Health

The promising effect of a smart virus in the treatment of invasive brain cancer

Published

11 months ago

22/05/2023

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The promising effect of a smart virus in the treatment of invasive brain cancer. Joint research by American and Canadian researchers shows that a combination therapy using an engineered virus can help treat aggressive brain cancer.

The promising effect of a smart virus in the treatment of invasive brain cancer

A new joint project by American and Canadian researchers has detailed the safe and promising use of an engineered oncolytic virus called DNX-2401 alongside immunotherapy for the treatment of glioblastoma.

Although this study did not reach its primary efficacy endpoint, it achieved a 12-month survival rate that exceeded the predetermined efficacy threshold. The combination of intratumoral DNX-2401 and intravenous pembrolizumab showed clinical benefit in more than half of the patients, with several experiencing significant tumor shrinkage.

This research, which was conducted by the researchers of “M.D. Cancer Center” “MD Anderson Cancer Center” and “University of Toronto” (UToronto) has been done, it opens new doors to provide potential combination strategies. This study met its primary safety expectation and showed that the compound was well tolerated by patients without causing dose-limiting toxicity.

“Frederick Lang”, director of neurosurgery at MD Anderson Cancer Center and one of the researchers of this project, said: This viral treatment is a different approach from the current standard of care.

He added: “Our previous experiment showed that the virus not only works by directly killing cancer cells but also effectively activates the innate immune system to turn immunologically cold tumors into hot tumors.” This prompted us to evaluate the combination with the presence of inhibitors. Now we see that this combination can improve survival in a subset of patients.

Glioblastoma is an aggressive brain cancer in that patients usually experience recurrence of the disease despite the use of standard methods of radiation therapy and chemotherapy.

Although blocking the immune checkpoint has improved outcomes in other types of cancer, glioblastoma’s unique immunosuppressive microenvironment protects it from infiltrating immune cells, making it extremely difficult to treat with immunotherapy. In contrast, the smart virus is efficient in killing glioblastoma cells and activating the immune response.

Long co-developed the DNX-2401 virus with Juan Fueyo and Candelaria Gomez-Manzano, both professors of neuro-oncology. It’s a cold virus that was engineered to selectively target and attack glioblastoma cells while avoiding normal cells.

In the results of a previous phase I trial, treatment with DNX-2401 alone effectively induced cancer cell death and altered the microenvironment to allow T-cell infiltration. This led to an anti-tumor immune response. Twenty percent of patients with recurrent glioblastoma survived for at least three years, and tumor shrinkage continued for more than one year in those who responded completely to treatment.

These results showed increased expression of PD-1 after treatment, indicating that the immune system may be primed to respond to anti-PD-1 immunotherapy. Clinical models confirmed this hypothesis, and treatment with pembrolizumab one week after DNX-2401 treatment improved survival compared to either treatment alone.

Foyo said: The purpose of injecting the virus into the patient’s brain tumor is to wake up the immune system and start healing from within the patient. Patients who respond well develop inflammation within the tumor after injection. This triggers an immune response that first kills the virus. Once the virus is gone, the continued immune response stimulated by additional immunotherapy kills cancer cells in a highly regulated manner without the side effects common to chemotherapy or radiation.

Combined treatment increases survival and improves the quality of life in patients. “Our research using this smart virus is ongoing, and we are encouraged to continue to see a small number of patients who show very dramatic tumor eradication,” Manzano said. These results motivate us to continue searching for the best combination strategy that can optimize the use of the virus to improve patient outcomes.

Clinical trials are currently underway using MSCs to deliver the smart virus to and within the tumor. Future clinical trials will evaluate alternative therapies such as checkpoint inhibitors or CAR T cell therapy in combination with DNX-2401.

This research was published in “Nature Medicine” magazine.

Health

Why do people listen to sad songs?

Published

1 week ago

14/04/2024

pouyan

Perhaps the main reason for listening to sad music is not to enjoy the feeling of sadness, and people listen to this type of music because of the sense of connection. So why do people listen to sad songs?

Why do people listen to sad songs?

There is a paradox in sad music: we don’t enjoy sadness in real life, but we enjoy art that makes us feel that way. Countless researchers since Aristotle tried to solve this contradiction. Perhaps through music, we experience a kind of catharsis of negative emotions. Catharsis here means refinement and cultivation of the soul. Maybe there is an evolutionary advantage in this feeling of sadness, or maybe we want to value our suffering. Maybe our body produces hormones in response to anxiety disorder, music that leads to a sense of comfort.

According to the New York Times, Dr. Nob, an experimental philosopher and psychologist at Yale University, in a new study published in the Aesthetic Education Journal, raised the question, “What is the purpose of sad music?” He tried to solve the contradiction of this kind of music. Over the years, he came to the conclusion that people often have two perceptions of the same thing. For example, they can consider people as artists if they have a set of characteristics such as an innate talent for working with a brush; But if they don’t have abstract values such as creativity, curiosity or interest and just recreate old masterpieces for profit, we can say they are not artists. According to Dr. Nob and his former student Tara Venkatsan, a cognitive scientist, perhaps sad music also has a dual nature.

The aforementioned research shows that our emotional response to music is multidimensional; You don’t necessarily feel happy when you listen to a beautiful song, and you don’t necessarily feel sad when you listen to a sad song. According to a 2016 study, the emotional response of 363 listeners to sad songs was divided into three categories: sadness and strong negative emotions such as anger, panic, and despair, nostalgia, quiet sadness and self-compassion, and finally sweet sadness is pleasant pain. It comes from consolation and understanding. Many respondents reported a combination of all three. The researchers called this research “Fifty Blue Spectrums”.

Given the layers of emotion and the ambiguity of language, it’s no wonder that sad music creates a paradox; But it is not clear why it induces a sense of pleasure or meaning. Some psychologists have investigated how certain aspects of music, such as position, pitch, rhythm, and resonance, are related to listeners’ emotions. According to research, certain forms of songs have an almost universal function: for example, among different countries and cultures, lullabies have similar acoustic characteristics that make children and adults feel safe. Thomas Irola, a musicologist at the University of Durham in England and researcher of the “Fifty Spectrum” study, says:

Throughout life, we learn to make connections between our feelings and what we hear. We recognize emotional expression in speech, and often these cues are used in a similar way in music.

Other researchers, such as Patrick Joslin, a music psychologist from Uppsala University in Sweden, believe that such findings reveal the value of sad music. Sad music, he writes in an essay, asks why “the second movement of Beethoven’s Eroica symphony evokes a sense of sadness?” It leads to the question, “Why does a slow step lead to a feeling of sadness?”

According to the findings of Joslin and his colleagues, there are cognitive mechanisms through which feelings of sadness are induced in listeners. These mechanisms include unconscious reactions in the brain stem, synchronization of the rhythm with the internal rhythm such as the heartbeat, conditional reactions to certain sounds, the arousal of memories, emotional contagion, and reflexive measurement of music. Perhaps because sadness is such a strong emotion, it can evoke an empathetic and positive response. In fact, understanding other people’s grief provokes a social response.

Why do people listen to sad songs?

The purpose of listening to sad music is not necessarily to convey sadness; Rather, it is creating a sense of connection.

Dr. Nob, along with Dr. Venkatsan and George Newman, a psychologist at the Rotman School of Management, designed a two-stage experiment to test the hypothesis. In the first part of the experiment, they gave one of four song descriptions to more than 400 participants. In the description of the first song, it was written: “transmitting complex and deep emotions, but technically full of errors.” The second track was described as: “music without technical errors that do not convey complex and deep emotions.” The third song was described as “highly emotional and technically flawless” and the fourth song was described as “technically flawed and non-emotional”.

Subjects were asked to indicate on a seven-point scale whether their song conveyed the intent of the music or not. Their goal was to show how important it is for music to express emotion and generally happiness, sadness, hate, or any other emotion on an intuitive level. Overall, subjects reported that deeply emotional but technically flawed songs best reflected the nature of music. In other words, the emotional expression had a more prominent value than the technical aspect.

In the second part of the experiment, which included 450 new subjects, the researchers gave each participant 72 descriptions of emotional songs that convey feelings such as “humiliation,” “narcissism,” “inspiration,” and “lust.” For comparison, they gave participants phrases that convey conversational interaction in expressing people’s feelings. For example, one of the phrases was: “An acquaintance is talking to you about the past week and his feeling of passion”. In general, the emotions that the subjects receive are strongly rooted in the “purpose of the music” and are similar to the emotions that make people feel close to each other in conversation: emotions such as love, joy, loneliness, sadness, ecstasy, and relaxation.

Mario Etti Picker, a philosopher at Lowell University of Chicago, finds the results of this study interesting. After reviewing the data, he came up with a relatively simple idea: “Perhaps the reason we listen to music is not just an emotional response, but we do it to understand the connection with others; Because, according to the reports of many subjects, sad music is not necessarily enjoyable despite its artistic dimensions. In other words, according to the paradox of sad music, our love of music is not the result of direct praise of sadness; Rather, it is the result of valuing communication with others.”

Dr. Irola also concluded in his research that empathic people are likely to be moved by unfamiliar sad music. They tend to engage in this kind of imaginary grief. These people also show significant hormonal changes in response to sad music. But sad music, like an onion, has many layers, and this explanation can give rise to other questions. For example, who should we communicate with? Artist or with our own past? Or even with an imaginary person?

Health

Inventing a new drug to treat influenza

Published

1 week ago

13/04/2024

pouyan

A new drug developed to treat severe influenza works in a unique way, unlike what a drug would expect, to treat lung disease and infection.

Inventing a new drug to treat influenza!

A new drug to treat severe flu successfully keeps patients at the right level of lung inflammation to protect against lung damage while still allowing the immune system to fight infection. This drug has been effective in mice even a few days after infection.

According to New Atlas, if you’ve ever had the flu, you’ve most likely contracted the influenza A virus (IAV). Compared to influenza B virus, infection with type A often causes more severe symptoms. But, while many of us have experienced the fever and chills, headache and muscle aches, fatigue, sore throat, and cough of the common flu, severe infection with the animal IAV strain is different and potentially life-threatening.

Severe infection of this type of influenza causes a special type of cell death called necroptosis in infected cells. While this is a natural process designed to limit viral spread by actively eliminating infected cells and mobilizing the immune system to respond, necroptosis can activate a hyperinflammatory response and cause collateral lung damage that is potentially fatal. Is. Other than managing its symptoms, there are few treatment options for treating severe influenza.

In a new study, researchers from Tufts University School of Medicine, St. Jude Children’s Research Hospital, the University of Houston, and Fox Chase Cancer Center collaborated to test a drug called UH15-38 that could prevent this flu-related lung damage in mice. It prevents and allows the immune system to fight the virus.

“Our drug significantly increased survival and reduced symptoms of influenza virus infection,” said Paul Thomas, co-author of the study. The new drug reduced dangerous inflammation and even seemed to improve the adaptive response to the virus.

Achieving the Goldilocks effect, or the effect of the right amount of the drug on inflammation, required researchers to use clever chemistry along with a thorough understanding of the underlying mechanisms of necroptosis.

Receptor-interacting protein kinase 3 (RIPK3) is an essential part of the necroptosis cell death pathway, but it also controls another cell death pathway called apoptosis. Both types of cell death trigger opposing immune responses. Apoptotic death usually results in muted immunological responses, while necroptosis releases molecules that cause inflammation. UH15-38 was designed to prevent the stimulation of the necroptosis pathway by RIPK3, while still allowing cell death and removing infected cells in a less inflammatory manner.

Alexei Degterev, an associate professor of developmental, molecular, and chemical biology at Tufts University School of Medicine and one of the authors of the paper, says: “If you eliminate necroptosis, you will still limit virus replication without severe damage to the lungs.” Necroptosis does not appear to be necessary to limit viral activity, so if we can block it, we can protect the host by reducing inflammation in the lungs.

The researchers tested the drug UH15-38 in mouse models and found that high doses of the drug provided protection against the usually fatal IAV influenza. At low doses, the UH15-38 drug protected mice against similar amounts of influenza that humans experience. Notably, the mice were protected even if they received the drug several days after being infected with the disease.

“This drug can do something we haven’t seen before,” says Thomas. We can start five days after the initial infection and still see benefits. Completely removing the RIPK3 protein is not a great choice because then the immune system cannot clear the virus. When we removed only the necroptosis, the animals did better because they still had apoptosis and could still get rid of the infectious cells, but their condition was not as severely inflammatory.

UH15-38 improved survival by preventing collateral necroptosis damage to type 1 alveolar epithelial cells, a special type of cell in the lungs that facilitates gas exchange. Damage to these cells can make it difficult for oxygen to enter the blood and carbon dioxide from it, and cause symptoms such as shortness of breath, wheezing, and chest tightness. The drug also reduced the number of immune cells associated with inflammation, such as neutrophils, in the mice.

Often, the worst part of the flu happens after the virus is under control when inflammation destroys lung cells, Thomas says. UH15-38 can reduce influenza-induced inflammation while leaving viral clearance and other functions of tissue and immune responses intact. This makes the drug a promising option to move towards clinical use.

The next step is clinical and human trials safely. Researchers are testing whether UH15-38 is effective in treating other respiratory diseases.

While the worst of COVID-19 may be upon us, another pandemic is expected, and we need something that protects the host regardless of how it is infected, Degtref says. This study demonstrates the possibility of achieving such a goal and renews interest in how cell death occurs against infections.

This study was published in the journal Nature.

Health

Testing a vaccine that reduces liver tumors

Published

2 weeks ago

12/04/2024

pouyan

Testing a vaccine that reduces liver tumors. A combination of a vaccine and an immunotherapy drug has reduced advanced liver cancer in trials.

Testing a vaccine that reduces liver tumors

A third of patients with advanced liver cancer who received a personalized vaccine in a small trial saw their liver tumors shrink.

According to IA, Geneos Therapeutics has announced the publication of positive safety data, immunogenicity, and effectiveness of its solution in Nature Medicine magazine.

According to this study, hepatocellular carcinoma is the most common type of primary liver cancer and is also one of the leading causes of cancer-related deaths worldwide. The disease is responsible for more than 12,000 deaths each year in the United States alone.

Hepatocellular carcinoma or hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. This disease is the third leading cause of cancer deaths worldwide.

Hepatocellular carcinoma occurs in conditions of chronic inflammation of the liver and is most associated with chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol, aflatoxin, or pyrrolizidine alkaloids.

Although advances have been made in the treatment of advanced liver cancer, the five-year survival rate remains below 10%.

current study

The first and last patients were enrolled in the study on June 16, 2020, and June 14, 2023, respectively, and all 36 patients in this study received their personalized vaccine.

In this study, researchers used samples from patients’ tumors to make vaccines based on the new mutations found in each patient’s tumor.

Liver cancer contains fewer mutations that reduce the effectiveness of immunotherapies. The results show that vaccines based on mutations present only in the patient’s tumor can boost the immune system. This is done in a way that improves the ability to detect and attack cancers.

The vaccine essentially trains the immune system to recognize antigens that are being ignored, says Dr. Mark Yarkwan, who led the study.

Patients were given vaccines along with widely used immunotherapy. With this combination, they experienced a 30% tumor reduction. Three of them had a complete response, meaning no detectable signs of tumor remained after a median follow-up of 21.5 months.

“This certainly shows that the vaccine has indeed increased clinical efficacy,” Yarkvan added.

Side effects and adverse reactions

There were no serious side effects for the patients, and the only complication was pain at the injection site.

Genius’ innovative treatment involves a DNA vaccine that delivers the genetic code of mutated proteins to cells via a tiny electrical impulse. Each vaccine can target up to 40 mutated genes.

Despite the small size of the study, its results are important for the advancement of the field, says Niranjan Sardsai, president of Genius. “Our mechanism validates every step from vaccination to tumor reduction that is necessary to explain the immunological basis of the observed clinical responses,” he said in a statement.

Yarkvan also said that larger trials were being planned, but declined to provide details.

According to this study, more than 800,000 people worldwide are diagnosed with this type of cancer every year. It is also the leading cause of cancer deaths worldwide and accounts for more than 700,000 deaths annually.

It is predicted that the number of new cases of liver cancer will increase by about 55% each year between 2020 and 2040. It is also predicted that 1.3 million people will die from liver cancer in 2040.

Preliminary findings of the study were presented at the American Association for Cancer Research in San Diego.