Hypercalcemia in Malignancy

----A Review----

Authors

  • Muhammad Amin Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan
  • Muhammad Yousaf Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan
  • Muhammad Barkhurdar Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan
  • Mohsin Ali Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan
  • Mir Abdul Qadir Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan

DOI:

https://doi.org/10.31580/pjmls.v2i2.1577

Keywords:

Hypercalcemia, Diverse Malignancies, Serum Calcium, Hemodialysis

Abstract

HypercalcemiaAis characterized as a rise in theKserumJcalcium rate over the usual limit, according to the reference value that is used in a laboratory. The differential diagnosis of hypercalcemia includes a number of medical factors but primarily focuses on predominant hyperparathyroidism and malignancy hypercalcemia given the highest incidence. It isJalso importantH to note that malignant hypercalcemia is particularlyUcommonPinKadvancedJstage cancer patients. PatientsSwith malignant hypercalcemiaAtend to be only few months’ survival and whether or not the low prognosis is clear.

It is uncertain whether the subsequent occurrence of cancer was affected by a symptomatic hypercalcemia. It has been retrospectively analyzed the charts of more than 52,000 patients for significant respond to this question. Hypercalcemia patients were minority patients, but their diagnosis of cancer was higher in 1 year (6.2% as contrasted to 3.0%). In the interpretation of the results of the study, however, the retrospective methodology should be considered.

Calcium is important for a number of biochemicalLreactions,LincludingMmuscle contractions, coagulationAandBboneDdevelopment. Calcium is primarily ingested into the smallLintestine and only 10-20% of the calcium obtained is consumed, with the rest being excreted by stools. Calcium is necessary for biochemical reactions.

References

Chang PY, Lee SH, Chao TK, Chao TY. Acute renal failure due to hypercalcemia-related nephrocalcinosis in a patient of non-Hodgkin's lymphoma featuring swelling of bilateral kidneys. Annals of hematology. 2008 Jun 1;87(6):489.

Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VL, Kronenberg HM, Mulligan RC. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes & development. 1994 Feb 1;8(3):277-89.

Nadella MV, Dirksen WP, Nadella KS, Shu S, Cheng AS, Morgenstern JA, Richard V, Fernandez SA, Huang TH, Guttridge D, Rosol TJ. Transcriptional regulation of parathyroid hormone-related protein promoter P2 by NF-κ B in adult T-cell leukemia/lymphoma. Leukemia. 2007 Aug;21(8):1752-62.

Richard V, Nadella MV, Green PL, Lairmore MD, Feuer G, Foley JG, Rosol TJ. Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. Leukemia. 2005 Jul;19(7):1175-83.

Ejima E, Rosenblatt JD, Massari M, Quan E, Stephens D, Rosen CA, Prager D. Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins. " (1993): 1017-1024.

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. The Journal of experimental medicine. 1990 Sep 1;172(3):759-65.

De Gortázar AR, Alonso V, Alvarez-Arroyo MV, Esbrit P. Transient exposure to PTHrP (107-139) exerts anabolic effects through vascular endothelial growth factor receptor 2 in human osteoblastic cells in vitro. Calcified tissue international. 2006 Nov 1;79(5):360-9.

Greenfield EM, Shaw SM, Gornik SA, Banks MA. Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption. The Journal of clinical investigation. 1995 Sep 1;96(3):1238-44.

Yang X, Halladay D, Onyia JE, Martin TJ, Chandrasekhar S. Protein kinase C is a mediator of the synthesis and secretion of osteoprotegerin in osteoblast-like cells. Biochemical and biophysical research communications. 2002 Jan 11;290(1):42-6.

Horwood NJ, Elliott J, Martin TJ, Gillespie MT. Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology. 1998 Nov 1;139(11):4743-6.

Nosaka K, Miyamoto T, Sakai T, Mitsuya H, Suda T, Matsuoka M. Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor κB ligand on adult T-cell leukemia cells. Blood, The Journal of the American Society of Hematology. 2002 Jan 15;99(2):634-40.

Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, Koller CA, Kurzrock R, Thomas DA, Faderl S, Lerner S. The clinical significance of tumor necrosis factor-α plasma level in patients having chronic lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2002 Aug 15;100(4):1215-9.

Li J, Karaplis AC, Huang DC, Siegel PM, Camirand A, Yang XF, Muller WJ, Kremer R. PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. The Journal of clinical investigation. 2011 Dec 1;121(12):4655-69.

Mundy GR, Martin TJ. The hypercalcemia of malignancy: pathogenesis and management. Metabolism. 1982 Dec 1;31(12):1247-77.

Roodman GD. Mechanisms of bone lesions in multiple myeloma and lymphoma. Cancer: Interdisciplinary International Journal of the American Cancer Society. 1997 Oct 15;80(S8):1557-63.

Stewart AF. Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic actions of parathyroid hormone and parathyroid hormone-related protein on the skeleton. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2002 May;17(5):758-62.

Chu CQ, Field M, Feldmann M, Maini RN. Localization of tumor necrosis factor α in synovial tissues and at the cartilage–pannus junction in patients with rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 1991 Oct 7;34(9):1125-32.

Horowitz MC. Cytokines and estrogen in bone: anti-osteoporotic effects. Science. 1993 Apr 30;260(5108):626-8.

Asanuma N, Hagiwara K, Matsumoto I, MATSUDA M, NAKAMURA F, KOUHARA H, MIYAMOTO M, MIYASHITA Y, NOGUCHI S, MORIMOTO Y. PTHrP-producing tumor: squamous cell carcinoma of the liver accompanied by humoral hypercalcemia of malignancy, increased IL-6 and leukocytosis. Internal medicine. 2002;41(5):371-6.

Roodman GD. Biology of osteoclast activation in cancer. Journal of Clinical Oncology. 2001 Aug 1;19(15):3562-71.

Tanaka S, Takahashi N, Udagawa N, Tamura T, Akatsu T, Stanley ER, Kurokawa T, Suda T. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. The Journal of clinical investigation. 1993 Jan 1;91(1):257-63.

Xu Z, Hurchla MA, Deng H, Uluçkan Ö, Bu F, Berdy A, Eagleton MC, Heller EA, Floyd DH, Dirksen WP, Shu S. Interferon-γ targets cancer cells and osteoclasts to prevent tumor-associated bone loss and bone metastases. Journal of Biological Chemistry. 2009 Feb 13;284(7):4658-66.

Liu, J., & Jiang, G. (2006). CD44 and hematologic malignancies. Cellular & molecular immunology, 3(5), 359-365.

Chattopadhyay N. Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy. American Journal of Physiology-Endocrinology and Metabolism. 2006 May;290(5):E761-70.

Lorch G, Viatchenko-Karpinski S, Ho HT, Dirksen WP, Toribio RE, Foley J, Györke S, Rosol TJ. The calcium-sensing receptor is necessary for the rapid development of hypercalcemia in human lung squamous cell carcinoma. Neoplasia (New York, NY). 2011 May;13(5):428.

Saidak Z, Brazier M, Kamel S, Mentaverri R. Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications. Molecular pharmacology. 2009 Dec 1;76(6):1131-44.

Habra MA, Weaver EJ, Prewitt PV. Primary cutaneous large B-cell lymphoma of the leg and acute hypercalcemia. Journal of clinical oncology. 2007;25(36):5825-6.

Narimatsu H, Morishita Y, Shimada K, Ozeki K, Kohno A, Kato Y, Nagasaka T. Primary cutaneous diffuse large B cell lymphoma: a clinically aggressive case. Internal medicine. 2003;42(4):354-7.

Nadella MV, Kisseberth WC, Nadella KS, Thudi NK, Thamm DH, McNiel EA, Yilmaz A, Boris‐Lawrie K, Rosol TJ. NOD/SCID mouse model of canine T‐cell lymphoma with humoral hypercalcaemia of malignancy: cytokine gene expression profiling and in vivo bioluminescent imaging. Veterinary and comparative oncology. 2008 Mar;6(1):39-54.

Bolliger AP, Graham PA, Richard V, Rosol TJ, Nachreiner RF, Refsal KR. Detection of parathyroid hormone—related protein in cats with humoral hypercalcemia of malignancy. Veterinary clinical pathology. 2002 Mar;31(1):3-8.

Engelman RW, Fulton RW, Good RA, Day NK. Suppression of gamma interferon production by inactivated feline leukemia virus. Science. 1985 Mar 15;227(4692):1368-70

de Wit M, Schoemaker NJ, Kik MJ, Westerhof I. Hypercalcemia in two Amazon parrots with malignant lymphoma. Avian Dis. 2003;47(1):223‐228. doi:10.1637/0005-2086(2003)047[0223:HITAPW]2.0.CO;2

Richard V, Nadella MV, Green PL, Lairmore MD, Feuer G, Foley JG, Rosol TJ. Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. Leukemia. 2005 Jul;19(7):1175-83

Fleisch HA. Bisphosphonates: preclinical aspects and use in osteoporosis. Annals of medicine. 1997 Jan 1;29(1):55-62.

Gao L, Deng H, Zhao H, Hirbe A, Harding J, Ratner L, Weilbaecher K. HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition. Blood. 2005 Dec 15;106(13):4294-302.

Fleisch H. Bisphosphonate bei Knochenerkrankungen. Hans Huber, Bern. 1998.

Shu ST, Nadella MV, Dirksen WP, Fernandez SA, Thudi NK, Werbeck JL, Lairmore MD, Rosol TJ. A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma. Cancer research. 2007 Dec 15;67(24):11859-66.

Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. InMayo Clinic Proceedings 2008 Sep 1 (Vol. 83, No. 9, pp. 1032-1045). Elsevier.

Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, Nakamura R, Tanaka T, Tomiyama H, Saito N, Fukata M. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nature biotechnology. 2007 Nov;25(11):1315-21.

Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. Jama. 2004 Jul 28;292(4):490-5.

Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. The Journal of clinical investigation. 2003 Apr 15;111(8):1221-30.

Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003 May;423(6937):337-42.

De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello MR, Aldinucci D, Pinto A, Normanno N. The role of the EGFR signaling in tumor microenvironment. Journal of cellular physiology. 2008 Mar;214(3):559-67.

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Published

2020-08-18