Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present herein a case of sigmoid colon cancer associated with primary hyperparathyroidism (PHP). PHP is known to be associated with malignancy, and decreased intracolonic calcium (Ca) resulting from increased vitamin D (VD) levels may play a role in colorectal carcinogenesis. PHP was diagnosed in this patient by preoperative screening blood chemistry examination. The blood level of intact parathyroid hormone (PTH) was elevated and a parathyroid gland scintigram demonstrated abnormal uptake near the right lower lobe of the thyroid. There was no evidence of bone metastasis, and a sigmoid colectomy was performed with curative intent. The patient had an uneventful postoperative course without a critical elevation of the serum Ca level. This case report suggests that a relationship exists between PHP and colon cancer, and the possible mechanisms of this association are presented in our discussion.
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PMID:Sigmoid colon cancer associated with primary hyperparathyroidism: report of a case. 1048 59

The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1-34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1-34)NH(2) and [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH-(1-31)NH(2) to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs' ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.
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PMID:The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation. 1456 63

The second type of multiple endocrine neoplasia syndromes can be described as rare syndromes, heritable in autosomal dominant manner and linking medullary thyroid carcinoma to different tumors of endocrine organ system and endocrinopathies. This syndrome is divided into multiple endocrine neoplasia syndrome type 2A (MEN 2A), characterized with combination of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism; type 2B (MEN 2B), characterized with combination of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and ganglioneuromatosis, and familial medullary thyroid carcinoma syndrome, characterized with the only indication, which is hereditary medullary thyroid carcinoma. Though type 2 multiple endocrine neoplasia syndrome has been known since 1961, yet, the cause of the syndrome, which is germline mutations of c-ret protooncogene, was detected just a decade ago and syndrome pathogenesis with its characterized endocrine neoplasia carcinogenesis machinery were detected. Implementation of progressive genetic researches in clinical practice enabled precise diagnosis of multiple endocrine neoplasia syndrome and its subtypes not only for ill patients but also for healthy syndrome inheritors, e.g. relatives of the sick. Stated genotype link to phenotype helps to prognosticate possible combinations of endocrine neoplasia and endocrinopathies, and to choose purposeful patient observation. Genetic screening of the inheritors of multiple endocrine neoplasia type 2 syndrome enabled purposeful researches and observations of patients with a huge risk of uprising endocrine neoplasia, it also enabled application of effective prophylaxis methods, avoidance or early diagnostic of malignant tumors and life prognosis improvement for patients with malignant tumors while practicing well-timed treatment adaptation. This literature review contains the newest data on multiple endocrine neoplasia syndrome type 2 and its pathogenesis, diagnostics, patient observation, endocrine cancer prophylaxis and methods of treatment, which are characteristic for syndrome and which are being chosen according to biochemical endocrine neoplasia symptoms and genetic diagnosis.
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PMID:[Multiple endocrine neoplasia syndromes. Type 2]. 1586 1

Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma.
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PMID:Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation with anaplastic transformation. 1915 65

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia.
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PMID:Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. 1992 10

Parathyroid cancer is a rare, clinically aggressive cause of primary hyperparathyroidism, and whether these malignancies generally evolve from pre-existing benign adenomas or arise de novo is unclear. Furthermore, while inactivation of the CDC73 (HRPT2) tumor suppressor gene, encoding parafibromin, is a major contributor, other genes essential to parathyroid carcinogenesis remain unknown. We sought to identify genomic regions potentially harboring such oncogenes or tumor suppressor genes, and to gain insight into the origins and molecular relationship of malignant versus benign parathyroid tumors. We performed genome-wide copy-number and loss of heterozygosity analysis using Affymetrix 50K SNP mapping arrays and/or comparative genomic hybridization on 16 primary parathyroid carcinomas, local recurrences or distant metastases, and matched normal controls, from 10 individuals. Recurrent regions of allelic loss were observed on chromosomes 1p, 3, and 13q suggesting that key parathyroid tumor suppressor genes are located in these chromosomal locations. Recurrent allelic gains were seen on chromosomes 1q and 16, suggesting the presence of parathyroid oncogenes on these chromosomes. Importantly, the most common alteration in benign parathyroid adenomas, loss of 11q, was not found as a recurrent change in the malignant parathyroid tissues. Molecular allelotyping using highly polymorphic microsatellite markers provided further confirmation that the prevalence of 11q loss is markedly and significantly lower in carcinomas as compared with adenomas. Our observations provide molecular support for the concept that sporadic parathyroid cancer usually arises de novo, rather than evolving from a pre-existing typical benign adenoma. Furthermore, these results help direct future investigation to ultimately determine which of the candidate genes in these chromosomal locations make significant contributions to the molecular pathogenesis of parathyroid cancer.
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PMID:Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins. 2343 13

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is essential because it is associated with increased risk of parathyroid cancer. A 30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was surgically removed and was histologically confirmed to be an adenoma. However, PHPT due to another parathyroid tumor reoccurred two years after the surgery. Although no HPT-JT-associated manifestations other than PHPT were detected, HPT-JT was strongly suspected based on the exclusion of multiple endocrine neoplasia (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73, which encodes the tumor suppressor protein parafibromin. The residual parathyroid glands were all removed without autotransplantation of parathyroid gland taking into consideration prospective parathyroid carcinogenesis. The resected parathyroid tumor was also an adenoma. The present case highlights that HPT-JT should be considered and CDC73 mutation analysis should be performed, especially in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid involvement, and PHPT presenting with severe hypercalcemia even if there is no positive family history.
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PMID:Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation. 2595 15