Modulation of the PI3K/mTOR pathways

Galstyan, Arpine; Cho, Janice; Johnson, Daniel E.; Grandis, Jennifer R.

doi:10.1016/b978-0-12-817868-3.00005-6

Cited by 5 publications

(4 citation statements)

References 55 publications

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“…Among mTOR inhibitors, we chose everolimus, a synthetic macrolide derivative known to be anti-proliferative and important immune-modulator, which is already used in the clinic for lung transplanted patients to enhance the activity of immunosuppressants, such as calcineurin inhibitors. Everolimus mechanism of action consists in forming a complex with FK binding protein (FKBP)-12, which binds to mTOR, blocking the PI3K/Akt/mTOR pathway [ 10 , 11 ], essential for several cellular processes such as cellular growth, proliferation, and metabolism [ 12 ]. The mTOR pathway is also important in in systemic sclerosis (SSc) pathogenesis because through its signaling in SSc fibroblasts it could mediate the immunoinflammatory process typical of ILD in these patients [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Pandolfi

Marengo

Japiassu

et al. 2021

IJMS

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Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells.

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Section: Introductionmentioning

confidence: 99%

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Pandolfi

Marengo

Japiassu

et al. 2021

IJMS

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“…Alpelisib is a selective PI3K inhibitor capable of inhibiting cell proliferation by suppressing signaling through both wild-type and mutated PI3K-alpha pathways [168,169]. Although alpelisib did not show survival benefits when given in ER+ HER2-BC, its usage with trastuzumab is being tested in the ALPHABET trial in advanced HER2+ BC and could provide insights about their adjunct effect in patients with PI3KCA mutations [170].…”

Section: De-escalation Of Adjuvant Therapymentioning

confidence: 99%

Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review

Giffoni de Mello Morais Mata,

Chehade,

Hannouf

et al. 2023

Cancers

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Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15–20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach. Methods: A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries. Conclusion: The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy.

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“…The PI3K/AKT signaling pathway triggers downstream effectors (protein kinases, lipid kinases, transcription factors, metabolic enzymes, regulators of small G proteins, and vesicle trafficking, etc.) and is crucial for growth and survival in response to the extracellular signals [63,64]. The PI3K/AKT signaling pathway downregulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism [63,65,66], and even telomere activity [67,68].…”

Section: Introductionmentioning

confidence: 99%

“…and is crucial for growth and survival in response to the extracellular signals [63,64]. The PI3K/AKT signaling pathway downregulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism [63,65,66], and even telomere activity [67,68].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Wound Healing Bioactive Potential of Extracts Obtained from Bark and Needles of Softwood Species

et al. 2023

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Interest in the extraction of phytochemical bioactive compounds, especially polyphenols from biomass, has recently increased due to their valuable biological potential as natural sources of antioxidants, which could be used in a wide range of applications, from foods and pharmaceuticals to green polymers and bio-based materials. The present research study aimed to provide a comprehensive chemical characterization of the phytochemical composition of forest biomass (bark and needles) of softwood species (Picea abies L., H. Karst., and Abies alba Mill.) and to investigate their in vitro antioxidant and antimicrobial activities to assess their potential in treating and healing infected chronic wounds. The DPPH radical-scavenging method and P–LD were used for a mechanistic explanation of the biomolecular effects of the investigated bioactive compounds. (+)-Catechin, epicatechin, rutin, myricetin, 4 hydroxybenzoic and p-cumaric acids, kaempherol, and apigenin were the main quantified polyphenols in coniferous biomass (in quantities around 100 µg/g). Also, numerous phenolic acids, flavonoids, stilbenes, terpenes, lignans, secoiridoids, and indanes with antioxidant, antimicrobial, anti-inflammatory, antihemolytic, and anti-carcinogenic potential were identified. The Abies alba needle extract was more toxic to microbial strains than the eukaryotic cells that provide its active wound healing principles. In this context, developing industrial upscaling strategies is imperative for the long-term success of biorefineries and incorporating them as part of a circular bio-economy.

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Modulation of the PI3K/mTOR pathways

Cited by 5 publications

References 55 publications

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review

Antioxidant and Wound Healing Bioactive Potential of Extracts Obtained from Bark and Needles of Softwood Species

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