Therapy-induced normal tissue damage promotes breast cancer metastasis

iScience, Год журнала: 2023, Номер 27(1), С. 108503 - 108503

Опубликована: Ноя. 22, 2023

Highlights•Prior chemotherapy treatment of mice enhances metastatic colonization and outgrowth•Chemotherapy induces SASP expression in normal tissues cultured cells•Chemotherapy fibroblast senescence sensitivity to navitoclax cultureSummaryDisseminated tumor cells frequently exhibit a period dormancy, rendering them insensitive; conversely, the systemic delivery chemotherapies can result tissue damage. Using multiple mouse human breast cancer models, we demonstrate that prior administration outgrowth. In vitro, chemotherapy-treated fibroblasts display pro-tumorigenic senescence-associated secretory phenotype (SASP) are effectively eliminated by targeting anti-apoptotic protein BCL-xL. vivo, tissues; however, accumulation senescent is limited, BCL-xL inhibitors unable reduce chemotherapy-enhanced metastasis. This likely reflects chemotherapy-exposed stromal do not enter BCL-xL-dependent or switch their dependency other BCL-2 family members. study highlights role microenvironment controlling outgrowth disseminated need identify additional approaches limit effects therapy-induced damage.Graphical abstract

Язык: Английский

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BCL-2 Modulates IRE1α Activation to Attenuate Endoplasmic Reticulum Stress and Pulmonary Fibrosis

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2023, Номер 70(4), С. 247 - 258

Опубликована: Дек. 20, 2023

BCL-2 family members are known to be implicated in survival numerous biological settings. Here, we provide evidence that injury and repair processes lungs, mainly acts attenuate endoplasmic reticulum (ER) stress limit extracellular matrix accumulation. Days after an intratracheal bleomycin challenge, mice lose a fraction of their alveolar type II epithelium from terminal ER driven by activation the critical sensor effector IRE1α. This is dramatically increased inhibition, because IRE1α dependent on its physical association with BCL-2-proapoptotic member BAX, found disrupt this

Язык: Английский

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Getting the Timing Right: Controlling BCL-2 Inhibition as an Antifibrotic Therapy

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2024, Номер 70(4), С. 231 - 232

Опубликована: Янв. 23, 2024

"Getting the Timing Right: Controlling BCL-2 Inhibition as an Anti-Fibrotic Therapy." American Journal of Respiratory Cell and Molecular Biology, 0(ja), pp.

Язык: Английский

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Venetoclax-associated interstitial pneumonitis

Respiratory Medicine Case Reports, Год журнала: 2024, Номер 50, С. 102038 - 102038

Опубликована: Янв. 1, 2024

Venetoclax is a selective inhibitor of the antiapoptotic protein B-cell lymphoma 2 (BCL-2). It approved for treatment chronic lymphocytic leukemia (CLL), small (SLL) and acute myeloid (AML) in combination with chemotherapy or hypomethylating agents. Interstitial pneumonitis due to venetoclax has not been described literature. We describe case 79-year-old female who experienced SLL relapse developed interstitial associated venetoclax, which completely resolved after discontinuation medication.

Язык: Английский

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Exosome miRNA profile and mitigating effect of miR-23a-3p/Cul3 axis on apoptosis in the pathogenesis of SiO2 dust-induced lung fibrosis

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 283, С. 116971 - 116971

Опубликована: Авг. 30, 2024

Silicosis is an irreversible interstitial lung fibrosis resulting from persistent inflammation induced by long-term inhalation of SiO

Язык: Английский

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