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)

We report here an autopsy case of primary squamous cell carcinoma of the liver in a 63-year-old man who had hypercalcemia and an elevated serum level of parathyroid hormone-related protein. At autopsy, primary squamous cell carcinoma of the liver was found, without distinct preceding or associated hepatic or biliary diseases; no extrahepatic primary focus of squamous cell carcinoma was found. Bone involvement was not demonstrated, either radiologically or pathologically. Immunohistochemically, parathyroid hormone-related protein was detectable in the squamous cell carcinoma cells and it may have been responsible for the hypercalcemia. Such a case has not been reported so far in the English-language or the Japanese literature.
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PMID:Primary squamous cell carcinoma of the liver producing parathyroid hormone-related protein. 1187 66

A 77-year-old man was admitted to our hospital showing symptoms of general fatigue and appetite loss. He had leukocytosis, thrombocytosis and hypercalcemia with elevated serum levels of parathyroid hormone related peptide (PTHrP) and interleukin-6 (IL-6). An increase in tumor markers SCC and CYFURA21-1 was observed. The liver contained a huge tumor, which was proved to be PTHrP producing squamous cell carcinoma by immuno-histochemical analysis. Since the tumor did not express IL-6, it was assumed to be induced by PTHrP in osteoblasts. This is the first report of PTHrP producing squamous cell carcinoma of the liver.
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PMID:PTHrP-producing tumor: squamous cell carcinoma of the liver accompanied by humoral hypercalcemia of malignancy, increased IL-6 and leukocytosis. 1205 86

Epidemiologic data suggest that low exposure to vitamin D or 1alpha,25-dihydroxycholecalciferol (calcitriol) increases the risk of prostate cancer. Calcitriol, a central factor in bone and mineral metabolism, is also a potent antiproliferative agent in a wide variety of malignant cell types. We have demonstrated that calcitriol has significant antitumor activity in vitro and in vivo in prostate and squamous cell carcinoma model systems. Calcitriol, in these models, induces a significant G0/G1 arrest and modulates p21(Waf1/Cip1) and p27(Kip1), the cyclin-dependent kinase inhibitors. Calcitriol induces poly (adenosine diphosphate-ribose) polymerase cleavage, increases bax/bcl-2 ratio, reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs; also known as extracellular signal-related kinase [ERK] 1/2) and phosphorylated Akt, induces caspase-dependent mitogen-activated protein kinase kinase (MEK) cleavage and upregulation of MEK kinase-1, all potential markers of the apoptotic pathway. We also have demonstrated that dexamethasone (dex) potentiates the antitumor effect of calcitriol through effects on the vitamin D receptor and decreases calcitriol-induced hypercalcemia. We initiated phase 1 and phase 2 trials of calcitriol, either alone or in combination with carboplatin, paclitaxel, or dex. Data from these studies indicate that high-dose calcitriol is feasible on an intermittent schedule, the maximum tolerated dose (MTD) is unclear, and dex or paclitaxel appear to ameliorate hypercalcemia. Studies continue to define the MTD of calcitriol on this intermittent schedule, either alone or with other agents, and to evaluate the mechanisms of calcitriol effects in prostate cancer models.
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PMID:Vitamin D receptor: a potential target for intervention. 1223 Oct 68

Hypercalcemia of malignancy is a common problem for cancer clinicians. Treatment of hypercalcemia of malignancy with pamidronate in a patient with advanced recurrent oral cancer is reported herein. The patient was a 36-year-old man who had neck lymph node metastases due to recurrence of squamous cell carcinoma of the buccal mucosa and complained of cloudiness of consciousness due to hypercalcemia. The patient was administered pamidronate. A fine reduction in serum calcium was observed and cloudiness of consciousness was also alleviated. Although treatment of hypercalcemia with pamidronate is palliative, it is effective against the deterioration of quality of life.
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PMID:[Treatment of hypercalcemia of malignancy with pamidronate in a patient with advanced recurrent oral cancer]. 1250 78

Hypercalcemia associated with malignancy has been attributed to osteolytic processes secondary to bony metastases and to humoral factors causing increased bone resorption and decreased renal excretion of calcium. Parathyroid hormone-related protein (PTH-rP) is a humoral factor that has been associated with hypercalcemia in renal cell carcinoma, squamous cell carcinoma, and bladder carcinoma. Hypercalcemia does occur in patients with melanoma; however, few studies have reported on hypercalcemia in these patients, and even fewer have described a direct connection to PTH-rP. We here report a patient with stage IV malignant melanoma presenting with severe hypercalcemia associated with elevated PTH-rP levels. Immunohistochemistry showed strong expression of PTH-rP in biopsy of the patient's subcutaneous masses. In addition, we found a 4.9% incidence of hypercalcemia in 1,146 consecutive patients treated for metastatic melanoma at the Surgery Branch of the National Cancer Institute between January 1, 1988 and March 31, 2000. Thus, PTH-rP may play a significant role in severe hypercalcemia in patients with metastatic melanoma. The discovery of PTH-rP and relevant literature will also be reviewed.
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PMID:Parathyroid hormone-related protein and hypercalcemia in patients with metastatic melanoma: case report and review. 1257 23

Hypercalcemia is one of the metabolic complications associated with cancer. To assess the frequency of hypercalcemia in patients with squamous cell carcinoma (SCC), 242 patients who were evaluated as having SCC in the oral cavity between July 1995 and June 2001 were investigated. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl. By this definition, hypercalcemia was detected in 12 of the 242 patients (5.0%). All 12 patients were at an advanced stage of oral SCC. In these 12 patients, the serum level of parathyroid hormone-related protein (PTH-rP) was also significantly elevated. Therefore, we diagnosed these diseases as humoral hypercalcemia of malignancy (HHM). Moreover, we studied the efficacy of anti-hypercalcemic therapy on the quality of life (QOL). The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 was used for estimation of QOL. The patients with HHM who were administrated drugs such as bisphosphonate and calcitonin showed a reduction in their Ca and PTH-rP levels, and the six of ten EORTC QLQ-C30 subscales (emotional functioning, cognitive functioning, fatigue, dyspnoea, nausea/vomiting and appetite loss) were also improved after the anti-hypercalcemic therapy. However, these suppressive effects were temporary. The median survival time after the diagnosis of HHM was only 54.9+/-18.3 days (range 27-86 days). Therefore, HHM in SCC appears to be an ominous prognostic sign. Although anti-hypercalcemic therapy has a palliative role, the patients may be in less discomfort during the terminal stage of their illness.
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PMID:Hypercalcemic complication in patients with oral squamous cell carcinoma. 1272 78

We report the case of a 63-year-old man who presented with weakness, fatigue, dehydration, confusion, abdominal pain, congestive heart failure and hypercalcemia. He expired and autopsy revealed an exulcerating carcinoma of the esophagus, invading the esophageal wall and metastasizing to the lungs, skin and lymph nodes. Histology demonstrated an epithelial tumor consisting of two components with transition between the two. One component was a keratinizing squamous cell carcinoma, whereas the other component consisted of pleomorphic small cells. The hypercalcemia was assumed to be due to parathyroid hormone related protein (PHRP), which was demonstrated by immunohistochemistry only in the pleomorphic small cells and not in the squamous cells. PHRP induced humoral hypercalcemia of malignancy is most often associated with squamous cell carcinomas. The finding that in our case, the pleomorphic small cell component was PHRP immunopositive and the squamous cell component showed no immunoreactivity, is intriguing and remains unexplained.
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PMID:Humoral hypercalcemia of malignancy due to bipartite squamous cell/small cell carcinoma of the esophagus immunoreactive for parathyroid hormone related protein. 1464

Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.
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PMID:Hypercalcemia induced by parathyroid hormone-related peptide after treatment of squamous cell carcinoma of oral cavity. 1471

An autopsy case of adenosquamous pancreatic cancer in a 61-year-old male patient with an elevated serum level of parathyroid hormone-related protein (PTH-rP) is reported. He was admitted to our hospital with a 1-month-long history of abdominal discomfort and progressive abdominal fullness. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass, approximately 10 cm in diameter, involving the pancreas, with round enhancement on contrast examination. Histological examination of a specimen taken by CT-guided needle biopsy suggested squamous cell carcinoma or transitional cell carcinoma. Laboratory data on admission revealed a high serum calcium level and high PTH-rP level. The calcium level initially responded to intravenous hydration, furosemide, calcitonin, and bisphosphonates, decreasing from 15.0 to 9.0 mg/dl. However, the hypercalcemia recurred after 10 days. The patient developed carcinomatous peritonitis and acute renal failure, and died on the 25th hospital day. Autopsy revealed a mass in the pancreatic body to tail, invading the retroperitoneum, with progressive carcinomatous peritonitis. Histological examination of the mass revealed infiltrating carcinoma, showing squamous differentiation with focal intracytoplasmic lumina formation, consistent with pancreatic adenosquamous carcinoma. Immunohistological examination showed positive staining for PTH-rP. Adenosquamous carcinoma of the pancreas is relatively rare; only a few cases associated with hypercalcemia and for which PTH-rP has been identified as a causative factor have been reported. This is the first case in which immunohistochemistry proved localized PTH-rP in adenosquamous pancreatic cancer cells, associated with persistent hypercalcemia.
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PMID:Adenosquamous pancreatic cancer producing parathyroid hormone-related protein. 1506 26

Parathyroid-hormone-related-peptide (PTHrP) has been shown to be important in the pathogenesis of hypercalcemia of malignancy. The malignancies most commonly associated with hypersecretion of PTHrP include squamous cell carcinoma and breast cancer. The pathogenesis of hypercalcemia associated with hepatocellular carcinoma was evaluated in this study. Two male patients with hepatocellular carcinoma were found to have severe hypercalcemia at initial presentation. PTHrP was measured with radioimmunoassay in these two patients before treatment as well as in nine other patients with hepatocellular carcinoma but without hypercalcemia. The levels were markedly elevated in the two patients with hypercalcemia (29.3 and 32.1 pM), but were less than 5 pM in the nine patients without hypercalcemia. These results suggest that PTHrP was important in the pathogenesis of hypercalcemia associated with hepatocellular carcinoma in these men.
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PMID:Humoral hypercalcemia of hepatocellular carcinoma associated with elevated levels of parathyroid-hormone-related-peptide. 1525 88


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