Wisconsin Alumni Research Foundation

William E Fahl

John A Kink

Arnold E Ruoho

Ming Zhu

Minesh Mehta

Nalini Raghavachari

Daniel D Peebles

Wyeth W Wasserman

Richard R Copp

Kathleen L Fahl

Richard C Copp

Ralph B Puchalski

T Herbert Manoharan

Andrew M Gulick

Cynthia E Ochsner

Katharine Kramer

Vasoconstrictors are administered topically to provide protection against the adverse effects, e.g., alopecia, mucositis or dermatitis, induced by chemotherapy or radiotherapy. Appropriate dosages and formulations of topical vasoconstrictors are provided. Methods for the use of such compositions are also provided.

Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy

Compositions, pharmaceutical preparations and methods are disclosed for protecting non-neoplastic cells from damage caused by cancer chemotherapeutic agents or radiation therapy, during the course of cancer therapy or bone marrow transplant. These are based on the use of chemoprotective inducing agents that induce or increase production of cellular detoxification enzymes in target cell populations. The compositions and methods are useful to reduce or prevent hair loss, gastrointestinal distress and lesions of the skin and oral mucosa that commonly occur in patients undergoing cancer therapy. Also disclosed is a novel assay system for identifying new chemoprotective inducing agents.

Compositions and methods for protecting cells during cancer chemotherapy and radiotherapy

The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule.

Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors

The invention provides novel polyamine compounds and pharmaceutical compositions for administration in conjunction with cancer chemotherapy or radiation therapy. The compounds are administered locally to provide protection against the adverse side-effects of chemotherapy or radiation therapy, such as alopecia, mucositis and dermatitis. Pharmaceutical preparations comprising one or more chemoprotective polyamines formulated for topical or local delivery to epithelial or mucosal cells are disclosed. Methods of administering the pharmaceutical preparations are also disclosed.

Polyamine compounds and compositions for use in conjunction with cancer therapy

The invention provides novel polyamine and amino thiol compounds and pharmaceutical compositions for administration in conjunction with cancer chemotherapy or radiation therapy. The compounds are administered locally to provide protection against the adverse side-effects of chemotherapy or radiation therapy, such as alopecia, mucositis and dermatitis. Pharmaceutical preparations comprising one or more chemoprotective polyamines or amino thiols formulated for topical or local delivery to epithelial or mucosal cells are disclosed. Methods of administering the pharmaceutical preparations are also disclosed.

Amino thiol compounds and compositions for use in conjunction with cancer therapy

Polyamine effectors are administered locally to provide protection against the adverse side-effects of chemotherapy or radiation therapy, such as alopecia, mucositis and dermatitis. Pharmaceutical preparations comprising one or more polyamine effectors formulated for topical or local delivery to epithelial or mucosal cells are disclosed. Methods of administering the pharmaceutical preparations are also disclosed.

Polyamines and analogs for protecting cells during cancer chemotherapy and radiotherapy

A method is described for the creation of novel isoforms of the enzyme glutathione S-transferase which have enhanced activity in host cells against specific toxic agents. The method includes site directed mutagenesis and selection with the targeted agent in the host cells. The sites of directed mutagenesis is the site of electrophile binding by the native form of the enzyme. This site has proven susceptible to manipulation without loss of enzymatic activity. Various techniques for enhancing the expression, activity, or localization of the expressed enzyme in mammalian cells are described. Genes for the mutant isoforms of the enzyme may be useful in cancer therapeutics to confer upon selected groups of cells heightened resistance to antineoplastic agents.

Glutathione S-transferase isoforms

A set of seven nuclear proteins were identified which bind to the antioxidant responsive element (ARE), a DNA sequence present in the promoters of inducible chemoprotective enzymes. One of these ARE binding proteins, here designated ARE-BP-1, has been found to exhibit binding characteristics that parallel the DNA sequences that are necessary for transcriptional induction of the chemoprotective enzymes. ARE-BP-1 is an approximately 160 kDa protein that appears to be a major control switch on the genes which act to protect cells from chemical agents. For binding by ARE-BP-1, a nucleotide sequence must include sequences outside of what was previously through to be the minimally sufficient DNA sequence for inducibility.

Growing community of inventors

Madison, WI, United States of America

William E Fahl