In vitro and in vivo effects of a cyclic peptide with affinity for the ανβ3 integrin in human melanoma cells

Allman, Richard; Cowburn, Pam; Mason, Malcolm David

doi:10.1016/s0959-8049(99)00279-8

Cited by 50 publications

(35 citation statements)

References 27 publications

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“…Antagonists of a v b 3 integrin, such as cyclic Arg-Gly-Asp (RGD)-containing peptides and c[RGDfV], 9,10 have been under investigation as antiangiogenic agents for decades. 11 These investigations produced Cilengitide (EMD: 121974), 12 which initially showed promising results for breast tumor therapy. 13 Phase II trials were then conducted for the treatment of prostate cancer, 14,15 followed by phase III trials for the treatment of glioblastoma; however, it was ultimately discontinued as an anticancer drug because it did not improve outcomes.…”

Section: Introductionmentioning

confidence: 99%

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

et al. 2017

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Melanoma is a highly metastatic and deadly form of cancer. Invasive melanoma cells overexpress integrin a v b 3 , which is a well-known target for Arg-Gly-Asp-based (RGD) peptides. We developed a sophisticated method to synthetize milligram amounts of a targeted vector that allows the RGD-mediated targeting, internalization, and release of a mitochondria-disruptive peptide derived from the pro-apoptotic Bax protein. We found that 2.5 mM Bax[109-127] was sufficient to destabilize the mitochondria in ten different tumor cell lines, even in the presence of the anti-apoptotic Bcl2 protein, which is often involved in tumor resistance. This pore-forming peptide displayed antitumor activity when it was covalently linked by a disulfide bridge to the tetrameric RAFT-c[RGD] 4 -platform and after intravenous injection in a human melanoma tumor model established in humanized immuno-competent mice. In addition to its direct toxic effect, treatment with this combination induced the release of the immuno-stimulating factor monocyte chimoattractant protein 1 (MCP1) in the blood and a decrease in the level of the pro-angiogenic factor FGF2. Our novel multifunctional, apoptosis-inducing agent could be further customized and assayed for potential use in tumortargeted therapy.

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Section: Introductionmentioning

confidence: 99%

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

et al. 2017

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“…In vitro work already performed with purinergic receptor agonists, such as ATP and 2′-3′-O-(4-benzoylbenzoyl) ATP (BzATP), has shown that they produce a reduction in melanoma cell number [13,14]. Inoculation of MF-1 immunocompromised mice, with A375 melanoma cells is a well-established model of cancer research [15,16]. Athymic mice are deficient in matured T cell maturity and make excellent models of cancer growth with a reported take of cancer cells of 100% after subcutaneous injection.…”

Section: Introductionmentioning

confidence: 99%

An in vivo model of melanoma: treatment with ATP

White

Knight

Butler

et al. 2009

Purinergic Signalling

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Athymic mice, injected with A375 human melanoma cells, were treated daily with intraperitoneal injections of adenosine 5′-triphosphate (ATP). The tumour volume and animal weight were measured over the course of the experiment and the final tumour nodule weight was measured at the end of the experiment. Tumour volume decreased by nearly 50% by 7 weeks in treated mice. Weight loss in untreated animals was prevented by ATP. Histological examination of the excised tumour nodules showed necrosis in the ATP-treated tumours only. The presence of P2Y 1 and P2X 7 receptors, previously proposed as extracellular targets for melanoma treatment with ATP, were demonstrated in the excised specimens by immunohistochemistry. This paper provides further support for the use of ATP as a treatment for melanoma.

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“…4 These compounds and anti-a v b 3 integrin monoclonal antibodies have been reported to inhibit angiogenesis without affecting preexisting vessels. 2,5,6 Because of its restricted expression, the a v b 3 integrin is an attractive targeting molecule for tumor imaging and therapy, leading to decreased side effects compared to conventional chemotherapy.The expression of the a v b 3 integrin has been reported to be associated with metastatic potential in melanoma, breast cancer, and colon cancer. 7-9 The development of radiopharmaceuticals for targeting the a v b 3 integrin would be clinically beneficial, not only for screening and for treating patients with a v b 3 integrin-positive tumors but also for monitoring therapeutic efficacy.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Yoshimoto

Ogawa

Washiyama

et al. 2008

Intl Journal of Cancer

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The a v b 3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress a v b 3 integrin, as in tumor neovascularization, and a v b 3 integrin expression in other microvascular beds and organs is limited. Therefore, a v b 3 integrin is a suitable receptor for tumor-targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to a v b 3 integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor-targeting properties and the therapeutic potential of 111 In-and 90 Y-labeled monomeric RGD peptides in BALB/c nude mice with SKOV-3 human ovarian carcinoma tumors. DOTA-c(RGDfK) was labeled with 111 In or 90 Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to a v b 3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111 In-DOTA-c(RGDfK) and 90 Y-DOTA-c(RGDfK) showed high uptake in tumors (7.3 6 0.6% ID/g and 4.6 6 0.8% ID/g, respectively) and gradually decreased over time (2.3 6 0.4% ID/g and 1.5 6 0.5% ID/g at 24 hr, respectively). High tumor-to-blood and -muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multipledose administration of 90 Y-DOTA-c(RGDfK) (3 3 11.1 MBq) suppressed tumor growth in comparison to the control group and a single-dose administration ( The a v b 3 integrin recognizes the amino acid sequence of arginine-glycine-aspartic acid (RGD peptide). On the basis of the RGD peptide, many peptidomimetic compounds and peptides have been designed to antagonize the a v b 3 integrin. 4 These compounds and anti-a v b 3 integrin monoclonal antibodies have been reported to inhibit angiogenesis without affecting preexisting vessels. 2,5,6 Because of its restricted expression, the a v b 3 integrin is an attractive targeting molecule for tumor imaging and therapy, leading to decreased side effects compared to conventional chemotherapy.The expression of the a v b 3 integrin has been reported to be associated with metastatic potential in melanoma, breast cancer, and colon cancer. 7-9 The development of radiopharmaceuticals for targeting the a v b 3 integrin would be clinically beneficial, not only for screening and for treating patients with a v b 3 integrin-positive tumors but also for monitoring therapeutic efficacy.Many RGD peptides labeled with gamma-emitting and positron-emitting nuclides ( 18 F, 64 Cu, 99m Tc, 125 I, etc.) have been reported as angiogenesis-imaging agents. 10 A recent trend in the development of RGD peptides is the multimerization of RGD peptides to improve the high tumor accumulation and retention of RGD peptides. 11 However, this also leads to the enhancement of radioactive accumulation in nontargeted organs such as kidney and liver. 12 Compared with antibody or multimeric RGD peptides, monomeric RGD ...

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In vitro and in vivo effects of a cyclic peptide with affinity for the ανβ3 integrin in human melanoma cells

Cited by 50 publications

References 27 publications

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

An in vivo model of melanoma: treatment with ATP

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

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In vitro and in vivo effects of a cyclic peptide with affinity for the ανβ3 integrin in human melanoma cells

Cited by 50 publications

References 27 publications

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

An in vivo model of melanoma: treatment with ATP

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

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α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide