BUFFALO, NY- July 26, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited.

In this new retrospective study, researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University, Oregon Health and Science University, Cancer Early Detection Advanced Research Center (CEDAR), and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020. 

“Our study significantly expands on prior work by De Azevedo et al. by encompassing a larger cohort of individuals, coupled with a comprehensive approach to defining high and low MIF and DDT expression.”

Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Their findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes. 

Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.

“Our study is the first to report survival findings in association with intratumor DDT expression and CD74:DDT expression level ratio. Thus, CD74:MIF and CD74:DDT expression ratio measurements offer promise as prognostic markers for survival outcomes and ICI response in patients with melanoma.”

DOI - https://doi.org/10.18632/oncotarget.28615

Correspondence to - Thuy Tran - thuy.tran@yale.edu

Video short - https://www.youtube.com/watch?v=ULlzscn0PvQ

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Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics

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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Oncotarget

Prognostic and Therapeutic Insights Into MIF, DDT, and CD74 in Melanoma

Cancer impacts the entire family of a patient, including the children. To help parents help their children through these difficult time periods, the James has created a team of certified child life specialists (CCLS).
“We help parents navigate these situations and conversations,” said Sami Rundo, CCLS. The help comes in many forms, Rundo explained. “It starts with understanding the medical situation [of the patient] … And then we prepare the family to navigate discussions and conversations. What does that conversation look like? And do they want our child life services to have these discussions with their children or provide the resources they can use in these conversations.” Rundo explained how these discussions can trigger emotions and that parents can “embrace the fact there will probably be some tears and the need for breaks and walks.” She also detailed why it can be important to explain the medical procedures that will take place, such as surgery and radiation treatments, and how their parent’s treatment could impact a child’s daily routine. The team has a doll they utilize to visually show children different medical procedures and what a port that delivers chemotherapy looks like.
“We also talk about the ways in which the children can be helpers, caregivers,” Rundo said. “And what’s appropriate for that child. Can I get you a blanket if you’re cold, but maybe not taking care of their other siblings.” The James certified child life specialists can let parents know about cancer-themed children’s book they might want to utilize in their discussion with their children, and “we can create customized books for a family,” Rundo said.
The James certified child life services team is relatively new and growing. “Over time [with a family] we develop trust and an openness of communications,” Rundo said. “I’ve learned so much about families and to see them grow and become stronger during these difficult times is really profound.”

Episode 187: The James Team of Certified Child Life Specialists, with Sami Rundo

THE Father Lizzie is back on The Leader's Way podcast, talking about her new devotional God Didn't Make Us to Hate Us. We talk about the alternative to "billboard Christianity" and how an expansive, inclusive God affects individual spirituality and corporate worship in church. Finally, the Golden Retriever Games are back, baby. Stay 'till the end for "Holy or Horror?"

52: God Didn’t Make Us to Hate Us with Lizzie McManus-Dail

BUFFALO, NY — May 7, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 4, 2025, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.”

A research team led by first author Mauricio Moel and corresponding author Stefanie L. Morgan from AgelessRx conducted a clinical trial to determine whether low-dose, intermittent rapamycin could safely improve healthspan in older adults. The findings suggest rapamycin may offer measurable benefits for physical function and overall well-being, reinforcing its potential as a safe intervention to support healthy aging.

Aging remains the leading cause of chronic conditions such as heart disease, diabetes, and dementia. While medical advances have extended lifespan, many people still experience declining health and reduced mobility in later years. This growing gap between lifespan and healthspan has driven interest in therapies that target aging itself. Rapamycin, an FDA-approved drug originally used in transplant medicine, has drawn attention for its ability to influence aging-related pathways in animal studies. Until recently, its safety and benefits in healthy human populations were largely unknown.

The PEARL trial is the longest study so far to explore rapamycin’s use for longevity in healthy aging adults. Researchers followed 114 participants aged 50 to 85 over 48 weeks in a randomized, double-blind, placebo-controlled design. Participants received either a placebo or 5 mg or 10 mg of compounded rapamycin once per week. The study’s primary goal was to measure changes in visceral fat, while secondary outcomes included lean muscle mass, blood markers, and quality-of-life assessments.

The trial found that low-dose rapamycin was safe and well-tolerated, with serious side effects reported at similar rates across all groups. The most frequent minor issue among rapamycin users was mild gastrointestinal discomfort. While no significant reductions in visceral fat were observed, women taking 10 mg of rapamycin showed significant gains in lean muscle and reported reduced pain. In addition, participants taking 5 mg weekly reported improvements in emotional well-being and general health, as measured by validated surveys.

“Our findings provide evidence that these rapamycin regimens are well tolerated with minimal adverse effects when administered for at least one year within normative aging individuals.”

Researchers noted some limitations, including the relatively small and health-conscious participant group, which may have limited the ability to detect larger effects. The compounded form of rapamycin used also had lower absorption than commercial versions, possibly reducing its impact.

Overall, the PEARL trial provides early clinical evidence that low-dose rapamycin may help support physical and emotional well-being in older adults. Further studies with larger and more diverse populations will be essential to confirm the study results and refine dosing strategies for broader application.

DOI: https://doi.org/10.18632/aging.206235

Corresponding author: Stefanie L. Morgan – stefanie@agelessrx.com

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Keywords: rapamycin, aging, healthspan, longevity, geroscience

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Aging (Aging-US)

Low-Dose Rapamycin Improves Muscle Mass and Well-Being in Aging Adults

A recent #study from Assiut University Hospital in Egypt, published in #Oncotarget, presents a promising strategy for patients with metastatic #colorectalcancer (mCRC). The #research introduces a gentler yet effective maintenance therapy that may extend survival, enhance quality of life, and offer a more accessible treatment option for mCRC patients worldwide.

The Challenge of Treating Metastatic Colorectal Cancer

Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. When it spreads to other parts of the body—a stage known as mCRC—it becomes much more difficult to treat. At this stage, clinicians often use strong drug combinations like FOLFOX or CAPOX, which mix chemotherapy drugs to stop cancer growth. FOLFOX combines three drugs given intravenously, while CAPOX includes two of the same drugs, with one taken as a pill.

While effective, these treatments can cause serious side effects. For example, one of the main drugs, oxaliplatin, can lead to nerve damage, making it painful or difficult to use the hands and feet. Fatigue, diarrhea, and other issues are also common. Over time, these side effects may force clinicians to stop or adjust the treatment, even if it is working.

That is where maintenance therapy comes in. After the cancer is controlled, clinicians often switch to a gentler treatment plan to keep it from returning. The challenge is finding a therapy that continues to work without causing too many side effects, especially in places where access to expensive or intensive treatments is limited.

Full blog - https://www.oncotarget.org/2025/05/07/panitumumab-and-low-dose-capecitabine-a-promising-maintenance-therapy-for-metastatic-colorectal-cancer/

Paper DOI - https://doi.org/10.18632/oncotarget.28687

Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.com

Video short - https://www.youtube.com/watch?v=wuPSS0EdK-8

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Keywords - cancer, Panitumumab, maintenance, colorectal cancer, Capecitabine

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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Panitumumab & Low-Dose Capecitabine: Promising Maintenance Therapy for Metastatic Colorectal Cancer

BUFFALO, NY - May 9, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on May 8, 2025, titled “METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis."

In this study, researchers Jayasree Peroth Jayaprakash, Pragati Karemore, and Piyush Khandelia from the Birla Institute of Technology and Science, India, discovered that a molecule called METTL3 contributes to the development and spread of oral squamous cell carcinoma (OSCC). The study shows that METTL3 increases the levels of a small RNA molecule called miR-146a-5p, which blocks SMAD4, a key tumor-suppressing gene. These findings help explain why oral cancers are difficult to treat and may offer a new target for more effective therapies.

Oral squamous cell carcinoma is a common and aggressive cancer affecting the mouth and throat. It has a high death rate, mainly due to late detection, treatment resistance, and the cancer’s ability to invade nearby tissues. In this study, the researchers focused on METTL3, an enzyme that adds chemical tags known as m6A marks to RNA, which change how genetic information is used by cells. They found that METTL3 is unusually active in OSCC cells, causing an increase in miR-146a-5p. This molecule, in turn, blocks the function of SMAD4, which helps control how cells grow and die in our bodies.

“METTL3, the primary m6A RNA methyltransferase, is significantly upregulated in OSCC cells leading to increased global m6A levels.”

When METTL3 was reduced or chemically blocked, miR-146a-5p levels dropped and SMAD4 levels increased. This shift slowed the growth of cancer cells, increased their death, and made them less likely to spread. When researchers reintroduced miR-146a-5p or lowered SMAD4 levels again, the cancer-promoting behavior returned. These results show that the METTL3–miR-146a-5p–SMAD4 pathway plays a key role in OSCC.

The findings open up new possibilities for treatment. Drugs that block METTL3 or miR-146a-5p or that restore SMAD4 could slow or stop tumor growth. One such drug, STM2457, which targets METTL3, has already shown promise in lab studies. As research progresses, targeting this molecular pathway may offer a new strategy in treating OSCC.

This discovery improves our understanding of how OSCC develops and avoids the body’s defenses. By interfering with this newly discovered pathway, future treatments may become more successful, improving survival rates and quality of life for people with this disease.

DOI - https://doi.org/10.18632/oncotarget.28717

Correspondence to - Piyush Khandelia - piyush.khandelia@hyderabad.bits-pilani.ac.in

Video short - https://www.youtube.com/watch?v=o5XuDlcIma8

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METTL3 Drives Oral Cancer by Blocking Tumor-Suppressing Gene

BUFFALO, NY — May 13, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 7, 2025, titled “Pharmacological recapitulation of the lean phenotype induced by the lifespan-extending sulfur amino acid-restricted diet.”

In this study, the research team, led by first author Naidu B. Ommi and corresponding author Sailendra N. Nichenametla from the Orentreich Foundation for the Advancement of Science Inc., investigated whether the drug buthionine sulfoximine (BSO) could replicate the effects of sulfur amino acid restriction (SAAR), a challenging diet known to reduce obesity. The study found that BSO produced similar reductions in fat mass and weight gain. This drug-based approach may offer a simpler and safer treatment for obesity, especially for those unable to follow strict dietary plans.

Obesity and metabolic disorders raise the risk of chronic illnesses like heart disease, diabetes, and Alzheimer’s disease. While SAAR, a diet low in the amino-acids methionine and cysteine, has shown powerful health benefits in animal studies, its translation to humans has been limited by adherence challenges. This new study explored whether BSO, a compound that lowers glutathione (GSH) levels in the body, could mimic SAAR’s effects without dietary restriction.

Researchers tested four groups of obese mice on high-fat diets. One group received the SAAR diet, another was given a regular diet plus BSO, while two control groups received either no treatment or a supplement that increased GSH levels. The BSO-treated mice showed lower fat mass, reduced liver fat, and prevented weight gain, results comparable to those on the SAAR diet. These benefits occurred without reducing food intake or muscle mass, making BSO a particularly promising treatment option.

“BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver.”

Additional findings revealed that both the SAAR diet and BSO influenced metabolic activity by activating pathways related to fat storage, but they did so in different organs. The SAAR diet had stronger effects in the liver, while BSO acted more in the kidneys. Both interventions increased levels of the amino acid serine, which is associated with lower fat production.

Unlike many obesity treatments that suppress appetite or reduce muscle, BSO helped prevent fat accumulation while preserving lean mass and food consumption. No signs of liver or kidney toxicity were observed during the 13-week study, suggesting the drug’s safety at the tested dose.

Since BSO has previously been evaluated in human clinical trials for other conditions, repurposing it for metabolic diseases may be relatively straightforward. However, the researchers point out that there should be further studies in both animals and humans. If successful, this strategy could provide a practical alternative to difficult-to-maintain diets and help more people manage weight long-term.

DOI: https://doi.org/10.18632/aging.206237

Corresponding author: Sailendra N. Nichenametla – snichenametla@orentreich.org

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Keywords: aging, buthionine sulfoximine, thiols, serine, anti-obesity drugs

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BSO Compound Mimics Diet-Induced Fat Loss Without Cutting Food Intake

This week’s episode of YBJM Science News discusses how our surroundings impact a variety of health outcomes. From air pollutants to sleep quality to pharmacy access and more, join Roxanna and Hanna as they discuss recent Yale-affiliated research in biology and medicine. 

Papers featured in this episode and associated links:
“Early-Life Exposure to Air and Light Pollution Linked to Increased Risk of Pediatric Thyroid Cancer” - https://ysph.yale.edu/news-article/early-life-exposure-to-air-and-light-pollution-linked-to-increased-risk-of-pediatric-thyroid-cancer
“Perinatal Exposures to Ambient Fine Particulate Matter and Outdoor Artificial Light at Night and Risk of Pediatric Papillary Thyroid Cancer” - https://doi.org/10.1289/EHP14849 
New York Times article on Environmental Health Perspectives journal - https://www.nytimes.com/2025/04/29/science/science-journal-environment-trump.html 
“Reduced Deep and REM Sleep Could be Early Markers of Alzheimer’s” - https://medicine.yale.edu/news-article/reduced-deep-and-rem-sleep-could-be-early-markers-of-alzheimers/
“Lower slow wave sleep and rapid eye movement sleep are associated with brain atrophy of AD-vulnerable regions” - https://doi.org/10.5664/jcsm.11630 
The Atherosclerosis In the Community Study - https://www5.cscc.unc.edu/aric9/ 
“Groundbreaking Study Highlights Critical Gap in Global Mental Health Research” - https://medicine.yale.edu/psychiatry/news-article/groundbreaking-study-highlights-critical-gap-in-global-mental-health-research/
“Psychiatric genetics in the diverse landscape of Latin American populations” - https://doi.org/10.1038/s41588-025-02127-z
Latin American Genomics Consortium - https://www.latinamericangenomicsconsortium.org/ 
“A New Metric to Identify – and Prevent – Pharmacy Deserts” - https://medicine.yale.edu/news-article/a-new-metric-to-identify-prevent-pharmacy-deserts/ 
“Vulnerability Index Approach to Identify Pharmacy Deserts and Keystone Pharmacies” - https://doi.org/10.1001/jamanetworkopen.2025.0715
“Timing of RSV Immunization Matters for Infant Protection” - https://medicine.yale.edu/news-article/timing-of-rsv-immunization-matters-for-infant-protection/ 
“Estimated Effectiveness of Nirsevimab Against Respiratory Syncytial Virus” - https://doi.org/10.1001/jamanetworkopen.2025.0380 

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YJBM Science News 33: Surroundings, Access, and Health

BUFFALO, NY — May 14, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 10, 2025, titled “Impact of Factor Xa inhibitors on cardiovascular events in older patients with nonvalvular atrial fibrillation.”

In this study, first author Masahiko Takahashi and corresponding author Keisuke Okawa led a research team from Kagawa Prefectural Central Hospital and Hyogo Medical University that investigated whether Factor Xa inhibitors (Xa-Is)—a type of blood thinner—can reduce the risk of heart-related complications in patients over 80 with nonvalvular atrial fibrillation (NVAF). The study found that patients using Xa-Is experienced significantly fewer cardiovascular problems than those on other anticoagulants. This finding is especially relevant, as older adults face a high risk of both stroke and heart disease.

Atrial fibrillation is a common heart rhythm disorder, particularly in the elderly, that increases the risk of blood clots, heart failure, and stroke. Anticoagulants are often prescribed to prevent clots, but not all types have the same effects on heart health. This study focused on comparing Xa-Is—specifically rivaroxaban, apixaban, and edoxaban—with commonly used drugs such as warfarin and dabigatran.

Researchers followed more than 1,000 patients aged 80 and above for up to five years to assess the long-term impact of these medications on cardiovascular outcomes. Patients who used Xa-Is had significantly lower rates of heart failure, artery disease, and cardiovascular death. The risk of cardiovascular problems in the Xa-I group was less than half that of those on non-Xa-I medications. These benefits remained even after adjusting for factors like age, existing heart conditions, and kidney function. Additionally, stroke and all-cause death rates were notably lower in the Xa-I group. 

“Xa-Is may be useful for not only anticoagulation but also the prevention of cardiovascular events in very old patients with NVAF.”

What makes Xa-Is different, according to the researchers, is their ability to inhibit a specific biological pathway—known as Factor Xa–PAR2—that contributes to inflammation, fibrosis, and damage in blood vessels and heart tissue. This effect extends beyond their traditional role in preventing blood clots. Although the study was conducted at a single medical center in Japan, its rigorous design and long follow-up period enhance the reliability of the findings for real-world clinical decision-making.

While further studies, especially across multiple centers, are needed to confirm the full range of benefits, this study strongly suggests that Xa-Is may offer broader cardiovascular protection for very old patients. The findings could influence how clinicians choose blood thinners for elderly individuals with atrial fibrillation, potentially improving both survival and quality of life in this growing population.

DOI - https://doi.org/10.18632/aging.206238

Corresponding author - Keisuke Okawa - k-ookawa@chp-kagawa.jp

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Keywords - aging, Factor Xa inhibitor, atrial fibrillation, older patient, cardiovascular events

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Blood Thinners Called Factor Xa Inhibitors Lower Heart Risk in Elderly with Atrial Fibrillation

Werner syndrome is a rare condition marked by accelerated aging. A recent study, featured as the cover paper in Aging (Aging-US), Volume 17, Issue 4, led by researchers at the University of Oslo and international collaborators, suggests that nicotinamide adenine dinucleotide (NAD+), a vital molecule involved in cellular energy production, may be key to understanding this disease and developing future strategies to manage it.

Understanding Werner Syndrome

Werner syndrome (WS) is a rare genetic condition that causes people to age more quickly than normal. By their 20s or 30s, individuals with WS often show signs typically associated with older age, such as cataracts, hair loss, thinning skin, and heart disease. This premature aging is caused by mutations in the WRN gene, which normally helps repair DNA and protect cells from damage. While the WRN gene’s role in maintaining genetic stability is well understood, the reasons behind the rapid decline of cells in WS patients are still not fully clear.

The Study: Investigating NAD+ in Werner Syndrome

Nicotinamide adenine dinucleotide levels naturally decline with age. In the study titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation,” researchers investigated whether this decline is more severe in people with WS and whether restoring NAD+ levels could help slow the aging process in these patients.

Full blog - https://aging-us.org/2025/05/fighting-premature-aging-how-nad-could-help-treat-werner-syndrome/

Paper DOI - https://doi.org/10.18632/aging.206236

Corresponding author - Evandro F. Fang - e.f.fang@medisin.uio.no

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Keywords - aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation

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Fighting Premature Aging: How NAD+ Could Help Treat Werner Syndrome

BUFFALO, NY - May 14, 2025 – A new #review paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis."

A comprehensive study, led by first authors Rahaf Alchazal from Yarmouk University and Khaled J. Zaitoun from Johns Hopkins University School of Medicine and Jordan University of Science and Technology, examined the potential link between blood type and breast cancer. The research team conducted a systematic review and meta-analysis of 29 previously published studies, involving more than 13,000 breast cancer patients and over 717,000 controls. 

“Researchers searched for studies on breast cancer patients and ABO blood groups across four major databases: PubMed, Scopus, Web of Science, and Google.“

Breast cancer is the most common cancer among women worldwide. Identifying risk factors is vital for early detection and prevention. While many studies have explored lifestyle and genetic causes, this analysis focused on the ABO blood group system. By pooling global data, the researchers found that blood type A was the most common among breast cancer patients and was significantly associated with an 18% increased risk compared to type O.

The study did not find a significant association between breast cancer and blood types B, AB, or Rh factor. Although the results do not prove causation, they point to a biological pattern worth further investigation. Blood group antigens are proteins found on the surface of cells, including breast tissue. These molecules may influence how cancer develops and spreads by interacting with the immune system or affecting cell behavior.

This meta-analysis is the most extensive review to date on this topic, based on studies conducted across Asia, Europe, Africa, and the Americas. While previous research found unclear conclusions, this large-scale evaluation provides stronger evidence for a possible connection between blood type A and breast cancer risk.

Researchers note that regional differences, genetic diversity, and study quality may affect individual results. Nevertheless, the overall trend supports considering blood type A as a potential risk marker. This insight could help shape screening guidelines, encouraging earlier or more frequent checkups for women with this blood type.

Further research is needed to understand why blood type A may play a role in cancer development. Future studies may explore genetic mechanisms, immune responses, and other biological pathways. These efforts could lead the way for more personalized cancer prevention and care strategies.

DOI - https://doi.org/10.18632/oncotarget.28718

Correspondence to - Khaled J. Zaitoun - kzaitou1@jh.edu

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Keywords - cancer, breast cancer, cancer risk factors, blood group antigens, tumor

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Blood Type A Identified as Potential Breast Cancer Risk Factor

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