PMID- 12536235
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 52
IP  - 1
DP  - 2003 Jan
TI  - Intra-arterial administration of TNF-alpha followed by arterial ablation is an 
      effective therapy for a regionally confined TNF-resistant rat mammary 
      adenocarcinoma.
PG  - 10-6
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an immunomodulatory cytokine that has 
      exhibited anti-tumor activity in a variety of experimental systems. However, the 
      toxicities associated with systemic administration of TNF-alpha have limited its 
      clinical utility and have led to the investigation of targeted delivery 
      techniques with the ability to present the TNF-alpha dose directly to the 
      vascular bed of the tumor. The intra-arterial (IA) administration of TNF-alpha to 
      patients with liver metastases represents one such approach, and recent work 
      suggests that subsequent ablation of the tumor's arterial supply via embolization 
      may enhance the efficacy of intra-arterial treatments (hepatic 
      chemoembolization). The present study was undertaken to test the hypothesis that 
      IA administration of TNF-alpha is superior to the intravenous (IV) route for 
      inhibition of tumor growth in a regionally confined rat mammary adenocarcinoma 
      model that provides for ablation of the arterial supply to the tumor following 
      cytokine therapy. Rats bearing hind limb mammary adenocarcinomas received single 
      IA or IV infusions of 8 x 10(5), 1 x 10(6), and 1.5 x 10(6) units of TNF-alpha 
      via the common femoral artery (CFA) followed 1 h later by ligation of the artery. 
      Control animals received either no treatment or IA infusion of 2% normal rat 
      serum (NRS) followed by ipsilateral CFA ligation. Tumor size was measured every 
      other day after treatment. Tumor growth inhibition occurred in the first 5 to 10 
      days after treatment. IV administration of TNF-alpha did not result in visual 
      tumor necrosis or significant reduction in the rate of tumor growth. IA 
      administration of TNF-alpha resulted in statistically significant diminution of 
      tumor size as compared to untreated controls and animals receiving IA 2% normal 
      rat serum (NRS; P<0.05 at days 6, 8 and 10), regardless of the dose employed. The 
      maximum growth inhibition with IA TNF-alpha was a 91% reduction in tumor volume 
      that was achieved with a dose of 1 x 10(6) U TNF-alpha. These results demonstrate 
      improved anti-tumor activity with the IA administration of TNF-alpha over the IV 
      route in a regionally confined mammary adenocarcinoma. IA administration of 
      biologic response modifiers like TNF-alpha may therefore be a useful approach for 
      the hepatic chemoembolization of breast adenocarcinomas metastatic to the liver.
FAU - Badgwell, Brian D
AU  - Badgwell BD
AD  - Department of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 
      West 10th Avenue, Columbus, OH 43210, USA.
FAU - Valentino, Daniel J
AU  - Valentino DJ
FAU - Jeffes, Edward B
AU  - Jeffes EB
FAU - Dieffenbach, Kevin
AU  - Dieffenbach K
FAU - Dulkanchainun, Sathit B
AU  - Dulkanchainun SB
FAU - Yamamoto, Robert S
AU  - Yamamoto RS
FAU - Granger, Gale A
AU  - Granger GA
FAU - Jakowatz, James G
AU  - Jakowatz JG
FAU - Carson, William E
AU  - Carson WE
LA  - eng
GR  - CA86016/CA/NCI NIH HHS/United States
GR  - P30 CA16058/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021101
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Immunologic Factors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adenocarcinoma/*drug therapy
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Femoral Artery/*surgery
MH  - Hindlimb
MH  - Immunologic Factors/pharmacology/*therapeutic use/toxicity
MH  - Infusions, Intravenous
MH  - Injections, Intra-Arterial
MH  - L Cells/drug effects
MH  - Ligation
MH  - Mammary Neoplasms, Experimental/*drug therapy
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Rats
MH  - Rats, Inbred F344
MH  - Recombinant Proteins/therapeutic use
MH  - Tumor Cells, Cultured/drug effects/transplantation
MH  - Tumor Necrosis Factor-alpha/pharmacology/*therapeutic use/toxicity
PMC - PMC11032911
EDAT- 2003/01/22 04:00
MHDA- 2003/03/13 04:00
PMCR- 2002/11/01
CRDT- 2003/01/22 04:00
PHST- 2002/04/23 00:00 [received]
PHST- 2002/08/15 00:00 [accepted]
PHST- 2003/01/22 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2003/01/22 04:00 [entrez]
PHST- 2002/11/01 00:00 [pmc-release]
AID - 0330 [pii]
AID - 10.1007/s00262-002-0330-2 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2003 Jan;52(1):10-6. doi: 10.1007/s00262-002-0330-2. 
      Epub 2002 Nov 1.