Glioblastoma Multiforme: Novel Therapeutic Approaches

The current therapy for glioblastoma multiforme involves total surgical resection followed by combination of radiation therapy and temozolomide. Unfortunately, the efficacy for such current therapy is limited, and newer approaches are sorely needed to treat this deadly disease. We have recently described the isolation of bacterial proteins and peptides with anticancer activity. In phase I human clinical trials, one such peptide, p28, derived from a bacterial protein azurin, showed partial and complete regression of tumors in several patients among 15 advanced-stage cancer patients with refractory metastatic tumors where the tumors were no longer responsive to current conventional drugs. An azurin-like protein called Laz derived from Neisseria meningitides demonstrates efficient entry and high cytotoxicity towards glioblastoma cells. Laz differs from azurin in having an additional 39-amino-acid peptide called an H.8 epitope, which allows entry and high cytotoxicity towards glioblastoma cells. Since p28 has been shown to have very little toxicity and high anti-tumor activity in advanced-stage cancer patients, it will be worthwhile to explore the use of H.8-p28, H.8-azurin, and Laz in toxicity studies and glioblastoma therapy in preclinical and human clinical trials

Final Report

This is the front matter for the 7th Biennial Symposium, International Society for Environmental Biotechnology, held at the Holiday Inn Chicago Mart Plaza, Chicago, Illinois on the dates of June 18-21, 2004. It contains a list of the symposium organizers, acknowledgements and the symposium overview

Exploring the anticancer potential of the bacterial protein azurin

Bacterial proteins and their derivative peptides have emerged as promising anticancer agents. Nowadays they represent a valuable set of candidate drugs with different origins and modes of action. Among these, monomeric cupredoxins, which are metalloproteins involved in the electron transport chain of prokaryotes, have been shown to possess potent anticancer activities. In particular, much attention has been focused on azurin produced by the pathogenic bacterium Pseudomonas aeruginosa. More recently, several in vitro and in vivo studies have reported the multi-targeting anticancer properties of azurin. Moreover, p28, a peptide derived from azurin, has completed two phase I clinical trials in cancer patients with promising results. In this updated review, we examine the current knowledge regarding azurin’s modes of action as an anticancer therapeutic protein. We also review the clinical trial results of p28 emphasizing findings that make it suited (alone or in combination) as a therapeutic agent for cancer treatment. Finally we discuss and address the challenges of using the human microbiome to discover novel and unique therapeutic cupredoxin-like proteins

Engineering of bacterial strains and their products for cancer therapy

The use of live bacteria in cancer therapies offers exciting possibilities. Nowadays, an increasing number of genetically engineered bacteria are emerging in the field, with applications both in therapy and diagnosis. In parallel, purified bacterial products are also gaining relevance as new classes of bioactive products to treat and prevent cancer growth and metastasis. In the first part of the article, we review the latest findings regarding the use of live bacteria and products as anti-cancer agents, paying special attention to immunotoxins, proteins and peptides. In particular, we focus on the recent results of using azurin or its derived peptide as anticancer therapeutic agents. In the second part, we discuss the challenges of using metagenomic techniques as a distinctive approach for discovering new anti-cancer agents from bacterial origin

Microbial-based therapy of cancer: Current progress and future prospects

The use of bacteria in the regression of certain forms of cancer has been recognized for more than a century. Much effort, therefore, has been spent over the years in developing wild-type or modified bacterial strains to treat cancer. However, their use at the dose required for therapeutic efficacy has always been associated with toxicity problems and other deleterious effects. Recently, the old idea of using bacteria in the treatment of cancer has attracted considerable interest and new genetically engineered attenuated strains as well as microbial compounds that might have specific anticancer activity without side effects are being evaluated for their ability to act as new anticancer agents. This involves the use of attenuated bacterial strains and expressing foreign genes that encode the ability to convert non-toxic prodrugs to cytotoxic drugs. Novel strategies also include the use of bacterial products such as proteins, enzymes, immunotoxins and secondary metabolites, which specifically target cancer cells and cause tumor regression through growth inhibition, cell cycle arrest or apoptosis induction. In this review we describe the current knowledge and discuss the future directions regarding the use of bacteria or their products, in cancer therapy

Regulation of Alginate Biosynthesis in Pseudomonas syringae pv. syringae

Both Pseudomonas aeruginosa and the phytopathogen P. syringae produce the exopolysaccharide alginate. However, the environmental signals that trigger alginate gene expression in P. syringae are different from those in P. aeruginosa with copper being a major signal in P. syringae. In P. aeruginosa, the alternate sigma factor encoded by algT (ς(22)) and the response regulator AlgR1 are required for transcription of algD, a gene which encodes a key enzyme in the alginate biosynthetic pathway. In the present study, we cloned and characterized the gene encoding AlgR1 from P. syringae. The deduced amino acid sequence of AlgR1 from P. syringae showed 86% identity to its P. aeruginosa counterpart. Sequence analysis of the region flanking algR1 in P. syringae revealed the presence of argH, algZ, and hemC in an arrangement virtually identical to that reported in P. aeruginosa. An algR1 mutant, P. syringae FF5.32, was defective in alginate production but could be complemented when algR1 was expressed in trans. The algD promoter region in P. syringae (PsalgD) was also characterized and shown to diverge significantly from the algD promoter in P. aeruginosa. Unlike P. aeruginosa, algR1 was not required for the transcription of algD in P. syringae, and PsalgD lacked the consensus sequence recognized by AlgR1. However, both the algD and algR1 upstream regions in P. syringae contained the consensus sequence recognized by ς(22), suggesting that algT is required for transcription of both genes