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  1. Artikel ; Online: MUC1-C regulates NEAT1 lncRNA expression and paraspeckle formation in cancer progression.

    Bhattacharya, Atrayee / Wang, Keyi / Penailillo, Johany / Chan, Chi Ngai / Fushimi, Atsushi / Yamashita, Nami / Daimon, Tatsuaki / Haratake, Naoki / Ozawa, Hiroki / Nakashoji, Ayako / Shigeta, Keisuke / Morimoto, Yoshihiro / Miyo, Masaaki / Kufe, Donald W

    Oncogene

    2024  

    Abstract: The MUC1 gene evolved in mammals for adaptation of barrier tissues in response to infections and damage. Paraspeckles are nuclear bodies formed on the NEAT1 lncRNA in response to loss of homeostasis. There is no known intersection of MUC1 with NEAT1 or ... ...

    Abstract The MUC1 gene evolved in mammals for adaptation of barrier tissues in response to infections and damage. Paraspeckles are nuclear bodies formed on the NEAT1 lncRNA in response to loss of homeostasis. There is no known intersection of MUC1 with NEAT1 or paraspeckles. Here, we demonstrate that the MUC1-C subunit plays an essential role in regulating NEAT1 expression. MUC1-C activates the NEAT1 gene with induction of the NEAT1_1 and NEAT1_2 isoforms by NF-κB- and MYC-mediated mechanisms. MUC1-C/MYC signaling also induces expression of the SFPQ, NONO and FUS RNA binding proteins (RBPs) that associate with NEAT1_2 and are necessary for paraspeckle formation. MUC1-C integrates activation of NEAT1 and RBP-encoding genes by recruiting the PBAF chromatin remodeling complex and increasing chromatin accessibility of their respective regulatory regions. We further demonstrate that MUC1-C and NEAT1 form an auto-inductive pathway that drives common sets of genes conferring responses to inflammation and loss of homeostasis. Of functional significance, we find that the MUC1-C/NEAT1 pathway is of importance for the cancer stem cell (CSC) state and anti-cancer drug resistance. These findings identify a previously unrecognized role for MUC1-C in the regulation of NEAT1, RBPs, and paraspeckles that has been co-opted in promoting cancer progression.
    Sprache Englisch
    Erscheinungsdatum 2024-05-27
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-024-03068-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Cellular response to spinal cord injury in regenerative and non-regenerative stages in Xenopus laevis.

    Edwards-Faret, Gabriela / González-Pinto, Karina / Cebrián-Silla, Arantxa / Peñailillo, Johany / García-Verdugo, José Manuel / Larraín, Juan

    Neural development

    2021  Band 16, Heft 1, Seite(n) 2

    Abstract: Background: The efficient regenerative abilities at larvae stages followed by a non-regenerative response after metamorphosis in froglets makes Xenopus an ideal model organism to understand the cellular responses leading to spinal cord regeneration.: ... ...

    Abstract Background: The efficient regenerative abilities at larvae stages followed by a non-regenerative response after metamorphosis in froglets makes Xenopus an ideal model organism to understand the cellular responses leading to spinal cord regeneration.
    Methods: We compared the cellular response to spinal cord injury between the regenerative and non-regenerative stages of Xenopus laevis. For this analysis, we used electron microscopy, immunofluorescence and histological staining of the extracellular matrix. We generated two transgenic lines: i) the reporter line with the zebrafish GFAP regulatory regions driving the expression of EGFP, and ii) a cell specific inducible ablation line with the same GFAP regulatory regions. In addition, we used FACS to isolate EGFP
    Results: In regenerative stage animals, spinal cord regeneration triggers a rapid sealing of the injured stumps, followed by proliferation of cells lining the central canal, and formation of rosette-like structures in the ablation gap. In addition, the central canal is filled by cells with similar morphology to the cells lining the central canal, neurons, axons, and even synaptic structures. Regeneration is almost completed after 20 days post injury. In non-regenerative stage animals, mostly damaged tissue was observed, without clear closure of the stumps. The ablation gap was filled with fibroblast-like cells, and deposition of extracellular matrix components. No reconstruction of the spinal cord was observed even after 40 days post injury. Cellular markers analysis confirmed these histological differences, a transient increase of vimentin, fibronectin and collagen was detected in regenerative stages, contrary to a sustained accumulation of most of these markers, including chondroitin sulfate proteoglycans in the NR-stage. The zebrafish GFAP transgenic line was validated, and we have demonstrated that is a very reliable and new tool to study the role of neural stem progenitor cells (NSPCs). RNASeq of GFAP::EGFP cells has allowed us to clearly demonstrate that indeed these cells are NSPCs. On the contrary, the GFAP::EGFP transgene is mainly expressed in astrocytes in non-regenerative stages. During regenerative stages, spinal cord injury activates proliferation of NSPCs, and we found that are mainly differentiated into neurons and glial cells. Specific ablation of these cells abolished proper regeneration, confirming that NSPCs cells are necessary for functional regeneration of the spinal cord.
    Conclusions: The cellular response to spinal cord injury in regenerative and non-regenerative stages is profoundly different between both stages. A key hallmark of the regenerative response is the activation of NSPCs, which massively proliferate, and are differentiated into neurons to reconstruct the spinal cord. Also very notably, no glial scar formation is observed in regenerative stages, but a transient, glial scar-like structure is formed in non-regenerative stage animals.
    Mesh-Begriff(e) Animals ; Neural Stem Cells ; Spinal Cord ; Spinal Cord Injuries ; Spinal Cord Regeneration ; Xenopus laevis ; Zebrafish
    Sprache Englisch
    Erscheinungsdatum 2021-02-02
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1749-8104
    ISSN (online) 1749-8104
    DOI 10.1186/s13064-021-00152-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Analysis of the early response to spinal cord injury identified a key role for mTORC1 signaling in the activation of neural stem progenitor cells.

    Peñailillo, Johany / Palacios, Miriam / Mounieres, Constanza / Muñoz, Rosana / Slater, Paula G / De Domenico, Elena / Patrushev, Ilya / Gilchrist, Mike / Larraín, Juan

    NPJ Regenerative medicine

    2021  Band 6, Heft 1, Seite(n) 68

    Abstract: Xenopus laevis are able to regenerate the spinal cord during larvae stages through the activation of neural stem progenitor cells (NSPCs). Here we use high-resolution expression profiling to characterize the early transcriptome changes induced after ... ...

    Abstract Xenopus laevis are able to regenerate the spinal cord during larvae stages through the activation of neural stem progenitor cells (NSPCs). Here we use high-resolution expression profiling to characterize the early transcriptome changes induced after spinal cord injury, aiming to identify the signals that trigger NSPC proliferation. The analysis delineates a pathway that starts with a rapid and transitory activation of immediate early genes, followed by migration processes and immune response genes, the pervasive increase of NSPC-specific ribosome biogenesis factors, and genes involved in stem cell proliferation. Western blot and immunofluorescence analysis showed that mTORC1 is rapidly and transiently activated after SCI, and its pharmacological inhibition impairs spinal cord regeneration and proliferation of NSPC through the downregulation of genes involved in the G1/S transition of cell cycle, with a strong effect on PCNA. We propose that the mTOR signaling pathway is a key player in the activation of NPSCs during the early steps of spinal cord regeneration.
    Sprache Englisch
    Erscheinungsdatum 2021-10-22
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2057-3995
    ISSN (online) 2057-3995
    DOI 10.1038/s41536-021-00179-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Epigenetic regulation of CD38/CD48 by KDM6A mediates NK cell response in multiple myeloma.

    Liu, Jiye / Xing, Lijie / Li, Jiang / Wen, Kenneth / Liu, Ning / Liu, Yuntong / Wu, Gongwei / Wang, Su / Ogiya, Daisuke / Song, Tian-Yu / Kurata, Keiji / Penailillo, Johany / Morelli, Eugenio / Wang, Tingjian / Hong, Xiaoning / Gulla, Annamaria / Tai, Yu-Tzu / Munshi, Nikhil / Richardson, Paul /
    Carrasco, Ruben / Hideshima, Teru / Anderson, Kenneth C

    Nature communications

    2024  Band 15, Heft 1, Seite(n) 1367

    Abstract: Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR ... ...

    Abstract Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.
    Mesh-Begriff(e) Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Epigenesis, Genetic ; Histones/metabolism ; ADP-ribosyl Cyclase 1 ; Killer Cells, Natural
    Chemische Substanzen Histones ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
    Sprache Englisch
    Erscheinungsdatum 2024-02-14
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45561-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification.

    Brown, Needa / Rocchi, Paul / Carmès, Léna / Guthier, Romy / Iyer, Meghna / Seban, Léa / Morris, Toby / Bennett, Stephanie / Lavelle, Michael / Penailillo, Johany / Carrasco, Ruben / Williams, Chris / Huynh, Elizabeth / Han, Zhaohui / Kaza, Evangelia / Doussineau, Tristan / Toprani, Sneh M / Qin, Xingping / Nagel, Zachary D /
    Sarosiek, Kristopher A / Hagège, Agnès / Dufort, Sandrine / Bort, Guillaume / Lux, François / Tillement, Olivier / Berbeco, Ross

    Theranostics

    2023  Band 13, Heft 14, Seite(n) 4711–4729

    Abstract: Background: ...

    Abstract Background:
    Mesh-Begriff(e) Humans ; Precision Medicine ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Nanoparticles ; Contrast Media ; Magnetic Resonance Imaging/methods ; Radiation Dosage ; Theranostic Nanomedicine/methods
    Chemische Substanzen AGuIX ; Contrast Media
    Sprache Englisch
    Erscheinungsdatum 2023-08-21
    Erscheinungsland Australia
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.85663
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.

    Chong, Stephen Jun Fei / Zhu, Fen / Dashevsky, Olga / Mizuno, Rin / Lai, Jolin Xh / Hackett, Liam / Ryan, Christine E / Collins, Mary C / Iorgulescu, J Bryan / Guièze, Romain / Penailillo, Johany / Carrasco, Ruben / Hwang, Yeonjoo C / Muñoz, Denise P / Bouhaddou, Mehdi / Lim, Yaw Chyn / Wu, Catherine J / Allan, John N / Furman, Richard R /
    Goh, Boon Cher / Pervaiz, Shazib / Coppé, Jean-Philippe / Mitsiades, Constantine S / Davids, Matthew S

    The Journal of clinical investigation

    2023  Band 133, Heft 22

    Abstract: The B cell leukemia/lymphoma 2 (BCL-2) inhibitor venetoclax is effective in chronic lymphocytic leukemia (CLL); however, resistance may develop over time. Other lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL) are frequently ... ...

    Abstract The B cell leukemia/lymphoma 2 (BCL-2) inhibitor venetoclax is effective in chronic lymphocytic leukemia (CLL); however, resistance may develop over time. Other lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL) are frequently intrinsically resistant to venetoclax. Although genomic resistance mechanisms such as BCL2 mutations have been described, this probably only explains a subset of resistant cases. Using 2 complementary functional precision medicine techniques - BH3 profiling and high-throughput kinase activity mapping - we found that hyperphosphorylation of BCL-2 family proteins, including antiapoptotic myeloid leukemia 1 (MCL-1) and BCL-2 and proapoptotic BCL-2 agonist of cell death (BAD) and BCL-2 associated X, apoptosis regulator (BAX), underlies functional mechanisms of both intrinsic and acquired resistance to venetoclax in CLL and DLBCL. Additionally, we provide evidence that antiapoptotic BCL-2 family protein phosphorylation altered the apoptotic protein interactome, thereby changing the profile of functional dependence on these prosurvival proteins. Targeting BCL-2 family protein phosphorylation with phosphatase-activating drugs rewired these dependencies, thus restoring sensitivity to venetoclax in a panel of venetoclax-resistant lymphoid cell lines, a resistant mouse model, and in paired patient samples before venetoclax treatment and at the time of progression.
    Mesh-Begriff(e) Mice ; Animals ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Drug Resistance, Neoplasm/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; bcl-X Protein/genetics ; Apoptosis Regulatory Proteins ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/genetics ; Myeloid Cell Leukemia Sequence 1 Protein/genetics ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism
    Chemische Substanzen venetoclax (N54AIC43PW) ; Proto-Oncogene Proteins c-bcl-2 ; Bridged Bicyclo Compounds, Heterocyclic ; bcl-X Protein ; Apoptosis Regulatory Proteins ; Antineoplastic Agents ; Myeloid Cell Leukemia Sequence 1 Protein
    Sprache Englisch
    Erscheinungsdatum 2023-11-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI170169
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Ubiquitin receptor PSMD4/Rpn10 is a novel therapeutic target in multiple myeloma.

    Du, Ting / Song, Yan / Ray, Arghya / Wan, Xueping / Yao, Yao / Samur, Mehmet K / Shen, Chen / Penailillo, Johany / Sewastianik, Tomasz / Tai, Yu-Tzu / Fulciniti, Mariateresa / Munshi, Nikhil C / Wu, Hao / Carrasco, Ruben D / Chauhan, Dharminder / Anderson, Kenneth C

    Blood

    2022  Band 141, Heft 21, Seite(n) 2599–2614

    Abstract: PSMD4/Rpn10 is a subunit of the 19S proteasome unit that is involved with feeding target proteins into the catalytic machinery of the 26S proteasome. Because proteasome inhibition is a common therapeutic strategy in multiple myeloma (MM), we investigated ...

    Abstract PSMD4/Rpn10 is a subunit of the 19S proteasome unit that is involved with feeding target proteins into the catalytic machinery of the 26S proteasome. Because proteasome inhibition is a common therapeutic strategy in multiple myeloma (MM), we investigated Rpn10 and found that it is highly expressed in MM cells compared with normal plasma cells. Rpn10 levels inversely correlated with overall survival in patients with MM. Inducible knockout or knockdown of Rpn10 decreased MM cell viability both in vitro and in vivo by triggering the accumulation of polyubiquitinated proteins, cell cycle arrest, and apoptosis associated with the activation of caspases and unfolded protein response-related pathways. Proteomic analysis revealed that inhibiting Rpn10 increased autophagy, antigen presentation, and the activation of CD4+ T and natural killer cells. We developed an in vitro AlphaScreen binding assay for high-throughput screening and identified a novel Rpn10 inhibitor, SB699551 (SB). Treating MM cell lines, leukemic cell lines, and primary cells from patients with MM with SB decreased cell viability without affecting the viability of normal peripheral blood mononuclear cells. SB inhibited the proliferation of MM cells even in the presence of the tumor-promoting bone marrow milieu and overcame proteasome inhibitor (PI) resistance without blocking the 20S proteasome catalytic function or the 19S deubiquitinating activity. Rpn10 blockade by SB triggered MM cell death via similar pathways as the genetic strategy. In MM xenograft models, SB was well tolerated, inhibited tumor growth, and prolonged survival. Our data suggest that inhibiting Rpn10 will enhance cytotoxicity and overcome PI resistance in MM, providing the basis for further optimization studies of Rpn10 inhibitors for clinical application.
    Mesh-Begriff(e) Humans ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Proteomics ; Leukocytes, Mononuclear/metabolism ; Carrier Proteins/genetics ; Proteins/metabolism ; RNA-Binding Proteins
    Chemische Substanzen Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Ubiquitin ; Carrier Proteins ; Proteins ; PSMD4 protein, human ; RNA-Binding Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-11-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2022017897
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma.

    Gulla, Annamaria / Morelli, Eugenio / Johnstone, Megan / Turi, Marcello / Samur, Mehmet K / Botta, Cirino / Cifric, Selma / Folino, Pietro / Vinaixa, Delaney / Barello, Francesca / Clericuzio, Cole / Favasuli, Vanessa Katia / Maisano, Domenico / Talluri, Srikanth / Prabhala, Rao H / Bianchi, Giada / Fulciniti, Mariateresa / Wen, Kenneth / Kurata, Keiji /
    Liu, Jiye / Penailillo, Johany / Bragoni, Alberto / Sapino, Anna / Richardson, Paul G / Chauhan, Dharminder / Carrasco, Ruben D / Hideshima, Teru / Munshi, Nikhil C / Anderson, Kenneth C

    Blood

    2024  

    Abstract: Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant anti-tumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and ... ...

    Abstract Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant anti-tumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABARAP is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in high-risk MM patients. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent anti-tumor T cell response. Low GABARAP was independently associated with shorter MM patient survival and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, like bortezomib, with an autophagy inducer, like rapamycin, may improve patient outcomes in MM, where low GABARAP in the form of del(17p) is common and leads to worse outcomes.
    Sprache Englisch
    Erscheinungsdatum 2024-03-29
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023022777
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Buch ; Online: Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification

    Brown, Needa / Rocchi, Paul / Carmès, Léna / Guthier, Romy / Iyer, Meghna / Seban, Léa / Morris, Toby / Bennett, Stephanie / Lavelle, Michael / Penailillo, Johany / Carrasco, Ruben / Williams, Chris / Huynh, Elizabeth / Han, Zhaohui / Kaza, Evangelia / Doussineau, Tristan / Toprani, Sneh M / Qin, Xingping / Nagel, Zachary D /
    Sarosiek, Kristopher A / Hagège, Agnès / Dufort, Sandrine / Bort, Guillaume / Lux, François / Tillement, Olivier / Berbeco, Ross

    2023  

    Abstract: Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX nanoparticles ( ... ...

    Abstract Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd$^{3+}$ cations with higher Z Bi$^{3+}$. These next-generation nanoparticles are based on the AGuIX platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX is used as an initial chelation platform to exchange Gd$^{3+}$ for Bi$^{3+}$. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi$^{3+}$. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi$^{3+}$ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi$^{3+}$ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.
    Schlagwörter Condensed Matter - Materials Science
    Thema/Rubrik (Code) 620
    Erscheinungsdatum 2023-10-02
    Erscheinungsland us
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel: Characterization of microsatellite markers for Broussonetia papyrifera (Moraceae)

    Peñailillo, Johany / Kuo, Wenhsi / Olivares, Gabriela / Silva‐Poblete, Gerardo / Peña‐Ahumada, Barbara / Muñoz, Sofía / Moncada, Ximena / Chung, Kuo‐Fang / Seelenfreund, Daniela / Seelenfreund, Andrea

    Applications in plant sciences. 2017 Aug., v. 5, no. 8

    2017  

    Abstract: PREMISE OF THE STUDY: Broussonetia papyrifera (Moraceae) is native to Asia and is used as a medicinal plant and as a source of fiber for making paper. It was dispersed into the Pacific region as a fiber source for making nonwoven textiles (barkcloth). ... ...

    Abstract PREMISE OF THE STUDY: Broussonetia papyrifera (Moraceae) is native to Asia and is used as a medicinal plant and as a source of fiber for making paper. It was dispersed into the Pacific region as a fiber source for making nonwoven textiles (barkcloth). Microsatellites were developed to trace the human‐mediated dispersal of this species into the Pacific region. METHODS AND RESULTS: A set of 36 microsatellites was isolated and initially assayed on 10 accessions to assess polymorphism. We found that 20 markers were polymorphic, with the number of alleles per marker ranging from four to 35 in 70 accessions genotyped from three Asian populations. Observed and expected heterozygosities ranged from 0.04 to 0.85 and from 0.19 to 0.94, respectively. These markers were tested in four Moraceae species and one Rosaceae species. CONCLUSIONS: These markers will be useful for the assessment of genetic diversity in B. papyrifera. They show low transferability to other species tested.
    Schlagwörter Broussonetia papyrifera ; Rosaceae ; genetic variation ; medicinal plants ; microsatellite repeats ; paper ; Asia
    Sprache Englisch
    Erscheinungsverlauf 2017-08
    Erscheinungsort Botanical Society of America
    Dokumenttyp Artikel
    Anmerkung JOURNAL ARTICLE
    ZDB-ID 2699923-7
    ISSN 2168-0450
    ISSN 2168-0450
    DOI 10.3732/apps.1700044
    Datenquelle NAL Katalog (AGRICOLA)

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