Possible Relationships Between
            <i>In Vivo</i>
            Antitumour Activity and Toxicity of Tumour Necrosis Factor‐α

Ma, Palladino; Js, Patton; Is, Figari; Mr, Shalaby

doi:10.1002/9780470513521.ch3

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…The role of TNF in carcinogenicity and tumor surveillance has not been established. Early cell culture studies indicated that TNF is cytotoxic for certain tumor cell lines ( Old 1985 ; Creasey et al 1986 ; Palladino, Patton, et al 1987 ; Palladino, Srivastava, et al 1987 ). Subsequent studies revealed that, for certain types of malignancies, TNF may act as a growth factor ( Freedman et al 1992 ; Warzocha et al 1995 ; Filella et al 1996 ; Warzocha and Salles 1998 ; Warzocha, Bienvenu, et al 1998 ; Warzocha, Ribero, et al 1998 ; Renard et al 1999 ; Moore et al 1999 ) and may even enhance the metastatic potential of certain tumors ( Balkwill et al 1990 ; Malik et al 1990 ).…”

Section: Adverse Eventsmentioning

confidence: 99%

The safety of etanercept for the treatment of plaque psoriasis

Papp

2007

Therapeutics and Clinical Risk Management

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Effective treatment with etanercept results from a congregation of immunological signaling and modulating roles played by tumor necrosis factor-alpha (TNF-alpha), a pervasive member of the TNF super-family of cytokines participating in numerous immunologic and metabolic functions. Macrophages, lymphocytes and other cells produce TNF as part of the deregulated immune response resulting in psoriasis or other chronic infl ammatory disorders. Tumor necrosis factor is also produced by macrophages and lymphocytes responding to foreign antigens as a primary response to potential infection. Interference with cytokine signaling by etanercept yields therapeutic response. At the same time, interference with cytokine signaling by etanercept exposes patients to potential adverse events. While the effi cacy of etanercept for the treatment of psoriasis is evident, the risks of treatment continue to be defi ned. Of the potential serious adverse events, response to infection is the best characterized in terms of physiology, incidence, and management. Rare but serious events: activation of latent tuberculosis, multiple sclerosis, lymphoma, and others, have been observed but have questionable or yet to be defi ned association with therapeutic uses of etanercept. The safe use of etanercept for the treatment of psoriasis requires an appreciation of potential adverse events as well as screening and monitoring strategies designed to manage patient risk

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Section: Adverse Eventsmentioning

confidence: 99%

The safety of etanercept for the treatment of plaque psoriasis

Papp

2007

Therapeutics and Clinical Risk Management

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“…Tumor necrosis factor-α (TNF-α) is a pleiotropic factor, which exhibits antitumor effects, alters endothelial barrier function, reduces tumor interstitial pressure and mediates immune responses (1). TNF-α is associated with a number of cell signalling events, is associated with cell necrosis and apoptosis, and is important for resistance to infection and cancer (2,3). However, due to its potential side effects, including cytotoxicity to healthy cells as well as cancer cells, for patients with cancer, it is not seen as a viable antitumor therapy, and its use is limited to locoregional treatments (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase-mediation of tumor targeting human recombinant tumor necrosis factor-α fusion protein

Ren

Shao

Zeng

et al. 2015

Molecular Medicine Reports

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The aim of the present study was to use genetic engineering in order to establish an efficient tumor necrosis factor (TNF)-α fusion protein with low toxicity, which may be used to target tumors. Four types of matrix metalloproteinase (MMP)-mediated tumor targeting human recombinant TNF-α (rhTNF-α) fusion protein vectors were constructed. These were subsequently introduced into Escherichia coli. rhTNF-α fusion protein with a glutathione S-transferase (GST)-tag was purified using GST resin affinity chromatography, and GST-tags were digested using factor Xa. The cytotoxic effects of the fusion protein on L929 cells were determined using MTT assays. At a concentration of 1 pM, the GST-tagged fusion protein exerted no cytotoxic effects on the cells, compared with the negative control cells (P=0.975>0.05). However, at a concentration of 1000 pM, the deblocking fusion protein exerted greater cytotoxic effects on L929 cells, compared with positive control cells (P<0.05). Treatment with the fusion protein also induced cell apoptosis in the nasopharyngeal cancer cell line, CNE-2Z, which secretes high levels of MMP-1. In conclusion, the results of the present study suggested that MMP-mediated rhTNF-α fusion protein induces CNE-2Z cells apoptosis. rhTNF-α exhibits high efficacy and tumor cell targeting capability, with low toxicity effects on healthy cells.

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Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan‐9‐yl‐xanthogenate and lauric acid

Amtmann

Sauer

1990

Intl Journal of Cancer

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Recombinant human tumor necrosis factor (rh TNF) when administered intravenously together with the phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate (D609) and lauric acid (C12), leads to the partial regression of various human tumor transplants in athymic mice. Extensive necrosis occurred after a single intravenous infusion, with no detectable side effects. TNF-mediated cytotoxicity was found to be correlated with the depletion of energy in HeLa cells. The activity of rh TNF was enhanced by the absence of glucose, while it was reduced by addition of extraneous ATP. In the presence of rh TNF, D609, and C12, cellular energy metabolism was almost completely switched to glycolysis. Under these conditions the cytocidal activity of rh TNF on HeLa cells was amplified at least 60-fold.

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Possible Relationships Between In Vivo Antitumour Activity and Toxicity of Tumour Necrosis Factor‐α

Cited by 6 publications

References 33 publications

The safety of etanercept for the treatment of plaque psoriasis

The safety of etanercept for the treatment of plaque psoriasis

Matrix metalloproteinase-mediation of tumor targeting human recombinant tumor necrosis factor-α fusion protein

Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan‐9‐yl‐xanthogenate and lauric acid

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