Researchers are rewriting the chemical tags on DNA and chromatin to tune gene expression.
Category: biotech/medical – Page 92
Early warning signs of potential drug resistance in schistosomiasis parasite revealed
Scientists have identified genetic changes in wild populations of the parasitic worm that causes schistosomiasis that may reduce its response to praziquantel, the only available treatment. The study provides an early warning for disease control and elimination programs.
Researchers from the Wellcome Sanger Institute, the Royal Veterinary College (RVC) and Medical College of Wisconsin (MCW) led a large-scale international collaboration analyzing hundreds of Schistosoma mansoni genomes collected from people in several African and Caribbean countries. The study is the largest genomic analysis of the parasite from human infections to date.
Published in Science Advances, the findings highlight the need for ongoing genomic surveillance to help protect the long-term effectiveness of praziquantel.
Current and future immunotherapeutic approaches in pancreatic cancer treatment
PDAC carcinogenesis like all the solid tumors is mediated by the gradual build-up of driver mutations, such as the oncogene KRAS (G12D mutation) [6– 9] and the tumor suppressor gene TP53 [10, 11]. These molecular modifications are accompanied by corresponding histological alterations during different stages of PDAC development [12]. The morphological progression initiates with the formation of precursor lesions known as pancreatic intraepithelial neoplasia (PanIN) [13], which then advance to invasive adenocarcinoma. Changes in the surrounding tissue stroma occur as cancer continues to advance. The non-transformed tissue stroma, composed of components such as immunological, vascular, and connective tissue, plays a vital role in maintaining homeostasis in response to damage. However, cancer exploits these physiological responses to create a favorable tumor microenvironment (TME) for its efficient growth [12, 14]. Indeed, cancer resembles “persistent wounds”, and alterations in the stroma are the outcome of “abnormal wound healing” [15].
Immunotherapeutic strategies possess a significant capability in inducing strong immune responses against tumors. Immunomodulators, immune checkpoint blockade (ICB), and adoptive cell transfer therapy could potentially offer hopeful strategies [16 – 18]. Remarkable outcomes have been achieved from 2010 to the present through clinical research that utilizes various immunotherapeutic approaches to treat patients with different types of cancer [19 – 22]. The immune responses specifically targeting cancer cells, triggered by immunotherapy, differ from those stimulated by tumor-directed therapies. Furthermore, these responses can endure for a prolonged period even after the treatment is discontinued [23, 24]. However, the application of immunotherapy yields insufficient results for the vast majority of PDACs. This is predominantly attributed to the characteristics of its TME, which is deficient in effector T cells that have previously been exposed to antigens [25].
Tumor immunotherapy has revolutionized the treatment of various solid tumors. Nevertheless, current immunotherapies have had limited success in improving survival for patients with PDAC [26, 27]. The immunological resistance of PDAC to immunotherapies can be attributed to its low mutational burden and the hostile TME characterized by fibrosis, hypoxia, and immunosuppression [28 – 30]. However, a meta-analysis suggested that targeted immunotherapy is more effective than standard treatments in increasing survival and enhancing immune responses in pancreatic cancer patients [31]. Moreover, combining chemotherapy and surgery with other immunotherapies may synergistically improve outcomes. Various cytotoxic drugs and adjuvant therapies have been shown to sensitize the TME to immunotherapy by inducing immunogenic cell death, modifying evasive immune processes, and reducing immune suppression [32, 33].
New machine-learning equation accurately assess LDL cholesterol risk
The Martin-Hopkins equation to assess low-density lipoprotein (LDL) cholesterol levels in blood samples has been used by laboratories in the U.S. and other countries to guide efforts to lower cardiovascular disease risk. Now, a simplified machine-learning version of this equation has been shown in a study of millions of U.S. adult and child blood samples to match the accuracy of the original—making it broadly accessible. The findings and code were published in JAMA Cardiology.
“We’ve optimized the calculation of LDL cholesterol and made this equation accessible and easier for all labs to implement,” says Seth Martin, M.D., M.H.S., the senior study author and director of the Advanced Lipid Disorders Program and Digital Health Lab at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease.
“Our goal is to enable clinicians and patients to make better decisions about starting treatments that prevent heart attacks and strokes and save lives.”
UCLA scientists develop offtheshelf immunotherapy for ovarian cancer
When the team tested the novel CAR-NKT therapy on 35 ovarian patient-derived tumor samples, the results were striking. The CAR-NKT cells successfully killed ovarian cancer cells in every single sample — including samples from both newly diagnosed patients and patients whose cancers had recurred after chemotherapy.
“Combating this high rate of recurrence in ovarian cancer is my career mission,” said co-senior author Memarzadeh, a professor of obstetrics and gynecology and a member of the UCLA Broad Stem Cell Research Center and the UCLA Health Jonsson Comprehensive Cancer Center. “When I see these results, I know we’re getting closer to offering patients like mine a more effective and permanent solution.”
Sugarcoated nanoparticles show promise for treating most aggressive form of brain cancer
Sugar-coated nanoparticles show promise against glioblastoma.
Researchers have developed mannose-coated lipid nanoparticles capable of crossing the blood-brain barrier and delivering therapeutic PTEN mRNA directly to glioblastoma cells, one of the deadliest forms of brain cancer.
Glioblastoma cells have an exceptionally high demand for glucose. By coating the nanoparticles with a sugar molecule called mannose, the researchers took advantage of this metabolic feature, allowing the particles to enter the brain more efficiently and accumulate within tumors.
Once inside the cancer cells, the nanoparticles restored production of PTEN, a critical tumor-suppressor protein that is frequently lost or dysfunctional in glioblastoma. In mouse models, this approach significantly slowed tumor growth, increased median survival by approximately 50%, and showed no measurable toxicity in major organs.
Although these findings are still preclinical and have not yet been tested in humans, they represent an exciting advance in overcoming one of neuro-oncology’s greatest challenges: safely delivering targeted therapies across the blood-brain barrier.
PORTLAND, Ore. – Researchers at Oregon State University have potentially found a new way to treat the most aggressive form of brain cancer, glioblastoma, whose two-year survival rate is less than 30%.
New research clears the way to healing lung diseases
Pulmonary fibrosis is a deadly disease in which scar tissue grows in the lungs, making breathing more difficult. Approximately 2,170 Australians are diagnosed annually with idiopathic pulmonary fibrosis (IPF), a form of the disease with no known cause and very few treatments.
“In pulmonary fibrosis, the normal wound-healing process in the body goes wrong. Instead of repairing damaged tissue, it starts to produce scar tissue in the lungs,” said Associate Professor Gang Liu from the University of Technology Sydney (UTS) School of Life Sciences.
“People with idiopathic pulmonary fibrosis have a very short survival time, usually only two to five years from diagnosis. Only two drugs are approved to treat it, and neither can reverse the scarring and cure the disease.”