A new research paper was published in Oncotarget's Volume 14 on June 21, 2023, entitled, “Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells.”

Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. The underlying mechanisms of toxicity of DPDT against tumor cells have previously been poorly explored.

In this new study, researchers André Luiz Mendes Juchem, Cristiano Trindade, Juliana Bondan da Silva, Miriana da Silva Machado, Temenouga Nikolova Guecheva, Jaqueline Cesar Rocha, Jenifer Saffi, Iuri Marques de Oliveira, João Antonio Pêgas Henriques, and Alexandre Escargueil from the Federal University of Rio Grande do Sul, Sorbonne Université, Federal University of Health Sciences of Porto Alegre, Lutheran University of Brazil, Bulgarian Academy of Sciences, and University of Vale do Taquari aimed to investigate the effects of DPDT against both human cancer and non-tumorigenic cells. 

“Together, our results will help to better define DPDT as a potential drug candidate for treating CRC [colorectal cancer].”

The researchers used the colonic HCT116 cancer cells and the MRC5 fibroblasts as models. Their results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells. 

Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, the results of this study show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning. 

“This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.”


Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28465

Correspondence to: João Antonio Pêgas Henriques, Alexandre Escargueil 

Email: pegas.henriques@ufrgs.br, alexandre.escargueil@gmail.com 

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Keywords - colorectal cancer, HCT116, diphenyl ditelluride, organotellurium, topoisomerase I

About Oncotarget

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. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

DPDT Anticancer Activity in Human Colon Cancer HCT116 Cells

On this episode, Isaac interviews RaShad Eas, aka Dr. Easley as a hip-hop artist, about his latest project titled D.E.I. RaShad Eas talks about the themes behind each track on the album, and the roles of family, friends, and faith in his personal journey. Join us for a glimpse into the creative mind of our own Dr. Easley as he moves from the interviewer seat to the other side of the mic.

Exploring the True Meaning of D.E.I. with RaShad Eas

BUFFALO, NY - November 6, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC”

This study, led by researchers from the Federal University of Ceará in Brazil and collaborating institutions in Brazil, Argentina and Spain, presents important findings on small cell lung cancer (SCLC), one of the most aggressive forms of lung cancer with limited treatment options. The research reveals how specific biomarkers in SCLC tumors could open new opportunities for more personalized and targeted therapies for these patients.

SCLC accounts for about 15% of all lung cancer cases and is known for its rapid spread and resistance to many treatments. Currently, the five-year survival rate for SCLC patients is below 5%. Recent advances in precision medicine aim to improve these outcomes by identifying and targeting the unique characteristics of each patient’s tumor.

Researchers Samuel Silva, Juliana C. Sousa, Cleto Nogueira, Raquel Feijo, Francisco Martins Neto, Laura Cardoso Marinho, Guilherme Sousa, Valeria Denninghoff, and Fabio Tavora analyzed tumor samples from 64 SCLC patients using both traditional and digital pathology tools. Their findings highlighted promising results for two of the analyzed biomarkers: Delta-like ligand 3 (DLL3) and Thyroid transcription factor-1 (TTF-1).

DLL3 was identified in over 70% of the tumors, highlighting its potential as a promising target for therapies like Tarlatamab. Another key finding involved TTF-1 expression; patients with TTF-1-positive tumors showed improved survival rates, underscoring its potential as a prognostic marker to refine diagnoses and predict patient outcomes.

The authors also noted that, “The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches.”

In conclusion, the study suggests that clinical trials targeting biomarkers like DLL3 and TTF-1 could enhance SCLC patient outcomes by tailoring treatments based on individual biomarker profiles. This research marks an important step forward in precision medicine for SCLC.

DOI - https://doi.org/10.18632/oncotarget.28660

Correspondence to - Fabio Tavora - fabio.tavora@argospatologia.com

Video short - https://www.youtube.com/watch?v=YYsZ0UHPszg

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Keywords - cancer, DLL3, pathology, biomarkers, qupath, small cell carcinoma

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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Precision Medicine in SCLC: DLL3, ASC1, TTF-1, and Ki-67 Expression

BUFFALO, NY- November 6, 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 20 on October 24, 2024, entitled “On the lifespan of Enchytraeus crypticus - impact of iron (nanomaterial and salt) on aging.”

This recent study reveals important insights into how iron oxide nanoparticles (Fe3O4 NMs)—tiny particles with unique magnetic properties widely used in medicine and environmental procedures—may affect soil health over time. Led by Susana I.L. Gomes, Janeck J. Scott-Fordsmand, and Mónica J.B. Amorim from the University of Aveiro in Portugal and Aarhus University in Denmark, the research focuses on how these particles interact with the soil-dwelling worm Enchytraeus crypticus, which plays an essential role in breaking down organic matter and supporting soil structure. 

Iron oxide nanoparticles are increasingly used in applications like magnetic resonance imaging, drug delivery, and environmental cleanup. Their effects on soil ecosystems remain largely unexplored. In this study, the team selected Enchytraeus crypticus, a globally present soil-dwelling worm, as an indicator species to assess potential risks to soil health. Over a 202-day period, they examined how iron oxide nanoparticles and traditional iron salt (FeCl3) impact the worm’s lifespan, aging, and reproductive ability.

Findings revealed that prolonged exposure to iron oxide nanoparticles reduced the lifespan, longevity, and reproductive success of Enchytraeus crypticus, particularly in isolated conditions. Worms in lower-density groups experienced greater harm, with shorter lifespans and fewer offspring, while those in larger groups faced less severe impacts. This suggests that population density and environmental factors may influence nanoparticle toxicity. Although iron chloride also showed toxic effects, iron oxide nanoparticles posed higher risks over time, likely due to a slower release of iron ions that extends exposure.

In conclusion, this research highlights the importance of comprehensive studies on the long-term effects of nanoparticles on the environment. As iron oxide nanoparticles become more prevalent, understanding their impact on soil ecosystems is crucial to protecting biodiversity and ensuring the sustainability of natural resources.

DOI - https://doi.org/10.18632/aging.206134

Corresponding author - Mónica J.B. Amorim - mjamorim@ua.pt

Video short - https://www.youtube.com/watch?v=ElhbSAhMeXw

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Keywords - aging, long-term, magnetite, nanobiomaterial, survival

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) 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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Aging (Aging-US)

Impact of Iron on Aging in Enchytraeus crypticus

In this special episode of the Yale Journal of Biology and Medicine podcast, hosts Shivesh Shourya and Mara Kushelman bring together a remarkable group of individuals transforming spinal cord injury (SCI) recovery through peer mentorship and advocacy. Joining us are Jonathan Sigworth, co-founder of More Than Walking, a nonprofit promoting independent living for SCI survivors; Dr. Benjamin Doolittle, Yale professor and Program Director of the Combined Internal Medicine-Pediatrics Residency Program with a focus on wellness and spirituality in medicine; and Yale medical students Teimur Kayani and Robert Cotter, who have conducted pivotal research on peer mentorship as a valuable intervention for SCI recovery.

Throughout the conversation, we explore how peer mentorship helps SCI survivors regain independence, the role of community support in recovery, and the potential for integrative medicine to enhance quality of life for SCI patients. The guests share insights from their personal and professional journeys, discussing the challenges, triumphs, and transformative impact of peer mentorship. Together, they highlight the importance of holistic, community-based approaches to recovery and inspire a reimagining of what’s possible for SCI survivors.

For more information, explore the resources below:

https://www.morethanwalking.com/

https://pmc.ncbi.nlm.nih.gov/articles/PMC11426298/

https://www.mayoclinic.org/diseases-conditions/spinal-cord-injury/symptoms-causes/syc-20377890

https://artofmentoring.net/peer-mentoring/

Join us to learn more about the power of peer mentorship in supporting SCI survivors and shaping new pathways to independence.

Peer Mentorship in Spinal Cord Injury Recovery: Independence, Community, and Integrative Care

Imagine a future where we not only live longer but stay healthy throughout those extra years. Thanks to recent breakthroughs in biotechnology and artificial intelligence (AI) in healthcare, this vision is closer to becoming a reality.

Advancements in Aging Research

Aging research has made significant progress in recent years by combining disciplines like biology, technology, and medicine to tackle the challenges of extending healthspans and reducing age-related diseases. While people today live longer than ever before, extending our “healthspan”—the years we stay active and illness-free—remains challenging. AI and health biomarkers (biological indicators of our body’s condition) are now key tools in the pursuit of longer, healthier lives.

In a recent paper, led by corresponding authors Yu-Xuan Lyu from Southern University of Science and Technology Shenzhen; Alex Zhavoronkov from Insilico Medicine AI Limited, Masdar City, Abu Dhabi; Morten Scheibye-Knudsen and Daniela Bakula from the Center for Healthy Aging, University of Copenhagen, along with numerous other collaborators, the transformative potential of AI in aging research was explored. The research paper, titled “Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity,” was published as the cover paper in Aging’s Volume 16, Issue 20.

Full blog - https://aging-us.org/2024/11/how-ai-and-longevity-biotechnology-are-revolutionizing-healthcare-for-healthier-longer-lives/

Paper DOI - https://doi.org/10.18632/aging.206135

Corresponding authors - Yu-Xuan Lyu - lvyx@sustech.edu.cn, Alex Zhavoronkov - alex@insilico.com, Morten Scheibye-Knudsen - mscheibye@sund.ku.dk, and Daniela Bakula - bakula@sund.ku.dk

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Keywords - aging, biotechnology, artificial intelligence, healthy longevity

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) 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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How AI and Longevity Biotechnology are Revolutionizing Healthcare for Healthier, Longer Lives

Dr. Allana Munro and Dr. Ronald George are two obstetric anesthesia experts whose research is focused on labor analgesia. Two years ago, they demonstrated that “achieving desired pain relief” is of utmost importance to our patients. The question remains: How can we safely achieve this while minimizing workload and side effects? In this episode, they discuss their study titled “An Innovative Approach to Determine Programmed Intermittent Epidural Bolus Pump Settings for Labor Analgesia: A Randomized Controlled Trial.” Using the response surface methodology, they identified optimal settings for the programmed intermittent epidural bolus pump (PIEB) that maximize maternal satisfaction, minimize clinician-administered boluses, and balance PCEA boluses delivered to those requested. 

An Innovative Approach to Determine Programmed Intermittent Epidural Bolus Pump Settings for Labor Analgesia: A Randomized Controlled Trial. https://pubmed.ncbi.nlm.nih.gov/38905148/

Patient Preferences for Outcomes Associated With Labor Epidural Analgesia. https://pubmed.ncbi.nlm.nih.gov/35355544/

Innovative approach for PIEB setting

BUFFALO, NY - November 11, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 7, 2024, titled “Beyond the hype: Navigating bias in AI-driven cancer detection.”

In this editorial, researchers from the Mayo Clinic emphasize the need to address potential biases in Artificial Intelligence (AI) tools used for cancer detection to ensure fair and equitable healthcare. Authors Yashbir Singh, Heenaben Patel, Diana V. Vera-Garcia, Quincy A. Hathaway, Deepa Sarkar, and Emilio Quaia discuss the risks of biased AI systems, which can lead to disparities in diagnosis and treatment outcomes across diverse patient groups.

While AI is transforming cancer care through early diagnosis and improved treatment planning, this study warns that AI models trained on limited or non-diverse data may misdiagnose or overlook certain populations, particularly those in underserved communities, thereby increasing healthcare disparities. As explained in the editorial, “For example, if an AI model is trained on Caucasian patients, it may struggle to detect skin cancer accurately in patients with darker skin, leading to missed diagnoses or false positives.” Such biases could result in unequal access to early diagnosis and treatment, ultimately leading to poorer health outcomes for certain groups. Beyond racial bias, factors such as socioeconomic status, gender, age, and geographic location can also affect the accuracy of AI in healthcare.

The authors propose a comprehensive approach to developing fair AI models in healthcare, highlighting six key strategies. They first emphasize the importance of using diverse and representative datasets to improve diagnostic accuracy across all demographics. Rigorous testing and validation across various population groups are necessary before AI systems are widely implemented. To promote ethical AI use, models should be transparent in their decision-making processes, enabling clinicians to recognize and address potential biases. The researchers also advocate for collaborative development involving data scientists, clinicians, ethicists, and patient advocates to capture a range of perspectives. Continuous monitoring and regular audits are essential to detect and correct biases over time. Finally, training healthcare providers on AI’s strengths and limitations will empower them to use these tools responsibly and make informed interpretations.

“The goal should not merely be to create AI systems that are more accurate than humans but to develop technologies that are fundamentally fair and beneficial to all patients.”

The authors also urge regulatory bodies, such as the U.S. Food and Drug Administration (FDA), to implement updated frameworks specifically aimed at addressing AI bias in healthcare. Policies that promote diversity in clinical trials and incentivize the development of fair AI systems will help ensure that AI benefits reach all populations equitably. They caution against over-reliance on AI without a full understanding of its limitations, as unchecked biases could undermine patient trust and slow the adoption of valuable AI technologies.

In conclusion, as AI continues to transform cancer care, the healthcare sector must prioritize fairness, transparency, and robust AI regulation to ensure that it serves all patients without bias. By addressing bias from development through to implementation, AI can fulfill its promise of creating a fair and effective healthcare system for everyone.

DOI -  https://doi.org/10.18632/oncotarget.28665

Correspondence to - Yashbir Singh - singh.yashbir@mayo.edu

To learn more about Oncotarget, please visit https://www.oncotarget.com.

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Navigating Bias in AI-Driven Cancer Detection

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/

DPDT Anticancer Activity in Human Colon Cancer HCT116 Cells

Oncotarget Podcast