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Tag: Medicine

Common Medications May Reduce Risk of Metastases after Colon and Rectal Cancer

Existing drugs to prevent anxiety, stress reactions and inflammation reduced the risk of the spread of cancer metastases after surgery to remove a colon tumor by tens of percent.

Although surgery to remove primary tumors is the mainstay of all cancer treatments, the risk of metastases after tumor removal is estimated at 35% among colon cancer patients, with higher risk in patients with more advance stages of the disease. However, a short, simple, and safe drug treatment developed at Tel Aviv University reduced the risk of the spread of cancer metastases after surgery to remove the primary tumor – according to the first clinical study of its kind conducted among 34 colon cancer patients operated on at Sheba Tel Hashomer Medical Center.

The research was led by Prof. Shamgar Ben-Eliyahu of TAU’s Sagol School of Neuroscience and School of Psychological Sciences at the Gershon H. Gordon Faculty of Social Sciences and Prof. Oded Zamora of TAU’s Sackler Faculty of Medicine, and its results were published in the European Journal of Surgical Oncology. At the same time, an overview of the theory and principles underlying the research was published in Nature Review Cancer.

“The stress during the waiting period for surgery, the stress and inflammation reactions that the body produces during the surgery itself and the physical recovery period, and finally the following anxiety of cancer recurring – all have an adverse effect on the body’s ability to fight metastatic processes,” explains Prof. Ben-Eliyahu. “These mental and physiological conditions create stress-inflammatory responses, which cause ample release of hormones from the prostaglandin and catecholamine families. These hormones suppress anti-metastatic immune activity, and thus encourage the development of metastases.”

“In addition, these hormones directly help the cancer cells that remain in the body even after surgery: due to exposure to these hormones, the cancerous tissue becomes more aggressive and metastatic. The good news is that we know how to treat both stress and inflammation using off-the-shelf medications.”

 

“This is a short, cheap drug treatment with no significant side effects. We deliberately sought the safest and cheapest drugs capable of lowering the body’s stress-inflammatory response to surgery, in order to save lives.” Prof. Shamgar Ben-Eliyahu

 

Significant and Encouraging Results

The researchers from Tel Aviv University gave 34 colon cancer patients two safe drugs that are available in every pharmacy: propranolol (Darlin), used to lower blood pressure and reduce anxiety, and etodolac (Etopan), used to prevent pain and inflammation.

Sixteen randomly chosen patients took the medication for 20 days – from five days before to two weeks after surgery at the Sheba Medical Center. The other 18 patients received placebo drugs (control group). Five years later, nine of the 18 patients who received the placebo (50%) developed cancer metastases, compared to two of the 16 patients who took Darlin and Etofen (12.5%).

“Although at five years after the operation, the statistical significance is clear, we need to conduct larger clinical studies,” says Prof. Ben-Eliyahu. “Our treatment reduced markers of metastasis in the tumor tissue and reduced the chances of cancer recurrence. This is a short, cheap drug treatment with no significant side effects. We deliberately sought the safest and cheapest drugs capable of lowering the body’s stress-inflammatory response to surgery, in order to save lives.”

“It sounds too good to be true, but similar results in breast cancer tissue were obtained in a study we conducted in 2017. Due to the small number of subjects in both studies, it is impossible to accurately estimate the magnitude of the beneficial effect, but the effects are statistically significant, meaning that they are not accidental.”

 

“We seek to save lives without financial gain, and we have received financial support from several Israeli and international sources, but these are insufficient for large clinical studies.” Prof. Shamgar  Ben-Eliyahu

 

Saving Lives Without Financial Gain

According to Prof. Ben-Eliyahu, part of the medical establishment distrusts the effects of stress-inflammatory reactions, particularly those resulting from psychological factors such as waiting for surgery or fear of the disease spreading. Another problem concerns the financing of clinical studies.

“One should bear in mind that the pharmaceutical companies have no financial incentive to support such studies. Our medicines are not patented; they are safe, cheap, and administered in a short treatment lasting just a few days. The drug companies look for patents on expensive drugs and prefer that the patient be dependent on the drug for the rest of their life.”

“Unfortunately, the major science foundations in Israel do not fund clinical research on drugs, assuming that the drug companies will fund them. We seek to save lives without financial gain, and we have received financial support from several Israeli and international sources, but these are insufficient for large clinical studies. I hope that funding will be found for a large-scale clinical study that we have now embarked on, with the intention of recruiting hundreds of colon and rectal cancer patients in Israel, because without such research – we will not be able to convince the medical establishment of the treatment’s effectiveness.”

The Superpowers of the Female Locust

She can stretch up to 2-3 times her original length when laying eggs in the ground, without causing irreparable damage.

Every mother will do anything to know that her offspring are in a safe place. The female locust, however, takes it to a whole new level: A new Tel Aviv University study has discovered that these females have superpowers. The female locust’s central nervous system has elastic properties, allowing her to stretch up to two or three times her original length when laying her eggs in the ground, without causing any irreparable damage.

“We are not aware of a similar ability in almost any living creature,” say the researchers. “Nerves in the human nervous system, for example, can stretch only up to 30% without tearing or being permanently damaged. In the future, these findings may contribute to new developments in the field of regenerative medicine, as a basis for nerve restoration and the development of synthetic tissues.”

 

“The superpower of the locust is almost something out of science fiction. There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have.” Prof. Amir Ayali

 

WATCH: TAU Researchers Describe their Surprising Discovery – The Female Locust has Superhero-like Abilities

 

Showing Flexibility

The study was conducted by a team of Tel Aviv University researchers led by Dr. Bat-El Pinchasik of the School of Mechanical Engineering in The Iby and Aladar Fleischman Faculty of Engineering and Prof. Amir Ayali of the School of Zoology in the George S. Wise Faculty of Life Sciences. Also participating in the study were Dr. Rakesh Das from the School of Mechanical Engineering, Dr. Moshe Guershon from the School of Zoology, and Prof. Eran Perlson and Amjd Ibraheem from the Department of Physiology and Pharmacology in the Sackler Faculty of Medicine. The research was published in iScience.

“When the female locust is ready to lay her eggs, she digs a hole in the ground that will offer them protection and optimal conditions for hatching,” explains Dr. Pinchasik. “For this purpose, she is equipped with a unique digging apparatus, consisting of two pairs of digging valves located at the tip of the abdomen, on either side of the ovipositor (a tube-like organ used for laying eggs).”

“As she digs, she extends her body, until sensors located along its length signal that she has reached a suitable point for depositing her eggs. Thus, an adult female, whose body length is about four to five centimeters, may, for the purpose of laying her eggs, stretch her body to a length of 10-15 centimeters, then quickly return to her normal length, and then extend again for the next egg-laying.”

“The superpower of the locust is almost something out of science fiction,” muses Prof. Ayali. “There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have. We sought to identify the biomechanical mechanism that gives the female locust its wonderful ability.”

 

From left to right: Prof. Amir Ayali, Dr. Rakesh Das and Dr. Bat-El Pinchasik

 

“Contrary to previous hypotheses and examples we are familiar with, we did not find any accordion-like mechanism. We discovered that the nervous system of the female locust has elastic properties, which enable it to elongate and then return by itself to its original state, ready for reuse, without any damage caused to the tissue. This finding is almost incomprehensible from a biomechanical and morphological point of view.” Dr. Bat-El Pinchasik

 

Key to Rehabilitation Treatments and Regenerative Medicine?

In the study, the researchers removed the central nervous systems from female locusts and placed them in a liquid simulating their natural environment, under physiological conditions similar to those inside the body. Using highly sensitive measuring instruments, they measured the forces needed to extend the nervous system.

Dr. Pinchasik: “Contrary to previous hypotheses and examples we are familiar with, we did not find any accordion-like mechanism. We discovered that the nervous system of the female locust has elastic properties, which enable it to elongate and then return by itself to its original state, ready for reuse, without any damage caused to the tissue. This finding is almost incomprehensible from a biomechanical and morphological point of view.”

Prof. Ayali adds that, “in further studies, we will investigate the matter in depth, with the aim of identifying the specific mechanism that enables this unique feature. We hope that in the future our findings will help to develop synthetic tissues with a high level of flexibility, and to restore nerves in regenerative medicine therapies.”

Are Today’s Gynecologists Ignoring Women’s Health Issues?

Women’s health and wellbeing receive little attention compared to childbirth and reproduction, both in research and in clinic.

A new preliminary study from Tel Aviv University reveals that due to masculine dominance of the gynecological science field, most gynecological research focuses on childbirth and reproduction rather than women’s health and wellbeing. Mapping scientific journals in the category of gynecology and obstetrics, the study found that the majority deal with fertility, pregnancy, fetuses, and childbirth, while many topics that are much more critical to women’s quality of life receive little attention, both in scientific research and in the clinic.

The study was conducted by Dr. Netta Avnoon of the Department of Sociology and Anthropology and the Coller School of Management at Tel Aviv University. The preliminary results were published in the prestigious journal Nature Reviews Urology

 

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices.” Dr Netta Avnoon

 

Male Dominated Discipline

According to the preliminary study important issues that have been marginalized for centuries include diseases and damage to the muscles and nerves of the female pelvis and sexual organs, female sexual pleasure, rights and autonomy in childbirth, the connection between the menstrual cycle and the immune system, menopause, and the later years of life, and more.

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices,” says Dr. Avnoon. “Even if they are unaware of their own bias and have the best intentions, men traditionally regard the female body as an object for producing babies or satisfying men’s sexual desires. The time has come for women to dominate the discipline that is meant to care for their health.”

Dr. Avnoon explains that no social activity is neutral, objective or contextless, and science and medicine are no exception. Inevitably, social positions and dispositions impact the attitudes of those who create science.

Extensive historical and feminist scholarship has shown that gynecology as a medical specialty was masculinized 800 years ago, and still adheres to patriarchal values. In ancient times women were usually treated by women-experts, who even wrote books on the subject, but during the Middle Ages, these women and their knowledge were gradually ousted and replaced by men.

Since the 16th century the specialty has been wholly dominated by males, and consequently they were the ones to determine which topics are ‘interesting’ and worth studying; they were the ones who set practices and protocols and introduced treatments, technologies, and techniques, all too often subjecting patients to medical practices that are not necessarily benevolent.

 

Dr. Netta Avnoon

Exposing Current Focus

To expose the actual focus of gynecological research today, in line with previous feminist studies, Dr. Avnoon chose a tell-tale indicator: the titles of international scientific journals in the ‘gynecology and obstetrics’ category.

She analyzed the list appearing in the Journal Citation Reports, a database that provides general and statistical information about scientific journals worldwide, and the results were clear-cut: of the 83 journals listed by title in the category, 49% are dedicated solely to reproductive functions, pregnancy, fetuses, and childbirth; 24% focus on both gynecology and obstetrics; only 12% deal with health issues in the female sexual organs that are unrelated to reproductive functions; 6% deal with breasts; 5% deal with gynecological cancers; and a mere 4% (3 journals) address the health of women before and after childbearing age, including menopause.

Dr. Avnoon notes a recent instance of gynecology’s gender bias: the transvaginal mesh scandal. In 2019 the FDA banned the use of the transvaginal mesh – a common gynecological procedure used since the 1950s to repair pelvis organ prolapse in the anterior vaginal compartment, which had caused extensive morbidity and even 77 documented deaths in the USA.

Patients’ activism moved the regulator to intervene, exposing the decades-long failure of gynecological science to clinically assess the outcomes of this surgical procedure, and revealing the bias in how researchers presented these results in scientific publications.

 

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.” Dr. Netta Avnoon

 

It’s Time: Women-Centered Gynecology

What solution does Dr. Avnoon have in mind? She proposes the following: “Obstetrics, focusing on fertility, reproduction, pregnancy, the fetus and childbirth, should be separated from gynecology, a specialty dedicated to women’s health.”

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.”

“Also, gynecology training must include a major chapter of gender and feminist studies, and existing medical protocols should be amended to focus on the needs of the women – rather than those of their babies, their spouses, or their doctors. Moreover, legislation and legal procedures are in order, especially in courts of human rights, to protect women’s right to health and optimal medical care.”

“The time has come for women-centered gynecology,” says Dr. Avnoon. “Women’s voices must be heard.”

“To date, medical schools offer their students very scant and unsatisfactory knowledge about female anatomy and physiology, specifically in terms of women’s sexuality. Even though the overall numbers of female gynecologists are on the rise (in the US there are by now more women than men in this profession), their education is still based on age-old masculine and chauvinistic traditions.”

“In order to generate real change, doctors must be trained to regard women’s rights, health, and sexuality as the focus of women’s medicine, and to treat their patients with respect. Greater emphasis should be given to patient experience and autonomy in medical settings, and to much-needed innovation in research, instruments, technologies, protocols, surgical procedures, and medications.”

Removal of Cancerous Tumors Without Surgery

New technology from Tel Aviv University, combining ultrasound and nanobubbles, destroys tumors, eliminating need for invasive treatments.

A new technology developed at Tel Aviv University makes it possible to destroy cancerous tumors in a targeted manner, via a combination of ultrasound and the injection of nanobubbles into the bloodstream. Unlike invasive treatment methods or the injection of microbubbles into the tumor itself, this latest technology enables the destruction of the tumor in a non-invasive manner.

The study was conducted under the leadership of doctoral student Mike Bismuth from the lab of Dr. Tali Ilovitsh at Tel Aviv University’s Department of Biomedical Engineering, in collaboration with Dr. Dov Hershkovitz of the Department of Pathology. Prof. Agata Exner from Case Western Reserve University in Cleveland also participated in the study. The study was published in the journal Nanoscale.

 

 

“Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”  Dr. Tali Ilovitsh

 

 

Bursting Bubbles – and Tumors

Dr. Tali Ilovitsh: “Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”

The researchers explain that today, the prevalent method of cancer treatment is surgical removal of the tumor, in combination with complementary treatments such as chemotherapy and immunotherapy.

 

The research team

Therapeutic ultrasound to destroy the cancerous tumor is a non-invasive alternative to surgery. This method has both advantages and disadvantages. On the one hand, it allows for localized and focused treatment; the use of high-intensity ultrasound can produce thermal or mechanical effects by delivering powerful acoustic energy to a focal point with high spatial-temporal precision. This method has been used to effectively treat solid tumors deep within in the body. Moreover, it makes it possible to treat patients who are unfit for tumor resection surgery. The disadvantage, however, is that the heat and high intensity of the ultrasound waves may damage the tissues near the tumor.

 

 

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor and reduces off-target toxicity.” Dr. Tali Ilovitsh

 

 

Reducing Off-target Damage

In the current study, Dr. Ilovitsh and her team sought to overcome this problem. In the experiment, which used an animal model, the researchers were able to destroy the tumor by injecting nanobubbles into the bloodstream (as opposed to what has been until now, which is the local injection of microbubbles into the tumor itself), in combination with low-frequency ultrasound waves, with minimal off-target effects.

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor, and reduces off-target toxicity,” explains Dr. Ilovitsh.

“Applying the low frequency to the nanobubbles causes their extreme swelling and explosion, even at low pressures. This makes it possible to perform the mechanical destruction of the tumors at low-pressure thresholds.”

“Our method has the advantages of ultrasound, in that it is safe, cost-effective, and clinically available, and in addition, the use of nanobubbles facilitates the targeting of tumors because they can be observed with the help of ultrasound imaging.”

Dr. Ilovitsh adds that the use of low-frequency ultrasound also increases the depth of penetration, minimizes distortion and attenuation, and enlarges the focal point. “This can help in the treatment of tumors that are located deep with the body, and in addition facilitate the treatment of larger tumor volumes. The experiment was conducted in a breast cancer tumor lab model, but it is likely that the treatment will also be effective with other types of tumors, and in the future, also in humans.”

Aerobic Activity can Reduce Risk of Metastatic Cancer by 72%

TAU researchers find that exercise defeats cancer by increasing glucose consumption.

A new study at Tel Aviv University found that aerobic exercise can reduce the risk of metastatic cancer by 72%. According to the researchers, intensity aerobic exercise increases the glucose (sugar) consumption of internal organs, thereby reducing the availability of energy to the tumor.  

The study was led by two researchers from TAU’s Sackler Faculty of Medicine: Prof. Carmit Levy from the Department of Human Molecular Genetics and Biochemistry and Dr. Yftach Gepner from the School of Public Health and the Sylvan Adams Sports Institute. The paper was published in the prestigious journal Cancer Research and chosen for the cover of the November 2022 issue

 

“If the general message to the public so far has been ‘be active, be healthy’, now we can explain how aerobic activity can maximize the prevention of the most aggressive and metastatic types of cancer.” Prof. Carmit Levy and Dr. Ytach Gepner

 

Enhanced Rate of Glucose Consumption

Previous studies have demonstrated that physical exercise reduces the risk for some types of cancer by up to 35%. This positive effect resembles the impact of exercise on other conditions, such as heart disease and diabetes.

In this study, Prof. Levy and Dr. Gepner added new insight, showing that high-intensity aerobic exercise, which derives its energy from sugar, can reduce the risk of metastatic cancer by as much as 72%. “If the general message to the public so far has been ‘be active, be healthy’,” they say, “now we can explain how aerobic activity can maximize the prevention of the most aggressive and metastatic types of cancer.”

The study combined lab models trained under a strict exercise regimen, with data from healthy human volunteers examined before and after running. The human data, obtained from an epidemiological study that monitored 3,000 individuals for about 20 years, indicated 72% less metastatic cancer in participants who reported regular aerobic activity at high intensity, compared to those who did not engage in physical exercise.

The animal model exhibited a similar outcome, enabling the researchers to identify its underlying mechanism. They found that aerobic activity significantly reduced the development of metastatic tumors in the lab models’ lymph nodes, lungs, and liver. The researchers hypothesized that in both humans and model animals, this favorable outcome is related to the enhanced rate of glucose consumption induced by exercise.

 

“Physical exercise, with its unique metabolic and physiological effects, exhibits a higher level of cancer prevention than any medication or medical intervention to date.” Dr. Yftach Gepner

 

From left to right: Prof. Carmit Levy and Dr. Yftach Gepner

“Exercise Changes the Whole Body”

“Our study is the first to investigate the impact of exercise on the internal organs in which metastases usually develop, like the lungs, liver, and lymph nodes,” explains Prof. Levy.

“Examining the cells of these organs, we found a rise in the number of glucose receptors during high-intensity aerobic activity – increasing glucose intake and turning the organs into effective energy-consumption machines, very much like the muscles. We assume that this happens because the organs must compete for sugar resources with the muscles, known to burn large quantities of glucose during physical exercise. Consequently, if cancer develops, the fierce competition over glucose reduces the availability of energy that is critical to metastasis.”

“Moreover,” she offers, “when a person exercises regularly, this condition becomes permanent: the tissues of internal organs change and become similar to muscle tissue. We all know that sports and physical exercise are good for our health. Our study, examining the internal organs, discovered that exercise changes the whole body, so that the cancer cannot spread, and the primary tumor also shrinks in size.”  

Prof. Levy emphasizes that by combining scientific knowhow from different schools at TAU, the new study has led to a very important discovery which may help prevent metastatic cancer – the leading cause of death in Israel.

“Our results indicate that unlike fat-burning exercise, which is relatively moderate, it is a high-intensity aerobic activity that helps in cancer prevention,” adds Dr. Gepner. “If the optimal intensity range for burning fat is 65-70% of the maximum pulse rate, sugar burning requires 80-85% – even if only for brief intervals.”

“For example: a one-minute sprint followed by walking, then another sprint. In the past, such intervals were mostly typical of athletes’ training regimens, but today we also see them in other exercise routines, such as heart and lung rehabilitation. Our results suggest that healthy individuals should also include high-intensity components in their fitness programs. We believe that future studies will enable personalized medicine for preventing specific cancers, with physicians reviewing family histories to recommend the right kind of physical activity. It must be emphasized that physical exercise, with its unique metabolic and physiological effects, exhibits a higher level of cancer prevention than any medication or medical intervention to date.”  

New Hope for Patients with Severe Bone Loss

Researchers induced bone regeneration with a special hydrogel that mimics the bone’s natural environment.

An innovative technology developed at Tel Aviv University will enable bone regeneration to correct large bone defects by means of a special hydrogel. Following successful tests in a lab model, the researchers now plan to move forward to clinical trials.

The groundbreaking study was conducted by experts from TAU’s Maurice and Gabriela Goldschleger School of Dental Medicine, led by Prof. Lihi Adler-Abramovich and Dr. Michal Halperin-Sternfeld, in collaboration with Prof. Itzhak Binderman, Dr. Rachel Sarig, Dr. Moran Aviv, and researchers from the University of Michigan in Ann Arbor. The paper was published in the Journal of Clinical Periodontology.

Prof. Adler-Abramovich: “Small bone defects, such as fractures, heal spontaneously, with the body restoring the lost bone tissue. The problem begins with large bone defects. In many cases, when substantial bone loss results from tumor resection (removal by surgery), physical trauma, tooth extraction, gum disease or inflammation around dental implants, the bone is unable to renew itself. In the current study, we developed a hydrogel that mimics the natural substances in the extracellular matrix of bones, stimulating bone growth and reactivating the immune system to accelerate the healing process.”

The researchers explain that the extracellular matrix is the substance surrounding our cells, providing them with structural support. Every type of tissue in our body has a specific extracellular matrix consisting of suitable substances with the right mechanical properties. The new hydrogel has a fibrillary structure that mimics that of the extracellular matrix of the natural bone. Furthermore, it is rigid, thus enabling the patient’s cells to differentiate into bone-forming cells.

 

WATCH: Lab of Bioinspired Materials: A Tour with TAU Prof. Lihi Adler-Abramovich

 

“As can be expected, the extracellular matrix of our bones is quite rigid,” says Prof. Adler-Abramovich. “In our study, we produced a hydrogel that mimics this specific matrix in both chemical and physical properties. At the nanometric level, the cell can attach itself to the gel, gaining structural support and receiving relevant mechanical signals from the fibers. At first, to test these properties, we grew cells in a 3D model of the gel. Then we examined the impact of the hydrogel on model animals with large bone defects that could not heal spontaneously. We monitored them for two months with various methods, including Micro C.T. To our delight, the bone defects were fully corrected through regeneration, with the bones regaining their original thickness, and generating new blood vessels.”

According to Prof. Adler-Abramovich, the innovative gel has extensive clinical applications in both orthopedic and dental medicine: “When we lose teeth due to extensive damage or bacterial infections, the standard treatment is dental implants. Implants, however, must be anchored in a sufficient amount of bone, and when bone loss is too substantial, physicians implant additional bone from a healthy part of the body – a complex medical procedure. Another option is adding bone substitutes from either human or animal sources, but these might generate an immune response. I hope that in the future the hydrogel we have developed will enable faster, safer, and simpler bone restoration.”  

Featured image: The research team

Pressure Chamber Therapy Effective in Improvement of Autism

TAU study shows that treatment may significantly improve social abilities and condition of the autistic brain.

A new Tel Aviv University study succeeded in significantly improving social skills and the condition of the autistic brain through pressure chamber therapy. The study was conducted on lab models of autism. In it, the researchers identified changes in the brain, including a reduction in neuroinflammation, which is known to be associated with autism. Moreover, a significant improvement was found in the social functioning of the animal models treated in the pressure chamber. The study’s success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy.

The breakthrough was made under the leadership of doctoral student Inbar Fischer, from the laboratory of Dr. Boaz Barak of Tel Aviv University’s Sagol School of Neuroscience and School of Psychological Sciences. The research was published in the International Journal of Molecular Sciences.

Considered Safe

Fischer and Barak explain that hyperbaric medicine is a form of therapy in which patients are treated in special chambers where the atmospheric pressure is higher than the pressure we experience at sea level, and in addition are delivered 100 percent oxygen to breathe.

Hyperbaric medicine is considered safe and is already being used to treat a long list of medical conditions, including here in Israel. In recent years, scientific evidence has been accumulating that unique protocols of hyperbaric treatments improve the supply of blood and oxygen to the brain, thereby improving brain function.

Improving Brain Function

“The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar,” explains Dr. Barak:. “About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioral problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, received treatments in the pressure chamber, conducted by Prof. Shai Efrati, director of the Sagol Center for Hyperbaric Medicine at the Shamir “Assaf Harofeh” Medical Center, faculty member at the Sagol School of Neuroscience, and a partner in the study. After the treatments, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr. Barak’s laboratory sought to understand what being in a pressurized chamber does to the brain. To this end, the researchers used lab models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber over several weeks.

“We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function,” explains Dr. Barak. “In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.”

 Increased Social Interest

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behavior, which is known to be impaired in autistic individuals,” adds Dr. Barak. “To our surprise, the findings showed a significant improvement in the social behavior of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes, “the mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Featured image: Members of the TAU research team (left to right): Dr. Nour Ershaid, Prof. Neta Erez and Lea Monteran (Photo Credit: TAU)

Breakthrough Treatment May Improve Efficacy of Chemotherapy in Breast Cancer Patients

TAU-developed treatment may reduce risk for lung metastasis following chemo from 52% to only 6%.

A new treatment developed at Tel Aviv University may significantly enhance the efficacy of chemotherapy in breast cancer patients, reducing the risk for lung metastasis following chemo from 52% to only 6%. Conducted in a lab model, the study identified the mechanism that generates a cancer-promoting inflammatory environment in response to chemotherapy. Moreover, the researchers found that by adding an anti-inflammatory agent to the chemotherapy, metastasis can be prevented.

The study was led by Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, and researchers from her group: Lea Monteran, Dr. Nour Ershaid, Yael Zait, and Ye’ela Scharff, in collaboration with Prof. Iris Barshack of the Sheba Medical Center and Dr. Amir Sonnenblick of the Tel Aviv Sourasky (Ichilov) Medical Center. The paper was published in Nature Communications. The study was funded by ERC, the Israel Cancer Association, and the Emerson Cancer Research Fund.

The Dark Side of Chemo

“In many cases of breast cancer, surgical removal of the primary tumor is followed by a chemotherapy regimen intended to kill any remaining malignant cells – either left behind by the surgeon or already colonizing in other organs,” explains Prof. Erez. “However, while effectively killing cancer cells, chemotherapy also has some undesirable and even harmful side effects, including damage to healthy tissues. The most dangerous of these, is probably internal inflammations that might paradoxically help remaining cancer cells to form metastases in distant organs. The goal of our study was to discover how this happens and try to find an effective solution.”

To this end, the researchers created an animal model for breast cancer metastasis. The animals received the same treatment as human patients: surgical removal of the primary tumor, then chemotherapy, followed by monitoring to detect metastatic relapse as early as possible. The disturbing results: metastatic tumors were detected in the lungs of a large percentage of the treated animals – similar to the percentage found in the control group.

 

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box.’ Working with an animal model, we could check what happens inside this ‘box’.” Prof. Neta Erez

 

What’s Going on Inside the “Black Box”?

To decipher these adverse effects, the researchers examined the animals’ lungs at an intermediate stage – when tiny micro-metastases may have already developed, but even advanced imaging technologies like CT cannot detect them.

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box’,” says Prof. Erez. “Working with an animal model we could check what happens inside this ‘box’.”

“We discovered a previously unknown mechanism: the chemotherapy generates an inflammatory response in connective tissue cells called ‘fibroblasts’, causing them to summon immune cells from the bone marrow. This, in turn, creates an inflammatory environment that supports the micro-metastases, helping them grow into full-fledged metastatic tumors. In this way, the chemotherapy, administered as a means for combating cancer, achieves the opposite result.”

The researchers also identified the mechanism through which fibroblasts recruit immune cells, and ‘train’ them to support the cancer. “We found that in response to chemotherapy, the fibroblasts secrete ‘complement proteins’ – proteins that mediate cell recruitment and intensify inflammation, often by summoning white blood cells to damaged or infected areas, a process called chemotaxis,” notes Prof. Erez. “When the immune cells reach the lungs, they create an inflammatory environment that supports cancer cells and helps them grow.”

 

“We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor.” Prof. Neta Erez

 

Potential to Save Many Lives

To combat this newly discovered process, the researchers combined the chemotherapy administered to the animals with a drug that blocks the activity of complement proteins.

The results were very encouraging: following the combined treatment, the percentage of lab models developing no metastases rose from 32% to 67%; and the percentage of those with extensive cancer colonization in their lungs decreased from 52% with regular chemotherapy to 6% when the inflammation inhibitor was added.

“We discovered the mechanism behind a severe problem in the treatment of breast cancer: many patients develop metastatic tumors following removal of the primary tumor plus chemotherapy,” says Prof. Erez, and concludes: “We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor. We hope that our findings will enable more effective treatment for breast cancer, and perhaps other types of cancer as well – to prevent metastatic relapse and save numerous lives worldwide.”  

Featured image: Members of the TAU research team (left to right): Dr. Nour Ershaid, Prof. Neta Erez and Lea Monteran

Ukrainian Citizens Display High Resilience Amid Fighting

Ukrainian People show more national resilience than Israelis did during Operation “Guardian of the Walls”.

A first-of-its-kind study conducted by Tel Aviv University has found that the national resilience of the citizens of Ukraine, who are currently fighting for their independence, is comparatively very high (4.35) on a scale of 1 to 6. It is, in fact, significantly higher than the national resilience that characterized Israeli citizens (3.89) at the height of “Operation Guardian of the Walls” in May 2021.

The researchers explain this difference by saying that whereas Ukrainian citizens now find themselves fighting for their homeland and are ready to do anything to win the war, the rounds of fighting in Gaza have become a kind of recurrent nuisance for the citizens of Israel, accompanied by a moderate level of national resilience.

The study was led by Prof. Bruria Adini and Prof. Shaul Kimhi of the ResWell Research Center at Tel Aviv University’s Sackler Faculty of Medicine.

Ukrainian Citizens Still Have Hope

According to the researchers, the current study constitutes the first attempt by academic researchers to assess Ukrainian citizens’ positive and negative coping indices during wartime. The study indicates that in such conditions of conflict, a population may experience high levels of stress and, simultaneously, high levels of societal resilience and hope for the future.

In the current situation in Ukraine, the population has also demonstrated a great deal of support for their government.

The study surveyed 1000 Ukrainian citizens, as well as a sample of about 650 Israeli citizens using data collected during Operation Guardian of the Walls. The study’s findings suggest that the danger, in the eyes of Ukrainian citizens, is perceived as much more tangible (3.7 on a scale of 1 to 5) than Israelis’ perception of danger in the rounds of fighting against Hamas in Gaza (2.45). The perception of threat amongst Ukrainians is also more significant (3.29) than among the citizens of Israel (2.79).

The researchers note that the younger population, those between the ages of 26 to 30, present higher levels of stress and post-traumatic stress symptoms compared to other age groups. Women report higher levels of all negative coping mechanisms in comparison to men.

Interestingly, despite the significant dangers and threats they face, Ukrainian citizens have not lost hope, with their ‘hope index’ being higher (an average of 3.95) than that of Israelis (an average of 3.5).

 

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts.” Prof. Adini and Prof. Kimhi

 

Israelis Adapted to ‘Emergency Routine’

Prof. Adini and Prof. Kimhi explain that “the perception of a threat as existential to the survival and sovereignty of the state and society is likely, under certain conditions, to enhance the population’s societal resilience and sense of hope. This is the case even when the population feels anxious and threatened by the situation. “

“Moreover, it appears that the war launched by Russia against Ukraine has actually contributed to the process of Ukrainian identity-building, which also leads to increased levels of resilience, as well as an extremely high sense of hope.”

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts. In light of this, they present lower levels of resilience relative to Ukrainians, but at the same time higher levels of well-being and morale.”

Improving the Well-being of Women with BRCA Gene, Responsible for Breast Cancer

Unique technique found by Tel Aviv University researchers to improve emotional well-being of women with increased risk of breast cancer, assist in decision making.

Many young women with increased risk of breast cancer (carriers of BRCA1/BRCA2 genes) suffer from a state of uncertainty regarding their future, mainly due to the realization that they are highly likely to contract breast cancer and/or ovarian cancer. There is currently no effective treatment for preventing the illness and the only active procedure available is a risk-reducing mastectomy [surgery to remove a breast] and/or oophorectomy [a surgical procedure to remove one or both ovaries] around the age of 40 (it was this procedure that Angelina Jolie underwent in 2013).

Due to fear and uncertainty, these women often suffer psychological and physical symptoms that significantly disrupt their normal lives. In a new study conducted at Tel Aviv University, researchers sought to examine whether workshops and tools for promoting personal health, relief of stress and tension, and strengthening of mental soundness can improve the emotional well-being and quality of sleep of these young women. The researchers determined that use of the Inquiry Based Stress Reduction (IBSR) technique can be very helpful in coping with stressful events, enhance emotional and psychological well-being, improve quality of sleep, and assist in decision making.

Doing “The Work”

The study was led by Dr. Shahar Lev-Ari of the Sackler Faculty of Medicine at Tel Aviv University, in cooperation with Prof. Eitan Friedman of Sheba Medical Center and assistance from other researchers, as part of PhD student Clara Landau’s dissertation. The study was published in the prestigious medical journal JAMA Network Open.

The study included 100 women, all carriers of BRCA1/BRCA2 genes and currently under supervision at the Meirav Breast Center at Sheba Medical Center. As part of the study, the women learned and practiced the IBSR method, a clinical application of “The Work” by Byron Katie, consisting of a mindful self-inquiry for increased mindfulness, work on stress-causing beliefs (the “Inquiry” process) for reduction of stress, and cognitive reframing.

Dr. Shahar Lev-Ari

 

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned.” 

 

Significant Improvements

The results were impressive. After participating in the workshops, as well as self-practice, the women showed great improvement in all aspects of personal growth, positive relations with others, life goals, and self acceptance. A clear improvement was seen in quality of sleep, which returned to normal.

Furthermore, a clear change of attitude was found among the participants with regard to previous doubts over whether to undergo surgical procedures such as mastectomy and oophorectomy. The technique helped the women make rational medical decisions, and some changed their position from ruling out the option of having any procedure done to scheduling a doctor’s appointment to discuss the option.

The researchers believe their findings indicate that study and practice of IBSR techniques might improve the psychological well-being of women with BRCA1/BRCA2 gene mutations, and form the basis (in conjunction with other studies) for recommending to consider providing this technique to women, along with their oncogenetic consultation.

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned,” says Dr. Shahar Lev-Ari.

“We think that healthcare services in Israel and worldwide should evaluate the impact of coping with the genetic information and surgical procedures offered to asymptomatic women carriers on their emotional well-being and quality of life, and offer them interventions to promote their health on the individual level, such that have been scientifically proven in improving the quality of life and emotional well-being of women with the BRCA1/BRCA2 genes,” he summarizes.

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