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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbits receiving intramuscular injections of VX-2 carcinoma cells in biceps femoris muscles developed rapidly progressive neoplastic growths at 14 to 21 days associated with a significant hypercalcemia. The biologic behavior of the VX-2 carcinoma was characterized by local infiltration and metastases to regional lymph nodes and lungs. No metastases to skeletal tissues were evident. Femora from intramuscularly injected rabbits had varying degrees of osteophytosis and lysis evident roentgenographically. Histopathologic evaluation of femoral sections revealed periosteal new bone growth, cortical osteolysis, endosteal new bone growth, and in a few long term rabbits, pathologic fractures. Bone lesions were evident histologically in the vicinity of neoplastic growth (i.e., femora, tibiae) but not at distant sites (i.e., humeri and vertebrae). Mineral analyses of VX-2 carcinoma tissues and kidneys from VX-2-bearing rabbits revealed concentrations of calcium 83 and 3 times greater, respectively, than those of skeletal muscle and kidneys from controls. These findings correlated well with histochemical evidence of excessive amounts of calcium in sections of kidneys and VX-2 carcinoma tissues. Rabbits receiving intraperitoneal injections of VX-2 carcinoma cells did not develop hypercalcemia despite an extensive, progressive neoplastic burden with metastases to abdominal and thoracic viscera. Roentgenographic, histopathologic, and physiochemical analyses of selected bones from these rabbits revealed no significant alterations. These findings indicate that VX-2 carcinoma cells need to be in close proximity to skeletal tissues in order to induce hypercalcemia. The development of a significant hypercalcemia in intramuscularly injected rabbits precedes the invasion of osseous tissues by VX-2 carcinoma cells. Therefore, it appears that VX-2 carcinoma cells have the ability to alter skeletal morphology and physiochemistry through a dual humoral/cellular mechanism. The clinicopathologic characteristics of the VX-2 carcinoma in the rabbit suggest that the neoplasm is a good experimental model to study osseous-mediated hypercalcemia of malignancy.
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PMID:Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study. 94 Mar 20

Cancer-associated hypercalcemia is due to the: (a) elaboration of systemically-acting humoral factors by neoplasms which alter calcium metabolism in bone, kidney, and intestine; or (b) stimulation of bone resorption at sites of tumor metastasis to bone. It is likely that both mechanisms occur in the same patient with certain neoplasms. There are many humoral factors that can be produced by tumors, secreted into the circulation, and have distant effects which induce hypercalcemia. The stimulation of increased osteoclastic bone resorption is a principal feature of humoral hypercalcemia of malignancy, but the kidney also plays an important role. In addition, intestinal absorption of calcium may be a factor in the pathogenesis of hypercalcemia in certain neoplasms. Parathyroid hormone-related protein plays a dominant role in the pathogenesis of HHM. PTHrP alone is able to induce nearly all of the clinical signs of HHM in experimental animals, but other humoral factors, such as cytokines, can interact with PTHrP to contribute to the development of hypercalcemia. Neoplasms which metastasize widely to bone and induce local osteoclastic bone resorption, such as multiple myeloma, also are capable of inducing hypercalcemia. Based upon existing data it is not clear what percentage of neoplasms which metastasize to bone and stimulate local bone resorption also are capable of stimulating hypercalcemia by systemic factors. Future research is needed to delineate the systemic and local factors associated with CAH; to define interactions of humoral factors in the pathogenesis of hypercalcemia; and to investigate the regulation of transcription, translation, modification, and secretion of hypercalcemia-inducing factors in normal and neoplastic tissues.
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PMID:Mechanisms of cancer-induced hypercalcemia. 146 Aug 60

The case of hypercalcemia secondary to metastasis to a benign parathyroid adenoma is reported. The patient had documented lung adenocarcinoma with multiple bone metastases and a mass in the lower anterior neck for at least 5 months before hypercalcemia and hypophosphatemia resistant to treatment developed. Autopsy revealed widespread metastatic disease including metastatic tumor invading a benign parathyroid adenoma. The analysis of four cases of metastatic cancer spread to a benign parathyroid adenoma reported previously revealed that two of them also had hypercalcemia during a late stage of the disease. There are data that the incidence of metastases to parathyroid gland might be as high as 11.9%, and the incidence of parathyroid adenomas in patients with cancer is significantly higher than in controls. The metastases to benign parathyroid adenomas might be another mechanism of hypercalcemia of malignancy.
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PMID:A case of adenocarcinoma of the lung associated with a neck mass and hypercalcemia. 191 81

Hypercalcemia is one of the most serious metabolic disorders associated with cancer. The incidence and clinical circumstances associated with hypercalcemia vary in different types of cancer. Hypercalcemia is the most frequent metabolic complication of breast cancer and is usually related to widespread osteolytic metastases; however, local and systemic humoral factors mediating bone resorption have been described. In some patients with breast cancer, hypercalcemia results from treatment with estrogens, antiestrogens, androgens, or progestins. Coexisting primary hyperparathyroidism rarely confounds the diagnosis. In patients with lung cancer, the incidence of hypercalcemia varies with histology and is often unrelated to bone metastases. Hypercalcemia may occur either late or early in the disease but is seldom a presenting symptom. In patients with cancers of the head and neck region, hypercalcemia is most often associated with advanced recurrent and terminal disease, presumably humorally mediated. In renal cell carcinoma, hypercalcemia is also an adverse prognostic indicator, commonly mediated by humoral factors. On the other hand, almost all patients with multiple myeloma have extensive osteolytic bone destruction and hypercalcemia is frequently a presenting symptom. Hypercalcemia is uncommon in most lymphomas; however, it is usually a prominent feature of adult T-cell lymphomas and also occurs in some large cell, diffuse B-cell lymphomas. Awareness of the setting in which hypercalcemia of malignancy occurs will lead to its prompt diagnosis and institution of appropriate therapy.
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PMID:Overview of cancer-related hypercalcemia: epidemiology and etiology. 218 51

We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino-terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concentrations were found in 2 of 39 control subjects. In 2 patients with breast cancer plasma PLP declined concomitantly with a reduction in tumor burden. Adenocarcinoma of the breast and squamous cell carcinomas were most frequently associated with high plasma PLP levels although a variety of histologic types were represented. The presence of metastases on bone scans did not correlate with either the severity of hypercalcemia or the extent of PLP elevation. Increased concentrations of plasma PLP were also observed in 4 of 20 patients with primary hyperparathyroidism and in 5 of 16 patients with chronic renal failure and secondary hyperparathyroidism. Gel filtration analysis of immunoreactive PLP in plasma from 2 hypercalcemic breast cancer patients revealed heterogeneity, with, in each case, both large (greater than 15 kD) and small (6-7 kD) molecular weight amino-terminal moieties. The results document the presence of PLP in the circulation of patients with cancer and are consistent with a pathogenetic role for PLP in the hypercalcemia of malignancy irrespective of whether skeletal metastases have occurred. PLP may also contribute to the skeletal and/or renal manifestations of hyperparathyroid states.
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PMID:Circulating concentrations of parathyroid hormone-like peptide in malignancy and in hyperparathyroidism. 231 98

An 18-year-old Appaloosa mare was examined because of squamous cell carcinoma of the vulva, anorexia with pronounced weight loss, and hypercalcemia. The tumor had developed rapidly over a period of 3 months and externally extended ventrally involving the perineum and the dorsal aspect of the udder. Necropsy examination demonstrated a large primary squamous cell carcinoma of the vulva, perineum, and mammary gland with metastases to the supramammary, sublumbar, deep inguinal, and mediastinal lymph nodes. No gross renal lesions were observed and, histologically, there was only mild vacuolation of renal tubular epithelium. Based on the normal concentration of serum parathyroid hormone, the absence of evidence of hypervitaminosis D, and normal renal function, a diagnosis was made of hypercalcemia of malignancy or pseudohyperparathyroidism. The mechanism responsible for hypercalcemia was not determined, but the histologic type of the neoplasm and the clinical course suggested possible production of a humoral hypercalcemic factor by the neoplasm, similar to that demonstrated in certain types of human squamous cell carcinoma.
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PMID:Pseudohyperparathyroidism in a mare associated with squamous cell carcinoma of the vulva. 231 41

A class of drugs called diphosphonates have been used for several years in benign disorders of ossification such as Paget disease. Recently, these compounds have been applied to treating hypercalcemia of malignancy and painful bone metastases. We have used one of the oral diphosphonates, etidronate disodium, to palliate pain in 12 patients suffering from multiple bone metastases from prostate cancer. All of the patients had progressive metastatic disease following earlier endocrine therapy. Ten of 12 (83%) patients had a positive subjective and clinical response to treatment with oral etidronate disodium. Daily narcotic usage and pain intensity (measured by a zero to 10 pain scale) both decreased significantly on the etidronate protocol. There were no side effects associated with the drug in our patients.
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PMID:Treatment of painful prostatic bone metastases with oral etidronate disodium. 246 Sep 88

Hypercalcaemia in malignancy is a major clinical problem. It contributes significantly to morbidity and mortality and can present difficult diagnostic and management dilemmas. Direct bony invasion by tumour cells rather than humorally mediated hypercalcaemia is probably the most common cause of malignant hypercalcaemia. Yet even in this situation the mechanism of bone resorption or the reason that the normal homeostatic mechanisms cannot cope with the calcium load are poorly understood. It is likely that the humoral and paracrine factors produced by tumours which result in hypercalcaemia or in osteosclerotic bone metastases, are interposing themselves into the normal regulatory processes and deranging them. Humoral hypercalcaemia of malignancy is an important model for studying these questions, and it also provides some insight into the normal regulation of bone turnover. This review will examine the animal models and human syndromes of malignant hypercalcaemia and show how animal models, although helpful, fail to delineate the relative importance of the various potential humoral factors. A most interesting recent development in this area is the description of a new hormone, the parathyroid hormone-related peptide, which may explain many of the cases of humoral hypercalcaemia of malignancy. It is also a useful model with multiple sites of action within the bone and calcium homeostatic process. The active hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3, may also be involved in a small proportion of cases, but again it is a useful model of some of the factors that may operate. Of considerable interest are the tumour derived factors, such as the transforming growth factors, and the cytokines, such as tumour necrosis factors, interleukins, and haemopoietic colony stimulating factors. Prostanoids are seldom of major importance, but may be important in certain tumour types. Osteosclerotic metastases, although seldom associated with hypercalcaemia, may provide insight into osteoblast regulating factors. Treatment of hypercalcaemia is discussed to show ways in which response to treatment may shed light on underlying pathophysiological mechanisms. Most effective treatments have many potential modes of action, and further study of the interactions of these agents and tumour types may help to unravel some of the enigmas in this human syndrome. The major advances in this complex problem involve the realisation of the necessity of multiple sites of action, including renal calcium handling as well as relative increases in bone resorption and/or intestinal calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Metastasis Rev 1989 Jun
PMID:Hypercalcaemia of malignancy. 266 84

Bone was collected for trabecular bone morphometry from 6 dogs with hypercalcemia of malignancy. Five of the dogs had lymphosarcoma and 1 had an anal sac apocrine gland carcinoma with vertebral metastases. Parathyroid gland weights varied around normal, with those for 1 dog being slightly low and those for another dog being moderately increased. As a group, the dogs had decreased bone volume, with increased resorption surfaces and increased numbers of osteoclasts. In 4 dogs, osteoid seams and osteoblasts were limited in extent and this distinguished them from dogs with hyperparathyroidism. Although most dogs had received corticosteroids, chemotherapy, or radiation treatment, the bone changes in these dogs were similar to 1 dog that had not received treatment. Also, the changes could not be related to uremia or renal mineralization that had developed in 2 of the dogs. Two of the dogs had somewhat greater amounts of osteoid-covered surface and slightly widened osteoid seams, ie, findings more like those of hyperparathyroidism. One of these dogs had anal sac apocrine gland carcinoma and the other had lymphosarcoma in which there was invasion of the bone cortex at the sampling site. It was concluded that bone remodeling changes do occur in hypercalcemia of malignancy and that these changes are varied and often are not those of hyperparathyroidism.
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PMID:Bone changes in hypercalcemia of malignancy in dogs. 668 16

The utility of bisphosphonates is well established in the treatment of acute hypercalcemia of malignancy. Bisphosphonates may also decrease the complications and morbidity of skeletal metastases. This article emphasizes the use of bisphosphonates in breast cancer patients with skeletal metastases.
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PMID:Bisphosphonates in breast cancer patients with skeletal metastases. 815 Jul 77


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