肿瘤恶液质及肿瘤治疗相关并发症的生物标记物
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摘要
肿瘤恶液质是一种涉及全身多个系统的多因素综合征,表现为患者正在丢失骨骼肌质量,而传统营养治疗不能完全逆转,继而引起功能损伤的持续恶化,最终导致体重、免疫功能及抗肿瘤治疗耐受性下降,是肿瘤患者常见并发症和致死的主要原因。同时,当肿瘤患者在接受放化疗等积极治疗时,因其治疗具有一定的创伤性,所以治疗相关并发症的发生风险很高,常常导致患者耐受性降低,依从性下降,进而影响患者的后续治疗,更严重者甚至危及患者的生命。由此可见,恶液质及肿瘤治疗相关并发症是目前困扰肿瘤治疗的两大难题,如何尽早诊断恶液质、监测恶液质的进程以及预测肿瘤治疗相关并发症已经成为目前亟待解决的问题。众所周知,生物标记物的测定可以获知机体当前所处的生物学过程中的进程,其以准确、敏感以及低水平的损害等特点在这方面有着独特的优势,目前针对肿瘤恶液质及治疗相关并发症的生物标记物已得到人们的初步认识,这将有助于有效的防止肿瘤恶液质的发生及调整肿瘤治疗方案。
Cancer cachexia is a multifactor syndrome involving multiple systems in the whole body. It is manifested in the loss of skeletal muscle mass, while traditional nutritional support can not be completely reversed, which leads to continuous deterioration of functional damage, resulting in loss of weight, immune function and resistance to cancer treatment, which is a common complication of cancer patients and the main cause of death. At the same time, when the cancer patients receive active treatment such as chemotherapy, radiotherapy and others, the treatment has a certain traumatic effect, so the risk of the treatment related complications is very high, which often leads to a decline in patient tolerance and compliance, which will affect the followup treatment, and even more serious may endanger the life of patients. Thus it can be seen, carcinemia and cancer treatment related complications are the two major problems that currently plaguing cancer treatment.It is highly demanded that cachexia be diagnosed, its progression be monitored and the complications of cancer treatment be predicted timely at present. As we all know, the determination of biomarkers can be used to understand the biological processes in the body, so biomarkers have unique advantages in identifying accurate, sensitive and low levels of damage. Moreover, the recognition of biomarkers' significance in carcinemia and its treatment related complications could facilitate the prevention of carcinemia and the adjustment of cancer treatment programs effectively.
Cancer cachexia is a multifactor syndrome involving multiple systems in the whole body. It is manifested in the loss of skeletal muscle mass, while traditional nutritional support can not be completely reversed, which leads to continuous deterioration of functional damage, resulting in loss of weight, immune function and resistance to cancer treatment, which is a common complication of cancer patients and the main cause of death. At the same time, when the cancer patients receive active treatment such as chemotherapy, radiotherapy and others, the treatment has a certain traumatic effect, so the risk of the treatment related complications is very high, which often leads to a decline in patient tolerance and compliance, which will affect the followup treatment, and even more serious may endanger the life of patients. Thus it can be seen, carcinemia and cancer treatment related complications are the two major problems that currently plaguing cancer treatment.It is highly demanded that cachexia be diagnosed, its progression be monitored and the complications of cancer treatment be predicted timely at present. As we all know, the determination of biomarkers can be used to understand the biological processes in the body, so biomarkers have unique advantages in identifying accurate, sensitive and low levels of damage. Moreover, the recognition of biomarkers' significance in carcinemia and its treatment related complications could facilitate the prevention of carcinemia and the adjustment of cancer treatment programs effectively.
引文
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2.Loberg RD,Bradley DA,Tomlins SA,et al.The lethal phenotype of cancer:the molecular basis of death due to malignancy.CACancer J Clin.2007;57(4):225-241.
3.罗智鹏,石华伟,薛瑶纯,等.常见恶性肿瘤患者的营养状况与临床结局的相关性研究.肿瘤代谢与营养电子杂志.2017;4(2):174-178.
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11.贾淑云,王敏.胃癌恶病质患者血清瘦素水平的变化.宁夏医科大学学报.2009;31(4):497-499.
12.Song YH,Li Y,Du J,et al.Muscle-specifc expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting.J Clin Invest.2005;115(2):451-458.
13.Trobec K,von Haehling S,Anker SD,et al.Growth hormone,insulinlike growth factor 1,and insulin signaling-a pharmacological target in body wasting and cachexia.J Cachexia Sarcopenia Muscle.2011;2(4):191-200.
14.Yoshida T,Tabony AM,Galvez S,et al.Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting:potential therapeutic targets for cardiac cachexia.Int J Biochem Cell Biol.2013;45(10):2322-2332.
15.Penafuerte CA,Gagnon B,Sirois J,et al.Identifcation of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.Br J Cancer.2016;114(6):680-687.
16.Sanders PM,Russell ST,Tisdale MJ.Angiotensin II directly induces muscle protein catabolism through the ubiquitinproteasome proteolytic pathway and may play a role in cancer cachexia.Br J Cancer.2005;93(4):425-434.
17.el-Far M,Fouda M,Yahya R,et al.Serum IL-10 and IL-6 levels at diagnosis as independent predictors of outcome in non-Hodgkin’s lymphoma.J Physiol Biochem.2004;60(4):253-258.
18.Tan BH,Deans DA,Skipworth RJ,et al.Biomarkers for cancer cachexia:is there also a genetic component to cachexia?Support Care Cancer.2008;16(3):229-234.
19.Kayacan O,Karnak D,Beder S,et al.Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.Am J Clin Oncol.2006;29(4):328-335.
20.Guttridge DC.A TGF-beta pathway associated with cancer cachexia.Nat Med.2015;21(11):1248-1249.
21.Lerner L,Hayes TG,Tao N,et al.Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.J Cachexia Sarcopenia Muscle.2015;6(4):317-324.
22.余日臻,许静.MicroRNA与肌肉萎缩.第二军医大学学报.2015;36(12):1339-1343.
23.He WA,Calore F,Londhe P,et al.Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7.Proc Natl Acad Sci USA.2014;111(12):4525-4529.
24.Kulyte A,Lorente-Cebrian S,Gao H,et al.MicroRNA profling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia.Am J Physiol Endocrinol Metab.2014;306(3):E267-E274.
25.Lutgens LC,Blijlevens NM,Deutz NE,et al.Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration:a comparison with sugar permeability tests.Cancer.2005;103(1):191-199.
26.Tooley KL,Howarth GS,Butler RN.Mucositis and noninvasive markers of small intestinal function.Cancer Biol Ther.2009;8(9):753-758.
27.van der Velden WJ,Herbers AH,Bruggemann RJ,et al.Citrulline and albumin as biomarkers for gastrointestinal mucositis in recipients of hematopoietic SCT.Bone Marrow Transplant.2013;48(7):977-981.
28.Stringer AM,Al-Dasooqi N,Bowen JM,et al.Biomarkers of chemotherapy-induced diarrhoea:a clinical study of intestinal microbiome alterations,inflammation and circulating matrix metalloproteinases.Support Care Cancer.2013;21(7):1843-1852.
29.Wierdsma NJ,Peters JH,Weijs PJ,et al.Malabsorption and nutritional balance in the ICU:fecal weight as a biomarker:a prospective observational pilot study.Crit Care.2011;15(6):R264.
30.Cannon B,Schwartz DL,Dong L.Metabolic imaging biomarkers of post radiotherapy xerostomia.Int J Radiat Oncol Biol Phys.2012;83(5):1609-1616.
31.Chai Y,Wang J,Gao Y,et al.Identifcation of biomarkers for radiation-induced acute intestinal symptoms(RIAISs)in cervical cancer patients by serum protein profiling.J Radiat Res.2015;56(1):134-140.
32.应丽美,陈芳芳,陈艺丹,等.国内肿瘤患者的营养风险及营养不良研究现状分析.肿瘤代谢与营养电子杂志.2017;4(2):226-231.
33.Baldwin C,Spiro A,Ahern R,et al.Oral nutritional interventions in malnourished patients with cancer:a systematic review and metaanalysis.J Natl Cancer Inst.2012;104(5):371-385.
2.Loberg RD,Bradley DA,Tomlins SA,et al.The lethal phenotype of cancer:the molecular basis of death due to malignancy.CACancer J Clin.2007;57(4):225-241.
3.罗智鹏,石华伟,薛瑶纯,等.常见恶性肿瘤患者的营养状况与临床结局的相关性研究.肿瘤代谢与营养电子杂志.2017;4(2):174-178.
4.Hsu TM,Suarez AN,Kanoski SE.Ghrelin:a link between memory and ingestive behavior.Physiol Behav.2016;162:10-17.
5.Mondello P,Lacquaniti A,Mondello S,et al.Emerging markers of cachexia predict survival in cancer patients.BMC Cancer.2014;14(1):828.
6.Nikolopoulos D,Theocharis S,Moutsios-Rentzos A,et al.The role of serum total ghrelin level elevation in colon cancer patients.JBUON.2014;19(2):388-393.
7.Takahashi M,Terashima M,Takagane A,et al.Ghrelin and leptin levels in cachectic patients with cancer of the digestive organs.Int J Clin Oncol.2009;14(4):315-320.
8.Garcia JM,Garcia-Touza M,Hijazi RA,et al.Active ghrelin levels and active to total ghrelin ratio in cancerinduced cachexia.J Clin Endocrinol Metab.2005;90(5):2920-2926.
9.Inacio Pinto N,Carnier J,Oyama LM,et al.Cancer as a proinflammatory environment:metastasis and cachexia.Mediators Inflamm.2015;2015:791060.
10.曲晓翰,韩立波.瘦素及其受体与肺癌关系的研究进展.中国肺癌杂志.2008;11(6):821-823.
11.贾淑云,王敏.胃癌恶病质患者血清瘦素水平的变化.宁夏医科大学学报.2009;31(4):497-499.
12.Song YH,Li Y,Du J,et al.Muscle-specifc expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting.J Clin Invest.2005;115(2):451-458.
13.Trobec K,von Haehling S,Anker SD,et al.Growth hormone,insulinlike growth factor 1,and insulin signaling-a pharmacological target in body wasting and cachexia.J Cachexia Sarcopenia Muscle.2011;2(4):191-200.
14.Yoshida T,Tabony AM,Galvez S,et al.Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting:potential therapeutic targets for cardiac cachexia.Int J Biochem Cell Biol.2013;45(10):2322-2332.
15.Penafuerte CA,Gagnon B,Sirois J,et al.Identifcation of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.Br J Cancer.2016;114(6):680-687.
16.Sanders PM,Russell ST,Tisdale MJ.Angiotensin II directly induces muscle protein catabolism through the ubiquitinproteasome proteolytic pathway and may play a role in cancer cachexia.Br J Cancer.2005;93(4):425-434.
17.el-Far M,Fouda M,Yahya R,et al.Serum IL-10 and IL-6 levels at diagnosis as independent predictors of outcome in non-Hodgkin’s lymphoma.J Physiol Biochem.2004;60(4):253-258.
18.Tan BH,Deans DA,Skipworth RJ,et al.Biomarkers for cancer cachexia:is there also a genetic component to cachexia?Support Care Cancer.2008;16(3):229-234.
19.Kayacan O,Karnak D,Beder S,et al.Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.Am J Clin Oncol.2006;29(4):328-335.
20.Guttridge DC.A TGF-beta pathway associated with cancer cachexia.Nat Med.2015;21(11):1248-1249.
21.Lerner L,Hayes TG,Tao N,et al.Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.J Cachexia Sarcopenia Muscle.2015;6(4):317-324.
22.余日臻,许静.MicroRNA与肌肉萎缩.第二军医大学学报.2015;36(12):1339-1343.
23.He WA,Calore F,Londhe P,et al.Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7.Proc Natl Acad Sci USA.2014;111(12):4525-4529.
24.Kulyte A,Lorente-Cebrian S,Gao H,et al.MicroRNA profling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia.Am J Physiol Endocrinol Metab.2014;306(3):E267-E274.
25.Lutgens LC,Blijlevens NM,Deutz NE,et al.Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration:a comparison with sugar permeability tests.Cancer.2005;103(1):191-199.
26.Tooley KL,Howarth GS,Butler RN.Mucositis and noninvasive markers of small intestinal function.Cancer Biol Ther.2009;8(9):753-758.
27.van der Velden WJ,Herbers AH,Bruggemann RJ,et al.Citrulline and albumin as biomarkers for gastrointestinal mucositis in recipients of hematopoietic SCT.Bone Marrow Transplant.2013;48(7):977-981.
28.Stringer AM,Al-Dasooqi N,Bowen JM,et al.Biomarkers of chemotherapy-induced diarrhoea:a clinical study of intestinal microbiome alterations,inflammation and circulating matrix metalloproteinases.Support Care Cancer.2013;21(7):1843-1852.
29.Wierdsma NJ,Peters JH,Weijs PJ,et al.Malabsorption and nutritional balance in the ICU:fecal weight as a biomarker:a prospective observational pilot study.Crit Care.2011;15(6):R264.
30.Cannon B,Schwartz DL,Dong L.Metabolic imaging biomarkers of post radiotherapy xerostomia.Int J Radiat Oncol Biol Phys.2012;83(5):1609-1616.
31.Chai Y,Wang J,Gao Y,et al.Identifcation of biomarkers for radiation-induced acute intestinal symptoms(RIAISs)in cervical cancer patients by serum protein profiling.J Radiat Res.2015;56(1):134-140.
32.应丽美,陈芳芳,陈艺丹,等.国内肿瘤患者的营养风险及营养不良研究现状分析.肿瘤代谢与营养电子杂志.2017;4(2):226-231.
33.Baldwin C,Spiro A,Ahern R,et al.Oral nutritional interventions in malnourished patients with cancer:a systematic review and metaanalysis.J Natl Cancer Inst.2012;104(5):371-385.