open access

Ahead of print
Review paper
Published online: 2022-04-06
Get Citation

Benefits of β-blockers in cancer treatment

Mohamad Arif1, Mardiah Suci Hardianti2, Nurina Tyagita3, Azizah Hikma Safitri3
DOI: 10.5603/OCP.2022.0016
Affiliations
  1. Division of Hematology and Medical Oncology, Department of Internal Medicine Science, Faculty of Medicine, Universitas Islam Sultan Agung (UNISSULA)/ Sultan Agung Islamic Hospital, Semarang, Indonezja
  2. Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr. Sardjito Hospital, Yogyakarta, Indonezja
  3. Department of Biochemistry, Faculty of Medicine, Universitas Islam Sultan Agung (UNISSULA), Semarang, Indonezja

open access

Ahead of print
REVIEW ARTICLES
Published online: 2022-04-06

Abstract

Cancer is one of the leading causes of death in the world. Researchers keep attempting to develop therapy modalities to decrease the mortality and morbidity of cancer patients by trying to comprehend the effect of sympathetic nerves (through catecholamine and adrenergic receptors) in cancer development. Catecholamine activation in β-adrenergic receptors (β1-AR, β2-AR, and β3-AR) may influence cytokine and cancer immunity system, initiate tumorigenesis, stimulate tumor-associated macrophage and angiogenesis, influence tumor microenvironment, and facilitate cancer cell metastasis, leading to increased progressivity of cancer cells. β-blockers may inhibit catecholamine on β-AR and various types of paths needed for cancer cells to develop. β-blockers also stimulate cancer cell apoptosis, decrease pro-inflammatory mediators and growth factors of cancer cells. In addition, β-blockers also have benefits as supplementary cancer therapy, increase chemoradiotherapy sensitivity, decrease cardiotoxicity, and improve cancer cachexia. The benefits of β-blockers are expected to reduce morbidity and increase the survival rates of cancer patients. This review comprehensively assesses the benefit of b-blockers as a part of the complete management of cancer patients.

Abstract

Cancer is one of the leading causes of death in the world. Researchers keep attempting to develop therapy modalities to decrease the mortality and morbidity of cancer patients by trying to comprehend the effect of sympathetic nerves (through catecholamine and adrenergic receptors) in cancer development. Catecholamine activation in β-adrenergic receptors (β1-AR, β2-AR, and β3-AR) may influence cytokine and cancer immunity system, initiate tumorigenesis, stimulate tumor-associated macrophage and angiogenesis, influence tumor microenvironment, and facilitate cancer cell metastasis, leading to increased progressivity of cancer cells. β-blockers may inhibit catecholamine on β-AR and various types of paths needed for cancer cells to develop. β-blockers also stimulate cancer cell apoptosis, decrease pro-inflammatory mediators and growth factors of cancer cells. In addition, β-blockers also have benefits as supplementary cancer therapy, increase chemoradiotherapy sensitivity, decrease cardiotoxicity, and improve cancer cachexia. The benefits of β-blockers are expected to reduce morbidity and increase the survival rates of cancer patients. This review comprehensively assesses the benefit of b-blockers as a part of the complete management of cancer patients.

Get Citation

Keywords

catecholamine; β-blockers; cancer; therapy

About this article
Title

Benefits of β-blockers in cancer treatment

Journal

Oncology in Clinical Practice

Issue

Ahead of print

Article type

Review paper

Published online

2022-04-06

Page views

441

Article views/downloads

192

DOI

10.5603/OCP.2022.0016

Keywords

catecholamine
β-blockers
cancer
therapy

Authors

Mohamad Arif
Mardiah Suci Hardianti
Nurina Tyagita
Azizah Hikma Safitri

References (102)
  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–249.
  2. Coelho M, Soares-Silva C, Brandão D, et al. β-Adrenergic modulation of cancer cell proliferation: available evidence and clinical perspectives. J Cancer Res Clin Oncol. 2017; 143(2): 275–291.
  3. Wehrwein EA, Orer HS, Barman SM. Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System. Compr Physiol. 2016; 6(3): 1239–1278.
  4. Rains SL, Amaya CN, Bryan BA. Beta-adrenergic receptors are expressed across diverse cancers. Oncoscience. 2017; 4(7-8): 95–105.
  5. Cole SW, Sood AK. Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res. 2012; 18(5): 1201–1206.
  6. do Vale GT, Ceron CS, Gonzaga NA, et al. Three Generations of β-blockers: History, Class Differences and Clinical Applicability. Curr Hypertens Rev. 2019; 15(1): 22–31.
  7. Berg T. β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats. Front Neurol. 2014; 5: 51.
  8. Peixoto R, Pereira Md, Oliveira M. Beta-Blockers and Cancer: Where Are We? Pharmaceuticals (Basel). 2020; 13(6).
  9. Gujral DM, Lloyd G, Bhattacharyya S. Effect of prophylactic betablocker or ACE inhibitor on cardiac dysfunction & heart failure during anthracycline chemotherapy ± trastuzumab. Breast. 2018; 37: 64–71.
  10. Chen H, Zhang W, Cheng X, et al. β2-AR activation induces chemoresistance by modulating p53 acetylation through upregulating Sirt1 in cervical cancer cells. Cancer Science. 2017; 108(7): 1310–1317.
  11. Qiao G, Chen M, Bucsek MJ, et al. Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response. Front Immunol. 2018; 9: 164.
  12. Qin Jf, Jin Fj, Li N, et al. Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment. BMB Rep. 2015; 48(5): 295–300.
  13. Shakhar G, Ben-eliyahu S. In Vivo Beta Adrenergic Stimulation Suppresses Natural Killer Activity and Compromises Resistance to Tumor Metastasis in Rats. J Immunol. 1998; 160(7): 3251–3258.
  14. Pu J, Zhang X, Luo H, et al. Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis. Biochem Biophys Res Commun. 2017; 493(3): 1273–1279.
  15. Drell TL, Joseph J, Lang K, et al. Effects of Neurotransmitters on the Chemokinesis and Chemotaxis of MDA-MB-468 Human Breast Carcinoma Cells. Breast Cancer Research and Treatment. 2003; 80(1): 63–70.
  16. Xia Y, Wei Ye, Li ZY, et al. Catecholamines contribute to the neovascularization of lung cancer via tumor-associated macrophages. Brain Behav Immun. 2019; 81: 111–121.
  17. Srinivas US, Tan BWQ, Vellayappan BA, et al. ROS and the DNA damage response in cancer. Redox Biol. 2019; 25: 101084.
  18. Dai S, Mo Y, Wang Y, et al. Chronic Stress Promotes Cancer Development. Front Oncol. 2020; 10: 1492.
  19. Lamboy-Caraballo R, Ortiz-Sanchez C, Acevedo-Santiago A, et al. Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells. Int J Mol Sci. 2020; 21(6).
  20. Flint MS, Baum A, Episcopo B, et al. Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts. Stress. 2013; 16(1): 114–121.
  21. Hara MR, Kovacs JJ, Whalen EJ, et al. A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. Nature. 2011; 477(7364): 349–353.
  22. Eng JWL, Kokolus KM, Reed CB, et al. A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response. Cancer Immunol Immunother. 2014; 63(11): 1115–1128.
  23. Allen LF, Lefkowitz RJ, Caron MG, et al. G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity. Proc Natl Acad Sci U S A. 1991; 88(24): 11354–11358.
  24. Jang HJ, Boo HJ, Lee HoJ, et al. Chronic Stress Facilitates Lung Tumorigenesis by Promoting Exocytosis of IGF2 in Lung Epithelial Cells. Cancer Res. 2016; 76(22): 6607–6619.
  25. Choi MJ, Cho KH, Lee S, et al. hTERT mediates norepinephrine-induced Slug expression and ovarian cancer aggressiveness. Oncogene. 2015; 34(26): 3402–3412.
  26. Chisholm KM, Chang KW, Truong MT, et al. β-Adrenergic receptor expression in vascular tumors. Mod Pathol. 2012; 25(11): 1446–1451.
  27. Chakroborty D, Sarkar C, Basu B, et al. Catecholamines regulate tumor angiogenesis. Cancer Res. 2009; 69(9): 3727–3730.
  28. Thaker PH, Han LY, Kamat AA, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006; 12(8): 939–944.
  29. Garg J, Feng YX, Jansen SR, et al. Catecholamines facilitate VEGF-dependent angiogenesis via β2-adrenoceptor-induced Epac1 and PKA activation. Oncotarget. 2017; 8(27): 44732–44748.
  30. Zahalka AH, et al. Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science (80-. ). 2017; 358: 321–326.
  31. Wang W, Li L, Chen N, et al. Nerves in the Tumor Microenvironment: Origin and Effects. Front Cell Dev Biol. 2020; 8: 601738.
  32. Santi A, Kugeratski FG, Zanivan S. Cancer Associated Fibroblasts: The Architects of Stroma Remodeling. Proteomics. 2018; 18(5-6): e1700167.
  33. Calvani M, Pelon F, Comito G, et al. Norepinephrine promotes tumor microenvironment reactivity through β3-adrenoreceptors during melanoma progression. Oncotarget. 2015; 6(7): 4615–4632.
  34. Chiarugi P, Filippi L. β3-adrenoreceptor and tumor microenvironment: a new hub. Oncoimmunology. 2015; 4(11): e1026532.
  35. Hanns P, Paczulla AM, Medinger M, et al. Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis. Cell Stress. 2019; 3(7): 221–235.
  36. Boilly B, Faulkner S, Jobling P, et al. Nerve Dependence: From Regeneration to Cancer. Cancer Cell. 2017; 31(3): 342–354.
  37. Hondermarck H, Jobling P. The Sympathetic Nervous System Drives Tumor Angiogenesis. Trends Cancer. 2018; 4(2): 93–94.
  38. Mravec B, Horvathova L, Hunakova L. Neurobiology of Cancer: the Role of β-Adrenergic Receptor Signaling in Various Tumor Environments. Int J Mol Sci. 2020; 21(21).
  39. Wang F, Liu H, Wang F, et al. Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells. Mol Med Rep. 2018; 17(4): 5213–5221.
  40. Bravo-Calderón DM, Assao A, Garcia NG, et al. Beta adrenergic receptor activation inhibits oral cancer migration and invasiveness. Arch Oral Biol. 2020; 118: 104865.
  41. Vojvodic A, Vojvodic P, Vlaskovic-Jovicevic T, et al. Beta Blockers and Melanoma. Open Access Macedonian Journal of Medical Sciences. 2019; 7(18): 3110–3112.
  42. De Giorgi V, Geppetti P, Lupi C, et al. The Role of β-Blockers in Melanoma. J Neuroimmune Pharmacol. 2020; 15(1): 17–26.
  43. Bustamante P, Miyamoto D, Goyeneche A, et al. Beta‐blockers exert potent anti‐tumor effects in cutaneous and uveal melanoma. Cancer Medicine. 2019; 8(17): 7265–7277.
  44. Zhao S, Fan S, Shi Y, et al. Propranolol induced apoptosis and autophagy the ROS/JNK signaling pathway in Human Ovarian Cancer. J Cancer. 2020; 11(20): 5900–5910.
  45. Barathova M, Grossmannova K, Belvoncikova P, et al. Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol-Impact on Progression and Metastatic Potential of Colorectal Cancer Cells. Int J Mol Sci. 2020; 21(22).
  46. Ashrafi S, Shapouri R, Shirkhani A, et al. Anti-tumor effects of propranolol: Adjuvant activity on a transplanted murine breast cancer model. Biomed Pharmacother. 2018; 104: 45–51.
  47. Liao P, Song K, Zhu Z, et al. Propranolol Suppresses the Growth of Colorectal Cancer Through Simultaneously Activating Autologous CD8 T Cells and Inhibiting Tumor AKT/MAPK Pathway. Clin Pharmacol Ther. 2020; 108(3): 606–615.
  48. Chang A, Yeung S, Thakkar A, et al. Prevention of skin carcinogenesis by the β-blocker carvedilol. Cancer Prev Res (Phila). 2015; 8(1): 27–36.
  49. Huang KM, Liang S, Yeung S, et al. Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis. Cancer Prev Res (Phila). 2017; 10(10): 598–606.
  50. Chen M, Shamim MdA, Shahid A, et al. Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention. Pharmaceutics. 2020; 12(12).
  51. Ma Z, Liu X, Zhang Q, et al. Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway. Oncol Rep. 2019; 41(2): 811–818.
  52. Nuevo-Tapioles C, Santacatterina F, Stamatakis K, et al. Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth. Nat Commun. 2020; 11(1): 3606.
  53. Chen Q, Jiang H, Wang Z, et al. Adrenergic Blockade by Nebivolol to Suppress Oral Squamous Cell Carcinoma Growth Endoplasmic Reticulum Stress and Mitochondria Dysfunction. Front Pharmacol. 2021; 12: 691998.
  54. Montoya A, Amaya CN, Belmont A, et al. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer. Oncotarget. 2017; 8(4): 6446–6460.
  55. Montoya A, Varela-Ramirez A, Dickerson E, et al. The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer. Biomed J. 2019; 42(3): 155–165.
  56. Barron TI, Connolly RM, Sharp L, et al. Beta blockers and breast cancer mortality: a population- based study. J Clin Oncol. 2011; 29(19): 2635–2644.
  57. Hiller J, Cole S, Crone E, et al. Preoperative β-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial. Clinical Cancer Research. 2019; 26(8): 1803–1811.
  58. Pantziarka P, Bryan BA, Crispino S, et al. Propranolol and breast cancer-a work in progress. Ecancermedicalscience. 2018; 12: ed82.
  59. Haldar R, Ricon-Becker I, Radin A, et al. Perioperative COX2 and β-adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial. Cancer. 2020; 126(17): 3991–4001.
  60. Chang CH, Lee CH, Ko JC, et al. Effect of β-Blocker in Treatment-Naïve Patients With Advanced Lung Adenocarcinoma Receiving First-Generation EGFR-TKIs. Front Oncol. 2020; 10: 583529.
  61. Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: A nationwide population-based study. PLoS One. 2019; 14(5): e0216828.
  62. Lin CS, Lin WS, Lin CL, et al. Carvedilol use is associated with reduced cancer risk: A nationwide population-based cohort study. Int J Cardiol. 2015; 184: 9–13.
  63. Wijarnpreecha K, Li F, Xiang Y, et al. Nonselective beta-blockers are associated with a lower risk of hepatocellular carcinoma among cirrhotic patients in the United States. Aliment Pharmacol Ther. 2021; 54(4): 481–492.
  64. Gillis RD, Botteri E, Chang A, et al. Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients. Eur J Cancer. 2021; 147: 106–116.
  65. Chaudhary KR, Yan SX, Heilbroner SP, et al. Effects of β-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. J Clin Med. 2019; 8(5).
  66. Saha J, Kim JH, Amaya CN, et al. Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux. Front Oncol. 2020; 10: 614288.
  67. Calvani M, Dabraio A, Bruno G, et al. β3-Adrenoreceptor Blockade Reduces Hypoxic Myeloid Leukemic Cells Survival and Chemoresistance. Int J Mol Sci. 2020; 21(12).
  68. Liao X, Chaudhary P, Qiu G, et al. The role of propranolol as a radiosensitizer in gastric cancer treatment. Drug Des Devel Ther. 2018; 12: 639–645.
  69. Duckett MM, Phung SK, Nguyen L, et al. The adrenergic receptor antagonists propranolol and carvedilol decrease bone sarcoma cell viability and sustained carvedilol reduces clonogenic survival and increases radiosensitivity in canine osteosarcoma cells. Vet Comp Oncol. 2020; 18(1): 128–140.
  70. Farhood B, Najafi M, Mortezaee K. CD8 cytotoxic T lymphocytes in cancer immunotherapy: A review. J Cell Physiol. 2019; 234(6): 8509–8521.
  71. Nissen MD, Sloan EK, Mattarollo SR. β-Adrenergic Signaling Impairs Antitumor CD8 T-cell Responses to B-cell Lymphoma Immunotherapy. Cancer Immunol Res. 2018; 6(1): 98–109.
  72. Oh MS, Guzner A, Wainwright DA, et al. The Impact of Beta Blockers on Survival Outcomes in Patients With Non-small-cell Lung Cancer Treated With Immune Checkpoint Inhibitors. Clin Lung Cancer. 2021; 22(1): e57–e62.
  73. Carrasco R, Castillo RL, Gormaz JG, et al. Role of Oxidative Stress in the Mechanisms of Anthracycline-Induced Cardiotoxicity: Effects of Preventive Strategies. Oxid Med Cell Longev. 2021; 2021: 8863789.
  74. Songbo M, Lang H, Xinyong C, et al. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett. 2019; 307: 41–48.
  75. Sawicki KT, Sala V, Prever L, et al. Preventing and Treating Anthracycline Cardiotoxicity: New Insights. Annu Rev Pharmacol Toxicol. 2021; 61: 309–332.
  76. Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, et al. Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial. J Am Coll Cardiol. 2018; 71(20): 2281–2290.
  77. Barbosa RR, Bourguignon TB, Torres LD, et al. Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers. Rev Assoc Med Bras (1992). 2018; 64(8): 745–754.
  78. Huang S, Zhao Q, Yang ZG, et al. Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol. Heart Fail Rev. 2019; 24(3): 325–333.
  79. Guglin M, Krischer J, Tamura R, et al. Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. J Am Coll Cardiol. 2019; 73(22): 2859–2868.
  80. Cochera F, Dinca D, Bordejevic DA, et al. Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer. Cancer Manag Res. 2018; 10: 2071–2081.
  81. Mohamed EA, Kassem HH. Protective effect of nebivolol on doxorubicin-induced cardiotoxicity in rats. Arch Med Sci. 2018; 14(6): 1450–1458.
  82. Cadeddu Dessalvi C, Deidda M, Noto A, et al. Antioxidant Approach as a Cardioprotective Strategy in Chemotherapy-Induced Cardiotoxicity. Antioxid Redox Signal. 2021; 34(7): 572–588.
  83. Shoukat S, Zheng D, Yusuf SW. Cardiotoxicity Related to Radiation Therapy. Cardiol Clin. 2019; 37(4): 449–458.
  84. Madan R, Benson R, Sharma DN, et al. Radiation induced heart disease: Pathogenesis, management and review literature. J Egypt Natl Canc Inst. 2015; 27(4): 187–193.
  85. Curigliano G, Lenihan D, Fradley M, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020; 31(2): 171–190.
  86. Ni J, Zhang Li. Cancer Cachexia: Definition, Staging, and Emerging Treatments. Cancer Manag Res. 2020; 12: 5597–5605.
  87. Argilés JM, López-Soriano FJ, Stemmler B, et al. Therapeutic strategies against cancer cachexia. Eur J Transl Myol. 2019; 29(1): 7960.
  88. Belloum Y, Rannou-Bekono F, Favier FB. Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review). Oncol Rep. 2017; 37(5): 2543–2552.
  89. Barkhudaryan A, Scherbakov N, Springer J, et al. Cardiac muscle wasting in individuals with cancer cachexia. ESC Heart Fail. 2017; 4(4): 458–467.
  90. Rolfe M, Kamel A, Ahmed MM, et al. Pharmacological management of cardiac cachexia: a review of potential therapy options. Heart Fail Rev. 2019; 24(5): 617–623.
  91. Murphy KT. The pathogenesis and treatment of cardiac atrophy in cancer cachexia. Am J Physiol Heart Circ Physiol. 2016; 310(4): H466–H477.
  92. Stewart Coats AJ, Ho GF, Prabhash K, et al. for and on behalf of the ACT‐ONE study group. Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer: a randomized, double-blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial). J Cachexia Sarcopenia Muscle. 2016; 7(3): 355–365.
  93. Zhong S, Yu D, Zhang X, et al. β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Eur J Cancer Prev. 2016; 25(5): 440–448.
  94. Choi CH, Song T, Kim TH, et al. Meta-analysis of the effects of beta blocker on survival time in cancer patients. J Cancer Res Clin Oncol. 2014; 140(7): 1179–1188.
  95. Na Z, Qiao X, Hao X, et al. The effects of beta-blocker use on cancer prognosis: a meta-analysis based on 319,006 patients. Onco Targets Ther. 2018; 11: 4913–4944.
  96. Powe D, Voss M, Zänker K, et al. Beta-Blocker Drug Therapy Reduces Secondary Cancer Formation in Breast Cancer and Improves Cancer Specific Survival. Oncotarget. 2010; 1(7): 628–638.
  97. Yap A, Lopez-Olivo MA, Dubowitz J, et al. Effect of beta-blockers on cancer recurrence and survival: a meta-analysis of epidemiological and perioperative studies. Br J Anaesth. 2018; 121(1): 45–57.
  98. Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Oncogenic. 2019; 173(2): 321–337.
  99. Cullen J, Breen M. An Overview of Molecular Cancer Pathogenesis, Prognosis, and Diagnosis. Tumors in Domestic Animals. 2016: 1–26.
  100. Rafiemanesh H, Mehtarpour M, Khani F, et al. Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world. J Thorac Dis. 2016; 8(6): 1094–1102.
  101. Weberpals J, Jansen L, Carr PR, et al. Beta blockers and cancer prognosis - The role of immortal time bias: A systematic review and meta-analysis. Cancer Treat Rev. 2016; 47: 1–11.
  102. Weberpals J, Jansen L, van Herk-Sukel MPP, et al. Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis. Eur J Epidemiol. 2017; 32(11): 1019–1031.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl