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BEDFORD, Mass.--(BUSINESS WIRE)--Augmenix, Inc., a medical technology company that develops, manufactures, and sells proprietary absorbable hydrogels that separate and protect organs at risk during radiotherapy, today announced that the first patients have been treated with SpaceOAR® hydrogel at the Chaim Sheba Medical Center in Tel Hashomer, Israel. SpaceOAR hydrogel is an absorbable prostate-rectum spacer that reduces rectal injury during prostate radiotherapy. “We are excited to offer our patients this new, innovative technology to significantly reduce risks of prostate cancer radiotherapy,” said Zvi Symon, M.D. from the Chaim Sheba Medical Center. “SpaceOAR hydrogel will provide meaningful long-term benefits, improving overall quality of life for our patients." “We are extremely pleased to bring our innovative SpaceOAR hydrogel to physicians and patients in Israel," commented John Pedersen, CEO of Augmenix. "Our growing body of clinical evidence demonstrates that SpaceOAR hydrogel significantly reduces the risk of rectal and urinary toxicities and loss of sexual function associated with prostate cancer radiotherapy. SpaceOAR hydrogel is making a significant difference in the lives of men around the world.” Radiation therapy in the treatment of prostate cancer can cause unintended injury to adjacent healthy tissue, which can lead to bowel, urinary and sexual symptoms that can affect patient health and quality of life. With SpaceOAR hydrogel, physicians can place a hydrogel barrier to separate the prostate from surrounding healthy tissue. In January 2017, Augmenix announced three-year post-treatment data from a prospective, randomized, multi-center, patient-blinded clinical trial showing that patients treated with SpaceOAR hydrogel technology prior to prostate cancer radiotherapy demonstrated significant rectal (bowel), urinary, and sexual benefit through three years of follow up. Overall patient wellness at three years was assessed by looking at the percent of patients with clinically significant declines in all three quality of life (QOL) domains (bowel, urinary and sexual). Fully 20% (1 in 5 patients) of men in the Control arm had clinically significant declines in all three QOL areas compared to only 2.5% (1 in 40 patients) of men in the SpaceOAR hydrogel arm (p=0.002).1 Among men who were potent at baseline, the analysis showed that SpaceOAR hydrogel treated men were better able to maintain erections sufficient for intercourse through 3 years of follow-up (p=0.03). Of the men treated with SpaceOAR hydrogel, 66.7% could achieve erections sufficient for intercourse at three years compared to 37.5% in the Control arm, a 77.8% improvement.2 Radiation therapy in the treatment of prostate cancer can cause unintended radiation injury to adjacent healthy tissue (organs at risk). This injury can lead to a range of bowel, urinary and sexual symptoms that can affect patient health and quality of life during radiotherapy, and for years afterward. In recent years, radiation oncologists have considered use of “spacing” techniques to reduce the risk of radiation injury to surrounding tissue during radiotherapy. SpaceOAR hydrogel is intended to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer and in creating this space it is the intent of SpaceOAR hydrogel to reduce the radiation dose delivered to the anterior rectum. The SpaceOAR hydrogel is injected as a liquid into the space between the prostate and rectum where it pushes the structures apart and then solidifies into a soft hydrogel. The hydrogel remains stable for three months during radiation therapy then liquefies and is completely absorbed by the body. See the Instructions for Use for complete information on potential risks, warnings and precautions. Augmenix, Inc. is a privately held U.S. company based in the Boston, Massachusetts area focused on the development and commercialization of radiation oncology products using its proprietary hydrogel technology. Focusing initially on protection during prostate radiation therapy, Augmenix next-generation products will address spacing and marking applications throughout the body to improve radiotherapy and interventional oncology procedure outcomes. The company’s lead product, SpaceOAR System, is FDA cleared and is currently being used in the majority of leading cancer centers in the United States. It is also CE marked, approved in Australia and licensed in Canada. SpaceOAR is a registered trademark of Augmenix, Inc. More information about Augmenix and the SpaceOAR hydrogel can be found at http://www.Augmenix.com. Chaim Sheba Medical Center is the largest medical center in Israel and the Middle-East and one of the most comprehensive and advanced hospitals in the world. Adjacent to Tel Aviv, it is renowned for its compassionate care and leading-edge medicine. It is also a major medical-scientific research center that collaborates internationally with the medtech and pharmaceutical industries to develop new treatments and technologies, and a foremost global center for medical education. Visit www.eng.sheba.co.il for more information. 1) Hamstra D, et al. Continued Benefit to Rectal Separation for Prostate RT: Final Results of a Phase III Trial. Int J Radiat Oncol Biol Phys; 2017 Volume 97, Issue 5, Pages 976–985. 2) Hamstra D, et al. Evaluation of sexual function on a randomized trial of a prostate rectal spacer. J Clin Oncol 35, 2017 (suppl 6S; abstract 69)


News Article | July 10, 2017
Site: www.chromatographytechniques.com

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time.


News Article | July 10, 2017
Site: www.biosciencetechnology.com

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Prof. Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Prof. Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time.


News Article | July 10, 2017
Site: www.reuters.com

(Reuters Health) - Torn from their homes and families, Jewish holocaust survivors endured starvation, enslavement and staggering physical and emotional abuse at the hands of the Nazis during World War II. Now, a study released on Monday shows that survivors suffer an elevated risk of cancer, especially lung and colorectal malignancies. Israeli researchers examined the medical records of more than 152,000 holocaust survivors over more than 45 years and compared those who qualified for compensation as a result of their persecution during the war to those whose compensation bids were rejected. Survivors whose compensation bids were rejected were generally those who had been caught up in the war but who spent little or no time in a closed ghetto or a concentration camp and who survived with minimal disability. Cancer was diagnosed in 22 percent of those granted compensation and 16 percent of those denied it, according to the report in the journal Cancer. The differences were most striking for lung and colon cancers. Survivors granted compensation had a 37 percent higher risk of lung cancer and a 12 percent higher risk of colorectal cancer than those denied compensation, after adjustments for age, gender and country of origin. “This study brings to light again that outside forces can cause cancer,” said cancer epidemiologist Electra Paskett of The Ohio State University in Columbus. “Stress really does get under your skin to cause disease.” “Many have not given this hypothesis its due justice,” she said in an email. Paskett was not involved with the study but was one of the authors of an accompanying editorial. The study also found heightened cancer risk for survivors born in countries occupied by Nazi Germany compared to survivors born elsewhere. Survivors born in Nazi-occupied countries had an 8 percent higher risk of developing cancer than survivors born elsewhere, the study found. Those born in occupied countries also had a 12 percent higher risk of lung cancer and an 8 percent higher risk of colorectal cancer. Holocaust survivors experienced a myriad of potential risk factors for cancer, including infectious disease, severe and prolonged hunger, mental stress, physical abuse and overcrowding, lead author Dr. Siegal Sadetzki of the Chaim Sheba Medical Center in Tel Hashomer, Israel said in a phone interview. Although the study cannot explain the reasons for heightened risk, Sadetzki speculated about a possible explanation for the increase in lung cancer among compensated holocaust survivors. “I believe the risk for lung cancer is by a secondary, indirect mechanism,” she said. “Due to the stress, maybe the holocaust survivors smoked more and experienced lifestyle habits that are not so good for you.” Previous studies have found that starvation might protect against colon cancer. But prolonged starvation and deprivations from all vitamins and nutrients, such as what holocaust survivors experienced, might have had a different effect, Sadetzki said. An alternative theory for the rise in colon cancer rates could be that survivors compensated for their lack of food during the war by overeating afterward, she said. A previous study also found an overall increased risk of cancer, and in particular colorectal and lung cancer, among Jewish holocaust survivors. The prior study also reported an increased risk of breast cancer among women survivors. The new study, however, showed no increase in risk for breast or gynecologic cancer among female survivors. Nearly 95 percent of Hungarian Jewish women held in concentration camps during the war stopped menstruating, another previous study found. Not menstruating appears to protect against breast cancer. The longer women menstruate, the more likely they are to be diagnosed with hormone-related cancers, like breast cancer, the authors write. In their editorial, Paskett and her colleagues draw parallels between the privations experienced by holocaust survivors and those experienced by poor racial minority groups in the United States today. “Both groups had or have stressors of violence, lack of food, housing insecurity, discrimination and loss of power,” Paskett said. “Today we can think about those living in urban neighborhoods or rural areas with crumbling housing, drug use and unemployment, or low wages, contributing to increasing violence, lack of good food in area food markets, discrimination and even environmental pollution caused by large businesses.” “We need people who are willing to go into these communities and work with the people who live there to develop strategies and solutions to be able to help themselves,” she said.


News Article | July 10, 2017
Site: www.eurekalert.org

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Prof. Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Prof. Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time. "Cancer Risk Among Holocaust Survivors in Israel--A Nationwide Study." Siegal Sadetzki, Angela Chetrit, Laurence S. Freedman, Nina Hakak, Micha Barchana, Raphael Catane, and Mordechai Shani. CANCER; Published Online: July 10, 2017 (DOI: 10.1002/cncr.30783). "Extreme Population-Level Events: Do They Have an Impact on Cancer?" Beti Thompson, Sarah Gehlert, and Electra D. Paskett. CANCER; Published Online: July 10, 2017 (DOI: 10.1002/cncr.30778). Author Contact: Lee Gat, of the Sheba Medical Center, at Lee.gat@sheba.health.gov.il or 03- 530 3296. CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online at http://wileyonlinelibrary. . Follow us on Twitter @JournalCancer and Facebook https:/ Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www. .


News Article | February 21, 2017
Site: www.eurekalert.org

In both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a blood cancer were associated with B-NHL. Each group had unique risk factors too. Non-Hodgkin lymphomas (NHL), tumors which may originate from B or T lymphocytes, account for approximately 3% of the worldwide cancer burden. Most epidemiological studies of NHL have been carried out in North American and European populations, with a few focusing on East Asian populations. Very few epidemiological studies have been conducted on B-cell non-Hodgkin lymphoma (B-NHL) in Middle Eastern populations. Since Israelis and Palestinians represent genetically and culturally diverse populations living in geographic proximity, research analyzing their risk factors can enrich our understanding of genes and environment in the causation of lymphoma. Despite sharing the same ecosystem, the populations differ in terms of lifestyle, health behaviors and medical systems. Yet both populations report high incidences of NHL, which represents the fifth most common malignancy in Israel and the eighth most common malignancy among West Bank Palestinians. (As of 2012, Israel also ranked first in the world in NHL incidence rates.) Now, Israeli and Palestinian researchers have conducted a large scale epidemiological study examining risk factors for B-NHL and its subtypes in these two populations. The team was led by Prof. Ora Paltiel, Director of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, in the Hebrew University's Faculty of Medicine, and a Senior Physician in Hadassah's Hematology Department. Recruiting from both the Palestinian Arab and Israeli Jewish populations, the researchers looked at medical history, environmental and lifestyle factors among 823 people with B-cell non-Hodgkin lymphoma (B-NHL) and 808 healthy controls. Using data from questionnaires, pathology review, serology and genotyping, they uncovered some risk factors common to both populations and other factors unique to each population. The data, reported in the peer-reviewed journal PLOS ONE, showed that in both populations, overall B-NHL was associated with recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a blood cancer. An inverse association was noted with alcohol use. Some exposures, including smoking and greater-than-monthly indoor pesticide use, were associated with specific subtypes of B-NHL. The data also pointed to differences between the populations. Among Palestinian Arabs only, risk factors included gardening and a history of herpes, mononucleosis, rubella, or blood transfusion, while these factors were not identified in the Israeli Jewish population. In contrast, risk factors that applied to Israeli Jews only included growing fruits and vegetables, and self-reported autoimmune diseases. The researchers concluded that differences in the observed risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by lymphoma subtypes infer specific causal factors for different types of the disease. These findings require further investigation as to their mechanisms. The fact that risk factors operate differently in different ethnic groups raises the possibility of gene-environment interactions, that is, that environmental exposures act differently in individuals of different genetic backgrounds. But this divergence may reflect differences in diet, cultural habits, socioeconomic, environmental and housing conditions, medical services, exposure to infections in early life or other factors. This study reflects a unique joint scientific effort involving Israeli and Palestinian investigators, and demonstrates the importance of cooperative research even in politically uncertain climates. Cancer epidemiology will be enriched through the broadening of analytic research to include under-studied populations from a variety of ethnicities and geographic regions. "Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions. The study provided opportunities for training Palestinian and Israeli researchers, and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations," said Prof. Ora Paltiel, Director of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, and a Senior Physician in Hadassah's Hematology Department. Participating institutions in this research included: Braun School of Public Health and Community Medicine, and Depts. of Hematology and Pathology, Hadassah-Hebrew University Medical Center; Dept. of Medical Laboratory Sciences and Dept. of Community Medicine, Faculty of Medicine, Al Quds University; Cancer Care Center, Augusta Victoria Hospital; Beit Jalla Hospital; Department of Statistics, Hebrew University; Department of Primary Health Care, Palestinian Ministry of Health; Tisch Cancer Institute and Institute for Translational Epidemiology, Mount Sinai School of Medicine; Rambam Medical Center and Rappaport Faculty of Medicine, Technion; Chaim Sheba Medical Center and Meir Medical Center and Tel Aviv University.


News Article | September 19, 2016
Site: www.biosciencetechnology.com

The spread of malignant cells around the body, known as metastasis, is the leading cause of mortality in women with breast cancer. Now, a new gene therapy technique being developed by researchers at MIT is showing promise as a way to prevent breast cancer tumors from metastasizing. The treatment, described in a paper published today in the journal Nature Communications, uses microRNAs — small noncoding RNA molecules that regulate gene expression — to control metastasis. The therapy could be used alongside chemotherapy to treat early-stage breast cancer tumors before they spread, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research in collaboration with Noam Shomron, an assistant professor on the faculty of medicine at Tel-Aviv University in Israel. “The idea is that if the cancer is diagnosed early enough, then in addition to treating the primary tumor [with chemotherapy], one could also treat with specific microRNAs, in order to prevent the spread of cancer cells that cause metastasis,” Artzi said. The regulation of gene expression by microRNAs is known to be important in preventing the spread of cancer cells. Recent studies by the Shomron team in Tel-Aviv have shown that disruption of this regulation, for example by genetic variants known as single nucleotide polymorphisms (SNPs), can have a significant impact on gene expression levels and lead to an increase in the risk of cancer. To identify the specific microRNAs that play a role in breast cancer progression and could therefore potentially be used to suppress metastasis, the research teams first carried out an extensive bioinformatics analysis. They compared three datasets: one for known SNPs; a second for sites at which microRNAs bind to the genome; and a third for breast cancer-related genes known to be associated with the movement of cells. This analysis revealed a variant, or SNP, known as rs1071738, which influences metastasis. They found that this SNP disrupts binding of two microRNAs, miR-96 and miR-182. This disruption in turn prevents the two microRNAs from controlling the expression of a protein called Palladin. Previous research has shown that Palladin plays a key role in the migration of breast cancer cells, and their subsequent invasion of otherwise healthy organs. When the researchers carried out in vitro experiments in cells, they found that applying miR-96 and miR-182 decreased the expression of Palladin levels, in turn reducing the ability of breast cancer cells to migrate and invade other tissue. “Previous research had discussed the role of Palladin in controlling migration and invasion (of cancer cells), but no one had tried to use microRNAs to silence those specific targets and prevent metastasis,” Artzi said. “In this way we were able to pinpoint the critical role of these microRNAs in stopping the spread of breast cancer.” The researchers then developed a method to deliver engineered microRNAs to breast cancer tumors. They embedded nanoparticles containing the microRNAs into a hydrogel scaffold, which they then implanted into mice. They found that this allowed efficient and precise delivery of the microRNAs to a target breast cancer tumor site. The treatment resulted in a dramatic reduction in breast cancer metastasis, said Artzi. “We can locally change the cells in order to prevent metastasis from occurring,” she said. To increase the effectiveness of the treatment even further, the researchers then added the chemotherapy drug cisplatin to the nanoparticles. This led to a significant reduction in both the growth of the primary tumor, and its metastasis. “We believe local delivery is much more effective (than systemic treatment), because it gives us a much higher effective dose of the cargo, in this case the two microRNAs and the cisplatin,” she said. “The research offers the potential for combined experimental therapeutics with traditional chemotherapy in cancer metastasis,” said Julie Teruya-Feldstein, a professor of pathology at Mount Sinai Hospital in New York, who was not involved in the study. The research team, which also includes MIT post doc Joao Conde and graduate student Nuria Oliva, both from IMES; graduate student Avital Gilam and postdoc Daphna Weissglas-Volkov, from Tel-Aviv University; and Eitan Friedman, an oncogeneticist from Chaim Sheba Medical Center in Israel, now hopes to move on to larger animal studies of the treatment. “We are very excited about the results so far, and the efficacy seems to be really good. So the next step will be to move on to larger models and then to clinical trials, although there is still a long way to go,” Artzi said.


News Article | September 19, 2016
Site: news.mit.edu

The spread of malignant cells around the body, known as metastasis, is the leading cause of mortality in women with breast cancer. Now, a new gene therapy technique being developed by researchers at MIT is showing promise as a way to prevent breast cancer tumors from metastasizing. The treatment, described in a paper published today in the journal Nature Communications, uses microRNAs — small noncoding RNA molecules that regulate gene expression — to control metastasis. The therapy could be used alongside chemotherapy to treat early-stage breast cancer tumors before they spread, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research in collaboration with Noam Shomron, an assistant professor on the faculty of medicine at Tel-Aviv University in Israel. “The idea is that if the cancer is diagnosed early enough, then in addition to treating the primary tumor [with chemotherapy], one could also treat with specific microRNAs, in order to prevent the spread of cancer cells that cause metastasis,” Artzi says. The regulation of gene expression by microRNAs is known to be important in preventing the spread of cancer cells. Recent studies by the Shomron team in Tel-Aviv have shown that disruption of this regulation, for example by genetic variants known as single nucleotide polymorphisms (SNPs), can have a significant impact on gene expression levels and lead to an increase in the risk of cancer. To identify the specific microRNAs that play a role in breast cancer progression and could therefore potentially be used to suppress metastasis, the research teams first carried out an extensive bioinformatics analysis. They compared three datasets: one for known SNPs; a second for sites at which microRNAs bind to the genome; and a third for breast cancer-related genes known to be associated with the movement of cells. This analysis revealed a variant, or SNP, known as rs1071738, which influences metastasis. They found that this SNP disrupts binding of two microRNAs, miR-96 and miR-182. This disruption in turn prevents the two microRNAs from controlling the expression of a protein called Palladin. Previous research has shown that Palladin plays a key role in the migration of breast cancer cells, and their subsequent invasion of otherwise healthy organs. When the researchers carried out in vitro experiments in cells, they found that applying miR-96 and miR-182 decreased the expression of Palladin levels, in turn reducing the ability of breast cancer cells to migrate and invade other tissue. “Previous research had discussed the role of Palladin in controlling migration and invasion (of cancer cells), but no one had tried to use microRNAs to silence those specific targets and prevent metastasis,” Artzi says. “In this way we were able to pinpoint the critical role of these microRNAs in stopping the spread of breast cancer.” The researchers then developed a method to deliver engineered microRNAs to breast cancer tumors. They embedded nanoparticles containing the microRNAs into a hydrogel scaffold, which they then implanted into mice. They found that this allowed efficient and precise delivery of the microRNAs to a target breast cancer tumor site. The treatment resulted in a dramatic reduction in breast cancer metastasis, says Artzi. “We can locally change the cells in order to prevent metastasis from occurring,” she says. To increase the effectiveness of the treatment even further, the researchers then added the chemotherapy drug cisplatin to the nanoparticles. This led to a significant reduction in both the growth of the primary tumor, and its metastasis. “We believe local delivery is much more effective (than systemic treatment), because it gives us a much higher effective dose of the cargo, in this case the two microRNAs and the cisplatin,” she says. “The research offers the potential for combined experimental therapeutics with traditional chemotherapy in cancer metastasis,” says Julie Teruya-Feldstein, a professor of pathology at Mount Sinai Hospital in New York, who was not involved in the study. The research team, which also includes MIT post doc Joao Conde and graduate student Nuria Oliva, both from IMES; graduate student Avital Gilam and postdoc Daphna Weissglas-Volkov, from Tel-Aviv University; and Eitan Friedman, an oncogeneticist from Chaim Sheba Medical Center in Israel, now hopes to move on to larger animal studies of the treatment. “We are very excited about the results so far, and the efficacy seems to be really good. So the next step will be to move on to larger models and then to clinical trials, although there is still a long way to go,” Artzi says.


Multiple Myeloma (MM) is a lymphatic neoplasm characterized by clonal proliferation of malignant plasma cell that eventually develops resistance to chemotherapy. Drug resistance, differentiation block and increased survival of the MM tumor cells result from high genomic instability. Chromosomal translocations, the most common genomic alterations in MM, lead to dysregulation of cyclin D, a regulatory protein that governs the activation of key cell cycle regulator--cyclin dependent kinase (CDK). Genomic instability was reported to be affected by over expression of another CDK regulator--cyclin E (CCNE). This occurs early in tumorigenesis in various lymphatic malignancies including CLL, NHL and HL. We therefore sought to investigate the role of cyclin E in MM. CCNE1 expression was found to be heterogeneous in various MM cell lines (hMMCLs). Incubation of hMMCLs with seliciclib, a selective CDK-inhibitor, results in apoptosis which is accompanied by down regulation of MCL1 and p27. Ectopic over expression of CCNE1 resulted in reduced sensitivity of the MM tumor cells in comparison to the paternal cell line, whereas CCNE1 silencing with siRNA increased the cell sensitivity to seliciclib. Adhesion to FN of hMMCLs was prevented by seliciclib, eliminating adhesion-mediated drug resistance of MM cells. Combination of seliciclib with flavopiridol effectively reduced CCNE1 and CCND1 protein levels, increased subG1 apoptotic fraction and promoted MM cell death in BMSCs co-culture conditions, therefore over-coming stroma-mediated protection. We suggest that seliciclib may be considered as essential component of modern anti MM drug combination therapy.


Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu. We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning. Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens. This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.

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