Potent anti-tumor activity of systemically-administered IL2-expressing Salmonella correlates with decreased angiogenesis and enhanced tumor apoptosis

al-Ramadi, Basel K.; Fernández-Cabezudo, Maria J.; Elhasasna, Hussain; Al-Salam, Suhail; Bashir, Ghada; Chouaı̈b, Salem

doi:10.1016/j.clim.2008.08.021

Cited by 88 publications

(62 citation statements)

References 50 publications

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“…58,59 Interestingly, a pronounced anti-tumor effect of IL-2-producing S. typhimurium was also recently shown in a mouse model of melanoma. 60 Moreover, this effect was clearly correlated with decreased tumor angiogenesis. In fact, previously unknown anti-angiogenic effects have recently been discovered for a variety of molecules involved in the immune response and cellular apoptosis mainly due to extensive ongoing research in the field of cancer therapy.…”

Section: Alternative Gene Therapymentioning

confidence: 93%

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy

et al. 2011

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Several bacterial species have inherent ability to colonize solid tumors in vivo. However, their natural anti-tumor activity can be enhanced by genetic engineering that enables these bacteria express or transfer therapeutic molecules into target cells. In this review, we summarize latest research on cancer therapy using genetically modified bacteria with particular emphasis on blocking tumor angiogenesis. Despite recent progress, only a few recent studies on bacterial tumor therapy have focused on anti-angiogenesis. Bacteria-mediated anti-angiogenesis therapy for cancer, however, is an attractive approach given that solid tumors are often characterized by increased vascularization. Here, we discuss four different approaches for using modified bacteria as anti-cancer therapeutics-bactofection, DNA vaccination, alternative gene therapy and transkingdom RNA interference-with a specific focus on angiogenesis suppression. Critical areas and future directions for this field are also outlined.

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Section: Alternative Gene Therapymentioning

confidence: 93%

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy

et al. 2011

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“…Liver tissue was processed for histological analysis following a previously published procedure (27). Briefly, livers were resected and fixed in 10% formalin, dehydrated through graded ethanol, and embedded in paraffin for permanent sections.…”

Section: Histology and Immunohistochemistry Of Liver Tissuementioning

confidence: 99%

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

Ramadi¹,

Mohamed²,

Al-Sbiei³

et al. 2016

Nanotoxicology

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Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1-20 mg/kg), on the early acute (4-24 h post-exposure) and late phase response (96 h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2 mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24 h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24 h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP.

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“…Other approaches employ S. Typhimurium to deliver cytokines to the tumor site in an attempt to activate immune cells or elicit an immune response against the tumor [8,10,35,36,37,38,39]. Antigens have also been linked to bacterial toxins that are highly immunogenic to sensitize the immune system against cancer cell antigens [10,40].…”

Section: Using Salmonella To Deliver Anti Cancer Compoundsmentioning

confidence: 99%

Targeting Tumors with Salmonella Typhimurium - Potential for Therapy

2010

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AbstrAct:When one considers the organism Salmonella enterica serotype Typhimurium (S. Typhimurium), one usually thinks of the Gram-negative enteric pathogen that causes the severe food borne illness, gastroentertitis. In this context, the idea of Salmonella being exploited as a cancer therapeutic seems pretty remote. However, there has been an escalating interest in the development of tumor-therapeutic bacteria for use in the treatment of a variety of cancers. This strategy takes advantage of the remarkable ability of certain bacteria to preferentially replicate and accumulate within tumors. In the case of S. Typhimurium, this organism infects and selectively grows within implanted tumors, achieving tumor/normal tissue ratios of approximately 1,000:1. Salmonella also has some attractive properties well suited for the design of a chemotherapeutic agent. In particular, this pathogen can easily be manipulated to carry foreign genes, and since this species is a facultative anaerobe, it is able to survival in both oxygenated and hypoxic conditions, implying this organism could colonize both small metastatic lesions as well as larger tumors. These observations are the impetus to a burgeoning field focused on the development of Salmonella as a clinically useful anti-cancer agent. We will discuss three cutting edge technologies employing Salmonella to target tumors.

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Potent anti-tumor activity of systemically-administered IL2-expressing Salmonella correlates with decreased angiogenesis and enhanced tumor apoptosis

Cited by 88 publications

References 50 publications

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

Targeting Tumors with Salmonella Typhimurium - Potential for Therapy

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