المؤلفون: Pinanti, Honesty Nurizza, Christina, Yuyun Ika, Widodo, Nashi, Rifa'i, Muhaimin, Djati, Muhammad Sasmito

المصدر: AIP Conference Proceedings; 2023, Vol. 2913 Issue 1, p1-11, 11p

مصطلحات موضوعية: PHYTOCHEMICALS, SELAGINELLA, AMINO acid residues, MOLECULAR docking, BINDING sites, MTOR inhibitors

مستخلص: Selaginella doederleinii Hieron has long been used traditionally by Indonesian to treat various diseases, including cancer. However, the anti-breast cancer activity of the plant has been little studied. This study aimed to identify the phytochemicals in Selaginella doederleinii Hieron extract and determine its anti-breast cancer potential, especially as PI3K/mTOR inhibitors using in silico approach. The phytochemicals were identified using LC-HRMS and analyzed for their physicochemical properties and potential anticancer activity through SwissADME, PASS prediction, and molecular docking. The LC-HRMS method tentatively identified 25 phytochemicals from the extract classified into four large groups. Among all these compounds, 14 compounds were predicted to possess good oral bioavailability and antineoplastic potential. Molecular docking studies showed that all compounds, except (6S,9R)Vomifoliol could interact with amino acid residues in the binding site of GDC-0326 in the PI3K p110α catalytic subunit. These compounds also had a comparable binding affinity with GDC-0326. Melosatin B, Bleekerine, and Affinisine had the lowest binding affinity scores and bound several residues interacting with the PI3K inhibitor. Meanwhile, all compounds could establish some chemical interactions with the binding site of Rapamycin in the FKBP51/FRB domain of mTOR, though they had a weaker binding affinity. Affinisine, Microhelenin C, and Alpinine had the lowest binding affinity scores and bound residues interacting with the mTOR inhibitor. Further in vitro and in vivo studies were required to validate the results. [ABSTRACT FROM AUTHOR]

: Copyright of AIP Conference Proceedings is the property of American Institute of Physics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Genetics, Molecular Biology, Pharmacology, Immunology, Developmental Biology, Cancer, Mental Health, Hematology, Infectious Diseases, Plant Biology, Computational Biology, PI3K/AKT/mTORC pathway, Pan PI3K inhibitors, Isoform-specific PI3K inhibitors, Dual PI3K/mTOR inhibitors, AKT inhibitors, Allosteric mTOR inhibitors, ATP-competitive mTOR inhibitors, Bi-steric mTOR inhibitors, PDK1 inhibitors

الوصف: Additional file 1: Supplementary figure 1.

العلاقة: https://figshare.com/articles/presentation/Additional_file_1_of_PI3K_AKT_mTOR_signaling_transduction_pathway_and_targeted_therapies_in_cancer/24597442Test

الإتاحة: https://doi.org/10.6084/m9.figshare.24597442.v1Test
https://figshare.com/articles/presentation/Additional_file_1_of_PI3K_AKT_mTOR_signaling_transduction_pathway_and_targeted_therapies_in_cancer/24597442Test

المؤلفون: Spirina, L. V., Gorbunov, A. K., Chigevskaya, S. Y., Usynin, Y. A., Kondakova, I. V., Slonimskaya, E. M., Usynin, E. A., Choinzonov, E. L., Zaitseva, O. S.

المصدر: AIP Conference Proceedings; 2017, Vol. 1882 Issue 1, p1-6, 6p, 4 Charts

مصطلحات موضوعية: MESSENGER RNA, TRANSCRIPTION factors, MTOR inhibitors, ANTINEOPLASTIC agents, MTOR protein

مستخلص: Transcription factors POU4F1 (neurogenic factor Brn-3α) play a pivotal role in cancers development. The aim of the study was to reveal the Brn-3α expression, AR, ER expression in cancers development, association with AKT/mTOR pathway activation. 30 patients with locally advanced prostate cancer, 20 patients with papillary thyroid cancer, T2-3N0-1M0 stages and 40 patients with renal cell cancer T2-3N0M0-1 were involved into the study. The expressions of Brn-3α, AR, ERα, components of AKT/m-TOR signaling pathway genes were performed by real-time PCR. The dependence of Brn-3α expression on mRNA levels of steroid hormone receptors and components of AKT/m-TOR signaling pathway in studied cancers were shown. High levels of mRNA of nuclear factor, steroid hormone receptors were found followed by the activation of this signaling pathway in prostate cancer tissue. The reduction of transcription factor Brn-3α was accompanied with tumor invasive growth with increasing rates of AR, ER and 4E-BP1 mRNA. Thyroid cancer development happened in a case of a Brn-3α and steroid hormone receptors decrease. The activation of AKT/m-TOR signaling pathway was established in the metastatic renal cancers, accompanied with the increase of ER mRNA. But there was no correlation between the steroid receptor and Brn-3α. One-direction changes of Brn-3α were observed in the development of prostate and thyroid cancer due to its effect on the steroid hormone receptors and the activation of AKT/m-TOR signaling pathway components. The influence of this factor on the development of the kidney cancer was mediated through m-TOR activity modifications, the key enzyme of oncogenesis. [ABSTRACT FROM AUTHOR]

: Copyright of AIP Conference Proceedings is the property of American Institute of Physics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Petroni, Vanessa, Fenech, Anthony G., Saliba, Christian, Camilleri Podesta, Marie Therese, Baldacchino, Shawn, Grech, Godfrey, Ninth Malta Medical School Conference

مصطلحات موضوعية: Breast -- Cancer -- Treatment, MTOR inhibitors, Rapamycin -- Effectiveness, Aurora Kinase A, MCF-7 cells

الوصف: Introduction: Breast cancer is classified into intrinsic molecular subtypes, each relating to predictive prognostic and clinical outcomes. Rapamycin inhibits the mammalian target of rapamycin (mTOR) pathway, which is often deregulated in various types of cancer. mTOR inhibitors are associated with antiproliferation and apoptosis. Aim: Investigating the differential expression of breast cancer signature genes following rapamycin treatment in various breast cancer subtypes. ; peer-reviewed

العلاقة: Petroni, V., Fenech, A.G., Saliba, C., Camilleri Podesta, M.T., Baldacchino, S., & Grech, G. (2015). Differential expression of breast cancer signature genes following rapamycin treatment. IX Malta Medical School Conference abstract book, OP3.18.; https://www.um.edu.mt/library/oar/handle/123456789/108908Test

الإتاحة: https://www.um.edu.mt/library/oar/handle/123456789/108908Test

المؤلفون: Mills, Cheyanne, Kee, Lynn

المصدر: Southeastern Biology; Jan-Dec2021, Vol. 68 Issue 1-4, p56-57, 2p

مصطلحات موضوعية: PAINTED lady (Insect), MTOR inhibitors, RAPAMYCIN, BUTTERFLIES, CATERPILLARS

مستخلص: The mechanistic target of rapamycin (mTOR) is a kinase that is conserved from yeast to mice to humans. mTOR functions in integrating signals to control cell and organismal growth, metabolism and ageing. Rapamycin, an inhibitor of mTOR extends the lifespan of many organisms, including worms, flies and mice. In this study, we investigated the effect of rapamycin on the development of Vanessa cardui, commonly known as painted lady butterflies. We observed that V. cardui caterpillars that have been fed rapamycin have a decreased growth rate and larval size. We also report that rapamycin fed caterpillars take a longer time to form chrysalis and do not hatch out of the chrysalis. These findings suggest that the butterflies cannot hatch due to impaired or delayed wing development. Future studies will investigate the effect of rapamycin treatment on mTOR target proteins. [ABSTRACT FROM AUTHOR]

: Copyright of Southeastern Biology is the property of Association of Southeastern Biologists (ASB) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: GIOVAGNOLI, Stefano, MAGINI, Alessandro, POLCHI, ALICE, TANCINI, Brunella, EMILIANI, Carla, Mazuryk, Jarosław, Gapinski, Jacek, Patkowski, Adam

المساهمون: Giovagnoli, Stefano, Magini, Alessandro, Polchi, Alice, Mazuryk, Jarosław, Gapinski, Jacek, Tancini, Brunella, Patkowski, Adam, Emiliani, Carla

مصطلحات موضوعية: mTOR inhibitors, rapamycin, solid lipid nanoparticles, brain delivery

الوصف: Recently, the use of mammalian target of rapamycin (mTOR) inhibitors, in particular rapamycin (Rp), has been suggested to improve the treatment of neurodegenerative diseases. However, as Rp is a strong immunosuppressant, specific delivery to the brain has been postulated to avoid systemic exposure. In this work, Rp loaded solid lipid nanoparticles (Rp-SLN) stabilized with polysorbate 80 (PS80) were prepared comparing two different methods and lipids. The formulations were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), wide angle X-ray scattering (WAXS), cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and particle tracking. In vitro release and short-term stability were assessed. Biological behavior of Rp-SLN was tested in SH-SY5Y neuroblastoma cells. The inhibition of mTOR complex 1 (mTORC1) was evaluated over time by a pulse-chase study compared to free Rp and Rp nanocrystals. Compritol Rp-SLN resulted more stable and possessed proper size and surface properties with respect to cetyl palmitate Rp-SLN. Rapamycin was entrapped in an amorphous form in the solid lipid matrix that showed partial crystallinity with stable Lbeta, sub-Lalfa and Lbeta’ arrangements. PS80 was stably anchored on particle surface. The SEM and AFM imaging and shape-modeling by the combined DLS-SANS analysis revealed that Rp-SLN with a hydrodynamic radius of ∼46 nm preserve a platelet-like or flat ellipsoidal structure with a thickness of 8–9 nm. These dimensions correlate with a single lipid bilayer, organized in a triclinic Lbeta polymorph, and covered with a 1–2-nm P80 shell. Consistently, FT-IR spectra acquired in the range 52–75◦C, confirmed that the Rp incorporation within the lipid matrix decreases the point of the gel-liquid crystal (Lbeta-Lalfa) phase transition. No drug release was observed over 24 h and Rp-SLN had a higher cell uptake and a more sustained effect over a week. The mTORC1 inhibition was increased with Rp-SLN. Overall, compritol Rp-SLN show ...

وصف الملف: ELETTRONICO

العلاقة: ispartofbook:Development of Pharmaceutical Nanosystems; Pharma+Bio Asia 2016; http://hdl.handle.net/11391/1387984Test

الإتاحة: http://hdl.handle.net/11391/1387984Test

المؤلفون: Shing, C. M., Brown, L., Fassett, R. G., Lexis, L. A., Coombes, J. S.

المساهمون: David Harris

مصطلحات موضوعية: Calcineurin, Mammalian, Rapamycin (mTOR) inhibitors, Vascular dysfunction, Inflammation, Oxidative stress, EX, 920103 Cardiovascular System and Diseases, 110602 Exercise Physiology

العلاقة: orcid:0000-0002-5318-6940; orcid:0000-0002-6990-3596

الإتاحة: https://doi.org/10.1111/j.1440-1797.2009.01176.xTest
https://espace.library.uq.edu.au/view/UQ:201689Test