Strong Enhancement of Recombinant Cytosine Deaminase Activity in<i>Bifidobacterium longum</i>for Tumor-Targeting Enzyme/Prodrug Therapy

Hamaji, Yoshinori; Fujimori, Minoru; Sasaki, Takayuki; Matsuhashi, Hitomi; Matsui-Seki, Keiichi; Shimatani-Shibata, Yuko; Kano, Yasunobu; Amano, Jun; Taniguchi, Shun’ichiro

doi:10.1271/bbb.60502

Cited by 30 publications

(21 citation statements)

References 26 publications

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“…1) and exhibited stability problems in B. longum, but it was more stable in B. breve (115). A point mutation in the CD gene, at the active site, was found to increase CD activity 10-fold, thus improving the efficacy of this antitumor activity (111). An analogous antitumor strategy was developed for expression of a human endostatin gene in B. longum and B. adolescentis, using the lambda P R P L promoter and a thetareplicating ori from the group V bifidobacterial plasmid pMB1 ( Fig.…”

Section: Development Of Cloning and Expression Vector Systems For Bifmentioning

confidence: 99%

Genomic Insights into Bifidobacteria

Lee

O’Sullivan

2010

Microbiol Mol Biol Rev

250

197

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SUMMARY Since the discovery in 1899 of bifidobacteria as numerically dominant microbes in the feces of breast-fed infants, there have been numerous studies addressing their role in modulating gut microflora as well as their other potential health benefits. Because of this, they are frequently incorporated into foods as probiotic cultures. An understanding of their full interactions with intestinal microbes and the host is needed to scientifically validate any health benefits they may afford. Recently, the genome sequences of nine strains representing four species of Bifidobacterium became available. A comparative genome analysis of these genomes reveals a likely efficient capacity to adapt to their habitats, with B. longum subsp. infantis exhibiting more genomic potential to utilize human milk oligosaccharides, consistent with its habitat in the infant gut. Conversely, B. longum subsp. longum exhibits a higher genomic potential for utilization of plant-derived complex carbohydrates and polyols, consistent with its habitat in an adult gut. An intriguing observation is the loss of much of this genome potential when strains are adapted to pure culture environments, as highlighted by the genomes of B. animalis subsp. lactis strains, which exhibit the least potential for a gut habitat and are believed to have evolved from the B. animalis species during adaptation to dairy fermentation environments.

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Section: Development Of Cloning and Expression Vector Systems For Bifmentioning

confidence: 99%

Genomic Insights into Bifidobacteria

Lee

O’Sullivan

2010

Microbiol Mol Biol Rev

250

197

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“…107 B. longum selectively produces CD in hypoxic mammary tumor tissues in rats, and converts 5-FC into 5-FU in vivo. [108][109][110] This system could be significantly improved by combination with MR imaging technology.…”

Section: Combined Imaging and Therapymentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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“…Probiotics were selected based on antioxidative and anti-inflammatory effects, which have been reported in the past studies (Fijan. 2014, Hamaji et al 2007, Messaoudi et al 2011, Pang et al 2012). Probiotics powder was colorless and odorless; at first, probiotics are inactive in water due to their special formulation, which includes a carrier compound that bonds to probiotics and allows probiotics activation in gut.…”

Section: Probiotics Preparationmentioning

confidence: 99%

Probiotics improve insulin resistance status in an experimental model of Alzheimer’s disease

Azm

Djazayery

Safa

et al. 2017

Med. J. Islam. Republic Iran

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↑What is "already known" in this topic: Studies have shown that probiotics can be a nutritional approach to improve metabolic markers such as FBS and lipid profile in patients with diabetes.→What this article adds: Disruption of insulin signaling cascade and insulin resistance can induce AD that causes systemic alterations in serum insulin, FBS levels, and lipid profile; however, probiotics can improve these markers. Probiotics improve insulin AbstractBackground: Nowadays, Alzheimer's disease (AD) is considered as Type 3 diabetes in which insulin resistance is the common cause of both diseases. Disruption of insulin signaling cascade and insulin resistance can induce AD; and central insulin resistance causes systemic alterations in serum insulin, FBS levels, and lipid profile. Studies have shown that probiotics (Lactobacillus and Bifidobacterium species) can be used as a nutritional approach to improve these metabolic changes. We assessed the probiotic effect (4 species of Lactobacillus and Bifidobacterium) on insulin resistance biomarkers in an experimental model of AD.Methods: A total of 60 rats were divided into 5 groups: (1) a control group without surgical and dietary intervention; (2) a controlprobiotics group receiving probiotics for 8 weeks, but not receiving any surgical intervention; (3) a group receiving a sham operation in which PBS was injected intrahippocampus but without dietary intervention; (4) an Alzheimer group for which Amyloid-ß (Aß) 1-42 was injected intrahippocampus but without dietary intervention; (5) and an Alzheimer-probiotics group for which Aß1-42 was injected intrahippocampus and given 2g probiotics for 8 weeks. The FBS levels and lipid profile were measured by a calorimetric method, insulin levels were detected by an ELISA kit, and HOMA-IR was calculated using a formula. ANOVA (one way analysis of variance followed by Bonferroni comparisons post hoc) was used to compare all the variables between groups.Results: Serum glucose, insulin levels, and HOMA-IR index increased in the Alzheimer group compared to the control (p<0.001), while probiotics decreased only insulin level and HOMA-IR index in AP group compared to Alzheimer group (p<0.001). Also, TG levels increased in the Alzheimer group (p<0.001), but no significant difference was detected between Alzheimer and Alzheimerprobiotics group.Conclusion: It seems that probiotics play an effective role in controlling glycemic status of Alzheimer's disease.

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Strong Enhancement of Recombinant Cytosine Deaminase Activity inBifidobacterium longumfor Tumor-Targeting Enzyme/Prodrug Therapy

Cited by 30 publications

References 26 publications

Genomic Insights into Bifidobacteria

Genomic Insights into Bifidobacteria

Bacterial vectors for imaging and cancer gene therapy: a review

Probiotics improve insulin resistance status in an experimental model of Alzheimer’s disease

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