In Vivo Models of Hypercalcemia of Malignancy

Schilling, Tobias

doi:10.1007/978-3-642-85073-8_3

“…PTHrP was originally thought to only play a role in HHM; however, in normocalcemic patients, PTHrP was also found in local bone neoplasms and metastasis that caused local osteolysis in normocalcemic patients [ 82 ]. This confirmed the important paracrine role of PTHrP, since it induces local osteoclastic bone resorption when primary cancers or metastases are present in bone ( Figure 2 ) [ 83 , 84 ]. This is particularly common in women with breast cancer, since 80% of breast cancer bone metastases express increased PTHrP in the bone microenvironment.…”

Section: Introductionsupporting

confidence: 59%

“…Spontaneous and experimental animal models have been invaluable to investigating these mechanisms. Examples of animal models include: (1) spontaneous cancers in domestic animals; (2) allogenic transplantation of rodent cancers; (3) xenogeneic transplantation of human and animal cancers to immunodeficient rodents; (4) drug-induced cancer in rodents; and (5) in vivo infusion of cancer-related humoral/paracrine factors responsible for CAH [ 84 ]. No single model can recapitulate all aspects of HHM or LOH; however, the information from the animal models has advanced the treatment of CAH and improved the understanding of the pathogenic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…Urinary excretion of calcium, cAMP and hydroxyproline and the rate of bone resorption and bone formation were increased. Histomorphometric analysis of the lumbar vertebrae revealed increased osteoid, resorptive surface and number of osteoclasts [ 25 , 27 , 84 ]. Intestinal calcium absorption or decreased urinary calcium excretion could not completely explain the HHM in these mice.…”

Section: Introductionmentioning

confidence: 99%

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Animal Models of Cancer-Associated Hypercalcemia

Kohart

¹

,

Elshafae

²

,

Breitbach

³

et al. 2017

Veterinary Sciences

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Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.

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“…Spontaneous and experimental animal models have been invaluable to investigating these mechanisms. Examples of animal models include: (1) spontaneous cancers in domestic animals; (2) allogenic transplantation of rodent cancers; 3xenogeneic transplantation of human and animal cancers to immunodeficient rodents; (4) drug-induced cancer in rodents; and (5) in vivo infusion of cancer-related humoral/paracrine factors responsible for CAH [84]. No single model can recapitulate all aspects of HHM or LOH; however, the information from the animal models has advanced the treatment of CAH and improved the understanding of the pathogenic mechanisms.…”

Section: Animal Models Of Hhm and Lohmentioning

confidence: 99%

“…(1) allogenic transplantation of tumors; (2) xenogenic transplantation of tumors; (3) drug-induced tumor development; and (4) infusion of potential factor/factors responsible for CAH [84]. The use of each method varies between rodent species and the research hypothesis.…”

Section: Spontaneous and Experimentally-induced Cah In Rodent Modelsmentioning

confidence: 99%

Animal Models of Cancer-Associated Hypercalcemia

Rosol¹

2020

Encyclopedia of Bone Biology

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Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.

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