Title:
SCREENING ASSAY FOR THE IDENTIFICATION OF AGENTS WHICH ALTER EXPRESSION OF PTH-RP
Document Type and Number:
WIPO Patent Application WO1998007844
Kind Code:
A3
Abstract:
A cell-based assay technique for identifying and evaluating chemical compounds and agents which affect the production of PTH-rP in mammalian cells and other cell types is set forth. Specifically, tumor cell lines are transformed with an expression vector comprising a DNA sequence encoding a promoter region of PTH-rP operatively linked to a reporter gene encoding an assayable product and cultured under conditions which permit expression of the assayable product. Chemical agents and factors can then be identified by their ability to modulate the expression of the reporter gene, thereby affecting the production of the assayable product. Such agents are then tested for inhibitory effects on tumor cell growth and for stimulatory effects on bone formation and repair.
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Inventors:
MUNDY GREGORY R (US)
GALLWITZ WOLFGANG E (US)
GALLWITZ WOLFGANG E (US)
Application Number:
PCT/US1997/014836
Publication Date:
August 27, 1998
Filing Date:
August 22, 1997
Export Citation:
Assignee:
OSTEOSCREEN (US)
MUNDY GREGORY R (US)
GALLWITZ WOLFGANG E (US)
MUNDY GREGORY R (US)
GALLWITZ WOLFGANG E (US)
International Classes:
A61K31/41; A61K31/473; A61K31/52; C07D219/08; C07D257/06; C07D473/24; C07K14/635; C12Q1/68; (IPC1-7): C12N15/10; C12N15/86; C12Q1/68; A61K31/41; A61K31/52; A61K31/435
Domestic Patent References:
| WO1996022790A1 | 1996-08-01 |
Other References:
WYSOLMERSKI ET AL.: "TRANSACTIVATION OF THE PTHRP GENE IN SQUAMOUS CARCINOMAS PREDICTS THE OCCURRENCE OF HYPERCALCEMIA IN ATHYMIC MICE", CANCER RESEARCH, vol. 56, 1996, pages 1043 - 1049, XP002051650
YU ET AL.: "VITAMIN D ANALOGS: NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF SQUAMOUS CANCER AND ITS ASSOCIATED HYPERCALCEMIA", ANTI-CANCER DRUGS, vol. 6, 1995, pages 101 - 108, XP002051651
MANGIN ET AL.: "IDENTIFICATION OF AN UP-STREAM PROMOTER OF THE HUMAN PARATHYROID HORMONE-RELATED PEPTIDE GENE", MOL. ENDOCRINOLOGY, vol. 4, 1990, pages 851 - 858, XP002051652
BOUIZAR ET AL.: "POLYMERASE CHAIN REACTION ANALYSIS OF PARATHYROID HORMONE-RELATED PROTEIN GENE EXPRESSION IN BREAST CANCER PATIENTS AND OCCURRENCE OF BONE METASTASES", CANCER RESEARCH, vol. 53, 1993, pages 5076 - 5078, XP002051653
ALAM J ET AL: "REPORTER GENES: APPLICATION TO THE STUDY OF MAMMALIAN GENE TRANSCRIPTION", ANALYTICAL BIOCHEMISTRY, vol. 188, no. 2, 1 August 1990 (1990-08-01), pages 245 - 254, XP000563914
S .BUDAVARI , EDITOR: "the merck index", 1996, MERCK RESEARCH LABORATORIES, WHITEHOUSE STATION, NJ, USA, XP002068022
S BUDAVARI, EDITOR: "the merck index", 1996, MERCK RESEARCH LABORATORIES, WHITEHOUSE STATION, NJ,USA, XP002068023
M.L. CASEY ET AL.: "Regulation of parathyroid hormone-related protein gene expression in human endometrial stromal cells in culture.", J. CLIN. ENDOCRINOL. METAB., vol. 77, no. 1, 1993, pages 188 - 194, XP002068021
YU ET AL.: "VITAMIN D ANALOGS: NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF SQUAMOUS CANCER AND ITS ASSOCIATED HYPERCALCEMIA", ANTI-CANCER DRUGS, vol. 6, 1995, pages 101 - 108, XP002051651
MANGIN ET AL.: "IDENTIFICATION OF AN UP-STREAM PROMOTER OF THE HUMAN PARATHYROID HORMONE-RELATED PEPTIDE GENE", MOL. ENDOCRINOLOGY, vol. 4, 1990, pages 851 - 858, XP002051652
BOUIZAR ET AL.: "POLYMERASE CHAIN REACTION ANALYSIS OF PARATHYROID HORMONE-RELATED PROTEIN GENE EXPRESSION IN BREAST CANCER PATIENTS AND OCCURRENCE OF BONE METASTASES", CANCER RESEARCH, vol. 53, 1993, pages 5076 - 5078, XP002051653
ALAM J ET AL: "REPORTER GENES: APPLICATION TO THE STUDY OF MAMMALIAN GENE TRANSCRIPTION", ANALYTICAL BIOCHEMISTRY, vol. 188, no. 2, 1 August 1990 (1990-08-01), pages 245 - 254, XP000563914
S .BUDAVARI , EDITOR: "the merck index", 1996, MERCK RESEARCH LABORATORIES, WHITEHOUSE STATION, NJ, USA, XP002068022
S BUDAVARI, EDITOR: "the merck index", 1996, MERCK RESEARCH LABORATORIES, WHITEHOUSE STATION, NJ,USA, XP002068023
M.L. CASEY ET AL.: "Regulation of parathyroid hormone-related protein gene expression in human endometrial stromal cells in culture.", J. CLIN. ENDOCRINOL. METAB., vol. 77, no. 1, 1993, pages 188 - 194, XP002068021
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