PMID- 23932230
OWN - NLM
STAT- MEDLINE
DCOM- 20140120
LR  - 20151119
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 49
IP  - 17
DP  - 2013 Nov
TI  - Inhibition of the tumour necrosis factor-alpha autocrine loop enhances the 
      sensitivity of multiple myeloma cells to anticancer drugs.
PG  - 3708-17
LID - S0959-8049(13)00560-1 [pii]
LID - 10.1016/j.ejca.2013.07.010 [doi]
AB  - Several autocrine soluble factors, including macrophage inflammatory protein-1alpha 
      and tumour necrosis factor-alpha (TNF-alpha), promote the survival and growth of 
      multiple myeloma (MM) cells. We hypothesised that inhibition of the TNF-alpha 
      autocrine loop may enhance the cytotoxic effect of anticancer drugs in MM cell 
      lines. In the present study, a TNF-alpha-neutralizing antibody suppressed cell 
      proliferation and enhanced the cytotoxic effect of anticancer drugs on MM cells. 
      In addition, combination treatment with the TNF-alpha-neutralizing antibody and the 
      chemotherapy agent melphalan inhibited nuclear factor kappaB (NF-kappaB) p65 nuclear 
      translocation and mammalian target of rapamycin (mTOR) activation and upregulated 
      the expression of Bax and Bim. Treatment of ARH-77 cells with the NF-kappaB inhibitor 
      dimethyl fumarate or the mTOR inhibitor rapamycin suppressed NF-kappaB p65 nuclear 
      translocation and enhanced the cytotoxic effect of melphalan. Furthermore, 
      infliximab, a monoclonal antibody against TNF-alpha, also enhanced the cytotoxic 
      effect of anticancer drugs in ARH-77 cells. These results indicated that 
      TNF-alpha-neutralizing antibodies or infliximab enhanced the cytotoxic effect of 
      anticancer drugs by suppressing the TNF receptor/mTOR/NF-kappaB pathways. The 
      inhibition of TNF-alpha may thus provide a new therapeutic approach to control tumour 
      progression and bone destruction in MM patients.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Tsubaki, Masanobu
AU  - Tsubaki M
AD  - Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, 
      Higashi-Osaka, Japan.
FAU - Komai, Makiko
AU  - Komai M
FAU - Itoh, Tatsuki
AU  - Itoh T
FAU - Imano, Motohiro
AU  - Imano M
FAU - Sakamoto, Kotaro
AU  - Sakamoto K
FAU - Shimaoka, Hirotaka
AU  - Shimaoka H
FAU - Ogawa, Naoki
AU  - Ogawa N
FAU - Mashimo, Kenji
AU  - Mashimo K
FAU - Fujiwara, Daichiro
AU  - Fujiwara D
FAU - Takeda, Tomoya
AU  - Takeda T
FAU - Mukai, Junji
AU  - Mukai J
FAU - Sakaguchi, Katsuhiko
AU  - Sakaguchi K
FAU - Satou, Takao
AU  - Satou T
FAU - Nishida, Shozo
AU  - Nishida S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130807
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Fumarates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - FO2303MNI2 (Dimethyl Fumarate)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology/therapeutic use
MH  - Antibodies, Neutralizing/pharmacology
MH  - Antineoplastic Agents/*therapeutic use
MH  - Autocrine Communication/drug effects
MH  - Dimethyl Fumarate
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Drug Synergism
MH  - Fumarates/*pharmacology/therapeutic use
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Infliximab
MH  - Melphalan/therapeutic use
MH  - Multiple Myeloma/*drug therapy/genetics
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
OTO - NOTNLM
OT  - Multiple myeloma
OT  - NF-kappaB
OT  - TNF-alpha
OT  - mTOR
EDAT- 2013/08/13 06:00
MHDA- 2014/01/21 06:00
CRDT- 2013/08/13 06:00
PHST- 2013/04/29 00:00 [received]
PHST- 2013/06/25 00:00 [revised]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/01/21 06:00 [medline]
AID - S0959-8049(13)00560-1 [pii]
AID - 10.1016/j.ejca.2013.07.010 [doi]
PST - ppublish
SO  - Eur J Cancer. 2013 Nov;49(17):3708-17. doi: 10.1016/j.ejca.2013.07.010. Epub 2013 
      Aug 7.