Murray Robinson - Boston MA, US Ronan O'Hagan - Brookline MA, US Karuppiah Kannan - Cambridge MA, US Ti Cai - Andover MA, US Maria Isabel Chiu - Newton Centre MA, US Lorena Lerner - Newton Centre MA, US Jie Lin - West Roxbury MA, US Yinghui Zhou - Belmont MA, US
Assignee:
AVEO Pharmaceuticals, Inc. - Cambridge MA
International Classification:
A61K 49/00 A61K 35/12
US Classification:
424 91, 424520, 424573
Abstract:
A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.
Joerg Heyer - Cambridge MA, US Murray Robinson - Boston MA, US William Rideout, III - Cambridge MA, US Ronald Depinho - Brookline MA, US Steven C. Clark - Winchester MA, US Yinghui Zhou - Belmont MA, US Tyler Jacks - West Newton MA, US Ronan C. O'Hagan - Arlington MA, US
Assignee:
AVEO Pharmaceuticals, Inc. - Cambridge MA
International Classification:
C12N 15/00 A01K 67/00 C12N 5/06
US Classification:
800 25, 800 10, 800 18, 435354
Abstract:
Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.
Murray Robinson - Boston MA, US Ronan O'Hagan - Brookline MA, US Karuppiah Kannan - Cambridge MA, US Ti Cai - Andover MA, US
International Classification:
A61K 49/00 C12N 5/06
US Classification:
424009200, 435354000, 435455000
Abstract:
A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.
Murray Robinson - Boston MA, US Ronan O'Hagan - Brookline MA, US Karuppiah Kannan - Cambridge MA, US Ti Cai - Andover MA, US
International Classification:
A61K 49/00 C12N 5/06
US Classification:
424009200, 435354000, 435455000
Abstract:
A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.
Gp131: Methods And Compositions For Treating Cancer
Ronan O'Hagan - Brookline MA, US Karuppiah Kannan - Cambridge MA, US David Bailey - Brighton MA, US Kirk Wright - Waltham MA, US Lizabeth Amaral - Metheun MA, US
International Classification:
A61K 48/00 C07H 21/02 A61K 39/395 C07K 16/30
US Classification:
514044000, 536023100, 424155100, 530388800
Abstract:
The use of molecules relating to the GP131 (ceramide kinase) gene for treating cancer and other hyperproliferative conditions is disclosed. Non-human mammals harboring a genetic modification relating to the GP131 gene, and their use as experimental cancer models, are disclosed.
A reporter gene operably linked to a transcriptional control element that is up-regulated by a tumor-induced transcription factor is disclosed. This reporter gene construct can be used to detect tumor formation in vivo in an experimental animal.
N3-Pyridyl-Thiamine And Its Use In Cancer Treatments
Jeno Gyuris - Lincoln MA, US Ronan C. O'Hagan - Arlington MA, US May Han - Brookline MA, US Murray Robinson - Boston MA, US Solly Weiler - Newton MA, US
Assignee:
AVEO PHARMACEUTICALS, INC. - Cambridge MA
International Classification:
A61K 31/51 C12N 5/00 A61P 43/00
US Classification:
514276, 435375
Abstract:
The invention provides methods using N3-pyridyl-thiamine compounds and pharmaceutical compositions comprising N3-pyridyl-thiamine, which are especially useful for preventing or reducing tumor growth in vivo. The invention is also directed to the benefits of reducing thiamine concentrations, e.g., by means of a thiamine reduced diet, as an effective step in a therapeutic regime for patients treated with N3-pyridyl-thiamine.
Identifying Cancers Sensitive To Treatment With Inhibitors Of Notch Signaling
Ronan O'Hagan - Arlington MA, US H. Heidi Okamura - Brookline MA, US Alisa C. Bell - Burlington MA, US Jeanine Lorusso - Ashland MA, US
Assignee:
AVEO Pharmaceuticals, Inc. - Cambridge MA
International Classification:
C12Q 1/68
US Classification:
435 6
Abstract:
The disclosure provides a method for identifying cancer tissue sensitive to treatment with an inhibitor of Notch receptor activation. The method comprises determining the level of HeyL gene expression in a sample derived from the cancer tissue, wherein an elevated level of HeyL gene expression alone in the sample indicates sensitivity to the cancer tissue to treatment with an inhibitor of Notch receptor activation.
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