R‐ketorolac ameliorates cancer‐associated cachexia and prolongs survival of tumour‐bearing mice

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(2), P. 562 - 574

Published: Feb. 1, 2024

Abstract Background Cancer‐associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced expectancy cancer patients. CAC characterized by unintended body weight reduction due to muscle adipose tissue loss. A major hallmark systemic inflammation. Several non‐steroidal anti‐inflammatory drugs (NSAIDs) have been suggested for treatment, yet no single medication has proven reliable. R‐ketorolac (RK) the R‐enantiomer commonly used NSAID. The effect RK on not evaluated. Methods Ten‐ 11‐week‐old mice were inoculated C26 or CHX207 cells vehicle control (phosphate‐buffered saline [PBS]). After onset, 2 mg/kg PBS was administered daily oral gavage. Body weight, food intake tumour size continuously measured. At study endpoints, blood drawn, sacrificed tissues excised. Immune cell abundance analysed using Cytek® Aurora spectral flow cytometer. Cyclooxygenase (COX) activity determined in lung homogenates fluorometric kit. Muscle mRNA protein expression quantitative real‐time PCR western blotting analysis, respectively. fibre histological slides after haematoxylin/eosin staining. Results Ten‐day survival rate C26‐bearing animals 10% while treatment resulted 100% ( P = 0.0009). Chemotherapy 14 days initiation, but all survived upon co‐medication cyclophosphamide 0.0001). Increased protection from loss (−0.61 ± 1.82 vs. −4.48 2.0 g, 0.0004) (−0.49 0.33 −2.49 0.93 0.0003) tumour‐bearing treated RK, compared untreated mice. ameliorated musculus quadriceps (−1.7 7.1% −27.8 8.3%, 0.0007) gonadal white (−18.8 49% −69 15.6%, 0.094) mice, Mechanistically, circulating interleukin‐6 (IL‐6) concentrations 334 151 164 123 pg/mL 0.047) 93 39 35 6 0.0053) Moreover, protected cancer‐induced T‐lymphopenia (+1.8 42% −49.2 12.1% respectively). ineffective ameliorating thymus‐deficient nude indicating that beneficial depends T‐cells. Conclusions improved decreased IL‐6 concentrations, resulting alleviation increased cachexigenic even under chemotherapy independent COX inhibition. Considering its potential, we propose use should be investigated patients suffering CAC.

Language: Английский

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Immune System Disorder and Cancer-Associated Cachexia

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1709 - 1709

Published: April 27, 2024

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that unresponsive to nutritional support contributes significantly morbidity mortality in patients with cancer. Immune dysfunction, driven cytokine imbalance, CAC progression. This review explores the potential relationship between anti-cancer immune response pre-clinical clinical studies. Pre-clinical studies showcase involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, TGF-β, CAC. IL-6 interacting adipose tissues, induce wasting through JAK/STAT NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate promoting inflammation. Clinical confirm elevated pro-inflammatory (IL-6, TNFα) markers neutrophil-to-lymphocyte ratio (NLR) Thus, immunomodulatory mechanisms involved may impact anti-neoplastic response. Inhibiting could enhance therapies, notably immunotherapy. R-ketorolac, new immunomodulator, reversed weight loss increased survival mice. Combining these agents immunotherapy benefit cancer experiencing Further research vital understand complex interplay tumor-induced dysregulation during

Language: Английский

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Current research status, applications and challenges of ketorolac-based sustained-release and controlled-release formulations

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125162 - 125162

Published: Jan. 8, 2025

Language: Английский

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IMMUNOSENESCENCE IN SKELETAL MUSCLE: THE ROLE-PLAY IN CANCER CACHEXIA CHESSBOARD

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 111, P. 48 - 59

Published: Feb. 26, 2025

With the increase in life expectancy, age-related conditions and diseases have become a widespread relevant social burden. Among these, immunosenescence cancer cachexia play significant often intertwined role. Immunosenescence is progressive aging decline of both innate adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, malignancies. Cancer affects elderly patients with causing severe weight loss, muscle wasting, inflammation, reduced response therapies. Whereas connections between been raising attention, molecular mechanisms still need be completely elucidated. This review aims at providing current knowledge about interplay immunosenescence, skeletal muscle, cachexia, analyzing pathways known so far involved. Finally, we highlight potential therapeutic strategies suited for population aimed block preserve mass also presenting analysis state-of-the-art related clinical trials.

Language: Английский

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Migrasome-Related Genes as Potential Prognosis and Immunotherapy Response Predictors for Colorectal Cancer

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 799 - 799

Published: March 26, 2025

Background: Studies highlight the role of migrasomes as mediators intercellular communication and signaling, critical in influencing tumorigenesis progression. Yet migrasome-related genes their potential colorectal cancer prognosis remain unexplored. Methods: Differentially expressed gene set A (DEG A) was identified TCGA-CRC dataset, Weighted Gene Co-expression Network Analysis (WGCNA) performed to identify most important modules associated with (MRG) scores. Single-cell RNA-seq dataset GSE231559 DEG B determined. Candidate were filtered by intersecting DGE A, key module genes, B. Prognostic subsequently screened through regression analysis, a risk model developed. Patients CRC TCGA cohort stratified into high- low-risk groups based on optimal cutoff score. Immunotherapy response-related analyses then performed. Finally, cell-to-cell analysis carried out for cells prognostic expression annotated cells. Results: The six candidate overlap 5158 1960 146 Further screening led selection T1MP1, CXCL8, MGP biomarkers. Immune-related indicated that high-risk group exhibited better response immunotherapy. Notably, showed elevated levels monocytes tissue stem cells, thereby designating them cell types. Conclusions: We conducted bioinformatic significant involvement immunotherapy response. Our research provides novel insights biology.

Language: Английский

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Immune System Disorder and Cancer-Associated Cachexia

Published: April 11, 2024

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, contributes significantly morbidity mortality in patients with cancer. Immune dysfunction, driven cytokine imbalance, CAC progression. This review explores the potential relationship between anti-cancer immune response pre-clinical clinical studies. Pre-clinical studies showcase involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, TGF-β, CAC. IL-6 interacting adipose tissues, induce wasting through JAK/STAT NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate promoting inflammation. Clinical confirm elevated pro-inflammatory (IL-6, TNFα) markers neutrophil-to-lymphocyte ratio (NLR) Thus, immunomodulatory mechanisms involved may impact anti-neoplastic response. Inhibiting could enhance therapies, notably immunotherapy. R-ketorolac, new immunomodulator, reversed weight loss increased survival mice. Combining these agents immunotherapy benefit cancer experiencing Further research vital understand complex interplay tumor-induced dysregulation during

Language: Английский

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Combination therapy of corylifol A and anamorelin attenuates cachexia by decreasing pro-inflammatory cytokines, inhibiting lipolysis and increasing food intake in a murine colon cancer model

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Sept. 17, 2024

Language: Английский

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