Parathyroid hormone-related peptide and hypercalcemia of malignancy

Goltzman, David; Henderson, Janet E.

doi:10.1007/978-1-4615-6355-6_10

Cited by 6 publications

(3 citation statements)

References 79 publications

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“…malignancy (HHM) (39,17). Features of HHM can be observed with tumors of the respiratory, gastrointestinal, and urogenital tracts as well as with hematological malignancies and breast cancer (12,32,34).…”

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confidence: 99%

Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Chattopadhyay

Evliyaoglu

Heese

et al. 2000

American Journal of Physiology-Cell Physiology

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Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral hypercalcemia of malignancy and of malignant osteolysis associated with skeletal metastases of common epithelial cancers. PTHrP secretion is regulated by the extracellular calcium concentration ([Ca(2+)](o)) in several types of normal and malignant cells. Because the [Ca(2+)](o)-sensing receptor (CaR) is a key mediator of [Ca(2+)](o)-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by parathyroid chief cells], we investigated the expression of the CaR and PTHrP in normal and neoplastic glial cells and studied the effects of [Ca(2+)](o) on PTHrP secretion. Our results show that primary embryonic human astrocytes (HPA) express CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively. Furthermore, astrocytomas and meningiomas also express the CaR at similar levels as assessed by RT-PCR and Northern and Western blot analyses. HPA and astrocytomas express transcripts encoding all three known isoforms of PTHrP [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas express only the first two of these. Finally, elevated levels of [Ca(2+)](o) and other polycationic CaR agonists dose dependently stimulate PTHrP secretion from HPA, astrocytomas, and meningiomas, although both basal and high [Ca(2+)](o)-stimulated rates of PTHrP secretion are approximately 2. 5-fold higher in HPA than in the glial tumors studied here. Therefore, our results show that HPA, astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR agonists stimulate PTHrP secretion.

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confidence: 99%

Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Chattopadhyay

Evliyaoglu

Heese

et al. 2000

American Journal of Physiology-Cell Physiology

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“…Four mechanisms underlying neoplastic hypercalcemia have been recognized: Production of a PTH-like protein (PTHrp: parathyroid hormone-related protein); Ectopic production of PTH; Osteolytic metastases; Release of 1,25-dihydroxycholecalciferol (especially in lymphomas) [ 72 , 73 , 74 ]. …”

Section: Discussionmentioning

confidence: 99%

Acute Oncologic Complications: Clinical–Therapeutic Management in Critical Care and Emergency Departments

Gri

Longhitano

Zanza³

et al. 2023

Current Oncology

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Introduction. It is now known that cancer is a major public health problem; on the other hand, it is less known, or rather, often underestimated, that a significant percentage of cancer patients will experience a cancer-related emergency. These conditions, depending on the severity, may require treatment in intensive care or in the emergency departments. In addition, it is not uncommon for a tumor pathology to manifest itself directly, in the first instance, with a related emergency. The emergency unit proves to be a fundamental and central unit in the management of cancer patients. Many cancer cases are diagnosed in the first instance as a result of symptoms that lead the patient’s admittance into the emergency room. Materials and Methods. This narrative review aims to analyze the impact of acute oncological cases in the emergency setting and the role of the emergency physician in their management. A search was conducted over the period January 1981–April 2023 using the main scientific platforms, including PubMed, Scopus, Medline, Embase and Google scholar, and 156 papers were analyzed. Results. To probe into the main oncological emergencies and their management in increasingly overcrowded emergency departments, we analyzed the following acute pathologies: neurological emergencies, metabolic and endocrinological emergencies, vascular emergencies, malignant effusions, neutropenic fever and anemia. Discussion/Conclusions. Our analysis found that a redefinition of the emergency department connected with the treatment of oncology patients is necessary, considering not only the treatment of the oncological disease in the strict sense, but also the comorbidities, the oncological emergencies and the palliative care setting. The need to redesign an emergency department that is able to manage acute oncological cases and end of life appears clear, especially when this turns out to be related to severe effects that cannot be managed at home with integrated home care. In conclusion, a redefinition of the paradigm appears mandatory, such as the integration between the various specialists belonging to oncological medicine and the emergency department. Therefore, our work aims to provide what can be a handbook to detect, diagnose and treat oncological emergencies, hoping for patient management in a multidisciplinary perspective, which could also lead to the regular presence of an oncologist in the emergency room.

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“…Humoral hypercalcemia of malignancy (HHM), one of the most common paraneoplastic syndromes, is associated with an elevated serum Ca level, a low serum 1,25(OH) 2 D concentration and overproduction of PTH-related protein (PTHrP) by tumors (Pierce 1993, Goltzman & Henderson 1997. In contrast, the circulating 1,25(OH) 2 D and Ca concentrations are elevated in a significant number of patients with primary hyperparathyroidism.…”

Section: Introductionmentioning

confidence: 99%

Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy

Michigami¹,

Yamato²,

Suzuki³

et al. 2001

Journal of Endocrinology

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In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH) 2 D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH) 2 D was markedly reduced when the animals exhibited severe hypercalcemia (Ca d15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH) 2 D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH) 2 D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH) 2 D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH) 2 D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 -hydroxylase (1 -hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 -hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 -hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH) 2 D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 -hydroxylase gene.

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Parathyroid hormone-related peptide and hypercalcemia of malignancy

Cited by 6 publications

References 79 publications

Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Acute Oncologic Complications: Clinical–Therapeutic Management in Critical Care and Emergency Departments

Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy

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Parathyroid hormone-related peptide and hypercalcemia of malignancy

Cited by 6 publications

References 79 publications

Regulation of secretion of PTHrP by Ca2+-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Regulation of secretion of PTHrP by Ca2+-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Acute Oncologic Complications: Clinical–Therapeutic Management in Critical Care and Emergency Departments

Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy

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Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas

Regulation of secretion of PTHrP by Ca²⁺-sensing receptor in human astrocytes, astrocytomas, and meningiomas