Verhoeff's query: is vitamin D effective against retinoblastoma?

In 1966, Verhoeff suggested that retinoblastomas might be sensitive to vitamin D because they sometimes undergo calcification and spontaneous regression. In recent years, the antineoplastic effect of vitamin D has been established in vitro and in vivo. This study presents evidence that vitamin D2 inhibits the growth of the human retinoblastoma cell line (Y-79) grown in athymic mice. In mice treated with ergocalciferol, the subcutaneous retinoblastomas were smaller and showed increased tumor necrosis and calcification. Unfortunately, the vitamin D caused significant toxic reactions. Further studies that reduce the toxicity of vitamin D will be needed before its use in children with retinoblastomas can be advocated. To our knowledge, this is the first demonstration of the activity of ergocalciferol against a tumor in vivo and it suggests that ergocalciferol or one of its derivatives may be an effective chemotherapeutic agent against retinoblastomas in humans.

Further studies of the effect of vitamin D on retinoblastoma. Inhibition with 1,25-dihydroxycholecalciferol.

We present evidence that calcitriol (1,25-dihydroxycholecalciferol) decreases tumor takes and tumor growth of subcutaneous retinoblastomas in athymic mice. Histopathologic studies showed that the calcitriol also induced necrosis of the retinoblastomas. The calcitriol, however, did not induce tumor calcification. Unfortunately, the dose of calcitriol used in this experiment caused significant toxic effects. If the toxicity of vitamin D can be alleviated without compromising its antineoplastic effect, vitamin D may be a useful chemotherapeutic agent against retinoblastoma.

Vitamin D and retinoblastoma. The presence of receptors and inhibition of growth in vitro.

The vitamin D receptor has been found in several human organs not involved in calcium metabolism and in several malignant neoplasms found in humans. The role of the receptor in these tissues is unclear. There is, however, a relationship between the presence and quantity of the vitamin D receptor in a malignant cell line and the antineoplastic effect of vitamin D on that cell line. We found that Y-79 retinoblastoma cells have receptors specific for calcitriol (1,25-dihydroxycholecalciferol). Scatchard analysis of the receptor data shows a quantity of 56,000 receptors per retinoblastoma cell. These receptors have a dissociation constant of 1.18 nmol/L. Retinoblastoma cells treated with 10(-9) mol/L of calcitriol for nine days had 15% less cell growth than the control cells. Further studies of the effect of vitamin D on retinoblastoma may warrant its inclusion in chemotherapeutic protocols for the treatment of this childhood affliction.

Effects of gentamicin on healing of transdifferentiating conjunctival epithelium in rabbit eyes.

We examined the effects of commercially prepared gentamicin, a wide-spectrum topical antibiotic, on the healing of epithelial defects of the rabbit cornea. Abrasions were created by: (1) removing the corneal epithelium and 3 mm of the conjunctival epithelium (Group 1); and (2) producing the same initial trauma and subsequently removing the central 8 mm of epithelium 28 days after initial healing (Group 2). The complete healing of the large corneal and conjunctival epithelial defects was not delayed when gentamicin solution was used four times a day (Group 1). When the healed epithelium was reinjured while transdifferentiating from conjunctival to corneal epithelium (day 28, Group 2), treatment with the gentamicin solution and its vehicle, both containing benzalkonium chloride, delayed epithelial healing significantly compared with treatment with saline (P less than .01).

The effects of pre-enucleation irradiation on the development of metastases from intraocular Greene melanoma in hamsters.

Using intraocular Greene melanoma in a hamster model, we studied the effect of pre-enucleation irradiation on the development of melanoma metastases. One group (No. = 111) was treated with 1,210 to 1,600 rads of cobaltous chloride Co 60 gamma irradiation before enucleation and the second group (No. = 100) received no irradiation. The groups did not differ with respect to presence of metastases in the 106 days after tumor implantation (chi 2 = 3.05; P = .08). However, Kaplan-Meier survival curves gave a longer time to melanoma-related death in the irradiated animals compared with the controls (log rank test, P = .0008).

An investigation into the association between liver damage and metastatic uveal melanoma.

We examined the effect of liver damage induced by carbon tetrachloride on the incidence of hepatic metastasis in the Greene hamster melanoma. Nine of 17 animals with liver damage had melanoma growth in the liver after the intraportal vein injection of tumor cells, whereas tumor growth occurred in four of 27 control animals (P less than .01). These results suggest that, in this model, liver damage predisposes to metastatic involvement by melanoma.