In Vitro Cytotoxicity of Recombinant Human-TNF-.ALPHA. and Actinomycin D on Canine Normal and Tumor Cells.

Aoki, Mica; Kuwamura, Mitsuru; Kotani, Takao; Katamoto, Hiromu; Kubo, Kihei; Nomura, Koichi; Sasaki, Nobuo; Ohashi, Fumihito

doi:10.1292/jvms.60.1087

“…Oedema was scored as no formation of oedema (7), or oedema resulting in leg diameter increase of 1.5-fold or more (+). vitro were seen (Mosende et al, 1977;Aoki et al, 1998). Especially the TNF sensitive tumour cell line WEHI-164 responded in a synergistic fashion to the combination of actinomycin D and TNF.…”

Section: Discussionmentioning

confidence: 99%

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Seynhaeve

¹

,

Wilt

²

,

Tiel

³

et al. 2002

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Previously we demonstrated that addition of Tumour Necrosis Factor-a to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan.

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“…b Oedema was scored as no formation of oedema (7), or oedema resulting in leg diameter increase of 1.5-fold or more (+). vitro were seen (Mosende et al, 1977;Aoki et al, 1998). Especially the TNF sensitive tumour cell line WEHI-164 responded in a synergistic fashion to the combination of actinomycin D and TNF.…”

Section: Discussionmentioning

confidence: 99%

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Seynhaeve

¹

,

Wilt

²

,

Tiel

³

et al. 2002

View full text Add to dashboard Cite

Previously we demonstrated that addition of Tumour Necrosis Factor-a to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan.

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“…actinomycin D) and translation (e.g. cycloheximide (CHX)) inhibitors (8,9). Cell activation and apoptosis are the two cellular processes that can increase the shedding of cell-derived microparticles.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Reduces Tumour Necrosis Factor-Enhanced Annexin V-Positive Microparticle Release in Human Vascular Endothelial Cells

Kam

¹

,

Li

²

,

Razmovski-Naumovski

³

et al. 2015

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-PURPOSE:Circulating microparticles have been highlighted as biomarkers of cardiovascular disease state and progression. The aim of this study was to evaluate the effects of curcumin on microparticle release from endothelial cells undergoing TNF-induced cell activation and apoptosis. METHODS: This study evaluated the effects of curcumin on microparticle release, cytotoxicity, apoptosis, cell adhesion molecule expression and monocyte adhesion in EAhy926 human endothelial cells. RESULTS:The results showed that the numbers of microparticles were increased by tumour necrosis factor (TNF) or the combination of TNF and cycloheximide (CHX). Curcumin attenuated microparticle release caused by TNF or TNF plus CHX treatments. The pretreatment by curcumin not only negated the accelerated cell death and apoptosis caused by TNF and CHX, but also diminished TNF-induced cell activation, as assessed by reduced surface expression of intercellular adhesion molecule 1, and adhesion of monocytes to endothelial monolayers. CONCLUSION: Curcumin reduced microparticle release from endothelial cells undergoing cell activation and apoptosis, which supports its protective role in TNF-associated endothelial dysfunction, and highlights its potential use as a nutraceutical agent for vascular inflammatory diseases.

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In Vitro Cytotoxicity of Recombinant Human-TNF-.ALPHA. and Actinomycin D on Canine Normal and Tumor Cells.

Cited by 6 publications

References 21 publications

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Curcumin Reduces Tumour Necrosis Factor-Enhanced Annexin V-Positive Microparticle Release in Human Vascular Endothelial Cells

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