University of Arizona Health Sciences researchers recently completed a study that has the potential to improve cancer treatment for colorectal cancer and melanoma by using nanotechnology to deliver chemotherapy in a way that makes it more effective against aggressive tumors. The findings were published today in Nature Nanotechnology.
“I’ve always been interested in harnessing the intrinsic immunity to fight against cancer,” said Jianqin Lu, BPharm, PhD, assistant professor of pharmaceutics and pharmacokinetics in the UArizona College of Pharmacy’s Department of Pharmacology and Toxicology and associate member of the UArizona Cancer Center. “To do this in a safe and effective way, nanotechnology comes into play because of its ability to improve drug movement and therapeutic efficacy, as well as the potential to reduce systemic toxicities. My hope is that these innovative nanotherapeutics and therapeutic regimens eventually will help cancer patients combat cancers more effectively and safely.”
Immunotherapies help boost the immune system’s ability to fight off cancer cells. Immune checkpoints are regulators of the immune system, which are pivotal in preventing the body from attacking healthy cells indiscriminately. Some types of cancer circumvent these checkpoints, allowing cancerous cells to avoid detection and continue to spread. Immune checkpoint blockade (ICB) is a newer therapy that can essentially “release the brakes” on the immune system and help the body fight back.
ICB therapies are effective for some types of cancer, but they don’t work for every patient. For example, only approximately 4% of patients with colorectal cancer, the second leading cause of cancer-related deaths in U.S., will respond to ICB therapy, Dr. Lu said.
Recent research has focused on ways to enhance the power of ICB therapies by combining them with chemotherapeutic agents such as camptothecin. Though camptothecin is potent, it is also unstable, has poor solubility in water and can have serious side effects for healthy cells.
Dr. Lu and the research team created the first nanotherapeutic platform of its kind to overcome these hurdles. Using a nanotechnology delivery method, researchers enhanced camptothecin’s ability to synergize with ICB therapies, making them more effective against aggressive tumors.
“To render a more effective ICB therapy, we have developed a nanotherapeutic platform that can switch the tumors from ‘immune-cold’ to ‘immune-hot,'” said Dr. Lu, who is also a member of the BIO5 Institute and the Southwest Environmental Health Sciences Center. “As a result, this nanotherapeutic platform was able to increase the effectiveness of the ICB therapy to eradicate a large portion of early-stage colorectal cancer tumors while concurrently activating the body’s memory immunity, preventing tumor recurrence.”
The team attached camptothecin to sphingomyelin, a naturally occuring lipid found on the surface of cells. The combination of the two molecules into a nanovesicle called camptothesome stabilized camptothecin, improving its efficacy and diminishing systemic toxicities. The nanotech delivery method also improved the tumor uptake of the camptothesome in a rodent model, where it deeply penetrated the tumour with efficient release of the chemotherapy.
Dr. Lu and the research team then created a way to load an immune checkpoint inhibitor targeting one of the key checkpoints, indoleamine 2,3-dioxygenase (IDO1), inside of the camptothesomes. When combined with inhibitors targeting other immune checkpoints known as PD-L1 and PD-1, this nanotherapeutic strategy eliminated a significant portion of clinically difficult-to-treat late-stage metastatic colorectal cancer and melanoma tumors, paving the pathway for further studies.
The researchers note that their nanotechnology platform can be used to deliver a range of cancer therapeutics, and it has a significant head start in the drug development pipeline as it is derived from sphingomyelin, a lipid that is already approved by the U.S. Food and Drug Administration.
Dr. Lu hopes to collaborate with oncologists at the UArizona Cancer Center to further optimize the nanotherapeutic system to make it suitable for an early phase clinical trial.

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue.
The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice.
The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.
The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors.
CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.
This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells — these effects are known as on-target, off-tumor toxicity.

Researchers have known from several lines of evidence that the ancient hominins known as the Denisovans interbred with modern humans in the distant past. Now researchers reporting in the journal Current Biology on August 12 have discovered that the Philippine Negrito ethnic group known as the Ayta Magbukon have the highest level of Denisovan ancestry in the world. In fact, they carry considerably more Denisovan DNA than the Papuan Highlanders, who were previously known as the present-day population with the highest level of Denisovan ancestry.
“We made this observation despite the fact that Philippine Negritos were recently admixed with East Asian-related groups — who carry little Denisovan ancestry, and which consequently diluted their levels of Denisovan ancestry,” said Maximilian Larena (@maxlarena) of Uppsala University. “If we account for and masked away the East Asian-related ancestry in Philippine Negritos, their Denisovan ancestry can be up to 46 percent greater than that of Australians and Papuans.”
In the new study, Larena and colleagues, including Mattias Jakobsson, aimed to establish the demographic history of the Philippines. Through a partnership between Uppsala University of Sweden and the National Commission for Culture and the Arts of the Philippines (NCCA), aided by collaboration with indigenous cultural communities, local universities, local government units, non-governmental organizations, and/or regional offices of the National Commission for Indigenous Peoples, they analyzed about 2.3 million genotypes from 118 ethnic groups of the Philippines including diverse self-identified Negrito populations. The sample also included high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos.
The study shows that Ayta Magbukon possess the highest level of Denisovan ancestry in the world, consistent with an independent admixture event into Negritos from Denisovans. Together with the recent discovery of a small-bodied hominin, called Homo luzonensis, the data suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related.
Altogether, the researchers say that the findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.
“This admixture led to variable levels of Denisovan ancestry in the genomes of Philippine Negritos and Papuans,” Jakobsson said. “In Island Southeast Asia, Philippine Negritos later admixed with East Asian migrants who possess little Denisovan ancestry, which subsequently diluted their archaic ancestry. Some groups, though, such as the Ayta Magbukon, minimally admixed with the more recent incoming migrants. For this reason, the Ayta Magbukon retained most of their inherited archaic tracts and were left with the highest level of Denisovan ancestry in the world.”
“By sequencing more genomes in the future, we will have better resolution in addressing multiple questions, including how the inherited archaic tracts influenced our biology and how it contributed to our adaptation as a species,” Larena said.
This work was supported by the Swedish Research Council and the Knut and Alice Wallenberg Foundation.
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An international study, led by researchers from Queen Mary University of London and St Bartholomew’s Hospital, has found a unique pair of gene variants that causes sudden onset high blood pressure in pregnant women.
The research in the UK was funded by the National Institute of Health Research, their EME programme in partnership with the Medical Research Council, the British Heart Foundation and Barts Charity.
Hypertension (high blood pressure) affects 30% of adults. Most cases are caused by a combination of inherited and acquired factors that require long-term treatment to prevent the complications of stroke and heart attacks.
For one in ten people with hypertension, a specific cause can be found and removed. The most common cause is a tiny benign nodule in one of the adrenals. These are glands near the kidneys that produce steroid hormones. The hormone aldosterone stimulates the kidneys to retain salt and hence increase blood pressure. As a result the condition known as primary aldosteronism typically leads to a type of hypertension which is resistant to conventional drugs, and is linked to an increased risk of stroke and heart attacks compared to other patients with hypertension.
Over the years, a research team at Queen Mary University of London and St Bartholomew’s Hospital has found a number of gene variants which cause the production of high levels of aldosterone from small adrenal nodules. Their latest study, published today in the journal Nature Genetics, is the discovery of a new type of primary aldosteronism caused by the coincidence of a unique pair of new variants which always occur together. The patients are predominantly women, who present with sudden onset of high blood pressure and low blood potassium in the early months of a pregnancy.
In partnership with Professor Christina Zennaro, Inserm Research Director at the Paris Cardiovascular Research Center, and colleagues in Paris, it emerged that the new variants switch on a receptor molecule in the adrenal cells which recognises the pregnancy hormone Human Chorionic Gonadotropin (HCG), the same as is measured in routine pregnancy testing — and that the receptor molecule triggers a surge of aldosterone production.
Professor Morris Brown, Professor of Endocrine Hypertension at Queen Mary University of London said: “What was particularly satisfying is that recognition of the cause of hypertension in these women enabled them to complete a successful pregnancy, and that afterwards they were completely cured of hypertension by a procedure to remove the adrenal nodule, and were able to stop all their drugs.”
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A new publication by Yale Cancer Center highlights recent breakthrough therapies developed to treat non-small cell lung cancer (NSCLC). The goal of the study is to provide views on how basic science advances will impact clinical research areas to help influence how NSCLC will be managed over the coming decade. The perspective is published online today in the journal Nature Medicine.
“Worldwide, lung cancer is the most common cause of cancer-related death,” said Meina Wang, PhD, associate research scientist at Yale Cancer Center and lead author of the perspective. “There have been many advances in the treatment NSCLC over the past two decades, but we need to keep the focus on new therapies to continue to make progress and treat this deadly disease.”
In the report, authors show molecular targeted therapies and immunotherapies for NSCLC have improved outcomes; however, most advanced NSCLC cases become resistant to current treatments and eventually progress. In the perspective, researchers discuss these recent breakthrough therapies and combinations developed for NSCLC to combat the problem and detail the current understanding of mechanisms of resistance and the importance of incorporating genomic analyses into clinical studies. The authors underscore the importance of the future role of neoadjuvant and maintenance combination therapy approaches to potentially cure early-stage disease. Researchers also note a major challenge to the successful development of rational combination therapies will be the application of robust predictive biomarkers for a clear-cut strategy for each patient.
“The biggest impact on long-term outcome for NSCLC could be the use of rational combination therapies tackling early disease, to maximize tumor eradication,” said Chris Boshoff, MD, PhD, Chief Development Officer, Oncology, Pfizer Global Product Development, and senior author of the perspective. “We provide our prospective on the latest insights into the management of lung cancer and emphasize the potential of personalized combination immunotherapy-based regiments to improve outcomes further.”
“We expect a continued trajectory of improved outcomes for NSCLC and lung cancer in general,” said Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, Disease Program leader at Yale, and co-senior author of the study. “But expansion and further investment in collaborative research using big data sets between industry, academia, government, and other non-profit organizations are essential to continue our promising journey towards a cure.”
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Materials provided by Yale University. Note: Content may be edited for style and length.

With the new strain of Covid, couples are once again scrambling to make sense of how — or even whether — to move forward with their marriage plans.Early this month, Fallon Carter was on the phone with a client working through a series of “what ifs.” Ms. Carter, who runs an event planning company in Manhattan, wanted to reassure a bride getting married in Anguilla next May that, should her guest count plummet, her bases were covered.“Part of my business now is figuring out whether people can travel, and what to do if they suddenly can’t,” she said. It is one of several new areas of expertise for Ms. Carter, who specializes in destination weddings, since the onslaught of the Delta variant.As the new and highly transmissible strain of Covid clamps down on the hospitality industry, planners, couples and venues are once again scrambling to make sense of how — and whether — to move forward with weddings, including many that were postponed because of the virus in 2020.“It’s on everybody’s mind,” Ms. Carter said. That includes a couple she’s working with who called her in a panic three weeks before their Aug. 27 wedding for 175 at Blue Hill at Stone Barns in Tarrytown, N.Y.The celebration was supposed to be indoors — “a nice air-conditioned moment in August,” Ms. Carter said — but with Delta on the rise and the news that Governor Andrew Cuomo would start asking private businesses to require vaccinations for admission, the couple got nervous. A spur of the moment shift to an outdoor tent is underway. “Now I’m reconfiguring the dance floor and deconstructing all the floor installations.”In Santa Barbara, Calif., Amy Nichols, the founder of Amy Nichols Special Events, is bracing for something even more disruptive. “As an industry in general, we’re seeing more couples who are hesitant to book for 2022 because of the Delta variant,” she said. “They don’t know what to expect, whether we’ll be in better shape or things will get worse.”The lack of a Covid crystal ball may be why some vendors are leaving nothing to chance. Daniela VillaRamos, a New York City officiant, is currently not asking couples and their guests for proof of vaccination. But she is attaching a hard “yet” to that policy. “If the Delta variant rates continue to exponentially grow as the weather cools and weddings begin to be held indoors, we may begin requiring it,” she said. “It’s important for everyone to remember that we’re human, too.”Ms. Nichols is working with couples who aren’t shy about asking that all vendors and guests be vaccinated. And Ms. Carter has gotten good at using Vow Digital Health, an app started in April that creates a centralized system for showing proof of vaccines or negative Covid tests. Guests get a text message asking them to upload their ID and the required documents. When it’s go time, Ms. Carter has that information at her fingertips and can admit or turn away attendees accordingly. (So far, she hasn’t had to add bouncer to her résumé.)[Sign up for Love Letter and always get the latest in Modern Love, weddings, and relationships in the news by email.]Despite the raging variant, which prompted the C.D.C.’s recent recommendation that all Americans, regardless of vaccination status, wear masks indoors in most of the country, asking for proof still feels uncomfortable to some. Brides like Mariah Hughes of Bangor, Maine, would rather use the honor system.“I think I’ll be able to make an educated assumption about whether my family and friends are vaccinated,” she said. Ms. Hughes and her fiancé, Stephen Cormier, had planned to be married in September but pushed their date to next June because the photographer they wanted to work with was booked solid. They are less frustrated than relieved. “With the Delta variant so prevalent, we feel like we made the right decision,” she said.Not that she, or anyone, can count on Covid being history next year. In Denver, Brittney Griffin, the venue director at the wedding site Blanc, is prepared to start pulling out masks again even though vaccination rates are high in Colorado. “We haven’t had to yet,” but new mandates could be coming, she said. “Sadly we’ve already been through this before, so if it becomes a requirement again, at least we’re prepared.”Niche vendors like McKenzi Taylor, the founder of Cactus Collective Weddings in Las Vegas, may be one of the few whose business picked up because of Delta. Ms. Taylor plans small weddings in remote outdoor settings.“We’re usually people’s second choice,” she said, meaning that most couples who contact her do so because Covid spoiled their original plans. She saw a 30 percent swell in bookings with the onset of the virus in 2020. Now, business is booming again. “Unfortunately, I think we’re in a whole new cycle with Delta. I’m getting a lot of calls about, ‘How quickly can we get married?’”Timing may not be everything, though. “Four years from now, we’re still going to be having breakthrough infections,” said Dr. Amesh Adalja, an infectious disease specialist and senior scholar at the Johns Hopkins University Center for Health Security. “It’s still going to be an issue.”Those who have their hearts set on big indoor weddings will have to roll the dice. “I think a good way to minimize the chance of anything really spiraling out of control is if everybody is vaccinated,” Dr. Adalja said. But even then, he added, “you still have to ask yourself, ‘Is it OK if I get mild symptoms?’ Because if you’re vaccinated and get a breakthrough infection, it’s unlikely to be severe.”Which may not be consolation to anyone banking on a perfect wedding day, according to Ms. Carter. “People are like, ‘What are we gonna do?’”

States with low initial use of HIV-prevention drugs are continuing to fall behind in usage among people at risk for the disease, a new study finds.
Researchers, clinicians and advocates had hoped that late-adopting states would see a surge in HIV prevention uptake once those states joined the prevention effort, but that’s largely not the case, the new research shows. Instead, there are worsening disparities between states that backed the drugs early on and those that did not.
“The low PrEP uptake that we found is concerning because it means that people are not benefiting from an HIV-prevention medication that has been approved and available for almost a decade,” said researcher Kathleen McManus, MD, of the University of Virginia School of Medicine. “The United States needs innovative interventions at the federal, state and clinic level in order to get PrEP to people who are at high risk of getting HIV.”
Ending the HIV Epidemic
The federal government has set a goal of preventing 250,000 HIV infections over 10 years as part its “Plan to End the HIV Epidemic.” Key to that are state and county-level partnerships to encourage use of HIV pre-exposure prophylaxis, or PrEP. These drugs can prevent HIV infection among people at higher risk for HIV, such as people who have condomless sex and people who inject drugs.
PrEP has been available for nearly a decade — the federal Food and Drug Administration approved it in 2012. Yet usage remains low. Fewer than 20% of people who would benefit from it are taking it, public health officials estimate.

As children head back for an uncertain school year, Dr. Anthony Fauci joins Times journalists for a vital Q. and A. for parents, educators and students everywhere.

Researchers are revisiting an age-old question in baseball: Do batters actually keep their eye on the ball?
A review of the few film- and lab-based studies on the subject suggests that yes, indeed, batters’ eyes are watching the pitched ball. But they’re moving their heads, and not their eyes, to direct their gaze.
And then, with little time to spare, some batters in studies shifted their gaze toward home plate, a move that researchers suspect is related to trying to anticipate where the ball will be when it is in batting range. But not all batters made this move to briefly take their eye off the ball.
After examining previous studies on head and eye movements in baseball batters, Ohio State University researchers concluded that there is no consensus on which head and eye movements are most likely to improve batting performance — but further investigation could get the sport to the point at which eye gaze-based batting training is feasible.
“One question we had was whether batters actually keep their eye on the ball, and if they do, does that lead to some advantage?” said Nick Fogt, professor of optometry at Ohio State and co-author of the review.
“What we’ve found, and it’s been replicated several times, is that they do keep their eye on the ball, but they don’t turn their eyes — they turn their head, which is fruitful in terms of a scientific question: Is there some reason why you would do it this way?

Results from a Michigan Medicine study reveal that targeting a protein found in the skin may reduce the severity of psoriasis.
Interferons play a major role in activating the body’s response to viral threats, but they have also been detected in the lesions of many psoriasis patients at abnormal levels. Psoriasis is an autoimmune disease that causes overproduction of skin cells and impacts nearly 30 million people in the world.
Using a model that mimics psoriasis in mice, researchers found that changing the levels of interferon kappa, a protein made by skin cells, altered the severity of inflammation and production of cell signaling molecules, called cytokines, that induce inflammation characteristic of psoriasis. Investigators found more psoriasis-like inflammation when more interferon kappa was present, while decreasing interferon kappa levels reduced disease.
The findings, published in the Journal of Investigative Dermatology, suggest using therapies to modulate interferon states may limit inflammation in psoriasis patients.
“We’ve known that psoriatic inflammation is marked by interferon-related gene expression, but how interferons alter the severity of the disease has not been clear,” said J. Michelle Kahlenberg, M.D., Ph.D., associate professor of rheumatology at Michigan Medicine and senior author of the paper. “Understanding how interferon kappa may modulate psoriasis brings us one step closer to optimizing our treatments.”
The research team induced psoriasis in mouse models, splitting them into groups with interferon kappa at low, normal or elevated levels. The overexpressed protein alone didn’t induce the disease, but it primed the skin for the inflammatory response that followed.
“This work shows how the context of the skin environment can shape inflammatory responses.” said Mehrnaz Gharaee-Kermani, DVM, M.P.H., Ph.D., lead author of the study and a senior research lab specialist at Michigan Medicine. “It will be exciting to see how this can be applied in clinic.”
The research team is conducting further studies to understand the role of interferon kappa in psoriasis patients through their Taubman Institute-sponsored study at Michigan Medicine and in partnership with Johann E. Gudhonsson, M.D., Ph.D., receiving funding through the National Psoriasis Foundation. Several treatments are used against the disease, but there is no cure.
A few current psoriasis drugs inhibit interferons, but many that are more specific are still in the trial phase. Coupled with the study’s findings, personalized medicine will be paramount as physicians attempt to treat this disease, Kahlenberg said.
“Until now, treatments have been tested by studying a drug in hundreds of patients, lumping the average of them all together and targeting the average of those patients,” Kahlenberg said. “As any patient who has been on these medications will tell you, this trial-and-error approach wastes patient time and money trying to get control of the disease. Understanding a patient’s background level of interferon might help us target things within that person to make their disease better faster and stay in remission.”
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Materials provided by Michigan Medicine – University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.