Biomedical subjects

Akihiko Kawaura

Publications and source records attributed to Akihiko Kawaura.

3 recordsLinked to original sources

PubMed2005

[Phosphorus intake and bone mineral density (BMD)].

Phosphorus regulates the bone formation and inhibits the bone resorption. It is still expected as one of anti-osteoporosis nutrients. The amounts of phosphorus intake with calcium are increasing from 1960 to 1995. Because phosphorus affects the regulation of calcium metabolism, the balance of these nutrients is important. Tuero suggested that more than 1,000 mg/day of calcium intake and more than 0.74 of Ca/P were associated with better bone mineral density (BMD) values in young women. However, there are few reports of correlations between appropriate phosphorus intake, Ca/P rate and BMD.

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PubMed2004

1 alpha,25-Dihydroxyvitamin D(3) is a preventive factor in the metastasis of lung cancer.

1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the major regulator of calcium homeostasis, has potent antiproliferative and anti-invasive properties in vitro in cancer cells. Studies in vivo demonstrated that 1alpha,25(OH)(2)D(3) slows the progression of breast, prostate and other carcinomas. A key question is whether 1alpha,25(OH)(2)D(3) exerts its anticarcinogenic effects in vivo by a mechanism that is dependent on its capacity to limit the proliferation and invasiveness of cancer cells in vitro. It has not been clear whether the calcemic activity and regulation of the host defenses by 1alpha,25(OH)(2)D(3) contribute to the effect on cancer cells. In this study we have focused on the influence of 1alpha,25(OH)(2)D(3) on the metastasis of lung cancer, without involvement of the calcemic activity and other effects of 1alpha,25(OH)(2)D(3) in the host. We used metastatic Lewis lung carcinoma cells expressing green fluorescent protein (LLC-GFP cells) and examined metastatic activity in vitamin D receptor (VDR) null mutant (VDR(-/-)) mice and their wild-type counterparts (VDR(+/+) mice). VDR(-/-) mice exhibit hypocalcemia and extremely high serum levels of 1alpha,25(OH)(2)D(3). We expected that serum 1alpha,25(OH)(2)D(3) would act in vivo to directly inhibit the metastatic growth of VDR-positive LLC-GFP cells in VDR(-/-) mice. The metastatic activities of LLC-GFP cells were remarkably reduced in VDR(-/-) mice compared with VDR(+/+) mice. To test the hypothesis that serum 1alpha,25(OH)(2)D(3) is an intrinsic factor that inhibits metastatic growth of lung cancer cells, we corrected hypocalcemia and/or hypervitaminosis D in VDR(-/-) mice by dietary manipulation. The metastatic growth of LLC-GFP cells was remarkably reduced in response to serum levels of 1alpha,25(OH)(2)D(3), but not to serum calcium levels. Furthermore, we found that VDR(+/+) mice fed the manipulated diets displayed an apparent inverse relationship between the physiological levels of serum 1alpha,25(OH)(2)D(3) (8-15 pg/ml) and tumorigenesis. Here we show that 1alpha,25(OH)(2)D(3) inhibits the metastatic growth of lung cancer cells in a defined animal model.

Animals↗

PubMed2004

Metastatic growth of lung cancer cells is extremely reduced in Vitamin D receptor knockout mice.

Lung metastatic neoplasms are the major cause of cancer mortality. Despite the progress of diagnostic techniques and improvements in surgical procedures, the prognosis of patients with lung cancer is generally poor, even in the early stages of cancer [Cancer: Principles and Practice of Oncology, vol. 1, fifth ed., Lippincott-Raven, New York, 1997, p. 849]. Epidemiological studies indicate a positive correlation with the prevalence of cancers and low serum levels of Vitamin D metabolites [Am. J. Clin. Nutr. 54 (1991) 193s; Cancer Epidemiol. Biomark. Prev. 9 (2000) 1059]. 1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] is a potent inhibitor of cancer cell proliferation in vitro [Proc. Natl. Acad. Sci. U.S.A. 78 (1981) 4990; Endocrinol. 139 (1998) 1046; Mol. Endocr. 15 (2001) 1127]. There is, however, no report demonstrating that 1alpha,25(OH)(2)D(3) is operative in vivo to inhibit metastatic growth of cancer cells. To verify this possibility, we generated a stable transfectant of the Lewis lung carcinoma (LLC) cell expressing green fluorescent protein (GFP) and examined its metastatic activity in wild-type mice and Vitamin D receptor (VDR) knockout mice that exhibit no Vitamin D-dependent calcemic activity and extremely high serum levels of 1alpha,25(OH)(2)D(3) due to the overexpression of the 1alpha-hydroxylase gene [Nat. Genet. 16 (1997) 391; Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 9831]. Here, we show that 1alpha,25(OH)(2)D(3) inhibits metastatic growth of lung cancer cells in the defined animal model and may work as an intrinsic factor for prevention of metastasis in intact animals. These findings establish a critical role for 1alpha,25(OH)(2)D(3) in lung metastatic neoplasms and provide a new model for metastasis of malignant cells.

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