Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment
In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial...
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| Published in | Cancers Vol. 16; no. 5; p. 1075 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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06.03.2024
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| ISSN | 2072-6694 2072-6694 |
| DOI | 10.3390/cancers16051075 |
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| Abstract | In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. |
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| AbstractList | In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. Currently, muscle testing remains underutilized in cancer cachexia research, since muscle biopsies are mainly performed at the end of experimental protocols. We aimed to introduce the concept of longitudinal muscle testing for cancer cachexia by initially demonstrating its feasibility and safety for the test subjects. Following that, we tested the hypothesis on a tumor-bearing rat model. Results were indicative of heterogeneity in cancer cachexia manifestation between different subjects and throughout the disease course. There is an abundance of researched pathways and mechanisms of cachexia, as well as interventions to target them. Thus, moving forward, developing biomarkers to suggest “what to target and when to do it” is essential. Sequential muscle biopsies can serve as a promising tool to guide personalized precision treatment for cancer cachexia, as well as to monitor the disease evolution and response to therapy. In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. Simple SummaryCurrently, muscle testing remains underutilized in cancer cachexia research, since muscle biopsies are mainly performed at the end of experimental protocols. We aimed to introduce the concept of longitudinal muscle testing for cancer cachexia by initially demonstrating its feasibility and safety for the test subjects. Following that, we tested the hypothesis on a tumor-bearing rat model. Results were indicative of heterogeneity in cancer cachexia manifestation between different subjects and throughout the disease course. There is an abundance of researched pathways and mechanisms of cachexia, as well as interventions to target them. Thus, moving forward, developing biomarkers to suggest “what to target and when to do it” is essential. Sequential muscle biopsies can serve as a promising tool to guide personalized precision treatment for cancer cachexia, as well as to monitor the disease evolution and response to therapy.AbstractIn the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. Currently, muscle testing remains underutilized in cancer cachexia research, since muscle biopsies are mainly performed at the end of experimental protocols. We aimed to introduce the concept of longitudinal muscle testing for cancer cachexia by initially demonstrating its feasibility and safety for the test subjects. Following that, we tested the hypothesis on a tumor-bearing rat model. Results were indicative of heterogeneity in cancer cachexia manifestation between different subjects and throughout the disease course. There is an abundance of researched pathways and mechanisms of cachexia, as well as interventions to target them. Thus, moving forward, developing biomarkers to suggest “what to target and when to do it” is essential. Sequential muscle biopsies can serve as a promising tool to guide personalized precision treatment for cancer cachexia, as well as to monitor the disease evolution and response to therapy. |
| Audience | Academic |
| Author | Korompilias, Anastasios Stagikas, Dimitrios Tsamis, Konstantinos I. Sarmas, Ioannis Dounousi, Evangelia Mauri, Davide Kosmas, Dimitrios Ntzani, Evangelia Tzavellas, Nikolaos P. Filis, Panagiotis Lekkas, Panagiotis Peschos, Dimitrios Simos, Yannis V. Zachariou, Christianna |
| AuthorAffiliation | 4 Department of Orthopaedic Surgery, School of Medicine, University of Ioannina, 45110 Ioannina, Greece 6 Department of Neurology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece 1 Department of Medical Oncology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece 7 Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Providence, RI 02912, USA 3 Department of Physiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece dimitriosstag@gmail.com (D.S.); chzachar@uoi.gr (C.Z.); ktsamis@uoi.gr (K.I.T.) 5 Department of Nephrology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece; evangeldou@gmail.com 2 Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece; entzani@uoi.gr |
| AuthorAffiliation_xml | – name: 2 Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece; entzani@uoi.gr – name: 7 Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Providence, RI 02912, USA – name: 5 Department of Nephrology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece; evangeldou@gmail.com – name: 1 Department of Medical Oncology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece – name: 3 Department of Physiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece dimitriosstag@gmail.com (D.S.); chzachar@uoi.gr (C.Z.); ktsamis@uoi.gr (K.I.T.) – name: 6 Department of Neurology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece – name: 4 Department of Orthopaedic Surgery, School of Medicine, University of Ioannina, 45110 Ioannina, Greece |
| Author_xml | – sequence: 1 givenname: Panagiotis orcidid: 0000-0003-3190-5753 surname: Filis fullname: Filis, Panagiotis – sequence: 2 givenname: Nikolaos P. surname: Tzavellas fullname: Tzavellas, Nikolaos P. – sequence: 3 givenname: Dimitrios surname: Stagikas fullname: Stagikas, Dimitrios – sequence: 4 givenname: Christianna surname: Zachariou fullname: Zachariou, Christianna – sequence: 5 givenname: Panagiotis surname: Lekkas fullname: Lekkas, Panagiotis – sequence: 6 givenname: Dimitrios orcidid: 0000-0003-2979-0512 surname: Kosmas fullname: Kosmas, Dimitrios – sequence: 7 givenname: Evangelia orcidid: 0000-0002-1172-1829 surname: Dounousi fullname: Dounousi, Evangelia – sequence: 8 givenname: Ioannis surname: Sarmas fullname: Sarmas, Ioannis – sequence: 9 givenname: Evangelia orcidid: 0000-0003-3712-4181 surname: Ntzani fullname: Ntzani, Evangelia – sequence: 10 givenname: Davide surname: Mauri fullname: Mauri, Davide – sequence: 11 givenname: Anastasios surname: Korompilias fullname: Korompilias, Anastasios – sequence: 12 givenname: Yannis V. orcidid: 0000-0003-1764-8906 surname: Simos fullname: Simos, Yannis V. – sequence: 13 givenname: Konstantinos I. orcidid: 0000-0002-7032-1630 surname: Tsamis fullname: Tsamis, Konstantinos I. – sequence: 14 givenname: Dimitrios surname: Peschos fullname: Peschos, Dimitrios |
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| SubjectTerms | Animal models Atrophy Biomarkers Biopsy Cachexia Cancer Diagnosis Eating behavior Euthanasia Medical research Metastases Musculoskeletal system Pain Tumors |
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| Title | Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment |
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