Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late ...Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identifi ed during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo , via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.展开更多
The objective of the study was to determine the role of vitamin D3(VD3) in regulating adaptation and mechanism of rats to low-phosphorus(P) diets. Rats were assigned to 4 diets containing 0.2%, 0.4%, 0.6%,or 0.8% P co...The objective of the study was to determine the role of vitamin D3(VD3) in regulating adaptation and mechanism of rats to low-phosphorus(P) diets. Rats were assigned to 4 diets containing 0.2%, 0.4%, 0.6%,or 0.8% P consisting of 5 replicate cages with 6 rats per replicate cage and fed for 7 days. Four rats from each replicate cage were treated with ethane-1-hydroxy-1,1-diphosphonicacid, tetrasodium salt(EHDP)and 2 rats remained untreated. Twelve hours prior to preparation on d 7, two of the EHDP-treated rats received an intraperitoneal injection of VD3 [1,25-(OH)_2 D_3] at 600 ng per kg body weight, while two rats did not receive the injection. Rats that did not receive VD_3 injection had decreased(P < 0.001) P absorption, but injection of VD3 resulted in increased(P < 0.001) absorption. The effect of VD3 injection was greater(P < 0.001) for rats fed 0.2% P diet than rats fed 0.8% P diet in ileum. Sodium dependent phosphate cotransporter type IIb(Na/Pi-IIb) and 25-hydroxyvitamin D 1-α hydroxylase(CYP27 B1) mRNA level showed the same trend with P absorption. Serum concentration of VD3 and la-hydroxylase activity in rats fed 0.2% P diet were lower than those fed 0.8% P diet. The injection of VD3 increased(P < 0.001)serum concentration of VD3 and la-hydroxylase activity. Thus, VD3 increased Na/Pi-Ⅱb and CYP27 B1 mRNA level and improved serum concentration of VD3 and la-hydroxylase activity in rats fed low-P diets.展开更多
文摘Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identifi ed during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo , via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.
基金supported by grants from the Nature Science Foundation (31201810, to M H Cao 31572419, to R J Fang)+1 种基金Education Department of Hunan Province(138039, to M H Cao)Innovation Team Funds Of Hunan Province (to J H He)
文摘The objective of the study was to determine the role of vitamin D3(VD3) in regulating adaptation and mechanism of rats to low-phosphorus(P) diets. Rats were assigned to 4 diets containing 0.2%, 0.4%, 0.6%,or 0.8% P consisting of 5 replicate cages with 6 rats per replicate cage and fed for 7 days. Four rats from each replicate cage were treated with ethane-1-hydroxy-1,1-diphosphonicacid, tetrasodium salt(EHDP)and 2 rats remained untreated. Twelve hours prior to preparation on d 7, two of the EHDP-treated rats received an intraperitoneal injection of VD3 [1,25-(OH)_2 D_3] at 600 ng per kg body weight, while two rats did not receive the injection. Rats that did not receive VD_3 injection had decreased(P < 0.001) P absorption, but injection of VD3 resulted in increased(P < 0.001) absorption. The effect of VD3 injection was greater(P < 0.001) for rats fed 0.2% P diet than rats fed 0.8% P diet in ileum. Sodium dependent phosphate cotransporter type IIb(Na/Pi-IIb) and 25-hydroxyvitamin D 1-α hydroxylase(CYP27 B1) mRNA level showed the same trend with P absorption. Serum concentration of VD3 and la-hydroxylase activity in rats fed 0.2% P diet were lower than those fed 0.8% P diet. The injection of VD3 increased(P < 0.001)serum concentration of VD3 and la-hydroxylase activity. Thus, VD3 increased Na/Pi-Ⅱb and CYP27 B1 mRNA level and improved serum concentration of VD3 and la-hydroxylase activity in rats fed low-P diets.
