Drug Discovery

Oncotarget

Oncotarget published this trending research paper on May 19, 2022 in Volume 13, entitled, "CancerOmicsNet: a multi-omics network-based approach to anti-cancer drug profiling" by researchers from the Center for Computation and Technology, Louisiana State University, Baton Rouge, LA; Department of Biological Sciences, Louisiana State University, Baton Rouge, LA; Division of Electrical and Computer Engineering, Louisiana State University, Baton Rouge, LA.

DOI - https://doi.org/10.18632/oncotarget.28234

Correspondence to - Michal Brylinski - michal@brylinski.org

Abstract

Development of novel anti-cancer treatments requires not only a comprehensive knowledge of cancer processes and drug mechanisms of action, but also the ability to accurately predict the response of various cancer cell lines to therapeutics. Numerous computational methods have been developed to address this issue, including algorithms employing supervised machine learning. Nonetheless, high prediction accuracies reported for many of these techniques may result from a significant overlap among training, validation, and testing sets, making existing predictors inapplicable to new data. To address these issues, we developed CancerOmicsNet, a graph neural network with sophisticated attention propagation mechanisms to predict the therapeutic effects of kinase inhibitors across various tumors. Emphasizing on the system-level complexity of cancer, CancerOmicsNet integrates multiple heterogeneous data, such as biological networks, genomics, inhibitor profiling, and gene-disease associations, into a unified graph structure. The performance of CancerOmicsNet, properly cross-validated at the tissue level, is 0.83 in terms of the area under the receiver operating characteristics, which is notably higher than those measured for other approaches. CancerOmicsNet generalizes well to unseen data, i.e., it can predict therapeutic effects across a variety of cancer cell lines and inhibitors. CancerOmicsNet is freely available to the academic community at https://github.com/pulimeng/CancerOmicsNet.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-anti-cancer-drug-profiling-with-canceromicsnet/

Keywords - cancer growth rate, kinase inhibitors, differential gene expression, gene-disease association, cancer-specific networks

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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Trending With Impact: CancerOmicsNet for Anti-Cancer Drug Profiling

Teach Me in 10

Research by a team of neuroscientists from the University of Nevada, Las Vegas (UNVL) has shown that it is possible to identify the molecular mechanisms underlying a host of adverse symptoms associated with unique subtypes of neurodevelopmental disorders. This work could one day improve the lives of millions of people worldwide.
Intellectual disability (ID) is a common neurodevelopmental disorder that can arise from genetic mutations ranging from trisomy to single nucleotide polymorphism. Trisomy of the 21st chromosome (Down syndrome) is the most common underlying cause of ID, but mutations in a growing number of single genes have been identified as causative in ID, including NONO and ARHGEF9. 

In this episode of Teach Me in 10, UNLV neuroscientist Dr. Rochelle Hines joins us to discuss the team’s latest findings, which show that mutations in ARHGEF9  — the gene that codes for collybistin — lead to ID through impaired α2 subunit function.

Want to learn more? Rochelle suggests you check out the following resources:  

https://www.nature.com/articles/s41380-022-01468-z
https://www.nature.com/articles/s41467-018-05481-1

Neurodevelopmental Disorders With Rochelle Hines

Aging (Aging-US)

Oncoscience published this trending research perspective in Volume 9, 2022, entitled, "Altos Labs and the quest for immortality: but can we live longer right now?" by Dr. Mikhail V. Blagosklonny from Roswell Park Cancer Institute, Buffalo, NY. 

DOI - https://doi.org/10.18632/oncoscience.552

Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com

Abstract

Some visionaries prefer to dream of immortality rather than to actually live longer. Here I discuss how combining rapamycin with other modalities may let us live long enough to benefit from future discoveries in cellular reprogramming and what needs to be done at Altos Labs to make this happen.

Press release - https://aging-us.com/news_room/altos-labs-quest-for-immortality

Keywords - aging, longevity, lifespan, geroscience, rapalogs, gerostatics

About Oncoscience

Oncoscience's mission is to cover the rapidly growing field of cancer research. It’s aim is to focus on emergent topics not currently covered by other journals.

Launched in 2014, Oncoscience is a peer-reviewed, traditional-style, bi-monthly journal with free access. Oncoscience also has a special mission: freeing researchers in oncology from publication costs. It is free for both readers and authors.

Please visit our website at http://www.Oncoscience.us​ and connect with us:

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Oncoscience is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Paper Spotlight: Altos Labs’ Quest for Immortality - Dr. Blagosklonny’s Perspective

Oncotarget published this trending research paper on May 5, 2022 in Volume 13, entitled, "Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells" by researchers from the Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX.

DOI - https://doi.org/10.18632/oncotarget.28227

Correspondence to - Xiaoqian Fang - xiaoqian.fang@utrgv.edu

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest cancers of the brain. Its ability to infiltrate healthy brain tissues renders it difficult to remove surgically. Furthermore, it exhibits high rates of radio- and chemoresistance, making the survival rates of patients with GBM poor. Therefore, novel effective therapies for GBM remain urgently in demand. Niclosamide is an anti-helminthic drug and recently it has been receiving attention due to its reported anticancer effects in cancer models, including GBM. Furthermore, camptothecin (CPT) is a naturally-occurring alkaloid and has been previously reported to be a potential chemotherapeutic agent by targeting the nuclear topoisomerase I. In the present study, the possible combined chemotherapeutic effects of niclosamide and CPT on the human glioblastoma cell line U87 MG was investigated by MTT assay and western blot analysis. Niclosamide exhibited synergistic activities with CPT to suppress the proliferation of U87 MG cells. Additionally, niclosamide suppressed cell proliferation and induced cell death mainly by triggering ER stress and autophagy, whilst CPT induced cell apoptosis mainly through p53-mediated mitochondrial dysfunction and activation of the MAPK (ERK/JNK) pathways. Overall, these findings suggest that co-administration of niclosamide and CPT may provide a novel therapeutic treatment strategy for GBM.

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Keywords - glioblastoma, niclosamide, camptothecin, cancer, chemotherapy

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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Trending With Impact: Combined Treatment Approach Fights Glioblastoma

Aging (Aging-US) published this trending editorial in Volume 14, Issue 8, entitled, “SNCA-AS1 in aging and Parkinson’s disease” by researchers from the Pediatric Research Center “Romeo ed Enrica Invernizzi”, Department of Biomedical and Clinical Sciences "L. Sacco", University of Milano, Milano, Italy; Department of Women, Mothers and Neonatal Care, Children's Hospital "V. Buzzi", Milano, Italy.

DOI - https://doi.org/10.18632/aging.204025

Corresponding author - Stephana Carelli - stephana.carelli@unimi.it

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Keywords - aging, SNCA-AS1, alpha-synuclein, SNCA, long non-coding RNA, Parkinson's disease

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ and connect with us:

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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Trending With Impact: SNCA-AS1 in Aging and Parkinson’s Disease

Aging (Aging-US) published this research paper as the cover for Volume 14, Issue 8, entitled, "Wild type and gain of function mutant TP53 can regulate the sensitivity of pancreatic cancer cells to chemotherapeutic drugs, EGFR/Ras/Raf/MEK, and PI3K/mTORC1/GSK-3 pathway inhibitors, nutraceuticals and alter metabolic properties" by researchers the Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC; Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy; Department of Medicine and Surgery, Re.Mo.Bio.S. Laboratory, Anatomy Section, University of Parma, Parma, Italy; Department of Molecular Physiology and Neurobiology, University of Wroclaw, Wroclaw, Poland.

DOI - https://doi.org/10.18632/aging.204038

Corresponding author - James A. McCubrey - mccubreyj@ecu.edu

Abstract

TP53 is a master regulator of many signaling and apoptotic pathways involved in: aging, cell cycle progression, gene regulation, growth, apoptosis, cellular senescence, DNA repair, drug resistance, malignant transformation, metastasis, and metabolism. Most pancreatic cancers are classified as pancreatic ductal adenocarcinomas (PDAC). The tumor suppressor gene TP53 is mutated frequently (50–75%) in PDAC. Different types of TP53 mutations have been observed including gain of function (GOF) point mutations and various deletions of the TP53 gene resulting in lack of the protein expression. Most PDACs have point mutations at the KRAS gene which result in constitutive activation of KRas and multiple downstream signaling pathways. It has been difficult to develop specific KRas inhibitors and/or methods that result in recovery of functional TP53 activity. To further elucidate the roles of TP53 in drug-resistance of pancreatic cancer cells, we introduced wild-type (WT) TP53 or a control vector into two different PDAC cell lines. Introduction of WT-TP53 increased the sensitivity of the cells to multiple chemotherapeutic drugs, signal transduction inhibitors, drugs and nutraceuticals and influenced key metabolic properties of the cells. Therefore, TP53 is a key molecule which is critical in drug sensitivity and metabolism of PDAC.

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Keywords - aging, TP53, targeted therapy, PDAC, metabolic properties, chemotherapeutic drugs 

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us:

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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Paper Spotlight: Restoration of Wild-Type TP53 in Pancreatic Cancer

Dr. Mark Woodford, Assistant Professor at the Department of Urology, SUNY Upstate Medical University, Syracuse, NY, describes his experience publishing the meeting report, “Seventh BHD international symposium: recent scientific and clinical advancement,” with Oncotarget.

DOI - https://doi.org/10.18632/oncotarget.28176

Correspondence to - Mehdi Mollapour - mollapom@upstate.edu

Abstract
The 7th Birt-Hogg-Dubé (BHD) International Symposium convened virtually in October 2021. The meeting attracted more than 200 participants internationally and highlighted recent findings in a variety of areas, including genetic insight and molecular understanding of BHD syndrome, structure and function of the tumor suppressor Folliculin (FLCN), therapeutic and clinical advances as well as patients’ experiences living with this malady.

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Keywords - Birt-Hogg-Dubé syndrome, folliculin, FLCN, tuberous sclerosis complex, LDHA

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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Author Testimonial: Dr. Mark Woodford - SUNY Upstate Medical University, Syracuse

BÜCHI Labortechnik AG

Evaporative Light Scattering Detection (ELSD) is one type of detection methods used in flash chromatography and prep HPLC. Briefly, the mechanism of ELSD involves measuring the amount of light scattered by particles of solvent, which have been dried through evaporation. In this quick video, enjoy a live demonstration by our Valentin Dubois, a BUCHI application chemist who explains how:

🔎 ELS detectors work
🔎 How ELSD can be used to optimize your purifications

‼️ Find out more on ELSD: https://bit.ly/3ko9Uv3

Insights into Evaporative Light Scattering Detection (ELSD) in Chromatography

Lonza

Do you wish to improve your drug discovery experimental setup? Ever wonder how to improve on cell line data. Explore your options with primary cells from multiple organs of the human body. Make the right choices for drug discovery. Learn more….

Drug Discovery

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