scholarly journals Glucocorticoid-mediated inhibition of endotoxin-induced intratumor tumor necrosis factor production and tumor hemorrhagic necrosis and regression.

1989 ◽  
Vol 170 (3) ◽  
pp. 703-710 ◽  
Author(s):  
R J North ◽  
E A Havell
Keyword(s):  
Tumor Necrosis Factor ◽  
Intravenous Injection ◽  
Subcutaneous Injection ◽  
Tumor Necrosis ◽  
Complete Regression ◽  
Tumor Necrosis Factor Production ◽  
The Core ◽  
Hemorrhagic Necrosis ◽  
Extensive Necrosis ◽  
Necrosis Factor

Intravenous injection of 25 micrograms of bacterial endotoxin on day 9 of growth of the SA1 sarcoma results in extensive necrosis of the core of this tumor and in its subsequent complete regression. Tumor hemorrhagic necrosis and regression failed to occur in mice that were given a subcutaneous injection of cortisone acetate or dexamethasone 12 h before being giving endotoxin. Inhibition of tumor hemorrhagic necrosis and regression by glucocorticoids was associated with inhibition of endotoxin-induced intratumor TNF production that normally takes place several h after endotoxin is given. In contrast, glucocorticoids had no effect on the ability of intravenously injected rTNF to cause tumor hemorrhagic necrosis and regression. The results lend further support to the belief that TNF is the predominant mediator of endotoxin-induced hemorrhagic necrosis of established murine tumors, and that hemorrhagic necrosis is a prerequisite for the immunologically mediated regression that follows.

scholarly journals The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity.

1988 ◽  
Vol 167 (3) ◽  
pp. 1067-1085 ◽  
Author(s):  
E A Havell ◽  
W Fiers ◽  
R J North
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Cells ◽  
Tumor Necrosis ◽  
Tumor Regression ◽  
Cytotoxic Action ◽  
Complete Regression ◽  
Severe Toxicity ◽  
Hemorrhagic Necrosis ◽  
Necrosis Factor

The ability of murine recombinant tumor necrosis factor (rTNF) and natural TNF in tumor-necrotizing serum (TNS) to cause regression of the SA1 sarcoma was investigated. We found that to cause regression of a 9-d SA1 sarcoma, near lethal quantities of rTNF and TNS had to be given to the host. However, even at these highly toxic doses, rTNF was not reliable at causing complete tumor regression. On the other hand, both types of TNF were reliable at causing a tumor hemorrhagic reaction that resulted in the destruction of greater than 75% of the tumor's center in 24 h. The TNF-induced hemorrhagic reaction involved the development of numerous petechial hemorrhages in the tumor's vascular bed, which apparently resulted from destruction of the tumor's blood vessels. It was possible to follow the development of the hemorrhagic reaction against time after giving rTNF or TNS by measuring the intratumor extravasation of 51Cr-labeled syngeneic red cells. According to this method, TNF-induced intratumor hemorrhaging was in progress within 1 h of giving TNF and continued for about a 6-h period. However, the hemorrhagic reaction was greatly reduced and complete regression of the rim of the living tumor tissue that survived hemorrhagic necrosis failed to occur, if SA1 sarcoma was growing in T cell-deficient (TXB) mice. This indicates that the TNF-induced hemorrhagic reaction is partly dependent, and the tumor regression that follows is completely dependent on host immunocompetence. This suggests in turn, that rTNF does not directly destroy SA1 tumor cells in vivo, even though it was shown that it can destroy SA1 tumor cells in vitro. This interpretation is supported by the additional findings that rTNF was no more therapeutic against a 3-d (3-mm) SA1 than against a 9-d (8-mm) SA1, and was no more therapeutic when injected directly into the tumor than when injected intravenously. Lastly it was possible to completely inhibit the ability of rTNF and TNS to cause tumor hemorrhagic necrosis and regression by infusing the host with a monospecific, polyvalent anti-rTNF antibody that neutralized the cytotoxic action of rTNF in vitro.

scholarly journals The core promoter region of the tumor necrosis factor alpha gene confers phorbol ester responsiveness to upstream transcriptional activators.

1992 ◽  
Vol 12 (3) ◽  
pp. 1352-1356 ◽  
Author(s):  
D C Leitman ◽  
E R Mackow ◽  
T Williams ◽  
J D Baxter ◽  
B L West
Keyword(s):  
Transcription Factors ◽  
Tumor Necrosis Factor ◽  
Promoter Region ◽  
Tumor Necrosis ◽  
Core Promoter ◽  
Core Promoter Region ◽  
Necrosis Factor Alpha ◽  
The Core ◽  
Factor Alpha ◽  
Necrosis Factor

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

scholarly journals Identification of a Major Locus, TNF1, That Controls BCG-Triggered Tumor Necrosis Factor Production by Leukocytes in an Area Hyperendemic for Tuberculosis

2013 ◽  
Vol 57 (7) ◽  
pp. 963-970 ◽  
Author(s):  
Aurelie Cobat ◽  
Eileen G. Hoal ◽  
Caroline J. Gallant ◽  
Leah Simkin ◽  
Gillian F. Black ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Production ◽  
Major Locus ◽  
Factor Production ◽  
Necrosis Factor

Inhibitors of Cytochrome P450 Suppress Tumor Necrosis Factor Production

1993 ◽  
Vol 150 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Giamila Fantuzzi ◽  
Lavinia Cantoni ◽  
Marina Sironi ◽  
Pietro Ghezzi
Keyword(s):  
Cytochrome P450 ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Production ◽  
Factor Production ◽  
Necrosis Factor

Differential Tumor Necrosis Factor Production by Human Monocyte Subsets

1990 ◽  
Vol 47 (3) ◽  
pp. 206-216 ◽  
Author(s):  
Gyongyi Szabo ◽  
Carol L. Miller-Graziano ◽  
Jia-Yan Wu ◽  
Thomas Takayama ◽  
Karen Kodys
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Monocyte ◽  
Monocyte Subsets ◽  
Tumor Necrosis Factor Production ◽  
Factor Production ◽  
Necrosis Factor

scholarly journals Mast cell tumor necrosis factor   production is regulated by MEK kinases

1997 ◽  
Vol 94 (12) ◽  
pp. 6358-6363 ◽  
Author(s):  
T. Ishizuka ◽  
N. Terada ◽  
P. Gerwins ◽  
E. Hamelmann ◽  
A. Oshiba ◽  
...  
Keyword(s):  
Mast Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Tumor ◽  
Tumor Necrosis Factor Production ◽  
Factor Production ◽  
Mast Cell Tumor ◽  
Necrosis Factor
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