TY  - JOUR
AB  - Primary mediastinal B cell lymphoma (PMBL) is characterized by specific molecular hallmarks including the expression of B Cell Lymphoma factor 6 (BCL6) and the presence of the activated Signal Transducers and Activators of Transcription factor 6 (STAT6). Recently we have shown that combined targeting of BCL6 and activated STAT6 by specific chemical inhibitors in PMBL resulted in additive efficacy regarding their negative effects on cell viability. Given that despite general efficient immuno-chemotherapy in PMBL the delayed treatment-related sequelae remains still a main challenge, we analyzed the role of BCL6 and activated STAT6 in the sensitivity of PMBL cells to the current treatment components. We found that the knock-down of BCL6 / STAT6 by siRNA sensitized the PMBL cells to the effects of R-CHOP components in two of three PMBL cell lines. In one cell line, MedB-1, which is marked by less expression of BCL6 and mutated STAT6, the knock-down of BCL6 / STAT6 did not enhance the efficiency of Doxorubicin, Rituximab, and Vincristin. Thus, the targeting of BCL6 and STAT6 in addition or prior to the treatment with components of the current immuno-chemotherapy may sensitize the PMBL tumor cells for drug effects, at least in parts of PMBL cases.
AU  - Häberle, M.-T.
AU  - Kelsch, E.*
AU  - Dorsch, K.*
AU  - Möller, P.*
AU  - Ritz, O.*
C1  - 43103
C2  - 36059
SP  - 283-286
TI  - Knock-down of BCL6 / STAT6 sensitizes primary B cell lymphoma cells for treatment with current therapeutic agents.
JO  - Oncoscience
VL  - 1
IS  - 4
PY  - 2014
ER  - 

TY  - JOUR
AB  - Epithelial-mesenchymal transition (EMT) contributes to the progression of cancer through enhanced invasion and stem-like properties of cancer cells. Additionally, EMT confers resistance towards many chemotherapeutics. We recently described a mechanism that mediates EMT-driven chemoresistance through augmented levels of Bcl-xL, an anti-apoptotic member of the Bcl-2 family (Keitel et al., Oncotarget, in press). Here, we elaborate on how these findings pertain to cancer cells dispersed in the tumor-adjacent stroma of breast cancer tissues, and how BH3-mimetics may provide a therapeutic strategy to eliminate cancer cell populations that have passed through an EMT.
AU  - Keitel, U.*
AU  - Scheel, C.
AU  - Dobbelstein, M.*
C1  - 43104
C2  - 36058
SP  - 706-708
TI  - Overcoming EMT-driven therapeutic resistance by BH3 mimetics.
JO  - Oncoscience
VL  - 1
IS  - 11
PY  - 2014
ER  -