PMID- 17136116
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20151119
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 21
IP  - 2
DP  - 2007 Feb
TI  - Antiproliferative activity of RAD001 (everolimus) as a single agent and combined 
      with other agents in mantle cell lymphoma.
PG  - 333-9
AB  - Mantle cell lymphoma (MCL) is an aggressive form of B-cell non-Hodgkin's 
      lymphoma, with a mean survival of only 3-5 years and suboptimal therapeutic 
      options. MCL is characterized by a balanced translocation t(11;14)(q13;q32), 
      resulting in overexpression of cyclin D1, a G(1) cyclin regulated by the 
      PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. As improved 
      therapy for MCL is required and the mTOR pathway may be involved in its 
      pathophysiology, the antiproliferative effects of RAD001 (everolimus), an mTOR 
      inhibitor, against three MCL cell lines were investigated. As a single agent, 
      RAD001 inhibited proliferation in MCL cell lines (Jeko1, SP49 and NCEB1) 
      approximately 40-65% compared to diluent control cells. This was associated with 
      G(1) cell-cycle arrest and reduced phosphorylation of the mTOR downstream target, 
      4E-BP1. Furthermore, combination drug studies revealed predominantly synergistic 
      cytotoxicity with RAD001 and several secondary agents, including doxorubicin, 
      vincristine or rituximab (components of the standard MCL regimen), as well as 
      paclitaxel, vorinostat and bortezomib. These data indicate that single agent 
      RAD001 is effective in inhibiting growth of MCL cells in vitro and combination 
      studies with secondary agents further demonstrate synergistic cytotoxicity. Thus, 
      these findings support future clinical studies of RAD001 in the treatment of MCL.
FAU - Haritunians, T
AU  - Haritunians T
AD  - Division of Hematology/Oncology, Cedars-Sinai Medical Center and UCLA School of 
      Medicine, Los Angeles, CA 90048, USA. haritunianst@cshs.org
FAU - Mori, A
AU  - Mori A
FAU - O'Kelly, J
AU  - O'Kelly J
FAU - Luong, Q T
AU  - Luong QT
FAU - Giles, F J
AU  - Giles FJ
FAU - Koeffler, H P
AU  - Koeffler HP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061130
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Antibiotics, Antineoplastic/administration & dosage/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Dimethyl Sulfoxide/pharmacology
MH  - Everolimus
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*pathology
MH  - Sirolimus/administration & dosage/*analogs & derivatives/pharmacology
EDAT- 2006/12/01 09:00
MHDA- 2007/09/26 09:00
CRDT- 2006/12/01 09:00
PHST- 2006/12/01 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2006/12/01 09:00 [entrez]
AID - 2404471 [pii]
AID - 10.1038/sj.leu.2404471 [doi]
PST - ppublish
SO  - Leukemia. 2007 Feb;21(2):333-9. doi: 10.1038/sj.leu.2404471. Epub 2006 Nov 30.