TY  - JOUR
A1  - Kuai, Yue
A1  - Gong, Xin
A1  - Ding, Liya
A1  - Li, Fang
A1  - Lei, Lizhen
A1  - Gong, Yuqi
A1  - Liu, Qingmeng
A1  - Tan, Huajiao
A1  - Zhang, Xinxia
A1  - Liu, Dongyu
A1  - Ren, Guoping
A1  - Pan, Hongyang
A1  - Shi, Yaoyao
A1  - Berberich-Siebelt, Friederike
A1  - Ma, Zhengrong
A1  - Zhou, Ren
T1  - Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90
JF  - Cell Communication and Signaling
N2  - Background
Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear.

Methods
Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation.

Results
WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro.

Conclusion
WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.
KW  - WTAP
KW  - BCL6
KW  - Hsp90
KW  - complex
KW  - DLBCL
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230168
VL  - 16
ER  - 
TY  - JOUR
A1  - Herrmann, Ken
A1  - Buck, Andreas K.
A1  - Schuster, Tibor
A1  - Abbrederis, Kathrin
A1  - Blümel, Christina
A1  - Santi, Ivan
A1  - Rudelius, Martina
A1  - Wester, Hans-Jürgen
A1  - Peschel, Christian
A1  - Schwaiger, Markus
A1  - Dechow, Tobias
A1  - Keller, Ulrich
T1  - Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL
JF  - Oncotarget
N2  - Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.
KW  - [18F]Fluorodeoxythymidine
KW  - FLT-PET
KW  - positron emission tomography
KW  - DLBCL
KW  - lymphoma
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120659
SN  - 1949-2553
VL  - 5
IS  - 12
ER  -