Health
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.
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.

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.
“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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Family
5 consejos para la salud del corazón para las fiestas
La comida, las bebidas, los regalos y el tiempo con la familia hacen de las fiestas una ocasión feliz para las personas de todo el país. Sin embargo, toda esa celebración a veces puede convertirse en una distracción para mantener la salud del corazón.

(Family Features) La comida, las bebidas, los regalos y el tiempo con la familia hacen de las fiestas una ocasión feliz para las personas de todo el país. Sin embargo, toda esa celebración a veces puede convertirse en una distracción para mantener la salud del corazón.
De hecho, las alegrías de la temporada pueden estropearse para muchos, ya que las investigaciones muestran un aumento en los eventos cardíacos y las muertes por ataques cardíacos durante la última semana de diciembre. Según un estudio publicado en la revista de la American Heart Association, “Circulation”, ocurren más muertes por problemas cardíacos el 25 de diciembre que cualquier otro día del año, seguidas por el segundo número más grande el 26 de diciembre y el tercero el 1 de enero.
“Las vacaciones son un momento ajetreado, a menudo estresante, para muchos de nosotros”, dijo Mitchell S.V. Elkind, MD, MS, FAHA, director de ciencias clínicas de la American Heart Association. “Las rutinas se interrumpen. Es posible que tendamos a comer y beber más y a hacer menos ejercicio y relajarnos menos. Dormimos muy poco y experimentamos demasiado estrés. Si bien no sabemos exactamente por qué hay más ataques cardíacos mortales durante este tiempo, es importante tener en cuenta que estos factores pueden incrementarse, aumentando el riesgo de un evento cardíaco mortal”.
Ser consciente de este fenómeno anual y tomar algunas medidas importantes y saludables para el corazón puede ayudar a salvar vidas. Considere estos consejos del Dr. Elkind y los expertos de la American Heart Association.
- Conozca los síntomas y tome medidas. Los signos de un ataque cardíaco varían en hombres y mujeres, pero es importante reconocerlos temprano y llamar al 9-1-1 para obtener ayuda. Cuanto antes comience el tratamiento médico, mayores serán las posibilidades de supervivencia y de prevención del daño cardíaco.
- Celebre con moderación. Comer saludablemente durante las fiestas no tiene por qué significar privarse. Hay maneras de comer de manera inteligente, como limitar la ingesta de sodio y buscar pequeños intercambios saludables para que continúe sintiéndose lo mejor posible mientras come y bebe con moderación.
- Practique la buena voluntad hacia sí mismo. Tómese un tiempo para cuidarse durante esta temporada ajetreada. Leer un libro favorito, meditar o incluso jugar con mascotas son formas productivas de reducir el estrés de las interacciones familiares, las finanzas tensas, los horarios agitados, los viajes y otros factores estresantes que pueden provocar las vacaciones.
- Siga moviéndose. El ajetreo y el bullicio de la preparación para las fiestas a menudo deja de lado el ejercicio, pero es importante mantenerse activo tanto como sea posible. Sea creativo para mantenerse en movimiento dando un paseo familiar o jugando juegos físicamente activos con sus seres queridos.
- Tome sus medicamentos. Los horarios ocupados pueden hacer que algunas personas se salten los medicamentos, a veces incluso los olvidan en casa o no renuevan las recetas a tiempo. Trate de usar un cuadro de medicamentos como recordatorio y asegúrese de controlar los números de su presión arterial.
Descubra más formas de vivir una vida saludable para el corazón durante las fiestas y durante todo el año en heart.org.
Foto cortesía de Getty Images
SOURCE:
American Heart Association
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fitness
Scaling Back: 5 ways to manage your weight
For many people who wish to work toward a healthier weight, one of the greatest obstacles is figuring out where to begin.

(Family Features) For many people who wish to work toward a healthier weight, one of the greatest obstacles is figuring out where to begin.
These tips from SlimFast consultant and registered dietitian Maryann Walsh show it doesn’t take a drastic lifestyle overhaul to make an impact.
Eat Mindfully
Many people who struggle with their weight benefit from being more conscious about what they’re eating and why. For example, consider your eating habits, such as eating even when you’re not hungry whether that’s because it’s mealtime and you think you should eat, you’re satisfying a craving or using a tasty snack to cope with stress.
Recognizing why you’re eating is an important step toward correcting destructive eating patterns, but so is paying attention to the other details of the eating experience, including what you eat and how it makes you feel. Ultimately, this may allow you to choose healthier foods that nourish your body for the long-term, rather than the brief satisfaction that comes with less nutritious choices.
Consider Intermittent Fasting
One weight-loss method many people find success using is intermittent fasting, which involves abstaining from all food and beverages for a specified time period each day or week. While going too long without food can sometimes lead to excess hunger then overeating later, in shorter, controlled fasting timeframes one can often more easily achieve a caloric deficit, which is required for weight loss.
Prepare for your fasting phase by choosing foods that support satiety. Options like SlimFast’s Intermittent Fasting line of meal bars and protein shakes can help avoid a sense of deprivation with tasty flavors like the Vanilla Cupcake Snack Shake Mix and Vanilla Almond Crunch Complete Meal Bar. The shake mixes deliver 15 grams of slow-digesting protein, compared to whey protein, to help curb hunger, along with more than 20 vitamins and minerals. The meal bars clock in with 15 grams of protein and 10 grams of fiber.
Manage Stress
When you’re stressed, your body produces cortisol, which also raises insulin and can drive hunger and trigger cravings for comfort foods. In fact, that’s the very reason people tend to overeat when they’re under pressure. Light exercise and meditative practices can help you manage your mental strain. You might also consider talk therapy with a friend or professional or spend time unwinding with a book or music.
Get Proper Sleep
Poor sleep habits affect your weight in numerous ways. One is that when you’re feeling tired, your hunger and satiety hormones, ghrelin and leptin, can be affected, leading to an increase in caloric intake and subsequent weight gain. Additionally, when you’re tired, you’re more likely to take shortcuts like skipping workouts or opting for unhealthy convenience foods. All are reasons to make better rest a bigger priority.
Track Eating and Exercise
When you’re not paying attention to what you eat and how you move, you may not even realize how your habits are affecting your health. Logging what you eat, especially if you use a tool like an app that helps you see the nutrition breakdown, may give you a clearer idea of the quality and quantity of your intake. Similarly, when you’re specifically writing down the time you’re committing to physical activity, you’ll find it easier to identify patterns and pinpoint where you can make adjustments to increase your exercise.
Visit SlimFast.com to find more resources on weight management and intermittent fasting.
3 Tips for Intermittent Fasting
If you’re new to the idea of intermittent fasting, these tips can help you find greater success so you can see results.
- Pace yourself. Make a gradual transition so your body gets used to going without food for shorter periods of time before you work up to extended fasting periods.
- Stay hydrated. Avoid confusing thirst for hunger by upping your fluid intake. Staying hydrated and energized while you fast helps keep fatigue and brain fog at bay. Options like fruit-flavored SlimFast Intermittent Fasting Energizing Hydration Supplement Drink Mix won’t break your fast and can help you add variety as a flavorful alternative to water. They can provide the energy and focus you need between meals and are perfect for those who feel groggy or run-down while fasting.
- Set goals. Know what you want to achieve and why, so your “why” can keep motivating you to follow your intermittent fasting plan even when you’re tempted to quit.
Photo courtesy of Getty Images (woman and man exercising)
SOURCE:
SlimFast
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Health
Spasticity 101: A debilitating yet treatable common condition after a stroke

(Family Features) In the year following a stroke, about 1 in 3 stroke survivors will experience spasticity, a common post-stroke condition which causes muscle stiffness due to involuntary muscle contractions. Most commonly affecting the elbow, wrist and ankle, the condition may make it difficult to do activities people were able to do before their stroke like dressing, brushing their teeth or walking.
More than 3 million stroke survivors may wrestle with reduced independence and increased reliance on caregivers due to spasticity. The condition is particularly common in younger stroke survivors.
After a stroke, the way your brain communicates with your muscles may change. Muscles may be stiff or resistant to stretching. They may involuntarily contract or have a smaller range of motion.
“While there’s no cure for spasticity, working with your care team to find the best treatment options for you can help provide comfort, relief and independence,” said Richard D. Zorowitz, MD, volunteer past chair of the American Heart Association’s Stroke Council Rehabilitation and Recovery Committee and chief medical informatics officer and outpatient attending physician at MedStar National Rehabilitation Network.
Some common symptoms include painful muscle spasms; difficulty stretching muscles; stiffness in the arm, hand, leg and ankle; an arm folded and pressed against the chest with a curled wrist and fingers; an involuntary tight fist; pointed foot; curled toes; and overactive reflexes.
If left untreated, spasticity can cause painful and debilitating bone and joint deformities. Experts stress seeing a doctor as soon as symptoms develop. Assessment of the condition is critical in developing a treatment plan based on individual needs and goals, the severity of the condition and overall health.
Management plans may include targeted injections of botulinum toxin, oral medications, intrathecal baclofen pump therapy, physical therapy or other methods to improve the muscles’ ability to stretch and regain range of motion. Home modifications such as assistive devices and other adaptations to increase independence and safety may also help.
If you or a loved one is dealing with spasticity after a stroke, talk to your doctor or health care team about options to treat and manage it. Find resources and tools to help at Stroke.org/Spasticity. Spasticity education made possible through funding by Ipsen.
Knowing the Signs of Stroke Saved One Man’s Life
When Herbert “Hub” Miller worked as a global leader for an international agriculture science company, his boss ended every meeting with a reminder of the “FAST” acronym to recognize the signs of stroke: Face drooping, Arm weakness, Speech difficulties and Time to call 911.
“I’d sit back and think, ‘Here comes the whole FAST speech again; let’s move on,’” Miller said. “I didn’t know I’d ever use it on myself.”
In April 2021, Miller was working from home when he experienced throbbing head pain. As other symptoms began appearing, the 42-year-old remembered those meetings and checked off the symptoms: His face was numb, his left arm drooped and he struggled to form words.
It turned out to be a hemorrhagic stroke, a ruptured blood vessel bleeding into the brain. Miller’s odds of surviving weren’t good, but it wasn’t until he was recovering in intensive care that he understood the full impact of the stroke. It caused abnormal increases in muscle tone causing stiffness, pain and spasms known as spasticity, leaving him with mobility and cognitive challenges.
After the stroke, Miller struggled with once-simple tasks like drawing a clock, completing a word puzzle and playing memory games.
“Spasticity changed my life and added an additional hurdle to my stroke recovery,” Miller said. “Without being able to open and close my left hand, I can’t write, type or drive like I used to. Those are things most of us take for granted until we can’t do them.”
Miller worked on his penmanship at the same time his youngest son learned to write in the first grade. Miller asked the teacher to send home extra worksheets, and father and son did homework together.
“I don’t measure my success day by day, but when I look back to a year ago and where I am today, I am grateful every day how far I have come,” he said.
Photo courtesy of Getty Images (patient undergoing physical therapy)
SOURCE:
American Heart Association
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