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)

Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC > 10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum, < 16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum, < 20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.
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PMID:[Simultaneous production of parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF) in lung cancer patients with hypercalcemia and leukocytosis]. 753 68

Parathyroid hormone-related protein (PTHRP) is expressed in a large number of tumors and is the mediator of parathyroid hormone-like effects seen in humoral hypercalcemia of malignancy. The gene coding for PTHRP has been localised to the short arm of chromosome 12. This is at the same region as the oncogene KRAS2, and amplification of KRAS2 has previously been found in human lung cancer. The BEN cell line which is known to express PTHRP was established from a patient who had squamous cell carcinoma of the lung with hypercalcemia. Cytogenetic analysis of the BEN cell line revealed a very complex karyotype with many marker chromosomes. Chromosomal in situ hybridization with biotinylated DNA probes visualized by a biotin-streptavidin-polyalkaline-phosphatase complex was used to analyse two dicentric marker chromosomes containing homogeneously staining regions (hsr) in BEN. The hsr were found to contain amplified PTHRP and KRAS2 at levels of 30-fold and 14-fold per cell, respectively. The higher level of amplification of the PTHRP gene would suggest that PTHRP is the target gene of amplification in the amplicon. This is the first report of gene amplification of PTHRP and in addition its co-amplification with KRAS2.
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PMID:Co-amplification of the gene for parathyroid hormone-related protein (PTHRP) and KRAS2 in a human lung cancer cell line. 769 47

Diagnosis and treatment of lung cancer can significantly affect a patient's quality of life. Survival rates are dismal, but improvements have been made in dealing with common symptoms and side effects. This article reviews the nature of the problem, pertinent risk factors, and symptoms associated with nausea and vomiting, cachexia, hypercalcemia, and pain. Physicians, nurses, and other health care professionals can play a vital role in the identification and management of these complications, and thereby help to improve quality of life.
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PMID:Quality of life issues in lung cancer. New symptom management strategies. 809 33

A 57-year-old man with lung cancer was reported. Primary tumor was located at left S1+2, and directly invaded to chest wall (from 1st. rib to 4th rib). Hypercalcemia and delirium were observed. Whole body examination showed that no distant metastasis except for nodal swelling of left axillary region. Left upper lobectomy combined with chest wall resection was performed. Hilar, mediastinal and axillary nodes were also dissected. Histological examination revealed that nodal involvement was not present at neither hilar or mediastinal region, but was present in axillary node. It was thought that lymphatic extension had occurred from trough chest wall to axillary nodes but not through mediastinal rout. So systematic dissection of locally invaded region as well as hilar and mediastinal region was recommended in each cases.
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PMID:[A case of lung cancer with axillary nodal involvement]. 820 93

Although hypercalcemia is a serious and frequent complication of lung cancer, it is not commonly investigated in our country. We studied the prevalence of hypercalcemia in 90 random lung cancer patients from the Department of Pneumology, Escola Paulista de Medicina. The following histological types were found: 35 Squamous cells carcinomas (CEC), 30 Adenocarcinomas (AdenoCa), 11 Small cells carcinomas (CIPC), 2 Large cells carcinomas (TGC), 1 Carcinoid, 1 Mesothelioma, 2 Undifferentiated carcinomas, 1 Adenosquamous, 1 in situ carcinoma and 4 metastatic tumors. Ionized Ca (Ca-i) was measured in blood samples of all patients. Hyperparathyroidism was excluded by PTH and cAMP determinations in the hypercalcemic patients (Ca-i > 1.29 mmol/L). We found elevated levels of Ca-i (range = 1.30 to 2.0 mmol/L) in 18 patients (20%), being: 12 CEC (66.7%), 3 AdenoCa (16.7%), 2 CIPC (11.1%) and 1 TGC (5.6%). The PTH levels were low or suppressed in all 18 patients, but cAMP determinations were elevated in 6 out of 12 patients. Hypercalcemia is then a very frequent complication of lung cancer (20%), and PTH measurement was able to exclude a hyperparathyroidism in all cases studied.
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PMID:[Prevalence of hypercalcemia in patients with lung cancer]. 824 7

Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.
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PMID:[Medical treatment of malignant hypercalcemia]. 825 44

We report a case of primary lung cancer in a 16-year-old boy. A histologic diagnosis of squamous cell carcinoma was made by bronchoscopic biopsy before surgery. The serum alphafetoprotein (AFP) level was markedly elevated at 193 ng/dl. Preoperative and postoperative evaluation revealed no evidence of scrotal mass. We performed right pneumonectomy with combined resection of the invaded portion of the left atrium under extracorporeal circulation. Despite the rapid improvement in the patient's general condition after surgery, the AFP level continued to increase without a transient decrease and reached 3160 ng/ml on the 23rd postoperative day. When the patient was readmitted because of dyspnea and headache on the 36th postoperative day, hypercalcemia of 13.9 mg/dl was noted, and this was resistant to subsequent treatment. The patient died on the 46th postoperative day.
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PMID:AFP-producing squamous cell carcinoma of the lung in an adolescent. 860 92

Nude mice bearing the human oral cavity carcinoma cell line OCC-1, and the lung cancer cell line LC-1, developed a triple paraneoplastic syndrome consisting of hypercalcemia, cachexia and leukocytosis. All of these abnormalities disappeared rapidly after surgical resection of the tumors, suggesting their ectopic humoral nature. Search for the factors responsible for the respective abnormalities revealed that the production of parathyroid hormone-related protein and colony-stimulating factors (CSFs), mainly granulocyte-CSF, by the tumors could explain the hypercalcemia and leukocytosis, respectively. With regard to the severe cachexia, the production of two cachexia-associated cytokines, interleukin-6 and leukemia inhibitory factor, was able to explain the syndrome in OCC-1 bearing nude mice; however, the factor responsible in LC-1 bearing nude mice could not be identified. The triple paraneoplastic syndrome that developed in these two animal models could be explained partly by concomitant production of the peptide hormone and cytokines by cancer cells. These animal models may be very useful for the evaluation of diagnostic and therapeutic modalities for humoral abnormalities.
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PMID:Triple paraneoplastic syndrome of hypercalcemia, leukocytosis and cachexia in two human tumor xenografts in nude mice. 860

Treatment for the paraneoplastic syndrome associated with lung cancer was reviewed. The principle of the treatment of paraneoplastic syndrome is to control cancer as an underlying disease. Therefore, the standard therapy for Cushing's syndrome associated with lung cancer is surgical treatment if the tumor is operable. There is no standard therapy for Cushing's syndrome associated with advanced small-cell lung cancer. Metyrapone is used in combination with systemic chemotherapy. The effects of ketoconazole and octreotide are under investigation. To control hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion, fluid restriction is standard. When hyponatremia cannot be controlled with fluid restriction, demeclocycline can be used. For life-threatening hyponatremia, hypertonic saline with intravenous furosemide is administered under careful monitoring. Followed by hydration with saline, pamidronate is effective for the control of symptomatic hypercalcemia. Combined use of calcitonin facilitates rapid normalization of serum calcium for critically ill cases. Heparin is used for patients with recurrent episodes of thrombosis resulting from chronic disseminated intravascular coagulation, although the efficacy is controversial. Thrombocytes and coagulation factors are combined with heparin for patients with uncontrollable bleeding, although the efficacy is not established.
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PMID:[Paraneoplastic syndrome]. 936 21

A human lung cancer xenograft, LC-GP, producing granulocyte-colony stimulating factor and parathyroid hormone-related protein was established by transplantation into severe combined immunodeficient (SCID) mice. The lung cancer patient and SCID mice bearing LC-GP showed leukocytosis and hypercalcemia. G-CSF and PTHrP gene expression were demonstrated in the primary lung cancer, metastatic lesions and LC-GP xenograft. Immunohistochemical analysis confirmed the presence of G-CSF protein in LC-GP xenograft cells. LC-GP possessed activated c-Ki-ras oncogene (point mutation at codon 12). This LC-GP lacked apparent G-CSF receptor expression. The expression of G-CSF and PTHrP may be coregulated by the activated c-Ki-ras oncogene, and autocrine stimulation of G-CSF is unlikely.
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PMID:A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein. 946 57


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