Primaquine as a Candidate for HHV-8-Associated Primary Effusion Lymphoma and Kaposi's Sarcoma Treatment.
Primaquine as a Candidate for HHV-8-Associated Primary Effusion Lymphoma and Kaposi's Sarcoma Treatment.
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DOI：
10.3390/cancers14030543
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发表时间：
2022-01-21
期刊：
影响因子：
5.2
通讯作者：
Calvez V
中科院分区：
文献类型：
--
作者：
Gothland A;Leducq V;Grange P;Faye O;Beauvais Remigereau L;Sayon S;Désiré N;Jary A;Laplantine E;Maiga AI;Dupin N;Marcelin AG;Calvez V
Primaquine diphosphate is introduced as a promising therapeutic candidate for HHV-8-associated diseases by inducing specific cytotoxicity in vitro through ROS- and ER stress-mediated apoptosis. PQ presented a promising anti-tumor effect in an in vivo PEL mouse model and in KS patients within a pilot clinical study. Human Herpesvirus 8 (HHV-8) is associated with three main severe orphan malignancies, Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL), which present few therapeutic options. We identified the antimalarial primaquine diphosphate (PQ) as a promising therapeutic candidate for HHV-8-associated PEL and KS. Indeed, PQ strongly reduced cell viability through caspase-dependent apoptosis, specifically in HHV-8-infected PEL cells. Reactive oxygen species (ROS)- and endoplasmic reticulum (ER) stress-mediated apoptosis signaling pathways were found to be part of the in vitro cytotoxic effect of PQ. Moreover, PQ treatment had a clinically positive effect in a nonobese diabetic (NOD)/SCID xenograft PEL mouse model, showing a reduction in tumor growth and an improvement in survival. Finally, an exploratory proof-of-concept clinical trial in four patients harboring severe KS was conducted, with the main objectives to assess the efficacy, the safety, and the tolerability of PQ, and which demonstrated a positive efficacy on Kaposi’s sarcoma-related lesions and lymphedema.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
通讯作者：
Tohyama, Masaya
影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P
影响因子：
5.2
作者：
Purushothaman P;Dabral P;Gupta N;Sarkar R;Verma SC
通讯作者：
Verma SC
DOI：
10.1098/rstb.2016.0275
发表时间：
2017-10-19
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Mariggiò G;Koch S;Schulz TF
通讯作者：
Schulz TF
影响因子：
2.5
作者：
Rozpedek W;Pytel D;Mucha B;Leszczynska H;Diehl JA;Majsterek I
通讯作者：
Majsterek I