Trabectedin and Lurbinectedin Extend Survival of Mice Bearing C26 Colon Adenocarcinoma, without Affecting Tumor Growth or Cachexia
| Autor: | Giorgia Careccia, Mara Forti, Giulia Benedetta Martinelli, Laura Pasetto, Rosanna Piccirillo, Simonetta Andrea Licandro, Roberto Latini, Giorgio Aquila, Lidia Staszewsky, Andrea David Re Cecconi, Emilie Venereau, Ilaria Russo, Deborah Novelli, Serge Masson, Eugenio Scanziani, Laura Talamini, Roberta Frapolli, Raffaella Giavazzi, Maurizio D'Incalci, Andrea Resovi, Ezia Bello |
|---|---|
| Přispěvatelé: | Aquila, G, Re Cecconi, A, Forti, M, Frapolli, R, Bello, E, Novelli, D, Russo, I, Licandro, S, Staszewsky, L, Martinelli, G, Talamini, L, Pasetto, L, Resovi, A, Giavazzi, R, Scanziani, E, Careccia, G, Vénéreau, E, Masson, S, Latini, R, D'Incalci, M, Piccirillo, R |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
muscle atrophy Cancer Research medicine.medical_specialty endocrine system lurbinectedin Inflammation lcsh:RC254-282 Article Cachexia Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Wasting Myogenin Trabectedin splenomegaly Myogenesis business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Muscle atrophy 030104 developmental biology Endocrinology Oncology inflammation 030220 oncology & carcinogenesis trabectedin lipids (amino acids peptides and proteins) medicine.symptom business medicine.drug cancer cachexia |
| Zdroj: | Cancers Volume 12 Issue 8 Cancers, Vol 12, Iss 2312, p 2312 (2020) |
| Popis: | Trabectedin (ET743) and lurbinectedin (PM01183) limit the production of inflammatory cytokines that are elevated during cancer cachexia. Mice carrying C26 colon adenocarcinoma display cachexia (i.e., premature death and body wasting with muscle, fat and cardiac tissue depletion), high levels of inflammatory cytokines and subsequent splenomegaly. We tested whether such drugs protected these mice from cachexia. Ten-week-old mice were inoculated with C26 cells and three days later randomized to receive intravenously vehicle or 0.05 mg/kg ET743 or 0.07 mg/kg PM01183, three times a week for three weeks. ET743 or PM01183 extended the lifespan of C26-mice by 30% or 85%, respectively, without affecting tumor growth or food intake. Within 13 days from C26 implant, both drugs did not protect fat, muscle and heart from cachexia. Since PM01183 extended the animal survival more than ET743, we analyzed PM01183 further. In tibialis anterior of C26-mice, but not in atrophying myotubes, PM01183 restrained the NF-&kappa B/PAX7/myogenin axis, possibly reducing the pro-inflammatory milieu, and failed to limit the C/EBP&beta /atrogin-1 axis. Inflammation-mediated splenomegaly of C26-mice was inhibited by PM01183 for as long as the treatment lasted, without reducing IL-6, M-CSF or IL-1&beta in plasma. ET743 and PM01183 extend the survival of C26-bearing mice unchanging tumor growth or cachexia but possibly restrain muscle-related inflammation and C26-induced splenomegaly. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|