scholarly journals Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians

2013 ◽  
Vol 169 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Shweta Varshney ◽  
Sanjay Kumar Bhadada ◽  
Uma Nahar Saikia ◽  
Naresh Sachdeva ◽  
Arunanshu Behera ◽  
...  
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Cyclin D1 ◽  
Vitamin D Receptor ◽  
Asian Indians ◽  
Parathyroid Tissue ◽  
Fold Change ◽  
Mrna Levels ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

BackgroundTo explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).Materials and methodsForty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (n=3) or from euthyroid patients without PHPT during thyroid surgery (n=7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR.ResultsImmunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, bothVDRandCASRmRNAs were reduced by 0.36- and 0.45-fold change (P<0.001) andCD1andPTHmRNAs were increased by 9.4- and 17.4-fold change respectively (P<0.001) in adenomatous parathyroid tissue.PTHmRNA correlated with plasma PTH (r=0.864;P<0.001), but not with adenoma weight, whileCD1mRNA correlated with adenoma weight (r=0.715;P<0.001). There were no correlations betweenVDRandCASRmRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases inVDRandCASRmRNA expressions and the increases inPTHandCD1mRNA expressions.ConclusionsThe expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition,CD1expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.

Vitamin D receptor, a tumor suppressor in skin

2015 ◽  
Vol 93 (5) ◽  
pp. 349-354 ◽  
Author(s):  
Daniel D. Bikle
Keyword(s):  
Vitamin D ◽  
Tumor Suppressor ◽  
Vitamin D Receptor ◽  
Tumor Formation ◽  
Calcium Sensing Receptor ◽  
Keratinocyte Proliferation ◽  
Calcium Sensing ◽  
Damage Repair ◽  
Proliferation And Differentiation ◽  
Active Investigation

Vitamin D and calcium are well-established regulators of keratinocyte proliferation and differentiation. Therefore, it was not a great surprise that deletion of the vitamin D receptor (VDR) should predispose the skin to tumor formation, and that the combination of deleting both the VDR and calcium sensing receptor (CaSR) should be especially pro-oncogenic. In this review I have examined 4 mechanisms that appear to underlie the means by which VDR acts as a tumor suppressor in skin. First, DNA damage repair is curtailed in the absence of the VDR, allowing mutations in DNA to accumulate. Second and third involve the increased activation of the hedgehog and β-catenin pathways in the epidermis in the absence of the VDR, leading to poorly regulated proliferation with reduced differentiation. Finally, VDR deletion leads to a shift in the expression of long noncoding RNAs toward a more oncogenic profile. How these different mechanisms interact and their relative importance in the predisposition of the VDR null epidermis to tumor formation remain under active investigation.

scholarly journals Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations

2009 ◽  
Vol 18 (9) ◽  
pp. 2485-2491 ◽  
Author(s):  
M. Jenab ◽  
J. McKay ◽  
H. B. Bueno-de-Mesquita ◽  
F. J.B. van Duijnhoven ◽  
P. Ferrari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
European Populations

scholarly journals Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal cancer survival in the Newfoundland population

2017 ◽  
Vol 117 (6) ◽  
pp. 898-906 ◽  
Author(s):  
Yun Zhu ◽  
Peizhong Peter Wang ◽  
Guangju Zhai ◽  
Bharati Bapat ◽  
Sevtap Savas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Cancer Survival ◽  
Calcium Sensing Receptor ◽  
Colorectal Cancer Survival ◽  
Calcium Sensing

scholarly journals Atypical Presentation of Familial Hypocalciuric Hypercalcemia: Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A183
Author(s):  
Dalal S Ali ◽  
Karel Dandurand ◽  
Aliya Aziz Khan
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Calcium Sensing Receptor ◽  
Clearance Ratio ◽  
Subtotal Parathyroidectomy ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Background: Differentiation between familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) can be challenging in certain cases in the absence of DNA analysis of the calcium sensing receptor gene. The distinction between those two clinical entities with overlapping biochemical features therefore relies on the calcium to creatinine clearance ratio (CCCR), which is expected to be low in FHH (&lt;0.01 in 80% of cases and between 0.01 and 0.02 in approximately 20% of patients)1. Patients with PHPT usually have a CCCR of&gt;= 0.02. A lower CCCR between 0.01 and 0.02 can be seen in approximately 20% of patients1,2and is more commonly seen in the presence of vitamin D insufficiency, impaired renal function, low calcium intake or being of African descent. It is advised to stop drugs which can contribute to hypercalcemia and lower the CCCR such as thiazide diuretics prior to evaluating the CCCR. Clinical Case: A 56-year-old lady was referred for evaluation of persistent hypercalcemia post parathyroidectomy and fatigue. She had mildly elevated ionized serum calcium (iCa) and a mid-normal PTH with a CCCR of 0.024. She had a normal BMD with no prior fragility fractures and passed a kidney stone prior to her presentation. Physical exam was unremarkable. She had previously travelled to Tampa and had a subtotal parathyroidectomy 3 glands (RU, LU, RL) for a possible diagnosis of PHPT, tissue biopsy showed hyperplastic parathyroids. Her MEN1 gene analysis was negative for MEN1 mutation and MRI of the abdomen was unremarkable. Her mother had a diagnosis of PHPT and osteoporosis. The iCa remained mildly elevated at 1.43 mmol/L (1.15–1.3) with a 24 hr urinary CCCR at 0.024 and a mid-normal PTH of 4.4 pmol/L (1.6–6.9). Her eGFR was 104 mls/min, 25 vitamin D 82 nmol/L (75–250), 1,25 dihydroxy vitamin D 122 pmol/L (60–206), PO4 0.90 mmol/L (0.8–1.45) and alkaline phosphatase 46 U/L (35–120) were all normal. She continued to have mild symptoms of hypercalcemia and her bone scan was negative for underlying skeletal pathology. DNA studies for mutations in the CaSR gene were completed. This confirmed the presence of a heterozygous loss of function mutation in the CASR gene at c493-2A&gt;G which appears to be pathogenic. Conclusion: The CCCR is useful in differentiating PHPT from FHH however in certain cases of FHH the CCCR may be higher then expected and we have now confirmed the presence of FHH with a molecular diagnosis in a patient with a CCCR as high as 0.02. References: 1 Gunn, IR, Gaffney, D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem 2004; 41:441–58 2 Stephen J. Marx, Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary Calcium, The Journal of Clinical Endocrinology & Metabolism, 2015

scholarly journals Investigation of effect of vitamin D receptor, calcium-sensing receptor and β-catenin on cutaneous squamous cell carcinoma

2020 ◽  
Vol 45 (1) ◽  
pp. 91-98
Author(s):  
Berrin Tuğrul ◽  
Sevinç Söylev ◽  
Peyker Temiz ◽  
Gülsüm Gençoğlan
Keyword(s):  
Vitamin D ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Vitamin D Receptor ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Beta Catenin ◽  
Calcium Sensing Receptor ◽  
Tissue Samples ◽  
Calcium Sensing

AbstractBackgroundCutaneous squamous cell carcinoma (cSCC) is a malignant and invasive tumor which is originated from epidermis with a high incidence among non-melanoma skin cancers. The aim of this study was to determine whether vitamin D receptor (VDR), calcium-sensing receptor (CaSR) and beta catenin (β-catenin) proteins have an effect on cSCC.Materials and methodsVDR, CaSR and β-catenin proteins in tissue samples of cSCC and control group were analyzed by immunohistochemistry (IHC) and Western blotting (WB) method. IHC findings were statistically evaluated.ResultsIHC staining density of VDR and β-catenin were higher in cSCC tissue samples than control. The difference between IHC staining density of VDR and β-catenin in the patient and the control groups were statistically significant (p = 0.021, p = 0.021, respectively), but not for CaSR (p = 0.237). While the VDR and β-catenin staining rates obtained by the IHC method could be supported by WB results, the WB bands for CaSR could not be shown.ConclusionThe findings suggest that VDR and β-catenin may have an effect on the disease. Further research is required to better understand the role of VDR and β-catenin together on cSCC.

scholarly journals Exclusive underexpression of vitamin D receptor exon 1f transcripts in tumors of primary hyperparathyroidism

2002 ◽  
pp. 671-675 ◽  
Author(s):  
P Correa ◽  
G Akerstrom ◽  
G Westin
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Direct Action ◽  
Parathyroid Glands ◽  
Mrna Levels ◽  
Vdr Gene ◽  
Dihydroxyvitamin D ◽  
Parathyroid Adenomas ◽  
Distal Promoter

OBJECTIVE: Primary hyperparathyroidism (pHPT) is characterized by excessive production of parathyroid hormone (PTH) due to parathyroid adenomas while uremic secondary HPT (sHPT) is caused by parathyroid hyperplasia in response to renal failure. Active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), with the vitamin D receptor (VDR) is involved in regulation of the calcium homeostasis together with PTH. In a feedback loop, 1,25-(OH)(2)D(3) has a direct action on the parathyroid gland to regulate PTH transcription, PTH secretion and cell proliferation. We have previously demonstrated reduced VDR mRNA expression in parathyroid adenomas and hyperplasia of sHPT using a probe detecting all 14 variant VDR transcripts expressed in parathyroid cells. Here we have assessed which of the 5'-terminal exon 1a, 1d and 1f variant VDR transcripts are reduced in pathological parathyroid glands. METHODS: The relative VDR/glyceraldehyde-3-phosphate dehydrogenase mRNA levels for each VDR exon were determined by real-time quantitative RT-PCR in five normal parathyroid glands, seventeen parathyroid adenomas and ten hyperplastic glands of sHPT. RESULTS: The results demonstrated exclusive underexpression of VDR exon 1f transcripts in parathyroid adenoma, while all measured VDR transcripts were reduced in secondary hyperplasia. CONCLUSIONS: We suggest that exclusive underexpression of VDR exon 1f transcripts in adenomas of pHPT, which derive from a distal promoter active in tIssues involved in calcium regulation by 1,25-(OH)(2)D(3), may either reflect a defective cell type-specific transcription factor or other physiologically important pathway(s) for tIssue-specific VDR gene expression.

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