Benita Katzenellenbogen

Benita S. Katzenellenbogen née Schulman (born 1945) is an American physiologist and cell biologist at the University of Illinois at Urbana-Champaign. She has studied cancer, endocrinology, and women's health, focusing on nuclear receptors. She also dedicated efforts to focusing on improving the effectiveness of endocrine therapies in breast cancer.

Benita S. Katzenellenbogen
Born
Benita Schulman

April 11, 1945
New York City
NationalityAmerican
Alma materHarvard University
OccupationCell biologist

Biography

Katzenellenbogen's work has delineated structure-function relationships and mechanisms of action of estrogen receptors alpha and beta. She has clarified the molecular basis of action of SERMs such as tamoxifen and raloxifene in treatment and prevention of breast cancer, and she has identified critical aggressiveness factors in breast tumors that promote metastasis and resistance to cancer therapies. She has studied approaches to inhibit them.[1][2]

Early life

Benita Schulman was born April 11, 1945, in New York City. Her father was a patent attorney and her mother was a school teacher in New York. She attended public schools and did her undergraduate training in biology at the City University of New York (Brooklyn College), receiving her BA summa cum laude in 1965. She obtained her Ph.D. in biology at Harvard University in 1970, doing research in Developmental Biology with Professor Fotis Kafatos.[3][4] She completed postdoctoral work in endocrinology and cancer biology at the University of Illinois at Urbana-Champaign from 1970 to 1971 with Professor Jack Gorski.[5][6]

Career

Katzenellenbogen began her academic career as an Assistant Professor of Physiology at the University of Illinois and College of Medicine at Urbana-Champaign in 1971. She was promoted to Associate Professor in 1976, and to Full Professor in 1982. She is currently the Swanlund Professor of Molecular and Integrative Physiology, Cell and Developmental Biology at the University of Illinois. She also holds affiliate appointments in the Institute for Genomic Biology[7] and the Beckman Institute for Advanced Science and Technology at Illinois.[8] Additionally, from September 1977 to June 1978, Katzenellenbogen did sabbatical research at the University of California at San Francisco, and in 2005 she conducted collaborative sabbatical research at the Genome Institute of Singapore.[9] Her professional career has been directed at elucidating cellular and molecular mechanisms of steroid hormone-mediated regulation of reproductive target tissues and of tumors that develop in these tissues, especially breast cancer.[2][10]

Katzenellenbogen has published more than 330 research articles, contributed 30 book chapters, and co-edited a book on hormone-dependent cancers.[11] She has trained more than 90 graduate students and postdoctoral scientists and has overseen numerous undergraduates in their biomedical research. For her activities in mentoring, she was recognized with the Mentor Award from Women in Endocrinology in 2011.[12] She is also the recipient of numerous other awards, honors, and special fellowships from governmental, private, and academic institutions. These include the MERIT Award from the National Cancer Institute of the NIH (1991-1999), the Brinker Award for Scientific Distinction from the Susan G. Komen for the Cure Breast Cancer Foundation (2009),[2] the Jill Rose Award from The Breast Cancer Research Foundation (1998),[13] the Ernst Oppenheimer Award (1984),[14] and the Roy O. Greep Lecture Award from The Endocrine Society (2006).[15] In 2016, she shared the Fred Conrad Koch Lifetime Achievement Award from The Endocrine Society with Dr. John Katzenellenbogen.[16] She was elected a Fellow of the American Academy of Arts and Sciences (1993),[17] and she received a Distinguished Alumni Award from The City University of New York in 2002[18] and an Honorary Degree from the University of Milan, Italy (2007).

She has served on many committees and review panels, journal editorial boards, and as President of The Endocrine Society (2000–2001).[19] She served full terms on the NIH Endocrinology (1979-1983) and Biochemical Endocrinology Study Sections (1995-1999), was Vice Chair of the American Cancer Society Review Panel on Biochemistry and Endocrinology (1992-1993), and was Chair of the NIH, NIDDK Board of Scientific Counselors (1988-1989). She served as a member of the External Advisory Committee for the NIH Nuclear Receptor Signaling Atlas (2002-2012) and on Review Panels for Komen for the Cure, the DOD Breast Cancer Program, and on NIH graduate and postdoctoral fellowship review committees. She co-chaired the Hormone Action Gordon Research Conference in 1988[20] and the Keystone Symposium on The Nuclear Receptor Superfamily in 2002.[21]

Research

Katzenellenbogen has clarified structure-function relationships and actions of estrogen receptors alpha and beta,[22][23][24][25][26] and demonstrated that estrogens have a broad spectrum of effects on gene networks and pathways in breast cancer and other cells.[27][28] This research has contributed to understanding of the molecular basis for the action of selective estrogen receptor modulators (SERMs) such as tamoxifen in target cells,[29][30][31][32] and for the development of anti-hormonal treatments used in breast cancer treatment and prevention.[33][34] Her laboratory demonstrated that estrogen receptors regulate and function along with multiple cell signaling pathways involving kinase cascades and growth factors,[35][36][37] and that these inputs converge at the level of chromatin to regulate gene expression and cell signaling.[26] This work presaged the current active interest in both the non-genomic actions of estrogens[36][38][39] and the cross-talk between nuclear receptors and other cell signaling pathways and their roles in endocrine resistance. Her laboratory has also identified factors associated with aggressiveness and early time to cancer recurrence[40][41][42][43][44][45][46] and their regulation in different subtypes of breast cancer.[47] She has also characterized the activities of estrogens in menopausal hormone replacement therapies and diverse ligands for estrogen receptors,[36][48] including environmental estrogens,[49] phytoestrogens such as genistein,[23][50][51] and estrogen receptor subtype-selective ligands in various estrogen target tissues.[52][53][54][55]

References
  1. "Endocrine Society Announces 2016 Laureate Award Winners | Endocrine Society". www.endocrine.org. Retrieved 2017-12-23.
  2. "Breast Cancer Awards & Recognition | Susan G. Komen®". ww5.komen.org. Retrieved 2017-12-23.
  3. Katzenellenbogen, Benita S; Kafatos, Fotis C (1971). "General esterases of silkmoth moulting fluid: Preliminary characterization". Journal of Insect Physiology. 17 (6): 1139–43. doi:10.1016/0022-1910(71)90016-3.
  4. Katzenellenbogen, Benita S; Kafatos, Fotis C (1971). "Proteinases of silkmoth moulting fluid: Physical and catalytic properties". Journal of Insect Physiology. 17 (4): 775–800. doi:10.1016/0022-1910(71)90123-5.
  5. Katzenellenbogen, B. S; Gorski, J (1972). "Estrogen action in vitro. Induction of the synthesis of a specific uterine protein". The Journal of Biological Chemistry. 247 (4): 1299–305. doi:10.1016/S0021-9258(19)45646-9. PMID 4335193.
  6. Ruh, Thomas S; Katzenellenbogen, Benita S; Katzenellenbogen, John A; Gorski, JAC (1973). "Estrone Interaction with the Rat Uterus: In Vitro Response and Nuclear Uptake1". Endocrinology. 92 (1): 125–34. doi:10.1210/endo-92-1-125. PMID 4681918.
  7. "People | Carl R. Woese Institute for Genomic Biology". www.igb.illinois.edu. Retrieved 2017-12-22.
  8. Technology, Beckman Institute for Advanced Science and. "Understanding the Nature of Cancer, One Cell at a Time, News, Beckman Institute, University of Illinois". beckman.illinois.edu. Retrieved 2017-12-22.
  9. Lin, Chin-Yo; Vega, Vinsensius B; Thomsen, Jane S; Zhang, Tao; Kong, Say Li; Xie, Min; Chiu, Kuo Ping; Lipovich, Leonard; Barnett, Daniel H; Stossi, Fabio; Yeo, Ailing; George, Joshy; Kuznetsov, Vladimir A; Lee, Yew Kok; Charn, Tze Howe; Palanisamy, Nallasivam; Miller, Lance D; Cheung, Edwin; Katzenellenbogen, Benita S; Ruan, Yijun; Bourque, Guillaume; Wei, Chia-Lin; Liu, Edison T (2007). "Whole-Genome Cartography of Estrogen Receptor α Binding Sites". PLOS Genetics. 3 (6): e87. doi:10.1371/journal.pgen.0030087. PMC 1885282. PMID 17542648.
  10. "Meet the 2016 Laureate Award Winners: Benita Katzenellenbogen, PhD, and John Katzenellenbogen, PhD - Endocrine News". Endocrine News. 2016-01-25. Retrieved 2017-12-23.
  11. Pasqualini, Jorge; Katzenellenbogen, Benita (1996). Hormone-Dependent Cancer. Taylor & Francis. ISBN 9780824796976.
  12. "Past Mentor Award Recipients | Women in Endocrinology". www.women-in-endo.org. Retrieved 2017-12-22.
  13. rayogram. "BCRF :: Jill Rose Award". legacy.bcrfcure.org. Retrieved 2017-12-22.
  14. "Ernst Oppenheimer Award | Endocrine Society". www.endocrine.org. Retrieved 2017-12-22.
  15. "Roy O. Greep Award for Outstanding Research | Endocrine Society". www.endocrine.org. Retrieved 2017-12-23.
  16. "Noteworthy - American Academy of Arts & Sciences". Archived from the original on 2017-12-23. Retrieved 2017-12-22.
  17. "American Academy of Arts and Sciences Fellows Listing" (PDF). amacad.org. January 1, 2017. p. 316. Retrieved December 22, 2017.
  18. Illinois, Inside. "News Bureau | ILLINOIS". news.illinois.edu. Retrieved 2017-12-22.
  19. "Hall of Presidents | Endocrine Society". www.endocrine.org. Retrieved 2017-12-22.
  20. "Mechanisms of Hormone Action - Gordon Research Conferences". www.grc.org. Retrieved 2017-12-22.
  21. "Keystone Symposia | Scientific Conferences on Biomedical and Life Science Topics". Keystone Symposia. Retrieved 2017-12-22.
  22. Stossi, Fabio; Barnett, Daniel H; Frasor, Jonna; Komm, Barry; Lyttle, C. Richard; Katzenellenbogen, Benita S (2004). "Transcriptional Profiling of Estrogen-Regulated Gene Expression via Estrogen Receptor (ER) α or ERβ in Human Osteosarcoma Cells: Distinct and Common Target Genes for These Receptors". Endocrinology. 145 (7): 3473–86. doi:10.1210/en.2003-1682. PMID 15033914.
  23. Chang, Edmund C; Charn, Tze Howe; Park, Sung-Hee; Helferich, William G; Komm, Barry; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2008). "Estrogen Receptors α and β as Determinants of Gene Expression: Influence of Ligand, Dose, and Chromatin Binding". Molecular Endocrinology. 22 (5): 1032–43. doi:10.1210/me.2007-0356. PMC 2366177. PMID 18258689.
  24. Stossi, F; Madak-Erdogan, Z; Katzenellenbogen, B. S (2009). "Estrogen Receptor Alpha Represses Transcription of Early Target Genes via p300 and CtBP1". Molecular and Cellular Biology. 29 (7): 1749–59. doi:10.1128/MCB.01476-08. PMC 2655624. PMID 19188451.
  25. Wrenn, C. K; Katzenellenbogen, B. S (1993). "Structure-function analysis of the hormone binding domain of the human estrogen receptor by region-specific mutagenesis and phenotypic screening in yeast". The Journal of Biological Chemistry. 268 (32): 24089–98. doi:10.1016/S0021-9258(20)80497-9. PMID 8226955.
  26. Madak-Erdogan, Z; Charn, T.-H; Jiang, Y; Liu, E. T; Katzenellenbogen, J. A; Katzenellenbogen, B. S (2014). "Integrative genomics of gene and metabolic regulation by estrogen receptors alpha and beta, and their coregulators". Molecular Systems Biology. 9: 676. doi:10.1038/msb.2013.28. PMC 3964312. PMID 23774759.
  27. Frasor, Jonna; Danes, Jeanne M; Komm, Barry; Chang, Ken C. N; Lyttle, C. Richard; Katzenellenbogen, Benita S (2003). "Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype". Endocrinology. 144 (10): 4562–74. doi:10.1210/en.2003-0567. PMID 12959972.
  28. Chang, Edmund C; Frasor, Jonna; Komm, Barry; Katzenellenbogen, Benita S (2006). "Impact of Estrogen Receptor β on Gene Networks Regulated by Estrogen Receptor α in Breast Cancer Cells". Endocrinology. 147 (10): 4831–42. doi:10.1210/en.2006-0563. PMID 16809442.
  29. Montano, M. M; Katzenellenbogen, B. S (1997). "The quinone reductase gene: A unique estrogen receptor-regulated gene that is activated by antiestrogens". Proceedings of the National Academy of Sciences of the United States of America. 94 (6): 2581–6. Bibcode:1997PNAS...94.2581M. doi:10.1073/pnas.94.6.2581. PMC 20131. PMID 9122238.
  30. Montano, M. M; Ekena, K; Delage-Mourroux, R; Chang, W; Martini, P; Katzenellenbogen, B. S (1999). "An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens". Proceedings of the National Academy of Sciences of the United States of America. 96 (12): 6947–52. Bibcode:1999PNAS...96.6947M. doi:10.1073/pnas.96.12.6947. PMC 22022. PMID 10359819.
  31. Frasor, J; Stossi, F; Danes, J. M; Komm, B; Lyttle, C. R; Katzenellenbogen, B. S (2004). "Selective estrogen receptor modulators: Discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells". Cancer Research. 64 (4): 1522–33. doi:10.1158/0008-5472.CAN-03-3326. PMID 14973112. S2CID 35304.
  32. Park, Sunghee; Zhao, Yuechao; Yoon, Sangyeon; Xu, Jianming; Liao, Lan; Lydon, John; Demayo, Franco; O'Malley, Bert W; Katzenellenbogen, Benita S (2011). "Repressor of Estrogen Receptor Activity (REA) is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice". Endocrinology. 152 (11): 4336–49. doi:10.1210/en.2011-1100. PMC 3199013. PMID 21862609.
  33. Katzenellenbogen, Benita S; Frasor, Jonna (2004). "Therapeutic targeting in the estrogen receptor hormonal pathway". Seminars in Oncology. 31 (1 Suppl 3): 28–38. doi:10.1053/j.seminoncol.2004.01.004. PMID 15052541.
  34. Tryfonidis, Konstantinos; Zardavas, Dimitrios; Katzenellenbogen, Benita S; Piccart, Martine (2016). "Endocrine treatment in breast cancer: Cure, resistance and beyond" (PDF). Cancer Treatment Reviews. 50: 68–81. doi:10.1016/j.ctrv.2016.08.008. PMID 27643748.
  35. Katzenellenbogen, Benita S; Jane Norman, Mary (1990). "Multihormonal Regulation of the Progesterone Receptor in MCF-7 Human Breast Cancer Cells: Interrelationships among Insulin/Insulin-Like Growth Factor-I, Serum, and Estrogen". Endocrinology. 126 (2): 891–8. doi:10.1210/endo-126-2-891. PMID 2404751.
  36. Madak-Erdogan, Z; Kim, S. H; Gong, P; Zhao, Y. C; Zhang, H; Chambliss, K. L; Carlson, K. E; Mayne, C. G; Shaul, P. W; Korach, K. S; Katzenellenbogen, J. A; Katzenellenbogen, B. S (2016). "Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues". Science Signaling. 9 (429): ra53. doi:10.1126/scisignal.aad8170. PMC 4896643. PMID 27221711.
  37. Madak-Erdogan, Z; Lupien, M; Stossi, F; Brown, M; Katzenellenbogen, B. S (2010). "Genomic Collaboration of Estrogen Receptor   and Extracellular Signal-Regulated Kinase 2 in Regulating Gene and Proliferation Programs". Molecular and Cellular Biology. 31 (1): 226–36. doi:10.1128/MCB.00821-10. PMC 3019850. PMID 20956553.
  38. Harrington, William R; Kim, Sung Hoon; Funk, Cory C; Madak-Erdogan, Zeynep; Schiff, Rachel; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2006). "Estrogen Dendrimer Conjugates that Preferentially Activate Extranuclear, Nongenomic Versus Genomic Pathways of Estrogen Action". Molecular Endocrinology. 20 (3): 491–502. doi:10.1210/me.2005-0186. PMID 16306086.
  39. Madak-Erdogan, Zeynep; Kieser, Karen J; Kim, Sung Hoon; Komm, Barry; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2008). "Nuclear and Extranuclear Pathway Inputs in the Regulation of Global Gene Expression by Estrogen Receptors". Molecular Endocrinology. 22 (9): 2116–27. doi:10.1210/me.2008-0059. PMC 2631368. PMID 18617595.
  40. Bergamaschi, Anna; Christensen, Barbara L; Katzenellenbogen, Benita S (2011). "Reversal of endocrine resistance in breast cancer: Interrelationships among 14-3-3ζ, FOXM1, and a gene signature associated with mitosis". Breast Cancer Research. 13 (3): R70. doi:10.1186/bcr2913. PMC 3218959. PMID 21707964.
  41. Madak-Erdogan, Zeynep; Ventrella, Rosa; Petry, Luke; Katzenellenbogen, Benita S (2014). "Novel Roles for ERK5 and Cofilin as Critical Mediators Linking ERα-Driven Transcription, Actin Reorganization, and Invasiveness in Breast Cancer". Molecular Cancer Research. 12 (5): 714–27. doi:10.1158/1541-7786.MCR-13-0588. PMC 4020978. PMID 24505128.
  42. Bergamaschi, Anna; Madak-Erdogan, Zeynep; Kim, Yu Jin; Choi, Yoon-La; Lu, Hailing; Katzenellenbogen, Benita S (2014). "The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells". Breast Cancer Research. 16 (5): 436. doi:10.1186/s13058-014-0436-4. PMC 4303117. PMID 25213081.
  43. Weis, K E; Ekena, K; Thomas, J A; Lazennec, G; Katzenellenbogen, B S (1996). "Constitutively active human estrogen receptors containing amino acid substitutions for tyrosine 537 in the receptor protein". Molecular Endocrinology. 10 (11): 1388–98. doi:10.1210/mend.10.11.8923465. PMID 8923465.
  44. Lazennec, Gwendal; Ediger, Tracy R; Petz, Larry N; Nardulli, Ann M; Katzenellenbogen, Benita S (1997). "Mechanistic Aspects of Estrogen Receptor Activation Probed with Constitutively Active Estrogen Receptors: Correlations with DNA and Coregulator Interactions and Receptor Conformational Changes". Molecular Endocrinology. 11 (9): 1375–86. doi:10.1210/mend.11.9.9983. PMID 9259327.
  45. Fanning, Sean W; Mayne, Christopher G; Dharmarajan, Venkatasubramanian; Carlson, Kathryn E; Martin, Teresa A; Novick, Scott J; Toy, Weiyi; Green, Bradley; Panchamukhi, Srinivas; Katzenellenbogen, Benita S; Tajkhorshid, Emad; Griffin, Patrick R; Shen, Yang; Chandarlapaty, Sarat; Katzenellenbogen, John A; Greene, Geoffrey L (2016). "Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation". eLife. 5. doi:10.7554/eLife.12792. PMC 4821807. PMID 26836308.
  46. Zhao, Yuechao; Laws, Mary J; Guillen, Valeria Sanabria; Ziegler, Yvonne; Min, Jian; Sharma, Abhishek; Kim, Sung Hoon; Chu, David; Park, Ben Ho; Oesterreich, Steffi; Mao, Chengjian; Shapiro, David J; Nettles, Kendall W; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2017). "Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors". Cancer Research. 77 (20): 5602–5613. doi:10.1158/0008-5472.CAN-17-1265. PMC 5645250. PMID 28904064.
  47. Bergamaschi, Anna; Frasor, Jonna; Borgen, Kristina; Stanculescu, Adina; Johnson, Patricia; Rowland, Kendrith; Wiley, Elizabeth L; Katzenellenbogen, Benita S (2012). "14-3-3ζ as a predictor of early time to recurrence and distant metastasis in hormone receptor-positive and -negative breast cancers". Breast Cancer Research and Treatment. 137 (3): 689–96. doi:10.1007/s10549-012-2390-0. PMC 3632437. PMID 23271328.
  48. Zhao, Y; Gong, P; Chen, Y; Nwachukwu, J. C; Srinivasan, S; Ko, C; Bagchi, M. K; Taylor, R. N; Korach, K. S; Nettles, K. W; Katzenellenbogen, J. A; Katzenellenbogen, B. S (2015). "Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis". Science Translational Medicine. 7 (271): 271ra9. doi:10.1126/scitranslmed.3010626. PMC 4790140. PMID 25609169.
  49. Katzenellenbogen, Benita S; Katzenellenbogen, John A; Mordecai, David (1979). "Zearalenones: Characterization of the Estrogenic Potencies and Receptor Interactions of a Series of Fungal β-Resorcylic Acid Lactones". Endocrinology. 105 (1): 33–40. doi:10.1210/endo-105-1-33. PMID 446414.
  50. Gong, Ping; Madak-Erdogan, Zeynep; Li, Jilong; Cheng, Jianlin; Greenlief, C. Michael; Helferich, William; Katzenellenbogen, John A.; Katzenellenbogen, Benita S. (2014). "Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens". Nuclear Receptor Signaling. 12: e001. doi:10.1621/nrs.12001. ISSN 1550-7629. PMC 4193135. PMID 25363786.
  51. Jiang, Y; Gong, P; Madak-Erdogan, Z; Martin, T; Jeyakumar, M; Carlson, K; Khan, I; Smillie, T. J; Chittiboyina, A. G; Rotte, S. C. K; Helferich, W. G; Katzenellenbogen, J. A; Katzenellenbogen, B. S (2013). "Mechanisms enforcing the estrogen receptor   selectivity of botanical estrogens". The FASEB Journal. 27 (11): 4406–18. doi:10.1096/fj.13-234617. PMC 3804744. PMID 23882126.
  52. Meyers, Marvin J; Sun, Jun; Carlson, Kathryn E; Marriner, Gwendolyn A; Katzenellenbogen, Benita S; Katzenellenbogen, John A (2001). "Estrogen Receptor-β Potency-Selective Ligands:  Structure−Activity Relationship Studies of Diarylpropionitriles and Their Acetylene and Polar Analogues". Journal of Medicinal Chemistry. 44 (24): 4230–51. doi:10.1021/jm010254a. PMID 11708925.
  53. Sun, Jun; Huang, Ying R; Harrington, William R; Sheng, Shubin; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2002). "Antagonists Selective for Estrogen Receptor α". Endocrinology. 143 (3): 941–7. doi:10.1210/endo.143.3.8704. PMID 11861516.
  54. Harris, Heather A; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2002). "Characterization of the Biological Roles of the Estrogen Receptors, ERα and ERβ, in Estrogen Target Tissues in Vivo through the Use of an ERα-Selective Ligand". Endocrinology. 143 (11): 4172–7. doi:10.1210/en.2002-220403. PMID 12399409.
  55. Sun, Jun; Baudry, Jerome; Katzenellenbogen, John A; Katzenellenbogen, Benita S (2003). "Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-β-Selective Ligand, Diarylpropionitrile". Molecular Endocrinology. 17 (2): 247–58. doi:10.1210/me.2002-0341. PMID 12554752.
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