Medical Bulletin 18/October/2022

Targeted and immune therapies to kill treatment-resistant cancer cells: Study

Cancer cells can swiftly adapt to stop targeted medicines from working by attaching directly to and hindering the proteins that cause cancer. Immunotherapies, a second class of drugs, use the immune system to combat cancer cells, but they frequently are unable to "see" the disease-causing alterations taking place inside cancer cells, which appear normal from the outside.

Now, a new study led by researchers from the Perlmutter Cancer Center at NYU Langone Health describes a strategy to overcome these limitations based on several insights. First, the research team recognized that certain targeted drugs called "covalent inhibitors" form stable attachments with the disease-related proteins they target inside cancer cells. They also knew that proteins once inside cells are naturally broken down and presented as small pieces (peptides) on cell surfaces by major histocompatibility complex (MHC) molecules. Once bound to MHC, peptides are recognized as foreign by the immune "surveillance" system if they are sufficiently different from the body's naturally occurring proteins.

Ref:

Shohei Koide et al,Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy,Cancer Discovery,DOI10.1158/2159-8290.CD-22-1074/709728

Brain molecule responsible for boosting body's ability to fight neurodegenerative diseases

Many neurodegenerative diseases, including Alzheimer's and MS, are thought to be caused by the brain's inability to cleanse itself of toxic buildup. Recent advances in neuroscience research have shed light on the importance of microglia in removing harmful debris from the brain, but recent UVA's new discovery offers practical insights into how this cleaning process occurs – and the dire consequences when it doesn't.

UVA Health researchers have discovered a molecule in the brain responsible for orchestrating the immune system's responses to Alzheimer's disease and multiple sclerosis (MS), potentially allowing doctors to supercharge the body's ability to fight those and other devastating neurological diseases.

Ref:

journal Cell. The team consisted of Ennerfelt,Frost, Daniel A. Shapiro, Holliday, Kristine E. Zengeler, Gabrielle Voithofer, Ashley C. Bolte, Catherine R. Lammert, Joshua A. Kulas, Tyler K. Ulland and Lukens.

Patients with lung disease poorly affected by vehicular and factory-related air pollution

According to recent research done by University of Pittsburgh experts, those who live in locations with greater levels of air pollution made up of chemicals linked to industrial sources and vehicular traffic have a higher risk of dying from a disease that causes lung scarring but has no known cause.

The study, which was published in JAMA Internal Medicine, is the first to establish a connection between worsening fibrotic interstitial lung disease (fILD) outcomes and the chemical makeup of fine particulate air pollution. Additionally, it is the largest study yet conducted to gauge how these individuals are affected by air pollution.

"Some people with these lung diseases have an expected lifespan from diagnosis to death of only a few years, and yet it's a mystery as to why they developed the disease, why their lungs become so scarred," said lead author Gillian Goobie, M.D., doctoral candidate in the Pitt School of Public Health's Department of Human Genetics. "Our study points to air pollution – specifically pollutants from factories and vehicles – as potentially driving faster disease progression and premature death in these patients."

Ref:

Gillian Goobie, et al,JAMA Internal Medicine,DOI:10.1001/jamainternmed.2022.4696

Harsh parenting can induce depressive symptoms later by hard-wiring changes into DNA

The way the body interprets the children's DNA can change as a result of strict parenting. Children who experience their parents as harshly can really experience these changes becoming "hard-wired" into their DNA, which increases their biological risk for depression in adolescence and later in life.

Presenting the work at the ECNP Congress in Vienna, Dr Evelien Van Assche said:

"We discovered that perceived harsh parenting, with physical punishment and psychological manipulation, can introduce an additional set of instructions on how a gene is read to become hard-wired into DNA. We have some indications that these changes themselves can predispose the growing child to depression. This does not happen to the same extent if the children have had a supportive upbringing".

Ref:

E. Van Assche1, E. Vangeel2, K. Van Leeuwen3, H. Colpin4, K. Verschueren4, W. Van den Noortgate5, L. Goossens4, S. Claes2 Strict parenting may hard-wire depression risk into a child's, DNA EUROPEAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY MEETING, 35th Congress of the European College of Neuropsychopharmacology (ECNP)