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Rethinking How Cancer Cells Evade Targeted Therapy

Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.  

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UCSF Researchers Identify the Cellular Source of Recurrent Glioma

Newswise — Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.  

In their study publishing December 20 in Nature Cancer, first author Lin Wang, PhD and senior author Aaron Diaz, PhD, found that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. They found that some cells shift to a mesenchymal, radiation-resistant phenotype (state) as a stress response following standard therapy.  

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Credit: UCSF
Aaron Diaz, PhD, Associate Professor, Neurological Surgery, UCSF Weill Institute for Neurosciences

“We asked if there is another mechanism that explains therapeutic resistance,” said Diaz, associate professor of neurological surgery at the UCSF Weill Institute for Neurosciences. “Our study concludes that, rather than a genetic evolution, there is a phenotypic plasticity or transition which allows these cells to evade therapy.”  

To identify what drives treatment resistance to standard therapy, as well as the cellular source of recurrent disease, UCSF researchers used single-nucleus RNA, open-chromatin, spatial profiling to analyze 86 primary-recurrent, patient-matched, paired GBM specimensThis unprecedented cohort represented decades of biobanking at UCSF. 

With access to thirty years’ worth of GBM’s, the scientists were able to present novel cell-intrinsic and cell-extrinsic targets as well as a single-cell multi-omics atlas of GBM under therapy. This was the first time that researchers were able to comprehensively map intra-cellular signaling in the tumor-anatomical niches of recurrent GBM and identify novel cell-extrinsic therapeutic targets.   

The 86 specimens contained the cellular tumor and adjacent non-malignant tissue from the surgical margin. This unique cohort enabled Diaz and his team to analyze communications between malignant and non-malignant glia. They found that cells in this surgical margin acted as niches of recurrence where non-malignant glia were broadcasting pro-growth signals that influenced the tumor cells to regrow. These paracrine (cell extrinsic) signals stimulated the activator protein (AP1) pathway, leading to mesenchymal transition, therapy resistance and tumor recurrence. 

These mesenchymal transitions were apparent in the tumor samples after therapy, along with increased numbers of cycling mesenchymal cells. Pro-growth signals from the tumor microenvironment, as well as the cell-intrinsic response to radiation therapy, drove the mesenchymal shift through a stress-response pathway mediated by AP1. 

The researchers were able to combine two techniques to achieve a map of paracrine signals – single-nucleus RNA-sequencing of frozen tissue specimens and spatial transcriptomics profiling of formalin-fixed specimens. From each tumor biopsy, they performed single-nucleus RNA-seq which measures transcriptome-wide gene expression in individual cells, for thousands of cells at a time. They compared the expression of signal receptors to that of their known ligands, between the different cell populations sequenced. They then validated that cells from these populations physically interact and signal in situ, using spatial transcriptomics.

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“This is the first single-cell longitudinal study of this scale in glioma,” said Diaz. “It’s also a study that could be done only at UCSF, because it represents decades of careful biobanking of surgical specimens. Since all the specimens came from UCSF, we know that the treatment histories are homogeneous, in that each patient received only standard-of-care therapy. It’s both this cohort’s scale and treatment uniformity that enable us to see past patient specific effects to the underlying biology of the disease.” 

The research was supported in part by the UCSF GBM Precision Medicine Program.

Authors: Other UCSF authors include: Jangham Jung, Husam Babikir, Karin Shamardani, Saket Jain, Xi Feng, Nalin Gupta, Susanna Rosi, Susan Chang, David Raleigh of the UCSF Department of Neurological Surgery; David Solomon of the UCSF Department of Pathology, and Joanna J. Phillips of the UCSF Departments of Neurological Surgery and Pathology.

Funding: This work has been supported by research awards from: NIH/NLM R01LM013897 and UC/CRCC CRN-19-586041 to A.D.; the UCSF Glioma Precision Medicine Program to A.D., S.C., J.J.P., D.S.; NIH/NINDS R01CA246722 to A.D, N.G., and S.R.; UCSF Brain Tumor SPORE Biorepository NIH/NCI 5P50CA097257 to J.J.P.; a gift from the Panattoni family to A.D. and J.J.P.

About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is ranked among the top 10 hospitals nationwide, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland, Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit https://ucsfhealth.org. Follow UCSF Health on Facebook or on Twitter.

Source: University of California, San Francisco (UCSF)

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Tips for a Safe and Festive Holiday Season

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(Family Features) As people prepare to gather with family and friends this holiday season, it’s important to think about health and safety.

“With the holidays just around the corner, now is the perfect time to think about how you can help protect yourself from serious illness from flu, COVID-19 and RSV – and support your loved ones in doing the same,” said Dr. Rachel Levine, assistant secretary for health at the U.S. Department of Health and Human Services (HHS). “Vaccination is an important step in having a happy and healthy celebration.”

While preparing for holiday festivities, keep these recommendations in mind to help protect yourself from severe flu, COVID-19 and RSV.

Flu: Flu season usually peaks during the winter months, so now is a great time to get the 2024-25 flu vaccine. It’s recommended for people 6 months and older to lower their risk of infection or serious illness from the flu. In fact, people who skipped their flu shot last year were twice as likely to need medical help for the flu. The best time to get vaccinated is at least a couple of weeks before a holiday gathering. But getting vaccinated later in the season can still help. Encourage your family and friends to get the flu vaccine, too. Together you can create safer holiday celebrations.

COVID-19: Getting vaccinated against COVID-19 is also important for everyone ages 6 months and older. The updated COVID-19 vaccines offer the best protection against serious illness from the virus, especially for those at higher risk. This includes people with certain health conditions or older adults, which may include parents, grandparents and great aunts or uncles. By getting vaccinated, people of all ages can lower their risk of getting severely sick. In fact, young adults are at higher risk of developing Long COVID than older adults. However, staying up to date on your COVID-19 vaccines lowers your risk of Long COVID, too.

RSV: RSV can be especially risky for older adults and babies. That’s why everyone 75 and older, people 60-74 with certain health conditions or who live in a nursing home and pregnant people should get the RSV vaccine. Pregnant people should get the RSV vaccine at 32-36 weeks of pregnancy to help protect their newborns from severe RSV during their first six months of life.

As you prepare for the holidays, remember that prevention is the best way to keep from getting seriously sick from flu, COVID-19 and RSV. By getting vaccinated now, you can enjoy the holiday season with greater confidence and less risk of missing time together. Being vaccinated helps keep your symptoms milder if you get infected after vaccination so you can do the things you want to do with less risk of spreading infection.

Talk with your doctor about which vaccines are right for you as well as for any loved ones you help care for. Visit cdc.gov/RiskLessDoMore for more information on vaccines, or visit vaccines.gov to get started.

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The Effects of Flu, COVID-19 and RSV on Different Populations

People who are Black, Hispanic or who live in rural areas may be at higher risk of severe illness from flu, COVID-19 and RSV than others. Getting vaccinated is the best protection from getting seriously sick from these viruses. According to the Centers for Disease Control and Prevention (CDC):

  • Last flu season, Black adults were more than twice as likely as white adults to be hospitalized for flu.
  • Last flu season, Hispanic adults were more likely than white adults to be hospitalized for flu.
  • One in 3 adults living in rural areas have never been vaccinated against COVID-19. For people living in rural areas, health services may be far away. That can mean it takes some planning to get vaccinated. But being far from medical care also means it’s even more important to lower your risk of serious illness by getting vaccinated.

Photos courtesy of Shutterstock

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SOURCE:
United States Department of Health and Human Services

Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.


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8 maneras de vivir de manera más saludable en 2025

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Tome medidas para limitar el riesgo de enfermedad cardiovascular

(Family Features) En la última década se ha producido un aumento de factores de riesgo cardiovascular, como la hipertensión arterial no controlada, la diabetes y la obesidad, cada uno de los cuales aumenta el riesgo de desarrollar enfermedades cardíacas y accidentes cerebrovasculares. Estas tendencias están llevando a los investigadores a concluir que la prevalencia de las enfermedades cardiovasculares (ECV) seguirá aumentando.

Más del 60 % de los adultos estadounidenses tendrán algún tipo de ECV para 2050, según las proyecciones previstas de la American Heart Association, que celebra 100 años de servicio salvando vidas como la principal organización mundial sin fines de lucro dedicada a la salud del corazón y el cerebro de todos. Además, se espera que los costos totales relacionados con las ECV casi se tripliquen en ese período hasta alcanzar más de 1.8 trillones de dólares.

El aumento será impulsado por una población más anciana y diversa, pero estos factores de riesgo están aumentando incluso entre niños y adultos.

“Reconocemos que el panorama de la salud cardiovascular cambiará en las próximas tres décadas debido al tsunami que se avecina de aumentos en los costos de la atención médica, una población de mayor edad que vive más tiempo y un número cada vez mayor de personas de poblaciones de pocos recursos”, dijo la voluntaria de la American Heart Association, Karen E. Joynt Maddox, M.D., M.P.H., FAHA. “Aun así, estas siguen siendo las principales causas de muerte y discapacidad en Estados Unidos”.

Si bien se necesitan cambios sistemáticos continuos en la ciencia, las políticas y la atención de salud, la mayoría de las ECV se pueden prevenir a nivel individual. Usted puede ayudar a cambiar el rumbo de las terribles perspectivas de la ECV y, al mismo tiempo, mejorar su propia salud siguiendo y alentando a otros a seguir los “Life’s Essential 8” de la American Heart Association.

Coma mejor. Intente seguir un patrón de alimentación saludable en general que incluya alimentos integrales, frutas y verduras, proteínas magras, frutos secos, semillas y cocinar con aceite de oliva y de canola.

Manténgase activo. Los adultos deben realizar 2 horas y media de actividad física moderada o 75 minutos de actividad física vigorosa por semana. Los niños deben tener 60 minutos cada día, incluidos juegos y actividades estructuradas.

Deje el tabaco. El uso de productos que suministran nicotina por inhalación, que incluyen cigarrillos tradicionales, cigarrillos electrónicos y vaporizadores, es la principal causa de muerte evitable en los EE. UU.

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Duerma bien. La mayoría de los adultos necesitan dormir entre 7 y 9 horas cada noche. Los niños de 5 años o menos necesitan entre 10 y 16 horas, incluidas las siestas; de 9 y 12 horas, en niños de 6 y 12 años, y entre 8 y 10 horas, entre los 13 y 18 años.

Controle el peso. Lograr y mantener un peso saludable tiene muchos beneficios. El índice de masa corporal es un indicador útil. El IMC óptimo es menor de 25, pero menor de 18.5 se considera bajo peso. Puede calcularlo en línea o consultar a un profesional de la salud.

Controle el colesterol. Los niveles altos de colesterol no HDL, o “malo”, pueden provocar enfermedades cardíacas. Su profesional de atención médica puede considerar el colesterol no HDL como el número preferido para monitorear, en lugar del colesterol total, porque se puede medir sin ayuno previo y se calcula de manera confiable entre todas las personas.

Controle el nivel de azúcar en sangre. La mayor parte de los alimentos que consume se convierten en glucosa (o azúcar en sangre) que su cuerpo utiliza como energía. Con el tiempo, los niveles altos de azúcar en sangre pueden dañar el corazón, los riñones, los ojos y los nervios.

Controle la presión arterial. Mantener su presión arterial dentro de rangos aceptables puede ayudarle a mantenerse saludable por más tiempo. Los niveles inferiores a 120/80 mmHg son óptimos. La presión arterial alta se define como una presión sistólica de 130 a 139 mm Hg (el número superior en una lectura) o una presión diastólica de 80 a 89 mm Hg (el número inferior).

Encuentre más formas de cuidar su salud en el nuevo año y más allá en heart.org.

Foto cortesía de Shutterstock

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SOURCE:
American Heart Association

Nuestra sección de estilo de vida en STM Daily News es un centro de inspiración e información práctica, que ofrece una variedad de artículos que tocan varios aspectos de la vida diaria. Desde consejos sobre finanzas familiares hasta guías para mantener la salud y el bienestar, nos esforzamos por empoderar a nuestros lectores con conocimientos y recursos para mejorar sus estilos de vida. Ya sea que esté buscando ideas de actividades al aire libre, tendencias de moda o recomendaciones de viaje, nuestra sección de estilo de vida lo tiene cubierto. Visítanos hoy en https://stmdailynews.com/category/lifestyle/ y embárcate en un viaje de descubrimiento y superación personal


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Why winter makes you more vulnerable to colds – a public health nurse explains the science behind the season

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Respiratory viruses rise in the wintertime, but not because people are outside in the cold. gilaxia/E+ via Getty Images

Libby Richards, Purdue University

You’ve probably heard “Don’t go outside in the winter with your hair wet or without a coat; you’ll catch a cold.”

That’s not exactly true. As with many things, the reality is more complicated. Here’s the distinction: Being cold isn’t why you get a cold. But it is true that cold weather makes it easier to catch respiratory viruses such as the cold and flu.

Research also shows that lower temperatures are associated with higher COVID-19 rates.

As a professor of nursing with a background in public health, I’m often asked about infectious disease spread, including the relationship between cold and catching a cold. So here’s a look at what actually happens.

Many viruses, including rhinovirus – the usual culprit for the common cold – influenza, and SARS-CoV-2, the virus that causes COVID-19, remain infectious longer and replicate faster in colder temperatures and at lower humidity levels. This, coupled with the fact that people spend more time indoors and in close contact with others during cold weather, are common reasons that germs are more likely to spread.

The flu and respiratory syncytial virus, or RSV, tend to have a defined fall and winter seasonality. However, because of the emergence of new COVID-19 variants and immunity from previous infections and vaccinations decreasing over time, COVID-19 is not the typical cold-weather respiratory virus. As a case in point, COVID-19 infection rates have surged every summer since 2020.

Virus transmission is easier when it’s cold

More specifically, cold weather can change the outer membrane of the influenza virus, making it more solid and rubbery. Scientists believe that the rubbery coating makes person-to-person transmission of the virus easier.

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It’s not just cold winter air that causes a problem. Air that is dry in addition to cold has been linked to flu outbreaks. That’s because dry winter air further helps the influenza virus to remain infectious longer. Dry air, which is common in the winter, causes the water found in respiratory droplets to evaporate more quickly. This results in smaller particles, which are capable of lasting longer and traveling farther after you cough or sneeze.

How your immune system responds during cold weather also matters a great deal. Inhaling cold air may adversely affect the immune response in your respiratory tract, which makes it easier for viruses to take hold. That’s why wearing a scarf over your nose and mouth may help prevent a cold because it warms the air that you inhale. https://www.youtube.com/embed/7JQ78oLFV9A?wmode=transparent&start=0 Cold weather can affect nasal immunity.

Also, most people get less sunlight in the winter. That is a problem because the sun is a major source of vitamin D, which is essential for immune system health. Physical activity, another factor, also tends to drop during the winter. People are three times more likely to delay exercise in snowy or icy conditions.

Instead, people spend more time indoors. That usually means more close contact with others, which leads to disease spread. Respiratory viruses generally spread within a 6-foot radius of an infected person.

In addition, cold temperatures and low humidity dry out your eyes and the mucous membranes in your nose and throat. Because viruses that cause colds, flu and COVID-19 are typically inhaled, the virus can attach more easily to these impaired, dried-out passages.

What you can do

The bottom line is that being wet and cold doesn’t make you sick. That being said, there are strategies to help prevent illness all year long:

Person's hands covered with suds under a running faucet.
Handwashing is a time-tested strategy for reducing the spread of germs at any time of year. Mike Kemp/Tetra Images via Getty Images

Following these tips can ensure you have a healthy winter season.

This is an updated version of an article originally published on Dec. 15, 2020.

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Libby Richards, Professor of Nursing, Purdue University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.

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