scholarly journals The Role of Network Science in Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1045
Author(s):  
Marta B. Lopes ◽  
Eduarda P. Martins ◽  
Susana Vinga ◽  
Bruno M. Costa
Keyword(s):  
Personalized Medicine ◽  
Drug Development ◽  
Information Flow ◽  
Clinical Studies ◽  
Network Science ◽  
Cancer Genomics ◽  
High Dimensional ◽  
Network Discovery ◽  
Software Implementations

Network science has long been recognized as a well-established discipline across many biological domains. In the particular case of cancer genomics, network discovery is challenged by the multitude of available high-dimensional heterogeneous views of data. Glioblastoma (GBM) is an example of such a complex and heterogeneous disease that can be tackled by network science. Identifying the architecture of molecular GBM networks is essential to understanding the information flow and better informing drug development and pre-clinical studies. Here, we review network-based strategies that have been used in the study of GBM, along with the available software implementations for reproducibility and further testing on newly coming datasets. Promising results have been obtained from both bulk and single-cell GBM data, placing network discovery at the forefront of developing a molecularly-informed-based personalized medicine.

Specific Targets in Sarcoma and Developmental Therapeutics

2010 ◽  
Vol 8 (6) ◽  
pp. 677-686 ◽  
Author(s):  
David M. Thomas ◽  
Andrew J. Wagner
Keyword(s):  
Targeted Therapy ◽  
Growth Factor ◽  
Personalized Medicine ◽  
Connective Tissue ◽  
Drug Development ◽  
Therapeutic Agents ◽  
Insulin Like Growth Factor ◽  
Developmental Therapeutics ◽  
Novel Therapeutic

Connective tissue tumors comprise a rich array of subtypes, many of which possess strong pathognomonic phenotypes and genotypes of therapeutic significance. This article describes recent applications of targeted and nontargeted therapeutic agents in connective tissue tumors that illustrate important themes in drug development. Targeted therapy has exploited the paradigms of oncogene and lineage addiction. In other cases, potential targets are more difficult to classify, such as the role of the insulin-like growth factor 1 pathway in Ewing's sarcoma. Understanding why these pathways seem critical in some cancers, and in some individuals but not others, is important in identifying novel therapeutic opportunities in an age of personalized medicine.

943-P: Role of Model-Informed Drug Development in Confirming Additional Clinical Benefits of Dulaglutide

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 943-P
Author(s):  
LAI-SAN THAM ◽  
JEANNE GEISER ◽  
CHENG CAI TANG ◽  
KAREN SCHNECK ◽  
DAVID COX ◽  
...  
Keyword(s):  
Drug Development ◽  
Clinical Benefits

Microbiological Detoxification of Hazardous Organic Contaminants: The Crucial Role of Substrate Interactions

1992 ◽  
Vol 25 (11) ◽  
pp. 403-410 ◽  
Author(s):  
B. E. Rittmann
Keyword(s):  
Organic Pollutants ◽  
Information Flow ◽  
Organic Contaminants ◽  
Crucial Role ◽  
Substrate Utilization ◽  
Energy Flows ◽  
Hazardous Pollutants ◽  
Primary Substrate ◽  
Substrate Types

Microbiological detoxification of hazardous organic pollutants is highly promising, but its reliable implementation requires a sophisticated understanding of several different substrate types and how they interact. This paper carefully defines the substrate types and explains how their interactions affect the bacteria's electron and energy flows, information flow, and degradative activity. For example, primary substrates, which are essential for growth and maintenance of the bacteria, also interact with degradation of specific hazardous pollutants by being inducers, inhibitors, and direct or indirect cosubstrates. The target contaminants, which often are secondary substrates, also have the interactive roles of self-inhibitor, inhibitor of primary-substrate utilization, inducer, and a part of an aggregate primary substrate.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

The mechanistic role of thymoquinone in Parkinson's disease: focus on neuroprotection in pre-clinical studies

2021 ◽  
Vol 14 ◽  
Author(s):  
Mohammad Najim Uddin ◽  
Mohammad Injamul Hoq ◽  
Israt Jahan ◽  
Shafayet Ahmed Siddiqui ◽  
Chayan Dhar Clinton ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Studies ◽  
Nigella Sativa ◽  
Biological Effects ◽  
Neuroprotective Activity ◽  
Substantia Nigra Pars Compacta ◽  
Movement Difficulties

: Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.

Predictivity/Translatability of Toxicities Observed in Nonclinical Toxicology Studies to Clinical Safety Outcomes in Drug Development: Case Examples

2019 ◽  
Vol 39 (2) ◽  
pp. 141-150
Author(s):  
Nicola J. Stagg ◽  
Hanan N. Ghantous ◽  
Robert Roth ◽  
Kenneth L. Hastings
Keyword(s):  
Drug Development ◽  
Annual Meeting ◽  
Clinical Studies ◽  
Early Termination ◽  
New Drugs ◽  
Clinical Safety ◽  
Case Examples ◽  
Palm Springs ◽  
Starting Dose ◽  
Good Concordance

Nonclinical toxicology studies are conducted to characterize the potential toxicities and establish a safe starting dose for new drugs in clinical studies, but the question remains as to how predictable/translatable the nonclinical safety findings are to humans. In many cases, there is good concordance between nonclinical species and patients. However, there are cases for which there is a lack of predictivity or translatability that led to early termination of clinical studies due to unanticipated toxicities or early termination of programs before making it to the clinic due to unacceptable nonclinical toxicities assumed to be translatable. A few case examples of safety findings that are translatable versus safety findings that are not translatable and why they are not translateable were presented as a symposium at the 38th Annual Meeting of the American College of Toxicology in Palm Springs, California, and are discussed in this article.

scholarly journals Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  
Keyword(s):  
Drug Development ◽  
Cathepsin L ◽  
Human Cells ◽  
New Drugs ◽  
Disease Course ◽  
Promising Target ◽  
First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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