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, Ann L.B.; Wilt, Johannes H. W. de; Tiel, Sandra T. van; Eggermont, A.M.M.; Hagen, Timo L.M. ten

doi:10.1038/sj.bjc.6600169

Cited by 27 publications

(5 citation statements)

References 22 publications

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“…At this regard, several studies showed an association between elevated circulating TNF- α levels and cancer development [ 120 , 121 ] stimulating cell proliferation [ 122 ], causing DNA damage [ 123 ] and promoting angiogenesis [ 124 ]. This data was not confirmed by other studies that reported a direct cytotoxic effect of TNF- α on tumoral cell [ 125 ], an indirect action on tumor vessels [ 126 ] and a synergic action with conventional antineoplastic agents [ 127 , 128 ].…”

Section: Resultscontrasting

confidence: 83%

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

Sereno

Breda

Laganà

et al. 2012

International Journal of Rheumatology

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Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported. The most frenquetly studied TNF-α SNP is located at −308 position, where a substitution of the G allele with the rare A allele has been found. The presence of the allele −308A is associated to JIA and to a poor prognosis. Besides, the −308G genotype has been associated with a better response to anti-TNF-α therapy in JIA patients, confirming adult data. Psoriatic and oligoarticular arthritis are significantly associated to the −238 SNP only in some works. Studies considering other SNPs are conflicting and inconclusive. Large scale studies are required to define the contribution of TNF-α gene products to disease pathogenesis and anti-TNF-α therapeutic efficacy in JIA.

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Section: Resultscontrasting

confidence: 83%

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

Sereno

Breda

Laganà

et al. 2012

International Journal of Rheumatology

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“…However, TNF-␣ alone shows only marginal activity, even with administration at high doses through local drug delivery systems. To increase ma- lignant cell sensitivity to TNF-␣, it is combined with conventional antineoplastic agents (e.g., melphalan, paclitaxel, and actinomycin D) in clinical use (Manusama et al, 1996;de Wilt et al, 2000;Seynhaeve et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

LYG-202 Augments Tumor Necrosis Factor-α-Induced Apoptosis via Attenuating Casein Kinase 2-Dependent Nuclear Factor-κB Pathway in HepG2 Cells

Chen

Zhang

et al. 2012

Mol Pharmacol

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Tumor necrosis factor-␣ (TNF-␣) is being used as an antineoplastic agent in treatment regimens of patients with locally advanced solid tumors, but TNF-␣ alone is only marginally active. In clinical use, it is usually combined with other chemical agents to increase its tumor response rate. Our previous studies reported that LYG-202 (5-hydroxy-8-methoxy-7-(4-(4-methylpiperazin-1-yl)butoxy)-2-phenyl-4H-chromen-4-one), a synthesized flavonoid with a piperazine substitution, has antiproliferative, antiangiogenic, and proapoptotic activities in multiple cancer cell lines. Here we evaluated the antineoplastic effect of TNF-␣ and analyzed the mechanism underlying its combination with LYG-202. Our results indicated that LYG-202 significantly increased the cytostatic and proapoptotic activity of TNF-␣ in HepG2 cells and heightened the protein level of apoptosis-related genes including caspase-3, caspase-8/9, cleaved poly(ADPribose) polymerase, and Bid. The fact that LYG-202 had a fitness score similar to that of the casein kinase 2 (CK2) inhibitor naphthyridine-8-carboxylate (CX-4945) implied to us that it may serve as a potential candidate for CK2 inhibitor, and the kinase activity assay suggested that LYG-202 significantly inhibited CK2 activity. Moreover, the electrophoretic mobility shift assay and luciferase assay showed that LYG-202 blocked the TNF-␣-induced nuclear factor-B (NF-B) survival signaling pathway primarily by inactivating protein kinase CK2. In murine xenograft models, we also found that LYG-202 enhanced TNF-␣ antineoplastic activity and inhibited CK2 activity and NF-B-regulated antiapoptotic gene expression. All these results showed that LYG-202 enhanced TNF-␣-induced apoptosis by attenuating the CK2-dependent NF-B pathway and probably is a promising agent in combination with TNF-␣.

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“…24,27,28 Antitumor effects of TNF are enhanced by a combination of this cytokine with several classic chemotherapeutics. [29][30][31] Proteasome inhibition prevents NFjB activation, therefore, enhancing proapoptotic effects of TNF in many but not all cancer cell types. [32][33][34] Moreover, proteasome inhibition may alleviate the inflammatory response elicited by TNF.…”

mentioning

confidence: 99%

TNF potentiates anticancer activity of bortezomib (Velcade®) through reduced expression of proteasome subunits and dysregulation of unfolded protein response

Nowis

McConnell

Dierlam

et al. 2007

Intl Journal of Cancer

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Bortezomib (Velcade 1 ) exploits proteasome inhibition as a unique mechanism of anticancer activity. The effectiveness of bortezomib is, however, limited, therefore, the search for therapeutic regimens combining bortezomib with other agents. In the present work we demonstrate enhanced anticancer activity of bortezomib by its combination with tumor necrosis factor (TNF) in the experimental model of C-26 colon carcinoma in mice. This interaction likely relies on the induction of a dysregulated response to ER stress, leading to apoptosis of cancer cells, evidenced by caspase-3 cleavage, p53 accumulation as well as increased SAPK/JNK phosphorylation. ER stress induced by the combination of TNF and bortezomib is corroborated by upregulation of BiP, PDI and calnexin as well as cleavage of caspase-12; however, in contrast to the classic pathway, it is also associated with decreased phosphorylation of eIF2a and prevention of XBP-1 splicing. TNF prevented the upregulation of Hsp27 induced by bortezomib, which may contribute to enhanced ER stress. Moreover, TNF interfered with bortezomib-induced upregulation of distinct subunits of the 26S proteasome. Bortezomib concentration used in this study was not sufficient to prevent TNF from inducing nuclear translocation of p65/RelA; however, the combination of both agents reduced total p65/RelA levels. Combined treatment of tumor-bearing mice with bortezomib and TNF not only inhibited tumor growth but also significantly prolonged animal survival. Therefore, combination of bortezomib with TNF is an attractive option for further clinical studies. ' 2007 Wiley-Liss, Inc.

show abstract

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

Cited by 27 publications

References 22 publications

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

LYG-202 Augments Tumor Necrosis Factor-α-Induced Apoptosis via Attenuating Casein Kinase 2-Dependent Nuclear Factor-κB Pathway in HepG2 Cells

TNF potentiates anticancer activity of bortezomib (Velcade®) through reduced expression of proteasome subunits and dysregulation of unfolded protein response

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