Tag Archives: cancer
Michael Wallace has performed hundreds of colonoscopies in his 20 years as a gastroenterologist. He thinks he’s pretty good at recognizing the growths, or polyps, that can spring up along the ridges of the colon and potentially turn into cancer. But he isn’t always perfect. Sometimes the polyps are flat and hard to see. Other times, doctors just miss them. “We’re all humans,” says Wallace, who works at the Mayo Clinic. After a morning of back-to-back procedures that require attention to minute details, he says, “we get tired.”
Colonoscopies, if unpleasant, are highly effective at sussing out pre-cancerous polyps and preventing colon cancer. But the effectiveness of the procedure rests heavily on the abilities of the physician performing it. Now, the Food and Drug Administration has approved a new tool that promises to help doctors recognize precancerous growths during a colonoscopy: an artificial intelligence system made by Medtronic. Doctors say that alongside other measures, the tool could help improve diagnoses.
“We really have the opportunity to completely wipe out colon cancer in anybody who gets screened,” says Wallace, who consulted with Medtronic on the project.
The Medtronic system, called GI Genius, has seen the inside of more colons than most doctors. Medtronic and partner Cosmo Pharmaceuticals trained the algorithm to recognize polyps by reviewing more than 13 million videos of colonoscopies conducted in Europe and the US that Cosmo had collected while running drug trials. To “teach” the AI to distinguish potentially dangerous growths, the images were labeled by gastroenterologists as either normal or unhealthy tissue. Then the AI was tested on progressively harder-to-recognize polyps, starting with colonoscopies that were performed under perfect conditions and moving to more difficult challenges, like distinguishing a polyp that was very small, only in range of the camera briefly, or hidden in a dark spot. The system, which can be added to the scopes that doctors already use to perform a colonoscopy, follows along as the doctor probes the colon, highlighting potential polyps with a green box. GI Genius was approved in Europe in October 2019 and is the first AI cleared by the FDA for helping detect colorectal polyps. “It found things that even I missed,” says Wallace, who co-authored the first validation study of GI Genius. “It’s an impressive system.”
No one enjoys getting a biopsy, in which a tissue sample is surgically taken and analyzed in a lab for signs of disease, such as cancer. It’s not only unpleasant for the patient, but has clinical drawbacks: A biopsy doesn’t always extract the diseased tissue and isn’t helpful in detecting disease at early stages. These concerns have encouraged researchers to find less invasive and more accurate diagnostic methods. Prof. Nir Friedman and Ronen Sadeh of the Hebrew University of Jerusalem have developed a blood test that enables lab technicians to diagnose cancer and diseases of the heart and liver by identifying and determining the state of the dead cells throughout the body.
Millions of cells die every day and are replaced by new cells. When cells die, their DNA is fragmented. Some of these DNA fragments reach the blood and can be “read” by advanced DNA sequencing methods.
“As a result of these scientific advancements, we understood that if this information is maintained within the DNA structure in the blood, we could use that data to determine the tissue source of dead cells and the genes that were active in those very cells. Based on those findings, we can uncover key details about the patient’s health,” Friedman said.
“We are able to better understand why the cells died — whether it’s an infection or cancer — and based on that, be better positioned to determine how the disease is developing,” he said. Co-author Israa Sharkia added the simple blood test could “be administered often and quickly, allowing the medical staff involved to follow the presence or development of a disease more closely.”
A startup company, Senseera, has been established to pursue clinical testing of this innovative approach in partnership with major pharmaceutical companies.
The multi-author study published in Nature Biotechnology explains the test can even identify markers that may differentiate between patients with similar tumors, which could help physicians develop personalized treatments.
For the second time, cancer researchers at Vanderbilt have discovered a protein that—when genetically manipulated to impede it from interacting with a gene responsible for cancer genesis—effectively melts tumors in days.
William Tansey, professor of cell and developmental biology, is dedicated to understanding how the oncogene MYC, an highly conserved, noodle-like protein, works. It performs important functions in normal human development, and it often becomes reactivated in the deadliest and most difficult to treat cancers.
Conducted experiment shows six tumor sizes grow for 15 days, at which point the MYC–HCF1 interaction is broken. After day 15, the tumors shrink and are gone. Cancer cells are dead by four days.
“MYC becomes the nitro in the tank, driving relentless rounds of cell duplication and division,” Tansey said. “The faster the cells grow and divide, they accumulate mutations, which give rise to cancer growth.”
MYC has been an elusive drug target for at least 30 years, Tansey says, and has been considered “undruggable” because of its lack of structure. To work around this roadblock, Tansey set out to identify MYC’s more structured partner proteins with the goal of engineering mutations that disrupt the partners’ interactions with MYC that cause cancer growth. “If we can validate the physical contact between MYC and a protein, we can go after it therapeutically,” Tansey explained.
Tansey and his collaborators have identified the protein Host Cell Factor-1 (HCF1) as a definite candidate for this type of therapeutic development. HCF1 is touched by MYC and is important for stimulating protein synthesis. When a cancer cell with MYC is genetically engineered to no longer interact with HCF1, the cancer cell begins to self-destruct. Developing a therapy that limits this interaction is a hugely promising step in cancer treatment.
The article, “MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1,” was published in the journal eLIFE on Jan. 8.
The aging global population is the greatest challenge faced by 21st-century healthcare systems. Even COVID-19 is, in a sense, a disease of aging. The risk of death from the virus roughly doubles for every nine years of life, a pattern that is almost identical to a host of other illnesses. But why are old people vulnerable to so many different things?
It turns out that a major hallmark of the aging process in many mammals is inflammation. By that, I don’t mean intense local response we typically associate with an infected wound, but a low grade, grinding, inflammatory background noise that grows louder the longer we live. This “inflammaging” has been shown to contribute to the development of atherosclerosis (the buildup of fat in arteries), diabetes, high blood pressure , frailty, cancer and cognitive decline.
Now a new study published in Nature reveals that microglia — a type of white blood cells found in the brain — are extremely vulnerable to changes in the levels of a major inflammatory molecule called prostaglandin E2 (PGE2). The team found that exposure to this molecule badly affected the ability of microglia and related cells to generate energy and carry out normal cellular processes.
Fortunately, the researchers found that these effects occurred only because of PGE2’s interaction with one specific receptor on the microglia. By disrupting it, they were able to normalize cellular energy production and reduce brain inflammation. The result was improved cognition in aged mice. This offers hope that the cognitive impairment associated with growing older is a transient state we can potentially fix, rather than the inevitable consequence of aging of the brain. Levels of PGE2 increase as mammals age for a variety of reasons — one of which is probably the increasing number of cells in different tissues entering a state termed cellular senescence. This means they become dysfunctional and can cause damage to tissue by releasing PGE2 and other inflammatory molecules.
But the researchers also found that macrophages — another type of white blood cells related to microglia — from people over the age of 65 made significantly more PGE2 than those from young people. Intriguingly, exposing these white blood cells to PGE2 suppressed the ability of their mitochondria — the nearest thing a cell has to batteries — to function. This meant that the entire pattern of energy generation and cellular behavior was disrupted.
Although PGE2 exerts its effects on cells through a range of receptors, the team were able to narrow down the effect to interaction with just one type (the “EP2 receptor” on the macrophages). They showed this by treating white blood cells, grown in the lab, with drugs that either turned this receptor on or off. When the receptor was turned on, cells acted as if they had been exposed to PGE2. But when they were treated with the drugs that turned it off, they recovered. That’s all fine, but it was done in a petri dish. What would happen in an intact body?
The researchers took genetically modified animals in which the EP2 receptor had been removed and allowed them to grow old. They then tested their learning and memory by looking at their ability to navigate mazes (something of a cliche for researchers) and their behavior in an “object location test.” This test is a bit like someone secretly entering your house, swapping your ornaments around on the mantelpiece and then sneaking out again. The better the memory, the longer the subject will spend looking suspiciously at the new arrangement, wondering why it has changed.
It turned out that the old genetically modified mice learned and remembered just as well as their young counterparts. These effects could be duplicated in normal old mice by giving them one of the drugs that could turn the EP2 receptor off for one month. So it seems possible that inhibiting the interaction of PGE2 with this particular receptor may represent a new approach to treating late-life cognitive disorders.
Chemotherapy could be up to 34 per cent more effective thanks to a new technique which combines the treatment with magnetic particles that fry cancerous cells. Researchers at University College London (UCL) found the combination of heat and chemo drugs makes the process more effective. Tiny magnetic nanoparticles attach themselves to the cancerous cells of a tumour and also carry the chemotherapy drug.
When doctors apply a harmless magnetic field to the area from outside the body it activates the nanoparticles’ magnetic properties and causes them to warm up, heating the trapped cancerous cells. Research reveals this damages the tumour and makes it more vulnerable to pre-existing drugs.
The research has so far only been tested in a lab, but researchers say the early findings are significant. Human breast cancer cells, glioblastoma (brain cancer) cells, and mouse prostate cancer cells were all treated, in a test tube, with this new technique. Doxorubicin — a commonly used chemo drug — was applied to the magnetic nanoparticles. Heat and doxorubicin together killed 98 per cent of brain cancer cells after 48 hours. The drug only killed 73 per cent of cells when applied without heat. For the breast cancer cells, 89 per cent of the cancer was eliminated by the combination, and this drops to just 77 per cent for the drug alone.
‘Our study shows the enormous potential of combining chemotherapy with heat treatment delivered via magnetic nanoparticles,” said Senior author Professor Nguyen T. K. Thanh. ‘While this combination of therapy is already approved for the treatment of fast-growing glioblastomas, our results suggest it has potential to be used more widely as a broad anti-cancer therapy. ‘This therapy also has potential to reduce the side effects of chemotherapy, by ensuring it is more highly targeted on cancer cells rather than healthy issue. This needs to be explored in further pre-clinical tests.’
The results have been published in the Journal of Materials Chemistry B,
Immunotherapies, such as checkpoint inhibitor drugs, have made worlds of difference for the treatment of cancer. Most clinicians and scientists understand these drugs to act on what’s known as the adaptive immune system, the T cells and B cells that respond to specific threats to the body.
New research from an international team co-led by George Hajishengallis of the University of Pennsylvania School of Dental Medicine suggests that the innate immune system, which responds more generally to bodily invaders, may be an important yet overlooked component of immunotherapy’s success.
Their work, published in the journal Cell, found that “training” the innate immune system with β-glucan, a compound derived from fungus, inspired the production of innate immune cells, specifically neutrophils, that were primed to prevent or attack tumors in an animal model.
“The focus in immunotherapy is placed on adaptive immunity, like checkpoint inhibitors inhibit the interaction between cancer cells and T cells,” says Hajishengallis, a co-senior author on the work. “The innate immune cells, or myeloid cells, have not been considered so important. Yet our work suggests the myeloid cells can play a critical role in regulating tumor behavior.”
The current study builds on earlier work published in Cell by Hajishengallis and a multi-institutional team of collaborators, which showed that trained immunity, elicited through exposure to exposure to the fungus-derived compound β-glucan, could improve immune recovery after chemotherapy in a mouse model.
In that previous study, the researchers also showed that the “memory” of the innate immune system was held within the bone marrow, in hematopoetic stem cells that serve as precursors of myeloid cells, such as neutrophils, monocytes, and macrophages.
We’ve long been warned of the risks of dyeing hair at home and in salons. Products used can cause allergies and skin irritation — an estimated one percent of people have an allergy to dye. Furthermore, repeated use of some dyes has been linked to cancer. But there soon may be a solution for the growing list of salons and hair color enthusiasts searching for natural alternatives to dyes and cosmetics.
Northwestern University researchers have developed a new way to create a spectrum of natural-looking hair colors, ranging from blond to black, by using enzymes to catalyze synthetic melanin. Melanin is an enigmatic and ubiquitous material often found in the form of brown or black pigment. Northwestern’s Nathan Gianneschi, the research lead and associate director for the International Institute for Nanotechnology, said every type of organism produces melanin, making it a readily available and versatile material to use in the lab.
Synthetic melanin can create colors ranging from blond to black
“In humans, it’s in the back of our eye to help with vision, it’s in our skin to help with protecting skin cells from UV damage,” Gianneschi said. “But birds also use it as a spectacular color display — peacock feathers are made of melanin entirely.”
Gianneschi is Professor of Chemistry in Northwestern’s Weinberg College of Arts and Sciences and a professor of materials science and engineering and biomedical engineering in Northwestern Engineering. Claudia Battistella, a postdoctoral fellow in Gianneschi’s lab, is the paper’s first author.
The research was published in the journal Chemistry of Materials.
Immunotherapy has revolutionized cancer treatment by stimulating the patient’s own immune system to attack cancer cells, yielding remarkably quick and complete remission in some cases. But such drugs work for less than a quarter of patients because tumors are notoriously adept at evading immune assault.
A new study in mice by researchers at Washington University School of Medicine in St. Louis has shown that the effects of a standard immunotherapy drug can be enhanced by blocking the protein TREM2, resulting in complete elimination of tumors. The findings, which are published in the journal Cell, point to a potential new way to unlock the power of immunotherapy for more cancer patients.
Immune cells infiltrate a human tumor in the four colorized images above. In a mouse study, researchers at Washington University School of Medicine in St. Louis have found that an antibody that targets the protein TREM2 empowers tumor-destroying immune cells and improves the effectiveness of cancer immunotherapy.
“Essentially, we have found a new tool to enhance tumor immunotherapy,” said senior author Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology. “An antibody against TREM2 alone reduces the growth of certain tumors, and when we combine it with an immunotherapy drug, we see total rejection of the tumor. The nice thing is that some anti-TREM2 antibodies are already in clinical trials for another disease. We have to do more work in animal models to verify these results, but if those work, we’d be able to move into clinical trials fairly easily because there are already a number of antibodies available.”
T cells, a kind of immune cell, have the ability to detect and destroy tumor cells. To survive, tumors create a suppressive immune environment in and around themselves that keeps T cells subdued. A type of immunotherapy known as checkpoint inhibition wakes T cells from their quiescence so they can begin attacking the tumor. But if the tumor environment is still immunosuppressive, checkpoint inhibition alone may not be enough to eliminate the tumor.
An expert on the immune system, Colonna has long studied a protein called TREM2 in the context of Alzheimer’s disease, where it is associated with underperforming immune cells in the brain. Colonna and first author Martina Molgora, PhD, a postdoctoral researcher, realized that the same kind of immune cells, known as macrophages, also were found in tumors, where they produce TREM2 and promote an environment that suppresses the activity of T cells.
“When we looked at where TREM2 is found in the body, we found that it is expressed at high levels inside the tumor and not outside of the tumor,” Colonna said. “So it’s actually an ideal target, because if you engage TREM2, you’ll have little effect on peripheral tissue.”
Colonna and Molgora — along with colleagues Robert D. Schreiber, PhD, the Andrew M. and Jane M. Bursky Distinguished Professor; and William Vermi, MD, an immunologist at the University of Brescia — set out to determine whether inhibiting TREM2 could reduce immunosuppression and boost the tumor-killing powers of T cells. As part of this study, the researchers injected cancerous cells into mice to induce the development of a sarcoma.
The mice were divided into four groups. In one group, the mice received an antibody that blocked TREM2; in another group, a checkpoint inhibitor; in the third group, both; and the fourth group, placebo. In the mice that received only placebo, the sarcomas grew steadily. In the mice that received the TREM2 antibody or the checkpoint inhibitor alone, the tumors grew more slowly and plateaued or, in a few cases, disappeared. But all of the mice that received both antibodies rejected the tumors completely. The researchers repeated the experiment using a colorectal cancer cell line with similarly impressive results.