HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression
Over-expression of Bcl-2, Bcl-xL and Bcl-w is frequently associated with cancer resistance to chemotherapy. Navitoclax (ABT-263), an orally bio-available small-molecule mimetic of the Bcl-2 homology domain 3, specifically inhibits Bcl-2, Bcl-xL and Bcl-w. Despite promising results obtained from the...
Gespeichert in:
| Hauptverfasser: | , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2016
|
| In: |
International journal of cancer
Year: 2015, Jahrgang: 138, Heft: 2, Pages: 507-514 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.29726 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.29726 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.29726 
|
| Verfasserangaben: | Mathias Witzens‐Harig, Marco Giaisi, Rebecca Köhler, Peter H. Krammer and Min Li‐Weber |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1703397460 | ||
| 003 | DE-627 | ||
| 005 | 20230426114631.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200702r20162015xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ijc.29726 |2 doi | |
| 035 | |a (DE-627)1703397460 | ||
| 035 | |a (DE-599)KXP1703397460 | ||
| 035 | |a (OCoLC)1341344497 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Witzens-Harig, Mathias |e VerfasserIn |0 (DE-588)1050736516 |0 (DE-627)784812322 |0 (DE-576)404988970 |4 aut | |
| 245 | 1 | 0 | |a HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression |c Mathias Witzens‐Harig, Marco Giaisi, Rebecca Köhler, Peter H. Krammer and Min Li‐Weber |
| 264 | 1 | |c 2016 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a First published: 11 August 2015 | ||
| 500 | |a Gesehen am 02.07.2020 | ||
| 520 | |a Over-expression of Bcl-2, Bcl-xL and Bcl-w is frequently associated with cancer resistance to chemotherapy. Navitoclax (ABT-263), an orally bio-available small-molecule mimetic of the Bcl-2 homology domain 3, specifically inhibits Bcl-2, Bcl-xL and Bcl-w. Despite promising results obtained from the clinical trials, the use of Navitoclax in patients is dose-limited due to induction of death of platelets via inhibition of Bcl-xL and subsequent thrombocytopenia. This side effect limits the use of Navitoclax in low doses and to very sensitive tumors. In this study, we show that HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) cells, which over-express Bcl-2, Bcl-xL and Bcl-w, show a 10- to 20-fold higher sensitivity (EC50 = ∼25-50 nM) to Navitoclax compared to non-HTLV-1-associated leukemic cells (EC50 = ∼1 μM). Investigation of the molecular mechanisms revealed that the HTLV-1 oncogenic protein Tax up-regulates expression of the pro-apoptotic protein Bax which enhances the therapeutic efficacy of Navitoclax. In addition, we show that agents that inhibit the transcription elongation or translation initiation such as Wogonin and Roc-A can further decrease the effective dose of Navitoclax. Our study suggests that HTLV-1 ATL may be a good candidate disease for low dose Navitoclax therapy and probably with less risk of thrombocytopenia. | ||
| 534 | |c 2015 | ||
| 650 | 4 | |a ABT-263 | |
| 650 | 4 | |a anti-cancer therapy | |
| 650 | 4 | |a Bax | |
| 650 | 4 | |a HTLV-1 | |
| 650 | 4 | |a Navitoclax | |
| 700 | 1 | |a Giaisi, Marco |e VerfasserIn |4 aut | |
| 700 | 1 | |a Köhler, Rebecca |e VerfasserIn |4 aut | |
| 700 | 1 | |a Krammer, Peter H. |d 1946- |e VerfasserIn |0 (DE-588)121766373 |0 (DE-627)081520255 |0 (DE-576)292873417 |4 aut | |
| 700 | 1 | |a Li-Weber, Min |e VerfasserIn |0 (DE-588)1157205399 |0 (DE-627)1021010324 |0 (DE-576)502732695 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of cancer |d Bognor Regis : Wiley-Liss, 1966 |g 138(2016), 2, Seite 507-514 |h Online-Ressource |w (DE-627)269532781 |w (DE-600)1474822-8 |w (DE-576)079876129 |x 1097-0215 |7 nnas |a HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression |
| 773 | 1 | 8 | |g volume:138 |g year:2016 |g number:2 |g pages:507-514 |g extent:8 |a HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression |
| 856 | 4 | 0 | |u https://doi.org/10.1002/ijc.29726 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.29726 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200702 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 1050736516 |a Witzens-Harig, Mathias |m 1050736516:Witzens-Harig, Mathias |d 910000 |d 910100 |e 910000PW1050736516 |e 910100PW1050736516 |k 0/910000/ |k 1/910000/910100/ |p 1 |x j | ||
| 999 | |a KXP-PPN1703397460 |e 3694830804 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedKey":"2016","dateIssuedDisp":"2016"}],"id":{"eki":["1703397460"],"doi":["10.1002/ijc.29726"]},"name":{"displayForm":["Mathias Witzens‐Harig, Marco Giaisi, Rebecca Köhler, Peter H. Krammer and Min Li‐Weber"]},"physDesc":[{"extent":"8 S."}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"publisherPlace":"Bognor Regis","dateIssuedDisp":"1966-","publisher":"Wiley-Liss","dateIssuedKey":"1966"}],"id":{"issn":["1097-0215"],"eki":["269532781"],"doi":["10.1002/(ISSN)1097-0215"],"zdb":["1474822-8"]},"titleTranslated":[{"translated":"Journal international du cancer"}],"pubHistory":["1.1966 -"],"part":{"pages":"507-514","issue":"2","year":"2016","extent":"8","volume":"138","text":"138(2016), 2, Seite 507-514"},"titleAlt":[{"title":"Predictive oncology"}],"disp":"HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expressionInternational journal of cancer","type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 28.02.08","Darin: Predictive oncology"],"language":["eng"],"corporate":[{"role":"isb","roleDisplay":"Herausgebendes Organ","display":"International Union against Cancer"}],"recId":"269532781","title":[{"title_sort":"International journal of cancer","title":"International journal of cancer","subtitle":"publication of the International Union against Cancer (UICC) = Journal international du cancer"}]}],"title":[{"title_sort":"HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression","title":"HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression"}],"person":[{"given":"Mathias","family":"Witzens-Harig","role":"aut","display":"Witzens-Harig, Mathias","roleDisplay":"VerfasserIn"},{"given":"Marco","family":"Giaisi","role":"aut","roleDisplay":"VerfasserIn","display":"Giaisi, Marco"},{"display":"Köhler, Rebecca","roleDisplay":"VerfasserIn","role":"aut","family":"Köhler","given":"Rebecca"},{"given":"Peter H.","family":"Krammer","role":"aut","display":"Krammer, Peter H.","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Li-Weber, Min","role":"aut","family":"Li-Weber","given":"Min"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["First published: 11 August 2015","Gesehen am 02.07.2020"],"language":["eng"],"recId":"1703397460"} | ||
| SRT | |a WITZENSHARHTLV1ASSOC2016 | ||