In vivo effects of tumor necrosis factor‐a on capillary permeability and vascular tone in a skeletal muscle

Jahr, John; Grände, Per‐Olof

doi:10.1111/j.1399-6576.1996.tb04429.x

Cited by 17 publications

(9 citation statements)

References 21 publications

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“…Furthermore, serial biopsies during TNF‐ILP have demonstrated upregulated multidrug resistance–associated genes and increased levels of major vault proteins in soft tissue sarcoma and malignant melanoma . In experimental studies, rhTNFα has led to increased vessel permeability and decreased interstitial pressure as immediate effects after administration . These early antivascular effects lead to an up to 6‐fold–increased uptake of melphalan into the tumor .…”

Section: Mode Of Action Of Tnf‐ilpmentioning

confidence: 99%

“…13 In experimental studies, rhTNFa has led to increased vessel permeability and decreased interstitial pressure as immediate effects after administration. 14,15 These early antivascular effects lead to an up to 6-fold-increased uptake of melphalan into the tumor. 16 Late antivascular effects are best demonstrated in pre-and post-TNF-ILP angiograms or gadolinium-based magnetic resonance imaging, which shows a complete shutdown of tumor vasculature; this is most likely mediated by tumor vessel disintegration and endothelial apoptosis ( Fig.…”

Section: Mode Of Action Of Tnf-ilpmentioning

confidence: 99%

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Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Jakob

Hohenberger

2016

Cancer

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Isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan (TNF-ILP) is a highly effective regional treatment for locally advanced soft tissue sarcoma. This review critically discusses the indication for TNF-ILP. AbstractManagement of locally advanced extremity soft tissue sarcoma of the limbs is challenging particularly in recurrent tumors and those adjacent to neurovascular bundles and joints. Typically the tumors are large, below the fascia and of high grade (T2b, stage III according to AJCC) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics.Isolated limb perfusion with recombinant human tumor necrosis factor α (TNF-ILP) adds a therapeutic option to radiation therapy and systemic chemotherapy. Although the procedure is somewhat sophisticated to learn, it is a safe method working for now almost two decades in more than 50 centers worldwide. TNF-ILP yields a high rate of pathologic complete or near-complete tumor remission. Combined with post-ILP surgical resection of the tumor remnant the limb salvage rate is close to 90%. Often adjuvant radiation therapy can be spared without compromising longterm local tumor control rates. Nevertheless, TNF-ILP has never been compared to other treatment regimen in a randomized trial. This review summarizes the mode of action and the standard application of TNF-ILP and focuses on a critical discussion on the role of TNF-ILP in multimodal treatment of locally advanced primary and recurrent extremity sarcoma.

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Section: Mode Of Action Of Tnf‐ilpmentioning

confidence: 99%

Section: Mode Of Action Of Tnf-ilpmentioning

confidence: 99%

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Jakob

Hohenberger

2016

Cancer

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“…In 1993, Wheatley's study also showed that TNF could increase the permeability of lung endothelial cell monolayers and that fibronectin could blunt this effect 96 , while Partridge revealed that the TNF-induced increase in endothelial permeability involves the loss of fibronectin and remodeling of the extracellular matrix 97 . It has also been shown that TNF can increase capillary permeability causing transcapillary filtration in vivo 98 .…”

Section: Effects Of Tnf On Permeability Of Epithelialendothelial Barriermentioning

confidence: 99%

The dual role of TNF in pulmonary edema

Yang¹,

Hamacher²,

Gorshkov³

et al. 2010

Journal of Cardiovascular Disease Research

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—Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema.Abbreviations:—tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);

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“…6). TNF also reduces IFP, as evidenced by an increase in capillary filtration with no effect on capillary tone [14]. Taken together, these results indicate a selective effect of TNF on angiogenic endothelial cells.…”

Section: Tnf-αmentioning

confidence: 56%

Improving drug penetration in tumors by targeting tumor vascularization

Lejeune

2006

Targ Oncol

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Clinical oncologists have not been paying enough attention to the fact that poor tumor penetration represents a major impediment to the efficiency of cancer chemotherapeutics. The cytokine tumor necrosis factor (TNF) was the first treatment shown to affect tumor vessel destruction and improve vascular permeability of drugs in a clinical setting. TNF produces an early increase of vessel permeability followed by a dual targeting: TNF induces apoptosis of intratumoral angiogenic endothelial cells and melphalan during the apoptosis of tumor cells. Given the systemic toxicity, TNF has to be administered by regional therapy. However, experimental data indicate that a systemic approach will be possible, thanks to TNF targeting. Three fusion proteins with TNF were shown to target tumors: anti-EDB fibronectin/TNF, Asn-Gly-Arg-TNF, and anti-gp240/TNF. Current approaches to blocking angiogenesis include strategies that target vascular endothelium growth factor (VEGF)-A. However, little attention has been paid to possible drawbacks, which may include vessel destruction and reduced penetration by chemotherapeutic agents administered simultaneously or subsequently. An antiangiogenic treatment is optimal when it is given at a critical dose and at a critical time. Current protocols seem not to take these prerequisites into consideration. Other new approaches to increased tumor vessel permeability include histamine and combretastatin analog. The current paradigm of antitumor strategy based on the synergism of empirical drug combinations is obsolete. Instead, the design of protocols based on new pharmacodynamic concepts should provide better efficiency of cancer treatment as exemplified in the use of TNF and anti-VEGF antibody.

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In vivo effects of tumor necrosis factor‐a on capillary permeability and vascular tone in a skeletal muscle

Abstract: TNF is a potent drug for increasing capillary permeability causing transcapillary filtration in vivo. Its release, e.g. during sepsis, may therefore contribute to the capillary leakage often seen in this clinical situation.

Cited by 17 publications

References 21 publications

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

The dual role of TNF in pulmonary edema

Improving drug penetration in tumors by targeting tumor vascularization

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