Study reveals new strategy to tackle cancer

A study led by the Institut de Neurociències (INc-UAB) describes a new strategy to tackle cancer, based on inducing a potent stress in tumor causing cell destruction by autophagy. The mechanism has been revealed using the new antitumor drug ABTL0812, currently in clinical trial. Results has been validated using samples from oncologic patients and published in Autophagy.

A study led by researchers from the Institut de Neurociències (INc-UAB), in collaboration with the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), describes a new mechanism by which the antitumor drug ABTL0812 induces stress in tumors, causing cell destruction by cytotoxic autophagy. This molecule is currently being tested in patients with advanced endometrial and squamous lung carcinoma, in combination with standard chemotherapy.

The findings were published in the Autophagy journal and show a new strategy to tackle cancer based on the manipulation of dihydroceramides, a group of cellular lipids. The authors also describe for the first time the detection of mRNAs of two stress-related proteins - CHOP and TRIB3- in blood samples from patients undergoing clinical trial, supporting their use as pharmacodynamic biomarkers.

The research team was coordinated by Jose Miguel Lizcano from the INC and the UAB Biochemistry and Molecular Biology Department. For the past years, this team has investigated how ABTL0812 exerts its antitumor action. This molecule was developed by the biopharmaceutical company AbilityPharma located at the UAB Research Park. AbilityPharma contacted Dr. Lizcano to uncover the antitumor mechanism of action of ABTL0812. Since then, clinical trials have advanced in parallel with research in the laboratory.

In 2016, when clinical studies began, Dr. Lizcano's laboratory discovered that this was the first anticancer drug in trials to induce toxic autophagy in tumor cells. Now, with this drug being tested in clinical phase II, the new study shows how toxic autophagy is produced.

"Cancer cell death comes from alterations in the levels of cellular dihydroceramides, a family of cellular lipids. Elevated levels of dihydroceramides provoke a severe stress of the endoplasmic reticulum, a cellular organelle in charge of protein synthesis, resulting in the accumulation of defective proteins. As a consequence, cells activate a compensatory response, called Unfolded Protein Response (UPR). This response, when sustained in time, can induce autophagy that results in cancer cell death", says Jose Miguel Lizcano.

The study also explains why ABTL0812 does not affect non-cancer cells: "The main advantage of this molecule lies in its specificity for tumor cells. To survive the hostile environment, cancer cells overtake it by having elevated levels of ER stress and UPR activity. Our drug provokes cancer cells to overpass the stress level in which this response has protective effects, causing their death, while healthy cells still have a wider margin", says Pau Muñoz, researcher at the INC and first author of the article.

Researchers consider that this new mechanism of action could be used safely in the treatment of different types of cancers. In fact, the study also served to present the preliminary results on pancreatic and other biliary tract cancer models.

This work will be presented by AbilityPharma at the American Association for Cancer Research (AACR) 2020 Congress.

The description of this mechanism of action is a very important step for AbilityPharma, and shows the excellent collaboration engaged by our company and the INc-UAB. Also, it supports a broader use of ABTL0812 in other cancer paradigms, apart from endometrial and squamous lung carcinoma."  

Carles Domènech, AbilityPharma's executive chairman

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Here is how you can train your brain to tackle stress

Opined by neuroscientist Dr Selena Bartlett, inculcating several healthy habits in life can train your brain to tackle stress. Bartlett, who has been mapping the way our brains react to stress for the last 25 years as a researcher, our brains often deal with stress and trauma through addictive behaviours such as the consumption of sugar and alcohol, reported the researchers.

The  researcher also said that the first step towards attaining a peaceful mind is to understand that you can 'train your brain' to handle stress efficiently. "People are just using alcohol and sugar as medication and I can't keep designing a medication for a medication. My lab looks at the capacity of using neuroplasticity, which is the ability of the brain to change itself, to help to reduce the impact of that stress and trauma on the brain and to use the power of the brain to drive in healthy habits," Bartlett, who develops drugs to treat addiction, said.

Adding that creating even the most basic healthy change takes time, she said: "Only when we start to become aware of our automatic, often unhealthy, responses to stress, then we can start to rewire them." "However, you can actually train the brain by doing small things every day, like how you wake up in the morning, what you eat, the exercise that you do, sleep and water," she added.

Bartlett, further said that prolonged over-consumption of sugar acts on the amygdala, emotional part of the brain, in a way that makes the brain more reactive to stress. Emphasising that one should understand that our brains process negative over positive information, the researcher said: "Gratitude works. When you wake up in the morning, set up your brain in a positive direction so it will start to take in more positive information than the negative ones."

"We can train our brains to become more resilient by using the principles of neuroplasticity. We can also teach ourselves to take a healthy path to stress-management rather than relying on substances," she added, according to the researchers.

Asserting that simple changes have transformed her capacity to cope with stress, Bartlett said: "I'm the happiest I've been. I can still get triggered by things because we all do and that's life. However, now I know how to handle stress in a way that I have control over it."

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7 new super-foods for men and women

Hormones can cause huge havoc in men and women. Whether it is severe acne and hair on the face, fatigue, yo-yo weight gain, irregular menstrual cycles, low libido, brittle hair, depression or poor fertility. The symptoms of hormonal imbalance and their severity may vary but they are very distressing. And are today an epidemic of sorts. Hormones sound complex (after all, there are about 200 of them). To keep your hormones happy include these seven foods in your diet on a regular basis.

Spirulina to tackle Estrogen
Estrogen imbalance shows up in abdominal obesity, bloating, cold hands and feet, hair loss, mental fogginess, hot flashes, night sweats and temperature swings.
Food pick: Spirulina has the essential fatty acids that help the liver metabolise excess estrogen. Have it mixed with water or add to smoothies.

Cinnamon to keep insulin stable
Insulin is the body’s sugar regulator. Imbalance shows up in the form of lethargy, hunger, brain fog and weight gain.
Food pick: Cinnamon helps keep your blood sugar stable through the day and insulin tamed.

Mackerel to keep thyroid healthy
Thyroid keeps our metabolism in shape, and its imbalance leads to us feeling cold or sluggish all the time.
Food pick: Thyroid has the highest selenium content, and its deficiency is often a primary cause of thyroid disorders. Mackerel is a good source of selenium.

Banana to cosy up melatonin
This sleep hormone helps you stay rested and sleep well. And sleep debt is associated with higher weight and hormonal imbalance. Its imbalance shows up as you begin to experience fatigue, impaired memory and lack of concentration.
Food pick: Pile on B6 rich foods, particularly banana, as it helps the body produce melatonin naturally.

Jamun to strengthen the liver
Liver is our body’s master filter – it cleans out toxins we are exposed to and is the powerhouse of all hormone production and metabolism.
Food pick: Jamun can keep it healthy as it prevents excessive lipid accumulation, which leads to fatty liver and multiple hormonal messes.

Ghee to keep cortisol low

When cortisol rises, it makes our body hoard fat as it encourages conversion of blood sugar into fat for long-term storage. It also leads to food cravings and, addictions and irritability, frequent headaches, anxiety, high blood pressure.
Food pick: Good fats are building blocks of all hormones – and are especially helpful with stabilising the production of stress hormone cortisol. Eat ghee from grass fed cows to keep cortisol low.

Spinach to boost adiponectin
This fat-burning hormone works on the brain to regulate inflammation and oxidative stress, both of which contribute to weight gain.
Food pick: Have spinach as it has certain enzymes and antioxidants, which stimulate this hormone.

Finally, the important thing to understand is that all our hormones are interconnected, and interact and work together synergistically – so even if one is out of whack, it can start a bad cascading effect. Don’t let that happen – for the sake of your weight and health. Eat a hormone stabilising diet. 

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Living alone ups risk of mental disorders

Mental health problems are more common in people living alone regardless of age and sex, says a study.
"The prevalence of common mental disorders was higher in individuals living alone than in those not living alone in all survey years," the study noted.
For the study, the researchers used data on 20,500 individuals aged 16-64 living in England who participated in the 1993, 2000, or 2007 in the Surveys.
Whether a person had a common mental disorder (CMD) was assessed using the Clinical Interview Schedule-Revised (CIS-R), a questionnaire focusing on neurotic symptoms.
The study found that the prevalence of people living alone in 1993, 2000, and 2007 was 8.8 per cent, 9.8 per cent, and 10.7 per cent. 
They found a positive association between living alone and common mental disorder. 
In different subgroups of people, living alone increased a person's risk for common mental disorder by 1.39 to 2.43 times, the study said. 
"Living alone is positively associated with common mental disorders in the general population in England," said study co-author .

Globally, the lifetime prevalence of CMDs is around 30 per cent. These disorders have a major impact on quality of life, physical illness and mortality. 
The researchers also suggest that interventions, which tackle loneliness, might aid the mental well-being of individuals living alone.

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Novel drug may help tackle treatment-resistant cancers

A new class of drug that has the potential to help cancer patients, especially those suffering from breast cancer and who no longer respond to existing therapies has been discovered.

Breast cancer patients frequently become resistant to existing treatments, leading to the disease becoming fatal.

Early lab-based tests of a drug named ICEC0942 were successful in targeting resistant breast cancers and indicated minimal side effects.

“Treatment-resistant tumours represent a significant threat for patients, as once a cancer stops responding to treatments there is increasingly little clinicians can do,” said a Professor.

“Drugs such as these could help to shift the balance back in favour of the patients, potentially providing a new option to patients for who existing treatments no longer work,” the Prof. added.

The findings, published in the journal, noted that the drug targets an enzyme called CDK7 — involved in directing cells through their life-cycle, which consists of growth, DNA replication and cell division.

CDK7 is also involved in the process of transcription — a vital step in gene expression — the creation of proteins to carry out cell functions.

Particular cancers, such as treatment-resistant breast cancers, have a unique dependence on transcription, meaning targeting CDK7 may be particularly effective.

By inhibiting transcription, ICEC0942 shuts down the ability of the cancer to spread.

In addition, cancers such as acute myeloid leukaemia and small-cell lung cancer are particularly transcription-dependent.

Therefore, ICEC0942 drug may also work well for these too, especially where they have become resistant to other treatments, the researchers suggested.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                                                                                                                                                                                      PS- THOSE INTERESTED IN RECIPES ARE FREE TO VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/   
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