TY  - JOUR
A1  - Zhang, Yonghong
A1  - Zheng, Lanlan
A1  - Zheng, Yan
A1  - Zhou, Chao
A1  - Huang, Ping
A1  - Xiao, Xiao
A1  - Zhao, Yongheng
A1  - Hao, Xincai
A1  - Hu, Zhubing
A1  - Chen, Qinhua
A1  - Li, Hongliang
A1  - Wang, Xuanbin
A1  - Fukushima, Kenji
A1  - Wang, Guodong
A1  - Li, Chen
T1  - Assembly and Annotation of a Draft Genome of the Medicinal Plant Polygonum cuspidatum
JF  - Frontiers in Plant Science
N2  - Polygonum cuspidatum (Japanese knotweed, also known as Huzhang in Chinese), a plant that produces bioactive components such as stilbenes and quinones, has long been recognized as important in traditional Chinese herbal medicine. To better understand the biological features of this plant and to gain genetic insight into the biosynthesis of its natural products, we assembled a draft genome of P. cuspidatum using Illumina sequencing technology. The draft genome is ca. 2.56 Gb long, with 71.54% of the genome annotated as transposable elements. Integrated gene prediction suggested that the P. cuspidatum genome encodes 55,075 functional genes, including 6,776 gene families that are conserved in the five eudicot species examined and 2,386 that are unique to P. cuspidatum. Among the functional genes identified, 4,753 are predicted to encode transcription factors. We traced the gene duplication history of P. cuspidatum and determined that it has undergone two whole-genome duplication events about 65 and 6.6 million years ago. Roots are considered the primary medicinal tissue, and transcriptome analysis identified 2,173 genes that were expressed at higher levels in roots compared to aboveground tissues. Detailed phylogenetic analysis demonstrated expansion of the gene family encoding stilbene synthase and chalcone synthase enzymes in the phenylpropanoid metabolic pathway, which is associated with the biosynthesis of resveratrol, a pharmacologically important stilbene. Analysis of the draft genome identified 7 abscisic acid and water deficit stress-induced protein-coding genes and 14 cysteine-rich transmembrane module genes predicted to be involved in stress responses. The draft de novo genome assembly produced in this study represents a valuable resource for the molecular characterization of medicinal compounds in P. cuspidatum, the improvement of this important medicinal plant, and the exploration of its abiotic stress resistance.
KW  - genome assembly
KW  - resveratrol biosynthesis
KW  - whole-genome duplication
KW  - medicinal plant
KW  - stress tolerance
KW  - Polygonum  cuspidatum
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189279
SN  - 1664-462X
VL  - 10
ER  - 
TY  - JOUR
A1  - Topp, Max S.
A1  - van Meerten, Tom
A1  - Houot, Roch
A1  - Minnema, Monique C.
A1  - Bouabdallah, Krimo
A1  - Lugtenburg, Pieternella J.
A1  - Thieblemont, Catherine
A1  - Wermke, Martin
A1  - Song, Kevin W.
A1  - Avivi, Irit
A1  - Kuruvilla, John
A1  - Dührsen, Ulrich
A1  - Zheng, Yan
A1  - Vardhanabhuti, Saran
A1  - Dong, Jinghui
A1  - Bot, Adrian
A1  - Rossi, John M.
A1  - Plaks, Vicki
A1  - Sherman, Marika
A1  - Kim, Jenny J.
A1  - Kerber, Anne
A1  - Kersten, Marie José
T1  - Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma
JF  - British Journal of Haematology
N2  - Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel–related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 106 anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14·8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.
KW  - toxicity
KW  - large B-cell lymphoma
KW  - axi-cel
KW  - CAR T
KW  - corticosteroids
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258342
VL  - 195
IS  - 3
ER  -