Abstract: The invention features methods for treating and preventing cancer (e.g., an estrogen receptor-positive (ER+) breast cancer) in a patient in need thereof by administering eribulin (e.g., eribulin mesylate) in combination with a cyclin dependent kinase (CDK) inhibitor.

Abstract: The invention features methods for treating and preventing cancer (e.g., a hormone sensitive cancer) in a patient in need thereof by administering eribulin (e.g., eribulin mesylate) in combination with a histone deacetylase (HDAC) inhibitor.

Abstract: The invention provides methods for predicting the efficacy of eribulin, an analog thereof, or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate), in the treatment of a subject suffering from breast cancer by determining the level of particular biomarkers in a sample derived from the subject.

Abstract: The invention features methods and kits for use in treating cancer in a patient in need thereof by administering eribulin or a pharmaceutically-acceptable salt thereof (e.g., eribulin mesylate) prior to a second agent.

Abstract: Methods for treating cancer (e.g., breast cancer, lung cancer, pancreatic cancer, primitive neuroectodermal tumors, lung cancer, ovarian cancer, endometrial cancer, pharyngeal cancer, esophageal cancer, and sarcoma) in a subject (such as an human patient) in need thereof by administering eribulin (e.g., eribulin mesylate, i.e., E7389, Halaven) in combination with one or more mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus, ridaforolimus, and temsirolimus), and kits therefor are provided.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer, and intermediates for the synthesis of such compositions.

Abstract: Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include halichondrin B analogs. It has been shown that the susceptibility of certain cancers to analogs of halichondrin B correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: The invention provides devices and methods for delivering therapeutic agents to patients.

Abstract: A method and system of split-streaming direct memory access (DMA) data transfer can transfer N words of data from a source device to two different sets of memory locations using only N data read cycles and 2N data write cycles. In a single data word transfer mode, a data read operation on the memory bus is followed by two consecutive data write cycles wherein the same data is written to two different memory addresses. In a data burst mode, a data burst read operation is followed by a series of paired data write cycles, wherein in each pair of data write cycles, one of the data words is written to two different memory addresses.

Abstract: Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include halichondrin B analogs. It has been shown that the susceptibility of certain cancers to analogs of halichondrin B correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.

Abstract: Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include hemiasterlin analogs. It has been shown that the susceptibility of certain cancers to analogs of hemiasterlin correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.

Abstract: The present invention provides a system for measuring the cytotoxicity of a test compound against quiescent cells. The inventive methods and reagents may also be used to determine whether a compound, such as a chemotherapeutic agent, will have undesired toxicity toward normal tissues, which generally do not include a significant number of cells that are proliferating. Thus, the assay of the invention can be used to identify in vitro compounds that demonstrate a good therapeutic index, thus, accelerating the development of drugs that are clinically useful.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: An integrated circuit having two or more power domains that include load circuits in different portions of the integrated circuit is disclosed. In order to conserve power, the circuits in one of the power domains are shut down by disconnecting the power source serving that domain. The load circuits in each power domain are buffered from the load circuits in other power domains by buffer cells. The buffer cells reduce leakage currents in the power domain that is shut down, by restricting data signals from the “live” power domain from reaching the shut-down power domain, and further by providing predetermined voltage signals to the load circuits in the shut-down power domain that are selected to minimize leakage currents in the inactive load circuits. The invention further provides a corresponding method for reducing power consumption in an integrated circuit having at least two power domains separated by a buffer cell.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: Novel intermediates of the formula They are used in the preparation of macrocyclic analogs.