The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointesti...The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the Ca SR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitisassociated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.展开更多
Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondar...Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondary hyperparathyroidism may reduce cardiac endpoints, the effect of the calcimimetic agent, cinacalcet, remains controversial. This retrospective study aimed at evaluating troponin levels in hemodialysis patients with severe secondary hyper parathyroidism (SHPT) who are on cinacalcet vs controls on conventional treatment. In addition, clinical outcomes including all-cause, cardiovascular morbidity and mortality were compared among both groups. A decline in Troponin I levels was observed in the cinacalcet group, this however was not translated clinically into improved survival. In fact, all-cause and cardiac mortality was similar in the two groups. Conversely, comparison of the incidence of cardiovascular events revealed lower rates in the cinacalcet group including cardiac, cerebral and peripheral vascular complications. Given some of our study limitations, further long-term, placebo-controlled trials are necessary to definitively establish the effect of cinacalet on cardiac biomarkers and ultimately its impact on clinical outcomes.展开更多
基金Supported by the European Union’s Horizon 2020 research and innovation programme,No.675228the Austrian Science Fund(FWF),No.P 29948-B28
文摘The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the Ca SR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitisassociated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.
文摘Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondary hyperparathyroidism may reduce cardiac endpoints, the effect of the calcimimetic agent, cinacalcet, remains controversial. This retrospective study aimed at evaluating troponin levels in hemodialysis patients with severe secondary hyper parathyroidism (SHPT) who are on cinacalcet vs controls on conventional treatment. In addition, clinical outcomes including all-cause, cardiovascular morbidity and mortality were compared among both groups. A decline in Troponin I levels was observed in the cinacalcet group, this however was not translated clinically into improved survival. In fact, all-cause and cardiac mortality was similar in the two groups. Conversely, comparison of the incidence of cardiovascular events revealed lower rates in the cinacalcet group including cardiac, cerebral and peripheral vascular complications. Given some of our study limitations, further long-term, placebo-controlled trials are necessary to definitively establish the effect of cinacalet on cardiac biomarkers and ultimately its impact on clinical outcomes.
