TEL AVIV, Israel –Researchers at Tel Aviv University (TAU) and the Leviev Cardiothoracic and Vascular Center at the Sheba Medical Center have found a mechanism responsible for increasing the risk of developing cancer among patients with heart disease. They say that small extracellular bubbles, or vesicles (sEVs), that are secreted from the sick heart to heal itself are released into the bloodstream and promote the growth of cancer cells throughout the body.
The discovery may improve the protocols for treating heart disease so that clinicians also consider the increased risk of cancer.
The research was conducted under the leadership of Professor Jonathan Leor from the Neufeld Cardiac Research Institute of TAU’s Faculty of Medical and Health Sciences and the Taman Institute at Sheba’s Leviev Center, and his student Tal Caller, a medical and research student at TAU’s School of Medicine. The research was published on March 15, 2024, in Circulation.
“In 2013, the Israeli cardiologist Tal Hasin showed for the first time that there is a connection between heart failure and cancer,” Caller explains. “Patients with heart disease are at a higher risk of developing cancer, and since heart disease is already a leading cause of death, many people are at risk. Our research revealed that the diseased heart secretes a cancer-promoting factor, which we identified as small extracellular vesicles (sEVs). These are tiny particles wrapped in a simple membrane, which all cells secrete, but because of heart damage, these vesicles are released in greater quantities and contain factors related to inflammation, healing, growth, creation of new blood vessels, and changes in the immune system. These vesicles move through the circulatory system and eventually reach the tumor or the pre-cancerous tissue.
“Following an injury in the heart muscle and deterioration to heart failure, sEVs containing growth factors and small nucleic acid molecules that promote cell division are released,” Caller continues. “These sEVs contribute to the healing of the injured cardiac tissue. However, released from the injured heart, those vesicles move within the body’s circulatory system, eventually targeting cancerous growths.”
“Many theories have been proposed to explain the increased risk of cancer in heart patients,” says Professor Leor. “They started with shared risk factors such as smoking, diabetes, and obesity and ended with a single protein or molecule. We showed for the first time that the diseased heart secretes sEVs that contain thousands of different growth factors. These bubbles directly promote the growth of certain tumors and also modulate the immune system, making the body more vulnerable to tumor growth.”
To test their hypothesis, the TAU researchers inhibited the formation of sEVs in animal models with heart disease and found that the risk of cancer decreases along with the inhibition of vesicle production. However, this is not a viable therapeutic option, since inhibiting the production of the vesicles causes severe undesired side effects.
“When you systemically inhibit the formation of sEVs, you get less cancer but you cause collateral damage along the way,” Professor Leor says. “That is why we tried a different strategy: we treated the patient’s heart to reduce the damage to the cardiac tissue so that it secretes fewer sEVs. We used spironolactone, which is a well-known and effective drug used to treat heart failure.
“We treated the animals with spironolactone at a very early stage of the disease and found that the heart secreted 30% fewer sEVs and the cancerous tumors grew more slowly. Our experiment shows that it is possible to intervene in heart disease in a way that reduces the risk of cancer among heart patients.”
“It may be necessary to adjust the existing treatments for the heart so that they also consider the risk of cancer,” Caller concludes. “In addition, it is possible to find biomarkers among heart patients that will indicate an increased risk of cancer, since not all patients are at an increased risk. This is basic research, and much work is still required to unravel the connection between the two.”
The study was funded by the Israel Cancer Association and the Israel Science Foundation.
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Space Monitors for Chickpea Cultivation
JERUSALEM — A new, non-invasive technique for evaluating chickpea water efficiency, developed by researchers at the Hebrew University of Jerusalem, offers farmers a powerful tool to fine-tune irrigation and potentially elevate the sustainability of chickpea cultivation.
The new study, published in Precision Agriculture, has the potential to transform chickpea management, amplifying both crop yields and water efficiency. Chickpeas, also known as garbanzo beans, are an important global grain legume and are a staple protein source around the world, especially in the Middle East, South Asia, and the Mediterranean.
The proposed method holds transformative potential for agriculture by enabling farmers to optimize irrigation schedules efficiently. This could lead to increased crop yields and improved water use efficiency, contributing to resource conservation and reduced environmental impact.
Furthermore, the innovation has broader implications for global food security, showcasing the impact of advanced precision-smart agricultural technologies on sustainable farming practices.
The remote sensing aspect of the project was led by researchers at the Hebrew University Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture including Dr. Ittai Herrmann and Ph.D. candidate Roy Sadeh. They trained and tested spectral models for quick and non-invasive assessment of chickpea water status based on leaf water potential estimation from space and the ground. The agronomical aspects of the study were conducted by Hebrew University Prof. Shahal Abbo and Ph.D. student Asaf Avneri under the guidance of Dr. Ran Lati and Dr. David Bonfil at the Agricultural Research Organization in Israel.
The study consisted of two farm experiments and two commercial fields, using ground-based hyperspectral imaging and satellite images from the Vegetation and Environment monitoring on a New Micro-Satellite (VENmS) program. It aimed to remotely measure the leaf water potential of field-grown chickpeas under different irrigation treatments. While doing so, the limited effect of leaf area index on the ability to remotely estimate leaf water potential was revealed.
Additionally, this tool holds promise for physiologists and breeders in screening for drought-tolerant chickpea genotypes, paving the way for sustainable farming practices on a larger scale. The next step of the project is combining space-borne spectral data to improve leaf water potential estimation is ongoing.
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A Six-Legged Mountain Gazelle (See Hebrew-Language Video Above)
JERUSALEM — Does this gazelle have a problem? In March, Nir Leichter, an army reservist who stopped for coffee in Nahal HaBashor, sent to Society for the Protection of Nature in Israel (SPNI) a photograph of an Israeli gazelle with “something strange on its back.” This picture started an inquiry that Amir Balaban, Direct of Urban Nature for SPNI, and the Gazelle Valley team in Jerusalem, an urban nature site that belongs to the Jerusalem Municipality and is managed by the SPNI.
The inquiry, conducted by Balaban with Nature and Parks Authority inspector Eliav Masalti, revealed that the photograph was of a familiar gazelle with an extra pair of front legs that grew from the back of its body. Amir immediately rushed to the field to try to document the rare phenomenon. “The gazelle, which began its life in the Kissufim area as a fawn in 2021, survived a complex litter and survived as a young individual, dealt with many predators that endanger young fawns, matured single and as an adult managed to lead an impressive life in the Nahal HaBasor reserve, one of the most important remaining strongholds for the Israeli gazelle in the western Negev, especially during the recent war. Contrary to expectations, the gazelle is healthy, strong, and has three female gazelles and a fawn from the previous fall. He has been seen hosting the females in the fields and the extra legs on his back pose no challenge to him,” Balaban says.
SPNI adds that organ proliferation (polymelia) is a well-known but very rare phenomenon. This is a genetic defect, probably hereditary. It is known for cattle, birds and reptiles, and this is the first time it has been documented in an Israeli gazelle. “I watched him survey a harvested field and wait for the females. They were very apprehensive and it was impossible to get close, but slowly I managed to shorten my range in order to document this special gazelle. They moved up the field, lounging and resting in the gentle heat of the rising sun. The Israeli gazelle is a protected wild animal by law and Israel is the last stronghold of this species. Spring is the peak of the calving season and there are small fawns in the area. If you encounter a fawn hiding in a field, it is not an orphan. In the first few weeks, the deer hide the fawns from predators. Move away immediately without leaving any odor marks or residue to avoid attracting predators that will devour the fawn. Chances are that the gazelle is watching from afar and will come to treat the fawn every few hours,” Balaban adds.
The general situation of the Israeli gazelle is not great; it is estimated that only about 5,000 gazelles of this species remain in the wild. The main danger to gazelle life in the wild is construction which destroys their natural habitats, and the construction of roads which interrupt their habitats and isolates them from their species. SPNI and other organizations are fighting to save every remaining open space and ecological corridor, while at the same time trying to improve the planning processes so that development will allow significant ecological transitions. “There is still a lot of work to be done, such as improving areas defined as open spaces, in practice blocked by fences, infrastructure and more. Other dangers to the lives of the gazelles are poachers, who hunt them mainly for the purpose of trading their meat”, and, adds Amir, “the extreme increase in stray dogs and jackals, which prey on the gazelles and their fawns”.
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Preceding stories provided by Tel Aviv University, Hebrew University of Jerusalem, and the Society for the Protection of Nature in Israel.