Stephen J. Waters

Learn More
Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114) is one of a new class of anticancer agents that are semisynthetic derivatives of the mushroom toxin illudin S. Preclinical studies and clinical trials have demonstrated that irofulven is effective against several tumor types. Mechanisms of action studies indicate that irofulven induces DNA damage, MAPK(More)
Targeted delivery of therapeutic drugs promises to become the norm to treat cancer. Here, we conjugated the cytotoxic agent 6-hydroxypropylacylfulvene (HPAF) to anginex, a peptide that targets galectin-1, which is highly expressed in endothelial cells of tumor vessels. In a human ovarian cancer model in mice, the conjugate inhibited tumor growth better than(More)
Combination of chemotherapeutic agents and angiogenesis inhibitors is now commonly employed in the clinic to treat cancer. Here, we used angiostatic agents anginex and 0118, in combination with the chemotherapeutic irofulven, to treat human ovarian tumor xenografts in mice. General linear mixed models were used to statistically analyze tumor growth curves.(More)
The minimum alveolar concentration (MAC) of I-653 was determined in six beagle dogs and four New Zealand white rabbits. The MAC values (+/- SD) were 7.2 +/- 1.0 atm % for dogs and 8.9 +/- 0.3 atm % for rabbits. Comparison of these results with published MAC values for other anesthetics indicate that I-653 is one-third to one-eighth as potent as currently(More)
Irofulven (hydroxymethylacylfulvene) is a novel antitumor drug, which acts by alkylating cellular macromolecular targets. The drug is a potent inducer of apoptosis in various types of tumor cells, whereas it is nonapoptotic in normal cells. This study defined molecular responses to irofulven involving mitochondrial dysfunction and leading to death of(More)
Irofulven (6-hydroxymethylacylfulvene, MGI-114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product obtained from the Omphalotus mushroom. Irofulven has demonstrated potent activity against a broad range of solid tumors in both cellular and xenograft models and has shown promising activity in clinical trials. To guide the clinical use(More)
The overexpression of Bcl-2 is implicated in the resistance of cancer cells to apoptosis. This study explored the potential of irofulven (hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863), a novel DNA- and protein-reactive anticancer drug, to overcome the anti-apoptotic properties of Bcl-2 in HeLa cells with controlled Bcl-2 overexpression. Irofulven(More)
PURPOSE To characterize the activities of irofulven, a novelanticancer agent derived from the mushroom natural productilludin S toward human cancer cells. EXPERIMENTAL DESIGN We have determined the activity spectrum of irofulven toward a human tumor cell panel comprised of 10 different tumor types in comparison with cisplatin and ET-743. We have also(More)
PURPOSE 6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the mushroom toxin illudin S that has been shown to be a potent cytotoxic agent with an improved therapeutic index compared with its parent compound. The studies were conducted to evaluate the antitumor activity of MGI 114 as a single agent and in combination with(More)
BACKGROUND Pancreatic carcinoma resists chemotherapeutic mediation of apoptosis. Irofulven (MGI 114, 6-hydroxymethylacylfulvene) is a novel illudin S analogue that we have shown to induce caspase-mediated apoptosis in pancreatic carcinoma cell lines. MATERIALS AND METHODS Westem blot analysis and kinase assays were used to demonstrate the activation of(More)