PMID- 10916754
OWN - NLM
STAT- MEDLINE
DCOM- 20001222
LR  - 20191210
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 23
IP  - 4
DP  - 2000 Jul-Aug
TI  - Tumor necrosis factor-alpha augments tumor effects in isolated hepatic perfusion 
      with melphalan in a rat sarcoma model.
PG  - 449-55
AB  - Isolated hepatic perfusion (IHP) is an attractive approach to treating 
      nonresectable liver tumors, because the effects of systemic chemotherapy are poor 
      and its application is hampered by severe general toxicity. In clinical and 
      experimental settings, the efficacy of isolated limb perfusion (ILP) with tumor 
      necrosis factor-alpha (TNF alpha) in combination with melphalan to treat melanoma 
      in transit and soft-tissue sarcoma has been well established. In an ILP model in 
      rats, the authors previously observed synergistic anti-tumor effects of TNF and 
      melphalan on BN 175 soft-tissue sarcoma extremity tumors. The aim of the current 
      study was to determine whether similar synergy in anti-tumor effects could be 
      achieved by treating experimental BN 175 soft-tissue sarcoma liver tumors by IHP 
      using these agents. The authors found that IHP with TNF and melphalan resulted in 
      a dramatic increase in regional concentrations of perfused agents with virtually 
      no concomitant systemic leakage. Isolated hepatic perfusion with only carrier 
      solution resulted in a significantly diminished growth rate of BN 175 liver 
      tumors compared with the growth rate of tumors in nonperfused rats. Perfusion 
      with melphalan alone resulted in minimal anti-tumor effects. Perfusion with only 
      TNF had a slight growth-stimulatory effect on the BN 175 liver tumors, but no 
      negative effects on tumor growth were observed. When TNF was added to melphalan, 
      a dramatic anti-tumor effect was observed. Thus, as in the rat ILP setting, the 
      anti-tumor effect is augmented when TNF is added to IHP with melphalan to treat 
      BN 175 soft-tissue sarcoma tumor-bearing rats. Strikingly, the tumor response was 
      potentiated at relatively low concentrations of TNF compared with concentrations 
      that elicited synergy with melphalan in ILP.
FAU - van Ijken, M G
AU  - van Ijken MG
AD  - Department of Surgical Oncology, University Hospital Rotterdam/Daniel den Hoed 
      Cancer Center, Rotterdam, The Netherlands.
FAU - van Etten, B
AU  - van Etten B
FAU - de Wilt, J H
AU  - de Wilt JH
FAU - van Tiel, S T
AU  - van Tiel ST
FAU - ten Hagen, T L
AU  - ten Hagen TL
FAU - Eggermont, A M
AU  - Eggermont AM
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - Q41OR9510P (Melphalan)
SB  - IM
CIN - J Immunother. 2000 Jul-Aug;23(4):505-6. PMID: 10916761
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/therapeutic use
MH  - Chemotherapy, Cancer, Regional Perfusion/*methods
MH  - Combined Modality Therapy
MH  - Liver/blood supply
MH  - Liver Neoplasms/*drug therapy/*therapy
MH  - Male
MH  - Melphalan/*therapeutic use
MH  - Rats
MH  - Sarcoma, Experimental/*drug therapy/*therapy
MH  - Tumor Necrosis Factor-alpha/*administration & dosage/analysis
EDAT- 2000/08/05 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/05 11:00
PHST- 2000/08/05 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/05 11:00 [entrez]
AID - 10.1097/00002371-200007000-00008 [doi]
PST - ppublish
SO  - J Immunother. 2000 Jul-Aug;23(4):449-55. doi: 10.1097/00002371-200007000-00008.