Cancer Cachexia: Its Mechanism and Clinical Significance

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8491 - 8491

Published: Aug. 6, 2021

The term "cachexia" is derived from the Greek words kakos (bad) and hexis (habit). Cachexia a malnutrition associated with chronic diseases such as cancer, heart failure, renal autoimmune diseases, characterized by decreased skeletal muscle mass. Cancer cachexia quite common in patients advanced cancer. Weight loss also characteristic symptom of cancer cachexia, along As nutritional supplementation alone cannot improve cytokines tumor-derived substances have been attracting attention its relevant factors. can be reduced chemotherapeutic effects, increased side effects treatment interruptions, even poorer survival. In 2011, consensus definition has proposed, number research reports significantly. However, pathogenesis not fully understood, there are currently few regulatory-approved standard treatments for cachexia. main reason this that multiple etiologies involved development review, we will outline current status mechanisms which elucidated recent years, especially perspective

Language: Английский

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Cancer cachexia: molecular mechanisms and treatment strategies

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: May 22, 2023

Abstract Muscle wasting is a consequence of physiological changes or pathology characterized by increased catabolic activity that leads to progressive loss skeletal muscle mass and strength. Numerous diseases, including cancer, organ failure, infection, aging-associated are associated with wasting. Cancer cachexia multifactorial syndrome mass, without the fat resulting in functional impairment reduced quality life. It caused upregulation systemic inflammation stimuli, leading inhibition protein synthesis enhancement catabolism. Here, we summarize complex molecular networks regulate function. Moreover, describe multi-organ roles cancer cachexia. Although one main causes cancer-related deaths, there still no approved drugs for Thus, compiled recent ongoing pre-clinical clinical trials further discussed potential therapeutic approaches

Language: Английский

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Integrating organoids and organ-on-a-chip devices

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(7), P. 588 - 608

Published: July 2, 2024

Language: Английский

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Triptolide prevents LPS‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 178(15), P. 2998 - 3016

Published: March 31, 2021

Increasing evidence suggests systemic inflammation-caused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook F possesses potent anti-inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects molecular mechanisms triptolide on inflammation-induced atrophy.The were investigated in LPS-treated C2C12 myotubes C57BL/6 mice. Protein expressions mRNA levels analysed by western blot qPCR, respectively. Skeletal mass, volume strength measured histological analysis, micro-CT grip strength, Locomotor activity was using open field test.Triptolide (10-100 fM) up-regulated protein synthesis signals (IGF-1/p-IGF-1R/IRS-1/p-Akt/p-mTOR) down-regulated degradation signal atrogin-1 myotubes. In LPS (100 ng·ml-1 )-treated myotubes, MyHC, IGF-1, p-IGF-1R, IRS-1 p-Akt. also ubiquitin-proteasome molecules (n-FoxO3a/atrogin-1/MuRF1), proteasome activity, autophagy-lysosomal (LC3-II/LC3-I Bnip3) inflammatory mediators (NF-κB, Cox-2, NLRP3, IL-1β TNF-α). However, AG1024, an IGF-1R inhibitor, suppressed triptolide-mediated myotube diameter, MuRF1 p62 (1 mg·kg-1 , i.p.)-challenged mice, (5 20 μg·kg-1 ·day-1 i.p.) decreased plasma TNF-α it increased volume, cross-sectional area myofibers, weights gastrocnemius tibialis anterior muscles, forelimb locomotion.These findings reveal that prevented LPS-induced inflammation have implications for discovery novel agents preventing wasting.

Language: Английский

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Ubiquitin-proteasome pathway in skeletal muscle atrophy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 17, 2023

Skeletal muscles underpin myriad human activities, maintaining an intricate balance between protein synthesis and degradation crucial to muscle mass preservation. Historically, disruptions in this balance—where overshadows synthesis—have marked the onset of atrophy, a condition diminishing life quality and, grave instances, imperiling itself. While multiple pathways exist—including autophagy-lysosome, calcium-dependent calpain, cysteine aspartate protease systems—the ubiquitin-proteasome pathway emerges as especially cardinal avenue for intracellular degradation, wielding pronounced influence over atrophy trajectory. This paper ventures panoramic view predominant types, accentuating pathway’s role therein. Furthermore, by drawing from recent scholarly advancements, we draw associations specific pathological conditions linked atrophy. Our exploration seeks shed light on significance skeletal dynamics, aiming pave way innovative therapeutic strategies against affiliated disorders.

Language: Английский

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Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes

JNCI Monographs, Journal Year: 2023, Volume and Issue: 2023(61), P. 84 - 103

Published: May 4, 2023

Abstract Intermittent fasting entails restricting food intake during specific times of day, days the week, religious practice, or surrounding clinically important events. Herein, metabolic and circadian rhythm mechanisms underlying proposed benefits intermittent for cancer population are described. We summarize epidemiological, preclinical, clinical studies in published between January 2020 August 2022 propose avenues future research. An outstanding concern regarding use among patients is that often results caloric restriction, which can put already prone to malnutrition, cachexia, sarcopenia at risk. Although trials do not yet provide sufficient data support general this summary may be useful patients, caregivers, clinicians who exploring as part their journey outcomes symptom management.

Language: Английский

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

Clinical Nutrition, Journal Year: 2024, Volume and Issue: 43(2), P. 552 - 566

Published: Jan. 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.

Language: Английский

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Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(2), P. 329 - 365

Published: Sept. 14, 2021

Muscle wasting disease indications are among the most debilitating and often deadly noncommunicable states. As a comorbidity, muscle is associated with different neuromuscular diseases myopathies, cancer, heart failure, chronic pulmonary renal diseases, peripheral neuropathies, inflammatory disorders, and, of course, musculoskeletal injuries. Current treatment strategies relatively ineffective can at best only limit rate degeneration. This includes nutritional supplementation appetite stimulants as well immunosuppressants capable exacerbating loss. Arguably, promising treatments in development attempt to disrupt myostatin activin receptor signaling because these circulating factors potent inhibitors growth regulators progenitor cell differentiation. Indeed, several studies demonstrated clinical potential "inhibiting inhibitors," increasing protein synthesis, decreasing degradation, enhancing mitochondrial biogenesis, preserving function. Such changes prevent various animal models yet many drugs targeting this pathway failed during trials, some from serious treatment-related adverse events off-target interactions. More often, however, failures resulted inability improve function despite mass. Drugs still include antibodies gene therapeutics, all targets thus, safety, efficacy, proposed use profiles. Each unique design if successful, could revolutionize both acute wasting. They also be used combination other developing therapeutics for related pathologies or even metabolic diseases.

Language: Английский

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Chemotherapy-Induced Myopathy: The Dark Side of the Cachexia Sphere

Cancers, Journal Year: 2021, Volume and Issue: 13(14), P. 3615 - 3615

Published: July 19, 2021

Cancer cachexia is a debilitating multi-factorial wasting syndrome characterised by severe skeletal muscle and dysfunction (i.e., myopathy). In the oncology setting, arises from synergistic insults both cancer–host interactions chemotherapy-related toxicity. The majority of studies have surrounded interaction side cancer cachexia, often overlooking capability chemotherapy to induce cachectic myopathy. Accumulating evidence in experimental models suggests that some chemotherapeutic agents rapidly myopathy, although underlying mechanisms responsible vary between agents. Importantly, we highlight capacity specific as not all chemotherapies been evaluated for cachexia-inducing properties—alone or clinically compatible regimens. Furthermore, discuss surrounding therapeutic strategies chemotherapy-induced models, with particular focus on exercise interventions adjuvant candidates targeted at mitochondria.

Language: Английский

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DeepGene Transformer: Transformer for the gene expression-based classification of cancer subtypes

Expert Systems with Applications, Journal Year: 2023, Volume and Issue: 226, P. 120047 - 120047

Published: April 14, 2023

Language: Английский

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