scholarly journals Cyclin-Dependent Kinases as Drug Targets for Cell Growth and Proliferation Disorders. A Role for Systems Biology Approach in Drug Development. Part I—Cyclin-Dependent Kinases as Drug Targets in Cancer

2011 ◽  
Vol 25 (4) ◽  
pp. 2583-2586 ◽  
Author(s):  
Michael A. Idowu
Keyword(s):  
Systems Biology ◽  
Cell Growth ◽  
Drug Development ◽  
Drug Targets ◽  
Cyclin Dependent Kinases ◽  
Cell Growth And Proliferation

scholarly journals Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach

2020 ◽  
Vol 20 (7) ◽  
pp. 483-490 ◽  
Author(s):  
Imlimaong Aier ◽  
Pritish K. Varadwaj
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Systems Biology ◽  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signalling Pathway ◽  
Ductal Adenocarcinoma ◽  
Apoptosis Pathway ◽  
Pathway Models ◽  
Cell Growth And Proliferation

Background: Gemcitabine is the standard chemotherapeutic drug administered in advanced Pancreatic Ductal Adenocarcinoma (PDAC). However, due to drug resistance in PDAC patients, this treatment has become less effective. Over the years, clinical trials for the quest of finding novel compounds that can be used in combination with gemcitabine have met very little success. Objective: To predict the driving factors behind pancreatic ductal adenocarcinoma, and to understand the effect of these components in the progression of the disease and their contribution to cell growth and proliferation. Methods: With the help of systems biology approaches and using gene expression data, which is generally found in abundance, dysregulated elements in key signalling pathways were predicted. Prominent dysregulated elements were integrated into a model to simulate and study the effect of gemcitabine- induced hypoxia. Results: In this study, several transcription factors in the form of key drivers of cancer-related genes were predicted with the help of CARNIVAL, and the effect of gemcitabine-induced hypoxia on the apoptosis pathway was shown to have an effect on the downstream elements of two primary pathway models; EGF/VEGF and TNF signalling pathway. Conclusion: It was observed that EGF/VEGF signalling pathway played a major role in inducing drug resistance through cell growth, proliferation, and avoiding cell death. Targeting the major upstream components of this pathway could potentially lead to successful treatment.

scholarly journals Enhanced Myc Expression in Silkworm Silk Gland Promotes DNA Replication and Silk Production

Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 361
Author(s):  
Wenliang Qian ◽  
Yan Yang ◽  
Zheng Li ◽  
Yuting Wu ◽  
Xuechuan He ◽  
...  
Keyword(s):  
Dna Replication ◽  
Cell Growth ◽  
Silk Gland ◽  
Biological Functions ◽  
Gland Cells ◽  
Silk Production ◽  
Myc Gene ◽  
Cell Growth And Proliferation ◽  
Silkworm Silk ◽  
Posterior Silk Gland

Silkworm is an economically important insect that synthetizes silk proteins for silk production in silk gland, and silk gland cells undergo endoreplication during larval period. Transcription factor Myc is essential for cell growth and proliferation. Although silkworm Myc gene has been identified previously, its biological functions in silkworm silk gland are still largely unknown. In this study, we examined whether enhanced Myc expression in silk gland could facilitate cell growth and silk production. Based on a transgenic approach, Myc was driven by the promoter of the fibroin heavy chain (FibH) gene to be successfully overexpressed in posterior silk gland. Enhanced Myc expression in the PSG elevated FibH expression by about 20% compared to the control, and also increased the weight and shell rate of the cocoon shell. Further investigation confirmed that Myc overexpression increased nucleus size and DNA content of the PSG cells by promoting the transcription of the genes involved in DNA replication. Therefore, we conclude that enhanced Myc expression promotes DNA replication and silk protein expression in endoreplicating silk gland cells, which subsequently raises silk yield.

microRNA 21-mediated suppression of sprouty1 by Pokemon affects liver cancer cell growth and proliferation

2013 ◽  
Vol 114 (7) ◽  
pp. 1625-1633 ◽  
Author(s):  
Xiu-Li Jin ◽  
Qin-Sheng Sun ◽  
Feng Liu ◽  
Hong-Wei Yang ◽  
Min Liu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Liver Cancer ◽  
Cancer Cell ◽  
Liver Cancer Cell ◽  
Cancer Cell Growth ◽  
Cell Growth And Proliferation

scholarly journals An integrated dataset for in silico drug discovery

2010 ◽  
Vol 7 (3) ◽  
Author(s):  
Simon J Cockell ◽  
Jochen Weile ◽  
Phillip Lord ◽  
Claire Wipat ◽  
Dmytro Andriychenko ◽  
...  
Keyword(s):  
Systems Biology ◽  
Drug Discovery ◽  
Drug Development ◽  
Data Integration ◽  
In Silico ◽  
Drug Repositioning ◽  
Integrated Systems ◽  
Integration Platform ◽  
Treatment Indications ◽  
New Treatment

SummaryDrug development is expensive and prone to failure. It is potentially much less risky and expensive to reuse a drug developed for one condition for treating a second disease, than it is to develop an entirely new compound. Systematic approaches to drug repositioning are needed to increase throughput and find candidates more reliably. Here we address this need with an integrated systems biology dataset, developed using the Ondex data integration platform, for the in silico discovery of new drug repositioning candidates. We demonstrate that the information in this dataset allows known repositioning examples to be discovered. We also propose a means of automating the search for new treatment indications of existing compounds.

scholarly journals The mechanism of full activation of tumor suppressor PTEN at the phosphatidylinositol-enriched membrane

2021 ◽  
Author(s):  
Hyunbum Jang ◽  
Iris Nira Smith ◽  
Charis Eng ◽  
Ruth Nussinov
Keyword(s):  
Drug Discovery ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Full Length ◽  
Detailed Mechanism ◽  
Explicit Solvent ◽  
Signaling Lipids ◽  
Cell Growth And Proliferation ◽  
First Time ◽  
Full Activation

AbstractTumor suppressor PTEN dephosphorylates signaling lipid PIP3 produced by PI3Ks. Abundant PIP3 promotes cell growth and proliferation. PTEN is the second most highly mutated protein in cancer and is drugless. The detailed mechanism at the membrane of this pivotal phosphatase is unknown hindering understanding and drug discovery. Here for the first time, exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane, its interaction with membranes composed of zwitterionic phosphatidylcholine and anionic phosphatidylserine and phosphatidylinositol, including signaling lipids PIP2 and PIP3, and moving away from the zwitterionic and getting absorbed onto the anionic membrane that harbors the PIP3. PIP3 then allosterically unfolds the N-terminal PIP2 binding domain, translocating it to the membrane where its polybasic motif interacts with PIP2, localizing on microdomains enriched in signaling lipids, as PI3K does. Finally, we determined PTEN catalytic action at the membrane, all in line with available experimental observations.

scholarly journals RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics

2020 ◽  
Vol 477 (15) ◽  
pp. 2893-2919
Author(s):  
Walaa E. Kattan ◽  
John F. Hancock
Keyword(s):  
Plasma Membrane ◽  
Cell Growth ◽  
Cancer Cells ◽  
Special Focus ◽  
Ras Proteins ◽  
Membrane Interactions ◽  
Multiple Methods ◽  
Membrane Biology ◽  
The Past ◽  
Cell Growth And Proliferation

The three human RAS proteins are mutated and constitutively activated in ∼20% of cancers leading to cell growth and proliferation. For the past three decades, many attempts have been made to inhibit these proteins with little success. Recently; however, multiple methods have emerged to inhibit KRAS, the most prevalently mutated isoform. These methods and the underlying biology will be discussed in this review with a special focus on KRAS-plasma membrane interactions.

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