Volume 11, Issue 4 (Jul-Aug 2017)                   mljgoums 2017, 11(4): 1-8 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Khadem Ansari M H, Meghrazi K. Functions of Obesity-related Hormones in Breast Cancer: A Review. mljgoums. 2017; 11 (4) :1-8
URL: http://mlj.goums.ac.ir/article-1-985-en.html
1- Department of Biochemistry, Urmia Medical Science University, Urmia, Iran
2- Department of Biochemistry, Urmia Medical Science University, Urmia, Iran , kmeghrazi@gmail.com
Abstract:   (8708 Views)
           Obesity is a health problem defined as abnormal or excessive fat accumulation in adipose tissue. Adipokines such as adiponectin, visfatin and resistin are bioactive polypeptides with pro- and anti-inflammatory properties that are secreted by the adipose tissue that are involved in the pathogenesis and prognosis of diseases such as type 2 diabetes, metabolic syndrome and cancer. This survey aimed to review the role of these hormones in the pathogenesis and prognosis of breast cancer in obese postmenopausal women. In obese individuals, increased level of leptin leads to tumorigenesis and progression of breast cancer though JAK/STAT3 pathway. These individuals have decreased level of adiponectin, which has a protective effect against carcinogenesis via AMPK pathway. Obese individuals also have increased level of visfatin, which induces the secretion of proinflammatory cytokines such as TNFα and triggers growth of cancer cells. Similarly, elevated resistin levels increases cell proliferation through PI3K and MAPK pathways. Obesity is associated with the dysregulated secretion of adipokines such as leptin, adiponectin, visfatin and resistin, which could be utilized for early diagnosis of breast cancer.
        Keywords: Obesity, Breast Cancer, Adiponectin, Leptin, Visfatin, Resistin.
Full-Text [PDF 497 kb]   (745 Downloads)    
Type of Study: Original Paper |
Received: 2017/08/8 | Accepted: 2017/08/8 | Published: 2017/08/8 | ePublished: 2017/08/8

1. Teoh SL, Das S. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment. Tumour Biol. 2016; 37(11): 14363-14380. [DOI:10.1007/s13277-016-5357-7]
2. Anastácio LR, de Oliveira MC, Diniz KG, Ferreira AM, Lima AS, Correia MI, et al. Adipokines, inflammatory mediators, and insulin-resistance parameters may not be good markers of metabolic syndrome after liver transplant. Nutrition. 2016; 32(9): 921-927. doi: 10.1016/j.nut.2015.12.038. [DOI:10.1016/j.nut.2015.12.038]
3. Triantafyllou GA, Paschou SA, Mantzoros. CS. Leptin and Hormones: Energy Homeostasis. Endocrinology and Metabolism Clinics of North America. 2016; 45(3): 633-645. doi: 10.1016/j.ecl.2016.04.012. [DOI:10.1016/j.ecl.2016.04.012]
4. Wintrob ZA, Hammel JP, Khoury T, Nimako GK, Fu HW, Fayazi ZS, et al. Insulin use, adipokine profiles and breast cancer prognosis. Cytokine. 2017; 89: 45-61. doi: 10.1016/j.cyto.2016.10.017. [DOI:10.1016/j.cyto.2016.10.017]
5. Mancuso P. The role of adipokines in chronic inflammation. Immuno Targets and Therapy. 2016; 5: 47-56. doi: 10.2147/ITT.S73223. [DOI:10.2147/ITT.S73223]
6. Wang X, Simpson ER, Brown KA. Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer. Journal of Steroid Biochemistry & Molecular Biology 2015; 153: 35-44. doi: 10.1016/j.jsbmb.2015.07.008. [DOI:10.1016/j.jsbmb.2015.07.008]
7. Goodwin PJ. Obesity, insulin resistance and breast cancer outcomes. The Breast 2015; 24(2): S56 - S59. doi: 10.1016/j.breast.2015.07.014. [DOI:10.1016/j.breast.2015.07.014]
8. Georgiou GP, Provatopoulou X, Kalogera E, Siasos G, Menenakos E, Zografos GC, et al. Serum resistin is inversely related to breast cancer risk in premenopausal women. The Breast. 2016; 29: 163e169. doi: /10.1016/j.breast.2016.07.025
9. Popovic DS, Popovic LS. Obesity and breast cancer-Association even more relevant in males? European Journal of Internal Medicine. 2016; 29: e11–e12. doi: 10.1016/j.ejim.2015.11.024. [DOI:10.1016/j.ejim.2015.11.024]
10. Herlevic VC, Mowad R, Miller JK, Darensburg NA, Li BD, Kim RH. Breast cancer outcomes in a population with high prevalence of obesity. J Surg Res. 2015; 198(2): 371-6. doi: 10.1016/j.jss.2015.03.088. [DOI:10.1016/j.jss.2015.03.088]
11. Ayeser T, Basak M, Arslan K, Sayan I. Investigating the correlation of the number of diagnostic criteria to serum adiponectin, leptin, resistin, TNF-alpha, EGFR levels and abdominal adipose tissue. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2016; 10S: 165–169. doi: 10.1016/j.dsx.2016.03.010 [DOI:10.1016/j.dsx.2016.03.010]
12. Aguilar-Valles A, Inoue W, Rummel Ch, Luheshi GN. Obesity, adipokines and neuroinflammation. Neuropharmacology. 2015; 96(Pt A):124-34. doi: 10.1016/j.neuropharm.2014.12.023. [DOI:10.1016/j.neuropharm.2014.12.023]
13. Procaccini C, La Rocca C, Carbone F, De Rosa V, Galgani M, Matarese G. Leptin as immune mediator: Interaction between neuroendocrine and immune system. Developmental and Comparative Immunology. 2017; 66: 120e129. doi: 10.1016/j.dci.2016.06.006. [DOI:10.1016/j.dci.2016.06.006]
14. Kyriakidis M, Caetano L, Anastasiadou N, Karasu T, Lashen H. Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice-systematic review. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2016; 198: 131–137. doi :10.1016/j.ejogrb.2016.01.018. [DOI:10.1016/j.ejogrb.2016.01.018]
15. Al-Shibli SM, Amjad NM, Al-Kubais MK, Mizan Sh. Subcellular localization of leptin and leptin receptor in breast cancer detected in an electron microscopic study. Biochemical and Biophysical Research Communications. 2017; 482(4): 1102- 1106. doi: 10.1016/j.bbrc.2016.11.165. [DOI:10.1016/j.bbrc.2016.11.165]
16. Ghasemi A, Hashemy SI, Aghaei M, Panjehpour M. RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells. Cellular Signalling. 2017; 32: 104–114. doi: 10.1016/j.cellsig.2017.01.020. [DOI:10.1016/j.cellsig.2017.01.020]
17. Lipsey CC, Harbuzariu A, Daley-Brown D, Gonzalez-Perez RR. Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer. World J Methodol 2016; 6(1): 43-55. doi: 10.5662/wjm.v6.i1.43. [DOI:10.5662/wjm.v6.i1.43]
18. Chandar AK, Devanna S, Lu Ch, Singh S, Greer K, Chak A, et al. Association of Serum Levels of Adipokines and Insulin With Risk of Barrett's Esophagus: A Systematic Review and Meta Analysis. Clinical Gastroenterology and Hepatology. 2015; 13(13): 2241-2255. doi: 10.1016/j.cgh.2015.06.041. [DOI:10.1016/j.cgh.2015.06.041]
19. Chang CC, Wu MJ, Yang JY, Camarillo IG, Chang CJ. Leptin–STAT3–G9a Signaling Promotes Obesity-Mediated Breast Cancer Progression. Cancer Res. 2015; 75(11): 2375-2386. doi: 10.1158/0008-5472.CAN-14-3076. [DOI:10.1158/0008-5472.CAN-14-3076]
20. Blanquer-Rosselló MM, Oliver J, Sastre-Serra J, Valle A, Roca P. Leptin regulates energy metabolism in MCF-7 breast cancer cells. The International Journal of Biochemistry & Cell Biology 2016; 72: 18–26. doi:org/10.1016/j.biocel.2016.01.002.
21. Santander AM, Lopez-Ocejo O, Casas O, Agostini Th, Sanchez L, et al. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue. Cancers. 2015; 7(1): 143-178. doi:10.3390/cancers7010143. [DOI:10.3390/cancers7010143]
22. Giordano C, Chemi F, Panza S, Barone I, Bonofiglio D, Lanzino M, et al. Leptin as a mediator of tumor–stromal interactions promotes breast cancer stem cell activity. Oncotarget. 2016, 7(2): 1262-1275. [DOI:10.18632/oncotarget.6014]
23. Babaei Z, Moslemi D, Hadi Parsian H, Khafri S, Pouramir M, Mosapour A. Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors. Journal of the Egyptian National Cancer Institute. 2015; 27(4): 223–229. doi: 10.1016/j.jnci.2015.09.001. [DOI:10.1016/j.jnci.2015.09.001]
24. Gan L, Liu Zh, Wu T, Feng F, Sun Ch. αMSH promotes preadipocyte proliferation by alleviating ER stress-induced leptin resistance and by activating Notch1 signal in mice. Biochimica et Biophysica Acta. 2017; 1863(1): 231-238. doi: 10.1016/j.bbadis.2016.10.001. [DOI:10.1016/j.bbadis.2016.10.001]
25. Lanier V, Gillespie C, Leffers M, Daley-Brown D, Milnera J, Lipsey C, et al. Leptin-induced transphosphorylation of vascular endothelial growth factor receptor increases Notch and stimulates endothelial cellangiogenic transformation. The International Journal of Biochemistry & Cell Biology 2016; 79: 139-150. doi: 10.1016/j.biocel.2016.08.023. [DOI:10.1016/j.biocel.2016.08.023]
26. Gorgui J, Gasbarrino K, Georgakis MK, Karalexi MA, Nauchec B, Petridou ET, et al. Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, andmortality:Asystematic review andmeta-analyses. Metabolism Clinical and Experimental. 2017; 69: 51-66. doi: 10.1016/j.metabol.2017.01.002. [DOI:10.1016/j.metabol.2017.01.002]
27. Liu D, Li Sh, Li Zh. Adiponectin: A biomarker for chronic hepatitis C? Cytokine. 2017; 89: 27–33. doi: 10.1016/j.cyto.2015.10.016. [DOI:10.1016/j.cyto.2015.10.016]
28. Nagarajua GP, Rajitha B, Aliya Sh, Kotipatruni RP, Madanraj AS, Hammond A, et al. The role of adiponectin in obesity-associated female-specific carcinogenesis. Cytokine & Growth Factor Reviews 2016; 31: 37–48. doi: 10.1016/j.cytogfr.2016.03.014. [DOI:10.1016/j.cytogfr.2016.03.014]
29. Panno ML, Naimo GD, Spina E, Ando S, Mauro L. Different molecular signaling sustaining adiponectin action in breast cancer. Current Opinion in Pharmacology 2016, 31: 1-7. doi: 10.1016/j.coph.2016.08.001. [DOI:10.1016/j.coph.2016.08.001]
30. Andel MV, Drent ML, Herwaarden AE, Ackermans MT, Heijboer AC. A method comparison of total and HMW adiponectin: HMW/total adiponectin ratio varies versus total adiponectin, independent of clinical condition. Clinica Chimica Acta. 2017; 465: 30–33. doi:10.1016/j.cca.2016.12.009. 31. Zhang L, Wen K, Han X, Liu R, Qu Q. Adiponectin mediates antiproliferative and apoptotic responses in endometrial carcinoma by the AdipoRs/AMPK pathway. Gynecologic Oncology. 2015; 137(2): 311-320. doi: 10.1016/j.ygyno.2015.02.012. https://doi.org/10.1016/j.ygyno.2015.02.012 [DOI:10.1016/j.cca.2016.12.009]
31. Fasshauer M, Bluher M. Adipokines in health and dis. Trends in Pharmacological Sciences 2015; 36(7): 461-470. doi: 10.1016/j.tips.2015.04.014. [DOI:10.1016/j.tips.2015.04.014]
32. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, Inflammation and cancer. Annu Rev Pathol. 2016; 11: 421-449. doi: 10.1146/annurev-pathol-012615-044359. [DOI:10.1146/annurev-pathol-012615-044359]
33. Iwasa T, Matsuzaki T, Matsui S, Tungalagsuvd A, Munkhzaya M, Takiguchi E. et al. The sensitivity of adipose tissue visfatin mRNA expression to lipopolysaccharide-induced endotoxemia is increased by ovariectomy in female rats. International Immunopharmacology. 2016; 35: 243-247. doi: 10.1016/j.intimp.2016.04.002. [DOI:10.1016/j.intimp.2016.04.002]
34. Pavlova T, Novaka J, Bienertova-Vasku B. The role of visfatin (PBEF/Nampt) in pregnancy complications. Journal of Reproductive Immunology 2015; 112: 102–110. doi: 10.1016/j.jri.2015.09.004. [DOI:10.1016/j.jri.2015.09.004]
35. Fahmida K, Farhana AJ, Imran Kh, Omar F, Zahid H, Liaquat A. Increased concentration of circulating visfatin associates with post-challenged hyperglycaemia and insulin resistance in IGT subjects. Journal of Taibah University Medical Sciences 2015; 10(4): 481- 487. doi: 10.1016/j.jtumed.2014.12.007. [DOI:10.1016/j.jtumed.2014.12.007]
36. Pitoulias MG, Skoura L, Pitoulias AG, Chatzidimitriou D, Margariti A, Arsenakis M, et al. The role of Visfatin in atherosclerotic peripheral arterial obstructive disease. Cytokine. 2017; 91: 140–144. doi: 10.1016/j.cyto.2016.12.027. [DOI:10.1016/j.cyto.2016.12.027]
37. Tsai IT, Wang CP, Yu TH, Lu YC, Lin CW, Lu LF, et al. Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection. Cytokine. 2017; 90: 54-59. doi; 10.1016/j.cyto.2016.10.007.
38. Assiria AM, Kamel HF. Evaluation of diagnostic and predictive value of serum adipokines: Leptin, resistin and visfatin in postmenopausal breast cancer. Obesity Research & Clinical Practice. 2016; 10(4): 442–453. doi: 10.1016/j.orcp.2015.08.017. [DOI:10.1016/j.orcp.2015.08.017]
39. Ke HL, Lin HH, Li WM, Li CC, Chang LL, Lee YC, et al. Prognostic Value of Visfatin Protein Overexpression in Upper Tract Urothelial Carcinomas in Taiwan. Abstracts / Urological Science. 2015; 26(2): 50-81. [DOI:10.1016/j.urols.2015.06.120]
40. Wang Y, Gao Ch, Zhang Y, Gao J, Teng F, Tian W, et al. Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways. Gynecologic Oncology 2016; 143(1): 168-178. doi: 10.1016/j.ygyno.2016.07.109. [DOI:10.1016/j.ygyno.2016.07.109]
41. Wang GJ, Shen NJ, Cheng L, Fang Y, Huang H, Li KH. Visfatin triggers the in vitro migration of osteosarcoma cells via activation of NF-κB / IL-6 signals. European Journal of Pharmacology. 2016; 791: 322-330. doi: 10.1016/j.ejphar.2016.08.029. [DOI:10.1016/j.ejphar.2016.08.029]
42. Preyat N, Leo O. Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways. Biochemical Pharmacology. 2016; 101: 13-26. doi: 10.1016/j.bcp.2015.08.110. [DOI:10.1016/j.bcp.2015.08.110]
43. Kim SR, Park HJ, Bae YH, Ahn SC, Wee HJ, Yun I, et al. Curcumin Down-Regulates Visfatin Expression and Inhibits Breast Cancer Cell Invasion. Endocrinology 2012, 153: 554-563. doi: 10.1210/en.2011-1413. PubMed PMID: 22186408. [DOI:10.1210/en.2011-1413]
44. Li Q, Cai Y, Huang J, Yu X, Sun J, Yang Z, et al. Resistin impairs glucose permeability in EA.hy926 cells by down regulating GLUT1 expression. Molecular and Cellular Endocrinology. 2016; 434: 127e134. doi: 10.1016/j.mce.2016.06.025. [DOI:10.1016/j.mce.2016.06.025]
45. Akram Z, Abdul Rahim ZH, Taiyeb-Alic TB, Shahdan MS, Baharuddin NA, Vaithilingam RD. Resistin as potential biomarker for chronic periodontitis: A systematic review and meta-analysis. Archives of Oral Biology. 2017; 73: 311-320. doi:10.1016/j.archoralbio.2016.08.016. [DOI:10.1016/j.archoralbio.2016.08.016]
46. Raghuraman G, Zuniga MC, Yuan H, Zhou W. PKCε mediates resistin-induced NADPH oxidase activation and inflammation leading to smooth muscle cell dysfunction and intimal hyperplasia. Atherosclerosis. 2016; 253: 29-37. doi: 10.1016/j.atherosclerosis.2016.08.015. [DOI:10.1016/j.atherosclerosis.2016.08.015]
47. Al-Asy HM, Mabrouk. MM. Serum resistin as an asthma marker and predictor of inhaled corticosteroid response in bronchial asthma in children. Egyptian Journal of Chest Diseases and Tuberculosis 2016; 66(3): 1-4. doi: 10.1016/j.ejcdt.2016.05.008. [DOI:10.1016/j.ejcdt.2016.05.008]
48. Li Z, Wang X, Pan H, Yang H, Li X, Zhang K, et al. Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-kB signaling pathways: implications for intervertebral disc degeneration. Osteoarthritis and Cartilage. 2017; 25: 341-350. doi: 10.1016/j.joca.2016.10.002. [DOI:10.1016/j.joca.2016.10.002]
49. Antonio de Luis D, Izaola O, Primo D, Aller R, Pacheco D. Effect of two polymorphisms of the resistin gene (rs10401670 and rs1862513) on resistin levels and biochemical parameters in morbidly obese patients 1 year after a biliopancreatic diversion surgery. Clinical Nutrition. 2016; 35(6): 1517-1521. doi: 10.1016/j.clnu.2016.04.005. [DOI:10.1016/j.clnu.2016.04.005]
50. Moreno LO, Lamacchia O, Fontana A, Copetti M, Salvemini L, Bonis CD, et al. The combined effect of adiponectin and resistin on all-cause mortality in patients with type 2 diabetes: Evidence of synergism with abdominal adiposity. Atherosclerosis. 2016; 250: 23-29. doi: 10.1016/j.atherosclerosis.2016.04.028. [DOI:10.1016/j.atherosclerosis.2016.04.028]
51. Ricci C, Corsini A, Accomazzo MR, Rovati G, Camera M, Rossetti L, et al. PCSK9 AND RESISTIN: NOT ONLY A STRUCTURAL SHARING. Abstracts the SISA. e 34. doi: 10.1016j.numecd.2016.11.094
52. Lee S, Lee HC, Kwon YW, Lee SE, Cho Y, Kim J, et al. Adenylyl Cyclase-Associated Protein 1 Is a Receptor for Human Resistin and Mediates Inflammatory Actions of Human Monocytes. Cell Metabolism. 2014; 19(3): 484-497. DOI: 10.1016/j.cmet.2014.01.013. [DOI:10.1016/j.cmet.2014.01.013]
53. Georgiou GP, Provatopoulou X, Kalogera E, Siasos G, Menenakos E, Zografos GC, et al. Serum resistin is inversely related to breast cancer risk in premenopausal women. The Breast. 2016; 29: 163-169. doi: 10.1016/j.breast.2016.07.025. [DOI:10.1016/j.breast.2016.07.025]
54. Dalamaga M, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E, Lekka A. Serum resistin: A biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters. Clinical Biochemistry. 2013; 46(7-8): 584-590. doi: 10.1016/j.clinbiochem.2013.01.001. [DOI:10.1016/j.clinbiochem.2013.01.001]
55. Codo-er-Franch P, Alonso-Iglesias E. Resistin: Insulin resistance to malignancy. Clinica Chimica Acta 2015; 438: 46–54. doi: 10.1016/j.cca.2014.07.043. [DOI:10.1016/j.cca.2014.07.043]
56. Mullen M, Gonzalez-Perez RR. Leptin-Induced JAK/STAT Signaling and Cancer Growth. Vaccines 2016; 4(3): 1-17. doi:10.3390/vaccines4030026. PubMed PMID: 27472371. [DOI:10.3390/vaccines4030026]
57. Barone I, Giordano C, Bonofiglio D, Andò S, Catalano S. Leptin, obesity and breast cancer: progress to understanding the molecular connections. Current Opinion in Pharmacology 2016; 31: 83-89. doi: 10.1016/j.coph.2016.10.003. [DOI:10.1016/j.coph.2016.10.003]
58. Qiao H, Cao Q, Fu Y, Guan W, Cheng F, Wu J, et al. Sex-determining region Y-box 9 acts downstream of NADPH oxidase to influence the effect of leptin on PPARγ1 expression in hepatic stellate cells. Biochimica et Biophysica Acta. 2016; 1862(11): 2186-2196. Doi: 10.1016/j.bbadis.2016.09.001. [DOI:10.1016/j.bbadis.2016.09.001]
59. Xing SQ, Zhang CG, Yuan JF, Yang HM, Zhao SD, Zhang H. Adiponectin induces apoptosis in hepatocellular carcinoma through differential modulation of thioredoxin proteins. Biochemical Pharmacology. 2015; 93(2): 221-231. doi: 10.1016/j.bcp.2014.12.001. [DOI:10.1016/j.bcp.2014.12.001]
60. Nepal S, Shrestha A, Park PH. Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells. Molecular and Cellular Endocrinology. 2015; 412: 44-55. doi:10.1016/j.mce.2015.05.029. [DOI:10.1016/j.mce.2015.05.029]
61. Wang Y, Gao Ch, Zhang Y, Gao J, Teng F, Tian W, et al. Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways. Gynecologic Oncology. 2016; 143(1): 168-178. doi: 10.1016/j.ygyno.2016.07.109. [DOI:10.1016/j.ygyno.2016.07.109]
62. Gumus U, Guzel AI, Topcu HO, Timur H, Yılmaz N, Danısman N. Plasma Visfatin Levels in Adolescents with Polycystic Ovary Syndrome: A Prospective Case-Control Study. Pediatr Adolesc Gynecol. 2015; 28(4): 249-253. doi: 10.1016/j.jpag.2014.08.007. [DOI:10.1016/j.jpag.2014.08.007]
63. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015; 16: 448-457. doi:10.1038/ni.3153. [DOI:10.1038/ni.3153]
64. Sabry D, Al-Ghussein MA, Hamdy G, Abul-Fotouh A, Motawi T, El Kazaz AY, et al. Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients. Therapeutics and Clinical Risk Management. 2015; 11: 279-288. doi:10.2147/TCRM.S66763. [DOI:10.2147/TCRM.S66763]

Add your comments about this article : Your username or Email:

Send email to the article author

© 2007 All Rights Reserved | Medical Laboratory Journal