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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The potential and pitfalls of using a large language model such as ChatGPT, GPT-4, or LLaMA as a clinical assistant

Journal of the American Medical Informatics Association, Journal Year: 2024, Volume and Issue: 31(9), P. 1884 - 1891

Published: July 17, 2024

Abstract Objectives This study aims to evaluate the utility of large language models (LLMs) in healthcare, focusing on their applications enhancing patient care through improved diagnostic, decision-making processes, and as ancillary tools for healthcare professionals. Materials Methods We evaluated ChatGPT, GPT-4, LLaMA identifying patients with specific diseases using gold-labeled Electronic Health Records (EHRs) from MIMIC-III database, covering three prevalent diseases—Chronic Obstructive Pulmonary Disease (COPD), Chronic Kidney (CKD)—along rare condition, Primary Biliary Cirrhosis (PBC), hard-to-diagnose condition Cancer Cachexia. Results In identification, GPT-4 had near similar or better performance compared corresponding disease-specific Machine Learning (F1-score ≥ 85%) COPD, CKD, PBC. excelled PBC use case, achieving a 4.23% higher F1-score “Traditional Learning” models. ChatGPT LLaMA3 demonstrated lower than across all almost metrics. Few-shot prompts also help achieve precision specificity but sensitivity Negative Predictive Value. Discussion The highlights potential limitations LLMs healthcare. Issues errors, explanatory ethical concerns like data privacy model transparency suggest that these would be supplementary clinical settings. Future studies should improve training datasets designs gain Conclusion shows have assist clinicians tasks such identification false positives negatives must mitigated before are adequate real-world assistance.

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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Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract Sarcopenia is defined as a muscle‐wasting syndrome that occurs with accelerated aging, while cachexia severe wasting associated conditions such cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. can considered component of cachexia, the bidirectional interplay between adipose tissue skeletal muscle potentially serving molecular mechanism for both conditions. However, underlying mechanisms differ. Recognizing distinctions these disorders essential advancing basic translational research in this area, enhancing diagnostic accuracy ultimately achieving effective therapeutic solutions affected patients. This review discusses microenvironment's changes contributing to conditions, recent approaches like lifestyle modifications, small molecules, interventions, emerging strategies gene editing, stem cell therapy, gut microbiome modulation. We also address challenges opportunities multimodal aiming provide insights into pathogenesis sarcopenia aiding innovative strategy development improved treatments.

Language: Английский

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Impact of time to treatment initiation on the development of cachexia and clinical outcomes in lung cancer

Japanese Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Abstract Background Pre-cancer onset of cachexia raises uncertainties regarding the optimal timing for early intervention in lung cancer patients. We aimed to examine changes physical function, nutritional status, and incidence patients with from initial visit treatment initiation determine effect these on treatment. Methods This single-center retrospective cohort study enrolled suspected having advanced who visited Kansai Medical University Hospital between January February 2023 were definitely diagnosed disease. Patients categorized into three groups based their status: those at diagnosis (group C), developed OC), without NC). Results Out 61 patients, 21 had first outpatient C). The time was 42.5 days. rate stage IV group OC significantly higher than that other stages (P = 0.008). Of 33 cancer, 11 received supportive care only. first-line induction low. Half declined chemotherapy best care; disease control (37.5%) worse 0.007). Conclusions Cachexia negatively impacts effectiveness treatment, necessitating anti-cachexia interventions clinical visit.

Language: Английский

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SIRT6 Ameliorates Cancer Cachexia–Associated Adipose Wasting by Suppressing TNFR2 Signalling in Mice

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

ABSTRACT Background Cachexia is a wasting syndrome associated with imbalanced energy metabolism and loss of adipose muscle tissues contributes to morbidity mortality in ageing as well patients severe chronic diseases, including cancer. At present, there are no treatments addressing cachexia that have reached validation be used the clinic. In this study, we investigate protective role SIRT6, an important regulator homeostasis health preservation, against Lewis lung carcinoma (LLC)–induced cachexia. Methods SIRT6 levels serum from gastric cancer ( n = 22, 65.27 ± 12.50 years old, 40.9% females) healthy controls 63.50 10.77 45.4% were measured evaluate correlation between circulating development. Ten‐week‐old transgenic (TG) wild type (WT) male mice injected LLC cells (1.5 × 10 6 per mouse) effects on cachexia‐associated browning lipolysis underlying mechanisms. We explored effect LLC‐conditioned medium induced mature adipocytes, differentiated primary mouse embryonic fibroblasts (MEFs). evaluated vitro activator by treatment MDL800. Results concentrations significantly higher non‐cachectic (3.41 0.30 ng/mL) compared cachectic (3.20 0.23 ng/mL, p < 0.01), suggesting negative level overexpression ameliorated tumour‐induced expenditure white (eWAT mass loss: 66% WT vs. 32% TG; iWAT 69% 40% TG) through suppression lipolysis. LLC‐induced cachexia, tumour necrosis factor‐α receptor 2 (TNFR2) mediated inhibition lipolytic signalling, because difference knockout group was almost eliminated TNFR2 neutralizing antibody. Increased concentration found (690.41 pg/mL 1166.98 patients, 0.05). A selective pharmaceutical activator, MDL800, could completely reverse adipocytes. Conclusion unexpected beneficial function demonstrating increased expression or activity capable protecting host tissue wasting, providing concept future therapies for

Language: Английский

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Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022

Obesity Pillars, Journal Year: 2022, Volume and Issue: 3, P. 100026 - 100026

Published: July 5, 2022

Language: Английский

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Quantitative and Qualitative Radiological Assessment of Sarcopenia and Cachexia in Cancer Patients: A Systematic Review

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(3), P. 243 - 243

Published: Feb. 24, 2024

Sarcopenia, an extremely common condition in cancer patients, is described as a progressive and generalized musculoskeletal disorder that associated with increased likelihood of adverse outcomes, including falls, fractures, physical disability, mortality. By contrast, cachexia defined syndrome characterized by weight loss the concomitant muscle and/or fat mass. Cancer leads to functional impairment, reduced performance, decreased survival, often accompanied progression response therapy. The literature states patients or sarcopenia have many more complications than without these conditions. interplay between physiologic is, part, responsible for complexity studying wasting disorders population, particularly geriatric population. For reasons, comprehensive assessment body composition function necessary. There are several modalities adapted measure skeletal mass, such dual-energy X-ray absorptiometry (DEXA), bioelectrical impedance analysis (BIA), computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US). gold standard measurement quantitative qualitative changes tissue density using CT scan. However, this technique remains poorly implemented clinical practice because use ionizing radiation. Similarly, DEXA, MRI, US been proposed, but their limited. In review, we present compare techniques developed so far nutritional patients.

Language: Английский

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Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial

World Journal of Surgical Oncology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 17, 2024

Abstract Background Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of recommendation is weak, level evidence low. The benefits still remain controversial. Patients methods 112 patients with cachexia were enrolled study randomly assigned a 1:1 ratio to receive either enteral support (IN, n = 56) or standard (SEN, 56). primary endpoint was incidence infectious complications, secondary endpoints included nutritional indicators, inflammatory markers, immune parameters, postoperative recovery complications gastrointestinal intolerance reactions. Results complications( P 0.040) overall ( 0.049)was significantly lower IN group compared SEN group. In terms laboratory indexes, demonstrated levels white blood cells (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), as well higher lymphocytes (LYMPH) immunoglobulin A (IgA), group, statistically significant differences. clinical outcomes, had shorter duration antibiotic use 0.048), hospital stay 0.018), total costs 0.034) also experienced less weight loss after 0.043). Conclusion Preoperative administration formula has positive impact on surgery. It improves patients’ status, shortens stays, reduces healthcare costs. may contribute improvement prognosis this high-risk population.

Language: Английский

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Real‐world safety and effectiveness of anamorelin for cancer cachexia: Interim analysis of post‐marketing surveillance in Japan

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(9)

Published: May 1, 2024

Abstract Background Anamorelin was approved in Japan 2021 to treat cancer cachexia associated with non‐small cell lung, gastric, pancreatic, or colorectal cancers. Post‐marketing surveillance is being conducted evaluate the real‐world safety and effectiveness of anamorelin. Methods This prospective, observational registered all patients who started treatment anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, their adverse events related were defined as main specifications. Body weight (BW) appetite assessed Results analysis based on data January 2023. The sets included 6016 4511 patients, respectively. Treatment‐related ≥1% hyperglycemia (3.9%) nausea (2.6%). incidences hyperglycemia, 4.8%, 1.2%, 1.1%, mean changes (standard error [SE]) BW from baseline weeks 3, 12, 24, 52 0.64 (0.05) kg, 1.19 (0.12) 1.40 (0.21) 1.42 (0.39) (SE) Functional Assessment Anorexia/Cachexia Treatment 5‐item Anorexia Symptom Scale total scores 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), 5.3 (0.47), respectively, exceeding clinically meaningful improvement score (2.0 points). Conclusion overall raised no new concerns, although continued caution may be required for nausea. Improvements also observed clinical settings.

Language: Английский

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