Effects of TNP-470 (Agm-1470) on Tumor-Growth, Angiogenesis and Serum Copper Levels in Liver-Cancer Bearing Rats

Matsuoka, Shinya; Uchino, J; Une, Yoshie; Ishimura, H; Tsuchimoto, Suguru; Kamiyama, Toshiya

doi:10.3892/or.2.4.583

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“…In particular, its effectiveness in arresting hepatic metastasis of neuroblastoma has been documented in [97] and [98]. In the light of [99], the antiangiogenic activity of TNP-470 is reasonably linked to its interference with the hepatic copper metabolism. In fact, the continuous administration of TNP-470 in both normal and tumourbearing rats has been shown to increase the serum copper levels, as a consequence of a limited hepatic retention [99].…”

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

“…In the light of [99], the antiangiogenic activity of TNP-470 is reasonably linked to its interference with the hepatic copper metabolism. In fact, the continuous administration of TNP-470 in both normal and tumourbearing rats has been shown to increase the serum copper levels, as a consequence of a limited hepatic retention [99]. This feature has been associated with a reduced density of hepatic tumour capillaries [99].…”

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

“…In fact, the continuous administration of TNP-470 in both normal and tumourbearing rats has been shown to increase the serum copper levels, as a consequence of a limited hepatic retention [99]. This feature has been associated with a reduced density of hepatic tumour capillaries [99]. Accordingly, when the administration of TNP-470 was interrupted, angiogenesis was activated and at the same time the serum copper levels fell down [99].…”

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

“…This feature has been associated with a reduced density of hepatic tumour capillaries [99]. Accordingly, when the administration of TNP-470 was interrupted, angiogenesis was activated and at the same time the serum copper levels fell down [99].…”

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

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Copper as a Target for Treatment of Neuroblastoma: Molecular and Cellular Mechanisms

Urso¹,

Maffia²

2013

Neuroblastoma

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Neuroblastoma 266 Copper uptake Ctr1 (Copper transporter 1). High-affinity Cu + importer, composed of three main domains: an extracellular N-terminal tail containing multiple copper-binding methionine residues; a transmembrane segment consisting of three α-helical regions; an intracellular C-terminal domain. Three subunits assemble to form a homo-trimeric channel (9 Å pore diameter) within the plasma membrane (see [118] for a review). Ctr2 (Copper transporter 2). Copper permease, whose structure resembles that of Ctr1. Predominantly localized to endosomes and lysosomes, it seems to provide a mechanism of copper recycling from degraded cuproenzymes [119]. PrP C (Cellular Prion protein). Endogenous copper-binding glycoprotein, mainly expressed in the central nervous system. The protein structure includes an unstructured N-terminal domain and a Cterminal globular region composed of three α-helices and two short beta-strands. When Cu 2+ ions bind to the N-terminal octapeptide repeats (residues 51-90), the protein undergoes endocytosis, that providing a route for cell copper entry [58,59]. Cytosolic transport CCS. Metallo chaperone required for copper delivery to Cu,Zn Superoxide dismutases 1; upregulated in response to copper deficiency [120]. Cox17. Metallo chaperone delivering copper to Sco1 and Cox11 proteins in order to catalyse the cytochrome c oxidase copper loading [121]. Atox1. Metallo chaperone that delivers copper to ATP7A and ATP7B Cu + efflux pumps [122]. Metallothioneins. Small cysteine-rich proteins tightly binding copper ions and buffering the ion excess [123]. Copper efflux ATP7A. Cu +-transporting P-type ATPase expressed by all cell types, with the exception of liver. Structural features include eight membrane-spanning domains and six N-terminal cysteine-rich metal binding motifs (MXCXXC) [25]. Box 1. Main proteins involved in cell copper homeostasis Neuroblastoma 268

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Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

Section: Anti-angiogenic Therapies Target the Neuroblastoma Copper Stmentioning

confidence: 99%

See 2 more Smart Citations

Copper as a Target for Treatment of Neuroblastoma: Molecular and Cellular Mechanisms

Urso¹,

Maffia²

2013

Neuroblastoma

View full text Add to dashboard Cite

show abstract

Effects of TNP-470 (Agm-1470) on Tumor-Growth, Angiogenesis and Serum Copper Levels in Liver-Cancer Bearing Rats

Cited by 1 publication

References 0 publications

Copper as a Target for Treatment of Neuroblastoma: Molecular and Cellular Mechanisms

Copper as a Target for Treatment of Neuroblastoma: Molecular and Cellular Mechanisms

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