scholarly journals Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms

Blood ◽  
2014 ◽  
Vol 123 (13) ◽  
pp. 2075-2083 ◽  
Author(s):  
Neha Bhagwat ◽  
Priya Koppikar ◽  
Matthew Keller ◽  
Sachie Marubayashi ◽  
Kaitlyn Shank ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Myeloproliferative Neoplasms ◽  
Murine Models ◽  
Hsp90 Inhibitors ◽  
Key Points ◽  
Genetic Deletion

Key Points Genetic deletion of JAK2 in vivo shows that MPN cells remain fully dependent on JAK2 signaling for survival. Dual JAK2 targeting with JAK and HSP90 inhibitors offers increased efficacy in murine models and primary samples.

scholarly journals HSP90 inhibition overcomes ibrutinib resistance in mantle cell lymphoma

Blood ◽  
2016 ◽  
Vol 128 (21) ◽  
pp. 2517-2526 ◽  
Author(s):  
Caron Jacobson ◽  
Nadja Kopp ◽  
Jacob V. Layer ◽  
Robert A. Redd ◽  
Sebastian Tschuri ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Hsp90 Inhibitors ◽  
Hsp90 Inhibition ◽  
Key Points ◽  
Mantle Cell ◽  
Ibrutinib Resistance

Key Points Inhibition of HSP90 targets multiple dependences in mantle cell lymphoma. Clinically available HSP90 inhibitors overcome ibrutinib resistance in vitro and in vivo.

scholarly journals The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm

Blood ◽  
2014 ◽  
Vol 124 (26) ◽  
pp. 3956-3963 ◽  
Author(s):  
Veena Sangkhae ◽  
S. Leah Etheridge ◽  
Kenneth Kaushansky ◽  
Ian S. Hitchcock
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Hematopoietic Stem ◽  
Thrombopoietin Receptor ◽  
Key Points

Key Points MPL is essential for the development of JAK2V617F-positive myeloproliferative neoplasms in vivo. Ablation or reduction of Mpl significantly reduces the pool of neoplastic hematopoietic stem cells.

scholarly journals ICAM-1–expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

Blood ◽  
2016 ◽  
Vol 127 (7) ◽  
pp. 898-907 ◽  
Author(s):  
Abigail Woodfin ◽  
Martina Beyrau ◽  
Mathieu-Benoit Voisin ◽  
Bin Ma ◽  
James R. Whiteford ◽  
...  
Keyword(s):  
De Novo ◽  
Ros Generation ◽  
Murine Models ◽  
Effector Functions ◽  
Key Points

Key PointsMurine neutrophils can be stimulated by LPS to express de novo ICAM-1 in vitro and in murine models of endotoxemia in vivo. Neutrophil ICAM-1 expression correlated with enhanced phagocytosis and ROS generation, and ICAM-1 deficiency caused defective phagocytosis.

scholarly journals Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura

2016 ◽  
Vol 1 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Liang Zheng ◽  
Yingying Mao ◽  
Mohammad S. Abdelgawwad ◽  
Nicole K. Kocher ◽  
Mandy Li ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Therapeutic Efficacy ◽  
Platelet Glycoprotein ◽  
Murine Models ◽  
Glycoprotein Ib ◽  
Thrombocytopenic Purpura ◽  
Key Points

Key Points Anfibatide potently inhibits platelet agglutination under static and arterial shear conditions. Anfibatide is efficacious in treating spontaneous or shigatoxin-induced murine models of thrombotic thrombocytopenic purpura.

scholarly journals A clinically relevant in vivo zebrafish model of human multiple myeloma to study preclinical therapeutic efficacy

Blood ◽  
2016 ◽  
Vol 128 (2) ◽  
pp. 249-252 ◽  
Author(s):  
Jianhong Lin ◽  
Weihong Zhang ◽  
Jian-Jun Zhao ◽  
Ariel H. Kwart ◽  
Chun Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Efficacy ◽  
Drug Sensitivity ◽  
Xenograft Model ◽  
Zebrafish Model ◽  
Zebrafish Larvae ◽  
Key Points ◽  
Drug Sensitivity Prediction ◽  
Human Multiple Myeloma

Key Points MM cell lines and primary MM cells can be engrafted and grown in vivo in Casper zebrafish larvae. The zebrafish MM in vivo xenograft model can be used as a pretreatment drug-sensitivity prediction platform for MM patients.

scholarly journals Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis

Blood ◽  
2016 ◽  
Vol 127 (13) ◽  
pp. 1666-1675 ◽  
Author(s):  
Rupali Das ◽  
Peng Guan ◽  
Leslee Sprague ◽  
Katherine Verbist ◽  
Paige Tedrick ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proinflammatory Cytokine ◽  
Cell Expansion ◽  
Cytokine Production ◽  
Janus Kinase ◽  
Murine Models ◽  
Proinflammatory Cytokine Production ◽  
Key Points ◽  
Janus Kinase Inhibition

Key Points Ruxolitinib treatment lessens immunopathology and prolongs survival in murine models of hemophagocytic lymphohistiocytosis. In vivo exposure to ruxolitinib limits CD8+ T-cell expansion and proinflammatory cytokine production.

scholarly journals Partial trisomy 21 contributes to T-cell malignancies induced by JAK3-activating mutations in murine models

2018 ◽  
Vol 2 (13) ◽  
pp. 1616-1627 ◽  
Author(s):  
Paola Rivera-Munoz ◽  
Anouchka P. Laurent ◽  
Aurelie Siret ◽  
Cecile K. Lopez ◽  
Cathy Ignacimouttou ◽  
...  
Keyword(s):  
T Cell ◽  
Trisomy 21 ◽  
Partial Trisomy ◽  
Murine Models ◽  
Activating Mutations ◽  
Key Points ◽  
T Cell Malignancies ◽  
Dose Dependent

Key Points Jak3A572V-induced CTCL-like disorders are mutant Jak3 dose-dependent, transplantable, and phenotypically heterogeneous. Trisomy 21, somatically acquired in human CTCL, functionally cooperates with activated Jak3 to enhance the CTCL-like phenotype in vivo.

Nanostructured Ketorolac-Tromethamine/MCF: Synthesis, Characterization and Application in Drug Release System

2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Controlled Drug Release ◽  
Delivery Systems ◽  
The Body ◽  
Fickian Diffusion ◽  
Ketorolac Tromethamine

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

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