The skeleton morphology of the azooxanthellate cold-water coral Lophelia pertusa can be strongly inXuenced by invasive boring sponges that infest corallites in the still living part of the colony. Atypically swollen corallites of live Lophelia pertusa from the Galway Mound (Belgica Carbonate Mound Province, Porcupine Seabight, NE Atlantic), heavily excavated by boring organisms, have been examined with a wide range of nondestructive and destructive methods: micro-computed tomography, macro-and microscopic observations of the outer coral skeleton, longitudinal and transversal thin sections and SEM analyses of coral skeleton casts. As a result, three excavating sponge species have been distinguished within the coral skeleton: Alectona millari, Spiroxya heteroclita and Aka infesta. Furthermore, four main coral/ sponge growth stages have been recognised: (1) cylindrical juvenile corallite/no sponge cavities; (2) Xared juvenile corallite/linear sponge cavities (if present); (3) slightly swollen adult corallites/chambered oval sponge cavities; (4) very swollen adult corallites/widespread cavities. The inferred correlation between corallite morphology and boring sponge infestation has been detected in micro-computed tomography (micro-CT) images and conWrmed in sponge trace casts and peculiar features of coral skeleton microstructure.

Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently and becomes more and more prevalent presumably because survival times among patients with disseminated cancers are increasing. Patients with bone metastases from renal cell carcinoma suffer from severe pain, nerve compression syndromes and pathologic fractures. Very little is known about the mechanisms of skeletal metastases of RCC. Thus, to better understand the molecular mechanism of renal cell cancer (RCC) bone metastasis, it is crucial to develop new animal models. We have established a new animal model of RCC metastasis to bone by inoculation of human 786-O/luciferase cells into the left cardiac ventricle of athymic nude mice. The animals developed aggressive osteolytic bone destruction as monitored by radiography and micro-CT-scans with the mean endpoint at 62 +/- 8 days. The extensive bone destruction observed was comparable to the clinical setting and mainly occurred in hind limbs, forelimbs and the spine. The tumors were primarily located within the bone and resulted in destruction of cortical bone. No soft tissue metastases were detected by BLI or histomorphometry. To increase the bone-metastatic potential of the 786-O cell line, an in vivo selection was done yielding a subpopulation causing osteolytic lesions with the mean endpoint of 47 +/- 3 days. The selected subline secreted more proangiogenic factors VEGF and bFGF in vitro compared to the parental cell line suggesting that these tumors are highly vascular. This model provides a reliable reproduction of the clinical situation and therefore, is suitable for designing and evaluating more effective treatments for RCC bone metastasis.

Purpose: Bone metastases have a considerable impact on quality of life in patients with breast and other cancers. Tumors produce osteoclast-activating factors, whereas bone resorption promotes the growth of tumor cells, thus leading to a "vicious cycle" of bone metastasis. Sagopilone, a novel, fully synthetic epothilone, inhibits the growth of breast cancer cells in vitro and in vivo, and here we report its activity in the MDA-MB-231(SA) breast cancer bone metastasis mouse model. Experimental Design: The potency of sagopilone was determined in treatment models simulating the adjuvant (preventive) and metastatic (therapeutic) settings in the clinic. Results: We showed that sagopilone inhibited tumor burden and bone destruction, in addition to reducing tumor-induced cachexia and paraplegia. The reduction in osteolytic lesions, tumor growth in bone, and weight loss was statistically significant in the preventive model compared with the vehicle group. In the therapeutic model, sagopilone treatment significantly lowered the number of activated osteoclasts and significantly reduced the osteolytic lesion area, bone volume loss, and bone resorption compared with vehicle treatment while simultaneously inhibiting tumor burden. An in vitro assay confirmed that sagopilone inhibited osteoclast activation without cytotoxic effects, whereas paclitaxel resulted in lower inhibition and high levels of cytotoxicity. Conclusions: Sagopilone seems to inhibit the vicious cycle at both the tumor growth and bone resorption stages, suggesting the possibility for substantial benefit in the treatment of patients with breast cancer at risk from bone metastases or with bone lesions already present. Phase II clinical trials with sagopilone in patients with breast cancer are ongoing.Bone is the most common site for a distant metastasis in women with breast cancer (1), with a reported incidence of up to 75% (2, 3) and an average survival time of ∼2 years after diagnosis (3). Symptoms of bone metastases include skeletal complications and bone pain, which affects up to 80% of patients and greatly impacts on their quality of life (4).Primary breast tumors express osteolytic and osteoblastic factors, stimulating different types of bone metastases, with osteolytic lesions occurring more commonly (5, 6). The development of osteolytic bone metastases has been described as a vicious cycle, with increased osteoclast activity implicated as the predominant mechanism of bone destruction (6). Tumor cells produce factors, such as parathyroid hormone-related protein, which are responsible for an increase of osteoclast activity and consequent bone resorption. Growth factors stored in bone and released during bone resorption in turn stimulate tumor cell growth, thus perpetuating the vicious cycle. The quality of life of breast cancer patients could be considerably increased by a potent inhibitor of bone metastasis (7), and a drug that could simultaneously and effectively inhibit both tumor cell growth and osteoclast activity would have great potential...

No abstract