Scientists May Have Found New Approach to Treating Rare Pediatric Tumors
Researchers with The University of Texas MD Anderson Cancer Center published research in the journal Cancer Cell describing potential new approaches to treating malignant rhabdoid tumors (MRT). MRT is a rare pediatric cancer that currently has no effective therapies. The team discovered that the cancers might be sensitive to drugs that block the cancer’s ability to remove misfolded proteins.
“Using an embryonic mosaic approach, we were able to overcome current limitations in technology and create a model that truthfully mimics features of human MRT,” stated Alessandro Carugo, institute research scientist at the Institute for Applied Cancer Science (ACS). “We demonstrated, in our model, that SMARCB1-deficient cells are characterized by dysregulation of protein synthesis and disposal, causing them to be loaded with misfolded protein aggregates.”
The group then designed a drug combination to test their theory. They targeted two mechanisms necessary for clearing protein waste, autophagy and proteasome degradation. When they blocked these in the mouse model, it led to tumor regression. They confirmed it in mouse transplants and human MRT cell lines. They have now initiated a Phase II clinical trial testing a proteasome inhibitor in combination with chemotherapy in patients with renal medullary carcinoma (RMC).
A Deeper Understanding of How Fungus Shut Down the Immune System
The fungus Aspergillus fumigatus is everywhere and for healthy people, it’s no problem. But for people with a weakened immune system, such as AIDS patients or people following an organ transplant, it can be deadly. Scientists with Friedrich Schiller University Jena in Germany have discovered how the fungus knocks out the immune system. They published their research in the journal Cell Chemical Biology.
It has been known for some time that the fungus’s gliotoxin is why the fungus is so deadly. What wasn’t known was that it also suppressed the immune system. The researchers synthetically produced a gliotoxin and brought it into contact with neutrophilic granulocytes, a specific type of immune cells. “Their task is to detect pathogens and eliminate them,” stated Oliver Werz, the study manager of the Institute of Pharmacy at the University of Jena.
When the cells come into contact with a germ, like a fungus, it releases leukotrienes into the blood, which signal to other immune cells. Once enough immune cells gather, they can kill the germ. But if Aspergillus fumigatus is the germ, this doesn’t happen. The gliotoxin inhibits the leukotrieneB4 so they are unable to send a signal to other immune cells. It uses an enzyme, LTA4 hydrolase, to do this.
Do Hibernating Hamsters Offer a Treatment for Alzheimer’s Disease?
Syrian hamsters, which have golden hair, can hibernate for three to four days at a time if it’s cold and dark. Researchers with the Universidad CEU San Pablo in Madrid, Spain and the Universidad Politecnica de Madrid published research in the Journal of Proteome Researchdescribing how in this process the animals’ brains undergo structural and metabolic changes that help neurons survive low temperatures. One of the significant events that occur is the phosphorylation of the tau protein, which is implicated in Alzheimer’s disease.
The researchers wrote, “Our results open up the debate about the possible significance of some metabolites during hibernation, which may possibly be related to tau phosphorylation and dephosphorylation events. In general, this study may provide insights into novel neuroprotective agents because the alterations described throughout the hibernation process are reversible.”
The group, using mass spectrometry to analyze metabolic changes in the hamster’s brain before, during and after hibernation, found a total of 337 compounds that changed during hibernation, including specific amino acids, endocannabinoids and brain cryoprotectants. They especially focused on a group of lipids known as long-chain ceramides, which helped prevent oxidative damage to the brain.
Study: Shorter Radiation Therapy Effective in Prostate Cancer
Researchers with the University of California, Los Angeles (UCLA) conducted a study on men with low- or intermediate-risk prostate cancer. They found that shorter duration of stereotactic body radiotherapy was safe and effective in treating the cancer. It was able to decrease the duration of treatment from 45 days to four to five days. They published their research in the journal JAMA Network Open.
“Most men with low- or intermediate-risk prostate cancer undergo conventional radiation, which requires them to come in daily for treatment and takes an average of nine weeks to complete,” stated lead author Amar Kishan, assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA. “That can be very burdensome on a patient and be a huge interruption in their life. With the improvements being made to modern technology, we’ve found that using stereotactic body radiotherapy, which has a higher dose of radiation, can safely and effectively be done in a much shorter timeframe without additional toxicity or compromising any chance of a cure.”
The researchers followed the men for 6.9 years. Over half had low-risk disease, 32 percent had intermediate-risk disease, and 12 percent had a more aggressive form of intermediate-risk disease. For the low-risk group, recurrence was 4.5 percent. For the less aggressive intermediate-risk group it was 8.6 percent. For the more aggressive intermediate-risk group recurrence was 14.9 percent. Overall, the recurrence was 10.2 percent.
We Like Gummy Bears, But Really? Gummy-Like Robots?
Researchers at the Ecole Polytechnique Federale de Lausanne in Switzerland developedmicroscopic, hydrogel-based muscles. These gummy-muscles can manipulate and mechanically stimulate biological tissues. The researchers believe they have the potential to be used for targeted therapy and for disease diagnosis and prevention. They published their work in the journal Lab on a Chip.
“Our soft actuators contract rapidly and efficiently when activated by near-infrared light,” stated Berna Ozkale, the study’s lead author. “When the entire nanoscale actuator network contracts, it tugs on the surrounding device components and powers the machinery.”
They assembled hydrogel components into a compliant skeleton. They then built tendon-like polymer connections between the skeleton and the microactuators. By doing this in different ways, they were able to build a variety of complicated micromachines.
How the Immune System Triggers Cancer-Promoting Chronic Inflammation
Scientists at Massachusetts General Hospital identified two elements that interact in the immune system to change a protective immune response into chronic, cancer-promoting inflammation. The researchers published their work in the journal PNAS.
“Our research has revealed a critical immunological axis that initiates the development of cancer-promoting chronic inflammation,” stated Shawn Demehri, senior author of the research. “This axis is chronic inflammation’s ‘Achilles heel,’ and blocking it promises to prevent cancer development in chronic inflammation, which accounts for almost 20 percent of all human cancer deaths worldwide.”
Cancers associated with chronic inflammation include colorectal cancer, liver cancer, stomach cancer, and skin cancers. They found that elevated levels of the immune factor IL-33 and regulatory T-cells (Tregs), which suppression tumor-fighting immune cells, create the environment for skin cancer associated with chronic dermatitis and colorectal cancer in colitis patients.