Experimental liver cancer: Improved response after hepatic artery ligation and infusion of tumor necrosis factor-alpha and interferon-gamma

Rong Yang, Qi Liu, Frederick Rescorla, Jay L. Grosfeld

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background. The aim of this study is to investigate whether regional infusion of tumor necrosis factoralpha (TNF-α) and interferon-gamma (IFN-γ) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. Methods. Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-γ 100,000 IU/rat/day (HAL+IFN group), TNF-α 30 μg/rat/day (HAL+TNF group), IFN+TNF (HAL+IFN+TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. Results. The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683±245 mm3 vs 2424±596 mm3, p<0.05 ANOVA). HAL+TNF (221±93 mm3) and HAL+IFN+TNF groups (74±31 mm3), but not the HAL+IFN group (493±164 mm3), were much more effective than the HAL group in controlling tumor growth (p<0.05). HAL+IFN+TNF achieved the best tumor control resulting in a 60% tumor-free rate (p<0.05 vs all other groups). Conclusions. These data suggest that HAL combined with regional infusion of TNF-α and IFN-γ significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.

Original languageEnglish
Pages (from-to)768-774
Number of pages7
JournalSurgery
Volume118
Issue number4
DOIs
StatePublished - 1995

Fingerprint

Hepatic Artery
Liver Neoplasms
Interferon-alpha
Interferon-gamma
Ligation
Tumor Necrosis Factor-alpha
Neoplasms
Necrosis
Tumor Burden
Growth
Inbred ACI Rats
Experimental Liver Neoplasms
Intra-Arterial Injections
Combined Modality Therapy
Sodium Chloride
Catheterization
Laparotomy
Analysis of Variance

ASJC Scopus subject areas

  • Surgery

Cite this

Experimental liver cancer : Improved response after hepatic artery ligation and infusion of tumor necrosis factor-alpha and interferon-gamma. / Yang, Rong; Liu, Qi; Rescorla, Frederick; Grosfeld, Jay L.

In: Surgery, Vol. 118, No. 4, 1995, p. 768-774.

Research output: Contribution to journalArticle

@article{232631a929d0462091539a281f55f336,
title = "Experimental liver cancer: Improved response after hepatic artery ligation and infusion of tumor necrosis factor-alpha and interferon-gamma",
abstract = "Background. The aim of this study is to investigate whether regional infusion of tumor necrosis factoralpha (TNF-α) and interferon-gamma (IFN-γ) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. Methods. Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-γ 100,000 IU/rat/day (HAL+IFN group), TNF-α 30 μg/rat/day (HAL+TNF group), IFN+TNF (HAL+IFN+TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. Results. The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683±245 mm3 vs 2424±596 mm3, p<0.05 ANOVA). HAL+TNF (221±93 mm3) and HAL+IFN+TNF groups (74±31 mm3), but not the HAL+IFN group (493±164 mm3), were much more effective than the HAL group in controlling tumor growth (p<0.05). HAL+IFN+TNF achieved the best tumor control resulting in a 60{\%} tumor-free rate (p<0.05 vs all other groups). Conclusions. These data suggest that HAL combined with regional infusion of TNF-α and IFN-γ significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.",
author = "Rong Yang and Qi Liu and Frederick Rescorla and Grosfeld, {Jay L.}",
year = "1995",
doi = "10.1016/S0039-6060(05)80048-0",
language = "English",
volume = "118",
pages = "768--774",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Experimental liver cancer

T2 - Improved response after hepatic artery ligation and infusion of tumor necrosis factor-alpha and interferon-gamma

AU - Yang, Rong

AU - Liu, Qi

AU - Rescorla, Frederick

AU - Grosfeld, Jay L.

PY - 1995

Y1 - 1995

N2 - Background. The aim of this study is to investigate whether regional infusion of tumor necrosis factoralpha (TNF-α) and interferon-gamma (IFN-γ) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. Methods. Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-γ 100,000 IU/rat/day (HAL+IFN group), TNF-α 30 μg/rat/day (HAL+TNF group), IFN+TNF (HAL+IFN+TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. Results. The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683±245 mm3 vs 2424±596 mm3, p<0.05 ANOVA). HAL+TNF (221±93 mm3) and HAL+IFN+TNF groups (74±31 mm3), but not the HAL+IFN group (493±164 mm3), were much more effective than the HAL group in controlling tumor growth (p<0.05). HAL+IFN+TNF achieved the best tumor control resulting in a 60% tumor-free rate (p<0.05 vs all other groups). Conclusions. These data suggest that HAL combined with regional infusion of TNF-α and IFN-γ significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.

AB - Background. The aim of this study is to investigate whether regional infusion of tumor necrosis factoralpha (TNF-α) and interferon-gamma (IFN-γ) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. Methods. Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-γ 100,000 IU/rat/day (HAL+IFN group), TNF-α 30 μg/rat/day (HAL+TNF group), IFN+TNF (HAL+IFN+TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. Results. The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683±245 mm3 vs 2424±596 mm3, p<0.05 ANOVA). HAL+TNF (221±93 mm3) and HAL+IFN+TNF groups (74±31 mm3), but not the HAL+IFN group (493±164 mm3), were much more effective than the HAL group in controlling tumor growth (p<0.05). HAL+IFN+TNF achieved the best tumor control resulting in a 60% tumor-free rate (p<0.05 vs all other groups). Conclusions. These data suggest that HAL combined with regional infusion of TNF-α and IFN-γ significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.

UR - http://www.scopus.com/inward/record.url?scp=0028889401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028889401&partnerID=8YFLogxK

U2 - 10.1016/S0039-6060(05)80048-0

DO - 10.1016/S0039-6060(05)80048-0

M3 - Article

C2 - 7570335

AN - SCOPUS:0028889401

VL - 118

SP - 768

EP - 774

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 4

ER -