Antivascular effects of TZT‐1027 (Soblidotin) on murine Colon26 adenocarcinoma

Watanabe, Junichi; Natsume, Tsugitaka; Kobayashi, Motohiro

doi:10.1111/j.1349-7006.2006.00330.x

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…In sharp contrast, the molecules that belong to the combretastatin family, such as CA-4P, AVE-8062 and Oxi-4503, can disrupt tumour microvasculature at low concentrations, well below the Maximum-Tolerated Dose (MTD) [32, 120, 166-168, 169, 170]. Besides the combretastatin family, the N-acetylcolchinol phosphate prodrug, ZD-6126 [121], the new dolastatin-10 derivative, TZT-1027 (Soblidotin ® ) [112,122,171], and the novel sulphonamide ABT-751 [172] have been also shown to effectively disrupt tumour vasculature at non-cytotoxic doses.…”

Section: Vascular-disrupting Activitymentioning

confidence: 99%

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

Pasquier¹,

André²,

Braguer³

2007

CCDT

125

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Anticancer agents that interfere with tubulin functions are widely used in the clinic and have a broad spectrum of activity against both haematological malignancies and solid tumours. These Microtubule-Targeting Agents (MTAs), such as the taxanes and Vinca alkaloids, bind to the beta subunit of alpha/beta tubulin and disrupt microtubule dynamics in tumour cells, ultimately leading to mitotic block and subsequent cell death. Recently, MTAs have received considerable interest as potential tumour-selective anti-angiogenic and vascular-disrupting agents. Angiogenesis is a keystone of tumour progression and metastasis and targeting the formation of new blood vessels within the tumour is therefore regarded as a promising strategy for cancer therapy. In this regard, conventional MTAs can be given on daily schedules at non-toxic doses (metronomic dosing) to disturb tumour angiogenesis. Some MTAs can also act as vascular-disrupting agents. After briefly reviewing the classical mechanisms involved in the anti-tumour action of MTAs, we will focus on the latest studies investigating the molecular and cellular processes underlying the anti-angiogenic and the vascular-disrupting properties of these agents. We will also review and discuss the potential clinical development and the limitations of MTAs used as tumour-specific anti-vascular molecules.

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Section: Vascular-disrupting Activitymentioning

confidence: 99%

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

Pasquier¹,

André²,

Braguer³

2007

CCDT

125

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“…Several studies have recently shown that treatment with VTAs enhances the therapeutic effect of radiotherapy (Li et al, 1998;Rojiani, 2002, 2005;Horsman and Murata, 2003;Masunaga et al, 2004), consistent with the idea that the components of such combination therapy act in a complementary manner, with VTAs attacking the poorly oxygenated cell population in the central region of tumours and radiation killing the well-oxygenated proliferating cells at the tumour periphery (Li et al, 1998;Siemann and Rojiani, 2002;Wachsberger et al, 2003). TZT-1027 was previously shown to increase vascular permeability and to induce a decrease in tumour blood flow followed by a marked increase in tissue necrosis in the central region of tumour xenografts (Otani et al, 2000;Watanabe et al, 2006b). We have now shown that TZT-1027 treatment resulted in congestion and occlusion of tumour blood vessels followed by extensive necrosis of the tumour core, with only a thin rim of viable tumour cells remaining, in the H460 tumour model, suggesting that TZT-1027 acts as a VTA.…”

Section: Discussionmentioning

confidence: 99%

The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo

et al. 2007

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TZT-1027 is a novel anticancer agent that inhibits microtubule polymerisation and manifests potent antitumour activity in preclinical models. We have examined the effect of TZT-1027 on cell cycle progression as well as the anticancer activity of this drug both in vitro and in vivo. With the use of tsFT210 cells, which express a temperature-sensitive mutant of Cdc2, we found that TZT-1027 arrests cell cycle progression in mitosis, the phase of the cell cycle most sensitive to radiation. A clonogenic assay indeed revealed that TZT-1027 increased the sensitivity of H460 cells to g-radiation, with a dose enhancement factor of 1.2. Furthermore, TZT-1027 increased the radiosensitivity of H460 and A549 cells in nude mice, as revealed by a marked delay in tumour growth and an enhancement factor of 3.0 and 2.2, respectively. TZT-1027 also potentiated the induction of apoptosis in H460 cells by radiation both in vitro and in vivo. Histological evaluation of H460 tumours revealed that TZT-1027 induced morphological damage to the vascular endothelium followed by extensive central tumour necrosis. Our results thus suggest that TZT-1027 enhances the antitumour effect of ionising radiation, and that this action is attributable in part to potentiation of apoptosis induction and to an antivascular effect. Combined treatment with TZT-1027 and radiation therefore warrants investigation in clinical trials as a potential anticancer strategy.

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“…( 3,7 ) TZT‐1027 displays a potent antivascular effect against advanced stage tumors, ( 6,9–11 ) and the mechanisms of its antivascular effect have recently been reported. ( 9 ) TZT‐1027 is currently undergoing clinical evaluation. ( 12–14 )…”

mentioning

confidence: 99%

“…( 16–18 ) Our study has demonstrated that TZT‐1027 has an antivascular effect as well as cytotoxity at a tolerable dose. ( 6,9 )…”

mentioning

confidence: 99%

“…Relative tissue perfusion was evaluated using the Evans blue dye perfusion technique, as reported previously. ( 9 ) Two mg/kg TZT‐1027 or 40 mg/kg docetaxel was administered once i.v. into mice bearing an MX‐1 breast tumor 20 days after tumor implantation, and then 0.5, 1, 3, 6, and 12 h later, 0.25 mL of 1% Evans blue in saline solution was administered i.v.…”

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confidence: 99%

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Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

et al. 2007

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Antivascular effects of TZT‐1027 (Soblidotin) on murine Colon26 adenocarcinoma

Cited by 13 publications

References 29 publications

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo

Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

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