ArticleJournal of the National Cancer Institute2008
A genetically enhanced anaerobic bacterium for oncopathic therapy of pancreatic cancer.
Article in Journal of the National Cancer Institute, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed.
- Benefits and challenges of host depletion methods in profiling the upper and lower respiratory microbiome.NPJ biofilms and microbiomes · 2025Article
- Engineering the gut microbiota to treat chronic diseases.Applied microbiology and biotechnology · 2020Review
- Spontaneous regression of tumour and the role of microbial infection--possibilities for cancer treatment.Anti-cancer drugs · 2016Review
- Effect of Heat-Inactivated Clostridium sporogenes and Its Conditioned Media on 3-Dimensional Colorectal Cancer Cell Models.Scientific reports · 2015Article
- Clostridium to treat cancer: dream or reality?Annals of translational medicine · 2015Article
- Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy.Gene therapy · 2011Review
- Orally administered bifidobacteria as vehicles for delivery of agents to systemic tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Retraction: A genetically enhanced anaerobic bacterium for oncopathic therapy of pancreatic cancer.Journal of the National Cancer Institute · 2010Article
- Prospects for the use of artificial chromosomes and minichromosome-like episomes in gene therapy.Journal of biomedicine & biotechnology · 2010Article
- The oncopathic potency of Clostridium perfringens is independent of its alpha-toxin gene.Human gene therapy · 2009Article
- Bacteria as vectors for gene therapy of cancer.Bioengineered bugsReview
Corrections and comments
- Retraction · 2010-02-24Duplication of/in Image · Falsification/Fabrication of Data · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Misconduct findings for Zhiyu Li: https://ori.hhs.gov/content/case-summary-li-zhiyu
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- Retracted
Authors and funding
5 authors.
Funding
Abstract
backgroundA major obstacle in treatment of solid tumors is the inefficient delivery of therapeutic agents to the hypoxic cores. Hypoxia offers the potential for anaerobic bacteria colonization and tumor destruction by the bacteria, and dormant spores of wild-type Clostridium perfringens (Cp) germinate and proliferate within the hypoxic cores of pancreatic tumors in mice. However, the oncopathic effects of Cp were limited by host inflammatory responses and by Cp's residual tolerance to oxygen, which caused toxic effects in animals.
methodsRecombinant Cp strains in which superoxide dismutase, a major oxygen tolerance gene, was deleted (Cp/sod(-)) were constructed to enhance its selective growth in tumors. In addition, Panton-Valentine Leukocidin (PVL), an inflammation-suppressing gene from Staphylococcus aureus, was inserted into the Cp/sod(-) genome to enhance its oncopathic potency. The ability of the recombinant Cp strains to kill tumors was investigated in C57/BL6 mice bearing murine PANC02 tumors. Systemic and organ toxic effects were assessed by monitoring serum chemistries and histopathological examination. Statistical tests were two-sided.
resultsCp/sod(-) showed reduced toxic effects compared with wild-type Cp when spores were administered intravenously into PANC02 tumor-bearing mice. Mice treated with Cp/sod(-)/PVL spores demonstrated a reduction in neutrophils and macrophages in tumors, logarithmically elevated growth of intratumoral bacteria, enhanced tumor necrosis, and substantially prolonged survival without apparent systemic and organ toxic effects, compared with mice treated with both wild-type Cp and Cp/sod(-) spores. Accordingly, 47% of Cp/sod(-)/PVL-treated mice (n = 15) achieved tumor-free survival for over 120 days, whereas all mice treated with Cp/sod(-) or phosphate-buffered saline (n = 10 per group) died within 50 days. The median survival for Cp/sod(-)/PVL-treated mice was 77 days (95% confidence interval [CI] = 45 to 120 days) and for Cp/sod(-)-treated mice was 30 days (95% CI = 23 to 36 days; P < .001).
conclusionsCp/sod(-)/PVL provides a prototype for a novel class of oncopathic microbes that may have potential for the safe and effective treatment of pancreatic cancer and other poorly vascularized tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.