Oncotarget published this trending research paper on May 1, 2018, entitled, "Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau" by researchers from the Massachusetts General Hospital, Boston, MA; Siamab Therapeutics, Inc., Newton, MA; Harvard Medical School, Boston, MA.

Abstract:
Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations.

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DOI - https://doi.org/10.18632/oncotarget.25289

Full text - https://www.oncotarget.com/article/25289/text/

Correspondence to - Bo R. Rueda - brueda@mgh.harvard.edu

Keywords - ovarian cancer, sialyl-Tn, antibody-drug conjugate, cancer stem cell, tumor-associated carbohydrate antigen

About Oncotarget

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

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Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

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Oncotarget

Oncotarget: Targeted Treatment for Recurrent Ovarian Cancer

Pelotonia has changed Joe Apgar’s life. “I’ll never forget how I felt in the moment someone told me I had cancer,” the CEO of Pelotonia said in this episode. “You feel completely lost and by yourself and you don’t have answers to the questions running around through your head.” Apgar was diagnosed with testicular cancer while a student at Penn State. Pelotonia is the fundraising cycling event that has raised more than $285 million for cancer research at the James. Apgar first rode in 2011, soon after he moved to Columbus to work for Rockbridge Capital, a private equity firm that sponsors a Pelotonia team Apgar helped create. “I remember standing at my first opening ceremony [of Pelotonia] and how uplifted and excited and supported I felt … that’s when I could flip the switch on it and feel empowered by my own story and experience,” Apgar said of the start of his first ride and crossing the finish line. Apgar talked about his cancer journey, how he connected with a James physician for his follow-up cancer care, his Pelotonia experiences as a rider and leader, and the future of the event. Apgar also talked about the importance of the Pelotonia “community” and how it has helped connect members of the James team with riders, volunteers and donors. “I think [the Pelotonia founders] hoped that some of this sense of community would happen, but I don’t think anyone could have dreamed it would happen at the scale it has,” he said.

Episode 163: The Incredible Impact of Pelotonia, with CEO Joe Apgar

Clinical Professor Muneer Ahmad explains why students are indispensable to the work of the Law School’s clinics. He discusses the Worker and Immigrant Rights Advocacy Clinic, including the extraordinary 24-hour period in which the clinic won a nationwide injunction against the Trump administration’s Muslim travel ban.

Season Two, Episode Eight: Muneer Ahmad

Father Lizzie and Mother Laura join us to talk about their vocation stories, how they each ended up doing digital ministry (accidentally), and why they joined forces to create their new podcast, “And Also With You.”

19: Digital Ministry with Lizzie McManus-Dail and Laura Di Panfilo

Jonathan Wilson-Hartgrove joins us from the Yale Center for Public Theology and Public Policy. He describes the making of white, Christian nationalism and helps us see a different path forward, following the teachings of Jesus. He walks us through the reality of the New Right in the 1970s as a way for us to understand our positionality headed into the 2024 election.

21: Christianity in American Politics

Dr. Nadia Kizenko joins Ariana Hones (MDiv '25) in conversation to discuss Kizenko's research on Orthodox liturgy in Ukraine. The conversation is twofold. First, Kizenko explores the liturgical practices of the Ukrainian Orthodox Church and the Orthodox Church of Ukraine. She discusses how these two competing churches, both which can claim canonical status, respond liturgically in times of crisis. Second, Kizenko speaks about her most recent project creating a vesper service and how liturgy functions as a means to include or exclude different identities. Throughout the conversation, Kizenko makes the case for paying close attention to liturgy and the ways in which Orthodox tradition across time provides elements of subversion for its participants.

Orthodox Liturgy as Refuge and Resistance

BUFFALO, NY- April 30, 2024 – A new #researchpaper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 8, entitled, “Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.”

In this new study, researchers Kohsaku Numa, Sandip Kumar Patel, Zhixin A. Zhang, Jordan B. Burton, Akifumi Matsumoto, Jun-Wei B. Hughes, Chie Sotozono, Birgit Schilling, Pierre-Yves Desprez, Judith Campisi (1948-2024), and Koji Kitazawa from Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine, University of Cambridge, and California Pacific Medical Center investigated the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A.

“We assessed cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation and expression of senescence markers (p16 and p21) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls.”

The researchers performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs — they also compared the results to non-senescent hCEnCs. Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-β-gal activity, decreased cell proliferation and elevated expression of p16 and p21. RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype.

“In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.”

DOI - https://doi.org/10.18632/aging.205761

Corresponding author - Koji Kitazawa - kkitazaw@koto.kpu-m.ac.jp

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About Aging-US

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

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

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MEDIA@IMPACTJOURNALS.COM

Aging (Aging-US)

Cover Paper: Senescent Characteristics of Human Corneal Endothelial Cells Upon UV-A Exposure

BUFFALO, NY- May 1, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 8, entitled, “A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training.”

The skeletal muscle proteome alterations to aging and resistance training have been reported in prior studies. However, conventional proteomics in skeletal muscle typically yields wide protein abundance ranges that mask the detection of lowly expressed proteins.

In this new study, researchers Michael D. Roberts, Bradley A. Ruple, Joshua S. Godwin, Mason C. McIntosh, Shao-Yung Chen, Nicholas J. Kontos, Anthony Agyin-Birikorang, Max Michel, Daniel L. Plotkin, Madison L. Mattingly, Brooks Mobley, Tim N. Ziegenfuss, Andrew D. Fruge, and Andreas N. Kavazis from Auburn University, Seer, Inc., and The Center for Applied Health Sciences adopted a novel deep proteomics approach whereby myofibril (MyoF) and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS). 

“Specifically, we investigated MyoF and non-MyoF proteomic profiles of the vastus lateralis muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6). Additionally, MA muscle was analyzed following eight weeks of resistance training (RT, 2d/week).” 

Across all participants, the number of non-MyoF proteins detected averaged to be 5,645±266 (range: 4,888–5,987) and the number of MyoF proteins detected averaged to be 2,611±326 (range: 1,944–3,101). Differences in the non-MyoF (8.4%) and MyoF (2.5%) proteomes were evident between age cohorts, and most differentially expressed non-MyoF proteins (447/543) were more enriched in MA versus Y. Biological processes in the non-MyoF fraction were predicted to be operative in MA versus Y including increased cellular stress, mRNA splicing, translation elongation, and ubiquitin-mediated proteolysis. RT in MA participants only altered ~0.3% of MyoF and ~1.0% of non-MyoF proteomes. 

“In summary, aging and RT predominantly affect non-contractile proteins in skeletal muscle. Additionally, marginal proteome adaptations with RT suggest more rigorous training may stimulate more robust effects or that RT, regardless of age, subtly alters basal state skeletal muscle protein abundances.”

DOI - https://doi.org/10.18632/aging.205751

Corresponding author - Michael D. Roberts - mdr0024@auburn.edu

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About Aging

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

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

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MEDIA@IMPACTJOURNALS.COM

Novel Deep Proteomic Approach Unveils Molecular Signatures Affected by Aging and Resistance Training

With an ever-increasing global population grappling with age-related ocular ailments like cataracts, dry eyes, glaucoma, and macular degeneration, the need for new research in this domain is more pressing than ever. 

In a new study, researchers Kohsaku Numa, Sandip Kumar Patel, Zhixin A. Zhang, Jordan B. Burton, Akifumi Matsumoto, Jun-Wei B. Hughes, Chie Sotozono, Birgit Schilling, Pierre-Yves Desprez, Judith Campisi (1948-2024), and Koji Kitazawa from the Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine, University of Cambridge, and California Pacific Medical Center shed light on a pivotal aspect of corneal health – the impact of ultraviolet-A (UV-A) radiation on corneal endothelial cells. Their research paper was published on the cover of Aging’s Volume 16, Issue 8, entitled, “Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.”

“The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A.”

Full blog - https://aging-us.org/2024/05/uv-a-exposure-cellular-senescence-and-vision-impairment/

Paper DOI - https://doi.org/10.18632/aging.205761

Corresponding author - Koji Kitazawa - kkitazaw@koto.kpu-m.ac.jp

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Keywords - aging, cellular senescence, senescence-associated secretory phenotype, RNA-Seq, proteomics, gene ontology analysis

About Aging-US

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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

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UV-A Exposure, Cellular Senescence, and Vision Impairment

BUFFALO, NY- May 6, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 3, 2024, entitled, “Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure.”

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 infection has led to worsened outcomes for patients with cancer. SARS-CoV-2 spike protein mediates host cell infection and cell-cell fusion that causes stabilization of tumor suppressor p53 protein. In-silico analysis previously suggested that SARS-CoV-2 spike interacts with p53 directly but this putative interaction has not been demonstrated in cells. In this new study, researchers Shengliang Zhang and Wafik S. El-Deiry from Brown University and Lifespan Health System examined the interaction between SARS-CoV-2 spike, p53 and MDM2 (E3 ligase, which mediates p53 degradation) in cancer cells using an immunoprecipitation assay. 

“We observed that SARS-CoV-2 spike protein interrupts p53-MDM2 protein interaction but did not detect SARS-CoV-2 spike bound with p53 protein in the cancer cells.”

The researchers further observed that SARS-CoV-2 spike suppresses p53 transcriptional activity in cancer cells including after nutlin exposure of wild-type p53-, spike-expressing tumor cells and inhibits chemotherapy-induced p53 gene activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2. The suppressive effect of SARS-CoV-2 spike on p53-dependent gene activation provides a potential molecular mechanism by which SARS-CoV-2 infection may impact tumorigenesis, tumor progression and chemotherapy sensitivity. In fact, cisplatin-treated tumor cells expressing spike were found to have increased cell viability as compared to control cells. 

Further observations on γ-H2AX expression in spike-expressing cells treated with cisplatin may indicate altered DNA damage sensing in the DNA damage response pathway. The preliminary observations reported here warrant further studies to unravel the impact of SARS-CoV-2 and its various encoded proteins including spike on pathways of tumorigenesis and response to cancer therapeutics. More efforts should be directed at studying the effects of the SARS-CoV-2 spike and other viral proteins on host DNA damage sensing, response and repair mechanisms. 

“A goal would be to understand the structural basis for maximal anti-viral immunity while minimizing suppression of host defenses including the p53 DNA damage response and tumor suppression pathway. Such directions are relevant and important including not only in the context of viral infection and mRNA vaccines in general but also for patients with cancer who may be receiving cytotoxic or other cancer treatments.”

DOI - https://doi.org/10.18632/oncotarget.28582

Correspondence to - Wafik S. El-Deiry - wafik@brown.edu

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About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Transfected SARS-CoV-2 Spike DNA Suppresses Cancer Cell Response to Chemotherapy

In this episode, Dr. David Bishop, a Specialist Anesthesiologist and Head of the Clinical Unit of Anaesthesia at Edendale Hospital in Pietermaritzburg talks about a vital topic and his recent publication, Tranexamic acid at cesarean delivery: drug-error deaths.



Tranexamic acid at cesarean delivery: drug-error deaths

https://pubmed.ncbi.nlm.nih.gov/36300729/

Spinal tranexamic acid - a new killer in town

https://pubmed.ncbi.nlm.nih.gov/30985919/

 

YouTube publication (Tranexamic acid during CS: Drug error warning (https://www.youtube.com/watch?v=jeFtFWeMwkw&t=184s)



Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

https://pubmed.ncbi.nlm.nih.gov/28456509/

Tranexamic Acid: Drug error deaths

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Oncotarget: Targeted Treatment for Recurrent Ovarian Cancer

Oncotarget Podcast

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