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City of Hope scientists develop targeted chemotherapy able to kill all solid tumors in preclinical research

The City of Hope-developed investigational small molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected, a new study reports.

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LOS ANGELES /PRNewswire/ — Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, today published a new study explaining how they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed a targeted chemotherapy that appears to annihilate all solid tumors in preclinical research. As the scientists continue to investigate the foundational mechanisms that make this cancer-stopping pill work in animal models, they note that there is an ongoing Phase 1 clinical trial testing the City of Hope-developed therapeutic in humans.

The City of Hope-developed small molecule AOH1996 targets a cancerous variant of the protein PCNA. In its mutated form, PCNA is critical in DNA replication and repair of all expanding tumors. Here we see untreated cancer cells (left) and cancer cells treated with AOH1996 (right) undergoing programmed cell death (violet). (Photo credit: City of Hope)

Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant, said Linda Malkas, Ph.D., professor in City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology. However, the cancer-killing pill Malkas has been developing over the past two decades, AOH1996, targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumors.

“PCNA is like a major airline terminal hub containing multiple plane gates. Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells. Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” said Malkas, senior author of the new study published in Cell Chemical Biology today. “Results have been promising. AOH1996 can suppress tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. The investigational chemotherapeutic is currently in a Phase 1 clinical trial in humans at City of Hope.”

AOH1996 has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers and is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Malkas co-founded and holds financial interest in.

The researchers tested AOH1996, a small molecule PCNA inhibitor, in more than 70 cancer cell lines and several normal control cells. They found that AOH1996 selectively kills cancer cells by disrupting the normal cell reproductive cycle. It targets something called transcription replication conflicts, which occur when mechanisms responsible for gene expression and genome duplication collide. The investigational therapy prevented cells with damaged DNA from dividing in G2/M phase and from making a copy of faulty DNA in S phase. As a result, AOH1996 caused cancer cell death (apoptosis), but it did not interrupt the reproductive cycle of healthy stem cells.

“No one has ever targeted PCNA as a therapeutic because it was viewed as ‘undruggable,’ but clearly City of Hope was able to develop an investigational medicine for a challenging protein target,” said Long Gu, Ph.D., lead author of the study and an associate research professor in the Department of Molecular Diagnostics and Experimental Therapeutics at Beckman Research Institute of City of Hope. “We discovered that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. Now that we know the problem area and can inhibit it, we will dig deeper to understand the process to develop more personalized, targeted cancer medicines.”

Interestingly, experiments showed that the investigational pill made cancer cells more susceptible to chemical agents that cause DNA or chromosome damage, such as the chemotherapy drug cisplatin, hinting that AOH1996 could become a useful tool in combination therapies as well as for the development of new chemotherapeutics.

“City of Hope has world leaders in cancer research. They also have the infrastructure to drive translational drug discovery from the laboratory into the clinic for patients in need,” said Daniel Von Hoff, M.D., study co-author and a distinguished professor at Translational Genomics Research Institute, part of City of Hope.

City of Hope’s groundbreaking translational research history includes developing the technology underlying synthetic human insulin, a breakthrough in diabetes management, and monoclonal antibodies, which are integral to widely used, lifesaving cancer drugs, such as trastuzumab, rituximab and cetuximab.

As a next step, the researchers will look to better understand the mechanism of action to further improve the ongoing clinical trial in humans. Individuals interested in the Phase 1 clinical trial should review the eligibility requirements at clinicaltrials.gov. If eligible, call 626-218-1133 or visit City of Hope’s clinical trials webpage.

The Cell Chemical Biology study entitled “Small Molecule Targeting of Transcription-Replication Conflict for Selective Chemotherapy” was supported by the Department of Defense (W81XWH-11-1-0786, W81XWH-19-1-0326 under BC181474 and BC181474P1), National Institutes of Health/National Cancer Institute (R01 CA121289, R01 CA225843), St Baldrick’s Foundation, the Alex Lemonade Stand Foundation, Tobacco-Related Disease Research Program (TRDRP-T31IP626), Melanoma Research Foundation (MRF-717178), the ANNA Fund, RDL Foundation, Analytical Pharmacology Core supported by the National Cancer Institute of the National Institutes of Health (P30CA033572).

About City of Hope
City of Hope’s mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on FacebookTwitterYouTubeInstagram and LinkedIn.

SOURCE City Of Hope

Health

6 Tips to Maintain Your Skin’s Health

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(Family Features) Your skin is your first line of defense against the outer world. As the body’s largest organ, it protects you from bacteria, viruses and other environmental hazards, including pollution, ultraviolet (UV) rays from the sun and more. It also helps regulate body temperature, recognizes pain sensations and alerts you to potential health problems, making it one of the body’s ultimate multitaskers.

While some factors that impact your skin – like genetics, aging, hormones and certain health conditions – are out of your control, there are steps you can take to support and maintain your skin’s health.

Protect Yourself from the Sun
No matter the season, exposure to UV rays from the sun can cause wrinkles, age spots and other types of damage, which could lead to skin cancer. To protect your skin from these harmful rays, use topical sunscreen daily with a sun protection factor (SPF) of at least 30 – even when it’s overcast – and reapply regularly.

Boost Your Diet with Antioxidants
A well-balanced diet consisting of plenty of fruits, vegetables, lean proteins and whole grains is an important part of maintaining healthy skin. However, diet alone isn’t always enough.

Many dermatologists recommend Heliocare Daily Use Antioxidant Formula as an oral dietary supplement. It contains Fernblock PLE technology, an exclusive plant extract rich in antioxidant properties that works to counteract the negative effects of free radicals, which are unstable atoms generated through everyday life that can damage skin cells. Free radical damage can cause wrinkles, discoloration and other signs of environmental aging. Taking a supplement daily, like Heliocare, can enhance antioxidant intake to help maintain skin health. Plus, it serves as a companion to topical SPF.

Keep Skin Moisturized
Daily use of a face and body moisturizer can help maintain a healthier skin barrier. This helps draw moisture to your skin from the air and lock it in. For best results and optimal hydration, moisturize within minutes of drying off after bathing to trap in moisture. Also remember to drink plenty of water, which can help keep skin hydrated, too.

Reduce Stress
Uncontrolled stress can trigger the release of hormones that dull skin and cause it to produce more oil, which can result in breakouts and other skin problems. To encourage clearer, healthier skin, take steps to reduce stress such as scaling back your to-do list, setting reasonable limits, making time for things you enjoy or trying a stress-reduction technique like yoga, meditation or tai chi.

Wear Protective Clothing
In addition to topical SPF, covering skin as opposed to leaving it exposed to the elements can protect from sun damage. When UV rays are at their peak, typically in the middle of the day, consider wearing long sleeves, pants and a large-brimmed hat.

Get a Good Night’s Rest
During sleep, your body repairs itself and regenerates skin cells. The National Sleep Foundation recommends adults get 7-9 hours of sleep each night, during which time the body produces higher levels of collagen, a protein that supports healthier looking (and functioning) skin. Lack of sleep and collagen loss go hand in hand.

Learn more about skin, antioxidants and free radical damage at heliocare.com.

Photo courtesy of Shutterstock


SOURCE:
Heliocare

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Exploring the Healthiest Communities in the United States: California Counties Shine Bright

Discover how California’s Marin County leads the healthiest U.S. communities, boasting high life expectancy and low obesity rates in a recent study.

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A recent study by MarketWatch has unveiled a list of the healthiest communities in the United States, with California counties claiming top spots. Marin County, nestled across the Golden Gate Bridge from San Francisco, emerged as the healthiest county, boasting a remarkable life expectancy of 85, a lower-than-average adult obesity rate, and a mere 5 percent of residents without health insurance.

The study evaluated 576 U.S. counties using 14 key metrics, including food insecurity, healthcare access, life expectancy, health insurance coverage, and environmental factors like water and air quality. Western states dominated the top 10 list, with Colorado, Hawaii, and Montana also showcasing exemplary county health profiles.

The findings emphasized a correlation between community health and wealth, with affluent areas exhibiting lower rates of food insecurity and higher levels of health insurance coverage. The presence of nature parks in many of the healthiest counties underscored the positive impact of green spaces on well-being, aligning with scientific research on the subject.

However, the study also shed light on disparities, highlighting that residents in the unhealthiest counties face challenges such as limited access to grocery stores, higher rates of food insecurity, and inadequate primary care services. Harris County, Texas, home to Houston, was identified as the least healthy county due to high uninsured rates and poor environmental quality.

In California, 37 out of 58 counties were ranked, with Marin, San Francisco, and San Mateo counties clinching top positions. The data revealed a stark contrast in median incomes between the healthiest and unhealthiest counties, with Marin County boasting a median income well above the national average.

This comprehensive analysis serves as a valuable resource for policymakers and healthcare professionals striving to address disparities and promote well-being across communities. It underscores the importance of factors such as access to healthcare, environmental quality, and socioeconomic status in shaping overall community health outcomes.

https://patch.com/california/sanrafael/ca-has-3-10-healthiest-counties-u-s-new-study-says

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Empoderar a los afroamericanos con el aprendizaje de habilidades que salvan vidas

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(Family Features) En el espíritu del Mes de la Historia Afroamericana, usted puede empoderarse, educar a otros y mejorar la salud cardíaca de su comunidad convirtiéndose en un defensor de la RCP (reanimación cardiopulmonar) y del DEA (desfibrilador externo automático). Compartir la importancia de estas habilidades que salvan vidas puede ayudar a crear un futuro más saludable para las generaciones futuras.

Según la American Heart Association, los afroamericanos tienen la mayor incidencia de paro cardíaco fuera del hospital y tienen muchas menos probabilidades de sobrevivir. El paro cardíaco en las colonias negros se asocia con bajas tasas de tratamiento y supervivencia; los estudios han demostrado tasas más bajas tanto de RCP como de uso de DEA por parte de transeúntes en estas colonias.

En Estados Unidos, las desigualdades en salud son diferencias sistemáticas en el estado sanitario de diferentes grupos demográficos y, a menudo, son el resultado de barreras como el racismo, la pobreza, la discriminación, la falta de vivienda asequible, educación de calidad y acceso a la atención médica.

El Mes de la Historia Afroamericana sirve como telón de fondo relevante para la campaña Nation of Lifesavers de la American Heart Association, cuyo objetivo es alinear los principios de empoderamiento, participación comunitaria y equidad en salud. Al celebrar la abundante herencia y la resiliencia de la comunidad afroamericana, también se puede reconocer la importancia de fomentar la educación sobre la salud cardíaca y construir un legado de salud.

Puede defender la importancia de la capacitación en RCP y DEA compartiendo esta importante información en su comunidad.

RCP
Debido a que alrededor del 70% de los paros cardíacos fuera del entorno hospitalario ocurren en el hogar, aprender RCP puede salvar la vida de alguien que conoce y ama. De hecho, si bien el 90% de las personas que sufren un paro cardíaco fuera de un entorno hospitalario no sobreviven, se pueden duplicar o triplicar las posibilidades de supervivencia de una víctima realizando RCP de inmediato. Consta de dos sencillos pasos:

  1. Llamar al 9-1-1 (o enviar a alguien para que lo haga).
  2. Presionar fuerte y rápido en el centro del pecho.

DEA
Un DEA es un dispositivo portátil y liviano que administra una descarga eléctrica a través del pecho hasta el corazón cuando detecta un ritmo anormal y luego cambia el ritmo a la normalidad. Más del 15% de los paros cardíacos fuera de un entorno hospitalario ocurren en lugares públicos, lo que significa que los DEA de acceso público y la capacitación comunitaria desempeñan un papel importante en la desfibrilación temprana. La RCP combinada con el uso de un DEA ofrece las mejores posibilidades de salvar una vida.

Las ambulancias, los vehículos policiales, muchos camiones de bomberos y otros vehículos de primera respuesta contienen DEA. Además, se pueden encontrar en áreas públicas, como recintos deportivos, centros comerciales, aeropuertos y aviones, empresas, centros de convenciones, hoteles, escuelas, piscinas y consultorios médicos. Por lo general, puede buscar cerca de ascensores, cafeterías, áreas de recepción y en las paredes de los pasillos principales donde se reúne un gran número de personas.

Siga estos pasos para utilizar un DEA:

  1. Encienda el DEA y siga las indicaciones de voz.
  2. Retire toda la ropa que cubra el pecho. Si es necesario, seque el pecho.
  3. Retire el protector de las almohadillas y colóquelas en el pecho desnudo de la persona siguiendo la ilustración de las almohadillas.
  4. Enchufe el conector de las almohadillas al DEA, si es necesario.
  5. El DEA verificará si la persona necesita una descarga y le indicará cuándo administrarla. Mientras el DEA analiza, asegúrese de que nadie toque a la persona.
  6. Reanude la RCP si no es necesaria ninguna descarga. Si es necesaria una descarga, asegúrese de que nadie toque a la persona y presione el botón de “descarga” y luego reanude inmediatamente la RCP.
  7. Continúe la RCP hasta que llegue el personal de emergencia.

Obtenga más información y descubra cómo empoderarse a sí mismo y a su comunidad en heart.org/blackhistorymonth.

Foto cortesía de Shutterstock


SOURCE:
American Heart Association

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