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At least 865 records · Page 48Linked to original sources
PubMed1999

Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.

Adenoma↗
PubMed1994

Human parathyroid hormone-related protein in ovarian small cell carcinoma. An immunohistochemical study.

BACKGROUND: Small cell carcinomas (SCC) are the most common ovarian tumors associated with hypercalcemia. Parathyroid hormone-related protein (PTHrp) is the most frequent cause of hypercalcemia of malignancy. METHODS: The presence of PTHrp in SCC has been studied by immunohistochemistry in formalin fixed, paraffin embedded tissues. A polyclonal antibody against a synthetic peptide corresponding to the first 36-N terminal amino acid residues of PTHrp was used. Normal dog skin, which is rich in PTHrp, was used as a positive control. Absorption tests using the synthetic peptide as antigen were done in all the cases. RESULTS: Immunoreactivity for PTHrp was found in five of seven cases of SCC. The serum calcium levels were elevated in two of these cases, normal in two, and unknown in one. The two negative cases were associated with high serum calcium levels. CONCLUSION: The lack of correlation between immunoreactivity and serum calcium levels can be explained on the basis that immunohistochemistry is dependent on the peptide content of cells rather than on the capability for hormone production and/or release. The results suggest that PTHrp plays a role in the development of hypercalcemia in patients with SCC of the ovary.

Adult↗
PubMed1995

Thyroid anaplastic carcinoma producing granulocyte-colony-stimulating factor and parathyroid hormone-related protein.

A 65-year-old woman noticed a rapidly enlarging neck mass with tenderness and complained of dyspnea. She was diagnosed as having anaplastic thyroid carcinoma. She died of respiratory failure 14 days after admission. Marked leukocytosis and hypercalcemia were observed in the clinical course. Both serum granulocyte-colony-stimulating factor and parathyroid hormone-related protein levels were elevated. The cancerous tissue was also immunohistochemically stained for both peptides. We conclude that the leukocytosis and hypercalcemia of this patient were induced by these two factors produced by the tumor.

Aged↗
PubMed2000

Increased upstream methylation has no influence on the overexpression of the parathyroid hormone-related protein gene in squamous cell carcinoma of the lung.

Humoral hypercalcaemia of malignancy (HHM) commonly results from the excessive production of a parathyroid hormone-related protein (PTHrP) by tumours. We have previously shown malignancy is associated with increased DNA methylation in the 5' region of the PTHrP gene. In a series of patients with lung carcinoma and relatively high serum calcium levels, 3 patients showed substantially increased PTHrP gene methylation while 5 patients showed no change in methylation status in this region. Patients showed marked tumour-specific expression of PTHrP through the P1 and P3 promoters with more general tumour and non-tumour expression through the P2 promoter. The lack of potential key regulatory CpG sites in the P1 promoter and the complete demethylation in the P2 and P3 promoters suggests methylation does not influence tumour-specific expression of PTHrP. Although demethylation may be a prerequisite for P2 and P3 expression, the overexpression of the PTHrP gene in cancer cells must be mediated through mechanisms other than DNA methylation.

Aged↗
PubMed2001

Histologic diagnosis of primary hyperparathyroidism: a concordance analysis between three pathologists.

Primary hyperparathyroidism (HPT) is caused by a parathyroid adenoma, hyperplasia or carcinoma. Difficulties for the histologic diagnosis of abnormal parathyroid tissue are widely recognized. The aim of the study was to evaluate the reproducibility of the morphologic criteria through a concordance study among three pathologists. Representative slides of 40 patients with biochemically primary HPT stained with hematoxylin and eosin were blindly reviewed by three pathologists. Each pathologist established the diagnosis of adenoma or hyperplasia and assessed the presence of fat cells, a rim of normal tissue, a fibrous capsule, the number of cellular types, the lobular pattern, and the characteristics of the blood vessel's wall. A concordance analysis was then performed. Mean age of the group was 55 +/- 14 yr, 7 were males and 33 females. The concordance analysis among the three pathologists for the differential diagnosis between adenoma and hyperplasia, showed a Kappa index of 0.5. Kappa index for the presence of fat cells was 0.56, for the presence of a rim of normal tissue 0.47, and for the number of cellular types 0.29. The concordance for the differential diagnosis between parathyroid adenoma and hyperplasia in this study was low.

Adenoma↗
PubMed1999

Extended esophagolaryngeal resection with parathyroid autotransplantation.

Esopharyngolaryngeal resection for carcinoma of the cervical esophagus must be accompanied by resection of the thyroid gland, parathyroid bodies, and regional lymph nodes. In order to reduce long-term morbidity associated with the procedure, we performed parathyroid autotransplantation in two patients who underwent esophagolaryngeal resections. Grafting of the upper two parathyroid glands into the sternocleidomastoid muscle was carried out successfully in both cases. Graft function was rapidly restored. During the third postoperative week, blood levels of intact parathormone (PTH) reached 20 pg ml(-1) in the first case and 15 pg ml(-1) in the second, and the patients were successfully weaned off calcium and vitamin D supplementation. Parathyroid autotransplantation should be attempted in all cases of esophagolaryngeal resections provided that parathyroid glands are free of malignancy.

Aged↗
PubMed1999

Immunohistochemical detection of parathyroid hormone-related protein in a cutaneous squamous cell carcinoma causing humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein is the main humoral factor implicated. In spite of the fact that normal keratinocytes produce parathyroid hormone-related protein, it is highly unusual for patients with squamous cell carcinomas of the skin to present with humoral hypercalcemia of malignancy. We present a well-documented case of cutaneous squamous cell carcinoma complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of high parathyroid hormone-related protein production by the tumoral cells.

Aged↗
PubMed1983

New perspectives in localizing enlarged parathyroids by technetium-thallium subtraction scan.

Double-tracer scanning (Tc-99m as pertechnetate and Tl-201 as chloride) with an Anger camera and computerized image subtraction was performed in 61 patients whose clinical and biochemical findings had suggested primary hyperparathyroidism. This study showed intra- or extrathyroidal focal uptake of thallium in 37 cases. Among these, 24 patients underwent surgery, and 18 parathyroid adenomas, five carcinomas, and one hyperplastic gland were found exactly in the sites predicted by scintigraphy. Among 24 patients with negative scans, only two underwent surgery; a hyperplastic parathyroid gland (diam less than 0.5 cm) was found in both. The success rate was 92% in the cases in which operation was performed. We believe that the new method may be useful in the preoperative detection of parathyroid enlargements.

Adenoma↗
PubMed2001

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

OBJECTIVES: To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. PATIENTS AND METHODS: The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. RESULTS: Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). CONCLUSIONS: These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

Adult↗
PubMed1994

Multiple endocrine neoplasia type 2. Clinical features and screening.

Prospective screening programs have changed the presenting clinical features of MEN 2, the association of medullary thyroid carcinoma, pheochromocytoma, and parathyroid disease. Currently, all manifestations of MEN 2 syndrome can be diagnosed at an early stage. Gene carrier status can be identified by characterization of specific mutations. Prospective screening for early medullary thyroid carcinoma by calcitonin testing and for pheochromocytoma by several techniques routinely permits identification of early manifestations.

Adrenal Gland Neoplasms↗
PubMed2005

[Two cases of hemodialysis patients with absolute hypoparathyroidism or normal parathyroid function who were suffering from prostate carcinoma].

In recent years, the incidence of prostate carcinoma in patients with renal failure is increasing. But it is difficult to diagnose the occurrence of this neoplasm because of decrease of urinary volume in these patients. Two hemodialysis patients (age: 64, 68 years, the duration of hemodialysis: 10, 8 years) suffering from prostate carcinoma were treated with androgen deprivation therapy, which accelerates bone resorption. (This kind of osteoporosis is often treated by bisphosphonate, but this treatment is prohibited in hemodialysis patients.) Both serum testosterone and estradiol went down to the extremely lower levels in these patients. Thereafter, one (case 2) of them was maintained under absolute hypoparathyroidism by the conservative therapy with vitamin D. As a result, bone mineral density of the patient (case 2) was well maintained during one year. In conclusion, hypoparathyroidism was helpful to prevent bone loss in patients receiving androgen deprivation therapy.

Aged↗
PubMed2004

Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype.

Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features. We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid beta precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3 genes. Cluster 2, characterized by HRPT2 mutations, was the most striking, suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors developing on a background of germ-line HRPT2 mutation follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation. These findings provide insights into the molecular pathways involved in parathyroid tumorigenesis and will contribute to a better understanding, diagnosis, and treatment of parathyroid tumors.

Gene Expression Profiling↗
PubMed1994

Evidence for the uptake of a vitamin D analogue (OCT) by a human carcinoma and its effect of suppressing the transcription of parathyroid hormone-related peptide gene in vivo.

The present study was undertaken to clarify the pharmacokinetics of 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-1,25-(OH)2D3, OCT), a vitamin D3 analogue with little calcemic activity, and its effect on the transcription of parathyroid hormone-related peptide (PTHRP) gene in nude mice bearing a human carcinoma (FA-6) associated with humoral hypercalcemia. FA-6 tumor expressed vitamin D receptor (VDR) mRNA, and its nuclear extract contained a specific and saturable 1,25-(OH)2D3 binding activity. Although [3H]OCT administered intravenously into FA-6 tumor-bearing nude mice was cleared from the circulation more rapidly than [3H]1,25-(OH)2D3, the uptake of [3H]OCT into the tumor tissue, relative to the radioactivity in the circulation, was greater than that of [3H]1,25-(OH)2D3. Intravenous or oral administration of OCT reduced the steady-state levels of PTHRP mRNA in FA-6 tumor, and nuclear run-off assays demonstrated that the effect of OCT on PTHRP gene expression occurred at a transcriptional level. RNase mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were down-regulated by OCT. Finally, OCT exerted a preventive as well as therapeutic effect on cancer-associated hypercalcemia with a marked prolongation of the survival time in tumor-bearing animals. These results suggest that OCT is effectively taken up by a VDR-positive human carcinoma in vivo and has a therapeutic potential for cancer-associated hypercalcemia through suppression of PTHRP gene transcription.

Animals↗
PubMed1986

Human prostate carcinoma causes hypercalcemia in athymic nude mice and produces a factor with parathyroid hormone-like bioactivity.

The mechanism of the calcium and phosphorus abnormalities associated with metastatic prostate carcinoma (CaP) is not yet understood. A tumor model was recently established in which 9479, a human CaP from a patient with prostate carcinoma-induced osteomalacia, was heterotransplanted into athymic nude mice (ANM). In the present study the effect of 9479 on ANM was evaluated. Serum calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) and urinary cAMP were measured. Ca was markedly elevated in ANM bearing 9479 vs. age-matched controls (C); the increased Ca returned to control level after tumor removal. Serum PTH was lower in 9479-bearing ANM vs. C while urinary cAMP and serum 1,25-(OH)2D3 levels were elevated. In the ANM bearing 9479, there was a decrease in serum P vs. C which returned to normal after tumor removal. Fractional P excretion was greater in 9479 animals than C. Extracts of 9479 were examined for the presence of parathyroid hormone-like bioactivity by measuring stimulation of intracellular cAMP in ROS 17/2.8 cells. Cyclic AMP stimulation which was found was shown to be inhibited by the competitive PTH antagonist [8Nle, 18Nle, 34Tyr]bPTH-(3-34) amide. These data suggest tumor induction of parathyroid hormone-like humoral modulation of calcium, phosphate and vitamin D metabolism in vivo associated with a parathyroid hormone-like prostate carcinoma product.

Animals↗
PubMed1987

A biologically active parathyroid hormone-like substance secreted by an adenosquamous carcinoma of the transverse colon.

Recently, controversy has emerged as to whether paraneoplastic hypercalcemia in nonparathyroid tumors is due to ectopic production of a parathyroid hormone (PTH)-like substance. A sensitive DNA hybridization technique was unable to reveal PTH mRNA in a collection of such tumors. However, there is growing evidence that squamous differentiation of tumors favors the expression of PTH-like substances. We report the case of a 41-year-old woman with an adenosquamous carcinoma of colonic origin associated with severe hypercalcemia. The squamous component of liver metastases showed immunoreactivity with two different PTH antisera, suggesting the production of a PTH-like substance.

Adenocarcinoma↗