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 have demonstrated that T3M-1 cells and T3M-5 cells, derived from squamous carcinomas of patients with leukocytosis and hypercalcemia, produced excessively G-CSF, IL-1 alpha and a small amount of PTH-like factor. We confirmed that G-CSF and IL-1 alpha (hemopoietin 1) enhanced granulocytopoiesis and caused marked leukocytosis in vivo. Furthermore, we also demonstrated that PTH-rP and IL-1 alpha (a potent osteoclast-activating factor) synergistically stimulated bone resorption in vitro and also synergistically increased serum calcium concentration in vivo. Since we have demonstrated that at least two clonal cell lines derived from patients with hypercalcemia and leukocytosis produced G-CSF and IL-1 alpha, we presume that hypercalcemia and leukocytosis associated with some solid tumors may constitute a new paraneoplastic syndrome.
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PMID:A paraneoplastic syndrome of hypercalcemia and leukocytosis associated with solid tumors: production of interleukin 1 alpha (IL-1 alpha) and granulocyte colony-stimulating factor (G-CSF) by clonal squamous cell carcinoma cells. 247 Jun 24

Hypercalcemia of cancer is due to secretion of substances with parathyroid hormone (PTH)-like activity from tumours of the respiratory, gastrointestinal and urogenital tract as well as hematologic malignancies and breast cancer. PTH-related Protein (PTHrP) is secreted mainly from solid tumours and it has been recently recognized as being responsible for hypercalcemia mediated primarily via an increased renal reabsorption of calcium and secondly by an increased bone resorption. PTHrP-mRNA is expressed in a variety of normal tissues and has multiple physiologic and paracrine actions. Bone resorbing factors like the cytokines-lymphokines, interleukins, prostaglandins, TNF-alpha/TNF-beta, GM-CSF/G-CSF, TGF-alpha and TGF-beta are produced by certain solid and hematologic cancers and have also been implicated in tumour-induced hypercalcemia. The recently introduced PTHrP antagonists are hopeful therapeutic measures for the future.
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PMID:Hypercalcemia of cancer: an update. 835 38

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

A patient with primary small cell carcinoma of the esophagus is reported, in whom we have studied the secretion of a variety of hormones and cytokines. The tumor was an intermediate cell type of small cell carcinoma and had either epithelial and neuroendocrinological characteristics. Furthermore, hypercalcemia and neutrophilia were present, and the tumor was shown to produce PTHrp, secretin, and G-CSF. The present case is the first report of primary small cell carcinoma of the esophagus with ectopic production of PTHrp, secretin, and G-CSF.
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PMID:Esophageal small cell carcinoma with ectopic production of parathyroid hormone-related protein (PTHrp), secretin, and granulocyte colony-stimulating factor (G-CSF). 1048 11

A 66-year-old man was admitted to our hospital complaining of non-productive cough and low-grade fever. Chest X-ray examination revealed a mass shadow in the right hilum. Transbronchial lung biopsy of the tumor mass yielded a diagnosis of adenocarcinoma. Despite repeated chemotherapy using CDDP and VDS, metastasis to the right adrenal gland and right femur occurred, and was accompanied by hypercalcemia and hypophosphatemia. Serological study revealed elevated levels of PTH-rP and G-CSF. Six months after adenocarcinoma was diagnosed, multiple skin metastases of the cancer were observed. Immunohistochemical staining for PTH-rP and G-CSF indicated that production of cytokines had caused a paraneoplastic syndrome including hypercalcemia and leukocytosis. It appeared that the elevation of G-CSF was induced by IL-6 produced from PTH-rP in cancer tissue. Documentation of similar cases is required.
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PMID:[A case of adenocarcinoma complicated with massive leukocytosis and hypercalcemia]. 1101 67

Cytokines have not been employed in clinical laboratory tests because of the many biological activities of individual cytokines and too complicated cytokine network. However, abnormal laboratory data and symptoms can be interpreted by blood cytokine levels. [Cytokines attributable to abnormal data and symptoms] For example, cytokines attributable to abnormal data and symptoms in rheumatoid arthritis are as follows: joint pain: TNFalpha, IL-1, IL-6, and IL-18; general fatigue and appetite loss: TNFalpha and IL-1; leukocytosis: G-CSF produced by IL-1-stimulated macrophages etc; thrombocytosis: megakaryocyte potentiating activity of IL-6; anemia: hepcidin up-regulated by IL-6, which inhibits iron absorption from the intestine, and IL-1, which decreases the blood iron level and promotes ferritin synthesis. [Differential diagnosis using blood cytokine levels] Blood cytokine levels are useful and important in the differential diagnosis of inflammatory disorders such as neutrophilia, eosinophilia, and especially in distinguishing tumoral fever from infectious fever in malignant lymphomas. [Disease/disorder-specific cytokines] In recent years, disease- or disorder specific cytokines have been identified, making cytokines more important in clinical use. For example, IL-18 for adult-onset Still disease; IFNgamma for hemophagocytic syndrome; IL-5 for allergic disorders; thrombopoietin for immune thrombocytopenic purpura; vascular endothelial growth factor for POEMS syndrome; PTH-rP for malignancy associated hypercalcemia. [Flow cytometric measurement of cytokines] Recently, a flow cytometric method has been developed in addition to ELISA. With this method, 30 cytokine concentrations can be measured simultaneously within four hours with a wide range of detection limit and high cost performance. Cytokines will be included in laboratory tests with this method.
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PMID:[Blood cytokine levels as a clinical laboratory test]. 1744 72