Hipercalcemia maligna en pacientes con tumores neuroendocrinos. Reporte de 2 casos de tumores pancreáticos productores de péptido relacionado con hormona paratiroidea / Malignant hypercalcaemia in patients with neuroendocrine tumours. Report of 2 cases of parathyroid hormone-related peptide-secreting pancreatic tumours

Resumen La hipercalcemia maligna mediada por péptido relacionado con hormona paratiroidea (PR-PTH) es una manifestación poco común en tumores neuroendocrinos. Presentamos dos pacientes con tumores neuroendocrinos de páncreas con metástasis a hígado pero sin compromiso óseo en quienes se evidenció hipercalcemia maligna asociada a elevación de PR-PTH, con PTH suprimida. En ambos casos se logró normalizar temporalmente la calcemia con el uso de análogos de somatostatina, pero durante la evolución se requirió adición de bisfosfonatos en uno de ellos. Con la discusión de estos casos, la revisión de la literatura y de los casos similares publicados esperamos contribuir al mejor conocimiento de esta enfermedad.

Abstract Parathyroid hormone-related peptide-mediated hypercalcaemia (PTH-rp) is rare in patients with neuroendocrine tumours. The clinical cases are thus presented on two patients with pancreatic neuroendocrine tumours with liver metastases, but without bone involvement and with hypercalcaemia associated with elevated PTH-rp and with PTH suppressed. In both cases, it was possible to temporarily bring the calcium levels back to normal with the use of somatostatin analogues, but during the course of the disease, the addition of bisphosphonates was required in one of them. With the discussion of these cases and the review of the literature and similar published cases, it is hoped to contribute to provide better knowledge of this disease.

Effects of dynamic pressure on the expression of PTHrP mRNA in metaphyseal cartilage stem cells of rats / 西安交通大学学报(医学版)

Objective To study the effect of dynamic pressure on the expression of parathyroid hormone-related protein (PTHrP)mRNA in metaphyseal cartilage stem cells of rats so as to further explore whether fiber actin (F-actin)is involved in the mechanical signal transduction process.Methods We isolated and cultured metaphyseal cartilage stem cells of rats by immunomagnetic beads.The third-generation rat metaphyseal cartilage stem cells were randomly divided into four groups:0%,3%,6%,and 12% deformed groups according to the size of dynamic pressure strength.We used a self-prepared dynamic tonic culture device to exert different intensity of pressure on each group of cells for 24 hours.Flow cytometry was used to detect the cell cycle distribution and apoptosis rate.The expression of PTHrP mRNA in each group was detected by Rea-l time quantitative PCR. Furthermore,the third-generation rat metaphyseal cartilage stem cells were randomly divided into four groups:control group,simple pressure group (6% deformation),pressure+cytoskeleton relaxin D group,and simple cytoskeleton relaxin D group according to whether or not to apply pressure and cytoskeleton relaxin D.F-actin fibers in each group of cells were stained with phalloidin and placed under a laser scanning confocal microscope.The expression of PTHrP mRNA in each group was detected by Real-time quantitative PCR.Results The results of flow cytometry showed no significant difference in G0/G1,G2/M and S phases between 0%,3%,6% and 12% deformed groups (P＞0.05).There was no significant difference in the apoptosis rate between 3% and 6% deformed groups compared with 0% deformed group (P＞0.05).The apoptosis rate was significantly higher in 1 2 % deformed group than in control group (P＜0.05).The results of laser confocal microscopy showed that the arrangement of F-actin fibers in the pressure group was neat and parallel compared with that in the control group, which was consistent with the direction of force.The intracellular F-actin fiber structure in pressure+cytoskeleton relaxin D group and simple cytoskeleton relaxin D group was destroyed and aggregated into clusters.Real-time quantitative PCR results showed that PTHrP mRNA expression did not significantly differ between 3% and 0% deformed groups (P＞0.05).The expression of PTHrP mRNA in 6% and 12% deformed groups was significantly higher than that in 0% group (P＜0.05).The expression of PTHrP mRNA in the cells of simple pressure group was significantly higher than that in the control group (P＜0.05).There was no significant difference in the expression of PTHrP mRNA between simple cytoskeleton relaxin D group and control group (P＞0.05).The mRNA expression of PTHrP was higher in pressure+cytoskeleton relaxin D group than that in control group,but lower than in simple pressure group (P＜0.05).Conclusion The dynamic pressure of proper intensity can increase the mRNA expression of PTHrP in chondrocytes of metaphyseal hypertrophy in rats,and F-actin is involved in the mechanical signal transduction process.

Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism

BACKGROUND: Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family. METHODS: Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control. RESULTS: We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained. CONCLUSION: Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

Hipercalcemia paraneoplásica de carcinoma anaplásico da tireoide / Paraneoplastic hypercalcemia of anaplastic thyroid carcinoma: case report

A hipercalcemia deve ser considerada no diagnóstico diferencial de alterações neuropsiquiátricas agudas. Em 90% dos casos, a etiologia corresponde a hiperparatireoidismo primário ou neoplasias. Valores séricos superiores a 14mg/dL e sintomáticos são frequentemente tradutores de causa maligna. O carcinoma anaplásico da tireoide consiste em um tumor indiferenciado, com progressão rápida e prognóstico reservado, que evolui, em alguns casos, a partir de lesões tireóideas preexistentes, benignas ou malignas (desdiferenciação). Embora a apresentação clínica mais frequente destes tumores consista no desenvolvimento de massa cervical, eles podem ser diagnosticados no esclarecimento etiológico de metástases ou síndromes paraneoplásicos. A hipercalcemia, associada à neoplasia, pode ocorrer em contexto de metástases ósseas, com libertação de citocinas, ou por mecanismo humoral, mediada pela proteína relacionada ao hormônio hormônio paratireóideo (PTHrP). Os autores descrevem o caso de uma mulher de 85 anos, com antecedentes de bócio multinodular benigno, internada para esclarecimento etiológico de hipercalcemia grave, com manifestações neuropsiquiátricas, diagnosticando-se, após avaliação, carcinoma anaplásico da tireoide. O caso foi abordado em reunião multidisciplinar, optando-se por limitação terapêutica a cuidados paliativos. A doente faleceu 3 meses após o diagnóstico.(AU)

Hypercalcaemia should be considered in the differential diagnosis of acute neuropsychiatric disorders. In 90% of the cases, the etiology corresponds to primary hyperparathyroidism or neoplasms. Serum values above 14mg/dL and symptomatic are often indicative of a malignant cause. The anaplastic thyroid carcinoma consists of an undifferentiated tumor, with rapid progression and poor prognosis, which in some cases progresses from pre-existing benign or malignant thyroid diseases (dedifferentiation). Although the most frequent clinical presentation of these tumors consists of the development of a cervical mass, they can be diagnosed in the etiological clarification of metastases or paraneoplastic syndromes. Neoplasm-associated hypercalcaemia may occur in the context of bone metastasis, with release of cytokines, or through a humoral mechanism, mediated by the parathyroid hormone (PTHrP)-related protein. The authors describe the case of an 85-year-old woman with a history of multinodular benign goiter, hospitalized for etiological elucidation of severe hypercalcaemia with neuropsychiatric manifestations, with a final diagnosis of anaplastic thyroid carcinoma, after the diagnostic evaluation. The case was approached in a multidisciplinary meeting, and the therapeutic limitation to palliative care was chosen. The patient died 3 months after the diagnosis.(AU)

Clinical Characteristics, Causes and Survival in 115 Cancer Patients with Parathyroid Hormone Related Protein-mediated Hypercalcemia

BACKGROUND: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. METHODS: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed. RESULTS: Of all 115 patients, solid organ malignancies were the most common etiology (98 cases, 85.2%), with squamous cell carcinoma (50 cases, 43.4%), adenocarcinoma (27 cases, 23.4%). Interestingly, hepatocellular carcinoma (HCC; 18 cases, 15.7%) and cholangiocarcinoma (11 cases, 9.6%) were much more common causes than other previous reports. Hematologic malignancy was less common (17 cases, 14.8%), with multiple myeloma (9 cases, 7.8%) and non-Hodgkin's lymphoma (5 cases, 4.3%). Overall median survival was only 37 days. There was significant difference in median survival between two groups (35 days for solid organ malignancy and 72 days for hematologic malignancy; P=0.015). Cox regression analysis identified age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis as independent predictive factors for survival time. CONCLUSIONS: PTHrP-mediated hypercalcemia was most frequently caused by solid organ malignancy. However, HCC and cholangiocarcinoma were important causes of PTHrP-mediated hypercalcemia may be due to geographic differences in cancer incidence in Korean population. Age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis were independent poor predictive factors for survival time.

Process of neovascularization in mediating regulation of parathyroid hormone on metabolism of target organs / 中华内分泌代谢杂志

Neovascularization plays an essential role in the process of renovation in tissue damage,tumor growth, and hormones action. Parathyroid hormone (PTH) is one of the basic hormones that regulate the serum calcium, phosphorus, and bone metabolism. In recent years, studies involving the neovascularization-mediated effects of PTH on metabolism are becoming more and more popular and wider. Based on recent researches, the purpose of this paper is to summarize the changes of angiogenesis while PTH interacts with its target organs, especially interacts with osseous tissue.

Hypercalcemia in a Patient with Systemic Lupus Erythematosus / 대한내과학회지

Hypercalcemia is a common clinical problem. The most frequent causes of hypercalcemia include primary hyperparathyroidism and malignancy; systemic lupus erythematosus (SLE) is a very rare cause of hypercalcemia. Here we describe a case of symptomatic severe hypercalcemia, which developed during a lupus flare. After treatment with intravenous fluids, diuretics, pamidronate, and hemodialysis, calcium levels normalized and were maintained on low-dose prednisolone treatment. To the best of our knowledge, this is the first case of hypercalcemia in a patient with SLE in Korea. Clinicians should consider lupus as a differential diagnosis for patients with severe hypercalcemia.

Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide / 대한소화기학회지

Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC.

Research advances of parathyroid hormone-related protein / 中国生化药物杂志

Parathyroid Hormone-related Protein( PTHrP) is a polyhormone secretory protein secreted by a variety of tissues and cells that plays fundamental roles in the growth and development of various organs, promotes migration and invasion in breast cancer, prostate cancer and non-small cell lung cancer and also plays a key role in osteolysis.With the development of scientific research, many unknown functions of the parathyroid hormone-related protein will be uncovered.

Emerging Therapies for Osteoporosis

Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients.

Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein / Journal of the Korean Cancer Association, 대한암학회지

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/computed tomography scan and bone marrow examination, which may be useful for early diagnosis.

Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

Influence of the Application of Low-Calcium Dialysate in Combination with Calcitriol in Serum Calcium-Phosphorus Levels / 天津医药

Objective To observe the changes of serum calcium, phosphorus, calcium-phosphorus product and para-thyroid hormone(PTH)levels after treatment with different concentrations of calcium dialysate in combination with calcitri-ol. Methods Thirty-six patients on maintenance hemodialysis were randomly divided into Dca1.25 group and Dca1.5 group, 18 cases in each group. Patients took different doses of calcitriol on the different values of PTH basis. Changes of se-rum calcium, phosphorus, calcium-phosphorus product,PTH and bone alkaline phosphatase (BAP) levels were recorded re-spectively on four time points from prior treatment and 1, 3 and 6 months of therapy. The levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also observed. Results There was an interaction between treatment effects and time effects in serum calcium, phosphorus, calcium-phosphorus product levels in two groups (P＜0.05). With the dura-tion of treatment, there was a trended to decrease and increase respectively in DCa 1.25 group and DCa 1.5 group, and trend-ed to stabilize for therapy 3 to 6 months. There was no interaction between serum PTH and BAP levels and time effects in two groups. There was no statistical difference in simple treatment effects and time effects. The serum PTH level showed a trend of increase gradually in DCa1.5 group with the duration of treatment. In DCa 1.25 group, the serum PTH level trended to stabilize after 3-month therapy and showed a trend of decrease gradually. There was an interaction between treatment effects and time effects in SBP in two groups, but no interaction in DBP. There was a significant difference in SBP before and after treatment in two groups. The level of SBP reduced tardily with time of treatment and reduced significantly after 3 and 6-month therapy. Conclusion The application of DCa1.25 dialysate in combination with calcitriol decreased serum calci-um effectively and kept the lower limit of normal value, which increased tolerability of active vitamin D and calcium carbon-ate therapy, and decreased SBP in maintenance hemodialysis patients.

The N- and C-terminal domains of parathyroid hormone-related protein affect differently the osteogenic and adipogenic potential of human mesenchymal stem cells

Parathyroid hormone-related protein (PTHrP) is synthesized by diverse tissues, and its processing produces several fragments, each with apparently distinct autocrine and paracrine bioactivities. In bone, PTHrP appears to modulate bone formation in part through promoting osteoblast differentiation. The putative effect of PTH-like and PTH-unrelated fragments of PTHrP on human mesenchymal stem cell (MSCs) is not well known. Human MSCs were treated with PTHrP (1-36) or PTHrP (107-139) or both (each at 10 nM) in osteogenic or adipogenic medium, from the start or after 6 days of exposure to the corresponding medium, and the expression of several osteoblastogenic and adipogenic markers was analyzed. PTHrP (1-36) inhibited adipogenesis in MSCs and favoured the expression of osteogenic early markers. The opposite was observed with treatment of MSCs with PTHrP (107-139). Moreover, inhibition of the adipogenic differentiation by PTHrP (1-36) prevailed in the presence of PTHrP (107-139). The PTH/PTHrP type 1 receptor (PTH1R) gene expression was maximum in the earlier and later stages of osteogenesis and adipogenesis, respectively. While PTHrP (107-139) did not modify the PTH1R overexpression during adipogenesis, PTHrP (1-36) did inhibit it; an effect which was partially affected by PTHrP (7-34), a PTH1R antagonist, at 1 microM. These findings demonstrate that both PTHrP domains can exert varying effects on human MSCs differentiation. PTHrP (107-139) showed a tendency to favor adipogenesis, while PTHrP (1-36) induced a mild osteogenic effect in these cells, and inhibited their adipocytic commitment. This further supports the potential anabolic action of the latter peptide in humans.

Effects of C-terminal fragment of parathyroid hormone-related protein on bone metabolism in ovariectomized rats / 中华风湿病学杂志

Objective To investigate the effects of C-terminal fragment of parathyroid hormonerelated protein (PTHrP107-139) on bone mineral density (BMD), bone histomorphometry and biomechanical properties in ovariectomized (OVX) rats and its effect on bone metabolism is also explored. Methods Forty 4-month old female Wistar rats in which 30 were ovariectomized and then divided into 3 groups: the placebo, the PTHrPC and the CT groups, the other 10 rats were Sham-operated as the control group (Sham). Five weeks later, the rats of PTHrPC and CT groups were subcutaneously injected with PTHrP107-139 (40 μg/kg) and Salmon Calcitonin (15 U/kg) respectively once every other day. The rats of the placebo and sham groups were injected with 0.2 ml saline once every other day. After treatment of 12 weeks, all rats were sacrificed and all samples were collected and analyzed. Results ① Compared with the placebo, the BMD and bone strength of PTHrPC and CT groups were significantly increased (P<0.05). ② Histomorphometry revealed that the tetracycline labeled bone surfaces, osteoid surfaces, mineral apposition rate and bone resorption rate were remarkably decreased in PTHrPC, and CT groups comparing with those of the placebo group. Conclusion Cter-minal PTHrP107-139 is effective in increasing the BMD, bone strength and quality when administered intermittently to ovariectomy-induced osteoporotic rats. Its increasing in bone quality may relate to reducing bone turnover and inhibiting resorption.

Effects of human parathyroid hormone related protein on osteoporosis of ovariectomized rats / 中华风湿病学杂志

Objective To investigate the therapeutic effects of human parathyroid hormone related protein (PTHrP1-34) on osteoporosis of ovariectomized osteoporotic rats. Methods Sixty 4-month-old female Wislar rats were involved in this study and 40 of them were ovariectomized and another 20 received sham operation. After 6 weeks of ovariectomy the osteoporosis model was confirmed by examing 10 ovariectomized and sham-operated rats. The 30 osteoporotic rats were randomly divided into 3 treatment groups, i.e. PTHrP, estradiol and placebo. Human 40 ?g/kg PTHrP1-34 was subcutaneously injected once daily to PTHrP group and the estradiol group was injected with 40 ?g/kg estradiol benzoate once every 3 days.The placebo and shamoperated rats were given 0.2 ml saline every 3 days. The bone mineral density (BMD), bone histomorphology, the bone weight of dry and ash and serum Ca,P,alkaline phosphatase (ALP) were measured after 3 months' therapy. Results After 6 weeks of ovariectomy, the lumbar BMD of ovariectomized rats were significantly declined compared with those of the sham-operated rats. After 12 weeks treatment the femoral and lumbar BMD and the rate of bone weight of dry and ash in the PTHrP group were increased obviously compared with those of placebo groups.There was no significant difference between PTHrP group and estradiol group, in PTHrP group the percent age of trabecular area,trabecular width,osteoblast surface and mineral apposition rate were obviously higher than those in placebo group.Conclusion Treatment with 40 ?g/kg dose of hPTHrP1-34 administered once daily is effective in treating ovariectomy-induced osteoporosis.

The Effects of Parathyroid Hormone-related Protein (PTHrP) (1-34) on the Detrusor Muscle Contraction of Rabbits / 대한비뇨기과학회지

Purpose: We have studied the effect of Parathyroid hormone-related protein (PTHrP) (1-34) on the contraction of bladder muscle induced by various stimulations. MATERIALS AND METHODS: Bladder muscle strips were prepared from the urinary bladder obtained from male New Zealand White rabbits (2-2.5Kg, n=20). The isometric contractile force responses were monitored via a FT03 force transducer. PTHrP (1-34) was introduced in spontaneous contraction, carbachol (CCh) (0.5microM)-induced the contraction, and a high potassium solution (60mM) induced the contraction to monitor the responses. In addition, the effect of PTHrP (1-34) was monitored in the pre-treatment of a calcium channel blocker, nicardipine. RESULTS: PTHrP (1-34) (10 10-10 7M) reduced most of the basal spontaneous contractile responses. According to the increasing concentration, PTHrP (1-34) (10 10 -10 7M) reduced 64.6+/-8.4% of the CCh (0.5microM) induced contractions, and 34.3+/-17.4% of the high concentration potassium solution (60mM) doses induced a contraction. After nicardipine (5.0microM) treatment, pretreating with PTHrP (1-34) (10 7M) showed a 33.5+/-15.5% CCh (0.5microM) increase in induced contractions compared to thr control. CONCLUSIONS: PTHrP (1-34) reduced the spontaneous phasic activity of the smooth muscle strip and caused a concentration-dependent relaxation of the contraction, which induced by carbachol or a high concentration potassium solution. These results support the hypothesis that PTHrP is a regulator of bladder tones. This study results suggested that there is some other mechanism of PTHrP (1-34) on the smooth muscles of the bladder, which is not related to a voltage-sensitive calcium channel.

Expression of PTHrP in the condyle cartilage after traction of the mandibular ramus and zygomatic arch in rabbits / 实用口腔医学杂志

Objective:To understand the roles of PTHrP in the pathogenesis of temporomandibular joint after over mechanical loading. Methods:Fifteen adult New Zealand rabbits were subjected to traction between the mandibular ramus and zygomatic arch in the postero-superior direction unilaterally using elastic force. The rabbits were killed respectively at 2, 4 and 6 weeks and the histologic changes were observed by Hematoxylin & Eosin staining. The expression of PTHrP in the condyle of TMJ was observed by immunohistochemistry. Results:Stronger expression of PTHrP could be found in proliferation cell layers and upper hypertrophy cell layers in the early stage after operation, and weaker expression in mid stage, but stronger near the chondrocyte clusters. Conclusion:It is suggested that PTHrP might relate to the regeneration of condyle cartilage.

Simultaneous elevation of serum parathyroid hormone(PTH) and parathyroid hormone-related protein(PTHrP) in a case of lung cancer with hypercalcemia / 결핵

The parathyroid hormone related protein(PTHrP) is the most common causative peptide of humoral hypercalcemia of malignancy. In contrast, the serum level of parathyroid hormone(PTH) is low to undetectable in the majority of patients with malignancy associated hypercalcemia. Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. To our knowledge, there is very rare case in which a nonparathyroid tumor expressed simultaneously both the PTH and PTHrP. We report a case of squamous cell carcinoma of the lung with hypercalcemia which presented with simultaneous elevation of serum PTH and PTHrP. Severe hypercalcemia (serum calcium, 7.5mEq/L) was found in a 65-year-old man who had a squamous cell carcinoma of the lung without any body metastasis and detectable parathyroid abnormalities on isotope scintigraphy. The serum level of intact parathyroid hormone (PTH) concentration was markedly elevated as measured in two site radioimmunoreactive PTH assays (intact PTH 150pg/mL ; normal 9~55). The serum level of a PTHrP was also increased as measured in C-terminal region specific radioimmunoassay (PTHrP 99.1 pmol/L ; normal 13.8~55.3). There are no evidences of coincidental primary hyperparathyroidism in parathyroid MIBI scan and other imaging studies including neck ultrasonography and computed tomography. These results suggest that simultaneous elevation of serum PTH and PTHrP in this patient can be caused by production of both PTHrP and PTH in other nonparathyroid lesions such as squamous cell carcinoma.

Human Parathyroid Hormone-Related Peptide Measurement in the Lung Cancer Patients / 결핵

BACKGROUND: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. METHOD: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. RESULT: Serum PTHrp(mean+/-S.E.) was 312+/-68.9pg/ml in 63 lung cancer patients and 158+/-38.2 pg/ml in 22 controls(p>0.05). PTHrp was 356+/-103.9pg/ml in 34 epidermoid carcinoma patients, 281 +/-148.7pg/ml in 15 adenocarcinoma patients and 316+/-140.8pg/ml in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was 570+/-472.3pg/ml in stage II(n=3; p<0.05 vs controls), 166+/-22.4pg/ml in stage IIIa(n=9), 282+/-113.3pg/ml in stage IIIb(n= 12) and 668+/- 367.9pg/ml in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases(1526+/-811.2 pg/ml; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. CONCLUSION: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases witn bone metastases or patients who might develop the malignancy associated hypercalcemia.