摘要:
The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.
摘要:
The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by receptor protein-tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently acquired sensitivity to inhibitors of other receptor protein-tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such “hybrid” tumor cells (e.g. determination of co-expression of vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.
摘要:
A corner protector and bulkhead protector for a cargo carrying vehicle such as a rail car are formed to have deep channels or corrugations that provide for both increased strength and rigidity while also providing support for load restraining web straps.
摘要:
A load restraining device that provides a system in which straps extending from one side of a web strap arrangement initially run parallel to the wall to which they are connected, as opposed to extending perpendicular to the wall as in the prior art. The anchor itself is a horizontal wall member running longitudinally along the wall of the railcar or trailer. An adjustable anchor is used to permit moving the attachment point several inches to allow for load variations. The attachment of the web strap arrangement is normally 14″ to 18″ behind the face of the load. Unlike previous systems, this provision of anchor points behind the load effectively “encapsulates” the load rather than merely providing a bulkhead effect.
摘要:
The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.
摘要:
A clip or hook assembly for use with a pin-like anchor assembly mounted in the side of a railcar for grasping the anchor assembly. The hook is part of a restraining system used to restrain lading loaded and shipped in the railcar. The hook includes a body port having a central aperture for receiving a magnet assembly which can be positioned against the anchor assembly for securing the hook to the anchor and the railcar sidewall.
摘要:
A system for restraining the movement of a vehicle having a wheel with a tire thereon during shipment of the vehicle on a support surface. A chock for engaging at least one of the front or back surfaces of the tire. A strap take-up mechanism engages the support surface and is positioned adjacent the other circumferential surface of the tire. An elongated restraining strap which at one end engages the chock, extends over tire and engages the tire, and at the other end engages the strap take-up mechanism. The strap take-up mechanism includes a pair of legs each engaging the support surface and having a cylindrically shaped, slotted and rotatable hinge pin mounted to the legs for receiving the take-up end of the strap and about which the strap can be wound upon rotation of the cylinder. A handle associated with the cylinder and legs for rotating the cylinder so as to wrap the strap about the cylinder and for securing the cylinder relative to the legs so as to prevent further rotation of the cylinder.
摘要:
The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.
摘要:
The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.
摘要:
The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.