Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation

Brewer, George J.

doi:10.1111/j.1582-4934.2003.tb00198.x

Cited by 79 publications

(61 citation statements)

References 72 publications

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“…We did not find any effect of zinc on the serum cytokine levels, although it is reported to increase serum levels of cytokines in literature. Our findings did not support the views of Brewer et al [11]. Serial analysis of cytokines before and after initiating treatment may establish the relationship.…”

Section: Discussioncontrasting

confidence: 99%

Do cytokines have any role in Wilson's disease?

Goyal¹,

Sinha²,

Patil

et al. 2008

Clinical and Experimental Immunology

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SummaryThe aim of this study was to determine the serum cytokine levels in patients with Wilson's disease (WD) and correlate with phenotype, therapeutic status and laboratory data. In this cross-sectional study, the serum levels of cytokines were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age: 13·8 Ϯ 8·6 and 19·6 Ϯ 9·03 years) and compared with 30 controls. The following serum cytokines were analysed using enzyme-linked immunosorbent assay: (i) tumour necrosis factor (TNF)-a, (ii) interferon (IFN)-g, (iii) interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-a (P < 0·001), IFN-g (P = 0·005) and IL-6 (P < 0·001) were detectable in WD compared with controls. However, serum level elevation of IL-4 (P = 0·49) and IL-2 (P = 0·11), although detectable compared with controls, was statistically insignificant. The disease severity and therapeutic status did not affect the cytokines. Presence of anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did not influence cytokine levels. There was a significant negative correlation between IL-6 and ceruloplasmin (P = 0·04) and antiinflammatory cytokines (IL-4) and copper level (P = 0·01). Serum cytokines, both proinflammatory and anti-inflammatory subtypes, were elevated significantly in patients with WD. Further studies would establish their role in its pathogenesis.

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Section: Discussioncontrasting

confidence: 99%

Do cytokines have any role in Wilson's disease?

Goyal¹,

Sinha²,

Patil

et al. 2008

Clinical and Experimental Immunology

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“…In 1980, it was first noticed that Cu played an important role in angiogenesis [23]. In normal adult tissues, there is no action of angiogenesis except for wound healing, inflammatory reaction or the menstrual cycles [24]. Tumors are dependent on angiogenesis for their growth, invasion and metastasis, a novel concept proposed by Dr Folkman in 1971 [25,26].…”

Section: Role Of Cu In Angiogenesis and Cancer Progressionmentioning

confidence: 99%

New uses for old copper-binding drugs: converting the pro-angiogenic copper to a specific cancer cell death inducer

Chen

Dou

2008

Expert Opinion on Therapeutic Targets

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Background-The conventional approach toward anticancer drug development is a timeconsuming and expensive procedure.Objective/methods-One approach to expedite this process and achieve more affordable means is to discover new applications of existing drugs, since their pharmacokinetics and pharmacological profiles are well known.Results-Our encouraging findings in recent studies reveal anticancer activities of several copper-binding ligands including disulfiram (an antialcoholism drug), clioquinol (used to treat Alzheimer's and Huntington's diseases) and diethyldithiocarbamate (an agent for HIV-1 infection treatment). Conclusion-These in vitro and in vivo studies have demonstrated that these archaic drugs cantarget and react with tumor cellular copper, forming complexes that act as potent proteasome inhibitors and apoptosis inducers.

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“…In particular, it has been shown that TM can sequester copper from several metallo-chaperones/ligands (e.g. ATOX1, ceruloplasmin, bovine serum albumin and metallothioneins), and interfere with their function in the regulation of angiogenic pathways [244,245]. Moreover, in vitro assays demonstrated that ATN-224 inhibits endothelial activation, migration and sprout formation by regulating several genes involved in angiogenesis, ion binding and inflammatory processes [246].…”

Section: Copper and Angiogenic Diseasesmentioning

confidence: 99%

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

Urso

Maffia²

2015

J Vasc Res

129

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Angiogenesis critically sustains the progression of both physiological and pathological processes. Copper behaves as an obligatory co-factor throughout the angiogenic signalling cascades, so much so that a deficiency causes neovascularization to abate. Moreover, the progress of several angiogenic pathologies (e.g. diabetes, cardiac hypertrophy and ischaemia) can be tracked by measuring serum copper levels, which are being increasingly investigated as a useful prognostic marker. Accordingly, the therapeutic modulation of body copper has been proven effective in rescuing the pathological angiogenic dysfunctions underlying several disease states. Vascular copper transport systems profoundly influence the activation and execution of angiogenesis, acting as multi-functional regulators of apparently discrete pro-angiogenic pathways. This review concerns the complex relationship among copper-dependent angiogenic factors, copper transporters and common pathological conditions, with an unusual accent on the multi-faceted involvement of the proteins handling vascular copper. Functions regulated by the major copper transport proteins (CTR1 importer, ATP7A efflux pump and metallo-chaperones) include the modulation of endothelial migration and vascular superoxide, known to activate angiogenesis within a narrow concentration range. The potential contribution of prion protein, a controversial regulator of copper homeostasis, is discussed, even though its angiogenic involvement seems to be mainly associated with the modulation of endothelial motility and permeability.

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Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation

Cited by 79 publications

References 72 publications

Do cytokines have any role in Wilson's disease?

Do cytokines have any role in Wilson's disease?

New uses for old copper-binding drugs: converting the pro-angiogenic copper to a specific cancer cell death inducer

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

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