Search

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.

Background: Some experimental data suggest that myokines may play an important role in developing cancer-associated cachexia (CAC), but their relevance in humans remains poorly explored. In our study, we tested the hypothesis that circulating myokines are associated with the pathogenesis of CAC in a model population of gastric cancer. Methods: A group of 171 treatment naïve patients with adenocarcinoma of the stomach were prospectively examined. Cachexia was defined as weight loss >5% or weight loss >2% with either BMI <20 kg/m2 or sarcopenia. A panel of 19 myokines was measured in portal and peripheral blood as well as tumour tissue and surrounding gastric mucosa. Moreover, a serum proteomic signature of cachexia was identified by a label-free quantitative proteomics with a nano LCMS/MS system and stored in a ProteomeXchange database (PXD049334). Results: One hundred (58%) patients were diagnosed with CAC. The concentrations of fatty acid-binding protein 3 (FABP3), follistatin-like 1 protein (FSTL-1), interleukin 6 (IL 6), and interleukin 8 (IL 8) were significantly higher in the peripheral blood of cachectic subjects, while leptin levels were lower. Of all the evaluated myokines, tumour tissues showed higher expression levels only for IL-15 and myostatin. However, the analysis of paired samples failed to demonstrate a decreasing concentration gradient between the portal and peripheral blood for any of the myokines, evidencing against their release by the primary tumour. Proteomic analysis identified 28 proteins upregulated and 24 downregulated in the peripheral blood of patients with cachexia. Differentially expressed proteins and 5 myokines with increased serum levels generated a significant proteinprotein interaction network. Conclusions: Our study provides clinical evidence that some myokines are involved in the pathogenesis of cachexia and are well integrated into the regulatory network of circulating blood proteins identified among cachectic patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Cachexia is a late consequence of various diseases that is characterized by systemic muscle loss, with or without fat loss, leading to significant mortality. Multiple signaling pathways and molecules that increase catabolism, decrease anabolism, and interfere with muscle regeneration are activated. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in cachexia muscle atrophy. This review mainly provides the mechanisms of specific ncRNAs to regulate muscle loss during cachexia and discusses the role of ncRNAs in cachectic biomarkers and novel therapeutic strategies that could offer new insights for clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the role of physiotherapy in early and traditional palliative care (PC) for cancer patients, focusing on its effects on patient-reported outcomes (PROMs) such as fatigue, pain, and quality of life (QoL). The findings suggest that certain physiotherapy interventions, like cognitive behavioral therapy (CBT) and massage, can improve these outcomes, while others show limited or no significant benefits. However, the overall quality of the studies reviewed was low, highlighting the need for more rigorous research in this area to better understand how physiotherapy can support patients in PC. Background: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning (PSF). The purpose is to assess the effectiveness of various physiotherapy interventions and identify gaps in the current research to understand their potential benefits in PC better. Methods: A systematic literature search was conducted across PubMed, Embase, and Web of Science, concluding on 21 December 2023. Two independent reviewers screened the articles for inclusion. The Cochrane Risk of Bias Tool 2 was employed to assess the risk of bias, while the GRADE approach was used to evaluate the certainty of the evidence. Results: Nine randomized controlled trials (RCTs) were included, with most showing a high risk of bias, particularly in outcome measurement and missing data. Cognitive behavioral therapy (CBT) was the only intervention that significantly reduced fatigue, enhanced PHF, and improved QoL and emotional functioning. Graded exercise therapy (GET) did not yield significant results. Combined interventions, such as education with problem-solving or nutritional counseling with physical activity, showed no significant effects. Massage significantly improved QoL and reduced pain, while physical application therapies were effective in pain reduction. Mindful breathing exercises (MBE) improved QoL but had a non-significant impact on appetite. The overall certainty of the evidence was low. Conclusions: Physiotherapy can positively influence PROMs in oncology PC; however, the low quality and high risk of bias in existing studies highlight the need for more rigorous research to confirm these findings and guide clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia is a serious complication that can arise in patients with head and neck cancer due to both the disease and its treatments. It causes severe weight loss, muscle and fat depletion, and systemic inflammation, which significantly diminish patients' quality of life and survival. This study uses advanced machine learning techniques to improve the prediction and understanding of cachexia. By analyzing detailed imaging and clinical data, the research seeks to identify early signs of cachexia, providing insights that could help shape future management strategies. Our findings suggest that specific imaging biomarkers, particularly pancreatic volume, could play a crucial role in predicting cachexia, potentially leading to improved treatment outcomes for affected patients. Background/Objectives: Cancer-associated cachexia in head and neck squamous cell carcinoma (HNSCC) is challenging to diagnose due to its complex pathophysiology. This study aimed to identify metabolic biomarkers linked to cachexia and survival in HNSCC patients using [18F]FDG-PET/CT imaging and machine learning (ML) techniques. Methods: We retrospectively analyzed 253 HNSCC patients from Vienna General Hospital and the MD Anderson Cancer Center. Automated organ segmentation was employed to quantify metabolic and volumetric data from [18F]FDG-PET/CT scans across 29 tissues and organs. Patients were categorized into low weight loss (LoWL; grades 0–2) and high weight loss (HiWL; grades 3–4) groups, according to the weight loss grading system (WLGS). Machine learning models, combined with Cox regression, were used to identify survival predictors. Shapley additive explanation (SHAP) analysis was conducted to determine the significance of individual features. Results: The HiWL group exhibited increased glucose metabolism in skeletal muscle and adipose tissue (p = 0.01), while the LoWL group showed higher lung metabolism. The one-year survival rate was 84.1% in the LoWL group compared to 69.2% in the HiWL group (p < 0.01). Pancreatic volume emerged as a key biomarker associated with cachexia, with the ML model achieving an AUC of 0.79 (95% CI: 0.77–0.80) and an accuracy of 0.82 (95% CI: 0.81–0.83). Multivariate Cox regression confirmed pancreatic volume as an independent prognostic factor (HR: 0.66, 95% CI: 0.46–0.95; p < 0.05). Conclusions: The integration of metabolic and volumetric data provided a strong predictive model, highlighting pancreatic volume as a key imaging biomarker in the metabolic assessment of cachexia in HNSCC. This finding enhances our understanding and may improve prognostic evaluations and therapeutic strategies. [ABSTRACT FROM AUTHOR]