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  1. Article: Minnelide reduces tumor burden in preclinical models of osteosarcoma

    Banerjee, Sulagna / Thayanithy, Venugopal / Sangwan, Veena / Mackenzie, Tiffany N / Saluja, Ashok K / Subramanian, Subbaya

    Cancer letters. 2013 July 28, v. 335, no. 2

    2013  

    Abstract: Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on ... ...

    Abstract Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.
    Keywords adolescents ; apoptosis ; children ; drugs ; heat shock proteins ; humans ; metastasis ; models ; osteosarcoma ; survival rate
    Language English
    Dates of publication 2013-0728
    Size p. 412-420.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2013.02.050
    Database NAL-Catalogue (AGRICOLA)

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Minnelide reduces tumor burden in preclinical models of osteosarcoma.

    Banerjee, Sulagna / Thayanithy, Venugopal / Sangwan, Veena / Mackenzie, Tiffany N / Saluja, Ashok K / Subramanian, Subbaya

    Cancer letters

    2013  Volume 335, Issue 2, Page(s) 412–420

    Abstract: Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on ... ...

    Abstract Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.
    MeSH term(s) Animals ; Antineoplastic Agents, Alkylating/pharmacology ; Apoptosis/drug effects ; Caspase 3/metabolism ; Caspase 7/metabolism ; Caspase 9/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Diterpenes/pharmacology ; Down-Regulation ; Epoxy Compounds/pharmacology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Heat-Shock Proteins/biosynthesis ; Humans ; Inhibitor of Apoptosis Proteins/biosynthesis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/secondary ; Mice ; Mice, Nude ; NF-kappa B/metabolism ; Neoplasm Transplantation ; Organophosphates/pharmacology ; Osteoblasts/drug effects ; Osteosarcoma/drug therapy ; Phenanthrenes/pharmacology ; Proto-Oncogene Proteins c-myc/biosynthesis ; Survivin ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents, Alkylating ; BIRC5 protein, human ; Diterpenes ; Epoxy Compounds ; Heat-Shock Proteins ; Inhibitor of Apoptosis Proteins ; MYC protein, human ; NF-kappa B ; Organophosphates ; Phenanthrenes ; Proto-Oncogene Proteins c-myc ; Survivin ; triptolide (19ALD1S53J) ; 14-O-phosphonooxymethyltriptolide disodium salt (1CIV2UMO40) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-) ; Caspase 9 (EC 3.4.22.-)
    Language English
    Publishing date 2013-03-14
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2013.02.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways.

    Mujumdar, Nameeta / Mackenzie, Tiffany N / Dudeja, Vikas / Chugh, Rohit / Antonoff, Mara B / Borja-Cacho, Daniel / Sangwan, Veena / Dawra, Rajinder / Vickers, Selwyn M / Saluja, Ashok K

    Gastroenterology

    2010  Volume 139, Issue 2, Page(s) 598–608

    Abstract: Background & aims: Pancreatic adenocarcinoma, among the most lethal human malignancies, is resistant to current chemotherapies. We previously showed that triptolide inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in ... ...

    Abstract Background & aims: Pancreatic adenocarcinoma, among the most lethal human malignancies, is resistant to current chemotherapies. We previously showed that triptolide inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. This study investigates the mechanism by which triptolide kills pancreatic cancer cells.
    Methods: Cells were treated with triptolide and viability and caspase-3 activity were measured using colorimetric assays. Annexin V, propidium iodide, and acridine orange staining were measured by flow cytometry. Immunofluorescence was used to monitor the localization of cytochrome c and Light Chain 3 (LC3) proteins. Caspase-3, Atg5, and Beclin1 levels were down-regulated by exposing cells to their respective short interfering RNA.
    Results: We show that triptolide induces apoptosis in MiaPaCa-2, Capan-1, and BxPC-3 cells and induces autophagy in S2-013, S2-VP10, and Hs766T cells. Triptolide-induced autophagy has a pro-death effect, requires autophagy-specific genes, atg5 or beclin1, and is associated with the inactivation of the Protein kinase B (Akt)/mammalian target of Rapamycin/p70S6K pathway and the up-regulation of the Extracellular Signal-Related Kinase (ERK)1/2 pathway. Inhibition of autophagy in S2-013 and S2-VP10 cells results in cell death via the apoptotic pathway whereas inhibition of both autophagy and apoptosis rescues cell death.
    Conclusions: This study shows that triptolide kills pancreatic cancer cells by 2 different pathways. It induces caspase-dependent apoptotic death in MiaPaCa-2, Capan-1, and BxPC-3, and induces caspase-independent autophagic death in metastatic cell lines S2-013, S2-VP10, and Hs766T, thereby making it an attractive chemotherapeutic agent against a broad spectrum of pancreatic cancers.
    MeSH term(s) Antineoplastic Agents, Alkylating/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Autophagy/drug effects ; Autophagy-Related Protein 5 ; Beclin-1 ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Diterpenes/pharmacology ; Dose-Response Relationship, Drug ; Epoxy Compounds/pharmacology ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Phenanthrenes/pharmacology ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases ; Time Factors
    Chemical Substances ATG5 protein, human ; Antineoplastic Agents, Alkylating ; Apoptosis Regulatory Proteins ; Autophagy-Related Protein 5 ; BECN1 protein, human ; Beclin-1 ; Diterpenes ; Epoxy Compounds ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Microtubule-Associated Proteins ; Phenanthrenes ; triptolide (19ALD1S53J) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Ribosomal Protein S6 Kinases, 70-kDa (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; CASP3 protein, human (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-)
    Language English
    Publishing date 2010-04-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2010.04.046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ui V Zs.44: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 572: Show issues

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  4. Article: Minnelide reduces tumor burden in preclinical models of osteosarcoma

    Banerjee, Sulagna / Thayanithy, Venugopal / Sangwan, Veena / Mackenzie, Tiffany N. / Saluja, Ashok K. / Subramanian, Subbaya

    Cancer letters

    Volume v. 335,, Issue no. 2

    Abstract: Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on ... ...

    Abstract Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.
    Keywords models ; heat shock proteins ; survival rate ; drugs ; apoptosis ; metastasis ; adolescents ; children ; humans ; osteosarcoma
    Language English
    Document type Article
    ISSN 0304-3835
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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