Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia

Oncogenesis, Год журнала: 2021, Номер 10(1)

Опубликована: Янв. 8, 2021

Abstract Cachexia is a severe complication of cancer that adversely affects the course disease, with currently no effective treatments. It characterized by progressive atrophy skeletal muscle and adipose tissue, resulting in weight loss, reduced quality life, shortened life expectancy. Although cachectic condition primarily muscle, tissue accounts for ~40% total body weight, cachexia considered multi-organ disease involves different tissues organs, among which cardiac stands out its relevance. Patients often experience abnormalities manifest symptoms are indicative chronic heart failure, including fatigue, shortness breath, impaired exercise tolerance. Furthermore, cardiovascular complications major causes death patients who experienced cachexia. The lack treatments underscores need to improve our understanding underlying mechanisms. Increasing evidence links wasting muscles metabolic alterations, increased energy expenditure, proteolysis, ensuing from activation proteolytic machineries cell, ubiquitin-dependent proteolysis autophagy. This review aims at providing an overview key mechanisms cachexia, focus on those shared muscles.

Язык: Английский

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Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Март 4, 2020

Cancer cachexia (CC) is a multifactorial syndrome characterized by systemic inflammation, uncontrolled weight loss and dramatic metabolic alterations. This includes myofibrillar protein breakdown, increased lipolysis, insulin resistance, elevated energy expediture, reduced food intake, hence impairing the patient's response to anti-cancer therapies quality of life. While decade ago was considered incurable, over most recent years much efforts have been put into study such disease, leading development potential therapeutic strategies. Several important improvements reached in management CC from both diagnostic-prognostic pharmacological viewpoint. However, given heterogeneity it impossible rely only on single variables properly treat patients presenting this syndrome. Moreover, symptoms are strictly dependent type tumor, stage specific cancer therapy. Thus, attempt translate experimentally effective clinical practice results great challenge. For reason, crucial importance further improve our understanding interplay molecular mechanisms implicated onset progression CC, giving opportunity develop new effective, safe treatments. In review we outline knowledge regarding mediators pathways involved skeletal muscle (SM) adipose tissue (AT) loss, mainly experimental standpoint, then retracing unimodal treatment options that developed present day.

Язык: Английский

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Effects of a 12-Week Multimodal Exercise Intervention Among Older Patients with Advanced Cancer: Results from a Randomized Controlled Trial

The Oncologist, Год журнала: 2021, Номер 27(1), С. 67 - 78

Опубликована: Сен. 9, 2021

Abstract Background Older patients with cancer are at risk of physical decline and impaired quality life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was investigate feasibility effect a multimodal exercise intervention in older advanced (stages III/IV). Patients Methods Eighty-four adults (≥65 years) pancreatic, biliary tract, or non-small cell lung who received systemic treatment were randomized 1:1 an group control group. 12-week exercise-based program including supervised twice weekly followed by protein supplement, home-based walking program, nurse-led support counseling. primary endpoint change function (30-second chair stand test) 13 weeks. Results Median age participants 72 years (interquartile range [IQR] 68-75). adherence sessions 69% (IQR 21-88) 75% 33-100) for program. At weeks, there significant difference scores 2.4 repetitions test, favoring (p < .0001). Furthermore, beneficial effects seen endurance (6-minute walk test), hand grip strength, activity, symptom burden, symptoms depression anxiety, global health status (quality life), lean body mass. No dose intensity, hospitalizations, survival. Conclusion A targeted proved effective improving

Язык: Английский

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Mitochondrial Dysfunction as an Underlying Cause of Skeletal Muscle Disorders

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 12926 - 12926

Опубликована: Окт. 26, 2022

Mitochondria are an important energy source in skeletal muscle. A main function of mitochondria is the generation ATP for through oxidative phosphorylation (OXPHOS). Mitochondrial defects or abnormalities can lead to muscle disease multisystem disease. dysfunction be caused by defective mitochondrial OXPHOS, mtDNA mutations, Ca2+ imbalances, mitochondrial-related proteins, chaperone and ultrastructural defects. In addition, imbalance between fusion fission, lysosomal due insufficient biosynthesis, and/or mitophagy result damage. this review, we explore association impaired disorders. Furthermore, emphasize need more research determine specific clinical benefits therapy treatment

Язык: Английский

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Addressing cancer anorexia-cachexia in older patients: Potential therapeutic strategies and molecular pathways

Clinical Nutrition, Год журнала: 2024, Номер 43(2), С. 552 - 566

Опубликована: Янв. 12, 2024

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and characterised by decreased energy intake upregulated skeletal catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, enteral nutrition have been utilised. However, pharmacological treatments that also shown promising results, such as megestrol acetate, anamorelin, thalidomide, delta-9-tetrahydrocannabinol, associated with gastrointestinal cardiovascular complications. Emerging evidence on the efficacy probiotics modulating gut microbiota presents adjunct to traditional therapies, potentially enhancing absorption systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved weight management patients undergoing chemotherapy, offering potential refinement current therapeutic approaches. This review aims elucidate molecular mechanisms underpinning particular focus role anorexia exacerbating propose non-pharmacological strategies mitigate this emphasising needs an demographic. Future research targeting CC should refining appetite-stimulating drugs fewer side-effects, specifically catering investigating factors can either enhance or minimise suppression individuals especially within vulnerable group.

Язык: Английский

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Computed Tomography-Based Sarcopenia and Pancreatic Cancer Survival—A Comprehensive Meta-Analysis Exploring the Influence of Definition Criteria, Prevalence, and Treatment Intention

Cancers, Год журнала: 2025, Номер 17(4), С. 607 - 607

Опубликована: Фев. 11, 2025

Background: Sarcopenia has been associated with poor outcomes in pancreatic cancer (PC). However, published results are heterogeneous terms of study design, oncological outcomes, and sarcopenia measurements. This meta-analysis aims to evaluate the impact computed tomography (CT)-based on overall survival (OS) progression-free (PFS) patients PC, considering potential confounders such as CT-based method thresholds used define sarcopenia, well treatment intention. Methods: We systematically searched databases for observational studies reporting hazard ratios (HRs) OS PFS PC stratified by status. Random-effects models were calculate pooled crude adjusted HRs (cHRs aHRs, respectively), subgroup analyses based measurement methods, cutoff values, prevalence, Heterogeneity was assessed using I2 τ2 statistics, publication bias evaluated funnel plots Egger's test. Results: Data from 48 included. significantly worse (pooled cHR = 1.58, 95% CI: 1.38-1.82; aHR 1.39, 1.16-1.66) 1.55, 1.29-1.86; 1.31, 1.11-1.55). Subgroup revealed different, stronger associations stricter cutoffs (<50 cm2/m2 males) undergoing curative treatments. substantial across (I2 > 67%), but generally low values (0.01-0.25). test indicated (p < 0.001), no significant observed 0.576). Conclusions: determined CT is an independent predictor this association varies depending its definition Therefore, routine assessment clinical practice could provide valuable prognostic information, future research should focus standardizing methods.

Язык: Английский

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Artificial Intelligence in the Management of Malnutrition in Cancer Patients: A Systematic Review

Advances in Nutrition, Год журнала: 2025, Номер unknown, С. 100438 - 100438

Опубликована: Май 1, 2025

Malnutrition is a critical complication among cancer patients, affecting up to 80% of individuals depending on type, stage, and treatment. Artificial Intelligence (AI) has emerged as promising tool in healthcare, with potential applications nutritional management improve early detection, risk stratification, personalized interventions. This systematic review evaluates the role AI identifying managing malnutrition focusing its effectiveness status assessment, prediction, clinical outcomes, body composition monitoring. A search was conducted across PubMed, Cochrane Library, Cumulative Index Nursing Allied Health Literature, Excerpta Medica Database from June July 2024, following Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines. Quantitative primary studies investigating AI-based interventions analysis, optimization oncology were included. Study quality assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools, evidence certainty evaluated Oxford Centre Evidence-Based Medicine framework. Eleven (n=52,228 patients) met inclusion criteria categorized into three overarching domains: Nutritional Status Assessment Prediction, Clinical Functional Outcomes, Body Composition Cachexia Monitoring. models demonstrated high predictive accuracy detection (AUC >0.80). Machine learning algorithms, including decision trees, random forests, support vector machines, outperformed conventional screening tools. Deep applied medical imaging achieved segmentation (Dice Similarity Coefficient: 0.92-0.94), enabling cachexia detection. AI-driven virtual dietitian systems improved dietary adherence (84%) reduced unplanned hospitalizations. AI-enhanced workflows streamlined referrals, reducing referral times by 2.4 days. significant optimizing screening, monitoring, patients. Its integration nutrition care could enhance patient outcomes optimize healthcare resource allocation. Further research necessary standardize ensure applicability. 10.17605/OSF.IO/A259M STATEMENT OF SIGNIFICANCE: highlights transformative demonstrating superior Unlike previous studies, which focused isolated applications, this work comprehensively multiple domains, emphasizing their routine treatment personalization, overall outcomes.

Язык: Английский

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The Skeletal Muscle as an Active Player Against Cancer Cachexia

Frontiers in Physiology, Год журнала: 2019, Номер 10

Опубликована: Фев. 17, 2019

The management of cancer patients is frequently complicated by the occurrence cachexia. This a complex syndrome that markedly impacts on quality life as well tolerance and response to anticancer treatments. Loss body weight, wasting both adipose tissue skeletal muscle reduced survival rates are among main features Skeletal has been shown depend, mainly at least, induction protein degradation above physiological levels. Such hypercatabolic pattern driven overactivation different intracellular proteolytic systems, which those dependent ubiquitin-proteasome autophagy. Selective rather than bulk altered proteins organelles was also proposed occur. Within picture described above, considered sort by-stander where external stimuli, directly or indirectly, can poise metabolism toward catabolic setting. By contrast, several observations suggest reacts drive imposed growth activating compensatory strategies include anabolic capacity, activation autophagy myogenesis. Even if eventually ill-fated, its supports idea in presence appropriate treatments development cancer-induced might not be an ineluctable event tumor hosts.

Язык: Английский

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Pathophysiological mechanisms explaining poor clinical outcome of older cancer patients with low skeletal muscle mass

Acta Physiologica, Год журнала: 2020, Номер 231(1)

Опубликована: Июнь 1, 2020

Abstract Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type stage of cancer. associated with poor clinical outcomes such as post‐operative complications, chemotherapy toxicity mortality patients. Little known about mediating pathophysiological mechanisms. In this review, we summarize proposed mechanisms underlying association between low including a) systemic inflammation; b) insulin‐dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics anticancer drugs. The altered myokine balance negatively affecting innate adaptive immune system, drugs leading a relative overdosage are best‐substantiated. effects intolerance circulating DNA consequence topics interest for future research. Restoring through physical exercise, exercise mimetics, neuro‐muscular activation adapting drug dosing could be targeted approaches improve mass.

Язык: Английский

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Sarcopenia predicts overall survival in patients with malignant hematological diseases: A meta-analysis

Clinical Nutrition, Год журнала: 2020, Номер 40(3), С. 1155 - 1160

Опубликована: Июль 23, 2020

Язык: Английский

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