scholarly journals Tumor-Targeting Bacteria: As Vectors, Immunotherapeutic Agents And Tumor-Targeting Probes For Cancer Detection And Therapy

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Lihini Ranesha Weerakkody ◽  
Сhamindri Witharana
Keyword(s):  
Anticancer Agents ◽  
Tumor Targeting ◽  
Bacterial Species ◽  
Bifidobacterium Longum ◽  
Anticancer Therapy ◽  
Genetically Engineered ◽  
Treatment Modalities ◽  
Bacterial Strains ◽  
Angiogenic Proteins

Cancer is the world's second leading cause of death in humans. Conventional anticancer therapies are often associated with lack of tumor specificity, failure to detect small metastases, increased resistance of tumors to anticancer drugs, and unintended adverse effects. Numerous alternative and better strategies in cancer treatment have been developed to overcome the negative effects of traditional cancer therapies. More than a century ago, William Coley, the father of cancer immounotherapy, laid the groundwork for bacterial anticancer therapy. Bacterial immunotherapy has been emerging as a potential anticancer therapy. Moreover, certain obligate and facultative anaerobic bacterial species are exploited as vectors for gene delivery to treat cancer. These genes encode for anticancer agents, cytokines, cytotoxic peptides, anti-angiogenic proteins, therapeutic molecules and prodrug-converting enzymes. Genetically engineered bacterial strains of Salmonella, Bifidobacterium, Clostridium and Listeria are widely used to deliver genes in anticancer therapy since they can selectively accumulate in solid tumors with a hypoxic/necrotic core in vivo, providing appealing delivery systems to target therapeutic agents and immunomodulatory molecules to the site of tumor. Certain genetically modified bacterial species such as Bifidobacterium longum and Bacillus licheniformis have been effectively used for the enzyme/prodrug therapy for cancer. Furthermore, certain anaerobic bacteria are emerging as potential tumor markers due to the increased mobility and the selectivity in germinating and multiplying in hypoxic/anoxic environments. Many of these novel developments have been studied extensively in different experimental models of cancer and certain clinical trials are ongoing for some treatment modalities. Although favourable results have shown so far, further studies and technological innovations are required to ensure the efficacy of bacterial anticancer therapy.

scholarly journals Modelling Pancreatic Neuroendocrine Cancer: From Bench Side to Clinic

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3170
Author(s):  
Alexander Ney ◽  
Gabriele Canciani ◽  
J. Justin Hsuan ◽  
Stephen P. Pereira
Keyword(s):  
Ex Vivo ◽  
Neuroendocrine Differentiation ◽  
Genetically Engineered ◽  
Treatment Modalities ◽  
Ductal Adenocarcinoma ◽  
Disease Models ◽  
Tissue Remodelling ◽  
In Vivo Models ◽  
Original Tumour

Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease.

scholarly journals Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats

2006 ◽  
Vol 97 (7) ◽  
pp. 649-657 ◽  
Author(s):  
Takayuki Sasaki ◽  
Minoru Fujimori ◽  
Yoshinori Hamaji ◽  
Yoshihisa Hama ◽  
Ken-ichi Ito ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Bifidobacterium Longum ◽  
Mammary Tumors ◽  
Genetically Engineered ◽  
Enzyme Prodrug Therapy

scholarly journals Strain-level Screening of Human Gut Microbes Identifies Blautia Producta as a Novel Anti-hyperlipidemic Probiotic Via the Production of 12-methylmyristic Acid

2021 ◽  
Author(s):  
Chongming Wu ◽  
Wenyi Xu ◽  
Jiaqi Yu ◽  
Zhuanyu Li ◽  
Yinghui Zhang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Throughput Screening ◽  
Large Scale ◽  
Bacterial Species ◽  
Strain Level ◽  
Bacterial Strains ◽  
Human Gut ◽  
Strain Specificity ◽  
Gut Microbes

Abstract Background: Compelling evidence has linked the commensal gut microbiota to human metabolic syndromes and provided new therapeutic potentials against diseases, such as hyperlipidemia. However, the precise regulatory effect of each bacterial species on human lipid homeostasis remains largely unknown.Results: We set up a cell-based high-throughput screening platform and screened 2250 human gut bacterial strains from 186 species for the lipid-decreasing activity in HepG2 cells, in which 388 strains steadily inhibited lipid accumulation. Different strains in the same species usually displayed distinct lipid-modulatory actions, revealing an obvious strain-specificity. Blautia producta, Lactobacillus gasseri, and Bifidobacterium pseudolongum contained a much higher portion of hypolipidemic strains. Among all the tested strains, the mucosal bacterium Blautia producta exhibited the most potency to suppress lipid accumulation, and gavage of live Bl. producta effectively ameliorated hyperlipidemia in mice. 12-Methylmyristic acid (12-MMA) was identified as an important active metabolite of Bl. producta by pan-genomics and comparative metabolomics, which exerted potent anti-hyperlipidemic effect in vivo and activated G protein-coupled receptor 120 (GPR120), thus stimulating white adipose tissue browning.Conclusions: Together, these data reveal a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, and raise the possibility of developing therapeutics based on Bl. producta and microbial metabolite 12-MMA to treat hyperlipidemia.

scholarly journals Probiotic Lactobacillus spp. act Against Helicobacter pylori-induced Inflammation

2019 ◽  
Vol 8 (1) ◽  
pp. 90 ◽  
Author(s):  
Yi-Hsing Chen ◽  
Wan-Hua Tsai ◽  
Hui-Yu Wu ◽  
Chun-Ya Chen ◽  
Wen-Ling Yeh ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Species ◽  
Lactobacillus Rhamnosus ◽  
Gastrointestinal Diseases ◽  
In Vivo Studies ◽  
Bacterial Strains ◽  
H Pylori ◽  
Lactobacillus Spp

The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the mouse stomach were also alleviated by these Lactobacillus strains. Furthermore, the abundance of beneficial gut bacteria, including Bifidobacterium spp. and Akkermansia muciniphilia, were significantly increased in H. pylori-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that Lactobacillus spp. ameliorate H. pylori-induced inflammation and supports beneficial gut specific bacteria that act against H. pylori infection.

Structural analysis of the photosynthetic membrane from Ectothiorhodospira halochloris

1983 ◽  
Vol 41 ◽  
pp. 740-741
Author(s):  
H. Engelhardt ◽  
R. Guckenberger ◽  
W. Baumeister
Keyword(s):  
Lattice Structure ◽  
Bacterial Species ◽  
Hexagonal Lattice ◽  
Reaction Centre ◽  
Photosynthetic Membrane ◽  
Rhodopseudomonas Viridis ◽  
Photosynthetic Membranes ◽  
Ectothiorhodospira Halochloris ◽  
Main Components

Bacterial photosynthetic membranes contain, apart from lipids and electron transport components, reaction centre (RC) and light harvesting (LH) polypeptides as the main components. The RC-LH complexes in Rhodopseudomonas viridis membranes are known since quite seme time to form a hexagonal lattice structure in vivo; hence this membrane attracted the particular attention of electron microscopists. Contrary to previous claims in the literature we found, however, that 2-D periodically organized photosynthetic membranes are not a unique feature of Rhodopseudomonas viridis. At least five bacterial species, all bacteriophyll b - containing, possess membranes with the RC-LH complexes regularly arrayed. All these membranes appear to have a similar lattice structure and fine-morphology. The lattice spacings of the Ectothiorhodospira haloohloris, Ectothiorhodospira abdelmalekii and Rhodopseudomonas viridis membranes are close to 13 nm, those of Thiocapsa pfennigii and Rhodopseudomonas sulfoviridis are slightly smaller (∼12.5 nm).

Production of Novel Bioactive Compounds by the Bacteria Associated with Some Marine Sponges of Gulf of Mannar and Palk Bay, Southeast Coast of India

2018 ◽  
Vol 6 (8) ◽  
pp. 183
Author(s):  
V. Ramadas ◽  
G. Chandralega
Keyword(s):  
Bioactive Compounds ◽  
Bacterial Species ◽  
Marine Sponges ◽  
Marine Organisms ◽  
Gulf Of Mannar ◽  
Bacterial Symbionts ◽  
Palk Bay ◽  
Excellent Source

Sponges, exclusively are aquatic and mostly marine, are found from the deepest oceans to the edge of the sea. There are approximately 15,000 species of sponges in the world, of which, 150 occur in freshwater, but only about 17 are of commercial value. A total of 486 species of sponges have been identified in India. In the Gulf of Mannar and Palk Bay a maximum of 319 species of sponges have been recorded. It has been proved that marine organisms are excellent source of bioactive secondary metabolites and number of compounds of originated from marine organisms had been reported to possess in-vitro and in-vivo immuno stimulatory activity. Extracts from 20 sponge species were tested for bacterial symbionts and bioactive compounds were isolated from such associated bacterial species in the present study.

Galacto- and Fructo-oligosaccharides Utilized for Growth by Cocultures of Bifidobacterial Species Characteristic of the Infant Gut

2020 ◽  
Author(s):  
Ian Sims ◽  
GW Tannock
Keyword(s):  
Breast Milk ◽  
Bacterial Species ◽  
Bifidobacterium Longum ◽  
Well Being ◽  
Bifidobacterium Bifidum ◽  
Child Rearing ◽  
Potential Growth ◽  
Human Infants ◽  
Infant Diet ◽  
Growth Substrates

Copyright © 2020 American Society for Microbiology. Bifidobacterial species are common inhabitants of the gut of human infants during the period when milk is a major component of the diet. Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum subspecies longum, and B. longum subspecies infantis have been detected frequently in infant feces, but B. longum subsp. infantis may be disadvantaged numerically in the gut of infants in westernized countries. This may be due to the different durations of breast milk feeding in different countries. Supplementation of the infant diet or replacement of breast milk using formula feeds is common in Western countries. Formula milks often contain galacto- and/or fructo-oligosaccharides (GOS and FOS, respectively) as additives to augment the concentration of oligosaccharides in ruminant milks, but the ability of B. longum subsp. infantis to utilize these potential growth substrates when they are in competition with other bifidobacterial species is unknown. We compared the growth and oligosaccharide utilization of GOS and FOS by bifidobacterial species in pure culture and coculture. Short-chain GOS and FOS (degrees of polymerization [DP] 2 and 3) were favored growth substrates for strains of B. bifidum and B. longum subsp. longum, whereas both B. breve and B. longum subsp. infantis had the ability to utilize both short- and longer-chain GOS and FOS (DP 2 to 6). B. breve was nevertheless numerically dominant over B. longum subsp. infantis in cocultures. This was probably related to the slower use of GOS of DP 3 by B. longum subsp. infantis, indicating that the kinetics of substrate utilization is an important ecological factor in the assemblage of gut communities.IMPORTANCE The kinds of bacteria that form the collection of microbes (the microbiota) in the gut of human infants may influence health and well-being. Knowledge of how the composition of the infant diet influences the assemblage of the bacterial collection is therefore important because dietary interventions may offer opportunities to alter the microbiota with the aim of improving health. Bifidobacterium longum subspecies infantis is a well-known bacterial species, but under modern child-rearing conditions it may be disadvantaged in the gut. Modern formula milks often contain particular oligosaccharide additives that are generally considered to support bifidobacterial growth. However, studies of the ability of various bifidobacterial species to grow together in the presence of these oligosaccharides have not been conducted. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of human nutrition on the development of the gut microbiota.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

Voltammetric Detection of Tetrodotoxin Real-Time In Vivo of Mouse Organs using DNA-Immobilized Carbon Nanotube Sensors

2019 ◽  
Vol 15 (5) ◽  
pp. 567-574
Author(s):  
Huck Jun Hong ◽  
Suw Young Ly
Keyword(s):  
Carbon Nanotube ◽  
Real Time ◽  
Anticancer Agents ◽  
Cancer Metastasis ◽  
Anodic Stripping Voltammetry ◽  
Stripping Voltammetry ◽  
Takifugu Rubripes ◽  
In Vivo Detection ◽  
Voltammetric Detection

Background: Tetrodotoxin (TTX) is a biosynthesized neurotoxin that exhibits powerful anticancer and analgesic abilities by inhibiting voltage-gated sodium channels that are crucial for cancer metastasis and pain delivery. However, for the toxin’s future medical applications to come true, accurate, inexpensive, and real-time in vivo detection of TTX remains as a fundamental step. Methods: In this study, highly purified TTX extracted from organs of Takifugu rubripes was injected and detected in vivo of mouse organs (liver, heart, and intestines) using Cyclic Voltammetry (CV) and Square Wave Anodic Stripping Voltammetry (SWASV) for the first time. In vivo detection of TTX was performed with auxiliary, reference, and working herring sperm DNA-immobilized carbon nanotube sensor systems. Results: DNA-immobilization and optimization of amplitude (V), stripping time (sec), increment (mV), and frequency (Hz) parameters for utilized sensors amplified detected peak currents, while highly sensitive in vivo detection limits, 3.43 µg L-1 for CV and 1.21 µg L-1 for SWASV, were attained. Developed sensors herein were confirmed to be more sensitive and selective than conventional graphite rodelectrodes modified likewise. A linear relationship was observed between injected TTX concentration and anodic spike peak height. Microscopic examination displayed coagulation and abnormalities in mouse organs, confirming the powerful neurotoxicity of extracted TTX. Conclusion: These results established the diagnostic measures for TTX detection regarding in vivo application of neurotoxin-deviated anticancer agents and analgesics, as well as TTX from food poisoning and environmental contamination.

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