Abstract: The invention is directed to cell-targeted cytotoxic agents, including sortase serine protease constructs. Methods for targeted cell killing for treatment of proliferative diseases, for example, cancer, are provided. Exemplary embodiments comprise an R-spondin ligand for targeting the cytotoxic agents to effect the cell killing.

Abstract: Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.

Abstract: The present invention is directed generally to cell-targeted cytotoxic constructs comprising a targeting polypeptide, a linking polypeptide and a cytotoxic polypeptide. Preferably, (a) the targeting polypeptide is a R-spondin1 (RSPO1), R-spondin2 (RSPO2) or yoked chorionic gonadotropin (YCG), the linking polypeptide comprises LPXT (SEQ ID NO: 56) or NPXT (SEQ ID NO: 60) as well as others, where X is any amino acid, the linking polypeptide being positioned between the targeting ligand and (c) the cytotoxic moiety is an auristatin or a truncated serine protease, the serine protease having an IIGG (SEQ ID NO: 91), IVGG (SEQ ID NO: 92) or ILGG (SEQ ID NO: 93) at its N-terminus. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer).

Abstract: Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.

Abstract: The present invention features a novel cellular injury reporter system in which a chimeric gene containing the GADD153 promoter linked to the coding region of an enhanced green fluorescent protein (EGFP) gene was stably integrated into the genome of carcinoma cells. Activation of the GADD153 promoter was quantified using flow cytometric measurement of EGFP expression following drug exposure. This reporter system is suitable for high. throughput in vitro and in vivo screening for agents capable of producing cytotoxicity via a wide variety of different mechanisms, and can be utilized to investigate the relative potency of structurally related DNA adducts.

Abstract: The present invention provides a novel composition of matter useful for the treatment of a wide variety of human cancers. The novel composition is synergistic and cytotoxic and comprised of platinum containing antineoplastic agent and tamoxifen. The present invention also provides for methods of treating cancer. That is, the present invention provides a novel method of treating non-melanoma cancers used the novel pharmacologic combination of the present invention. Other embodiments of the invention provide novel methods of reducing or overcoming resistance that develops to platinum containing antineoplastic agents, such as, cisplatin.

Abstract: The present invention features a novel cellular injury reporter system in which a chimeric gene containing the GADD153 promoter linked to the coding region of an enhanced green fluorescent protein (EGFP) gene was stably integrated into the genome of carcinoma cells. Activation of the GADD153 promoter was quantified using flow cytometric measurement of EGFP expression following drug exposure. This reporter system is suitable for high throughput in vitro and in vivo screening for agents capable of producing cytotoxicity via a wide variety of different mechanisms, and can be utilized to investigate the relative potency of structurally related DNA adducts.

Abstract: Disclosed are multivesicular liposomes containing biologically active substances, and having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a modulated release of the biologically active substance. The liposomes are made by a process comprising dissolving a lipid component in volatile organic solvents, adding an immiscible aqueous component containing at least one biologically active substance to be encapsulated, and adding to either or both the organic solvents and the lipid component, a hydrochloride effective to control the release rate of the biologically active substance from the multivesicular liposome. A water-in-oil emulsion is made from the two components, the emulsion is immersed into a second aqueous component, and then divided into small solvent spherules which contain even smaller aqueous chambers. The solvents arc finally removed to give an aqueous suspension of multivesicular liposomes encapsulating biologically active substances.

Abstract: The present invention provides DNA encoding a human ARSA-I protein selected from the group consisting of: (a) isolated DNA which encodes a human ARSA-I protein; (b) isolated DNA which hybridizes to isolated DNA of (a) above and which encodes a human ARSA-I protein; and (c) isolated DNA differing from the isolated DNAs of (a) and (b) above in codon sequence due to the degeneracy of the genetic code, and which encodes a human ARSA-I protein. Also provided are pharmaceutical compositions comprising human human ARSA-I protein and a pharmaceutically acceptable carrier and host cells transfected with the vector of the present invention said vector expressing a human ARSA-I protein.

Abstract: The present invention provides a composition of matter for the treatment of non-melanoma cancers, wherein said composition comprises a platinum anti-neoplastic compound and tamoxifen, wherein said platinum anti-neoplastic compound and tamoxifen exert a synergistic anti-tumor effect on said non-melanoma cancer. Also provided are various methods of treating non-melanoma cancers and methods of preventing or overcoming resistance to platinum-containing anti-neoplastic compounds.

Abstract: Disclosed are multivesicular liposomes containing biologically active substances, the multivesicular liposomes having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a modulated rate of the biologically active substance in contrast to the previous art.

Abstract: The present invention provides a vector with a DNA sequence coding for a cellular injury element promoter from nucleotides -74 to -35 of the GADD153 promoter, relative to the start of transcription. The vector includes an origin of replication in operable linkage with a DNA sequence coding for the promoter. Also, a host cell is transfected with the vector and expresses the cellular injury response element promoter.

Abstract: Disclosed are multivesicular liposomes containing biologically active substances, the multivesicular liposomes having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a modulated rate of the biologically active substance in contrast to the previous art.

Abstract: The present invention comprises a method of sensitizing various types of cancer cells derived from different tissues of origin to various cytotoxic agents and augmenting the sensitivity of cancer cells to these cytotoxic agents. The invention provides a method to treat cancer and other cell proliferative diseases by the administration of a sensitizing agent prior to or concurrently with the administration of a cytotoxic agent.

Abstract: A method for ameliorating a neurological disorder in a human by administration to the cerebrospinal fluid (CSF) of a therapeutic agent in a dispersion system which allows the therapeutic agent to persist in the cerebro-ventricular space.

Abstract: A method for ameliorating a neurological disorder in a human by administration to the cerebrospinal fluid (CSF) of a therapeutic agent in a dispersion system which allows the therapeutic agent to persist in the cerebro-ventricular space.

Abstract: This invention relates to DNA encoding drug resistance to cis-platin. The invention also includes expression products of, and vectors and hosts comprising the DNA sequence encoding cis-platin resistance. Also included are immunodiagnostic assays of cis-platin resistance and assays for screening materials having a modulating effect on DNA encoding the cis-platin resistance gene and on the expression product thereof. The invention is further directed to antagonists to the cis-platin resistance gene and the expression product thereof. Recombinant and pharmaceutical means making use of the cis-platin resistance gene and its expression product are also provided.

Abstract: The present invention comprises a method of sensitizing cancer cells to cisplatin or other cytotoxic agents and augmenting the sensitivity of cancer cells to these cytotoxic agents. The invention provides a method to treat cancer and other cell proliferative diseases by the administration of a sensitizing agent prior to or concurrently with the administration of a cytotoxic agent.