Abstract: The present technology relates generally to compounds, compositions, and methods useful for treating, preventing, and/or ameliorating pathogenic cellular proliferation, angiogenesis, cancer, metastatic disease, and/or a pathogenic vascular proliferative disease in a subject.

Abstract: Conjugates for the efficient delivery of sequence-specific antisense to cells of a selected type for the inhibition of a target protein have the general formula: peptide-HBL-antisense in which the peptide is a homing peptide which directs the conjugate to cells of a particular type, antisense is an antisense oligonucleotide having a sequence selected to provide sequence-specific inhibition of the target protein, and HBL is a heterobifunctional linker having reactivity towards amino and sulfhydryl groups.

Abstract: The present invention relates generally to compositions and methods for treating cancer patients with a poor prognosis, and to therapeutic modalities for improving prognosis by combating metastasis and abrogating chemoresistance in cancer cells. In particular, the invention relates to the role of white blood cells, i.e. neutrophils and neutrophil-like cells, in preventing the spread of cancer from a primary tumor to secondary locations in the body. The invention provides methods for reducing or delaying the spread of metastatic cancer cells in a patient at risk for metastatic tumor development, at risk for metastatic relapse, i.e. prophylactic methods, and treating patients suffering from metastatic tumors.

Abstract: Conjugates for the efficient delivery of sequence-specific antisense to cells of a selected type for the inhibition of a target protein have the general formula: peptide-HBL-antisense in which the peptide is a homing peptide which directs the conjugate to cells of a particular type, antisense is an antisense oligonucleotide having a sequence selected to provide sequence-specific inhibition of the target protein, and HBL is a heterobifunctional linker having reactivity towards amino and sulfhydryl groups.

Abstract: Conjugates for the efficient delivery of sequence-specific antisense to cells of a selected type for the inhibition of a target protein have the general formula: peptide-HBL-antisense in which the peptide is a homing peptide which directs the conjugate to cells of a particular type, antisense is an antisense oligonucleotide having a sequence selected to provide sequence-specific inhibition of the target protein, and HBL is a heterobifunctional linker having reactivity towards amino and sulfhydryl groups.

Abstract: The present invention relates generally to compositions and methods for treating cancer patients with a poor prognosis, and to therapeutic modalities for improving prognosis by combating metastasis and abrogating chemoresistance in cancer cells. In particular, the invention relates to the role of white blood cells, i.e. neutrophils and neutrophil-like cells, in preventing the spread of cancer from a primary tumor to secondary locations in the body. The invention provides methods for reducing or delaying the spread of metastatic cancer cells in a patient at risk for metastatic tumor development, at risk for metastatic relapse, i.e. prophylactic methods, and treating patients suffering from metastatic tumors.

Abstract: Conjugates for the efficient delivery of sequence-specific antisense to cells of a selected type for the inhibition of a target protein have the general formula: peptide-HBL-antisense in which the peptide is a homing peptide which directs the conjugate to cells of a particular type, antisense is an antisense oligonucleotide having a sequence selected to provide sequence-specific inhibition of the target protein, and HBL is a heterobifunctional linker having reactivity towards amino and sulfhydryl groups.

Abstract: Inhibitor of DNA Binding-1 (Id-1) is a marker protein found in stem cells, including adult stem cells, which can be used an indicator of the “stem-ness” of the cells. This allows Id1 expression to be used in a method for identifying cells as potential stem cells involving the step of screening the cells for expression of Id1; and a method for isolating cells as potential stem cells comprising the step of separating cells that express Id1 from cells that do not. Expression of GFAP can be used as a secondary screen to isolate rare B1 type adult neuronal stem cells.

Abstract: Oligonucleotide primers and polynucleotide probes provide selective amplification and detection of Id genetic sequences and are selected both (1) to provide the desired specificity so that they amplify only the specific Id type to which they are targeted; and (2) to introduce terminal restriction endonuclease cleavage sites into the amplicon that facilitate the incorporation of the amplicon into plasmid-based vectors. Detection of Id genetic sequences can be carried out using the labeled-amplicon by reamplifying the amplicon with the primers in the presence of labeled, for example radiolabeled, deoxynucleotide triphosphates. The probes of the invention correspond in sequence to the amplicons produced using the primers of the invention, after cleavage at the restriction endonuclease sites.

Abstract: The invention relates to Id knockout mammals having a disruption in at least one and at most three alleles of inhibitor of differentiation genes, Id1 and Id3. This results in reduction or prevention of a cell proliferative disorder in the mammal as compared to a wild-type mammal. In particular, tumor growth and/or metastasis is shown to be inhibited. Further, tumor growth is shown to have poor vascularization and extensive necrosis in Id knockout mammals lacking 3 out of 4 of the Id1, Id3 alleles (Id1?/?Id3±). Drug screening methods to select agents useful to affect activity or expression of Id1 or Id3 gene products are disclosed. Therapeutic methods employing selected agents in subjects in need of treatment and diagnostic methods and test kits to identify subjects having, or at risk of having, a neurological or cell proliferative disorder are also described.

Abstract: Oligonucleotide primers and polynucleotide probes provide selective amplification and detection of Id genetic sequences and are selected both (1) to provide the desired specificity so that they amplify only the specific Id type to which they are targeted; and (2) to introduce terminal restriction endonuclease cleavage sites into the amplicon that facilitate the incorporation of the amplicon into plasmid-based vectors. Detection of Id genetic sequences can be carried out using the labeled-amplicon by reamplifying the amplicon with the primers in the presence of labeled, for example radiolabeled, deoxynucleotide triphosphates. The probes of the invention correspond in sequence to the amplicons produced using the primers of the invention, after cleavage at the restriction endonuclease sites.

Abstract: This invention relates to Id knockout mammals having a disruption in at least one and at most three alleles of inhibitor of differentiation genes, Id1 and Id3. This results in reduction or prevention of a cell proliferative disorder in the mammal as compared to a wild-type mammal. In particular, tumor growth and/or metastasis is shown to be inhibited. Further, tumor growth is shown to have poor vascularization and extensive necrosis in Id knockout mammals lacking 3 out of 4 of the Id1,Id3 alleles (Id1−/−Id3+/−). Drug screening methods to select agents useful to affect activity or expression of Id1, or Id3 gene products are disclosed. Therapeutic methods employing selected agents in subjects in need of treatment and diagnostic methods and test kits to identify subjects having, or at risk of having a neurological or cell proliferative disorder are also described.

Abstract: Provided herein is a new and useful method for modulating, and particularly inhibiting angiogenesis in an animal. Since numerous diseases and disorders are dependent upon angiogenesis for continued growth in an animal, modulating and particularly inhibiting angiogenesis permits ultimately ameliorating a variety of diseases and disorders. Also provided are novel assays for screening compounds which may have applications in modulating and particularly inhibiting angiogenesis.

Abstract: This invention provides isolated nucleic acid encoding human MAD2, isolated human MAD2 protein. This invention further provides a method of detecting the presence of MAD2 in a tissue sample, a method of determining whether a tumor is susceptible to treatment with a mitotic spindle inhibitor by detecting the presence of MAD2 in the tumor and a method of suppressing tumor formation in a subject which comprises administering the nucleic acid encoding human MAD2 to the subject in an amount effective to enhance expression of MAD2. This invention also provides a nucleic acid reagent capable of detecting the MAD2 gene or gene product and a method for in situ identification of tumors which may be susceptible to treatment with mitotic spindle inhibitors by detecting the absence of nucleic acid encoding MAD2 in the tumor.

Abstract: This invention provides isolated nucleic acid encoding human MAD2, isolated human MAD2 protein. This invention further provides a method of detecting the presence of MAD2 in a tissue sample, a method of determining whether a tumor is susceptible to treatment with a mitotic spindle inhibitor by detecting the presence of MAD2 in the tumor and a method of suppressing tumor formation in a subject which comprises administering the nucleic acid encoding human MAD2 to the subject in an amount effective to enhance expression of MAD2. This invention also provides a nucleic acid reagent capable of detecting the MAD2 gene or gene product and a method for in situ identification of tumors which may be susceptible to treatment with mitotic spindle inhibitors by detecting the absence of nucleic acid encoding MAD2 in the tumor.