebert, Philip J., Calley, John N., Wulur, Isabella H., Gopalappa, Thejaswini, Wong, Swee Seong, Qian, Hui-Rong, Ting, Jason C., Liu, Jiangang, Willard, Melinda D., Novosiadly, Ruslan D., Park, Young Suk, Park, Joon Oh, Lim, Ho Yeong, Kang, Won Ki, Aggarwal, Amit, Kim, Hee Cheol, and Reinhard, Christoph

Published
2019
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31. Correction: Separation of low and high grade colon and rectum carcinoma by eukaryotic translation initiation factors 1, 5 and 6

Author

Golob-Schwarzl, Nicole, primary, Schweiger, Caroline, additional, Koller, Carina, additional, Krassnig, Stefanie, additional, Gogg-Kamerer, Margit, additional, Gantenbein, Nadine, additional, Toeglhofer, Anna M., additional, Wodlej, Christina, additional, Bergler, Helmut, additional, Pertschy, Brigitte, additional, Uranitsch, Stefan, additional, Holter, Magdalena, additional, El-Heliebi, Amin, additional, Fuchs, Julia, additional, Punschart, Andreas, additional, Stiegler, Philipp, additional, Keil, Marlen, additional, Hoffmann, Jens, additional, Henderson, David, additional, Lehrach, Hans, additional, Reinhard, Christoph, additional, Regenbrecht, Christian, additional, Schicho, Rudolf, additional, Fickert, Peter, additional, Lax, Sigurd, additional, and Haybaeck, Johannes, additional

Published
2023
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33. A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer

Author

Pfohl, Ulrike, primary, Loskutov, Jürgen, additional, Bashir, Sanum, additional, Kühn, Ralf, additional, Herter, Patrick, additional, Templin, Markus, additional, Mamlouk, Soulafa, additional, Belanov, Sergei, additional, Linnebacher, Michael, additional, Bürtin, Florian, additional, Vetter, Marcus, additional, Reinhard, Christoph, additional, Wedeken, Lena, additional, and Regenbrecht, Christian R. A., additional

Published
2022
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35. Abstract 6223: PD3D®models: New age in cancer research and clinical diagnostics

Author

Pflaume, Alina, primary, Exner, Samantha, additional, Herrera-Glomm, Katja, additional, Loskutov, Jürgen, additional, Pfohl, Ulrike, additional, Regenbrecht, Manuela, additional, Sankarasubramanian, Sushmitha, additional, Wedeken, Lena, additional, Finkler, Sabine, additional, Ruhe, Larissa, additional, Adelmann, Quirin Graf, additional, Reinhard, Christoph, additional, Stroebel, Philipp, additional, and Regenbrecht, Christian R., additional

Published
2022
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37. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes

Author

Cristescu, Razvan, Lee, Jeeyun, Nebozhyn, Michael, Kim, Kyoung-Mee, Ting, Jason C., Wong, Swee Seong, Liu, Jiangang, Yue, Yong Gang, Wang, Jian, Yu, Kun, Ye, Xiang S., Do, In-Gu, Liu, Shawn, Gong, Lara, Fu, Jake, Jin, Jason Gang, Choi, Min Gew, Sohn, Tae Sung, Lee, Joon Ho, Bae, Jae Moon, Kim, Seung Tae, Park, Se Hoon, Sohn, Insuk, Jung, Sin-Ho, Tan, Patrick, Chen, Ronghua, Hardwick, James, Kang, Won Ki, Ayers, Mark, Hongyue, Dai, Reinhard, Christoph, Loboda, Andrey, Kim, Sung, and Aggarwal, Amit

Subjects
Gene expression -- Health aspects, Tumor proteins -- Identification and classification, Stomach cancer -- Genetic aspects -- Development and progression, Biological sciences, Health
Abstract

Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease. We aim to establish clinically relevant molecular subtypes that would encompass this heterogeneity and provide useful clinical information. We use gene expression data to describe four molecular subtypes linked to distinct patterns of molecular alterations, disease progression and prognosis. The mesenchymal-like type includes diffuse-subtype tumors with the worst prognosis, the tendency to occur at an earlier age and the highest recurrence frequency (63%) of the four subtypes. Microsatellite-unstable tumors are hyper-mutated intestinal-subtype tumors occurring in the antrum; these have the best overall prognosis and the lowest frequency of recurrence (22%) of the four subtypes. The tumor protein 53 (TP53)-active and [TP53.sup.-]inactive types include patients with intermediate prognosis and recurrence rates (with respect to the other two subtypes), with the [TP53.sup.-]active group showing better prognosis. We describe key molecular alterations in each of the four subtypes using targeted sequencing and genome-wide copy number microarrays. We validate these subtypes in independent cohorts in order to provide a consistent and unified framework for further clinical and preclinical translational research., Gastric cancer (GC) is the fourth-most-common cancer globally and the second-leading cause of cancer deaths (1). It accounts for 989,600 cases annually, with East Asia accounting for more than half [...]

Published
2015
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38. Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

Author

Wu Xiaogang, Reinhard Christoph, Li Shuyu D., Huang Hui, Wei Tao, Pandey Ragini, and Chen Jake Y.

Subjects
Biotechnology, TP248.13-248.65
Abstract

In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease), and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA) for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI) database, and pathway enrichment from the human pathway database (HPD). We use a recently-published microarray dataset (GSE24215) related to insulin resistance and type 2 diabetes (T2D) as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

Published
2012
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40. Precision oncology beyond genomics: the future is here - it is just not evenly distributed

Author

Pfohl, Ulrike, Pflaume, Alina, Regenbrecht, Manuela, Finkler, Sabine, Adelmann, Quirin Graf, Reinhard, Christoph, Regenbrecht, Christian René Alexander, and Wedeken, Lena

Subjects
ddc:570, ddc:610
Abstract

Cancer is a multifactorial disease with increasing incidence. There are more than 100 different cancer types, defined by location, cell of origin, and genomic alterations that influence oncogenesis and therapeutic response. This heterogeneity between tumors of different patients and also the heterogeneity within the same patient’s tumor pose an enormous challenge to cancer treatment. In this review, we explore tumor heterogeneity on the longitudinal and the latitudinal axis, reviewing current and future approaches to study this heterogeneity and their potential to support oncologists in tailoring a patient’s treatment regimen. We highlight how the ideal of precision oncology is reaching far beyond the knowledge of genetic variants to inform clinical practice and discuss the technologies and strategies already available to improve our understanding and management of heterogeneity in cancer treatment. We will focus on integrating multi-omics technologies with suitable in vitro models and their proficiency in mimicking endogenous tumor heterogeneity.

Published
2021

41. Laser-induced sublimation extraction for cm-resolution multi-species greenhouse gas analysis on ice cores.

Author

Mächler, Lars, Baggenstos, Daniel, Krauss, Florian, Schmitt, Jochen, Bereiter, Bernhard, Walther, Remo, Reinhard, Christoph, Tuzson, Béla, Emmenegger, Lukas, and Fischer, Hubertus

Subjects
GREENHOUSE gas analysis, ICE cores, QUANTUM cascade lasers, DRILLING fluids, ANTARCTIC ice, LASER-induced fluorescence
Abstract

Precision, accuracy, and temporal resolution are key to make full use of atmospheric trace gas records in ice cores. These aspects will become especially crucial for ice cores that aim to extend the ice core record to the last 1.5 Myr, i.e., across the Mid Pleistocene Transition (as currently drilled within the European project Beyond EPICA - Oldest Ice Core (BE-OIC)). The ice from this period is expected to be close to bedrock and, due to glacier flow, extremely thinned with 15,000 years of climate history contained in only one meter of ice. Accordingly, for a century-scale resolution, the sample vertical extent must be reduced to a few cm containing only about 1-2mL air STP. We present a novel combined system for the extraction and the simultaneous measurement of CO2, CH4, and N2O concentrations, as well as δ13CO2, which achieves a vertical resolution of 1-2 cm with precisions of 0.4 ppm, 3 ppb, 1 ppb and 0.04 ‰, respectively. This is accomplished by employing a directional and continuous laser induced sublimation followed by analysis of the sample gas by quantum cascade laser absorption spectroscopy (QCLAS). Besides the low sample volume requirements and the vertical resolution capabilities, the described method holds additional advantages over previous methods, including the immunity of the highly specific QCLAS analysis to drilling fluid contamination as well as the non-destructive nature of the spectroscopic gas analysis. The combined extraction and analysis system was extensively tested by sublimating gas-free ice with introduction of a standard gas to determine the accuracy and characterize potential artefacts. Moreover, Antarctic ice samples were measured to confirm the measurement performance, covering the range of variability expected in Pleistocene ice and to highlight the vertical resolution capabilities critical for its application within BE-OIC. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Applying a Process Organization Perspective in the Context of Corporate Sustainability

Author

Königstorfer, Jörg (Prof. Dr.), Belz, Frank-Martin (Prof. Dr.), Jungnik Freiherr von Wittken, Reinhard Christoph, Königstorfer, Jörg (Prof. Dr.), Belz, Frank-Martin (Prof. Dr.), and Jungnik Freiherr von Wittken, Reinhard Christoph

Abstract

This dissertation applies a process organization perspective to various phenomena which are of particular importance in the context of corporate sustainability. The first essay elaborates on the role of organizational products in the evolution of organizational identity. The second essay investigates how organizations can navigate the paradox of authenticity and market commercialization over time. The third essay critically discusses how organizations can translate the inherently processual character of sustainable development from the societal level to the organizational level in corporate sustainability accounting., Diese Dissertation wendet eine Process Organization Perspective auf verschiedene Phänomene an, die im Kontext unternehmerischer Nachhaltigkeit von besonderer Bedeutung sind. Das erste Essay richtet den Fokus auf die Rolle organisationaler Produkte in der Entwicklung organisationaler Identität. Das zweite Essay untersucht, wie Organisationen über die Zeit hinweg mit dem Paradox zwischen organisationaler Authentizität und Marktkommerzialisierung umgehen können. Das dritte Essay diskutiert kritisch, wie Organisationen im Nachhaltigkeitsaccounting das prozessuale Verständnis Nachhaltiger Entwicklung von der gesellschaftlichen auf die organisationale Ebene übertragen können.

Published
2020

45. Applying a Process Organization Perspective in the Context of Corporate Sustainability

Author

Belz, Frank-Martin (Prof. Dr.), Belz, Frank-Martin (Prof. Dr.);Königstorfer, Jörg (Prof. Dr.), Jungnik Freiherr von Wittken, Reinhard Christoph, Belz, Frank-Martin (Prof. Dr.), Belz, Frank-Martin (Prof. Dr.);Königstorfer, Jörg (Prof. Dr.), and Jungnik Freiherr von Wittken, Reinhard Christoph

Abstract

This dissertation applies a process organization perspective to various phenomena which are of particular importance in the context of corporate sustainability. The first essay elaborates on the role of organizational products in the evolution of organizational identity. The second essay investigates how organizations can navigate the paradox of authenticity and market commercialization over time. The third essay critically discusses how organizations can translate the inherently processual character of sustainable development from the societal level to the organizational level in corporate sustainability accounting., Diese Dissertation wendet eine Process Organization Perspective auf verschiedene Phänomene an, die im Kontext unternehmerischer Nachhaltigkeit von besonderer Bedeutung sind. Das erste Essay richtet den Fokus auf die Rolle organisationaler Produkte in der Entwicklung organisationaler Identität. Das zweite Essay untersucht, wie Organisationen über die Zeit hinweg mit dem Paradox zwischen organisationaler Authentizität und Marktkommerzialisierung umgehen können. Das dritte Essay diskutiert kritisch, wie Organisationen im Nachhaltigkeitsaccounting das prozessuale Verständnis Nachhaltiger Entwicklung von der gesellschaftlichen auf die organisationale Ebene übertragen können.

Published
2020

46. Unraveling condition‐dependent networks of transcription factors that control metabolic pathway activity in yeast

Author

Sarah‐Maria Fendt, Ana Paula Oliveira, Stefan Christen, Paola Picotti, Reinhard Christoph Dechant, and Uwe Sauer

Subjects
metabolic flux, omics data, regulatory network, transcription factor, transcriptionalregulation, Biology (General), QH301-705.5, Medicine (General), R5-920
Abstract

Which transcription factors control the distribution of metabolic fluxes under a given condition? We address this question by systematically quantifying metabolic fluxes in 119 transcription factor deletion mutants of Saccharomyces cerevisiae under five growth conditions. While most knockouts did not affect fluxes, we identified 42 condition‐dependent interactions that were mediated by a total of 23 transcription factors that control almost exclusively the cellular decision between respiration and fermentation. This relatively sparse, condition‐specific network of active metabolic control contrasts with the much larger gene regulation network inferred from expression and DNA binding data. Based on protein and transcript analyses in key mutants, we identified three enzymes in the tricarboxylic acid cycle as the key targets of this transcriptional control. For the transcription factor Gcn4, we demonstrate that this control is mediated through the PKA and Snf1 signaling cascade. The discrepancy between flux response predictions, based on the known regulatory network architecture and our functional 13C‐data, demonstrates the importance of identifying and quantifying the extent to which regulatory effectors alter cellular functions.

Published
2010
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47. Regulation of cellular growth by the Drosophila target of rapamycin dTOR

Author

Zhang, Hongbing, Stallock, James P., Ng, Joyce C., Reinhard, Christoph, and Neufeld, Thoms P.

Subjects
Immunocytochemistry -- Research, Growth factors -- Physiological aspects, Growth -- Regulation, Cell cycle -- Genetic aspects, Drosophila -- Genetic aspects, Cellular signal transduction -- Research, Rapamycin -- Physiological aspects, Mammals -- Genetic aspects, Nutrition -- Genetic aspects, Biological sciences
Abstract

Cellular growth and its regulation by the Drosophila target of rapamycin are discussed. Mutations in the Drosophila TOR homolog, dTOR, were generated, and it was seen that dTOR mutant phenotypes recapitulate aspects of both P13K-dependent signaling and nutritional sensing. That would be consistent with dTOR's acting at the junction of the pathways examined.

Published
2000

48. Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Author

Du, Jian, primary, Yan, Lei, additional, Torres, Raquel, additional, Gong, Xueqian, additional, Bian, Huimin, additional, Marugán, Carlos, additional, Boehnke, Karsten, additional, Baquero, Carmen, additional, Hui, Yu-Hua, additional, Chapman, Sonya C., additional, Yang, Yanzhu, additional, Zeng, Yi, additional, Bogner, Sarah M., additional, Foreman, Robert T., additional, Capen, Andrew, additional, Donoho, Gregory P., additional, Van Horn, Robert D., additional, Barnard, Darlene S., additional, Dempsey, Jack A., additional, Beckmann, Richard P., additional, Marshall, Mark S., additional, Chio, Li-Chun, additional, Qian, Yuewei, additional, Webster, Yue W., additional, Aggarwal, Amit, additional, Chu, Shaoyou, additional, Bhattachar, Shobha, additional, Stancato, Louis F., additional, Dowless, Michele S., additional, Iversen, Phillip W., additional, Manro, Jason R., additional, Walgren, Jennie L., additional, Halstead, Bartley W., additional, Dieter, Matthew Z., additional, Martinez, Ricardo, additional, Bhagwat, Shripad V., additional, Kreklau, Emiko L., additional, Lallena, Maria Jose, additional, Ye, Xiang S., additional, Patel, Bharvin K.R., additional, Reinhard, Christoph, additional, Plowman, Gregory D., additional, Barda, David A., additional, Henry, James R., additional, Buchanan, Sean G., additional, and Campbell, Robert M., additional

Published
2019
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50. Abstract 1761: Inhibition of PI3K/AKT/mTOR signaling by a dual PI3K/mTOR inhibitor (LY3023414) potentiates the antitumor efficacy of the Chk1 inhibitor prexasertib (LY2606368) in models of human high-grade serous ovarian cancer (HGSOC)

Author

Dempsey, Jack, primary, Donoho, Greg, additional, Iversen, Philip, additional, Stephens, Jennifer, additional, McNulty, Ann, additional, Martinez, Ricardo, additional, Reinhard, Christoph, additional, Stancato, Louis, additional, Lin, Aimee, additional, and Wu, Wenjuan, additional

Published
2019
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