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The pattern of the temporal distribution of solid cancer incidence after irradiation in childhood is not well known, although, its importance in radioprotection is well known. We studied a cohort of 1,055 children from 8 European cancer centres, who received radiotherapy between 1942 and 1985 for a first cancer in childhood. After a mean follow-up of 19 years, 26 children developed a solid second malignant neoplasm (SMN), as compared to 5.6 expected from general population rates. Both the excess relative risk and the excess of absolute risk of solid SMN were higher among children who were younger at time of the irradiation. After reaching a maximum 15 to 20 years after irradiation, the excess relative risk of SMN decreased with time after irradiation, when controlling for age at irradiation and sex. The analysis of the risk of thyroid, brain and breast cancer together, as a function of the dose averaged on these 3 organs lead to similar results.

Chondrosarcoma is currently defined as a malignant cartilage tumour arising de novo or within a pre-existing benign cartilage tumour. Chondrosarcoma can be surgically resected, but all grades have significant rates of local recurrence. The purpose of the present study was to develop an animal intraosseous chondrosarcoma model simulating the progression of human chondrosarcoma and elucidating its behaviour and biology. An intraosseous Swarm rat model was designed to assess interactions between bone and chondrosarcoma. A comparison of tumour grading was carried out according to transplantation site. The effects of chondrosarcoma cells (SRC cells) on the mineralisation capacities of osteoblasts and on osteoclast differentiation were studied in relation to modifications observed in vivo at the cellular level. Transplantation of Swarm rat chondrosarcoma within bone marrow or contiguous to induced periosteal lesions led to extensive bone remodelling with trabecular bone rarefaction and periosteal apposition. Transplantation in close contact to bone but without any periosteal lesion had no effect on bone, suggesting that bone healing factors interact with tumour development. With the intramedullary model, the development of tumours of different grade confirms that bone environment is an important factor in malignancy. A decrease of bone nodule formation was noted after cocultures of SRC cells with rat bone marrow, but there was no modification of osteoclast differentiation after cultures of total rabbit bone cells with SRC cells. These data reveal the importance of interactions between bone environment and tumour in inducing bone remodelling and variations in tumour malignancy.

The frequency of thyroid nodules has been studied among 396 children irradiated for a hemangioma, from 1946 to 1973. 226Ra, 192Ir, 90Y, 32P, 90Sr, as well as X-rays had been used for treatments. The doses of radiation received by the thyroid of each child have been estimated retrospectively. The irradiations have been classified in two categories based on their duration: less than 30 min., and more than 30 min. The doses received with each of these two types of irradiation were summed for each patient. The risk of thyroid nodule increased as a function of the dose to thyroid only for the dose delivered with the short duration. This study emphases the importance of the role of the dose rate in the risk of radio-induced tumour.

Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteineproteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-1 (IGF-1) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-1 collagen) on hGHand hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type 1 collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-avB3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by avB3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly'mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with avB3 integrin, by another adhesion molecule.