Lifeboat Foundation

K-Ras mutations are all too familiar as drivers of cancer. And until recently, they were considered all but undruggable. But ever since the arrival of sotorasib and adagrasib—two FDA-approved K-Ras-G12C inhibitors—K-Ras mutations have had the distinction of being somewhat druggable. Even better, K-Ras mutations may soon become yet more druggable. Scientists at the University of California, San Francisco, have found a way to target K-Ras-G12D mutations, which are especially prevalent in pancreatic ductal adenocarcinoma.

The scientists were led by Kevan Shokat, PhD, a professor in the department of cellular and molecular pharmacology. Back in 2013, Shokat and colleagues developed the first K-Ras-G12C inhibitors. And today, in Nature Chemical Biology, they present a paper (“Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D”) describing how they designed a candidate drug that could help make pancreatic cancer, which is almost always fatal, a treatable and perhaps even curable condition.

“[Covalent] inhibition of G12D, the most frequent K-Ras mutation particularly prevalent in pancreatic ductal adenocarcinoma, has remained elusive due to the lack of aspartate-targeting chemistry,” the article’s authors wrote. “Here we present a set of malolactone-based electrophiles that exploit ring strain to crosslink K-Ras-G12D at the mutant aspartate to form stable covalent complexes.”

An endoscopic mapping device, developed over the course of a decade by scientists at the Auckland Bioengineering Institute, consists of an inflatable sphere covered in sensors, delivered down the esophagus and able to measure electrical activity in the gut.

In the same way, abnormal heart electrical signals can cause serious heart problems, research has found faulty bioelectric gut waves can lead to stomach pain, nausea, vomiting and bloating.

But often doctors can’t find out what the problem is. That’s because gut electrics aren’t nearly as strong or as easily measured as heart waves; without surgery it’s hard to know if someone has a so-called ‘dysrhythmic’ gut—and if so, where the problem is.

As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina, which are impaired because of a genetic mutation, to manufacture the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a group of disorders of varying severity and prevalence that affect one out of every few thousand people worldwide.

An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that results in persistent lung infection and affects 30,000 people in the U.S., with about 1,000 new cases identified every year. One faulty gene—the cystic fibrosis transmembrane conductance regulator, or CFTR—causes the disease, which is characterized by lung dehydration and mucus buildup that blocks the airway.

The thiophene-based LNP study, which involved mice and non-human primates, stems from a $3.2 million grant from the National Eye Institute. The grant’s purpose is addressing limitations associated with the current primary means of delivery for gene editing: adeno-associated virus, or AAV.

Lymphedema is a chronic condition that affects many cancer survivors. It’s swelling caused by a buildup of lymph fluid, often as a result of cancer treatment. While it can’t be prevented, treatment can help to relieve swelling and improve the ability to function day to day.

Lymphedema is a side effect of some cancer treatments. Learn about symptoms and ways you can manage and treat swelling in your arm or leg caused by

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A significant reduction of GABA and monoamine oxidase B (MOAB), the latter of which is an astrocytic enzyme that produces GABA, was also observed in Crym KO mice. These observations suggest that increased synaptic excitation from IOFC terminals leads to lower levels of tonic GABA, which causes reduced presynaptic inhibition.

Study significance

Continue reading “Key brain cells linked to repetitive behaviors in psychiatric diseases” »

Durable remission was achieved with front-line dasatinib plus blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

NEJM Journal Watch reviews over 250 scientific and medical journals to present important clinical research findings and insightful commentary.

For decades, scientists and pathologists have tried, without much success, to come up with a way to determine which individual lung cancer patients are at greatest risk of having their illness spread, or metastasize, to other parts of the body.

Now a team of scientists from Caltech and the Washington University School of Medicine in St. Louis has fed that problem to artificial intelligence (AI) algorithms, asking computers to predict which cancer cases are likely to metastasize. In a novel pilot study of non-small cell lung cancer (NSCLC) patients, AI outperformed expert pathologists in making such predictions.

These predictions about the progression of lung cancer have important implications in terms of an individual patient’s life. Physicians treating early-stage NSCLC patients face the extremely difficult decision of whether to intervene with expensive, toxic treatments, such as chemotherapy or radiation, after a patient undergoes lung surgery. In some ways, this is the more cautious path because more than half of stage I–III NSCLC patients eventually experience metastasis to the brain. But that means many others do not. For those patients, such difficult treatments are wholly unnecessary.

Colchicine reduced cardiovascular events in patients with diabetes and recent myocardial infarction in a randomized study.

NEJM Journal Watch reviews over 250 scientific and medical journals to present important clinical research findings and insightful commentary.

A Tufts School of Medicine researcher is developing a test to predict lung cancer risk more accurately and reduce the number of scans to detect the condition.