Exploring the therapeutic effect of Xiaoyan d ecoction on lung cancer cachexia skeletal muscle atrophy based on L3-SMI

Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a persistent decline in muscle mass that cannot be reversed by conventional nutrition Xiaoyan d ecoction can promote appetite and improve skeletal muscle mass in patients with lung cancer cachexia,while the third lumbar skeletal muscle index(L3-SMI)is able to determine whole-body skeletal muscle mass.To analyze the relationship between L3-SMI and hematological indexes and lung cancer cachexia,and to study the clinical efficacy of Xiaoyan decoction on skeletal muscle atrophy in lung cancer cachexia patients,with the aim of providing a reference basis for the early diagnosis and treatment of lung cancer cachexia patients and skeletal muscle atrophy.Methods:148 patients who were diagnosed with lung cancer in the Department of Oncology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to December 2022 were included,and were divided into cachexia and non-cachexia groups according to the diagnostic criteria of cachexia,and analyzed the differences of hematological indexes and L3-SMI between cachexia patients and non-cachexia patients.And the patients with cachexia were divided into control group and treatment group,analyzed and compared the changes of body mass index(BMI),L 3-SMI,Karnofsky functional status score,albumin and other hematological indexes of the two groups before and after the treatment,and evaluated the safety of the Xiaoyan decoction in the treatment of cachexia.Results:A total of 148 lung cancer patients were included in this study,including 67 patients in the cachexia group and 81 patients in the non-cachexia group.According to the pre-treatment statistical analysis,the BMI of patients in the cachexia group was lower than that of patients in the non-cachexia group(P<0.05);among the biochemical function indexes,the proportions of creatinine(P<0.05),total protein(P<0.05),The levels of albumin in the cachexia group were significantly lower(P<0.05)compared to the non-cachexia group;in the cachexia group,both males and females had lower L3-SMIs than in the non-cachexia group(P<0.05).A total of 62 cases of lung cancer cachexia were studied,30 cases in the control group and 32 cases in the treatment group,according to statistical analysis,BMI was significantly different before and after treatment(P<0.05);L3-SMI was significantly different in the treatment group before and after treatment(P<0.05);Karnofsky significantly differed in the treatment group before and after treatment(P<0.05);and there was a significant difference in albumin before and after(P<0.05).Conclusion:Cachexia patients had significantly lower third lumbar skeletal muscle mass than non-cachexia patients,according to this study;Xiaoyan decoction was able to improve skeletal muscle mass,nutritional status as well as functional status of patients with cachexia in lung cancer,among others.

Treatment of cancer cachexia with exercise

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.

Advances in pharmacotherapies in cancer-related cachexia

Cancer-related cachexia is highly prevalent in patients with advanced cancer, affecting approximately 50%–80% of patients and seriously interfering with active therapy, quality of life, and survival time. There arecurrently no effective treatments for cachexia. Therefore, new therapeutic strategies are required. In recentyears, advances in understanding the mechanisms underlying cachexia have been made, and new drugshave been developed to combat cachexia muscle wasting and weight loss due to cancer. In this systematicreview, we discuss these novel targets and drug treatments.

Impact of weight Loss on the progression of cancer cachexia and the patient prognosis:insights from a retrospective study

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.

Cancer cachexia,mechanism and treatment

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.

Cachexia and pancreatic cancer: Are there treatment options?

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 cancerassociated 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.

Molecular therapeutic strategies targeting pancreatic cancer induced cachexia

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.

Frailty,sarcopenia and cachexia in heart failure patients:Different clinical entities of the same painting

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.

Exosomal miR-155 from gastric cancer induces cancerassociated cachexia by suppressing adipogenesis and promoting brown adipose differentiation via C/EPBβ

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.

Relationship between cachexia and perineural invasion in pancreatic adenocarcinoma

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.

Prognostic factors in heart failure patients with cardiac cachexia

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.

Gut microbiome and pancreatic cancer cachexia:An evolving relationship

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.

Advances in Immunonutrient Application to Treat Cancer Cachexia Syndrome

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.

Managing Cachexia and Improving Quality of Life in Cancer Patients Using Novel Nutritional Supplements: A PAN India Study

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.

Role of β-Hydroxy β-Methylbutyrate (HMB) in Cancer Cachexia/ Sarcopenia

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.

The animal cachexia score(ACASCO)

Background:None of the published studies involving cancer cachexia experimental models have included a measure of the severity of the syndrome like the scoring system previously developed for human subjects.The aim of the present investigation was to define and validate a cachexia score usable in both rat and mouse tumor models.Methods:In order to achieve this goal,we included in the study one rat model(Yoshida AH‐130ascites hepatoma)and two mouse models(Lewis lung carcinoma and Colon26 carcinoma).The Animal cachexia score(ACASCO)includes five components:(a)body and muscle weight loss,(b)inflammation and metabolic disturbances,(c)physical performance,(d)anorexia,and(e)quality of life measured using discomfort symptoms and behavioral tests.Results:Using the ACASCO values,three cut‐off values were estimated by applying hierarchical cluster analysis.Four groups were originally described,one exactly below the observed mean,a second exactly over the mean,and two other groups adjusted to every cue(inferior and superior).The three cut‐off values were estimated through maximization of the classification function.This was accomplished by using a similarity matrix based on the metric properties of the variables and assuming multinormal distribution.The results show that the four groups were:no cachexia,mild cachexia,moderate cachexia and advanced cachexia.Conclusions:The results obtained allow us to conclude that the score could be very useful as an endpoint in pre‐clinical studies involving therapeutic strategies for cancer cachexia.The potential usefulness of ACASCO relates to the primary endpoint in pre‐clinical cancer cachexia drug evaluations.

Cancer, Malnutrition and Cachexia: We Must Break the Triad

Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments causing malabsorption. The cachexia-anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, anorexia, early satiety, fatigue and weakness due to shifts in metabolism caused by tumour by-products and cytokines. Cachexia is a distressing and debilitating condition, affecting significant numbers of patients with advanced disease and is the primary cause of death in about 20% of all patients with cancer. Though cachexia is most commonly associated with particular tumours, such as head and neck, gastrointestinal tract, pancreas, central nervous system and lung, it may affect any patient with any tumour at any site;no patient and no tumour are excluded. Current treatment for principally depends on its prevention rather than reversing the present disease state, and the clinical results are far from being satisfactory. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. Treatment should be directed toward improvement in the quality of life of the patient and should often include nutritional counseling. It should take into consideration both disease and treatment related factors as well as the cachexia syndrome itself.

Study on possible synergistic anticancer cachexia effects of the main active compounds of Radix Sophorae flavescentis

Background:Cancer cachexia is a complex disease secondary to cancer,and no specific therapy for it has been found.The Chinese herb Kushen(Radix Sophorae flavescentis)is the dried root of Sophora flavescens Aiton,which has been widely applied in treating digestive and urinary inflammatory diseases.Matrine,one of the main components of Radix Sophorae flavescentis,can alleviate cancer cachexia.Methods:Compounds from Radix Sophorae flavescentis were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The targets related to cancer cachexia were queried from the Therapeutic Target Database(http://db.idrblab.net),DisGeNET database(http://www.disgenet.org),and Search Tool for Interacting Chemicals database,related literature,and constructed cancer cachexia-protein network.Cancer cachexia-protein network was merged with compound-protein networks respectively using Cytoscape software as well as network topology data and key targets counting.Pathway enrichment analysis was conducted via the Database for Functional Annotation Bioinformatics Microarray Analysis.Protein crystal structures and compound structures were queried from RCSB and PubChem databases,respectively.Molecular docking was conducted using Discovery Studio software.Results:The anticancer cachexia compounds of Radix Sophorae flavescentis were screened as oxymatrine,matrine,and kurarinol,and targets such as BIRC2,TNF and STAT3 were found.The mechanisms of oxymatrine,matrine,and kurarinol have the characteristics of synergy and complementarity.Kurarinol has a mechanism similar to that of matrine,which includes the FoxO signaling pathway,insulin resistance and mTOR signaling pathway.TNF signaling pathway is a common signaling pathway of kurarinol,oxymatrine and matrine.Adipocytokine signaling pathway is the other common pathway of kurarinol and oxymatrine except for the TNF signaling pathway.Kurarinol can be successfully docked with CYCS,GPX2,BIRC7,etc.,and kushenol C can be successfully docked with IKBKB and PIK3CD.Conclusion:Kurarinol,matrine,oxymatrine,and kushenol C may be the key compounds of Radix Sophorae flavescentis treating cancer cachexia.Additionally,TNF signaling pathway is the key pathway for the synergistic action of kurarinol,matrine and oxymatrine.

EON Therapy Ameliorates Cachexia and Quality of Life in Cancer Patients

Cancer induced cachexia, a gross loss of skeletal muscle with or without adipose tissue wasting, remains a clinical impasse resulting in poor prognosis and Quality of Life (QoL). It is characterized by an inflammation driven anorexia and aberrant energy and protein balance. Indubitably, nutritional rehabilitation is required to address various daunting challenges of this multifactorial syndrome. Esperer Onco Nutrition has come up with an optimal clinical nutrition formulation with promising anti-cachexia effects. Towards validating the efficacy and ensuring the safety of EON Therapy (Es-Invigour plus Es-Fortitude-Protect) under clinical settings, a phase IV post marketing surveillance (PMS) study with 63 patients from various hospitals across India was undertaken. This multi-nutrient and multi-targeted nutritional intervention, being concurrent with mainstream therapy, demonstrated potential to ameliorate the cachectic condition which was measured by body weight of the volunteers at each visit. Biochemical parameters improved or remained same. Overall QoL assessment was performed by using ECOG Scale and Malnutrition Screening Tool (MST) which showed significant improvement in physical wellness and nutritional status of the volunteers. No adverse effect was observed during the entire period. These observations reinforce the need of research based nutritional intervention for clinical use in cachectic cancer patients.

Research progress on pathogenesis and related pathways of Cancer cachexia

Cancer cachexia is a complex syndrome of metabolic changes caused by many factors in tumor patients,which characterized by emaciation,weight loss,muscle atrophy,anemia and hypoproteinemia,it's seriously affects the quality of life,cycle and therapeutic effect of patients.At present,there is no curative effect in the treatment of cancer cachexia,because the pathogenesis is still unclear.So it is particularly important to study the pathogenesis,mechanism and related pathway of cancer cachexia.In this paper,the definition,stage and diagnosis of cachexia,traditional Chinese medicine theoretical research,related anorexia mechanism,protein decomposition mechanism,fat decomposition mechanism,sugar metabolism mechanism,inflammatory factor mechanism and other aspects were analyzed and summarized to provide theoretical basis for the study of cachexia pathogenesis and clinical application selection.