University of California

Leland Stanford Junior University

Other

Children's Hospital & Research Center Oakland

Ervin H Epstein, Jr

Matthew Peter Scott

Ronald L Johnson

Lisa V Goodrich

Philip Arden Beachy

Jayakumar Rajadas

Jean Tang

Tony Oro

James Kim

Zhilan Hu

Jeanette Bonifas

Methods of transdermally delivering a therapeutic amount of a triazole-triazolone compound are provided, e.g. for the prevention or treatment of basal cell carcinoma (BCC) in a subject. A therapeutic level of a triazole-triazolone compound such as itraconazole is delivered transdermally to a subject. Also provided are topical triazole-triazolone compositions that find use in practicing the subject methods.

Topical itraconazole formulations and uses thereof

Methods for isolating patched genes, including the mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Decreased expression of patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The patched and hedgehog genes are useful in creating transgenic animal models for these human cancers. The patched nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.

Patched polypeptides and uses related thereto

Patched genes and uses related thereto

Methods are provided for identifying agents that decrease hedgehog signal transduction for ameliorating an effect of loss of function of a patched gene in a mammalian cell.

Methods for isolating patched genes, particularly mammalian patched genes, including the mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Decreased expression of patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. The patched and hedgehog genes are useful in creating transgenic animal models for these human cancers. The patched nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated 15 physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.

Methods for isolating patched genes, particularly mammalian patched genes, including the mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Decreased expression of patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. The patched and hedgehog genes are useful: in creating transgenic animal models for these human cancers. The patched nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated 15 physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.

Methods for isolating patched genes, particularly mammalian patched genes, including mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Loss-of function of the patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. Therefore, methods for using the patched gene as a diagnostic for assessing a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene, are disclosed.

Patched genes and their use for diagnostics

A mutation in the human sonic hedgehog gene is associated with tumorigenesis. A variety of human tumors, including basal cell carcinomas, breast carcinomas, medulloblastomas, etc., have a somatic mutation that results in an amino acid substitution at position 133 �*his133 SHH!, or in a mutation at position 114. Such mutated genes and fragments thereof, encoded protein, and antibodies specific for the mutated protein are useful in characterizing the phenotype of associated tumors. The mutant protein is useful in drug screening for compositions that antagonize or otherwise modulate HH activity or expression. The encoded protein is also used as a therapeutic, to modulate cell proliferation and differentiation, and treatment of pathological conditions associated with decreased hedgehog signaling.

Growing community of inventors

Oakland, CA, United States of America

Ervin H Epstein, Jr