Publisher Health

Overall cancer death rates continued to decline among men, women, children, and adolescents and young adults in every major racial and ethnic group in the United States from 2015 to 2019, according to the latest Annual Report to the Nation on the Status of Cancer. From 2014 to 2018, overall cancer incidence, or new cases of cancer, remained stable for men and children but increased for women and adolescents and young adults. This year’s report, published October 27, 2022, in Cancer, also highlights longer-term trends in pancreatic cancer, as well as racial and ethnic disparities in incidence and death rates for many individual cancer sites.
All of the findings in this report are based on data from before the COVID-19 pandemic.
“Today’s report is good news in our fight against cancer and is a reminder of the importance of President Biden’s Cancer Moonshot initiative,” said Department of Health and Human Services Secretary Xavier Becerra. “I’m deeply impressed by the progress we’re making against cancer and firmly believe we can meet the President’s goal of reducing the death rate from cancer by at least 50% over the next 25 years. We can and must end cancer as we know it.”
The Annual Report to the Nation on the Status of Cancer is a collaborative effort among the National Cancer Institute (NCI), part of the National Institutes of Health; the Centers for Disease Control and Prevention (CDC); the American Cancer Society (ACS); and the North American Association of Central Cancer Registries (NAACCR).
The report is based on a combined cancer incidence data set from NAACCR composed of data collected by CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, as well as mortality data from CDC’s National Center for Health Statistics.
The report shows that from 2015 to 2019, overall cancer death rates decreased by 2.1% per year in men and women combined. Among men, death rates decreased by 2.3% per year; among women, death rates decreased by 1.9% per year. The annual declines in death rate accelerated from 2001 to 2019 in both men and women.

Atrial fibrillation — a form of irregular heartbeat, or arrhythmia — leads to more than 454,000 hospitalizations and nearly 160,000 deaths in the United States each year. Globally, it is estimated that approximately 60 million people are affected by the condition.
Pacemakers are lifesaving devices that regulate the heartbeats of people with chronic heart diseases like atrial fibrillation and other forms of arrhythmia. However, pacemaker implantation is an invasive procedure, and the lifesaving pacing the devices provide can be extremely painful. Additionally, pacemakers can only be used to treat a few specific types of disease.
In a paper published Wednesday in Science Advances, a University of Arizona-led team of researchers detail the workings of a wireless, battery-free pacemaker they designed that could be implanted with a less invasive procedure than currently possible and would cause patients less pain. The study was helmed by researchers in the Gutruf Lab, led by biomedical engineering assistant professor and Craig M. Berge Faculty Fellow Philipp Gutruf.
Currently available pacemakers work by implanting one or two leads, or points of contact, into the heart with hooks or screws. If the sensors on these leads detect a dangerous irregularity, they send an electrical shock through the heart to reset the beat.
“All of the cells inside the heart get hit at one time, including the pain receptors, and that’s what makes pacing or defibrillation painful,” Gutruf said. “It affects the heart muscle as a whole.”
The device Gutruf’s team has developed, which has not yet been tested in humans, would allow pacemakers to send much more targeted signals using a new digitally manufactured mesh design that encompasses the entire heart. The device uses light and a technique called optogenetics.

A University of Kentucky Markey Cancer Center researcher’s team developed new chemical compounds that show promise as a potential anticancer therapy to treat aggressive tumors.
The study led by Samuel G. Awuah, Ph.D., was published in Chemical Communications with Adedamola Arojojoye, a graduate student in Awuah’s lab as the paper’s first author.
The new gold-derived compounds created by Awuah’s lab were toxic to cancer cells but well-tolerated by mice, giving them potential in the development of new cancer drugs that could make it to the clinic.
Many metal-based therapies have proven to be effective against cancer, with platinum-based drugs a first line chemotherapy for testicular, bladder, lung, colon and ovarian cancers. Some metal-based compounds, like gold(III), have promise as anticancer agents, but lack the stability needed to continue therapeutic development.
Awuah’s lab synthesized a new class of gold(III), which had a different structure that was more tolerant to therapeutic use.
In the lab, the new chiral gold(III) compounds were studied on a panel of cancer cell lines to test their effectiveness and understand how they attack cancer cells.
The compounds showed anticancer activity against aggressive triple negative breast cancer cells. They also possessed a new mechanism that caused the cells’ mitochondria to dysfunction.
Awuah says developing drugs that cause mitochondria dysfunction deprive cancer cells of energy and is a new relevant strategy to inhibit cancer growth that would be useful in combination with existing therapies.
“Continuing to develop gold-based compounds has the potential to generate new mechanisms of drug action and understanding how they alter cancer cells has significant implications in drug design and is of clinical relevance,” Awuah said.
Awuah is an assistant professor in the College of Arts and Sciences’ Department of Chemistry and holds a joint appointment in the College of Pharmacy’s Department of Pharmaceutical Sciences. His lab focuses on developing new methods to create chemical tools that interrogate complex biological processes as therapeutics for several diseases, including cancer.
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Materials provided by University of Kentucky. Original written by Elizabeth Chapin. Note: Content may be edited for style and length.

Viral DNA in human genomes, embedded there from ancient infections, serve as antivirals that protect human cells against certain present-day viruses, according to new research.
The paper, “Evolution and Antiviral Activity of a Human Protein of Retroviral Origin,” published Oct. 28 in Science, provides proof of principle of this effect.
Previous studies have shown that fragments of ancient viral DNA — called endogenous retroviruses — in the genomes of mice, chickens, cats and sheep provide immunity against modern viruses that originate outside the body by blocking them from entering host cells. Though this study was conducted with human cells in culture in the lab, it shows that the antiviral effect of endogenous retroviruses likely also exists for humans.
The research is important because further inquiry could uncover a pool of natural antiviral proteins that lead to treatments without autoimmune side effects. The work reveals the possibility of a genome defense system that has not been characterized, but could be quite extensive.
“The results show that in the human genome, we have a reservoir of proteins that have the potential to block a broad range of viruses,” said Cedric Feschotte, professor of molecular biology and genetics in the College of Agriculture and Life Sciences. John Frank, Ph.D. ’20, a former graduate student in Feschotte’s lab and now a postdoctoral researcher at Yale University, is the study’s first author.
Endogenous retroviruses account for about 8% of the human genome — at least four times the amount of DNA that make up the genes that code for proteins. Retroviruses introduce their RNA into a host cell, which is converted to DNA and integrated into the host’s genome. The cell then follows the genetic instructions and makes more virus.

“Dicamba drift” — the movement of the herbicide dicamba off crops through the atmosphere — can result in unintentional damage to neighboring plants. To prevent dicamba drift, other chemicals, typically amines, are mixed with dicamba to “lock” it in place and prevent it from volatilizing, or turning into a vapor that more easily moves in the atmosphere.
Now, new research from the lab of Kimberly Parker, an assistant professor of energy, environmental and chemical engineering at Washington University in St. Louis’ McKelvey School of Engineering, has shed new light on this story by demonstrating for the first time that these amines themselves volatilize, often more than dicamba itself.
Their findings were published Sept. 23 in the journal Environmental Science and Technology.
The volatilization of amines when applied with dicamba may help explain the processes that cause dicamba drift. However, amines are used in other herbicides as well, including as glyphosate, the most-used herbicide in the world. Regardless of the herbicide, the researchers found that amines still volatilized.
If amines, themselves, are released into the atmosphere, they can have a negative impact on human health as they can form cancer-promoting substances. They also affect the climate and atmospheric chemistry. Because of their potential danger and prevalence, the scientific literature is full of research looking at the ways they are released into the atmosphere — except when it comes to their use in herbicide-amine formulations.
“Amines also undergo reactions to form particulate matter — tiny particles that can make their way into the body when inhaled,” Parker said. “Those particles are also toxic and carcinogenic,” and they carry consequences for atmospheric chemistry by affecting climate.

Researchers at Great Ormond Street Hospital for Children (GOSH) and UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) have used CRISPR/Cas9 technology to engineer donor T cells to try to treat seriously ill children with resistant leukemia, who had otherwise exhausted all available therapies.
This Phase I trial, published in Science Translational Medicine, is the first use of ‘universal’ CRISPR-edited cells in humans and represents a significant step forward in the use of gene-edited cells for cancer treatment. As part of the trial the research team, built and applied a new generation of ‘universal’ genome-edited T cells, which builds on previous work1 that had used older, less accurate technology.
T cells were modified using CRISPR which makes a cut in the cells’ DNA and insert a genetic code. In this case this piece of genetic code allows the T cells to express a receptor — called a chimeric antigen reception (CAR) — that can recognise a marker on the surface of cancerous B cells and then destroy them. The T cells were then gene edited using CRISPR so that they could be used ‘off the shelf’ without any donor matching needed.
While a number of CAR T-cell therapies are now being provided by the NHS, they rely on collecting and engineering a patient’s own cells. This is expensive and is not always feasible or possible in a short period of time. Genome editing is being investigated to allow donated cells to be pre-manufactured and used in multiple patients, aiming to reduce costs and make the treatments more accessible.
In specialist clean rooms at GOSH, researchers manufactured their banks of donor CAR T-cells using a single disabled virus to transfer both the CAR and a CRISPR guidance system, and then applied cutting-edge mRNA technology to activate the gene editing steps. Donors were all healthy volunteers from the UK and provided by the Anthony Nolan Registry.
The trial
Six children aged 14 months to 11 years with relapsed and treatment-resistant B-ALL have been treated up to February 2022. All of the children had previously been through standard UK treatments for B-ALL but had sadly seen their disease return multiple times.

Johns Hopkins Medicine researchers say they have successfully used a cell’s natural process for making proteins to “slide” genetic instructions into a cell and produce critical proteins missing from those cells. If further studies verify their proof-of-concept results, the scientists may have a new method for targeting specific cell types for a variety of disorders that could be treated with gene therapies. Such disorders include neurodegenerative diseases that affect the brain, including Alzheimer’s disease, forms of blindness and some cancers.
For those looking to develop treatments for diseases where cells lack a specific protein, it’s critical to precisely target the cell causing the disease in each structure, such as the brain, to safely kickstart the protein-making process of certain genes, says Seth Blackshaw, Ph.D., professor of neuroscience in the Sol Snyder Department of Neuroscience and member of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. Therapies that don’t precisely target diseased cells can have unintended effects in other healthy cells, he adds.
Two methods currently used to deliver protein-making packages into cells vary widely in their effectiveness in both animal models and people. “We wanted to develop a gene expression delivery tool that’s broadly useful in both preclinical and clinical models,” says Blackshaw.
One current method of sending biochemical packages involves so-called “mini promoters” that direct the expression, or protein-making process of certain stretches of DNA. Blackshaw says this method often fails to express genes in the right cell type.
Another method, called serotype-mediated gene expression, involves delivering tools that latch on to proteins that stud the surface of certain types of cells. However, Blackshaw says such methods are hit-or-miss in their ability to specifically target only one type of cell, and they often fail to work in people even after successful testing in animal models.
The current proof-of-principle study, described Oct. 1 in Nature Communications, has roots in previous research by Johns Hopkins Assistant Professor of Pathology Jonathan Ling, Ph.D., who published “maps” depicting how various cell types use alternative splicing of messenger RNA, a cousin of DNA, to construct genetic templates that produce an ever-changing set of proteins in the cell. The changes depend on a cell’s type and location. Cells normally use alternative splicing to vary the types of proteins a cell can make.

A Yale-designed nasal vaccine can help bolster immune responses to COVID-19 in previously vaccinated animals and reduce viral transmission, Yale researchers report Oct. 27 in the journal Science.
The new vaccine approach developed by Yale researchers — which is known as “prime and spike” — is designed to jumpstart immune response in the respiratory system, which is the first part of the body to be infected by the virus.
Intramuscular vaccine shots, which are what most people have received to protect against COVID-19 infection, provide a broad-based immune response throughout the body and help avert serious illness. However, that protection has tended to wane after about four months, leaving people susceptible to breakthrough infections and emerging variants.
The new “prime” and “spike” approach may help prevent breakthrough infections of vaccinated individuals by bolstering immune response within the mucosal lining of the respiratory tract, which are the first cells attacked by COVID-19. (“Prime” refers to the process of injecting the vaccine directly into the muscle, as is typically done. “Spike” refers to a follow-up vaccination with spike proteins, known to derive from the coronavirus, directly into the nostril, where the virus is known to enter the body.)
“The nasal vaccine promotes the development of immunity within the respiratory system, which can respond more quickly to infection,” said Dr. Benjamin Goldman-Israelow, assistant professor of medicine (infectious diseases) at the Yale School of Medicine and co-corresponding author of the paper. “By creating mucosal immunity, the vaccine helps stop the virus at its entry point, rather than waiting until later to fight back.”
The Yale team, led by Goldman-Israelow and Tianyang Mao, a graduate student in the lab of fellow co-corresponding author Akiko Iwasaki, Sterling Professor of Immunobiology, delivered the nasal vaccine to both vaccinated and unvaccinated mice. They found increased immune system response in the respiratory tracks of vaccinated mice only. Mice that had not been previously vaccinated, and vaccinated mice that did not receive nasal vaccine, died from infection. Meanwhile, mice that received the intranasal spike booster were completely protected from death and disease.
In hamsters that received the nasal vaccine, the Yale team found decreased duration and total amount of viral shedding, which is when an infected individual releases copies of the virus including through sneezing or coughing. Hamsters vaccinated with the prime and spike method were also found to have reduced viral loads when housed in the same cage with infected, unvaccinated hamsters, suggesting that the strategy reduces trains of transmission.
Researchers also found increased breadth of immune response among animals that received the nasal vaccine, indicating that the approach would be effective against a broad spectrum of coronaviruses with pandemic potential.
Goldman-Israelow noted that the Yale approach does not use live viruses, viral vectors, or adjuvants, which may make the vaccine safer.
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Genetic mutations kick start cancers. Some mutations shuffle the genetic code, others come from the deletion of key genes.
At La Jolla Institute for Immunology (LJI), researchers have made a major breakthrough in understanding how deletion of the genes that encode TET proteins can lead to cancer growth. Their new study, published in Nature Communications, is the first to show the immediate consequences of deleting all three genes from the TET family in mouse embryonic stem cells.
By using this mouse model, the researchers discovered that TET proteins are critical for keeping the process of cell and DNA replication running smoothly. Without TET proteins, important genes go missing, leading to the mutations, or aneuploidies (an-new-ploy-dees).
Aneuploidies are cases where genetic material is added or deleted on a massive scale. Cells with aneuploidies aren’t just missing a gene. Instead, genes go missing across an entire chromosome. “Aneuploidies are a common feature of cancer cells,” says LJI Postdoctoral Researcher Hugo Sepulveda, Ph.D.
Uncovering this direct connection between TET loss of function and aneuploidies is a major discovery in the field of cell biology, and it gives researchers a clue to how to find genes that underpin cancer development. “We can now understand the mechanisms behind aneuploidy development, although we can’t say these changes always happen through the same genes in other cell types,” says LJI Postdoctoral Researcher Hugo Sepulveda, Ph.D.
Sepulveda co-led the research with former LJI postdoctoral researcher Romain Georges, Ph.D., who generated the mouse model and derived the stem cells for the project. LJI Professor Anjana Rao, Ph.D., served as the study’s senior author.

All living cells harbor nuclei — key biological structures that play an important role in information storage, retrieval, and duplication of genetic information. In mammals, these nuclei possess the nuclear envelope (NE) — the biological shield that protect nuclei from environmental stimuli (e.g., mechanical stress) and the associated damage. However, certain external stimuli can cause damage to the NE. When this happens, various mechanisms kick in to initiate the process of NE repair. However, the precise mechanism of NE repair has remained elusive.
Quite recently, an international team of researchers led by Dr. Takeshi Shimi, Specially Appointed Associate Professor at Tokyo Institute of Technology (Tokyo Tech), was able to identify the precise role of the key components involved in this important physiological process. Using a high-power laser to induce NE rupture, the researchers demonstrated how a “repair army” comprising lamin C, Barrier-to-autointegration factor (BAF), and cytoplasmic cyclic GMP-AMP synthase (cGAS), important proteins with key biological functions, synergistically facilitated the process of NE repair in mouse embryonic fibroblasts. The findings of their study were published in Journal of Cell Biology.
“In mammalian cell nuclei, the nuclear lamina underlies the NE to maintain nuclear structure. The nuclear lamins is the major structural components of the nuclear lamina and is involved in the protection against NE rupture caused by mechanical stress. Our analyses using immunofluorescence and live-cell imaging revealed that a nucleoplasmic pool of lamin C rapidly accumulates at the sites of laser-microirradiation-induced NE rupture in mammalian cells,” explains Dr. Shimi, elaborating on their findings.
The process of NE repair is sometimes hampered owing to the presence of certain mutations. In their study, the research team successfully identified key lamin C mutations — structural and functional modifications that adversely affect the repair process. For instance, they found that rapid repair did not occur or was weakened in lamin C mutants, namely R435C, R471C, R527H, A529V, and K542N, compared to wild type (control) lamin C that did not have these mutations. Moreover, the two mutants are found in patients with laminopathies and are responsible for causing cardiac and skeletal muscle diseases, dysplasia, and progeroid syndrome.
Based on these findings, Dr. Shimi concludes, “The accumulation of nuclear BAF and cGAS at the rupture sites was in part dependent on lamin A/C. Our results suggest that nucleoplasmic lamin C, BAF, and cGAS concertedly accumulate at sites of NE rupture for rapid repair.”
Let us hope that the insights gained from this breakthrough will lead to a better understanding of various rare genetic disorders, such as laminopathies.
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Materials provided by Tokyo Institute of Technology. Note: Content may be edited for style and length.