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Vision 2020 – Meet brilliant Technion researchers in their labs.

Come take part in the Technion International Board of Governors for 2020. This is the year of new vision, new possibilities, and new dimensions of engagement.

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Novel Method Can Diagnose Cancer and Determine Metastatic Risk Within Two Hours

Professor Daphne Weihs’ mechanobiology-based technology can predict the metastatic potential of a tumor. The method entails seeding tumor-sampled cells on a specialized gel that mimics tissue-stiffness and quantifying the number of cells that push into the gel surface and other measures.

Metastasis, the spread of cancer cells from the primary tumor to new areas of the body and the generation of secondary tumors, is responsible for 90% of cancer-related deaths. A research team led by Professor Daphne Weihs of the Technion Faculty of Biomedical Engineering has developed and tested a mechanobiology-based technology to predict whether a tumor is cancerous and, if so, its clinical metastatic potential. The study was published in the scientific journal Annals of Biomedical Engineering.

Prof. Weihs’ technology can rapidly determine metastatic risk by evaluating the invasiveness of cells sampled from a tumor by seeding them on a synthetic gel that mimics tissue stiffness and wherein invasive cells will rapidly and forcefully push into the gel’s surface. Quantification of the number of indenting cells and other measures provides the likelihood of metastasis formation. 

Currently, Prof. Weihs and her team successfully tested the technology on pancreatic tumor cell samples collected from volunteers at the Rambam Health Care campus and on established breast and pancreatic cell lines. The results were validated against the current standard clinical protocols and agreed with the clinical diagnoses, prognoses, and patient outcomes. The results also matched established cell lines of the same cancer types. The mechanical invasiveness assay, which may be applied to many, and potentially all, solid tumor types, successfully differentiates between benign (not cancerous), non-metastatic, and metastatic tumor samples, and concurrently gages their metastatic likelihood.

Cancer morbidity is caused by uncontrolled tumor progression, which results in tumor growth and, potentially, metastatic spread. Early prediction of increased metastatic risk can significantly affect disease management and improve treatment outcomes. Current methods used to estimate the likelihood of metastasis and tumor recurrence are time-consuming, qualitative, and require extensive examinations that take days or even weeks – valuable time that cancer patients may not have. Rapidly progressing tumors require swift and aggressive treatment. Moreover, current methods are not infallible. For example, 30% of cancer-negative lymph node assessments in breast cancer patients fail to predict eventual metastases development.      

In previous research, Prof. Weihs established that invasive, cancerous cells will push into synthetic, polyacrylamide gels to cell-scale depths within 1-2 hours, while normal or non-invasive cells do not significantly indent the gel. Prof. Weihs explained: “The gels are a customized platform that mimics the physiological stiffness of soft tissue. The invasiveness of cells sampled from tissues is rapidly and quantitatively evaluated using our innovative mechanical invasiveness assay, which we are currently developing into a clinically applicable technology.” 

The great advantage of this technology is that it rapidly provides physicians with quantitative measures to determine patient-specific treatment protocols within hours after an initial biopsy. Consequently, informed decisions can be made, such as, if an aggressive chemotherapy course is needed (for highly invasive tumor cells) or an aggressive surgical approach is warranted (for less invasive tumor cells, where the tumor will likely remain localized). Such a swift assessment, at first diagnosis, can improve disease management and patient survival by increasing the precision of the chosen treatment plan and reducing psychological and physical stress brought on by long wait times and potentially overly aggressive treatments.   

The research was partially funded by the Elias Fund for Medical Research, the Polak Fund for Applied Research, the Ber-Lehmsdorf Foundation and the Gerald O. Mann Charitable Foundation. 

For the article in Annals of Biomedical Engineering click here

Epigenetics lies behind the ability of a human reproductive function to adapt to the environment

Addressing the mystery of how reproduction is shaped by childhood events and the environment, an international team of researchers recently published a paper in Nature Reviews Endocrinology on the role of epigenetics in human reproduction. The team included Professor Philippa Melamed, together with Ph.D. student Ben Bar-Sadeh, Postdoctoral researcher Dr. Sergei Rudnizky, and colleagues Dr. Lilach Pnueli and Prof. Ariel Kaplan, all from the Technion Faculty of Biology, and collaborators from the UK, Prof. Gillian R. Bentley from Durham University and Prof. Reinhard Stöger from the University of Nottingham.

Epigenetics refers to the packaging of DNA, which can be altered in response to external signals (environment) through the addition of chemical “tags” to the DNA or the histone proteins that organize and compact the DNA inside the cell. This packaging affects the ability of a gene to be accessed and thus also its expression levels. As a result, environmentally induced changes in this epigenetic packaging can lead to major variations in the phenotype (observable characteristics or traits) without changing the genetic code. This reprogramming of gene expression patterns underlies some of our ability to adapt.  

Reproductive characteristics are highly variable and responsive particularly to early life environments, a time when they appear to be programmed to optimize an individual’s reproductive success in accordance with the surroundings. Although some of these adaptations can be beneficial, they also carry negative health consequences that may be far-reaching. These include the age of pubertal onset and duration of the reproductive lifespan for women and the levels of circulating reproductive hormones. In addition to their effects on fertility, such adaptations can also increase the predisposition to hormone-dependent cancers and other age-related diseases.

While epigenetic modifications are believed to play a role in the plasticity of reproductive traits, the actual mechanisms are still not clear. Moreover, reproductive hormones also modify the epigenome and epigenetic aging, which complicates distinguishing cause from effect, particularly when trying to understand human reproductive phenotypes in which the relevant tissues are inaccessible for analysis. Integrated studies are needed, including observations and whatever measurements are possible in human populations, incorporation of animal models, cell culture, and even single-molecule studies, in order to determine the mechanisms responsible for the human reproductive phenotype. 

The review emphasizes that there is a clinical need to understand the characteristics of epigenetic regulation of reproductive function and the underlying mechanisms of adaptive responses for properly informed decisions on treating patients from diverse backgrounds. In addition, this knowledge should form the basis for formulating lifestyle recommendations and novel treatments that utilize the epigenetic pathway to alter a reproductive phenotype.

According to Prof. Melamed, “a multifaceted cross-disciplinary approach is essential for elucidating the involvement of epigenetics in human reproductive function, spanning the grand scale of human cohort “big data” and anthropological studies in unique human populations, through animal models and cell culture experiments, to the exquisitely high resolution of single-molecule biophysical approaches. This will continue to require collaboration and co-operation.” 

For the article in Nature Reviews Endocrinology click here

Technion researchers have developed a method for predicting the safety and effectiveness of diabetes treatment methods for specific patients.  The patented discovery will help physicians determine which treatments to use and which to avoid when caring for their diabetic patients.  

The research was led by Professor Andrew P. Levy, MD, Ph.D., of the Technion’s Rappaport Faculty of Medicine, along with Leah E. Cahill, Ph.D. and doctoral candidate Allie S. Carew of the Harvard T.H. Chan School of Public Health and Department of Medicine of Dalhousie University in Nova Scotia, Canada. The researchers investigated 5,805 diabetic patients, and their work has been patented and published in the Journal of the American College of Cardiology (JACC). 

Diabetes is one of the most common diseases in the developed world. The disease, which affects roughly 10% of Israelis, is a metabolic condition characterized by high concentrations of glucose, or simple sugars, in the patients’ bloodstream. The disease is caused by a malfunction of the insulin absorption process. When functioning correctly, the pancreas produces the hormone insulin to help cells convert glucose into energy to power the body. However, among people with diabetes, the process is disrupted for one of two reasons: either the body does not produce enough insulin, or the cells are insulin resistant. The result in both cases is hyperglycemia, an excessive accumulation of glucose in the blood.

Hyperglycemia poses a significant danger, damaging the inner blood vessel walls and leading to a narrowing of the arteries and veins. According to Prof. Levy, “Hyperglycemia harms numerous bodily functions, including vision and kidney function. However, when it impairs cardiovascular activity, the results can be catastrophic. And in fact, most deaths of diabetic patients are caused by heart disease.” 

The most common treatment of diabetes focuses on intensive therapy to reduce blood sugar levels. However, today researchers know that this drastic reduction can actually be harmful and significantly increase mortality rates. This was demonstrated a decade ago in a landmark American study called ACCORD, published by The New England Journal of Medicine.  The study showed that intensive treatment could actually increase mortality rates amongst diabetic patients. 

The revelations of the ACCORD study posed a significant ethical dilemma for doctors. Should they treat diabetes if it risks causing cardiovascular damage? 

Enter Prof. Andrew Levy, who has spent more than 20 years searching for a simple blood test for identifying diabetic patients at high risk of heart attacks. His discovery began in past research showing that certain haptoglobin protein types in diabetic patients could predict patients’ level of risk for cardiovascular complications. For example, patients with type 2-2 haptoglobin are nearly five times as likely to suffer heart attacks than patients without. Building on that data, Prof. Levy then examined the patients in the ACCORD study to see if their response to aggressive treatment correlated with their haptoglobin protein type.

The study just published in the JACC reveals that among diabetics with type 2-2 haptoglobin, an intensive reduction in blood sugar levels reduced heart attacks by approximately 30%, but did not change mortality rates. However, among diabetes patients with other types of haptoglobin protein, intensive treatment did not affect the number of heart attacks and even increased mortality rates by a dramatic 40%. 

Prof. Levy and the research team concluded that checking haptoglobin could allow doctors to predict the success of aggressive treatment. According to Prof. Levy, “The ACCORD research was curtailed because of the rise in the number of patients who died as a result of treatment. However, today we can identify the specific patients who will indeed respond positively to treatment. Currently, more studies are being planned that will verify and strengthen this research.”

An alliance of leading European universities of science and technology is starting an international study programme with the goal of jointly shaping the engineering education of the future. This “EuroTeQ Engineering University” will be open not only to students enrolled at the partner universities, but also to engineers working in industry who are interested in life-long learning. The initiative will reinvigorate the symbiosis between society and technology together with various stakeholders and orient its programme towards human-centred engineering. The concept was now successful in the European Union’s “European Universities” Initiative.

The EU will fund the project with approximately five million euros over the next three years. The initiative emerges from the EuroTech Universities Alliance, a strategic partnership of Technical University of Denmark (DTU), École Polytechnique (L’X), Eindhoven University of Technology (TU/e), Technical University of Munich (TUM) as well as Ecole polytechnique fédérale de Lausanne (EPFL) and the Technion – Israel Institute of Technology. For this project, they have brought two other strong partners on board: Tallinn University of Technology (TalTech) and Czech Technical University in Prague (CTU). EPFL and Technion, being located in non-EU countries and hence not eligible for funding, will contribute to the implementation of the programme.

Individually designed curricula

The partners will establish a joint engineering sciences study programme across different disciplines as well as across national and institutional boundaries, reaching well beyond individual technologies. The goal of the alliance is to look at technology developments on a holistic level. “Today, we can’t talk about mobility without considering climate impacts, and robotics and artificial intelligence will not succeed without winning over human trust,” says Professor Thomas F. Hofmann, President of TUM, which coordinates the project. “A modern engineering education must provide students not only with in-depth technical knowledge but also with an extended educational horizon, an entrepreneurial mindset and socio-political sensitivity.”

In order to promote this understanding Europe-wide, the “EuroTeQ Engineering University” will not be restricted to students enrolled at the respective partner institutions. It will also be open to those who do not hold an academic degree yet, but who play an important role in value creation and communication processes. Students will be able to design their curricula in line with their learning objectives and career aspirations and benefit from new digital formats. In the spirit of life-long learning, they will be able to continue their education throughout their entire career.

Interaction between students and vocational trainees

The alliance will furthermore bring their university students together with vocational trainees pursuing a technical career and with a large number of stakeholders from industry, trade associations and various areas of society to explore the grand challenges of the 21st century and jointly formulate solution strategies. The project has already won the support of 45 collaboration partners. Thanks to this, the “EuroTeQ Engineering University” will gain comprehensive experience with the various qualification structures in Europe and will learn about the needs of the younger generation. These findings will, in turn, be integrated in the design of teaching at all partner universities.

“With EuroTeQ, we are building on the strengths of existing cooperation between the EuroTech Universities and our partners from Estonia and the Czech Republic, and on our multidisciplinary research-based curricula,” says Tatiana Panteli, Head of the EuroTech Universities Alliance Brussels Office. “We are also thrilled to add many exciting and challenging elements to this new European university, which will provide lifelong learning opportunities for students and professionals, to ‘engineer’ talents for the industry and society of the future.”

Prestigious project of the European Commission

The European Universities, introduced by French President Emmanuel Macron, are a flagship initiative of the European Commission, which aims at establishing ambitious European university alliances that will make the European university landscape even stronger in the fierce competition with the USA and Asia.

Researchers at the Technion and Tel Aviv University have deciphered the sophisticated movement pattern of coral tentacles, which improves the rate of food supply and oxygen fluxes around the coral. The discovery sheds light on how the species adapt to the complex reef environment.

Researchers at the Technion and Tel Aviv University have discovered a surprising pattern to the oscillating motions of coral’s flexible appendages with respect to the wave-induced water flow in its direct vicinity. The movement pattern optimizes the coral’s oxygen and food supply. The research, published in Proceedings of The Royal Society B, was conducted by the graduate student Dror Malul and his advisors, Professor Uri Shavit of the Technion Faculty of Civil and Environmental Engineering and Professor Roi Holzman of the Department of Zoology at Tel Aviv University.

Corals are marine animals that are fixed to a substrate and therefore unable to roam in search of food. They depend on water flow for food and oxygen supply and waste disposal. Although the coral’s body is sedentary, it has tentacles that extend into the water around it, where they interact and oscillate with the waves. Corals can use their reduced muscular system and internal hydro-skeleton to extend and contract their tentacles to catch prey or defend against predators but are unable to move the tentacles from side to side.

The researchers filmed the coral tentacle movement underwater, at the coral reef, and in a laboratory wave facility at the Interuniversity Institute for Marine Sciences in Eilat, Israel. They made an unexpected discovery that the oscillating movements of the tentacles are not passive. In other words, the coral tentacles precede the movement of the waves in an out-of-phase motion.

According to Prof. Shavit: “In the experiments, we measured the movement of the tentacles and the speed of water near them, and we were surprised to find that the tentacles precede the motion of the water. They move at the same frequency as the wave frequency, but with a phase difference of nearly ¼ of the wave cycle. The result was intriguing because it was clear to us that corals do not have a muscular system capable of moving the tentacles sideways.”

The study shows that the out-of-phase motion results from the tentacles’ elasticity, which can presumably be modified by the animal. At the beginning of the motion, the elastic tentacles move with the wave. Towards halfway of the cycle, the water flow weakens and the elastic force returns the tentacle to its central position before the water speed changes its direction again. Using mathematical modeling, simulations, and other measurements, the researchers found that the phase difference and the movement of the tentacles relative to the water improve three important functions: the amount of oxygen the coral absorbs at night; removal of excess oxygen during daily photosynthesis; and the rate of food supply (plankton).

Photographing the tentacle movement of other coral species suggests that this mechanism is typical of all coral tentacles. According to Dror Malul, “In the dense and competitive environment of the reef, any mechanism that provides the coral with a competitive advantage over its neighbors can determine which of the coral species will survive. To date, many biological mechanisms that help coral adapt to the complex reef environment have been revealed, but the path to fully understanding all of its physical mechanisms is still long.”

Following the discovery, the researchers focused on the following areas: learning the mechanism that creates the phase difference by developing a dynamic model for calculating the periodic movement of coral tentacles; developing a method of measuring the elastic properties of the tentacles, and; exploring the mechanisms that influence the ability of corals to increase the inlet and outlet fluxes depending on water velocity and the phase difference. The researchers postulate that the out-of-phase motion and the resulting elevated fluxes are general and occur not only with coral tentacles but also in river vegetation, natural forests, and agricultural fields.

Click here for the paper in Proceedings of the Royal Society 

Researchers at the Technion have developed a new method for rapid and inexpensive analysis of the chemical composition of blood samples, which may hasten the early diagnosis of diseases. The first application to be tested will be the early detection of various cancerous tumors based on blood tests.

The innovative technology, which was published in Nature Communications, was developed by Professor Tomer Shlomi and doctoral students Shoval Lagziel and Boris Sarvin. It is based on a unique combination of mass spectrometry and computational methods developed by the research group.

A mass spectrometer is a common device used to determine the concentrations of molecules in biological samples. Testing using this device typically requires a preliminary process called chromatography that entails the separation of the materials in the sample according to chemical properties.

Chromatography, which increases the sensitivity of the spectrometric measurement, is time-consuming and therefore makes the process expensive. One sample typically costs hundreds of dollars. As a result, it is desirable to find a way to skip the chromatographic step without compromising the sensitivity of the analysis, that is, the ability to identify many molecules and quantify their concentrations.

In the current study, Prof. Shlomi’s research group presents a method that skips the chromatography step and makes it possible to directly use mass spectrometry without significantly impairing the quality of the analysis. The test is completed in just 30 seconds, thus shortening the process by about 98% and reducing its cost by a similar rate. 

According to Prof. Shlomi, the novelty lies in the use of a computational method developed by the research group. They employ a method that identifies optimal working configurations in the mass spectrometer, which allows for a high-sensitivity analysis for specific types of biological samples.

The computational analysis also corrects the measured raw information and accurately quantifies concentrations of thousands of molecules in blood samples.

Prof. Tomer Shlomi is a faculty member in the Faculties of Computer Science and Biology and a member of the Lorry I. Lokey Center for Life Sciences and Engineering. The research was funded by an ERC grant and by the Israel Science Foundation.

For the full article on Nature Communications click here.

Vision 2020 – Meet brilliant Technion researchers in their labs.

Come take part in the Technion International Board of Governors for 2020. This is the year of new vision, new possibilities, and new dimensions of engagement.

Tune in live with the Technion global family!

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Inspired by the potassium channel in cells: The future of ion-selective synthetic membranes is vast

A Nature Nanotechnology perspective piece highlights the importance of ion-specific membranes and “paves pathways for new research avenues.”

A Nature Nanotechnology perspective piece by new Assistant Professor Razi Epsztein, of the Technion Faculty of Civil and Environmental Engineering, and his postdoc mentor, Professor Menachem Elimelech from Yale University, highlights the future of synthetic membranes, which are used widely in desalination and other technologies. The focus of the researchers’ piece is on the future fabrication of membranes with sub-nanoscale pores that possess the ability to selectively distinguish between specific ions in water, even extremely similar ones, such as sodium and potassium.

Currently, membrane technology is predominantly used in reverse osmosis desalination, an energy-efficient way to ideally remove all salts from water. However, reverse osmosis and other types of synthetic membranes lack the ability to discriminate between ions, which results, for example, in the redundant step of re-adding the ions that are necessary for drinking water to be safe. Moreover, the waste, or brine, resulting from current non-selective desalination is an environmental concern.

Based on the potassium channel found in cells, synthetic ion-selective membranes take their inspiration from nature’s ingenuity. Such ion-selective technology would pave the way for membranes that can be used to remove a contaminant from groundwater while leaving “good” ions behind; membranes with the ability to mine important elements from water such as lithium, which is a valuable resource for batteries in our wireless world; a method to pre-treat and remove calcium and magnesium from seawater, before desalination, to reduce scale buildup that shortens the lifespan of reverse osmosis membranes; filtering or sensing target compounds in medicine; and much more.

Emphasizing the potential of ion-selective membranes, Prof Epszstein said that, “Selectivity is fascinating and important at the same time. Improving our ability to discriminate and separate between small ions and molecules can be super beneficial for water-treatment processes, as well as for resource recovery, energy production, sensing, and even medicine.”

Prof. Epsztein’s lab will focus on the development of “selective separation technologies for a wide range of environmental applications, with a focus on membrane technologies at the water-energy nexus.” This will entail the fundamental study of transport in polymeric (organic) membranes and advanced materials followed by the fabrication of selective membranes for various applications that require high selectivity.

In a big step forward toward making BIO-photoelectrochemical cells (BIOcells) a mainstream clean energy source in the future, researchers from the Technion – Israel Institute of Technology and Ruhr-Universität Bochum (RUB) have overcome an efficiency hurdle by successfully combining the power of efficient light absorption by photosynthetic light-harvesting complexes with the electrochemical power of Photosystem II (PSII), nature’s water splitting enzyme. The breakthrough is a functional solution to overcoming previously limited efficiency due to a “green-light gap” in the absorption spectrum of biosolar energy devices. The findings were published in the Journal of Materials Chemistry A.

As the world strives to replace fossil fuel with clean energy sources, solar energy – because of its abundance and total lack of polluting elements – is considered a particularly valuable energy source. In nature, bacteria, algae, and plant life have evolved to efficiently convert solar energy into chemical energy via photosynthesis. BIOcells are an innovative concept in the field of renewable energy aimed at harnessing this natural process semi-artificially for the development of clean, affordable, and efficient energy sources.

BIOcells utilize large protein complexes called photosystems, which have the capacity to convert sunlight into electrical energy. Isolated from plants, algae, or cyanobacteria, photosystems are responsible for natural sunlight to energy conversion in nature. PSII is a valuable type of photosystem because it uses water as an electron source for the generation of electricity. It is the source of all the oxygen that we breathe and all the food that we eat. 

But BIOcells containing only PSII complexes only have limited efficiency. The efficiency is measured by the amount of electrical power coming out of the cell divided by the sunlight energy coming in, and PSII alone can only convert a limited range of light. They are unable to convert green light, which constitutes about 50% of visible light, into energy. In cyanobacteria and red algae, this is rectified by the Phycobilisome (PBSs) light harvesting complex. PBSs are protein structures found in cyanobacteria that enable them to harvest light that is not absorbed efficiently by the chlorophyll molecules in PSII. PBSs function as a light-absorbing transmitter, directing excitation energy into the reaction centers of PSII.

“As unique as PSII is, its efficiency is limited, because it can use merely a percentage of the sunlight,” explained Professor Marc Nowaczyk, head of the Molecular Mechanisms of Photosynthesis project group at RUB. “Cyanobacteria have solved the problem by forming special light-collecting proteins, i.e. the PBS, which also make use of this light. This cooperation works in nature, but not yet in the test tube.” Professor Noam Adir of the Schulich Faculty of Chemistry added that, “just as in nature, our two groups collaborated, bringing our expertise in isolating the PBS with Prof. Nowaczyk’s groups expertise in isolating PSII. Together we overcame the obstacles of putting it all together in the BIOcell.”

In order to make the collaboration between cyanobacteria and plant photosynthesis functional in an artificial BIOcell, the two teams succeeded in producing a two-component bioelectrode. This included the difficult task of functionally joining the PBS and PSII multiprotein complexes.  some of which were combined across species. 

The researchers, led by Dr. Volker Hartmann (RUB) and Dr. Dvir Harris (Technion), stabilized the interaction between PSII and PBS by permanently fixing the proteins at a very short distance from each other using crosslinkers. Crosslinkers are molecules with two or more reactive ends that are capable of chemically attaching to specific functional groups on proteins. After crosslinking PSIIs with PBSs, the team was then able to insert the super complexes into the appropriate electrode structures. 

Integration of the PBS–PSII super-complexes within a hydrogel on macro-porous indium tin oxide electrodes (MP-ITO) improved the incident photon-to-electron conversion efficiencies (IPCE). IPCE values in the “green gap” were doubled compared to PSII electrodes without PBS and the IPCE in the green light gap reached a maximum of 10.9%. 

The capacity to assemble these proteins is a breakthrough in biological solar cell development. This means that protein complexes from different species can be functionally combined to create semi-artificial systems that have the cumulative advantages of the different species utilized. 

In their future BIOcell research, the teams will mainly focus on optimizing the production and life span of the biological components. 

The research was funded by the German-Israeli research project Nano-engineered Opto-bioelectronics with Biomaterials and Bio-inspired Assemblies under the auspices of the German Research Foundation (DFG) and the Israel Science Foundation and the Ruhr Explores Solvation Resolv Cluster of Excellence (www.solvation.de) and the GRK 2341 Microbial Substrate Conversion Research School (Micon), which is financed by the DFG.

Professor Noam Adir is a member of The Nancy and Stephen Grand Technion Energy Program (GTEP), and Dr. Dvir Harris is a GTEP PhD track graduate.

Click here for the paper in Journal of Materials Chemistry A

There is a connection between heart disease and cancer, a novel study has revealed. The findings, published in Circulation, could potentially help cardio-oncologists slow cancer progression and improve cancer outcomes. Researchers led by Professor Ami Aronheim, Professor Yuval Shaked, and Dr. Shimrit Avraham have determined that early changes in the heart resulting from cardiac disease or damage (cardiac remodeling) promotes cancer progression. 

Recently, studies have indicated that cancer and cardiovascular diseases are connected, and that heart failure and stress correlate with a poor cancer prognosis. While it has been determined that chemotherapy drugs can be damaging to heart muscle, the effects of cardiac remodeling on cancer are not well known. To uncover the connection between cardiac remodeling and cancer, a research team led by Professor Ami Aronheim, Professor Yuval Shaked, and Dr. Shimrit Avraham, from the Rappaport Faculty of Medicine at the Technion, and their colleagues Professor Walid Saliba and Professor Avinoam Shiran from Carmel Hospital, have investigated whether early cardiac remodeling in the absence of heart failure promotes cancer. 

To mimic cardiac remodeling, the research team collaborated with the Preclinical Research Authority, led by Dr. Rona Shofti and Dr. Tali Haas, and used a laboratory technique called transverse aortic constriction (TAC) to exert mechanical pressure on the hearts of laboratory mice. TAC stresses the mouse heart with a pressure overload resulting in an increase in heart cell growth called hypertrophy, which is a common effect of cardiovascular complications. The team then implanted cancer cells into the TAC-operated mice to see if the early cardiac remodeling affects tumor progression.

The researchers found that the TAC-operated mice developed larger tumors at the site of the implanted cancer cells. In addition, TAC-operated mice displayed a higher rate of cancer cells seeding to the lungs, representing metastases (secondary tumors spread from the original lesion) as compared to non-operated mice. 

The investigators also found that serum from TAC-operated mice resulted in enhanced cancer cell proliferation in cell cultures (in vitro), suggesting that tumor-promoting proteins are present in the blood from the TAC-operated mice. Specifically, a protein called Periostin, which is highly expressed in the hearts of the TAC-operated mice. To investigate the effects of Periostin, on cancer cells, the researchers studied how it affected cancer cells in vitro. They found that the addition of purified Periostin enhanced cancer cell proliferation, and that the depletion of Periostin from mouse serum lowered cancer cell proliferation (in vitro). 

The results of the study, published in Circulation highlight the connection between cardiovascular disease and cancer, and the importance of early diagnosis and treatment of cardiac disease in cancer patients. Such intervention has the potential to significantly attenuate cancer progression and improve cancer outcomes. 

“As a result of the study, we recommend that you treat heart problems early, when the body is still successfully coping with the problem, and not wait for a chronic condition,” said Prof. Aronheim. “Such problems can be detected with a simple echocardiography test, and in many cases, early catheterization may help to slow cancerous development.”

The research was supported by the Israel Science Foundation (ISF). 

Click here for the paper in Circulation