Vascular attack as a therapeutic strategy for cancer

Denekamp, Juliana

doi:10.1007/bf00046365

Cited by 239 publications

(140 citation statements)

References 57 publications

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“…These factors could be involved in decreasing and/or shutting off the blood flow in tumours British Journal of Cancer (1998) compared with normal tissues. Subsequently, if the tumour cannot get enough oxygen and nutrients, then their growth is impaired (Denekamp, 1990).…”

Section: Discussionmentioning

confidence: 99%

The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation

Johansson

Landström²,

Hellstrand³

et al. 1998

Br J Cancer

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Summary A syngeneic, androgen-sensitive Dunning R3327 rat prostatic adenocarcinoma was transplanted bilaterally in the flanks of male Copenhagen Fisher rats. Approximately 3 months after implantation, when the tumours had a median volume of 150 mm3, one group of rats was treated with histamine alone (4 mg kg-1 subcutaneously on week days), another group with human recombinant interleukin 2 (IL-2) alone (425 IU kg-' continuous infusion) and a third group with both histamine and IL-2 during 6 weeks. Tumours on one flank were irradiated (6 Gy once daily for 3 days to a total dose of 18 Gy) beginning 1 week after the onset of treatment with histamine and / or IL-2. The contralateral tumour served as the intra-animal control. The tumour volumes were determined weekly. The growth curves showed that all three drug treatments were effective in delaying growth, but when used individually did not cause tumour shrinkage. Radiation was the most effective single agent, but when used alone the shrinkage did not occur until 2 weeks after irradiation. When combined with the drugs, more rapid and extensive growth delay and/or shrinkage was seen. The growth curves showed clear differences between the different treatments. The combination of the three agents was the most effective of all. The most striking difference between radiation alone and radiation plus biotherapy was the time at which a tumour response was detectable. Thus, active biotherapy alone and especially in a combination with histamine and radiotherapy warrants further investigation as a potential therapeutic approach to prostate cancer.

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Section: Discussionmentioning

confidence: 99%

The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation

Johansson

Landström²,

Hellstrand³

et al. 1998

Br J Cancer

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“…It has been reported that damage to a single vessel can cause the death of thousands of dependent tumour cells and only a small number of endothelial cells need to be affected to disrupt a vessel. 6 It would therefore be advantageous to alter the tumour blood supply locally without causing damage to normal vasculature.…”

Section: Introductionmentioning

confidence: 99%

Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

et al. 2000

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“…However, by the time the cancer is diagnosed, most tumours already have an intact, functional vascular network (Folkman, 1992). Significantly, tumour vasculature seems to be fundamentally different from normal vasculature (Denekamp, 1990). For example, tumour endothelium is characterised by tortuous, leaky vessels with chaotic blood flow (Fukumura et al, 1997) and a significant proportion of immature, proliferating endothelial cells, which is in contrast to the ordered vessels and quiescent endothelial cells found in normal tissues (Skinner et al, 1995;Brown and Giaccia, 1998).…”

mentioning

confidence: 99%

“…A wide range of potentially effective vascular-targeting approaches has been described, each exploiting distinctive features of the tumour vasculature (Denekamp, 1990;Bloemendal et al, 1999;Thorpe et al, 2003). Vascular-targeting activity is a common feature of tubulin-binding microtubule destabilising agents such as colchicines and vinca alkaloids.…”

mentioning

confidence: 99%

ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer

et al. 2004

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The purpose of this study was to examine the effects of ZD6126, a novel vascular-targeting agent, on tumour growth and angiogenesis in an orthotopic model of gastric cancer. TMK-1 human gastric adenocarcinoma cells were injected into the gastric wall of nude mice. After the tumours were established (day 14), therapy was initiated. Mice (n ¼ 11 -12/group) received (a) vehicle, (b) ZD6126 at 100 mg kg day À1 i.p. one time per week or (c) ZD6126 at 100 mg kg day À1 i.p. five times per week. Tumour mass, volume and the presence or absence of peritoneal carcinomatosis were determined at sacrifice on day 38. Tumours from each group were stained for markers of blood vessels, proliferation and apoptosis. To further define the time frame of the vascular-targeting effects of chronic therapy with ZD6126, TMK-1 cells were again injected into the gastric wall of mice in a second experiment. On day 14, a single i.p. injection of ZD6126 100 mg kg À1 mouse À1 or vehicle was delivered. Groups of three mice each were killed and the tumours harvested at days 1, 3 and 5 post-ZD6126 injection. Tumours were processed and stained for endothelial and tumour cell apoptosis and proliferation. No overt toxicity was observed with ZD6126 therapy. ZD6126 led to a marked inhibition of tumour growth (82% decrease vs control (Po0.001)). ZD6126 also led to a significant decrease in the incidence of peritoneal carcinomatosis (10 out of 12 controls, vs one out of 12 ZD6126) (Po0.01). Histological analysis of tumours revealed large regions of central necrosis in the treated group, as well as a dramatic increase in tumour cell apoptosis (7.4-fold increase (Po0.001)), consistent with the vascular-targeting activity of ZD6126. Mice treated with ZD6126 demonstrated a 59% decrease in PCNA-positive cells (Po 0.02), indicating reduced tumour cell proliferation. In addition, tumours treated with ZD6126 exhibited a 40% decrease in microvessel density (Po0.05). Results from mice treated with a single injection of ZD6126 demonstrated the acute effects this agent has on the tumour vasculature. The ratio of endothelial cell apoptosis to endothelial cell proliferation was increased within 24 h of a single injection. In conclusion, ZD6126 significantly inhibited tumour growth and metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable problematic adverse effects. These data suggest that ZD6126 may be worthy of investigation in the treatment of primary gastric adenocarcinoma.

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Vascular attack as a therapeutic strategy for cancer

Cited by 239 publications

References 57 publications

The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation

The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation

Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer

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