Development and Characterization of a Cancer Cachexia Rat Model Transplanted with Cells of the Rat Lung Adenocarcinoma Cell Line Sato Lung Cancer (SLC) DOI Creative Commons
Eiji Kasumi,

Miku Chiba,

Yoshie Kuzumaki

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2824 - 2824

Published: Oct. 18, 2023

Cancer cachexia is a complex malnutrition syndrome that causes progressive dysfunction. This accompanied by protein and energy losses caused reduced nutrient intake the development of metabolic disorders. As many as 80% patients with advanced cancer develop cachexia; however, an effective targeted treatment remains to be developed. In this study, we developed novel rat model mimics human pathology during elucidate mechanism underlying onset progression syndrome. We subcutaneously transplanted rats SLC cells, lung adenocarcinoma cell line, evaluated rats’ pathophysiological characteristics. To ensure our observations were not attributable simple starvation, characteristics under tube feeding. observed SLC-transplanted exhibited severe anorexia, weight loss, muscle atrophy, weakness. Furthermore, they showed obvious signs cachexia, such anemia, inflammation, low serum albumin. The also despite sufficient nutrition delivered Our promising tool pathogenesis conduct further research on treatments supportive care for disease.

Language: Английский

Ponsegromab for the Treatment of Cancer Cachexia DOI
John D. Groarke,

Jeffrey Crawford,

Susie M. Collins

et al.

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

Cachexia is a common complication of cancer and associated with an increased risk death. The level growth differentiation factor 15 (GDF-15), circulating cytokine, elevated in cachexia. In small, open-label, phase 1b study involving patients cachexia, ponsegromab, humanized monoclonal antibody inhibiting GDF-15, was improved weight, appetite, physical activity, along suppressed serum GDF-15 levels.

Language: Английский

Citations

42
R‐ketorolac ameliorates cancer‐associated cachexia and prolongs survival of tumour‐bearing mice DOI Creative Commons

Sophia E. Chrysostomou,

Sandra Eder,

Isabella Pototschnig

et al.

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

Citations

7
Age-related and cancer-related sarcopenia: is there a difference? DOI
Federico Bozzetti

Current Opinion in Clinical Nutrition & Metabolic Care, Journal Year: 2024, Volume and Issue: 27(5), P. 410 - 418

Published: March 15, 2024

The aim of this review is the attempt to differentiating pathophysiologic and clinical features aging-related sarcopenia from cancer-related sarcopenia. In fact, there some controversy among experts mainly regarding two points: always sarcopenia, even that one, expression a generalized disease or may exist independently without major alteration muscle function? Are completely separated entities?

Language: Английский

Citations

6
Moderating AKT signaling with baicalein protects against weight loss by preventing muscle atrophy in a cachexia model caused by CT26 colon cancer DOI Creative Commons
Gahee Song, Woo Yong Park, Wenjun Jiao

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(3), P. 119670 - 119670

Published: Jan. 13, 2024

Language: Английский

Citations

4
The lipocalin saga: Insights into its role in cancer-associated cachexia DOI

Srusti Dave,

Bhoomika M. Patel

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167684 - 167684

Published: Jan. 1, 2025

Language: Английский

Citations

0
Novel dual-targeting PROTAC degraders of GSK-3β and CDK5: A promising approach for pancreatic cancer treatment DOI
Neerasa Jayaprakash, Byeonggwan Kim, Hye Jin Chung

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 120, P. 118085 - 118085

Published: Jan. 29, 2025

Language: Английский

Citations

0
IMMUNOSENESCENCE IN SKELETAL MUSCLE: THE ROLE-PLAY IN CANCER CACHEXIA CHESSBOARD DOI Creative Commons
Matteo Giovarelli, Emanuele Mocciaro, Carla Carnovale

et al.

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

Citations

0
Defeating lethal cancer: Interrupting the ecologic and evolutionary basis of death from malignancy DOI Open Access
Kenneth J. Pienta,

Patrick L. Goodin,

Sarah R. Amend

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved survival, globally, there is an increased incidence cancer-related deaths. Although each patient tumor wholly unique, tipping point incurable disease common across patients: dual capacity for cancers metastasize resist systemic treatment. The discovery genetic mutations epigenetic variation that emerges during progression highlights evolutionary ecology principles can be used understand how evolves a lethal phenotype. By applying such eco-evolutionary framework, authors reinterpret our understanding metastatic process as one ecologic invasion define paths evolving therapy resistance. With this understanding, draw from successful strategies optimized strategic interventions with goal altering trajectory cancer. Ultimately, studying, treating using provides opportunity improve lives patients

Language: Английский

Citations

0
Advanced High-Content Phenotypic Screening to Identify Drugs That Ameliorate the Inhibition of Skeletal Muscle Cell Differentiation Induced by Cancer Cachexia Serum DOI Creative Commons

Atsushi Nakane,

Hiroyuki Nakagawa, Hidetaka Nagata

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 445 - 445

Published: March 21, 2025

Background/Objectives: Cancer cachexia (CC) is a prevalent and debilitating syndrome in cancer patients, characterized by severe muscle weight loss, leading to increased mortality reduced quality of life. Despite the significant impact, effective treatments are lacking due an incomplete understanding its underlying mechanisms. In this study, we aim develop drugs that ameliorate inhibition differentiation induced CC. We established advanced, high-content phenotypic screening system using serum patients identified potential compounds. Methods: used patients’ sera as pathophysiological stimuli our evaluate their effects on atrophy differentiation. Various histone deacetylase (HDAC) inhibitors were tested for efficacy. The system’s translational relevance was validated comparing results with clinical data vivo models. Results: Using system, evaluated several found they reflect features cachexia. addition, HDAC inhibitors, particularly those broad-spectrum inhibition, showed promise agents CC sera. This findings consistent data, highlighting identifying new drugs. Conclusions: effectively mimics some key aspects pathophysiology skeletal muscle, providing valuable tool drug discovery offers promising avenue therapeutic advancements management cachexia, improve patient outcomes

Language: Английский

Citations

0
Cancer Cachexia: Causes and Therapeutic Strategies DOI
Ismail Ibrahim Al-Janabi

Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), Journal Year: 2025, Volume and Issue: 8(2), P. 1 - 10

Published: April 3, 2025

Cancer cachexia affects approximately 80% of cancer patients and is characterized by skeletal muscle wasting reduced fat mass, resulting in weight loss short survival time. An in-depth understanding the mechanisms can provide platforms for drug non-pharmacological management this condition that claims life around 20% patients. Most current work field pre-clinical stages. However, such preliminary knowledge anticipated to help guide design large comprehensive clinical trials establish safety efficacy therapeutic interventions treat cachexia.

Language: Английский

Citations

0