BUFFALO, NY- February 7, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance.”

The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings.

In this new study, researchers Shiue-Wei Lai, Yi-Chiao Cheng, Kee-Thai Kiu, Min-Hsuan Yen, Ying-Wei Chen, Vijesh Kumar Yadav, Chi-Tai Yeh, Kuang-Tai Kuo, and Tung-Cheng Chang from Taipei’s National Defense Medical Center, Taipei Medical University, Taipei Medical University Shuang-Ho Hospital, and National Taitung University used the ULCAN portal and noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Their assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations.

“Our study emphasized the connection between PROX1 and α-SMA in CAFs.”

Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship.

PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition.

“As we advance in this field, the development and clinical validation of small-molecule inhibitors targeting PROX1/α-SMA become imperative, paving the way to refine and optimize CRC therapeutic interventions.”

DOI - https://doi.org/10.18632/aging.205447

Corresponding author - Tung-Cheng Chang - 09432@s.tmu.edu.tw

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.

Visit our website at https://www.Aging-US.com​​.

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Aging (Aging-US)

PROX1/α-SMA Correlated With Colorectal Cancer Progression, Poor Outcomes and Therapeutic Resistance

BUFFALO, NY- February 21, 2024 – A new research #perspective was #published in Oncotarget's Volume 15 on February 8, 2024, entitled, “Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.”

As discussed in this new paper, researchers Alberto Moscona-Nissan, Karl J. Habashy, Victor A. Arrieta, Adam M. Sonabend, and Crismita Dmello from Universidad Panamericana School of Medicine, Northwestern University and Universidad Nacional Autónoma de México recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. 

“To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680).”

The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations.

“Precision and personalized medicine can lead to a transition from a stochastic treatment response into predictable scenarios. Further identification of predictive biomarkers, validation, and study of combinations as predictive models is critical to generate a greater impact that can be translated to the bedside of patients.”

DOI - https://doi.org/10.18632/oncotarget.28549

Correspondence to - Crismita Dmello - crismita.dmello@northwestern.edu, and Adam M. Sonabend - adam.sonabend@northwestern.edu

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Keywords - cancer, glioblastoma, predictive biomarker, CRISPR screen, paclitaxel

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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Oncotarget

Combining Causal and Correlative Approaches to Discover Response Biomarkers to Paclitaxel

BUFFALO, NY- March 15, 2024 – A new #research paper 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 5, entitled, “Genome-wide transcriptome profiling and development of age prediction models in the human brain.”

Aging-related transcriptome changes in various regions of the healthy human brain have been explored in previous works, however, a study to develop prediction models for age based on the expression levels of specific panels of transcripts is lacking. Moreover, studies that have assessed sexually dimorphic gene activities in the aging brain have reported discrepant results, suggesting that additional studies would be advantageous. The prefrontal cortex (PFC) region was previously shown to have a particularly large number of significant transcriptome alterations during healthy aging in a study that compared different regions in the human brain. 

In this new study, researchers Joseph A. Zarrella and Amy Tsurumi from the Harvard T.H. Chan School of Public Health, Massachusetts General Hospital, Harvard Medical School, and Shriner's Hospitals for Children-Boston aimed to profile PFC transcriptome changes during healthy human aging overall and comparing potential differences between female and male samples, as well as developing chronological age prediction models by various methods.

“We harmonized neuropathologically normal PFC transcriptome datasets obtained from the Gene Expression Omnibus (GEO) repository, ranging in age from 21 to 105 years, and found a large number of differentially regulated transcripts in the old and elderly, compared to young samples overall, and compared female and male-specific expression alterations.” 

The team assessed the genes that were associated with age by employing ontology, pathway, and network analyses. Furthermore, they applied various established (least absolute shrinkage and selection operator (Lasso) and Elastic Net (EN)) and recent (eXtreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM)) machine learning algorithms to develop accurate prediction models for chronological age and validated them. Studies to further validate these models in other large populations and molecular studies to elucidate the potential mechanisms by which the transcripts identified may be related to aging phenotypes would be advantageous.

“Our results support the notions that specific gene expression changes in the PFC are highly correlated with age, that some transcripts show female and male-specific differences, and that machine learning algorithms are useful tools for developing prediction models for age based on transcriptome information.”

DOI - https://doi.org/10.18632/aging.205609

Corresponding author - Amy Tsurumi - atsurumi@mgh.harvard.edu

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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.

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MEDIA@IMPACTJOURNALS.COM

Age Prediction Models in the Human Brain: Genome-wide Transcriptome Profiling and Development

The human brain is a complex organ, and its aging process is influenced by a plethora of factors, both genetic and environmental. Aging-related changes in the brain can lead to cognitive decline and susceptibility to neurodegenerative diseases. Therefore, understanding the molecular mechanisms underlying these changes is crucial for developing therapeutic strategies to delay or prevent age-related cognitive decline.

Over the past few years, a myriad of scientific studies have been conducted to understand the intricate relationship between our genes and the aging process. In a new study, researchers Joseph A. Zarrella and Amy Tsurumi from Harvard T.H. Chan School of Public Health, Massachusetts General Hospital, Harvard Medical School, and Shriner’s Hospitals for Children-Boston explored the concept of genome brain age prediction, a groundbreaking area of study that employs advanced bioinformatics tools to analyze changes in gene expression associated with aging. On February 28, 2024, their research paper was published and chosen as the cover paper for Aging’s Volume 16, Issue 5, entitled, “Genome-wide transcriptome profiling and development of age prediction models in the human brain.”

“[…] we aimed to profile transcriptome changes in the aging PFC [prefrontal cortex] overall and compare females and males, and develop prediction models for age.”

Full blog - https://aging-us.org/2024/03/predicting-brain-age-with-machine-learning-and-transcriptome-profiling/

Paper DOI - https://doi.org/10.18632/aging.205609

Corresponding author - Amy Tsurumi - atsurumi@mgh.harvard.edu

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Keywords - aging, machine learning, prediction model, biomarker, transcriptome

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 https://www.Aging-US.com​​ and connect with us:

Facebook - https://www.facebook.com/AgingUS/
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Predicting Brain Age With Machine Learning and Transcriptome Profiling

Cancer therapy has come a long way from its one-size-fits-all beginning to the awakening era of personalized medicine. This change has been largely driven by the discovery of biomarkers. Biomarkers can help refine patient selection for specific therapies. A blend of causal and correlative approaches is needed to elucidate the full potential of biomarkers in cancer research. This fusion of methodologies allows for a comprehensive exploration of biomarker efficacy, leading to more accurate predictions of drug response.

In a new paper, researchers Alberto Moscona-Nissan, Karl J. Habashy, Victor A. Arrieta, Adam M. Sonabend, and Crismita Dmello from the Universidad Panamericana School of Medicine, Northwestern University and Universidad Nacional Autónoma de México discuss causal and correlative approaches to identify potential biomarkers for predicting response to paclitaxel — a commonly used chemotherapeutic agent. On February 8, 2024, their research perspective was published in Oncotarget’s Volume 15, entitled, “Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.”

“[…] studying the combination of non-overlapping biomarkers’ expression, in addition to clinical and sociodemographic data could generate predictive models for paclitaxel susceptibility.”

Full blog - https://www.oncotarget.org/2024/03/28/identifying-biomarkers-for-predicting-paclitaxel-response/

Paper DOI - https://doi.org/10.18632/oncotarget.28549

Correspondence to - Crismita Dmello - crismita.dmello@northwestern.edu, and Adam M. Sonabend - adam.sonabend@northwestern.edu

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Keywords - cancer, glioblastoma, predictive biomarker, CRISPR screen, paclitaxel

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.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Identifying Biomarkers for Predicting Paclitaxel Response

Das Reizdarmsyndrom RDS ist eine häufige gastrointestinale Störung, die mit chronischen abdominellen Schmerzen, Diarrhoe und/oder Obstipation einhergeht. Aufgrund der komplexen Natur der Symptome und der Vielfalt möglicher Ursachen erfordert die Behandlung des Reizdarmsyndroms einen ganzheitlichen und individualisierten Ansatz. Vor einer Behandlung des Reizdarmsyndroms ist eine sorgfältige Anamnese und der systematische Ausschluss anderer gastrointestinaler Erkrankungen notwendig. Bei der Mehrzahl der Patient*innen, die glauben an einer Zöliakie oder einer Weizenunverträglichkeit zu leiden, ist die Erkrankung nicht ärztlich bestätigt und eine Diät nicht begründet.

Veränderungen im Lebensstil und der Ernährung einschließlich einer FODMAP-armen Diät und der Erhöhung des Ballaststoffanteils spielen bei der Behandlung des Reizdarmsyndroms eine wichtige Rolle. Das Spektrum an zugelassenen und wirksamen Medikamenten, abhängig davon ob eine eher durch Diarrhoe oder durch Obstipation geprägte Erkrankungsform vorliegt, ist eingeschränkt. Da auch psychologische Faktoren bei der Manifestation und Aufrechterhaltung von Reizdarmsymptomen relevant sind, haben Entspannungstechniken und Methoden der kognitiven Verhaltenstherapie einen Stellenwert, die auch als DiGA verfügbar sind.

Dr. Martin Fedder stellt in diesem Podcast die Schwerpunkte einer eCME-Fortbildung von Prof. Dr. Oliver Bachmann vor.  Prof. Bachmann ist Facharzt für Innere Medizin mit dem Schwerpunkt Gastroenterologie und leitet als Chefarzt die Medizinische Klinik 1 am Siloah St. Trudpert Klinikum in Pforzheim. 
Mit freundlicher Unterstützung von Mylan-Viatris.

Zur Folgen-Übersicht: medical-tribune.de/blitzlicht-fortbildung

Blitzlicht Fortbildung

Reizdarm – oder doch ein Morbus Crohn?

BUFFALO, NY- June 19, 2024 – A new research paper was published in Oncotarget's Volume 15 on June 13, 2024, entitled, “Assessment of serum tumor markers CEA, CA-125, and CA19-9 as adjuncts in non-small cell lung cancer management.”

Conventional tumor markers may serve as adjuncts in non-small cell lung cancer (NSCLC) management. In this new study, researchers Scott Strum, Mark Vincent, Meghan Gipson, Eric McArthur, and Daniel Breadner from the Schulich School of Medicine and Dentistry, London Health Sciences Centre, and Royal College of Surgeons in Ireland analyzed whether three tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in NSCLC. 

“The aim of this retrospective study was to provide additional evidence for the clinical use of conventional serum tumor markers CEA, CA19-9, and CA-125 in NSCLC management.”

It constituted a single-center study of NSCLC patients treated with systemic therapy at the London Regional Cancer Program. Serum tumor markers were analyzed for differences in radiographic responses (RECIST v1.1 or iRECIST), associations with clinical characteristics, and all-cause mortality. A total of 533 NSCLC patients were screened, of which 165 met inclusion criteria. A subset of 92 patients had paired tumor markers and radiographic scans. 

From the latter population, median (IQR) fold-change from nadir to progression was 2.13 (IQR 1.24–3.02; p < 0.001) for CEA, 1.46 (IQR 1.13–2.18; p < 0.001) for CA19-9, and 1.53 (IQR 0.96–2.12; p < 0.001) for CA-125. Median (IQR) fold-change from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p < 0.001) for CEA, 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9, and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125. 

“In conclusion, tumor markers are positioned to be used as adjunct tools in clinical decision making, especially for their associations with radiographic response (CEA/CA-125) or progression (CEA/CA-125/CA-19-9).”

DOI - https://doi.org/10.18632/oncotarget.28566

Correspondence to - Daniel Breadner - daniel.breadner@lhsc.on.ca

Video short - https://www.youtube.com/watch?v=8LO-Hn0fbrg

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Keywords - cancer, tumor marker, biomarker, lung cancer; NSCLC, translational research

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.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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

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Assessment of CEA, CA-125, and CA19-9 as Adjuncts in Non-small Cell Lung Cancer Management

In this episode, I’m joined by Michael Dubrovsky, a materials chemist, engineer, and serial entrepreneur who is transforming the world of healthcare with SiPhox Health. As the co-founder and Chief Product Officer of SiPhox Health, Michael is on a mission to make preventative healthcare accessible and affordable for everyone. We dive into how SiPhox Health offers the most comprehensive at-home blood testing solution on the market, allowing you to take control of your health with regular biomarker testing, personalized assessments, and tailored action plans. Michael shares the challenges facing traditional blood tests, the unique offerings of SiPhox Health, and the future of health monitoring. Whether you're a health enthusiast or simply curious about the future of diagnostics, this episode is packed with insights you won’t want to miss!

Hosted by Leanne Vogel.

20% off SiPhox Blood Testing: http://siphoxhealth.com/leanne

Coaching and other supports available at: https://shop.healthfulpursuit.com/ 

Podcast Sponsors, links and offers available at: https://www.healthfulpursuit.com/podcast/

At-Home Blood Testing with Michael Dubrovsky {SiPhox Health}

In this episode, we talk with Dr. Chris Davlantes about the evolution of blood tests to detect and risk stratify traumatic brain injuries. Over the last few years, we have seen tests emerge, but now have access to POC technology that may assist emergency physicians and others to get patients the care they need and avoid unnecessary imaging if possible. 

This episode was supported by Abbott Point of Care. 

The Evolution and Emergence of TBI Biomarkers with Dr. Chris Davlantes

Medikamente müssen nicht nur zur Krankheit passen, sondern auch zum Patienten oder zur Patientin – nach diesem Prinzip funktioniert die Präzisionsmedizin, auch personalisierte Medizin genannt. Dank immer genauerer molekularer und genetischer Analysen lassen sich Therapien heute passgenauer abstimmen – oder sogar individuelle Medikamente herstellen. Was durch künstliche Intelligenz noch besser werden kann und was das alles bringt, dazu befragen wir vfa-Forschungssprecher Rolf Hömke.

Präzisionsmedizin – Therapien mit individuell ausgewählten oder hergestellten Medikamenten

„Blitzlicht Fortbildung“ bietet Ärzt:innen eine zeitsparende und abwechslungsreiche Zusammenfassung der wichtigsten Lerninhalte verschiedener Fortbildungen. Zahlreiche Fachbereiche kompakt präsentiert in wenigen Minuten – so macht das Lernen von unterwegs Spaß.

Das Fortbildungsangebot der Medical Tribune: https://www.medical-tribune.de/fortbildung/

ACEP Frontline, hosted by Dr. Ryan Stanton, features in-depth conversations on the hottest topics in emergency medicine and critical care.

Join Functional Medicine Practitioner and Holistic Nutritionist, Leanne Vogel as we seek answers on the fringes of the health space. Together we'll explore the principles of functional health to help you thrive in mind, body, and spirit. In each episode, we'll delve into the latest research, practical tips, and insightful interviews with experts in the field of functional medicine and holistic health. Join me on Tuesdays as we work to shift your perspective, and up-level your approach to a healthful life... because your health is worth pursuing.

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/

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

New tracks tagged #Biomarker