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Breast Cancer

Mapping the Origins of Stomach Cancer: Uncovering Early Mutations and Risk Factors

Researchers have made significant advancements in understanding the earliest stages of stomach cancer, a leading cause of cancer-related deaths worldwide, through two recent innovative studies. With a prevalence rates particularly high in East Asia, including China, this cancer often stems from chronic inflammation caused by Helicobacter pylori infection, which affects approximately 15% of the Hong Kong population. This inflammation can lead to a pre-cancerous stage known as intestinal metaplasia. The innovative studies have uncovered crucial insights into the earliest changes in the stomach that contribute to the development of stomach cancer, laying the foundation for improved prevention and early detection, ultimately saving lives.
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The researchers at the Department of Pathology, School of Clinical Medicine at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) have made significant strides in understanding the earliest stages of stomach cancer, a leading cause of cancer-related deaths worldwide. Through two innovative studies, they have uncovered crucial insights into the early changes in the stomach that contribute to the development of stomach cancer, laying the foundation for improved prevention and early detection.

While the stomach’s acidic environment aids digestion, it can induce cancer-causing mutations in normal stomach tissues as individuals age. However, the timing and mechanisms of these early changes and how they promote the progression to cancer remain largely unknown. The HKUMed researchers provided valuable insights into these processes.

Mapping the Origins of Stomach Cancer

In a collaborative study, researchers from HKUMed, the Wellcome Sanger Institute, and the Broad Institute of MIT and Harvard analyzed genetic mutations in normal stomach lining tissue using advanced genome sequencing. For the first time, they sequenced whole genomes from 238 samples and performed targeted sequencing on an additional 829 samples from individuals with and without stomach cancer in Hong Kong, the US, and the UK.

The study revealed that despite the stomach’s harsh acidic environment, the stomach lining has protective mechanisms that prevent significant mutations. The researchers found that the number of mutations increases with age, with normal stomach glands accumulating approximately 28 mutations annually. In stomach cancer patients, the mutation rate is more than double, especially in the metaplastic glands.

Professor Leung Suet-yi, co-lead author of the research and Chairperson of the Department of Pathology, School of Clinical Medicine, HKUMed, said, “By age 60, nearly 10% of the stomach lining has mutations in known cancer genes, highlighting a gradual accumulation of potential cancer-causing changes over decades. The most surprising finding was that some stomach regions exhibited chromosome abnormalities linked to chronic inflammation.”

Risk Factors and Pre-cancer Model

The researchers identified risk factors for stomach cancer, including smoking, excessive alcohol drinking, a high salt diet, and a Helicobacter pylori infection. Professor Leung elaborated, “Our multinational team found that individuals with long-term stomach inflammation had significantly more mutations or extra chromosomes, indicating the potential role of inflammation in shaping a pre-cancer environment from an early age.”

World’s First Biobank of ‘Intestinal Metaplasia’ Organoid Models

In a related study, researchers from HKUMed and the InnoHK Centre for Oncology and Immunology investigated intestinal metaplasia (IM) in which stomach cells are transformed to resemble intestine cells. This transformation significantly increases the risk of developing stomach cancer, but the process remains poorly understood.

Co-led by Professor Helen Yan Hoi-ning, Assistant Professor in the Department of Pathology at HKUMed, and Professor Suet Yi Leung, the study used organoid culture to make a 3D model of IM. Organoids, tiny versions of organs grown in the lab from a patient’s tissue, provide a realistic model for studying the progression of IM to cancer.

The study revealed that IM organoids contain ‘hybrid’ cells with a mix of both stomach and intestinal characteristics. Typically associated with cancer cells, these traits facilitate tissue spread and make identifying early warning signs crucial. Professor Yan explained, “Using organoid technology, we can identify early changes when stomach cells become pre-cancerous.”

Harnessing Innovation for Early Detection and Prevention

By uncovering the earliest mutations and risk factors associated with stomach cancer and developing a sophisticated pre-cancer model, these studies offer invaluable insights for current prevention and early detection strategies. Professor Leung Suet-yi said, “With a living cell model now available, the potential for drug development to reverse IM becomes increasingly achievable.”

These breakthroughs provide new hope in the fight against stomach cancer, potentially transforming patient outcomes and clinical practices. The findings of these studies have significant implications for the prevention and early detection of stomach cancer, offering new avenues for research and treatment that can improve patient lives worldwide.

Source:The University of Hong Kong
Original Link:https://www.sciencedaily.com/releases/2025/04/250416135743.htm
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Anxiety

Single Psilocybin Dose Delivers Long-Term Depression Relief for Cancer Patients

Psilocybin, the active ingredient in magic mushrooms, might just revolutionize how depression and anxiety are treated in cancer patients. In a groundbreaking trial, a single dose combined with therapy significantly reduced emotional suffering, and these effects often lasted over two years. As follow-up studies expand the research to multiple doses and larger samples, scientists are eyeing a possible new standard of care that merges psychedelics with psychological support.
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June 17, 2025

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A groundbreaking clinical trial has revealed that a single dose of psilocybin, a naturally occurring psychedelic compound found in mushrooms, can provide sustained reductions in depression and anxiety in individuals with cancer suffering from major depressive disorder. The findings, published in the peer-reviewed journal CANCER, suggest that this treatment approach may offer long-term relief for cancer patients struggling with depression.

The study involved 28 participants who received psychological support from a therapist prior to, during, and after receiving a single 25-mg dose of psilocybin. Two years later, a significant proportion of these individuals demonstrated lasting reductions in depression and anxiety. Specifically:

* 53.6% (15 patients) showed a sustained reduction in depression.
* 50% (14 patients) experienced remission from depression as well as reduced anxiety.
* 42.9% (12 patients) reported reduced anxiety at the two-year mark.

Building on these promising results, an ongoing randomized, double-blind trial is currently evaluating up to two doses of 25 mg of psilocybin versus placebo for treating depression and anxiety in cancer patients. This study aims to determine whether repeating the treatment can resolve depression for more than half of the participants.

According to lead author Manish Agrawal, MD, from Sunstone Therapies, “One dose of psilocybin with psychological support has a long-term positive impact on relieving depression for as much as 2 years for a substantial portion of patients with cancer. If randomized testing shows similar results, this could lead to greater use of psilocybin to treat depression in patients with cancer.”

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Brain Tumor

Groundbreaking Treatment Breakthrough: Electric Fields Supercharge Immune Assault on Brain Cancer

A breakthrough study from Keck Medicine of USC may have found a powerful new triple therapy for glioblastoma, one of the deadliest brain cancers. By combining Tumor Treating Fields (TTFields), which deliver electric waves into tumors, with immunotherapy and chemotherapy, researchers saw a major boost in survival.
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June 10, 2025

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A new study has made a groundbreaking discovery in the treatment of glioblastoma, a type of brain cancer with few effective treatments available. Researchers from Keck Medicine of USC have found that combining Tumor Treating Fields (TTFields) therapy with immunotherapy and chemotherapy can significantly extend survival rates among patients diagnosed with glioblastoma.

Glioblastoma is a highly aggressive form of brain cancer, with an average survival rate of only eight months. The National Brain Tumor Society reports that the prognosis for glioblastoma remains poor, even with aggressive treatment. However, this new study has shown promising results, demonstrating a 70% increase in overall survival when TTFields are used alongside immunotherapy and chemotherapy.

TTFields work by delivering targeted waves of electric fields directly into tumors to stop their growth and signal the body’s immune system to attack cancerous tumor cells. This approach is particularly effective for glioblastoma, as it disrupts the tumor’s ability to evade the immune response.

In this study, patients who received TTFields combined with chemotherapy and immunotherapy lived approximately 10 months longer than those who had used the device with chemotherapy alone in the past. Those with large, inoperable tumors showed an even stronger immune response to TTFields, living approximately 13 months longer compared to patients who underwent surgical removal of their tumors.

The lead researcher on this study, Dr. David Tran, a neuro-oncologist at Keck Medicine, explained that by using TTFields with immunotherapy, the body is “primed” to mount an attack on the cancer, enabling the immunotherapy to have a meaningful effect in ways it could not before. This approach represents a significant breakthrough in the treatment of glioblastoma.

This study demonstrates that combining TTFields with immunotherapy triggers a potent immune response within the tumor – one that ICIs can then amplify to bolster the body’s own defense against cancer. “Think of it like a team sport – immunotherapy sends players in to attack the tumor (the offense), while TTFields weaken the tumor’s ability to fight back (the defense),” Dr. Tran explained.

The findings of this study have significant implications for the treatment of glioblastoma and offer new hope for patients who previously had limited options. Further studies are needed to determine the optimal role of surgery in this setting, but these results may offer a glimmer of light for those affected by this devastating disease.

As Dr. Tran noted, “Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option.” The multicenter Phase 3 clinical trial is currently underway at 28 sites across the United States, Europe, and Israel, with over 740 patients expected to be enrolled through April 2029.

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Brain Tumor

The Hidden DNA Repair System: Unlocking New Cancer Treatment Strategies

A powerful new discovery reveals that Nup98 a protein once thought to only ferry molecules through the nucleus plays a vital role in safeguarding the most vulnerable areas of DNA. By forming droplet-like ‘bubbles’ around damaged DNA within dense regions called heterochromatin, Nup98 safely escorts the damaged segments to repair zones and times the involvement of risky repair proteins. This precise choreography prevents genetic errors that could trigger cancer or speed up aging.
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June 8, 2025

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The Hidden DNA Repair System: Unlocking New Cancer Treatment Strategies

Imagine your body’s cells as tiny factories, working tirelessly to repair damaged DNA strands. When these repairs go awry, it can lead to devastating consequences – including cancer. A recent breakthrough by scientists at USC Dornsife College of Letters, Arts and Sciences has revealed a crucial protein called Nup98 that plays a surprising role in guiding the cell’s delicate repairs.

Nup98 forms droplet-like structures deep within the nucleus, creating protective bubbles around broken DNA strands. These “condensates” act as temporary shields, keeping out certain repair proteins that can cause trouble if they arrive too soon. By coordinating this carefully staged process, Nup98 helps cells avoid genetic mistakes that can lead to cancer.

Researchers Irene Chiolo and Chiara Merigliano, with support from the National Institutes of Health, the National Science Foundation, and the American Cancer Society, have made groundbreaking discoveries about Nup98’s role in DNA repair. Their findings, published in Molecular Cell, shed light on how this protein guides damaged heterochromatin – a densely packed zone within the nucleus where accurate repairs are especially challenging.

By mobilizing damaged sites out of tightly packed heterochromatin and into safer areas for repair, Nup98 reduces the risk of genetic mix-ups that can lead to cancer. This process is essential for maintaining genome stability and slowing processes responsible for aging and disease.

The implications of this discovery are significant, particularly in the context of acute myeloid leukemia, where mutations in Nup98 have been linked to the development of the disease. By understanding how Nup98 guides DNA repair, scientists hope to uncover why its mutations are so dangerous – and how to harness these mutations to disrupt cancer cells in targeted treatments.

In the long term, this research may also lead to therapies that enhance or mimic Nup98’s protective functions, reducing the risk of genome instability, which is a major factor not only in cancer but also in aging and other genome instability disorders. The potential for new cancer treatment strategies and improved understanding of DNA repair mechanisms is vast – and holds promise for the future of human health.

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