Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

Albertsson, Per; Lennernäs, Bo; Norrby, Klas

doi:10.1080/02841860701558781

Cited by 14 publications

(11 citation statements)

References 40 publications

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“…The effect on VEGF‐mediated angiogenesis of metronomic mono‐chemotherapy in the rat mesentery model is drug‐specific (and dose‐related). Thus, previous studies have reported that these agents are pro‐angiogenic, e.g., ironotecan and, mitoxantrone (as reported here), as well as cisplatin and 5‐fluorouracil (19, 42), anti‐angiogenic, e.g., cyclophosphamide, paclitaxel, and vinblastine (19, 41), or have no effect on angiogenesis, e.g., doxorubicin and epirubicin (19, 20). Low‐level oxidative stress in ECs appears to induce pro‐angiogenic effects following certain types of low‐dosage metronomic chemotherapy in this model.…”

Section: Discussionsupporting

confidence: 61%

“…There are numerous discrepancies in the literature concerning the angiogenesis‐modulating effects of various standard cytotoxic agents in tumors and tumor‐free assays (19, 41, 42). This is not surprising considering the differences in species used, experimental design, test tissues used, modes of administration, dosages, and the biological features of the assays (17).…”

Section: Discussionmentioning

confidence: 99%

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Low‐dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF‐A‐mediated angiogenesis

Albertsson¹,

Lennernäs²,

Norrby

2011

APMIS

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Albertsson P, Lennernäs B, Norrby K. Low-dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF-A-mediated angiogenesis. APMIS 2011.Metronomic chemotherapy with cytotoxic agents has been shown to inhibit angiogenesis and, consequently, tumor growth by targeting vascular endothelial cells (ECs). In these regimens, anti-tumor activities additional to anti-angiogenesis may operate. Moreover, chemotherapy typically generates reactive oxygen species in targeted ECs, which can affect angiogenesis. The aim of the present study was to assess the systemic effect of low-dosage metronomic treatment with either irinotecan or mitoxantrone on angiogenesis induced by VEGF-A. Angiogenesis was induced in normal adult rat mesentery by intraperitoneal injection of a low dosage of VEGF-A. Thereafter, irinotecan and mitoxantrone were infused separately continuously at minimally toxic dosages for 14 consecutive days via a subcutaneous osmotic minipump. Angiogenesis was assessed in terms of objective and quantitative variables using morphologic and computerized image analyses. Irinotecan or mitoxantrone significantly stimulated angiogenesis, with ironotecan increasing angiogenesis by 104%, when compared with the vehicle-treated animals. Low-dosage metronomic chemotherapy with irinotecan or mitoxantrone stimulates angiogenesis in the normal mesentery of rats, probably by inducing low-level oxidative stress in the targeted ECs. Whether or not this pertains to tumor angiogenesis may be difficult to confirm, as several anti-tumor modes may operate during low-dosage metronomic chemotherapy.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Low‐dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF‐A‐mediated angiogenesis

Albertsson¹,

Lennernäs²,

Norrby

2011

APMIS

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“…Although colchicine significantly inhibits angiogenesis in vitro at concentration of 10 −6 ~10 −8 M, the effective anti-angiogenic dose is toxic to human subjects [77]. However, continuous administration of vinblastine at a dose of 2.0 mg/kg/week produced inhibitory effects on VEGF-mediated angiogenesis in mammalian models, but the mechanisms underlying the anti-angiogenic actions of these compounds are still unknown [77, 78]. …”

Section: Natural Anti-angiogenic Compounds Derived From Plantsmentioning

confidence: 99%

Plants and their active compounds: natural molecules to target angiogenesis

Bhat

Basu

2016

Angiogenesis

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Angiogenesis, or new blood vessel formation, is an important process in the pathogenesis of several diseases and thus has been targeted for the prevention and treatment of many disorders. However, the anti-angiogenic agents that are currently in use are mainly synthetic compounds and humanized monoclonal antibodies, which are either expensive or toxic, thereby limiting their use in many patients. Therefore, it is necessary to identify less toxic, inexpensive, novel and effective anti-angiogenic molecules. Several studies have indicated that natural plant products can meet these criteria. In this review, we discuss the anti-angiogenic properties of natural compounds isolated from plants and the molecular mechanisms by which these molecules act. Finally, we summarize the advantages of using plant products as anti-angiogenic agents. Compared with currently available anti-angiogenic drugs, plant products may not only have similar therapeutic potential but are also inexpensive, less toxic and easy to administer. However, novel and effective strategies are necessary to improve their bioavailability for clinical use.

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“…ous low-dose administration of 5-fluorouracil or cisplatin could sometimes promote VEGF-A mediated angiogenesis, an effect that was not observed when 5-fluorouracil or cisplatin compounds were administered at higher doses (Albertsson et al 2008;Albertsson et al 2009). The angiogenic response to 5-fluorouracil or cisplatin may therefore be bellshaped.…”

Section: Hormesis and Anti-angiogenic Therapymentioning

confidence: 99%

Potential Relevance of Bell-Shaped and U-Shaped Dose-Responses for the Therapeutic Targeting of Angiogenesis in Cancer

Reynolds¹

2010

Dose-Response

101

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ᮀ Tumor angiogenesis, the growth of new blood vessels into tumors, facilitates tumor growth and thus represents an attractive therapeutic target. Numerous experimental angiogenesis inhibitors have been characterised and subsequently trialled in patients. Some of these agents have failed to show any substantial activity in patients. In contrast, others have been more successful, but even these provide only a few months extra patient survival. Recent work has focused on understanding the effects of anti-angiogenic agents on tumor biology and has revealed a number of new findings that may help to explain the limited efficacy of angiogenesis inhibitors. Herein, I review the evidence that hormetic dose-responses (i.e. bell-shaped and U-shaped dose-response curves) are often observed with anti-angiogenic agents. Agents reported to exhibit these types of dose-response include: 5-fluorouracil, ATN-161, bortezomib, cisplatin, endostatin, enterostatin, integrin inhibitors, interferon-α, plasminogen activator-1 (PAI-1), rapamycin, rosiglitazone, statins, thrombospondin-1, TGF-α1 and TGF-α3. Hormesis may also be relevant for drugs that target the vascular endothelial growth factor (VEGF) signalling pathway and for metronomic chemotherapy. Here I argue that hormetic dose-responses present a challenge for the clinical translation of several anti-angiogenic agents and discuss how these problems might be circumvented.

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Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

Cited by 14 publications

References 40 publications

Low‐dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF‐A‐mediated angiogenesis

Low‐dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF‐A‐mediated angiogenesis

Plants and their active compounds: natural molecules to target angiogenesis

Potential Relevance of Bell-Shaped and U-Shaped Dose-Responses for the Therapeutic Targeting of Angiogenesis in Cancer

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