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Hypercalcemia of Malignancy

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References

  1. Zondek H, Petrow H, Siebert W. Die bedeutung der calciumbestimmung im blute fur die diagnose der niereninsuffizienz. Z Klin Med 1924;99:129-132.

    Google Scholar 

  2. Gutman AB, Tyson TL, Gutman EB. Serum calcium, inorganic phosphorus, and phosphatase activity in hyperparathyroidism, paget's disease, multiple myeloma and neoplastic disease of bones. Archives of Internal Medicine 1936;57:379-413.

    Google Scholar 

  3. Albright F. Case records of the massachusetts general hospital (case 27401). N Engl J Med 1941;225:789-791.

    Google Scholar 

  4. Berson SA, Yalow RS. Parathyroid hormone in plasma in adenomatous hyperparathyroidism, uremia and bronchogenic sarcoma. Science 1966;154:907-909.

    Google Scholar 

  5. Knill-Jones RP, Buckle RM, Parsons V, Caine RY, Williams R. Hypercalcaemia and increased parathyroid hormone activity in a primary hepatoma. Studies before and after hepatic transplantation. N Engl J Med 1970;282:704-708.

    Google Scholar 

  6. Greenberg PB, Martin TJ, Sutcliffe HS. Synthesis and release of parathyroid hormone by a renal carcinoma in cell culture. Clini Sci Mol Med 1973;45:183-187.

    Google Scholar 

  7. Riggs BL, Arnaud CD, Reynolds JC, Smith LH. Immunological differentiation of primary hyperparathyroidism from hyperparathyroidism due to non-parathyroid cancer. J Clin Invest 1971;50:2079-2083.

    Google Scholar 

  8. Roof BS, Carpenter B, Fink DJ, Gordan GS. Some thoughts on the nature of ectopic parathyroid hormones. Am J Med 1971;50:686-691.

    Google Scholar 

  9. Powell D, Singer FR, Murray TM, Minkin C, Potts JT. Nonparathyroid humoral hypercalcemia in patients with neoplastic disease. N Engl J Med 1973;289:176-181.

    Google Scholar 

  10. Martin TJ, Atkins D. Biochemical regulators of bone resorption and their significance in cancer. Essays in Medical Biochemistry 1979;4:49-82.

    Google Scholar 

  11. Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer-associated hypercalcemia. Evidence for humoral and non-humoral groups. N Engl J Med 1980;303:1377-1381.

    Google Scholar 

  12. Kukreja SC, Shermerdiak WP, Lad TE, Johnson PA. Elevated nephrogenous cyclic AMP with normal serum parathyroid hormone levels in patients with lung cancer. The J Clin Endocrinol Metab 1980;51:167-169.

    Google Scholar 

  13. Rude RK, Sharp CF Jr, Fredericks RS, Oldham SB, Elbaum N, Liuk J, Irvin L, Singer FR. Urinary and nephrogenous adenosine 3' 5'-monophosphate in the hypercalcemia of malignancy. J Clin Invest 1981;52:765-771.

    Google Scholar 

  14. Stewart AF, Insogna KL, Goltzman D, Broadus AE. Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphatedehydrogenase-stimulating activity in extracts of tumours from patients with humoral hypercalcemia of malignancy. Proc Nat Acad Sci USA 1983;80:1454-1458.

    Google Scholar 

  15. Goltzman D, Stewart AF, Broaus AE. Malignancy-associated hyperaclecmai evaluation with a cytochemial bioassay for parathryoid hormone. J Clin Endocrinol Metab 1981;53:899-904.

    Google Scholar 

  16. Rodan SB, Insogna KL, Vignery AM-C, Stewart AF, Broadus AE, D'Souza S, Bertolini DR, Mundy GR, Rodan GA. Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells. J Clin Invest 1983;72:1511-1515.

    Google Scholar 

  17. Simpson EL, Mundy GR, D'Souza SM, Ibbotson KJ, Bockman R, Jacobs JW. Absence of parathyroid hormone messenger RNA in non-parathyroid tumors associated with hypercalcemia. N Engl J Med 1983;309:325-330.

    Google Scholar 

  18. Moseley JM, Kubota M, Diefenbach-Jagger H, Wettenhall REH, Kemp BE, Suva LJ, Rodda CP, Ebeling PR, Hudson PJ, Zajac JD, Martin TJ. Parathyroid hormone-related protein puri®ed from a human lung cancer cell line. Proc Natl Acad Sci USA 1987;84:5048-5052.

    Google Scholar 

  19. Suva LJ, Winslow GA, Wettenhall REH et al. A parathyroid hormone-related protein implicated in malignant hypercalcemia: Cloning and expression. Science 1987;237:893-896.

    Google Scholar 

  20. Strewler GJ, Stern PH, Jacobs JW, Eveloff J, Klein RF, Leung SC, Rosenblatt M, Nisseuson RA. Parathyroid hormone-like protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. J Clin Invest 1987;80:1803-1807.

    Google Scholar 

  21. Burtis WJ, Wu J, Bunch CM, Wysolmerski TJ, Jusogna KL, Weir EC, Broadus AE, Stewart AF. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem 1987;262:7151-7156.

    Google Scholar 

  22. Shaw G, Karmen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selecetive mRNA degradation. Cell 1986;46:659-667.

    Google Scholar 

  23. Moseley JM, Gillespie MT. Parathyroid hormone-related protein. Crit Rev Clin Lab Sci 1995;32:299-343.

    Google Scholar 

  24. Danks JA, Ebeling PR, Hayman JA, Chou ST, Moseley JM, Dunlop J, Kemp BE, Martin TJ. Parathyroid hormone-related protein: immunohistochemical localization in cancers and in normal skin. Bone Min Res 1989;4:273-278.

    Google Scholar 

  25. Southby J, Kissin MW, Danks JA, Hayman JA, Moseley JM, Henderson MA, Bennett RC, Martin TJ. Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res 1990;50:7710-7716.

    Google Scholar 

  26. Kukreja SC, Schavin DH, Wimbuscus S, Ebeling PR, Danks JA, Rodda CP, Wood WI, Martin TJ. Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy associated hypercalcemia due to human tumors. J Clin Invest 1988;82:1798-1802.

    Google Scholar 

  27. Grill V, Ho P, Body JJ, Lee SC, Kukreja SC, Moseley JM, Martin TJ. Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab 1991;73:1309-1315.

    Google Scholar 

  28. Ralston SH, Fogelman I, Gardner MD, Boyle IT. Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcemia of malignancy. Br Med J 1984;288:1405-1408.

    Google Scholar 

  29. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987;55:6166.

    Google Scholar 

  30. Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 1991;51:3059-3061.

    Google Scholar 

  31. Vargas SJ, Gillespie MT, Powell GJ, Southby J, Danks JA, Moseley JM, Martin TJ. Localization of parathyroid hormone-related protein mRNA in breast cancer and metastatic lesions by in situ hybridization. J Bone Min Research 1992;7:971-979.

    Google Scholar 

  32. Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 1996;98:1544-1549.

    Google Scholar 

  33. Smith DC, Tucker JA, Trump DL. Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature. J Clin Oncol 1992;10:499-505.

    Google Scholar 

  34. Iwamura M, di Sant'Agnese PA, Wu G, Benning CM, Cockett ATK, Deftos LJ, Abrahamsson P-A. Immunohistochemical localization of parathyroid hormone-related protein in human prostate cancer. Cancer Res 1993;53:1724-1726.

    Google Scholar 

  35. Cramer SD, Peehl DM, Edgar MG, Wong ST, Deftos LJ, Feldman D. Parathyroid hormone-related protein (PTHrP) is an epidermal growth factor-regulated secretory product of human prostatic epithelial cells. Prostate 1996;29:20-29.

    Google Scholar 

  36. Iwamura M, Wu G, Abrahamsson P-A, di Sant'Agnese PA, Cockett ATK, Deftos LJ. Parathyroid hormone-related protein is expressed by prostatic neuroendocrine cells. Urology 1994;43:667-674.

    Google Scholar 

  37. Iwamura M, Abrahamsson P-A, Schoen S, Cockett ATK, Deftos LJ. Immunoreactive parathyroid hormone-related protein is present in human seminal plasma and is of prostate origin. J Androl 1994;15:410-414.

    Google Scholar 

  38. Iwamura M, Abrahamsson P-A, Foss KA, Wu G, Cockett ATK, Deftos LJ. Parathyroid hormone related protein: a potential autocrine growth regulator in human prostate cancer cell lines. Urology 1994;43:675-679.

    Google Scholar 

  39. Iwamura M, Gershagen S, Lapets O, Moynes R, Abrahamsson P-A, Cockett ATK, Deftos LJ, di Sant'Agnese PA. Immunohistochemical localization of parathyroid hormone-related protein in prostatic intraepithelial neoplasia. Hum Pathol 1995;26:797-801.

    Google Scholar 

  40. Firkin F, Seymour JF, Watson AM, Grill V, Martin TJ. Parathyroid hormone-related protein in hypercalcaemia associated with haematological malignancy. Br J Haematol 1996;94:486-492.

    Google Scholar 

  41. Breslau NA, McGuire JL, Zerwekh JE, Frenkel EP, Pak CYC. Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma. Ann Intern Med 1984;100:1-7.

    Google Scholar 

  42. Rosenthal N, Insogna KL, Godsall JW, Smaldone L, Waldron JA, Stewart AF. Elevations in circulating 1,25-dihydroxyvitamin D in three patients with lymphoma-associated hypercalcemia. J Clin Endocrinol Metab 1985;60:29±33.

    Google Scholar 

  43. Fukumoto S, Matsumoto T, Ikeda K, Yamashita T, Watanabe T, Yamaguchi K, Kiyokawa T, Takatsuki K, Shibuya N, Ogata E. Clinical evaluation of calcium metabolism in adult T-cell leukemia/lymphoma. Arch Intern Med 1988;148:921-925.

    Google Scholar 

  44. Watanabe T, Yamaguchi K, Takatsuki K, Osame M, Yoshida M. Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. J Exp Med 1990;172:759-765.

    Google Scholar 

  45. Moseley JM, Danks JA, Grill V, Lister TA, Horton MA. Immunohistochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukemia/ lymphoma: implications for the mechanism of hypercalcemia. Brit J Cancer 1991;64:745-748.

    Google Scholar 

  46. Mundy GR, Raisz LG, Cooper RA, Schechter GP, Salmon SE. Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl J Med 1974;291:1041-1046.

    Google Scholar 

  47. Roodman GD. Osteoclast function in Paget's disease and multiple myeloma. Bone 1995;17:57S-61S.

    Google Scholar 

  48. Schneider H-G, Kartsogiannis V, Zhou H, Chou ST, Martin TJ, Grill V. Parathyroid hormone-related protein mRNA and protein expression in multiple myeloma: A case report. J Bone Miner Res 1998;13:1-4.

    Google Scholar 

  49. Budayr AA, Nissenson RA, Klein RF, Pun KK, Clark OH, Diep D, Arnaud CD, Strewler GJ. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia. Ann Intern Med 1989;111:807-812.

    Google Scholar 

  50. Henderson JE, Shustik C, Kremer R, Rabbani SA, Hendy GN, Goltzman D. Circulating concentrations of parathyroid hormonelike peptide in malignancy and in hyperparathyroidism. J Bone Min Res 1990;5:105-113.

    Google Scholar 

  51. Kao PC, Klee GG, Taylor RL, Heath H. Parathyroid hormonerelated peptide in plasma of patients with hypercalcemia and malignant lesions. Mayo Clin Proc 1990;65:1399-1407.

    Google Scholar 

  52. Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RP, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med 1990;322:1106-1112.

    Google Scholar 

  53. Ratcliffe WA, Norbury S, Heath DA, Ratcliffe JG. Development and validation of an immunoradiometric assay of parathyrin-related protein in unextracted plasma. Clin Chem 1991;37:678-685.

    Google Scholar 

  54. Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T, Hirose S, Mori S, Takeuchi Y, Fukumoto S, Terukina S, Iguchi H, Kiriyama T, Ogata E, Matsumoto T. Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/ lymphoma and B-cell lymphoma. J Clin Endocrinol Metab 1994;79:1322-1327.

    Google Scholar 

  55. Fleisch H. Bisphosphonates in bone disease. From the laboratory to the patient. London: Parthenon Publishing Group, 1995.

    Google Scholar 

  56. Hosking DJ, Stone MD, Foote JW. Potentiation of calcitonin by corticoteroids during the treatment of hypercalcemia of malignancy. Eur J Clin Pharmacol 1990;38:37-41.

    Google Scholar 

  57. Suki WN, Yium JJ, von Minden M, Saller-Herbert C, Eknovan G, Martinez-Maldonado M. Acute treatment of hypercalcemia with furosemide. N Eng J Med 1970;283:836-840.

    Google Scholar 

  58. Brown JH, Kennedy BJ. Mithramycin in the treatment of testicular cancer. N Eng J Med 1965;272:111-118.

    Google Scholar 

  59. Gurney H, Grill V, Martin TJ. Parathryoid hormone-related protein level predicts response to Pamidronate in the treatment of tumorinduced hypercalcemia. Lancet 1993;2:241-244.

    Google Scholar 

  60. Murayama E, Miyamoto K, Kubodera N, Mori T, Matsunaga I. Synthetic studies of Vitamin D3 analogues. VIII. Synthesis of 22-oxavitamin D3 analogues. Chem Pharm Bull (Tokyo) 1986;34:4410-4413.

    Google Scholar 

  61. Brown AJ, Ritter CR, Finch JL, Morrissey J, Martin KJ, Murayama E, Nishii Y, Slatopolsky E. The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion. J Clin Invest 1989;84:728-732.

    Google Scholar 

  62. Ikeda K, Lu C, Weir EC, Mangin M, Broadus AE. Transcriptional regulation of the parathyroid hormone-related protein gene by glucocorticoids and vitamin D in a human C-cell line. J Biol Chem 1989;264:15743-15746.

    Google Scholar 

  63. Falzon M, Zong J. The noncalcemic vitamin D analogs EB1089 and 22-oxacalcitriol suppress serum-induced parathyroid hormonerelated peptide gene expression in a lung cancer cell line. Endocrinology 1998;139(3):1046-1053.

    Google Scholar 

  64. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennet L, Boone T. Osteoprotogerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-319.

    Google Scholar 

  65. Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclasogenesis. Biochem Biophys Res Commun 1997;234:137-142.

    Google Scholar 

  66. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S-I, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Moringa T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotogerin/ osteoclastogenesis inhibitory factor and identical toTRANCE/RANKL. Proc Natl Acad Sci USA 1998;95:3597-3602.

    Google Scholar 

  67. Lacey DM, Timms E, Tan H-L, Kelley MJ, Dunstan CR, Burgess T, Elliot R, Colombero A, Elliot G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Caprelli C, Eli A, Qian Y-K, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotogerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-176.

    Google Scholar 

  68. Quinn JMW, Elliott J, Gilllespie MT, Martin TJ. A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro. Endocrinol 1998;139:4424-4427.

    Google Scholar 

  69. Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayan E, Bartlett F, Frankel W, Lee SY, Choi Y. TRANCE is a novel ligand of the tumor necrosisi factoe receptor family that activates c-Jun N-terminal kinase in T-cells. J Biol Chem 1997;272:25190-25194.

    Google Scholar 

  70. Horwood NJ, Kartsogiannis V, Quinn JMW, Romas E, Martin TJ, Gillespie MT. Activated T lymphicytes supoport osteoclast formation in vitro. Biochem Biophys Res Com 1999;265:144-150.

    Google Scholar 

  71. Thomas RJ, Guise TA, Yin JJ, Elliot J, Horwood NJ, Martin TJ, Gillespie MT. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinol 1999;140:4451-4458.

    Google Scholar 

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    Vivian Grill & T. John Martin

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Grill, V., Martin, T.J. Hypercalcemia of Malignancy. Rev Endocr Metab Disord 1, 253–263 (2000). https://doi.org/10.1023/A:1026597816193

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