Potentiation of the radiation response of hypoxic mammalian cells by<i>cis</i>-dichlorobis(isopropylamine)trans-dihydroxy platinum IV (CHIP)

Laverick, M; Nias, A. H. W.

doi:10.1259/0007-1285-54-642-529

Cited by 22 publications

(3 citation statements)

References 6 publications

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“…The uptake of CHIP into the tumour eventually rose to the same level as found in the small intestine and the blood. This confirms the potential of CHIP for cancer chemotherapy and also as a radiosensitizing agent (Laverick & Nias, 1981).…”

Section: Discussionsupporting

confidence: 72%

Evaluation of the biochemical effects of CHIP in normal and tumour-bearing C3H mice

Laverick¹,

Gordon²,

Kind³

et al. 1986

Br J Cancer

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Section: Discussionsupporting

confidence: 72%

Evaluation of the biochemical effects of CHIP in normal and tumour-bearing C3H mice

Laverick¹,

Gordon²,

Kind³

et al. 1986

Br J Cancer

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“…Several trials, including our own, involving a variety of experimental systems have indicated that antituniorigenic platinum complexes enhance the lethal ef fect of irradiation [10][11][12], Cis-DDP potentiates the damage due to X-rays in aerated Chinese hamster ovary cells [12], while the platinum (IV) complex cisdichloro-bis (isopropylamine) trans-dihydroxy plati num (IV) exhibits potentiation of X-ray damage under hypoxic conditions [14], We have very recently treated Chinese hamster V-79 cells with cis-DDP before ir radiation, which reduced the slope of the irradiation response curve, while treatment after irradiation en hanced the cytotoxicity of the irradiated cells in a synergistic manner [15], Our results have shown that the influence of the synergistic effect on survival is not associated with an increased mutation frequency in V-79 cells. In our studies we have used the hypoxantine guanine phosphoribosiltransferase (HGPRT) loc us as a marker.…”

Section: Introductionmentioning

confidence: 99%

Combined cis-Platinum plus Radiation Antitumor Activity in Locoregionally Advanced Squamous Cell Esophageal Cancer

Kolarić¹,

Nagy²,

Roth³

et al. 1988

Oncology

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The synergistic activity we have observed in vitro in V-79 hamster lung cells after treatment with cis-platinum combined with irradiation, stimulated a pilot study of 31 patients with inoperable locoregionally advanced squamous cell esophageal cancer. The 27 evaluable cases (22 men and 5 women-mean age 59 years) had undergone no prior radiation or cytostatic drug therapy. Histological evidence of the tumor (26 squamous cell, 1 adenocarcinoma) was obtained by endoscopy in all patients before treatment began. The patients were irradiated in two opposite thoracic fields with a total dosage of 3,000–4,000 cGy (200 cGy daily, 1,000 weekly) concurrently with 2 cycles of cis-platinum in the dosage of 30 mg/m² iv. daily × 4 (120 mg/m² per cycle). The results showed that cis-platinum combined with radiation showed an evident antitumor activity which included 4 complete clinical remissions and 11 partial remissions with a response rate of 56% (15/27). In two complete responders even a pathologic remission was evident (biopsy specimen) and they are now 16+ and 18+ months free of the disease. The median remission duration has been 8+ months (14+ months in complete responders) and the median survival period for the entire group is 10+ months (for responders 15+ months, p < 0,05). Toxicity was moderate and reversible, and mainly accounted for radiation mucositis, retrosternal pain and vomiting. A mild bone marrow suppression was observed. In 2 cases esophagotracheal fistulae occurred. The results of this study show that the combination of cis-platinum and radiation might constitute successful palliative or neoadjuvant treatment for squamous cell esophageal cancer.

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“…(CHIP), exhibits potentiation of X-ray damage under hypoxic conditions (Laverick & Nias, 1981). Nitroheterocycles have also been widely studied as hypoxic cell radiosensitizers on account of the high electron affinity of the nitro group (Adams et al, 1978;Willson, 1977).…”

mentioning

confidence: 99%

Hypoxic cell sensitization to radiation damage by a new radiosensitizer: cis-dichloro-bis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole-N3)platinum(II) (flap)

Bales¹,

Sadler²,

Coulson³

et al. 1982

Br J Cancer

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Summary.-A new, stable platinum coordination complex (FLAP) containing the 5-nitroimidazole, metronidazole, has been prepared and characterized. The squareplanar platinum(II) complex has two metronidazole molecules and two chlorine atoms in the cis configuration. The properties of FLAP differ significantly from metronidazole alone or other platinum complexes tested in the same system. It has a low toxicity towards Chinese hamster ovary cells and is a very effective radiosensitizer toward hypoxic cells in vitro: a one-h pretreatment with a non-toxic dose of 50 ytM gave an enhancement ratio of 2-4. No potentiation of aerated cells to Xirradiation damage was observed after a similar schedule of pretreatment at the higher dose of 100 /uM FLAP.

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Potentiation of the radiation response of hypoxic mammalian cells bycis-dichlorobis(isopropylamine)trans-dihydroxy platinum IV (CHIP)

Cited by 22 publications

References 6 publications

Evaluation of the biochemical effects of CHIP in normal and tumour-bearing C3H mice

Evaluation of the biochemical effects of CHIP in normal and tumour-bearing C3H mice

Combined cis-Platinum plus Radiation Antitumor Activity in Locoregionally Advanced Squamous Cell Esophageal Cancer

Hypoxic cell sensitization to radiation damage by a new radiosensitizer: cis-dichloro-bis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole-N3)platinum(II) (flap)

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