PMID- 11747620
OWN - NLM
STAT- MEDLINE
DCOM- 20020219
LR  - 20061115
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 21
IP  - 11
DP  - 2001 Nov
TI  - Liposome-encapsulated tumor necrosis factor-alpha enhances the effects of 
      radiation against human colon tumor xenografts.
PG  - 885-97
AB  - Recent reports have shown that tumor necrosis factor-alpha (TNF-alpha) can 
      augment the effects of radiation against certain tumor types. However, the high 
      concentrations of intravenous infusion of TNF-alpha needed to cause tumor 
      regression can induce many systemic side effects. The aims of this study were to 
      determine if TNF-alpha encapsulated in sterically stabilized (Stealth, ALZA 
      Corporation, Mountain View, CA), PEGylated liposomes (SL) augments the antitumor 
      effects of radiation and to compare its efficacy and possible toxicity with free 
      TNF-alpha in the LS174T human colon tumor xenograft model. Nude mice were 
      injected subcutaneously (s.c.) with LS174T cells and treated intravenously (i.v.) 
      with Stealth-liposomal TNF-alpha (SL-TNF-alpha) with and without radiation or 
      TNF-alpha with or without radiation when tumor size was approximately 200 mm(3). 
      In phase 1, a significant decrease (p = 0.047) in tumor growth was observed with 
      radiation at day 21 but not with SL-TNF-alpha or free TNF-alpha alone. By the end 
      of phase 1 (day 27) with continued treatments, the SL-TNF-alpha plus radiation 
      group had significantly smaller tumors (p = 0.044) than those in the free 
      TNF-alpha plus radiation group. In phase 2, where a similar tumor growth 
      reduction pattern was observed, the addition of TNF-alpha to radiation, either as 
      free protein or within SL, increased lymphocyte activation and natural killer 
      (NK) cell numbers in both blood and spleen. The effect was generally more 
      pronounced with SL-TNF-alpha. Systemic toxicity, based on hematologic analyses 
      and body weight, was absent or minimal. Collectively, the data show that 
      pretreatment with SL-TNF-alpha can enhance more effectively, and possibly more 
      safely, the effects of radiation against human colon tumor xenografts than can 
      free TNF-alpha and that the increased antitumor action may involve upregulation 
      of lymphocytes.
FAU - Kim, D W
AU  - Kim DW
AD  - Department of Microbiology & Molecular Genetics, Loma Linda University School of 
      Medicine, Loma Linda, CA 92350, USA.
FAU - Andres, M L
AU  - Andres ML
FAU - Li, J
AU  - Li J
FAU - Kajioka, E H
AU  - Kajioka EH
FAU - Miller, G M
AU  - Miller GM
FAU - Seynhaeve, A L
AU  - Seynhaeve AL
FAU - Ten Hagen, T L
AU  - Ten Hagen TL
FAU - Gridley, D S
AU  - Gridley DS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Liposomes)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Blood Cell Count
MH  - Body Weight/drug effects/radiation effects
MH  - Cell Division/drug effects/radiation effects
MH  - Chemotherapy, Adjuvant
MH  - Colonic Neoplasms/*drug therapy/immunology/pathology/*radiotherapy
MH  - Humans
MH  - Immunophenotyping
MH  - Kinetics
MH  - Liposomes
MH  - Lymphocyte Activation/drug effects/radiation effects
MH  - Lymphocyte Subsets/classification/drug effects/radiation effects
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Organ Size/drug effects/radiation effects
MH  - Radiation-Sensitizing Agents/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Spleen/immunology/pathology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Xenograft Model Antitumor Assays
EDAT- 2001/12/19 10:00
MHDA- 2002/02/20 10:01
CRDT- 2001/12/19 10:00
PHST- 2001/12/19 10:00 [pubmed]
PHST- 2002/02/20 10:01 [medline]
PHST- 2001/12/19 10:00 [entrez]
AID - 10.1089/107999001753289497 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2001 Nov;21(11):885-97. doi: 
      10.1089/107999001753289497.