NIH-funded, four-marker panel could one day help catch one of deadliest cancers at more treatable stages.
National Institutes of Health (NIH)-supported investigators have developed a blood test to find pancreatic ductal adenocarcinoma, one of the deadliest forms of cancer. The new test could improve survival rates from pancreatic cancer, which tends to be diagnosed at late stages when therapy is less likely to be effective. The findings were published in Clinical Cancer Research.
Overall, only about 1 in 10 pancreatic cancer patients survive more than five years from diagnosis. However, experts expect that when the cancer is found and treated at an earlier stage, survival would improve. While finding the cancer early is key, there are no current screening methods to do so.
Although DNA is tightly packed and protected within the cell nucleus, it is constantly threatened by damage from normal metabolic processes or external stressors such as radiation or chemical substances. To counteract this, cells rely on an elaborate network of repair mechanisms. When these systems fail, DNA damage can accumulate, impair cellular function, and contribute to cancer, aging, and degenerative diseases.
One particularly severe form of DNA damage are the so-called DNA–protein crosslinks (DPCs), in which proteins become attached to DNA. DPCs can arise from alcohol consumption, exposure to substances such as formaldehyde or other aldehydes, or from errors made by enzymes involved in DNA replication and repair. Because DPCs can cause serious errors during cell division by stalling DNA replication, DNA–protein crosslinks pose a serious threat to genome integrity.
The enzyme SPRTN removes DPCs by cleaving the DNA-protein crosslinks. SPRTN malfunctions, for example as a result of mutations, may predispose individuals to developing bone deformities and liver cancer in their teenage years. This rare genetic disorder is known as Ruijs-Aalfs syndrome. Its underlying mechanism remains poorly understood, and there are no specific therapies.
Researchers are continually looking for new ways to hack the cellular machinery of microbes like yeast and bacteria to make products that are useful for humans and society. In a new proof-of-concept study, a team from the Carl R. Woese Institute for Genomic Biology showed they can expand the biosynthetic capabilities of these microbes by using light to help access new types of chemical transformations.
The paper, published in Nature Catalysis, demonstrates how the bacteria Escherichia coli can be engineered to produce these new molecules in vivo, using light-driven enzymatic reactions. This framework sets the foundation for future development in the emerging field of photobiocatalysis.
“Photobiocatalysis is basically light-activated catalysis by enzymes. Without light, the target enzyme cannot catalyze a reaction. When light is added, the target enzyme will be activated,” said Huimin Zhao (BSD leader/CAMBERS/CGD/MMG), Steven L. Miller Chair of Chemical and Biomolecular Engineering. “We have published many papers showing that it is possible to combine photocatalysis with enzyme catalysis to create a new class of photoenzymes. These artificial photoenzymes can catalyze selective reactions that cannot be achieved by natural enzymes and are also very difficult, or sometimes even not possible, with chemical catalysis.”
The lower hinge of immunoglobulin G (IgG), an overlooked part of the antibody, acts as a structural and functional control hub, according to a study by researchers at Science Tokyo. Deleting a single amino acid in this region transforms a full-length antibody into a stable half-IgG1 molecule with altered immune activity.
The findings provide a blueprint for engineering next-generation antibody therapies with precisely tailored immune effects for treating diseases such as cancer and autoimmune diseases.
Antibodies are Y-shaped proteins that help the immune system recognize and eliminate foreign threats such as bacteria and viruses. The dominant antibody in the bloodstream is immunoglobulin G (IgG), which accounts for about 75% of circulating antibodies. Its structure is divided into two main functional units connected by a flexible hinge that must work together seamlessly.
A groundbreaking study from Brown University Health researchers has identified a crucial factor that may help improve treatment for glioblastoma, one of the most aggressive and common forms of adult brain cancer. The findings, published November 10 in Cell Reports, reveal how differences among cells within a single tumor influence the cancer’s response to chemotherapy, and introduce a promising new therapy designed to tip the odds in the patients’ favor.
Glioblastoma is notoriously difficult to treat. One of the key reasons is that no two cells within the tumor behave exactly alike. Even inside one tumor, some cells may respond to treatment while others resist it, allowing the cancer to persist and grow. For decades, scientists have known that tumors are composed of diverse cells, but the biological forces driving these differences, and their impact on treatment, have remained elusive.
“Traditionally, researchers have focused on the overall behavior of a tumor by studying the average response across all the individual cells, using differences between the cells to interpret the average,” said senior author Clark Chen, MD, PhD, professor and director of the brain tumor program, department of neurosurgery at Brown University Health. “Our study fundamentally flipped that approach. Rather than focusing on the average response, we focused on the differences between individual cells within the same tumor, and what we found could change how we treat glioblastoma.”
Plants display a wide range of life spans and aging rates. Although dynamic changes to DNA methylation are a hallmark of aging in mammals, it is unclear whether similar molecular signatures reflect rates of aging and organism life span in plants. In this work, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, which causes DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing life span and that shoot apical meristems are protected from these epigenetic changes. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging and that mutants of this program display a complete absence of epigenetic decay while physical aging remains unaffected.
Cancer patients who suffer a heart attack face a dangerous mix of risks, which makes their clinical treatment particularly challenging. As a result, patients with cancer have been systematically excluded from many clinical trials and available risk scores. Until now, doctors had no standard tool to guide treatment in this vulnerable group.
An international team led by researchers from the University of Zurich (UZH) has now developed the first risk prediction model designed specifically for cancer patients who have had a heart attack. The study, published in The Lancet, analyzed more than one million heart attack patients in England, Sweden and Switzerland, including over 47,000 with cancer.
Overall, the results show that cancer patients have a strikingly poor prognosis: nearly one in three died within six months, while around one in 14 suffered a major bleed and one in six experienced another heart attack, stroke or cardiovascular death.