Treatment with 1-alpha,25-dihydroxyvitamin D3 (vitamin D3) to inhibit carcinogenesis in the hamster buccal pouch model

Abstract

OBJECTIVE: To investigate whether systemic therapy with 1-alpha,25-dihydroxyvitamin D(3) (vitamin D(3) [hereinafter, VD(3)]) prevents tumor formation in a hamster buccal pouch model of carcinogenesis.

DESIGN: Randomized trial in which a known carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was applied to the buccal pouch of 40 hamsters. Animals were randomized to receive systemic VD(3) or no treatment and killed at 2, 6, and 14 weeks after the initiation of DMBA exposure.

SETTING: Academic medical center.

SUBJECTS: Forty male golden Syrian hamsters, aged 5 to 6 weeks, were used.

INTERVENTIONS: A dose of 0.25 mug/kg of VD(3) via intraperitoneal injection was given to 20 animals 3 times per week. Of the remaining 20 control animals, 5 received placebo vehicle injection, and 15 received no further treatment.

MAIN OUTCOME MEASURES: Timing, size, and number of tumors that developed in the 2 groups.

RESULTS: Only 1 hamster treated with VD(3) developed a confirmed neoplasm compared with 7 of the control animals (P < .01). The mean +/- SD total diameter of gross lesions per animal in the VD(3)-treated group was 1.2 +/- 1.9 mm compared with 6.8 +/- 6.6 mm in the control group (P = .03). The time to onset of lesion formation was significantly delayed in those animals treated with VD(3), with a mean +/- SD time to development of 13.4 +/- 0.9 weeks, while the control animals developed lesions at 11.2 +/- 1.7 weeks (P = .02).

CONCLUSIONS: Systemic VD(3) therapy delays carcinogenesis in the hamster buccal pouch model. Further investigation into the mechanisms through which VD(3) inhibits carcinogenesis may lead to development of effective chemopreventive agents to combat head and neck cancer.

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See also:

- Official Web Site: The Di Bella Method;

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.