Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CAC...Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.展开更多
Objective:To investigate the therapeutic effects and safety of Dioscorea Decoction combined with Coix Seed in treating cancer cachexia(spleen-kidney Yang deficiency syndrome)in malignant tumor patients.Methods:A total...Objective:To investigate the therapeutic effects and safety of Dioscorea Decoction combined with Coix Seed in treating cancer cachexia(spleen-kidney Yang deficiency syndrome)in malignant tumor patients.Methods:A total of 90 patients with cancer cachexia admitted between June 2024 and June 2025 were randomly divided into a control group and a study group(45 cases each)using a random number generator.Both groups received antitumor therapy,oral megestrol acetate capsules,and conventional nutritional intervention.The study group additionally received oral Dioscorea Decoction combined with Coix Seed.Differences in TCM syndrome scores,nutritional indicators(serum albumin,hemoglobin),and adverse reactions were compared before and after treatment.Results:Baseline TCM syndrome scores and nutritional indicators were comparable between the two groups before treatment.After treatment,both groups showed significant reductions in TCM syndrome scores and increases in serum albumin and hemoglobin levels.The study group exhibited lower TCM syndrome scores and higher serum albumin and hemoglobin levels than the control group,with statistically significant differences.No significant difference in adverse reaction rates was observed between the two groups.Conclusion:Dioscorea Decoction combined with Coix Seed can further improve nutritional status,alleviate clinical symptoms,and demonstrate good safety in treating cancer cachexia patients.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
Objective: The aim of this study is to summarize preclinical studies on herbal medicines used to treat cancer cachexia and its underlying mechanisms. Methods: We searched four representing databases, including Pub Med...Objective: The aim of this study is to summarize preclinical studies on herbal medicines used to treat cancer cachexia and its underlying mechanisms. Methods: We searched four representing databases, including Pub Med, EMBASE, the Allied and Complementary Medicine Database, and the Web of Science up to December 2016. Randomized animal studies were included if the effects of any herbal medicine were tested on cancer cachexia. The methodological quality was evaluated by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies(CAMARADE) checklist. Results: A total of fourteen herbal medicines and their compounds were identified, including Coptidis Rhizoma, berberine, Bing De Ling, curcumin, Qing-Shu-Yi-Qi-Tang, Scutellaria baicalensis, Hochuekkito, Rikkunshito, hesperidin, atractylodin, Sipjeondaebo-tang, Sosiho-tang, Anemarrhena Rhizoma, and Phellodendri Cortex. All the herbal medicines, except curcumin, have been shown to ameliorate the symptoms of cancer cachexia through anti-inflammation, regulation of the neuroendocrine pathway, and modulation of the ubiquitin proteasome system or protein synthesis. Conclusions: This study showed that herbal medicines might be a useful approach for treating cancer cachexia. However, more detailed experimental studies on the molecular mechanisms and active compounds are needed.展开更多
Pancreatic cancer(PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly...Pancreatic cancer(PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies. Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta(TGF-β), myostatin and activin, IGF-1/PI3 K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3(IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting.Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6(IL-6), tumor necrosis factoralpha(TNF-α), and interferon gamma(INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.展开更多
Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and...Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.展开更多
Heart Failure(HF)in elderly patients is a systemic syndrome where advanced age,comorbidities with organ system deterioration,frailty and impaired cognition significantly impact outcome.Cardiac cachexia,sarcopenia and ...Heart Failure(HF)in elderly patients is a systemic syndrome where advanced age,comorbidities with organ system deterioration,frailty and impaired cognition significantly impact outcome.Cardiac cachexia,sarcopenia and frailty despite overlap in definitions are different clinical entities that frequently coexist in HF patients.However,these co-factors often remain unaddressed,resulting in poor quality-of-life,prolonged physical disability and exercise intolerance and finally with higher rehospitalization rates and mortality.Strategy aim to increase muscle mass and muscle strength and delay the occurrence of frailty state appear essential in this regard.Common HF drugs therapy(b-blockers,angiotensinconverting enzyme inhibitors)and prescription of physical exercise program remain the cornerstone of therapeutic approach in HF patients with new promising data regarding nutritional supplementation.However,the treatment of all these conditions still remain debated and only a profound knowledge of the specific mechanisms and patterns of disease progression will allow to use the appropriate therapy in a given clinical setting.For all these reasons we briefly review current knowledge on frailty,sarcopenia and cachexia in HF patients with the attempt to define clinically significant degrees of multiorgan dysfunction,specific"red alert"thresholds in clinical practice and therapeutic approach.展开更多
AIM:To investigate the roles of the adipocytokines,ghrelin and leptin in gastric cancer cachexia. METHODS:Resistin,ghrelin,leptin,adiponectin,insulin and insulin-like growth factor(IGF-Ⅰ),were measured in 30 healthy ...AIM:To investigate the roles of the adipocytokines,ghrelin and leptin in gastric cancer cachexia. METHODS:Resistin,ghrelin,leptin,adiponectin,insulin and insulin-like growth factor(IGF-Ⅰ),were measured in 30 healthy subjects,and 60 gastric cancer patients of which 30 suffered from cancer-induced cachexia and 30 served as a control group. The relationships between hormones,body mass index(BMI) loss ratio,age,gender,and Glasgow Prognostic Score(GPS) were investigated. RESULTS:Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients(P < 0.05). Ghrelin,resistin,leptin,adiponectin and IGF-Ⅰ,showed a significant correlation with BMI loss ratio and GPS(P < 0.05). A strong correlation was seen between GPS and BMI loss(R = -0.570,P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin,resistin,leptin and IGF-Ⅰ(P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted. CONCLUSION:These results showed that serum ghrelin,leptin,adiponectin,and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationshipwas found between resistin and cancer cachexia. Also,because of the correlation between these parameters and GPS,these parameters might be used as a predictor factor.展开更多
Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipo...Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer(GC)-associated adipocytes.Methods:Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ,C/EPBα,PPARγ,and UCP1 in adipose mesenchymal stem cells(A-MSCs)to evaluate the function of exosomal miR-155.BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results:Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets.Similarly,A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression(P<0.05).Mechanistically,exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ,accompanied by downregulated C/EPBαand PPARγand upregulated UCP1(P<0.05).Moreover,overexpression of miR-155 in GC exosomes improved CAC in vivo,which was characterized by fat loss,suppressed expressions of C/EPBβ,C/EPBα,and PPARγin A-MSCs,and high expression of UCP1(P<0.05).Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions:GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβof A-MSCs,which played a crucial role in CAC.展开更多
BACKGROUND Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma(PDAC).The rapid disease progression and patient deterioration seems related to perineural invasion,but the relationship betwe...BACKGROUND Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma(PDAC).The rapid disease progression and patient deterioration seems related to perineural invasion,but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied.As perineural invasion is difficult to be highlighted,a biomarker such as the neurotrophic factor Midkine(MK)which promotes the neuronal differentiation and the cell migration could be helpful.Also,Activin(ACV)has been described as cachexia related to PDAC.However,their role for assessing and predicting the disease course in daily practice is not known.AIM To assess the relationship between perineural invasion and cachexia and their biomarkers,MK and ACV,respectively,and their prognostic value.METHODS This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies.Patients with other causes of malnutrition were excluded.The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data.These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease.RESULTS The study comprised 114 patients with PDAC,125 controls and a supplementary group of 14 benign pancreatic tissue samples.ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls(63% vs 32% for ACV,P<0.001;47%vs 16%for MK,P<0.001),with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage(P=0.006),the presence of metastasis(P=0.04),perineural invasion(P=0.03)and diabetes(P=0.002),but with no influence on survival.No correlation between clinicopathological factors and ACV expression was noted.Cachexia,present in 19%of patients,was unrelated to ACV or MK level.Higher ACV expression was associated with a shorter survival(P=0.008).CONCLUSION The MK was a biomarker of perineural invasion,associated with tumor stage and diabetes,but without prognostic value as ACV.Cachexia was unrelated to perineural invasion,ACV level or survival.展开更多
Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been ...Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life.Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support,pancreatic enzyme replacement therapy,and/or pharmacologic interventions.Despite current interventions to mitigate PDAC cachexia,a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome.We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC.Additionally,we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia.Novel insights into the relationship between enteral nutritional support,cachexia,and the gut microbiome are presented.These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.展开更多
Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination ...Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination of a body mass index of<20 kg/m^2 and at least one of the following biochemical abnormalities:C-reactive protein>5 mg/L;hemoglobin<12 g/dL;and/or albumin<3.2 g/d L.We divided 1608 hospitalized HF patients into a CC group(n=176,10.9%)and a non-CC group(n=1432,89.1%).The primary endpoints were cardiac event and all-cause death.Results The presence of CC showed significant interactions with other risk factors including cancer,estimated glomerular filtration rate(eGFR),and sodium in predicting these endpoints.Multiple Cox proportional analysis revealed that use of a blockers[hazard ratio(HR)=1.900,95%confidence interval(CI):1.045–3.455,P=0.035]and eGFR(HR=0.989,95%CI:0.980–0.998,P=0.018)were independent predictors of cardiac event in the CC group,while age(HR=1.020,95%CI:1.002–1.039,P=0.029)and hemoglobin(HR=0.844,95%CI:0.734–0.970,P=0.017)were independent predictors of all-cause death.The survival classification and regression tree analysis showed the optimal cut-off points for cardiac event(eGFR:59.9 m L/min per 1.73 m^2)and all-cause death(age,83 years old;hemoglobin,10.1 g/dL)in the CC group.Conclusions In predicting prognosis,CC showed interactions with several risk factors.Renal function,age,and hemoglobin were pivotal markers in HF patients with CC.展开更多
AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic...AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implanta- tion. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.展开更多
Objective Cachexia occurs in approximately half of hepatocellular carcinoma(HCC)patients as the disease progresses and is correlated with a poor prognosis.Therefore,early identification of HCC patients at risk of deve...Objective Cachexia occurs in approximately half of hepatocellular carcinoma(HCC)patients as the disease progresses and is correlated with a poor prognosis.Therefore,early identification of HCC patients at risk of developing cachexia and their prognosis is crucial.This study investigated the functional liver imaging score(FLIS)derived from gadoxetic acid-enhanced magnetic resonance imaging(MRI)to identify cachexia in HCC patients and their prognosis.Methods Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected.Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia.The FLIS was calculated as the sum of the enhancement quality score,the excretion quality score,and the portal vein sign quality score.A Cox proportional hazards model was used to determine the significant factors affecting overall survival(OS).Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients,which were subsequently used to predict OS.Results Cox regression analysis revealed a significant association between cachexia and worse OS.Both FLIS(0–4 vs.5–6 points)(OR,9.20;95%CI:4.68–18.10;P<0.001)andα-fetoprotein>100 ng/mL(OR,4.08;95%CI:2.13–7.83;P<0.001)emerged as significant predictors of cachexia in patients with HCC.Furthermore,FLIS(0–4 vs.5–6 points)(HR,1.73;95%CI:1.19–2.51;P=0.004)was significantly associated with OS.Patients in the FLIS 0–4 points group had shorter OS than those in the FLIS 5–6 points group[20 months(95%CI,14.7–25.3)vs.43 months(95%CI,27.7–58.3);P=0.001].Conclusion Cachexia was associated with worse OS.The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.展开更多
Cachexia is a multifactorial syndrome characterized by the loss of body weight,and has been observed in more than 50%of cancer patients.It arises as a result of anorexia and increased energy expenditure,leads to a red...Cachexia is a multifactorial syndrome characterized by the loss of body weight,and has been observed in more than 50%of cancer patients.It arises as a result of anorexia and increased energy expenditure,leads to a reduced tolerance of cancer therapy and a reduced quality of life,resulting in a poorer prognosis and decreased survival.In the past few years,tremendous achievements have been made in cancer cachexia research.Systemic inflammation has been proven to play important roles in the etiology of cancer cachexia,leading to functional impairment and rapid deterioration,which suggests that anti-inflammatory agents may represent a promising strategy for cancer cachexia treatment.Thus,a variety of agents have been postulated to treat cachexia,with modulation of inflammation,the immune response,and reactive oxygen species being the most promising.Some immune-enhancing nutrients,‘immunonutrients’,such asω-3 fatty acids,arginine,nucleotides,L-carnitine,probiotics,phytochemicals,and specific minerals have been tested for their anti-inflammatory and anti-oxidative properties.They have also been used to treat,prevent or attenuate cancer cachexia in both experimental models and clinical trials.A number of studies on the use of immunonutrients for the treatment of cancer cachexia have been published over the past decade,with some promising results supporting the routine use of immune-enhancing formulas in patients with cachexia.However,the effects and efficacy of these substances have not been conclusively proven.In this review,we discuss recent studies on the molecular mechanisms underlying cancer cachexia and the application of several immunonutrients.展开更多
Cachexia is a common complication with an incidence rate of 50%–80% in cancer patients. It is also responsible for 20% of mortality among these patients. Cachexia can significantly reduce the efficacy of antitumor th...Cachexia is a common complication with an incidence rate of 50%–80% in cancer patients. It is also responsible for 20% of mortality among these patients. Cachexia can significantly reduce the efficacy of antitumor therapies and increase treatment-related toxicity and adverse effects in cancer patients. This increases the symptom burden in patients, affects their quality of life, and ultimately shortens their survival time. The mechanism underlying the development of cachexia is complex and diverse and involves various factors and pathways, each playing an important role. Treatment approaches for cachexia are multimodal, including nutrition support therapy, appetite stimulants, and therapeutic drugs that specifically target the mechanism behind the disease. In recent years, we have gradually gained a better understanding of cachexia, and significant progress has been made in delineating molecular mechanisms, staging and diagnosis, and therapeutic drug treatment of cancer cachexia. This article reviews the research progress of cancer cachexia based on these contexts.展开更多
Cancer patients develop cachexia due to systemic inflammation, negative protein and energy balance. Esperer Onco Nutrition (EON) has come up with innovative nutritional supplements (EON Therapy) that help patients tak...Cancer patients develop cachexia due to systemic inflammation, negative protein and energy balance. Esperer Onco Nutrition (EON) has come up with innovative nutritional supplements (EON Therapy) that help patients take the rigours of cancer therapy thereby improving prognosis and Quality of Life (QoL). This Post-marketing surveillance study was undertaken on 38 volunteers to assess the impact of EON therapy on cachexia and QoL of patients undergoing curative treatment. Body weight and biochemical parameters of the volunteers were recorded at each visit. Volunteers were assessed using ECOG Scale and Malnutrition Screening Tool (MST) to assess impact of nutritional supplements on QoL. Weight loss was observed in most of the patients for first two visits but the patients gained weight over subsequent visits and average weight at end of the study was higher than initial weight. At the end of study 22 of 38 volunteers gained weight and 7 volunteers maintained initial weight. The biochemical parameters either showed improvement or remained same. The QoL analysis indicated a marked improvement in physical wellness and nutritional status and no adverse effects were reported. In conclusion, the study underlines importance of research based on nutritional supplements for cancer patients for better disease management and prognosis.展开更多
Cancer cachexia is a complex multifactorial syndrome that has a substantial impact on the quality of life of cancer patients. Although some treatment options exist to counteract cachexia, very few options counteract s...Cancer cachexia is a complex multifactorial syndrome that has a substantial impact on the quality of life of cancer patients. Although some treatment options exist to counteract cachexia, very few options counteract sarcopenia (loss of muscle mass). HMB may be a viable component in multi-modal approaches targeting treatment of cancer cachexia/sarcopenia. Evidence suggests that HMB promotes myogenic events, suppresses proteasome activity, and activates protein synthesis. HMB also represses inflammation, reduces tumor growth, and increases lifespan.展开更多
Cancer cachexia is a multifactorial syndrome characterized by the irreversible loss of body weight,fat,and muscle.Its main characteristics include nutrient intake and absorption disorders,systemic inflammation,mitocho...Cancer cachexia is a multifactorial syndrome characterized by the irreversible loss of body weight,fat,and muscle.Its main characteristics include nutrient intake and absorption disorders,systemic inflammation,mitochondrial dysfunction,immune imbalance,and protein and fat consumption,which ultimately lead to patient death.So far,there has been no effective method identified to combat the malignant progression of cancer cachexia.The effects of a single nutritional supplement or drug intervention strategy are insufficient.Exercise training is considered a potential treatment for cancer cachexia.Both clinical studies and animal experiments suggest that exercise training can help improve the intake and absorption of nutrients,inhibit inflammatory signaling pathways,regulate immunity andmetabolism,alleviate insulin resistance,promote protein synthesis,maintain muscle mass,and so on.The use of multimodal methods that combine nutritional support and/or other treatments with exercise provides a potential prospect for the treatment of cancer cachexia.However,the optimal prescription of exercise for the treatment of cancer cachexia is still unclear.The main purpose of this review is to summarize the growing body of research on the impact of exercise on cancer cachexia and to provide evidence supporting the use of exercise as an intervention for cancer cachexia in the clinical setting.展开更多
Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its...Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its impact on the patient prognosis.Methods:A total of 2990 cancer patients were enrolled in this retrospective study.Demographic information,clinical materials,and follow-up data were collected for all patients.A receiver operating characteristic curve was used to determine threshold values for weight loss within the past six months(WL).Kaplan-Meier curves and Cox proportional hazard regression models were adopted for survival analyses.Results:After excluding ineligible patients,2480 patients were included in the analysis,705(28.4%)of whom were considered to be ca-chexic.A WL of 10%was determined to be the optimal threshold for diagnosing malnutrition according to the Patient-Generated Subjective Global Assessment.Notably,WL>10%was a predictor of survival outcomes only in the general population(HR=1.218,95%Cl=1.002-1.481,P=0.048),but not in the cachexic population,based on the multivariable Cox regression model.A larger proportion of cachexic pa-tients with WL>10%had a nutritional risk screening 2002 score≥3(25.7%vs 13.7%,P<0.001)and a modified Glasgow Prognosis Score=2(12.8%vs 7.8%,P=0.032).No significant difference was observed in the degree of decreased muscle strength or quality of life(P>0.05).Conclusions:Weight loss is a predictor of impaired survival in the general population,but not in the cachexic population.The present study shows that cachexic patients with severe weight loss had a higher risk of malnutrition,a worse systemic inflammation status,and more severe malnutrition,but that the weight loss itself was not associated with the prognosis of these patients or the progression of their cachexia.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81970219, 82170261, 82200289 and 82370283National Key Research and Development Program of China,Grant/Award Number:2023YFF0724900。
文摘Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.
文摘Objective:To investigate the therapeutic effects and safety of Dioscorea Decoction combined with Coix Seed in treating cancer cachexia(spleen-kidney Yang deficiency syndrome)in malignant tumor patients.Methods:A total of 90 patients with cancer cachexia admitted between June 2024 and June 2025 were randomly divided into a control group and a study group(45 cases each)using a random number generator.Both groups received antitumor therapy,oral megestrol acetate capsules,and conventional nutritional intervention.The study group additionally received oral Dioscorea Decoction combined with Coix Seed.Differences in TCM syndrome scores,nutritional indicators(serum albumin,hemoglobin),and adverse reactions were compared before and after treatment.Results:Baseline TCM syndrome scores and nutritional indicators were comparable between the two groups before treatment.After treatment,both groups showed significant reductions in TCM syndrome scores and increases in serum albumin and hemoglobin levels.The study group exhibited lower TCM syndrome scores and higher serum albumin and hemoglobin levels than the control group,with statistically significant differences.No significant difference in adverse reaction rates was observed between the two groups.Conclusion:Dioscorea Decoction combined with Coix Seed can further improve nutritional status,alleviate clinical symptoms,and demonstrate good safety in treating cancer cachexia patients.
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.
基金Project supported by the Korea Institute of Oriental Medicine(Nos.K18041(SSY)and K18043(MSL))the Basic Science Research Program Through the National Research Foundation(NRF)of Korea(Nos.NRF-2015R1D1A1A02062410(SSY)and NRF-2017R1A2B4005357(JYC))
文摘Objective: The aim of this study is to summarize preclinical studies on herbal medicines used to treat cancer cachexia and its underlying mechanisms. Methods: We searched four representing databases, including Pub Med, EMBASE, the Allied and Complementary Medicine Database, and the Web of Science up to December 2016. Randomized animal studies were included if the effects of any herbal medicine were tested on cancer cachexia. The methodological quality was evaluated by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies(CAMARADE) checklist. Results: A total of fourteen herbal medicines and their compounds were identified, including Coptidis Rhizoma, berberine, Bing De Ling, curcumin, Qing-Shu-Yi-Qi-Tang, Scutellaria baicalensis, Hochuekkito, Rikkunshito, hesperidin, atractylodin, Sipjeondaebo-tang, Sosiho-tang, Anemarrhena Rhizoma, and Phellodendri Cortex. All the herbal medicines, except curcumin, have been shown to ameliorate the symptoms of cancer cachexia through anti-inflammation, regulation of the neuroendocrine pathway, and modulation of the ubiquitin proteasome system or protein synthesis. Conclusions: This study showed that herbal medicines might be a useful approach for treating cancer cachexia. However, more detailed experimental studies on the molecular mechanisms and active compounds are needed.
文摘Pancreatic cancer(PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies. Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta(TGF-β), myostatin and activin, IGF-1/PI3 K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3(IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting.Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6(IL-6), tumor necrosis factoralpha(TNF-α), and interferon gamma(INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.
文摘Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.
文摘Heart Failure(HF)in elderly patients is a systemic syndrome where advanced age,comorbidities with organ system deterioration,frailty and impaired cognition significantly impact outcome.Cardiac cachexia,sarcopenia and frailty despite overlap in definitions are different clinical entities that frequently coexist in HF patients.However,these co-factors often remain unaddressed,resulting in poor quality-of-life,prolonged physical disability and exercise intolerance and finally with higher rehospitalization rates and mortality.Strategy aim to increase muscle mass and muscle strength and delay the occurrence of frailty state appear essential in this regard.Common HF drugs therapy(b-blockers,angiotensinconverting enzyme inhibitors)and prescription of physical exercise program remain the cornerstone of therapeutic approach in HF patients with new promising data regarding nutritional supplementation.However,the treatment of all these conditions still remain debated and only a profound knowledge of the specific mechanisms and patterns of disease progression will allow to use the appropriate therapy in a given clinical setting.For all these reasons we briefly review current knowledge on frailty,sarcopenia and cachexia in HF patients with the attempt to define clinically significant degrees of multiorgan dysfunction,specific"red alert"thresholds in clinical practice and therapeutic approach.
基金Gazi University Scientific Research Projects Centers, No. 01/2006-37
文摘AIM:To investigate the roles of the adipocytokines,ghrelin and leptin in gastric cancer cachexia. METHODS:Resistin,ghrelin,leptin,adiponectin,insulin and insulin-like growth factor(IGF-Ⅰ),were measured in 30 healthy subjects,and 60 gastric cancer patients of which 30 suffered from cancer-induced cachexia and 30 served as a control group. The relationships between hormones,body mass index(BMI) loss ratio,age,gender,and Glasgow Prognostic Score(GPS) were investigated. RESULTS:Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients(P < 0.05). Ghrelin,resistin,leptin,adiponectin and IGF-Ⅰ,showed a significant correlation with BMI loss ratio and GPS(P < 0.05). A strong correlation was seen between GPS and BMI loss(R = -0.570,P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin,resistin,leptin and IGF-Ⅰ(P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted. CONCLUSION:These results showed that serum ghrelin,leptin,adiponectin,and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationshipwas found between resistin and cancer cachexia. Also,because of the correlation between these parameters and GPS,these parameters might be used as a predictor factor.
基金supported by a grant from National Natural Science Foundation of China(Grant Nos.82072664,81772629,81802363,81702431,81702437,81772843,81974374).
文摘Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer(GC)-associated adipocytes.Methods:Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ,C/EPBα,PPARγ,and UCP1 in adipose mesenchymal stem cells(A-MSCs)to evaluate the function of exosomal miR-155.BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results:Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets.Similarly,A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression(P<0.05).Mechanistically,exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ,accompanied by downregulated C/EPBαand PPARγand upregulated UCP1(P<0.05).Moreover,overexpression of miR-155 in GC exosomes improved CAC in vivo,which was characterized by fat loss,suppressed expressions of C/EPBβ,C/EPBα,and PPARγin A-MSCs,and high expression of UCP1(P<0.05).Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions:GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβof A-MSCs,which played a crucial role in CAC.
基金partially funded by the“Iuliu Hatieganu”University of Medicine and Pharmacy,Cluj-Napoca,through the Doctoral Research Project-2015(No.7690/36/15.04.2016)
文摘BACKGROUND Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma(PDAC).The rapid disease progression and patient deterioration seems related to perineural invasion,but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied.As perineural invasion is difficult to be highlighted,a biomarker such as the neurotrophic factor Midkine(MK)which promotes the neuronal differentiation and the cell migration could be helpful.Also,Activin(ACV)has been described as cachexia related to PDAC.However,their role for assessing and predicting the disease course in daily practice is not known.AIM To assess the relationship between perineural invasion and cachexia and their biomarkers,MK and ACV,respectively,and their prognostic value.METHODS This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies.Patients with other causes of malnutrition were excluded.The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data.These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease.RESULTS The study comprised 114 patients with PDAC,125 controls and a supplementary group of 14 benign pancreatic tissue samples.ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls(63% vs 32% for ACV,P<0.001;47%vs 16%for MK,P<0.001),with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage(P=0.006),the presence of metastasis(P=0.04),perineural invasion(P=0.03)and diabetes(P=0.002),but with no influence on survival.No correlation between clinicopathological factors and ACV expression was noted.Cachexia,present in 19%of patients,was unrelated to ACV or MK level.Higher ACV expression was associated with a shorter survival(P=0.008).CONCLUSION The MK was a biomarker of perineural invasion,associated with tumor stage and diabetes,but without prognostic value as ACV.Cachexia was unrelated to perineural invasion,ACV level or survival.
基金Supported by UCLA Clinical and Translational Science Institute UL1TR001881 Award.
文摘Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life.Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support,pancreatic enzyme replacement therapy,and/or pharmacologic interventions.Despite current interventions to mitigate PDAC cachexia,a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome.We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC.Additionally,we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia.Novel insights into the relationship between enteral nutritional support,cachexia,and the gut microbiome are presented.These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.
基金supported in part by a Grant-in-Aid for Scientific Research (No. 16K09447) from the Japan Society for the Promotion of Sciencesupported by Fukuda-denshi Co, Ltd.
文摘Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination of a body mass index of<20 kg/m^2 and at least one of the following biochemical abnormalities:C-reactive protein>5 mg/L;hemoglobin<12 g/dL;and/or albumin<3.2 g/d L.We divided 1608 hospitalized HF patients into a CC group(n=176,10.9%)and a non-CC group(n=1432,89.1%).The primary endpoints were cardiac event and all-cause death.Results The presence of CC showed significant interactions with other risk factors including cancer,estimated glomerular filtration rate(eGFR),and sodium in predicting these endpoints.Multiple Cox proportional analysis revealed that use of a blockers[hazard ratio(HR)=1.900,95%confidence interval(CI):1.045–3.455,P=0.035]and eGFR(HR=0.989,95%CI:0.980–0.998,P=0.018)were independent predictors of cardiac event in the CC group,while age(HR=1.020,95%CI:1.002–1.039,P=0.029)and hemoglobin(HR=0.844,95%CI:0.734–0.970,P=0.017)were independent predictors of all-cause death.The survival classification and regression tree analysis showed the optimal cut-off points for cardiac event(eGFR:59.9 m L/min per 1.73 m^2)and all-cause death(age,83 years old;hemoglobin,10.1 g/dL)in the CC group.Conclusions In predicting prognosis,CC showed interactions with several risk factors.Renal function,age,and hemoglobin were pivotal markers in HF patients with CC.
文摘AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implanta- tion. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.
基金supported by grants from National Natural Science Foundation of China(No.82272064)Jiangsu Provincial Science and Technique Program(No.BK20221461)Zhongda Hospital Affiliated to Southeast University,Jiangsu Province High-level Hospital Paring Assistance Construction(No.zdlyg08).
文摘Objective Cachexia occurs in approximately half of hepatocellular carcinoma(HCC)patients as the disease progresses and is correlated with a poor prognosis.Therefore,early identification of HCC patients at risk of developing cachexia and their prognosis is crucial.This study investigated the functional liver imaging score(FLIS)derived from gadoxetic acid-enhanced magnetic resonance imaging(MRI)to identify cachexia in HCC patients and their prognosis.Methods Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected.Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia.The FLIS was calculated as the sum of the enhancement quality score,the excretion quality score,and the portal vein sign quality score.A Cox proportional hazards model was used to determine the significant factors affecting overall survival(OS).Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients,which were subsequently used to predict OS.Results Cox regression analysis revealed a significant association between cachexia and worse OS.Both FLIS(0–4 vs.5–6 points)(OR,9.20;95%CI:4.68–18.10;P<0.001)andα-fetoprotein>100 ng/mL(OR,4.08;95%CI:2.13–7.83;P<0.001)emerged as significant predictors of cachexia in patients with HCC.Furthermore,FLIS(0–4 vs.5–6 points)(HR,1.73;95%CI:1.19–2.51;P=0.004)was significantly associated with OS.Patients in the FLIS 0–4 points group had shorter OS than those in the FLIS 5–6 points group[20 months(95%CI,14.7–25.3)vs.43 months(95%CI,27.7–58.3);P=0.001].Conclusion Cachexia was associated with worse OS.The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.
文摘Cachexia is a multifactorial syndrome characterized by the loss of body weight,and has been observed in more than 50%of cancer patients.It arises as a result of anorexia and increased energy expenditure,leads to a reduced tolerance of cancer therapy and a reduced quality of life,resulting in a poorer prognosis and decreased survival.In the past few years,tremendous achievements have been made in cancer cachexia research.Systemic inflammation has been proven to play important roles in the etiology of cancer cachexia,leading to functional impairment and rapid deterioration,which suggests that anti-inflammatory agents may represent a promising strategy for cancer cachexia treatment.Thus,a variety of agents have been postulated to treat cachexia,with modulation of inflammation,the immune response,and reactive oxygen species being the most promising.Some immune-enhancing nutrients,‘immunonutrients’,such asω-3 fatty acids,arginine,nucleotides,L-carnitine,probiotics,phytochemicals,and specific minerals have been tested for their anti-inflammatory and anti-oxidative properties.They have also been used to treat,prevent or attenuate cancer cachexia in both experimental models and clinical trials.A number of studies on the use of immunonutrients for the treatment of cancer cachexia have been published over the past decade,with some promising results supporting the routine use of immune-enhancing formulas in patients with cachexia.However,the effects and efficacy of these substances have not been conclusively proven.In this review,we discuss recent studies on the molecular mechanisms underlying cancer cachexia and the application of several immunonutrients.
文摘Cachexia is a common complication with an incidence rate of 50%–80% in cancer patients. It is also responsible for 20% of mortality among these patients. Cachexia can significantly reduce the efficacy of antitumor therapies and increase treatment-related toxicity and adverse effects in cancer patients. This increases the symptom burden in patients, affects their quality of life, and ultimately shortens their survival time. The mechanism underlying the development of cachexia is complex and diverse and involves various factors and pathways, each playing an important role. Treatment approaches for cachexia are multimodal, including nutrition support therapy, appetite stimulants, and therapeutic drugs that specifically target the mechanism behind the disease. In recent years, we have gradually gained a better understanding of cachexia, and significant progress has been made in delineating molecular mechanisms, staging and diagnosis, and therapeutic drug treatment of cancer cachexia. This article reviews the research progress of cancer cachexia based on these contexts.
文摘Cancer patients develop cachexia due to systemic inflammation, negative protein and energy balance. Esperer Onco Nutrition (EON) has come up with innovative nutritional supplements (EON Therapy) that help patients take the rigours of cancer therapy thereby improving prognosis and Quality of Life (QoL). This Post-marketing surveillance study was undertaken on 38 volunteers to assess the impact of EON therapy on cachexia and QoL of patients undergoing curative treatment. Body weight and biochemical parameters of the volunteers were recorded at each visit. Volunteers were assessed using ECOG Scale and Malnutrition Screening Tool (MST) to assess impact of nutritional supplements on QoL. Weight loss was observed in most of the patients for first two visits but the patients gained weight over subsequent visits and average weight at end of the study was higher than initial weight. At the end of study 22 of 38 volunteers gained weight and 7 volunteers maintained initial weight. The biochemical parameters either showed improvement or remained same. The QoL analysis indicated a marked improvement in physical wellness and nutritional status and no adverse effects were reported. In conclusion, the study underlines importance of research based on nutritional supplements for cancer patients for better disease management and prognosis.
文摘Cancer cachexia is a complex multifactorial syndrome that has a substantial impact on the quality of life of cancer patients. Although some treatment options exist to counteract cachexia, very few options counteract sarcopenia (loss of muscle mass). HMB may be a viable component in multi-modal approaches targeting treatment of cancer cachexia/sarcopenia. Evidence suggests that HMB promotes myogenic events, suppresses proteasome activity, and activates protein synthesis. HMB also represses inflammation, reduces tumor growth, and increases lifespan.
基金The Key Supporting Project of Talent Bank Funded by Army Medical University(No.2019R035)The Joint Research Project of Science,Health and Medicine of Chongqing(No.2020MSXM115).
文摘Cancer cachexia is a multifactorial syndrome characterized by the irreversible loss of body weight,fat,and muscle.Its main characteristics include nutrient intake and absorption disorders,systemic inflammation,mitochondrial dysfunction,immune imbalance,and protein and fat consumption,which ultimately lead to patient death.So far,there has been no effective method identified to combat the malignant progression of cancer cachexia.The effects of a single nutritional supplement or drug intervention strategy are insufficient.Exercise training is considered a potential treatment for cancer cachexia.Both clinical studies and animal experiments suggest that exercise training can help improve the intake and absorption of nutrients,inhibit inflammatory signaling pathways,regulate immunity andmetabolism,alleviate insulin resistance,promote protein synthesis,maintain muscle mass,and so on.The use of multimodal methods that combine nutritional support and/or other treatments with exercise provides a potential prospect for the treatment of cancer cachexia.However,the optimal prescription of exercise for the treatment of cancer cachexia is still unclear.The main purpose of this review is to summarize the growing body of research on the impact of exercise on cancer cachexia and to provide evidence supporting the use of exercise as an intervention for cancer cachexia in the clinical setting.
基金provided by the Doctor of Excellence Program from The First Hospital of Jilin University(No.JDYY-DEP-2022024)
文摘Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its impact on the patient prognosis.Methods:A total of 2990 cancer patients were enrolled in this retrospective study.Demographic information,clinical materials,and follow-up data were collected for all patients.A receiver operating characteristic curve was used to determine threshold values for weight loss within the past six months(WL).Kaplan-Meier curves and Cox proportional hazard regression models were adopted for survival analyses.Results:After excluding ineligible patients,2480 patients were included in the analysis,705(28.4%)of whom were considered to be ca-chexic.A WL of 10%was determined to be the optimal threshold for diagnosing malnutrition according to the Patient-Generated Subjective Global Assessment.Notably,WL>10%was a predictor of survival outcomes only in the general population(HR=1.218,95%Cl=1.002-1.481,P=0.048),but not in the cachexic population,based on the multivariable Cox regression model.A larger proportion of cachexic pa-tients with WL>10%had a nutritional risk screening 2002 score≥3(25.7%vs 13.7%,P<0.001)and a modified Glasgow Prognosis Score=2(12.8%vs 7.8%,P=0.032).No significant difference was observed in the degree of decreased muscle strength or quality of life(P>0.05).Conclusions:Weight loss is a predictor of impaired survival in the general population,but not in the cachexic population.The present study shows that cachexic patients with severe weight loss had a higher risk of malnutrition,a worse systemic inflammation status,and more severe malnutrition,but that the weight loss itself was not associated with the prognosis of these patients or the progression of their cachexia.
