Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs.

BACKGROUND: Low blood 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations. OBJECTIVES: (1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs. ANIMALS: Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client-owned dogs (n = 23). METHODS: An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2 D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone-related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations. RESULTS: Cancer type (P = 0.004), plasma 24,25(OH)2 D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs.

Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells.

Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins.

All- trans-retinoic acid increases cytotoxicity of 1-beta-D-arabinofuranosylcytosine in NB4 cells.

PURPOSE: Clinically, the benefits of combining all- trans-retinoic acid (ATRA) with chemotherapy have been well documented in the treatment of acute promyelocytic leukemia (APL). Changes in nucleoside transporter expression and activity have been shown to occur in NB4 cells in vitro following treatment with ATRA. In this study we investigated whether ATRA treatment increases sensitivity to ara-C in NB4 cells. Specifically, we examined the role of ATRA-associated changes in nucleoside transporter expression and activity in eliciting ara-C cytotoxicity. METHODS: Cellular uptake of [(3)H]-ara-C and nucleoside transporter abundance were determined in untreated cells and cells treated with 1 microM ATRA for 12-72 h using an inhibitor and oil stop procedure, and an equilibrium [(3)H]-NBMPR binding assay, respectively. Cytotoxicity of ara-C and the apoptotic response prior to and following ATRA treatment were determined using the MTT viability assay and the TUNEL assay, respectively. RESULTS: ATRA treatment increased ara-C cytotoxicity and potency, ara-C transport, and augmented ara-C-induced apoptosis. The combination effect was supraadditive under some conditions and sequence-dependent whereby the maximum effect was seen when the addition of ATRA preceded the addition of ara-C, and when ara-C administration closely followed ATRA administration. CONCLUSIONS: The ATRA-induced increase in cytotoxicity of ara-C was, in part, the result of an increase in the functional expression of nucleoside transporters, and a role for bcl-2 was also indicated. Our results would suggest that timing of ara-C therapy should be tied to maximal es transporter expression, which is likely to be 24 h after ATRA treatment begins. It remains to be seen whether the response in the clinic can be further enhanced in APL by taking advantage of ara-C transporter regulation by ATRA.