scholarly journals The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 517
Author(s):  
Patrick Ball ◽  
Robert Hobbs ◽  
Simon Anderson ◽  
Emma Thompson ◽  
Vanessa Gwenin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Bacillus Licheniformis ◽  
Maximum Dosage ◽  
Superparamagnetic Nanoparticles ◽  
Enzyme Prodrug Therapy ◽  
Hydroxylamine Derivative ◽  
Therapy Approach ◽  
Potential Use

The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy. One such enzyme that has proved promising is the YfkO nitroreductase from Bacillus Licheniformis. Upon investigation, the YfkO nitroreductase was shown to have a much lower Km (below the maximum dosage) than that of NfnB as well as the fact that when reacting with the prodrug it produces a much more favourable ratio of enzymatic products than NfnB, forming more of the desired 4-hydroxylamine derivative of CB1954.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

scholarly journals Progress in Gene Therapy to Prevent Retinal Ganglion Cell Loss in Glaucoma and Leber’s Hereditary Optic Neuropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Sara E. Ratican ◽  
Andrew Osborne ◽  
Keith R. Martin
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Genome Editing ◽  
Optic Neuropathy ◽  
Single Gene ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Potential Use ◽  
Hereditary Optic Neuropathy

The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber’s congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clinical trials of gene therapy for other single-gene defect diseases of the retina and optic nerve are also currently underway. However, for optic nerve diseases not caused by single-gene defects, gene therapy strategies are likely to focus on slowing or preventing neuronal death through the expression of neuroprotective agents. In addition to these strategies, there has also been recent interest in the potential use of precise genome editing techniques to treat ocular disease. This review focuses on recent developments in gene therapy techniques for the treatment of glaucoma and Leber’s hereditary optic neuropathy (LHON). We discuss recent successes in clinical trials for the treatment of LHON using gene supplementation therapy, promising neuroprotective strategies that have been employed in animal models of glaucoma and the potential use of genome editing techniques in treating optic nerve disease.

Treatment and secondary prevention of venous thrombo -embolism in cancer patients

2012 ◽  
Vol 32 (02) ◽  
pp. 139-144 ◽  
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Initial Period ◽  
Factor Xa ◽  
Secondary Prophylaxis ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancer-associated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3–6 months. New oral anti-coagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE also in cancer patients. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

scholarly journals Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

2019 ◽  
Vol 10 (4) ◽  
pp. 45 ◽  
Author(s):  
Anderson ◽  
Hobbs ◽  
Gwenin ◽  
Ball ◽  
Bennie ◽  
...  
Keyword(s):  
Magnetic Nanoparticle ◽  
Genetically Modified ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Tumour Site ◽  
Enzyme Prodrug Therapy ◽  
Delivery Vector ◽  
Cell Penetrating ◽  
Subsequent Activation ◽  
Potential Use

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.

scholarly journals International consensus on a proposed score system for muscle biopsy evaluation in patients with juvenile dermatomyositis: A tool for potential use in clinical trials

2007 ◽  
Vol 57 (7) ◽  
pp. 1192-1201 ◽  
Author(s):  
Lucy R. Wedderburn ◽  
Hemlata Varsani ◽  
Charles K. C. Li ◽  
Katy R. Newton ◽  
Anthony A. Amato ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Muscle Biopsy ◽  
Juvenile Dermatomyositis ◽  
International Consensus ◽  
Score System ◽  
Potential Use

scholarly journals The “growing” evidence of the bottle and the bump: how does alcohol use during pregnancy affect infant and childhood growth?

2014 ◽  
pp. 138-141
Author(s):  
Linda Marie O’Keeffe
Keyword(s):  
Clinical Trials ◽  
Preterm Birth ◽  
Pregnant Women ◽  
Health Professionals ◽  
Harmful Effect ◽  
Advertising Campaign ◽  
Moderate Drinking ◽  
Childhood Growth ◽  
The Past ◽  
Potential Use

“Guinness is good for you!” And it’s not just Guinness who, in the past, peddled this message as part of their global advertising campaign! In fact, pregnant women in Ireland were once advised to drink a glass of Guinness a day to fortify themselves and their babies! Although a practice that has been completely abandoned since the 1980s and one which would surely cause a stir today, it is astonishing to ever imagine pregnant women consuming alcohol on the recommendation of their doctor or midwife. Indeed, clinical trials of the potential use of alcohol to prevent preterm birth were on-going up until the 1970s, and some health professionals used alcohol for this purpose in obstetric practice. These days there is a greater focus on the harmful effect of alcohol and media attention on the issue of “moderate” drinking during pregnancy has never been more intense. Today it is estimated that, ...

scholarly journals FAVIPIRAVIR AS A POTENTIAL DRUG IN THE TREATMENT OF COVID-19

2020 ◽  
Vol 8 (4) ◽  
pp. 7-12
Author(s):  
Dany Geraldo Kramer ◽  
Maria Josilene Leonardo Da Silva ◽  
Gislanne Stéphanne Estevam Da Silva ◽  
Ana Maria Marinho Andrade De Moura ◽  
Geraldo Barroso Cavalcanti Junior ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Rna Polymerase ◽  
Randomized Clinical Trials ◽  
Rna Viruses ◽  
Potential Drug ◽  
Potential Use

Favipiravir is a drug developed for use against influenza and has been used successfully in other infectious conditions. After being internalized in the cell, the substance is phosphoribosylated acting on the RNA polymerase, and thus inhibiting replication and RNA viruses. Thus, the present study aimed to discuss the potential use of favipiravir in coronovavirus infections. There have been few studies involving favipiravir in COVID 19, however there is a report of recovery in more than 70% of patients diagnosed with pneumonia. However, new studies need to be carried out, mainly randomized clinical trials, so that the potential use of favipiravir in coronoviruses is adequately grounded.

Bacillus Licheniformis Coated Bioparticles for Hydrogen Peroxide Degradation

2012 ◽  
Vol 59 (1) ◽  
Author(s):  
Wei Kheng Teoh ◽  
Zaharah Ibrahim ◽  
Shafinaz Shahir
Keyword(s):  
Hydrogen Peroxide ◽  
Bacillus Licheniformis ◽  
Extracellular Polymeric Substances ◽  
Exponential Phase ◽  
Bacterial Suspension ◽  
Late Exponential Phase ◽  
Repeated Use ◽  
Biofilm Development ◽  
Potential Use ◽  
Second Use

The potential use of Bacillus licheniformis coated bioparticles for hydrogen peroxide (H2O2) degradation was assessed in this study. Bioparticles were made by mixing zeolite, activated carbon and cement in ratio 20:5:6 for attachment of biofilm. The efficiency of H2O2 degradation was examined in the presence and absence of biofilm (control) on bioparticles. Optimisation of biofilm development (7 and 10 days) and reusability were also investigated for H2O2degradation. Actively growing bacterial suspension (late exponential phase) of B.licheniformis was used in development of pure culture biofilm. The 7–day biofilm coated bioparticles system successfully achieved complete H2O2 degradation within an hour (highest rate = 1.17 % H2O2 degraded per minute) while the control showed no significant H2O2 degradation. After repeated use of biofilm coated bioparticles, the rate of H2O2 degradation declined to 0.654 % H2O2degraded per minute, and second use, the rate of H2O2 degradation was 0.166 % H2O2 degraded per minute. Field Emission Scanning Electron Microscope (FESEM) images of the biofilm coated bioparticles showed the attachment of cells and formation of extracellular polymeric substances (EPS), whereas the control showed no biofilm formed.

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