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.”  

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

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

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.”