Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytok...Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation.While the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,cachexia.In this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome.展开更多
It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by sys...It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.展开更多
文摘Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation.While the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,cachexia.In this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome.
基金Supported by NIH,No.R01CA160688 and No.T32CA085159-10
文摘It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.
文摘目的探讨消岩汤治疗肺癌恶病质的可能作用机制。方法将40只小鼠随机分为健康组、模型组、消岩汤组、醋酸甲地孕酮组,每组10只。除健康组外,其余各组通过接种肿瘤细胞建立肺癌恶病质模型。造模成功后模型组小鼠每日灌服生理盐水1 ml,消岩汤组每日灌服消岩汤0.42 g,醋酸甲地孕酮组每日灌服醋酸甲地孕酮3.75 mg/d,均给药14天。测定腓肠肌重量,血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量及肌肉萎缩盒F基因(MAFbx)和肌肉环状指基因1(MURF-1)m RNA表达。结果与健康组比较,模型组腓肠肌重量下降,模型组和醋酸甲地孕酮组TNF-α、IL-6水平及MAFbx、MURF-1m RNA表达均明显上升(P<0.01);与模型组比较,消岩汤组腓肠肌重量明显增加,血清TNF-α、IL-6水平及MAFbx、MURF-1 m RNA表达均明显下降(P<0.05或P<0.01),醋酸甲地孕酮组TNF-α、IL-6水平均明显下降(P<0.05);醋酸甲地孕酮组腓肠肌重量明显低于消岩汤组(P<0.01),血清TNF-α、IL-6水平及MAFbx、MURF-1 m RNA表达明显高于消岩汤组(P<0.05或P<0.01)。结论消岩汤可能通过减少炎症细胞因子产生,抑制MAFbx和MURF-1基因表达,改善肺癌恶病质肌肉蛋白质降解,从而改善肺癌恶病质状态。
