Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiproliferative action of 1,25-dihydroxyvitamin D3 in osteosarcoma, breast carcinoma, and colon carcinoma cell lines has been described. In this study, the level of vitamin D receptor was analyzed in a panel of colon adenoma and adenocarcinoma cell lines and the receptor level was correlated with the response to treatment with 1,25-dihydroxyvitamin D3. Ribonuclease protection and ligand-binding assays quantitated the level of vitamin D receptor mRNA expression and the level of functional receptors, respectively. The more well-differentiated cell lines, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, clonogenic assay, and growth curve study in HT29 and SW620 cell lines assessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at concentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, but growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent normal tissue, and in 9 cases, the tumor expressed a lower vitamin D receptor level. Our results suggest that the level of vitamin D receptor correlates with the degree of differentiation in human colon cancer cell lines and may serve as a useful biological marker in predicting clinical outcome in patients.
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PMID:1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. 839 79

Polymorphisms in the vitamin D receptor (VDR) gene have been hypothezised to interfere with VDR expression. VDR alleles (Bb, Aa and Tt) were examined in 254 Caucasian patients with sporadic primary hyperparathyroidism (spHPT, n = 206), HPT of multiple endocrine neoplasia type 1 (MEN-1; n = 17), and HPT of uremia (n = 31). In comparison to age- and sex-matched controls, the b, a and T alleles were overrepresented in 100 menopausal females with spHPT (p = 0.006-0.0004), equivalent to an odds ratio of 2.6-3.4 for spHPT in homozygotes for the b, a and, T alleles. The association between VDR genotypes and spHPT was restricted to female patients and those with parathyroid adenoma (p = 0.0006-0.0001), whereas HPT of MEN 1 and uremia seemed unrelated to the VDR polymorphisms (p = 0.26-0.96). The results suggest that the VDR alleles b, a, and T are novel risk factors in the essentially uncharacterized pathogenesis of spHPT.
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PMID:Vitamin D receptor alleles b, a, and T: risk factors for sporadic primary hyperparathyroidism (HPT) but not HPT of uremia or MEN 1. 907 Feb 72

Clonal analysis has shown that in renal hyperparathyroidism (2-HPT), parathyroid glands initially grow diffusely and polyclonally after which the foci of nodular hyperplasia are transformed to monoclonal neoplasia. There is a great deal of information about genetic abnormalities contributing to the tumourigenesis of parathyroid neoplasia in primary hyperparathyroidism. It is speculated that allelic loss of the MEN1 suppressor gene and overexpression of cyclin D1 induced by rearrangement of the parathyroid hormone gene may be the major genetic abnormality in sporadic parathyroid adenoma but not in 2-HPT. The pathogenesis of 2-HPT, abnormality of the Ca2+-sensing receptor (CaR) gene and the vitamin D receptor gene may possibly contribute to parathyroid tumourigenesis in 2-HPT. However, this is not yet clear and heterogeneous and multiple genetic abnormalities may be responsible for the progression of secondary parathyroid hyperplasia.
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PMID:Mechanism of parathyroid tumourigenesis in uraemia. 1004 55

Primary hyperparathyroidism is the third most frequent endocrine disorder. The condition required for diagnosis is inappropriately elevated secretion of parathyroid hormone (PTH) with respect to calcemia. Most often, the disease is due to a parathyroid adenoma, i.e. a monoclonal benign parathyroid tumor, less often to a parathyroid hyperplasia. The main tumorogenic mechanisms currently proposed are a DNA rearrangement in the PTH locus (transposition of the PTH promoter upstream to Cyclin D1/PRAD 1 gene) and a mutation of the gene responsible for multiple endocrine neoplasia type I. The clinical presentation has strikingly evolved towards a milder, asymptomatic form, frequently diagnosed on systematic screenings. Though the mechanism of hypercalcemia is better understood, several hypothesis are still being considered about the regulation of tumoral PTH secretion: the role of the expression of calcium-receptor in parathyroid gland cells, vitamin D receptor and estrogen receptor polymorphisms, etc. Surgery is still advised for symptomatic forms of the disease, either because of a bone involvement, or because of an evolutive nephrolithiasis. In the near future, the new calcium-receptor agonists could be a relevant therapeutic approach.
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PMID:[Primary hyperparathyroidism]. 1111 7

Primary hyperparathyroidism (pHPT), generally caused by a monoclonal parathyroid adenoma, is a common endocrinopathy. Until recently, the genesis of the disease was poorly understood but during the past decade the molecular pathology of parathyroid tumor development has begun to be unveiled. This review summarizes recent advances in our understanding of genetic predisposition to pHPT, and the role of vitamin D receptor gene (VDR) variants in development of the disease. It has been shown that the multiple endocrine neoplasia tumor suppressor gene (MEN1) is mutated in parathyroid adenomas, and overexpression of the cyclin D1 oncogene [PRAD1 (parathyroid adenoma 1)] seems to contribute to parathyroid tumorigenesis. Several familial hyperparathyroid disorders have been studied, and the identification and characterization of the disease-causing genes have contributed to our understanding of parathyroid physiology and pathophysiology.
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PMID:Molecular pathology of parathyroid tumors. 1116 22

Laboratory studies and epidemiological investigations suggest that vitamin D plays a role in the etiology of colorectal adenomas, possibly through a mechanism mediated by the vitamin D receptor (VDR). We conducted a clinic-based case-control study to examine the association between VDR polymorphisms and colorectal adenomas. We selectively identified a random subset of 393 cases of colorectal adenomas and 406 colonoscopy-negative controls from a clinic-based case-control study conducted in the metropolitan Minneapolis/St. Paul area during 1991-1994. A self-administered questionnaire was used to collect data on dietary and supplement intake of vitamin D and calcium, as well as on demographics, physical activity, medical information, lifestyle factors, reproductive history, and anthropometry. DNA was extracted from whole blood and assayed for the BsmI VDR polymorphism using an ABI 7700 TaqMan assay. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were evaluated using logistic regression. Compared with the bb genotype (33% of controls), neither the Bb (48.8% of controls) nor the BB (18.2% of controls) genotypes was strongly associated with risk of colorectal adenomas (OR = 0.86, CI = 0.63-1.19 and OR = 0.77, CI = 0.50-1.18, respectively). However, those with the lowest tertile of vitamin D intake and the BB genotype had a lower risk of colorectal adenoma (OR = 0.24, CI = 0.08-0.76) than those with the highest tertile of intake and the bb genotype. Similarly, those with the lowest tertile of calcium intake and the BB genotype had a reduced risk of colorectal adenoma (OR = 0.34, CI = 0.11-1.06). Although it has generally been shown that higher calcium and vitamin D intake are associated with a modestly reduced risk of colorectal neoplasia, our data suggest that those with the BB BsmI VDR genotype may be at reduced risk of colorectal adenoma in the presence of lower calcium and vitamin D intake.
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PMID:Vitamin D receptor polymorphism and the risk of colorectal adenomas: evidence of interaction with dietary vitamin D and calcium. 1148 53

Experimental studies suggest that vitamin D and calcium protect against cancer by reducing proliferation and inducing differentiation. The effects of vitamin D and calcium may be mediated by the vitamin D receptor (VDR), which is encoded by the VDR gene. The present study investigated whether calcium intake and serum vitamin D, as an integrated measure of intake and endogenous production, were associated with risk of colorectal adenoma, known precursors of invasive colorectal cancer. In addition, the interrelation among vitamin D, calcium, and FokI polymorphism of the VDR gene was investigated. Persons (239) with histologically confirmed colorectal adenomas and 228 control individuals without colorectal adenomas confirmed by sigmoidoscopy were enrolled in this case control study conducted at the National Naval Medical Center, Bethesda, MD. We observed an inverse association of serum 25-OH vitamin D [25-(OH)D] with colorectal adenoma. With each 10 ng/ml increase of serum 25-(OH)D, the risk of colorectal adenoma decreased by 26% (odds ratio 0.74, 95% confidence interval 0.60-0.92). The results provided limited evidence for a weak association between calcium intake and colorectal adenoma (odds ratio 0.97, 95% confidence interval 0.93-1.01 per each 100-mg calcium intake). However, the inverse association of serum 25-(OH)D with colorectal adenoma is suggested to be stronger in subjects with calcium intake above the median (P for multiplicative interaction 0.13). The VDR FokI polymorphism was not significantly associated with colorectal adenoma and did not modify the effect of vitamin D or calcium. In conclusion, the study results suggested a protective effect for vitamin D on colorectal adenoma.
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PMID:Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas. 1175 44

Previous epidemiological studies have been inconclusive in demonstrating an inverse association among calcium, vitamin D, and risk for colorectal adenoma. The purpose of this analysis was to evaluate the associations among calcium and vitamin D and risk for incident, sporadic colorectal adenoma according to the vitamin D receptor BsmI polymorphism and nonsteroidal anti-inflammatory drug (NSAID) use. We analyzed data from a colonoscopy-based case-control study (n = 177 cases, 228 controls) conducted in North Carolina between 1995 and 1997. Adjusted odds ratios (ORs) comparing participants in the highest to those in the lowest tertiles of total calcium and vitamin D intakes were 0.64 [95% confidence interval (CI), 0.35-1.15], P(trend) = 0.14 and 0.69 (95% CI, 0.41-1.18), and P(trend) = 0.19, respectively. Adjusted ORs for those in the upper tertile of total calcium intake relative to those in the lower were 0.25 (95% CI, 0.08-0.80) among those who had a Bb genotype, 0.57 (95% CI, 0.18-1.82) among those who had a bb genotype, and 0.36 (95% CI, 0.15-0.85) among those who did not take NSAIDs. The ORs for the highest tertile of calcium intake was 0.05 (95% CI, 0.01-0.41), P(trend) < 0.01 among those who were Bb and did not take NSAIDs, and 0.16 (95% CI, 0.02-1.36), P(trend) = 0.47 among those who were bb and did not take NSAIDs. These data support the hypotheses that higher calcium intakes may decrease risk for colorectal neoplasms, and that such a relationship is more readily detectable among those who do not take NSAIDs, and may be strongest among those who have at least one vitamin D receptor BsmI b allele.
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PMID:Calcium, vitamin D, and risk for colorectal adenoma: dependency on vitamin D receptor BsmI polymorphism and nonsteroidal anti-inflammatory drug use? 1286 2

The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.
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PMID:The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism. 1659 60

The lack of overt elevation of serum calcium concentration in some patients suffering from primary hyperparathyroidism is an intriguing clinical phenomenon. Previous studies have substantiated abnormal parathyroid tissue in these patients, but the extent and mode of derangements remained largely undefined. The parathyroid tissues from patients of normocalcemic primary hyperparathyroidism (NCPHPT) and those having normal parathyroid glands, hypercalcemic primary hyperplasia, secondary hyperplasia, and adenoma were compared by undertaking quantitative immunohistochemistry analysis on tissue microarray. The statistic results suggested that the parathyroid tissue of NCPHPT approximates more to normal gland than to its counterpart in other groups of parathyroid proliferative diseases in terms of the lack of significant alterations of calcium-sensing receptor (CaSR), chromogranin A (CGA), parathyroid hormone (PTH), and proliferation index (Ki67). On the other hand, the depressed vitamin D receptor (VitDR) and elevated cyclin D1 (CyD1) of NCPHPT indicated the inherent functional abnormalities in parathyroid cells. Our results imply that inherent functional disengagement may exist between CaSR and CyD1 or between CaSR and VitDR or both in parathyroid cells of symptomatic NCPHPT. Lack of enhanced release of CGA and PTH and discordance between proliferative activity and CyD1 expression in parathyroid cells may further hinder the development of hypercalcemia.
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PMID:Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands. 1667 Sep 29


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