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This is the first study to demonstrate that benzo(a)-pyrene (BaP) was able to enhance the production of parathyroid hormone‑related protein (PTHrP) by human non‑small cell lung cancer H460 cells. Such effect would further contribute to bone metastasis of lung cancer by increasing osteoclastogenesis. This study is also the first to reveal that tricetin (TCN), a flavonoid derivative found in Myrtaceae pollen and Eucalyptus honey, was able to reverse BaP‑mediated bone resorption activity of lung cancer cells. Human non‑small cell lung cancer H460 cells were treated with BaP to generate conditioned medium. When osteoblasts were cultured with BaP‑H460‑CM, their expression of osteoclastogenesis activator macrophage colony‑stimulating factor (M‑CSF) and receptor activator of nuclear factor κB ligand (RANKL) was increased. BaP‑H460‑CM reduced the production of osteoprotegerin (OPG), an osteoclastogenesis inhibitor, in osteoblasts. Osteoclastogenesis and bone resorption activity of H460 cells were increased by BaP‑H460‑CM. With BaP‑mediated PTHrP upregulation, IL‑8 secretion in H460 cells was increased contributing to human non‑small cell lung cancer‑mediated osteoclast differentiation and bone resorption. Moreover, TCN suppressed BaP‑mediated bone resorption. Therefore, TCN may be a novel agent for treatment of non‑small cell lung cancer patients with bone metastasis.

Background: Rodent models are often suboptimal for translational research on human prostate cancer (PCa). To better fill the gap with human, we refined the previously described orthotopic dog prostate cancer (DPC)-1 model., Methods: Cyclosporine (Cy) A was used for immune suppression at varying doses and time-periods prior and after orthotopic DPC-1 cell implantation in the dog prostate (n = 12). Follow up included digital rectal examination, ultrasound prostate imaging and biopsies of hypoechoic areas. At necropsy, the prostate, iliosacral lymph nodes (LN), lung nodules, and suspicious bone segments were collected for histopathology., Results: 15 mg CyA/kg daily for 10 days was optimal for tumor take. Maintaining these conditions post-implantation resulted in a rapid tumor development within and beyond the prostate and in iliosacral LNs. To minimize tumor burden, 10 times less DPC-1 cells were implanted. A series of dogs was next followed for 3-4 months, under continuous immune suppression (n = 3) or with CyA interruption at 8.5 weeks (n = 2). In all instances, multifocal tumors were found within the prostate. Predominant patterns were micropapillary and cribriform. Metastases were present in iliosacral LNs and lungs. Moreover, pelvic bone metastases producing a mixed osteoblastic/osteolytic reaction were confirmed in two dogs, one per group. Lastly, the release of CyA 1-2 weeks post-implantation (n = 3) did not prevent tumor growth and spreading to LNs., Conclusions: The continuing growth of DPC-1 tumors despite the release of CyA and, for the first time, spreading to bones renders this refined model closer to the spontaneous canine and hormone-refractory phase of human PCa., (Copyright © 2011 Wiley Periodicals, Inc.)

Beryllium is a proven bone carcinogen in rabbits, and proven pulmonary carcinogen in rats. Median effective doses or concentrations can be computed only with considerable uncertainty; they appear to be in the 10 mg area (as total dose, in divided intravenous injections, expressed as Be for zinc beryllium silicate) for rabbits, and in the 20 alpha/m3 area (as atmospheric concentration for inhalation exposures lasting for at least three months, expressed as Be for beryllium sulfate) for rats. It is also proven that, at least from inhalation, guinea pigs do not develop beryllium cancers. Epidemiologic studies in humans are thus far unconfirmed but do not show increased cancer morbidity among beryllium workers. Current research is aimed at explaining the mechanism of carcinogenic action in the susceptible species, which seems to involve nucleic acid transcriptional interference, or the species specificity, which seems to involve immune mechanisms. No experiments were reported thus far besides the carcinogenesis studies to show that beryllium is a chemical mutagen. In the species thus far tested, there appeared to be mutual exclusion of development of a delayed (cell-mediated) hypersensitivity to beryllium and development of neoplasia from beryllium. Further research on this subject might lead to new possibilities in the understanding of cancer susceptibility.