Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
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PMID:Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. 786 50

Humoral hypercalcemia secondary to the production of parathyroid hormone-related peptide has been reported to occur in up to 17% of patients with renal cell carcinoma but has been reported only rarely in patients with other genitourinary cancers and never in patients with testicular or extragonadal nonseminomatous cancers. A 54-year-old man is reported who had an extragonadal nonseminomatous germ cell tumour with hypercalcemia that masqueraded as a renal cell carcinoma with metastases. The hypercalcemia was suspected to be humorally mediated.
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PMID:Extragonadal nonseminomatous germ cell tumour with hypercalcemia, masquerading as renal cell carcinoma: a case report. 788 17

Parathyroid hormone-related protein is responsible for the hypercalcaemia caused by many tumours. Measurement of parathyroid hormone-related protein is becoming more accessible with the introduction of commercial assays. We report a case of hypercalcaemia of malignancy secondary to parathyroid hormone-related protein in a woman with renal carcinoma. The parathyroid hormone-related protein was assayed using a new immunoradiometric assay. We demonstrated an initial fall in parathyroid hormone-related protein and calcium levels after surgery and a rise in both before clinical relapse. However, the clinical relapse was itself associated with a fall in serum parathyroid hormone-related protein, nephrogenous cAMP and calcium, suggesting that the tumour had stopped producing parathyroid hormone-related protein or perhaps that post-translational processing had occurred as the tumour advanced. The tumour was investigated for parathyroid hormone-related protein mRNA content using reverse transcriptase polymerase chain reaction, both at diagnosis in surgically removed material, and using post-mortem specimens. The level of parathyroid hormone-related protein mRNA, while present, was much reduced in the recurrent tumour suggesting that active parathyroid hormone-related protein production fell substantially as the tumour advanced. This case suggests that, although demonstration of parathyroid hormone-related protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this product may alter.
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PMID:Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity. 828 89

Parathyroid hormone related protein (PTHRP) has been implicated in humoral hypercalcaemia of malignancy (HHM). We describe a patient with a renal carcinoma and hypercalcaemia, and for the first time have demonstrated a 4-fold PTHRP concentration gradient across a renal tumour bed. This provides further strong evidence that the primary tumour was the source of the PTHRP. The PTHRP 1-86 content of the tumour tissue was 4.8 ng/g, similar to that previously found in tumours associated with HHM. In PTHRP-secreting tumours, PTHRP may be a useful oncological marker after surgical resection.
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PMID:Humoral hypercalcaemia in renal carcinoma due to parathyroid hormone related protein. 830 45

Metastatic lesions from renal cell carcinoma are commonly recognized in the lung and bone, however, thyroid metastasis has rarely been reported in the literature. We present herein a case of a man with lung and thyroid metastatic tumors from renal cell carcinoma. Although making a preoperative diagnosis of thyroid metastasis is difficult because there is no established diagnostic criteria, we were able to identify this thyroid lesion as a metastatic tumor from renal cell carcinoma by the pathological findings. Interestingly, hypercalcemia was recognized in this patient whose serum parathyroid hormone (PTH) level was not increased. Moreover, this patient also had early gastric cancer simultaneously, being a so-called 'double cancer'. After surgical resection of the right kidney and stomach, interferon was administered without any efficacy against the metastatic lesions of the lung and thyroid gland.
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PMID:A case of renal cell carcinoma with metastasis to the thyroid gland and concomitant early gastric cancer. 846 61

Renal cell carcinoma accompanied with ossification reported in Japan is very rare. We report a case of renal cell carcinoma with ossification pathologically in a 61-year-old woman. She suddenly presented with hypercalcemia that caused acute renal failure, 6 months after the operation and died shortly thereafter. We discuss the relationship between the tumor and the hypercalcemia.
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PMID:[Renal cell carcinoma accompanied with ossification: a case report]. 871 87

Paraneoplastic manifestations are present in up to 20% of patients with renal cell carcinoma (RCC). There is convincing evidence that RCC tumor cells elaborate proteins that serve as mediators of endocrine (eg, ectopic production of parathyroid hormone-related protein or erythropoietin) as well as nonendocrine paraneoplastic syndromes. A paraneoplastic syndrome may be the initial clinical presentation of RCC in a significant number of patients, and recognition of these syndromes may facilitate early diagnosis. Most paraneoplastic syndromes associated with RCC remit after resection of the primary RCC or treatment of metastatic sites. The natural history of metastatic RCC is extremely variable. A significant proportion of patients may survive several years with slowly progressing metastatic disease. In these patients, the accurate diagnosis and management of paraneoplastic syndromes may be important in palliative management. Except for hypercalcemia, conventional medical therapies are seldom helpful. Other paraneoplastic manifestations of RCC include cachexia, fever, hepatic dysfunction, anemia, and amyloidosis, although our understanding of the underlying pathophysiology remains incomplete.
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PMID:Paraneoplastic manifestations of renal cell carcinoma. 894 20

Pamidronate is a second generation bisphosphonate used for treating tumor-induced hypercalcemia and for preventing the development of new bone metastasis. A 47-year-old man with renal cell carcinoma was admitted in our institution because of hypercalcemia with multiple metastasis in bone, lung and lymph nodes. After embolization of the right renal artery, the patient was treated with pamidronate and interferon-alpha. Intravenous pamidronate significantly reduced bone pain and normalized the serum calcium level. The pulmonary metastasis responded to interferon therapy after 2 months of therapy. Radical nephrectomy was then carried out. Paraaortic lymph nodes were found to be necrosed completely. Ossification of osteolytic lesions was observed after two months of therapy and metastatic lesions in the lung showed complete remission (CR) after six months of therapy.
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PMID:[Effect of pamidronate and interferon-alpha on bone and lung metastases and hypercalcemia in a patient with renal cell carcinoma]. 897 39

Hypercalcemia is a well known complication of renal cell carcinoma (RCC). As RCCs can produce IL-6, and IL-6 may stimulate bone resorption and cause mild hypercalcemia, we examined whether IL-6 is involved in renal cancer-associated hypercalcemia in vivo. Three human renal cell carcinoma tumor lines (RC-8, RC-9, and NC-65) growing in nude mice were studied. Tumors were implanted s.c., and parameters of bone metabolism and serum human IL-6 levels were determined in relation to tumor volume (TV). All three tumor lines secreted human IL-6, although in different quantities. The maximum level of IL-6 in RC-8 was 434 pg/ml (TV, 200 mm3), that in RC-9 was 81 pg/ml (TV, 1800 mm3), and that in NC-65 was 2368 pg/ml (TV, 1800 mm3). Hypercalcemia developed in RC-8 and RC-9 tumor-bearing animals, but not in NC-65-bearing animals. The hypercalcemia in both RC-8 and RC-9 tumor lines was associated with elevated levels of PTH-related peptide (PTHrP) and loss of trabecular bone volume. Serum calcium and phosphate concentrations showed an almost linear relationship with plasma PTHrP independently of the tumor line and serum IL-6 levels. No hypercalcemia occurred in the NC-65 animals, which had the highest levels of IL-6, but no detectable plasma PTHrP and PTHrP messenger RNA expression in the tumor. Administration of neutralizing antibodies to IL-6 to RC-8 animals normalized serum calcium concentrations and PTHrP values and induced a significant inhibition of tumor growth. No such effect on tumor growth of anti-IL-6 was seen in the other two tumor lines. The normalization of serum calcium in RC-8 mice is most likely attributed to the growth-inhibiting effect of anti-IL-6 on RC-8 tumor. We conclude that IL-6 secreted by RCC does not contribute directly to hypercalcemia, but may enhance hypercalcemia by stimulating the tumor growth of a subpopulation of PTHrP-secreting carcinomas.
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PMID:The role of interleukin-6 in the induction of hypercalcemia in renal cell carcinoma transplanted into nude mice. 911 82


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