Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than untransformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than untransformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Aplidine and aplidine analogues are used in the manufacture of a medicament for treating multiple myeloma.

Abstract: Aplidine and aplidine analogues are of use for the treatment of cancer, in particular in the treatment of leukemias and lymphomas, especially in combination therapies.

Abstract: Aplidine and aplidine analogues are used in the manufacture of a medicament for treating multiple myeloma.

Abstract: A method is provided for use in producing a selected protein in mammalian cells, and to cDNA molecules useful in the method, and fusion proteins produced from expression of the cDNA. In the method, cDNA encoding a fusion protein that includes a mammalian DHFR and the selected protein is introduced into mammalian cells such that it is expressed. The naturally occurring repression of DHFR translation is overcome by treatment of the cells with a folate or antifolate or similar composition. The relief from this repression extends to the selected protein which is the second part of the expressed fusion, such that the treatment results in controllable and enhanced production of the selected protein.

Abstract: This invention also provides a method for treating a cancer subject comprising administering to the subject a combination of ATP-depleting agents at concentrations which deplete the ATP level to, or close to, at least 15% of normal in cancer cells wherein at least one of the ATP-depleting agents is a mitochondrial ATP-inhibitor, a methylthioadenosine phosphorylase inhibitor or an inhibitor of De Novo purine synthesis other than 6-Methylmercaptopurine riboside, wherein said composition produces a substantially better effect than a composition without at least one of the ATP-depleting agents: a mitochondrial ATP-inhibitor, a glycolytic inhibitor, a methylthioadenosine phosphorylase inhibitor and an inhibitor of De Novo purine synthesis other than 6-Methylmercaptopurine riboside.

Abstract: A method is provided for use in producing a selected protein in mammalian cells, and to cDNA molecules useful in the method, and fusion proteins produced from expression of the cDNA. In the method, cDNA encoding a fusion protein that includes a mammalian DHFR and the selected protein is introduced into mammalian cells such that it is expressed. The naturally occurring repression of DHFR translation is overcome by treatment of the cells with a folate or antifolate or similar composition. The relief from this repression extends to the selected protein which is the second part of the expressed fusion, such that the treatment results in controllable and enhanced production of the selected protein.

Abstract: Recombinant lentiviral vectors having a region encoding a functional &bgr;-globin gene; and large portions of the &bgr;-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of &bgr;-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including &bgr;-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.