Angiogenetics Sweden Ab

Index Pharmaceuticals Ab

Pharmacia & Upjohn Ab

Lorenz Poellinger

Anders Berkenstam

Patrik Andersson

Göran Bertilsson

Yuichi Makino

Petra Von Stein

Nikolai Kouznetsov

Annika Hanberg Wiklund

Jaqueline McGuire

Agents useful for modulating the dioxin/aryl hydrocarbon receptor (AhR) can now be identified by determining the binding to said receptor and whether said agent suppresses or inhibits the expression of a gene substantially consisting of a sequence according to one of SEQ. ID. NO. 1 and SEQ. ID. NO. 2; a nucleotide sequence functionally homologous, or substantially homologous, or at least 90% identical to one of SEQ. ID. NO. 1 and SEQ. ID. NO. 2; and a nucleotide sequence complementary to the nucleotide sequence of SEQ. ID. NO. 1 or SEQ. ID. NO. 2. Such agents find utility in pharmaceutical compositions and methods for the prevention, alleviation or treatment of diseases involving gastrointestinal hyperplasia, such as gastrointestinal cancer or gastric cancer.

Method for identifying modulators of the dioxin/aryl hydrocarbon receptor (AHR)

A pharmaceutical composition comprises the sequence of SEQ ID NO:s 3-5 or pharmaceutically equivalent sequences. Methods employing the pharmaceutical compositions include treatments to increase angiogenesis, to stimulate HIF-1&#x3b1; function, to treat hypoxia-related conditions, and to maintain normal cell functions under hypoxia.

Regulation of hypoxia-inducible gene expression with antisense Inhibitory PAS domain protein

A mammalian polypeptide designated Inhibitory PAS Domain Protein (IPAS) is useful for the inhibition of angiogenesis and/or tumor progression. Screening methods exist to identify compounds potentially useful as medicaments for the treatment of medical conditions related to angiogenesis or tumor progression.

Screening methods

The present invention relates a mammalian polypeptide designated Inhibitory PAS Domain Protein (IPAS) which polypeptide is useful for the inhibition of angiogenesis and/or tumor progression. The invention also relates to screening methods for compounds potentially useful as medicaments for the treatment of medical conditions related to angiogenesis or tumor progression.

Screening Methods

The present invention makes available powerful tools for the study of cancer, based on a novel expression construct for a constitutively active hydrocarbon receptor CA-AhR. The invention further comprises transgenic non-human animals, preferably mammals, expressing CA-AhR in one or more tissues thereof. An animal model based on the transgenic non-human animals forms the basis for novel methods e.g. for the study of cancer; for the screening of compounds, such as drug candidates; for the investigation of the molecular mechanisms of cancer, in particular stomach cancer; for the investigation of the mechanisms of highly differentiated adenocarcinoma etc. Likewise, in vitro models based on transformed cells or cell lines, functionally incorporating the inventive construct are disclosed.

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Stockholm, Sweden

Lorenz Poellinger