Abstract: The present invention relates to promoters, enhancers and other regulatory elements that direct expression within tumor and tissue cells with calcification potential. In particular, it relates to compositions comprising nucleotide sequences from the 5′ regulatory region, and transcriptionally active fragments thereof, that control expression of a bone sialoprotein (“BSP”). Specifically provided are expression vectors, host cells and transgenic animals wherein a BSP regulatory region is capable of controlling expression of a heterologous coding sequence, over-expressing an endogenous BSP coding sequence or an inhibitor of a pathological process or knocking out expression of a specific gene believed to be important for a calcification-related disease in tumor and tissue cells with calcification potential.

Abstract: The present invention relates to methods for the production of high titers of serum-free lytic viruses in a hollow fiber cartridge capillary system. The invention further relates to methods of infecting target cells at high multiplicity and for producing high concentrations of transduced target cells.

Abstract: Homing bone marrow cells deposited at ATTC CRL-12424 can be transfected with a toxic gene which expresses a compound which alone, or in the company of a triggering agent, kills neighboring cancer cells in the bone marrow of a patient receiving the therapy. Toxic genes include cytotoxin such as thymidine kinase, immune stimulating compounds such as interleuken-2 and radiation repair inhibitors, such as Ku protein. The transfected cells can be administered directly to the site of the tumor or systemically, or regionally, intramedullary (into the marrow) through intravascular administration. The latter alternative permits the delivery of very high doses of the effective agent.

Abstract: A therapeutic agent based on a recombinant adenovirus which employs an osteocalcin promoter for the expression of thymidine kinase can be administered intravascularly to treat metastatic cancer, including osteosarcoma, breast cancer, prostate cancer, ocular melanoma or brain cancer. Systemic administration of this agent provides a preferred route over previous disclosure of local direct administration. The same therapeutic agent can be effectively employed in the treatment of benign conditions, including benign prostatic hypertrophy and arteriosclerosis.

Abstract: A new prostate cancer cell line is a continuous line of androgen-repressed metastatic prostate cancer cells. Androgen-repressed prostate cancer cells are linked with aggressive, malignant prostate cancer, in the identification and establishment of androgen-repressed prostate cancer cell lines, which are stable and continuous, allows the examination of therapeutic agents therefor, as well as identification of biological markers for the same.

Abstract: A recombinant adenovirus Ad-OC-TK was constructed, with cell specific gene expression, which contains osteocalcin (OC) promoter that drives the expression of herpes simplex virus thymidine kinase (TK); the addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, to Ad-OC-TK resulted in the induction of osteoblast-specific cell death in vitro. The Ad-OC-TK virus plus ACV treatment is highly selective in blocking the growth of both murine and human osteosarcoma cell lines in vitro and murine osteosarcoma in vivo.

Abstract: The role for a substantially purified human growth factor preparation is shown to contain a distinct polypeptide with apparent M.sub.r on SDS/PAGE of about 220 kD, and to be distinct from bFGF, with a most active fraction at about 220 kD. A human growth factor polypeptide of 157 kD was identified, in human bone marrow aspirates and from bone stromal cells, by immunoblotting with the mAb MS 329, and by affinity isolation using a MS 329 antibody column. A PSA stimulating autocrine factor, PSAF, that is precipitable in ammonium sulfate at between 60-80% saturation is able to induce PSA expression and secretion, and serves as an indicator of androgen independent prostate cell growth.

Abstract: The role of tumor cell-host stromal interaction and stromal-specific growth factors in prostate cancer growth, progression and metastasis to the axial skeleton were investigated. Following co-inoculation of athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts, human prostate-like tumor formation was consistently induced by human bone (MS) fibroblasts (62%), embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney (NRK), or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. A novel in vivo method in which a slowly adsorbed matrix (Gelfoam) was employed to deliver concentrated prostate and bone fibroblast-derived conditioned media was also found to induce LNCaP tumor formation in vivo.