Aging preclinical models in oncology field: from cells to aging

Bouleftour, Wafa; Magné, Nicolas

doi:10.1007/s40520-021-01981-1

Cited by 3 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, the studies of the mechanisms of action are important aspects, which may be required by regulatory agencies. In addition, we have to consider that, traditionally, there is a low inclusion of geriatric patients in clinical trials, and most therapies were validated on experimental models using young animals [ 270 ]. Considering this, ideally experimental models that reflect exactly the same sudden biological changes undergone by the aging of the human body should be used.…”

Section: The Challenge To Implement a Therapy Based On Errisc For Agi...mentioning

confidence: 99%

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

Fraile

Eiró

Costa

et al. 2022

Biology

View full text Add to dashboard Cite

Aging and frailty are complex processes implicating multifactorial mechanisms, such as replicative senescence, oxidative stress, mitochondrial dysfunction, or autophagy disorder. All of these mechanisms drive dramatic changes in the tissue environment, such as senescence-associated secretory phenotype factors and inflamm-aging. Thus, there is a demand for new therapeutic strategies against the devastating effects of the aging and associated diseases. Mesenchymal stem cells (MSC) participate in a “galaxy” of tissue signals (proliferative, anti-inflammatory, and antioxidative stress, and proangiogenic, antitumor, antifibrotic, and antimicrobial effects) contributing to tissue homeostasis. However, MSC are also not immune to aging. Three strategies based on MSC have been proposed: remove, rejuvenate, or replace the senescent MSC. These strategies include the use of senolytic drugs, antioxidant agents and genetic engineering, or transplantation of younger MSC. Nevertheless, these strategies may have the drawback of the adverse effects of prolonged use of the different drugs used or, where appropriate, those of cell therapy. In this review, we propose the new strategy of “Exogenous Restitution of Intercellular Signalling of Stem Cells” (ERISSC). This concept is based on the potential use of secretome from MSC, which are composed of molecules such as growth factors, cytokines, and extracellular vesicles and have the same biological effects as their parent cells. To face this cell-free regenerative therapy challenge, we have to clarify key strategy aspects, such as establishing tools that allow us a more precise diagnosis of aging frailty in order to identify the therapeutic requirements adapted to each case, identify the ideal type of MSC in the context of the functional heterogeneity of these cellular populations, to optimize the mass production and standardization of the primary materials (cells) and their secretome-derived products, to establish the appropriate methods to validate the anti-aging effects and to determine the most appropriate route of administration for each case.

show abstract

Section: The Challenge To Implement a Therapy Based On Errisc For Agi...mentioning

confidence: 99%

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

Fraile

Eiró

Costa

et al. 2022

Biology

View full text Add to dashboard Cite

show abstract

“…Но о влиянии возраста опухоленосителей на фенотипическую пластичность опухолевых клеток практически ничего не известно. Доклинические испытания противоопухолевой терапии проводятся на молодых животных, тогда как онкологические проблемы возникают по большей части в старших возрастных группах [41,42]. То же относится к клиническим испытаниям [43].…”

Section: системные метаболические факторы фенотипической пластичности...unclassified

The systemic factors of mitigating the contribution of the reversible phenotypic transitions of malignant cells to therapeutic resistance

Голубев¹,

Anisimov²

2022

Voprosy Onkologii

View full text Add to dashboard Cite

Анализ литературы, имеющей отношение к фенотипической пластичности трансформированных клеток при развитии резистентности опухолей к терапии, привел с учетом основных характеристик эпителиального, мезенхимального, стволового и сенесцентного состояний опухолевых клеток к выводу, что ключевым фактором терапевтической резистентности является обратимость переходов между этими состояниями. Молекулярные механизмы таких переходов могут включать стохастические переключения активных генов между участием и неучастием в транскрипции. Кинетика переходов и соответствующее равновесие между разными фенотипическими состояниями существенно зависят от среды, где это происходит, а значит от возраста опухоленосителя и от его гормонально-метаболического статуса. Таким образом, воздействия на метаболические параметры организма могут влиять на эффективность противоопухолевой терапии без изменений жизнеспособности и пролиферации опухолевых клеток в любом из возможных для них состояний. С таких позиций рассмотрены данные о противоопухолевых эффектах антидиабетических бигуанидов. Сделан вывод, что, если анализировать в терминах обратимости фенотипических состояний трансформированных клеток противоопухолевые эффекты воздействий, цитотоксические или цитостатические последствия которых неочевидны, это может не только помочь в понимании того, каким образом такие воздействия могут влиять на опухоли, но и расширить круг критериев для поисков новых противораковых средств.

show abstract

Age‐related features of lung cancer treatment using reprogrammed CD8 positive T cells in mice subjected to injection of Lewis lung carcinoma cells

Skurikhin,

Zhukova,

Ermakova

et al. 2024

Thoracic Cancer

View full text Add to dashboard Cite

BackgroundAwareness of age‐related features of carcinogenesis and the importance of cellular immunity is crucial for developing effective antitumor therapies for specific patient groups.MethodsIn this study, we examined different populations of cancer stem cells (CSCs) and circulating tumor cells (CTCs) in "young" (8‐10 weeks) and "aged" (80‐82 weeks) C57BL/6 male mice. We used an orthotopic model of Lewis lung carcinoma (LLC) to evaluate the effectiveness of cell therapy targeting lung cancer through reprogrammed CD8‐positive T cells (rCD8+ T cells) in mice from two different ages.ResultsThe findings revealed that tumor progression with age is primarily caused by impaired recruitment of T cells to the lungs. Additionally, a lower number of CTCs and CSCs were observed in younger mice compared to the older mice. The antitumor effect of rCD8+ T cells in aged mice was found to be inferior to that in young mice, which can be attributed to the reduced impact of therapy on specific CSCs populations.ConclusionsThese results offer new insights into the treatment of lung cancer using rCD8+ T cells. Considering the age‐related characteristics influencing disease progression, this therapy has the potential to significantly enhance the effectiveness of treatment methods.

show abstract

Aging preclinical models in oncology field: from cells to aging

Cited by 3 publications

References 43 publications

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

The systemic factors of mitigating the contribution of the reversible phenotypic transitions of malignant cells to therapeutic resistance

Age‐related features of lung cancer treatment using reprogrammed CD8 positive T cells in mice subjected to injection of Lewis lung carcinoma cells

Contact Info

Product

Resources

About