Scientists uncover new target for brain cancer treatment

A new study is giving researchers hope that novel targeted therapies can be developed for glioblastoma multiforme (GBM), the most common and most aggressive form of brain cancer, after demonstrating for the first time that a gene known as melanoma differentiation associated gene-9/syntenin (mda-9/syntenin) is a driving force behind the disease’s aggressive and invasive nature.

Recently published in the journal Neuro-Oncology, the study led by Virginia Commonwealth University Massey Cancer Center and VCU Institute of Molecular Medicine (VIMM) researchers used cell cultures and animal models to uncover the mechanisms by which mda-9/syntenin causes GBM to grow and invade normal brain tissue. Additionally, by using publicly available cancer genomic database information (bioinformatics) and analyzing tissue samples from patients with GBM, the researchers found that increased levels of mda-9/syntenin correlated with more advanced tumors and shorter survival. The study’s discoveries pinpoint molecular targets that could be used to develop new therapies, and also suggest that the gene could be used to help stage and monitor this aggressive disease.

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“Our current study represents a major breakthrough in understanding what drives GBM, and it is a starting point for the development of future therapies,” says the study’s lead author Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at Virginia Commonwealth University Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM. “Because mda-9/syntenin is expressed more in advanced disease, we are also hopeful that we may be able to use the gene to monitor for disease progression and test whether certain therapies are working.”

Mda-9/syntenin was originally discovered by Fisher, and through bioinformatics he has found that the gene is overexpressed in a majority of cancers. He and his colleagues also found that mda-9/syntenin interacts with a predicted 151 cancer-related proteins through its PDZ domains, which are chains of amino acids that enable cell signaling by facilitating interactions between proteins.

In GBM, Fisher and his colleagues demonstrated that overexpression of mda-9/syntenin enhanced the cells’ ability to invade healthy tissue. In contrast, blocking expression of mda-9/syntenin in animal models reduced invasion, suppressed cell migration and caused tumors to shrink. Additionally, blocking the expression of mda-9/syntenin decreased the production and secretion of interleukin 8 (IL-8) proteins, which are signaling proteins that contribute to tumor growth and progression by promoting cell migration and the development of new blood vessels, a process known as angiogenesis.

“We are now focusing on developing small molecules, or drugs, that block the binding of specific cancer-promoting proteins that interact with mda-9/syntenin through its PDZ domains,” says Fisher. “If successful, these PDZ-targeted therapies could potentially lead to effective treatments for GBM.”

Fisher collaborated on this research with Timothy P. Kegelman, graduate student in the M.D./Ph.D. program at VCU School of Medicine; Manny Bacolod, Ph.D., instructor in the Department of Human and Molecular Genetics at VCU School of Medicine; Bin Hu, Ph.D., postdoctoral researcher in the VCU Department of Human and Molecular Genetics; Devanand Sarkar, M.B.B.S., Ph.D., Harrison Research Scholar and member of the Cancer Molecular Genetics research program at VCU Massey, associate professor in the VCU Department of Human and Molecular Genetics and associate scientific director of cancer therapeutics at VIMM; Swadesh K. Das, Ph.D., instructor in the VCU Department of Human and Molecular Genetics and VIMM member; Luni Emdad, M.B.B.S., Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey, assistant professor in the VCU Department of Human and Molecular Genetics and VIMM member; Santanu Dasgupta, Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey, assistant professor in the VCU Department of Human and Molecular Genetics and VIMM member; Mitchell E. Menezes, Ph.D., postdoctoral research scientist in the VCU Department of Human and Molecular Genetics; Christine E. Fuller, M.D., professor and director of neuropathology in the Department of Pathology at VCU School of Medicine; Paul Dent, Ph.D., Universal Corporation Distinguished Professor for Cancer Cell Signaling and member of the Developmental Therapeutics research program at VCU Massey and professor and chair of research in the Department of Neurosurgery at VCU School of Medicine; Albert S. Baldwin, Ph.D., professor at the University of North Carolina; Jeffrey N. Bruce, M.D., professor and vice-chair at Columbia University; and Maurizio Pellecchia, Ph.D., professor at Sanford-Burnham Medical Research Institute.

This study was supported by National Institutes of Health grant R01 CA134721, the National Foundation for Cancer Research, Goldhirsh Foundation for Brain Tumor Research, the Dana Foundation and, in part, by VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059.

The full manuscript of this study is available online at: http://neuro-oncology.oxfordjournals.org/content/early/2013/12/03/neuonc.not157.full?keytype=ref&ijkey=7bky3mv0fplTyPb

Researchers hope newly discovered gene interaction could lead to novel cancer therapies

Scientists from Virginia Commonwealth University have revealed how two genes interact to kill a wide range of cancer cells. Originally discovered by the study’s lead investigator Paul B. Fisher, M.Ph., Ph.D., the genes known as mda-7/IL-24 and SARI could potentially be harnessed to treat both primary and metastatic forms of brain, breast, colon, lung, ovary, prostate, skin and other cancers.

Fisher-suit-at-deskIn the study, recently published in the online version of the journal Cancer Research, Fisher’s team found that forced expression of MDA-7/IL-24 (melanoma differentiation associated gene-7/interlukin-24) stimulates SARI (suppressor of AP-1, induced by interferon) expression in what is known as an autocrine/paracrine loop, which ultimately causes cancer cells to undergo a form of cell suicide known as apoptosis. Autocrine/paracrine loops occur when the expression of a particular gene or its encoded protein causes cells to secrete molecules that bind to surface receptors and force the expression of more of the same protein in an ongoing cycle.

“Many previous studies show that MDA-7/IL-24 can selectively kill diverse cancer cells through multiple mechanisms, but what was unclear was how exactly MDA-7/IL-24 interacted with other genes to promote cancer toxicity,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, and chairman of the Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine (VIMM) at VCU School of Medicine. “Our study uncovered multiple signaling pathways used by MDA-7/IL-24 that facilitate cancer cell death through the induction of SARI.”

Fisher and his team identified an existing combination of receptors, IL-20R1 and IL-20R2, and a discovered new combination of receptors, IL-22R1 and IL-20R1, through which signaling occurs to induce the MDA-7/IL-24 autocrine/paracrine loop. Once activated by the MDA-7/IL-24 protein, these receptors cause both normal and cancer cells to produce and secrete the MDA-7/IL-24 protein, which, in turn, activates SARI. The process was shown to culminate in apoptosis in cancer cells. Normal, healthy cells were not affected in the experiments.

The researchers are now focusing on developing small molecule drugs that induce MDA-7/IL-24 and/or SARI in cancer cells. They have also been experimenting with cancer-selective replicating viruses that seek out cancer cells and infect them with the toxic genes—an approach that has already been successfully employed in a phase 1 clinical trial using engineered viruses that deliver MDA-7/IL-24.

“This study helped us better understand how MDA-7/IL-24 works to kill a broad range of cancer cells through the induction of SARI,” says Fisher. “In addition to giving us another target for the development of new therapies, our research also suggests that we may be able to monitor the expression of SARI in order to determine the effectiveness of future therapies under development that target MDA-7/IL-24.”

Fisher collaborated on this research with Praveen Bhoopathi, Ph.D., postdoctoral research scientist in the Department of Human and Molecular Genetics at the VCU School of Medicine; Swadesh K. Das, Ph.D., instructor in the VCU Department of Human and Molecular Genetics and VIMM member; Devanand Sarkar, M.B.B.S., Ph.D., Harrison Research Scholar and member of the Cancer Molecular Genetics research program at VCU Massey, associate professor in the VCU Department of Human and Molecular Genetics and associate scientific director of cancer therapeutics at VIMM; Luni Emdad, M.B.B.S., Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey, assistant professor in the VCU Department of Human and Molecular Genetics and VIMM member; Santanu Dasgupta, Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey, assistant professor in the VCU Department of Human and Molecular Genetics and VIMM member; and Rupesh Dash, Ph.D., former postdoctoral research scientist in the VCU Department of Human and Molecular Genetics and now assistant professor at the Institute of Life Sciences in Bhubaneshwar, India.

This research was supported by National Institutes of Health grants 5 R01 CA097318, P01 CA104177 and 1 R01CA127641; and, in part, by VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059.

The full manuscript of this study is available online at: http://cancerres.aacrjournals.org/content/early/2013/11/26/0008-5472.CAN-13-1062.full.pdf+html

Massey researcher Steven Grant to play key role at prestigious international cancer research conference

Grant,Stevennew cropVCU Massey Cancer Center researcher Steven Grant, M.D., was recently selected to serve as chairperson of the Small Molecule Therapeutic Agents Section of the Molecular Therapeutics Subcommittee of the Program Committee for the American Association of Cancer Research (AACR) 2014 Annual Meeting.

Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, co-leader of the Developmental Therapeutics research program and member of the Cancer Cell Signaling program at VCU Massey Cancer Center, Grant is a world-renown leader in the field of targeted anti-cancer agents and in the development of novel combination therapies for hematologic malignancies. As chairperson, he will be responsible for leading a team of cancer researchers in rating abstracts submitted for presentation in the Small Molecule Therapeutic Agents Section of the annual meeting and in organizing the overall program.

“It’s an honor to be selected for this role, and I am proud to support an organization that has contributed so much to the field of cancer research,” says Grant. “This year’s annual meeting will highlight some of the most exciting and promising new discoveries for the treatment and prevention of cancer, and I’m pleased to be involved.”

The AACR Annual Meeting takes place April 5-9, 2014, in San Diego, Ca. More than 7,000 scientists are expected to attend the event, which will feature more than 6,000 papers submitted by cancer researchers from all over the world.

Enter the “Mos for Massey” Social Media Contest!

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Enter the Mos for Massey contest

“Movemeber” is a campaign that encourages men to grow moustaches during the month of November to help raise awareness for testicular cancer, prostate cancer and mental health issues. VCU Massey Cancer Center invites everyone to join the “Movember” movement and help us raise awareness for men’s cancers by taking part in our “Mos for Massey” contest. “Mos for Massey” encourages people to submit pictures of their (real or fake) moustaches for a chance to win prizes, be recognized on VCU Massey’s social media Websites and help raise awareness for men’s cancers! Please continue reading for contest rules and prizes.

Rules:

  1. Take a picture of your (real or fake) moustache and email it to TeamMassey@vcu.edu with “Mos for Massey” in the subject line. Be sure to include your full name, general location and contact information in the email.
  2. Contestants are limited to one entry for each week of the Contest. Continue reading for submission deadlines.
  3. New entries will be posted in a “Mos for Massey” album on VCU Massey Cancer Center’s Facebook page each week—on Monday, November 11, 18 and 25—and the entry with the most “likes” each week will win a Massey t-shirt and goody bag!
  4. The submission with the most overall “likes,” regardless of when it was submitted, wins a $100 Amazon gift card and will be recognized on VCU Massey’s Facebook page!
  5. Bearded ladies welcome!

Reminder: Be sure to “like” our Facebook page to see your photo, tag yourself and encourage your friends to “like” your entry. Also, help us spread the word on social media by using the hashtag #Mos4Massey.

Week 1 submission deadline: November 10 at midnight
– Voting for this round will take place November 11-15.
– The submission with the most “likes” by Friday, November 15 at noon wins for that week!

Week 2 submission deadline: November 17 at midnight
– Voting for this round will take place November 18-22
– The submission with the most “likes” by Friday, November 22 at noon wins for that week!

Week 3 submission deadline: November 24 at midnight
– Voting for this round will take place November 25-29
– The submission with the most “likes” by Friday, November 29 at noon wins for that week!

Grand prize:
– The submission with the most overall “likes” at the end of the month, regardless of when it was submitted, wins a $100 Amazon gift card!

By submitting an entry to the “Mos for Massey” contest, contestants agree to the contest rules and grant Virginia Commonwealth University and VCU Massey Cancer Center permission to publish each contestant’s name, photograph and or likeness in any promotion or advertising for VCU Massey Cancer Center and the “Mos for Massey” contest without compensation or additional approval. All pictures will be reviewed for inappropriate content and published at the discretion of VCU Massey Cancer Center. Questions about the contest can be sent to TeamMassey@vcu.edu.

VCU Massey introduces new, high-tech radiation technology to improve cancer care

VCU Massey Cancer Center has made a significant investment in improving the region’s cancer care by becoming the only cancer care provider in Richmond to utilize the TrueBeam™ linear accelerator. This advanced machine made by Varian Medical Systems incorporates the latest image-guided radiation therapy technologies and higher dose rates to more accurately target patients’ tumors while sparing healthy tissue, reducing side effects and decreasing treatment times.

IMG_3608 350pxThe advanced capabilities of the TrueBeam™ system allow physicians to better treat complex cancers such as lung, liver, prostate and head and neck tumors that are close to vital organs and delicate tissue. With advanced imaging techniques, physicians can monitor and adapt to changes in a patient’s anatomy caused by the radiation therapy to personalize treatment plans based on each patient’s unique physiology. The optical camera system even allows physicians to see patient motion during treatments so they can monitor and adjust as needed.

“The TrueBeam™ system offers some very exciting and state-of-the-art features, but if you don’t know how to use them you may as well be using a normal linear accelerator. This is where our experts at VCU Massey Cancer Center set us apart from other institutions,” says Jatinder Palta, Ph.D., chief physicist in the Department of Radiation Oncology at VCU Massey Cancer Center. “We have pioneers in image-guided radiation therapy who have developed advanced radiation therapy techniques that are now being used nationwide. It is this experience that allows us to take full advantage of all of the benefits of TrueBeam™.”

Massey’s downtown location started using TrueBeam™ in June 2013, and the radiation oncology team is already pioneering ways to improve radiation therapy using its advanced features. Elizabeth Weiss, M.D., radiation oncologist at Massey, and Geoffrey Hugo, Ph.D., medical physicist at Massey, have received a grant to study image-guided radiation therapy in the treatment of lung cancers. Using advanced imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) scans coupled with the advanced targeting abilities of TrueBeam™, they are monitoring changes in patients’ tumors throughout treatments in order to determine whether patients have better outcomes when their treatment protocol is adjusted to match the changes that are happening in their body. If successful, Weiss and Hugo will help develop new treatment protocols that could be adopted worldwide.

IMG_3655-350x233In addition to the incorporation of advanced imaging technologies, TrueBeam™ also offers a unique advanced motion package that allows doctors to more accurately compensate for movement caused by the patient’s breathing. In addition, TrueBeam™ can deliver much higher doses of radiation compared to other linear accelerators. The increased dose delivery combined with advanced imaging techniques can shorten a 10-minute treatment to just two or three minutes while delivering the same amount of radiation.

“Historically, physicians treated patients as if no physiological changes occur throughout the course of the radiation treatments,” says Palta. “We know this is not the case, and now advanced image-guided radiation therapy using equipment such as TrueBeam™ potentially opens a lot of possibilities for improving patient outcomes by personalizing treatment plans.”

In addition to its downtown location, TrueBeam™ is already in use at Massey’s partner clinic at Spotsylvania Regional Medical Center. Massey also plans to install the TrueBeam™ system at its Hanover facility and at Hunter Holmes McGuire VA Medical Center, where Massey provides cancer care to area veterans.

Massey rated the top cancer center in Virginia by U.S. News two years in a row

RICHMOND, VA_cancer2For the second year in a row, Virginia Commonwealth University Massey Cancer Center was rated the top hospital in Virginia providing high-performing cancer care in U.S. News & World Report’s annual Best Hospitals list. Massey received the highest score in cancer care of the 20 Virginia cancer providers that made the list.

VCU Medical Center, which includes Massey’s oncology patient care, also established itself as a No. 1 hospital overall in Virginia for a second consecutive year. It saw two specialty areas rank in the top 50 in the nation, nephrology at 41 and orthopedics in the No. 39 spot.

This is the 24th year of the annual rankings, which recognize hospitals that excel in treating the most challenging patients.

“The recognition from U.S. News affirms VCU Massey Cancer Center’s quality cancer care,” says Gordon D. Ginder, M.D., director of VCU Massey Cancer Center. “We are thankful for those who trust in us to provide their care, and for our committed staff who deliver that care with compassion and leading expertise.”

U.S. News publishes Best Hospitals to help guide patients who need a high level of care because they face conditions that require particularly difficult and specialized treatment. The rankings are based upon many factors, including reputation, patient survival, patient safety and care-related factors such as nursing and patient services.

“We are ecstatic that the VCU Medical Center once again achieved this rank,” said Sheldon Retchin, M.D., CEO of the VCU Health System and senior vice president for VCU Health Sciences. “The level of clinical excellence and research at our academic medical center is unsurpassed, and we are very proud of the entire health care team.”

In addition to Massey’s cancer care, VCU Medical Center had seven other specialties recognized as high performing:

  • Cardiology and heart surgery
  • Diabetes and endocrinology
  • Gastroenterology and GI surgery
  • Geriatrics
  • Neurology and neurosurgery
  • Pulmonology
  • Urology

The complete rankings are available online at http://health.usnews.com/best-hospitals.

VCU Massey Cancer Center hosts annual research retreat

Research Retreat Banner

The annual Virginia Commonwealth University Massey Cancer Center Research Retreat showcases the most promising cancer research being conducted at Massey and throughout VCU and provides student researchers an opportunity to show off their contributions in the poster session, where they can receive up to $250 as Excellence in Cancer Research Awards winners. In addition to presentations from members of Massey’s research programs, this year’s keynote presentation featured Timothy Ley, M.D., who shared his work involving the acute myeloid leukemia (AML) genome.

Research program presentations

The research program presentations this year were intended to highlight collaborative research projects that bring together investigators with different areas of expertise, with the goal of accelerating the translation of basic science to new therapeutic approaches. There was barely a seat left in the Molecular Medicine Research Building’s conference room as the retreat got underway. After brief opening remarks by VCU Massey Cancer Center Director Gordon Ginder, M.D., Matthew Hartman, Ph.D., from Massey’s Developmental Therapeutics program, and Lawrence Povirk, Ph.D., from the Radiation Biology and Oncology program, started off the lectures by discussing their collaboration on the development of a novel drug that could increase the effectiveness of radiation therapy by reducing cancer cells’ ability to repair DNA damage.

Next, Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program, chairman of VCU School of Medicine’s Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine (VIMM), presented on efforts to develop a viral gene therapy intended to induce expression of melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24 (mda-7/IL-24), which was originally cloned in Fisher’s laboratory and has been shown in experiments to kill a variety of different types of cancer cells at the primary tumor site and in distant, untreated tumors. The research was a collaboration between Fisher and Paul Dent, Ph.D., Universal Corporation Distinguished Professor for Cancer Cell Signaling, director and chair of the Division of Research in the Department of Neurosurgery at VCU School of Medicine and member of the Development Therapeutics program at Massey. Fisher discussed the entire process, starting with basic research findings and ending with efforts to initiate phase 1 clinical trials. He also commented on the challenges that face all cancer researchers attempting similar work.

Continuing on the mda-7 theme, Charles Chalfant, Ph.D., member of the Cancer Cell Signaling program, and Michael Shultz, Ph.D., from the Department of Biochemistry and Molecular Biology at VCU School of Medicine, presented their research on the connection between mda-7 and lung cancer. Chalfant and Schultz talked about findings from recent studies that have uncovered a novel regulatory mechanism that is “hijacked” by lung cancer cells and allows for resistance to current therapies. Furthermore, their research suggests that there is potential in developing a novel nanoparticle that harnesses both mda-7/IL-24 and reinstatement of the “highjacked” mechanism to effectively treat lung cancer.

Ley, Lewis T. and Rosalind B. Apple Chair in Oncology, professor of medicine and genetics and director of the Section of Stem Cell Biology at Washington University, and associate director of cancer genomics at The Genomics Institute, provided the keynote address on his work exploring the genetic changes that contribute to the development of AML. In 2008, Ley led a team that sequenced the full genome from a patient’s AML cells, making them the first to sequence an entire cancer genome. Whole genome sequencing is a process that can show all of the genetic components that combine to make a specific type of cell. Using the information they gained from sequencing AML samples, Ley and his colleagues were able to identify specific genetic mutations responsible for the development of AML. They discovered two key mutations, that are now being examined as targets for the development of new gene therapies. Ley also discussed future implications of genome sequencing in cancer research.

Poster session and Excellence in Cancer Research Awards

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Every year, students in graduate level programs throughout VCU as well as postdoctoral fellows are invited to display their research relating to cancer and compete for Excellence in Cancer Research Awards. A panel of Massey judges awarded first, second and third place prizes totaling $250, $200 and $150 to students presenting the most promising cancer research. This year, nearly 60 research studies were on display throughout the halls and conference rooms of VCU Massey’s Goodwin Research Laboratory.

Award Winnerscaption2This year’s first place winner was Bridget A. Quinn, a student in VCU School of Medicine’s M.D.-Ph.D program. Quinn’s research focused on the potential use of a novel drug known as sabutoclax to treat pancreatic cancer, a disease for which there are few effective therapies. Quinn demonstrated that sabutoclax is capable of inducing apoptosis, a form of cell death, as well as growth arrest in pancreatic cancer cells. Further, she showed that sabutoclax, when combined with the commonly used antibiotic, minocycline, synergizes to produce profound growth inhibition and cell death in pancreatic cancer cells and mouse models.

Second place went to Chadia Robertson, a Ph.D. student in the Department of Human and Molecular Genetics at VCU School of Medicine. Robertson’s research focused on a gene, astrocyte elevated gene-1 (AEG-1), that has been shown to be over-expressed in many cancer types. In her study, she helped to develop the first mouse model that confirmed AEG-1’s role in the development and progression of liver cancer, a contribution that will be invaluable in future experiments testing new treatments for this disease.

Lauren Folgosa, also a student in VCU School of Medicine’s M.D.-Ph.D. program, received third place for her research that unveiled the effects of two genes known as ADAM10 and ADAM17 in the expression of tumor necrosis factor alpha (TNFa). TNFa is a signaling molecule that helps regulate processes essential to cancer cell survival, including inflammation, apoptosis and a variety of other biological functions. Using mouse models, Folgosa and her colleagues provided evidence of the processes by which dysregulation of the ADAM10 and ADAM17 genes impact the production of TNFa and lead to the development of cancer.

 

Targeted viral therapy destroys breast cancer stem cells in preclinical experiments

A promising new treatment for breast cancer being developed at Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine (VIMM) has been shown in cell culture and in animal models to selectively kill cancer stem cells at the original tumor site and in distant metastases with no toxic effects on healthy cells, including normal stem cells. Cancer stem cells are critical to a cancer’s ability to recur following conventional chemotherapies and radiation therapy because they can quickly multiply and establish new tumors that are often therapy resistant.

Fisher lab coatThe study, published in the International Journal of Cancer, focuses on a gene originally cloned in the laboratory of primary investigator Paul B. Fisher, M.Ph., Ph.D. The gene, melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24, has been shown to directly impact two forms of cell suicide known as apoptosis and toxic autophagy, regulate the development of new blood vessels and also play a role in promoting cancer cell destruction by the immune system. In the present study, the researchers used a recombinant adenovirus vector, an engineered virus with modified genetic material, known as Ad.mda-7 to deliver the mda-7/IL-24 gene with its encoded protein directly to the tumor.

“Therapy with the mda-7/IL-24 gene has been shown to be safe in a phase I clinical trial involving patients with advanced cancers, and prior studies in my laboratory and with collaborators have shown that the gene could also be effective against breast, prostate, lung, colorectal, ovarian, pancreatic and brain cancers,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program at VCU Massey, chairman of VCU School of Medicine’s Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine (VIMM). “Our study demonstrates that this therapy may someday be an effective way to eradicate both early and advanced stage breast cancer, and could even be used to reduce the risk of cancer recurrence.”

The researchers found that infection of human breast cancer cells with the adenovirus decreased the proliferation of breast cancer stem cells without affecting normal breast stem cells. It was also shown to induce a stress response in the cells that led to apoptosis by disrupting Wnt/B-catenin signaling, a process cells rely upon to transmit signals that initiate biological functions critical to survival. In mouse models, the therapy profoundly inhibited the growth of tumors generated from breast cancer stem cells and also killed cancer cells in distant, uninjected tumors.

Since discovering the mda-7/IL-24 gene, Fisher and his team have worked to develop better ways to deliver it to cancer cells, including two cancer “terminator” viruses known as Ad.5-CTV and Ad.5/3-CTV. Cancer terminator viruses are unique because they are designed to replicate only within cancer cells while delivering immune-modulating and toxic genes such as MDA-7/IL-24. Coupled with a novel stealth delivery technique known as ultrasound-targeted microbubble destruction (UTMD), researchers can now systemically deliver viruses and therapeutic genes and proteins directly to tumors and their surrounding tissue (microenvironment) at both primary and metastatic tumor sites. UTMD uses microscopic, gas-filled bubbles that can be paired with viral therapies, therapeutic genes and proteins, and imaging agents and can then be released in a site and target-specific manner via ultrasound. Fisher and his colleagues are pioneering this approach and have already reported success in experiments utilizing UTMD technology and mda-7/IL-24 gene therapy in prostate and colorectal cancer models.

“We are hopeful that this targeted gene therapy could be safely combined with conventional chemotherapies to significantly improve outcomes for patients with breast cancer and potentially a variety of other cancers,” says Fisher. “When paired with promising new delivery techniques such as UTMD, physicians may one day be able to better target site-specific cancers and also monitor the effectiveness of these types of therapies in real time.”

Fisher collaborated on this study with Paul Dent, Ph.D., member of the Developmental Therapeutics program at VCU Massey, professor in the Department of Neurosurgery at VCU School of Medicine and member of VIMM; Xiang-Yang Wang, Ph.D., member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics and associate scientific director of immunology and infectious diseases of VIMM; Devanand Sarkar, M.B.B.S., Ph.D., Harrison Scholar and member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics at VCU School of Medicine, and associate scientific director of cancer therapeutics at VIMM; Belal Azab, Ph.D., and Michelle E. Menezes, Ph.D., both postdoctoral scientists from the Department of Human and Molecular Genetics at VCU School of Medicine; and Sujit K. Bhutia, Ph.D., Department of Human and Molecular Genetics at VCU School of Medicine, now an assistant professor in the Department of Life Science, National Institute of Technology, Rourkela, India.

This study was supported by National Cancer Institute grants R01 CA097318 and P01 CA104177.

The full manuscript of this study is available at: http://onlinelibrary.wiley.com/doi/10.1002/ijc.28289/abstract;jsessionid=EAF95F3253E44B492D50B8E862E1F55E.d03t03

Biodegradable implant may lessen side effects of radiation to treat prostate cancer

Several years ago, Virginia Commonwealth University Massey Cancer Center became the first center in the United States to test an Israeli-invented device designed to increase the space between the prostate and the rectum in prostate cancer patients undergoing radiation therapy. Now, results from the international Phase I clinical trial show that the device has the potential to significantly reduce rectal injury, a side effect caused by unwanted radiation exposure that can leave men with compromised bowel function following treatment.

BioProtect CT BlogResults of the 27-patient prospective trial were recently published in the journal Radiation Oncology. The device known as the BioProtect Balloon Implant was tested on patients with localized prostate cancer. It is designed to reduce radiation exposure to the rectum by expanding to increase the space between the rectum and the prostate. It remains in place throughout the treatment process and is designed to biodegrade completely within six months.

Anscher-Blog“We found that the addition of BioProtect reduced the radiation dose delivered to the rectum by an average of about 30 percent,” says local primary investigator Mitchell Anscher, M.D., Florence and Hyman Meyers Chair of Radiation Oncology at VCU Massey Cancer Center. “Most notable was the device’s ability to reduce exposure at higher radiation levels, which indicates that the cancer could be safely treated with more aggressive protocols.”

The researchers observed a greater reduction in radiation exposure to the rectum at increasing radiation dose levels. At 50 percent of prescribed dose, there was little difference in rectal tissue exposure. However, there was a 55.3 percent reduction at 70 percent of the prescribed dosage, a 64 percent reduction at 80 percent of the prescribed dosage, a 72 percent reduction at 90 percent of the prescribed dosage and an 82.3 percent reduction at 100 percent of the prescribed dosage.

As anticipated, all implanted balloons started to degrade three months after implantation. The researchers concluded that the device could be especially useful in hypofractionated radiation therapy. Hypofractionated radiation therapy uses larger doses of radiation applied over a shorter number of treatments instead of delivering a small percentage of the total dose during daily treatments spread over a longer period of time.

“Massey has many patients that travel from rural areas for care. If this device allows us to deliver the prescribed radiation dose over a shorter period of time, we can reduce the overall burden on the patient and they can spend less time away from work and their family,” says Anscher. “We hope to initiate a Phase II clinical trial in a larger cohort of patients in order to determine the effectiveness of the device in reducing rectal injury in comparison to standard treatment protocols.”

Anscher collaborated with the study’s lead investigator Gyorgy Kovacs, M.D., Ph.D., from the University of Lubeck, Germany; Dieter Jocham, M.D., and Gunther Bohlen, M.D., also from the University of Lubeck; Eliahu Gez, M.D., Rami Ben Yosef, M.D., Benjamin W. Corn, M.D., and Fabrizio Dal Moro, M.D., all from the Department of Radiation Oncology at Tel Aviv Sourasky Medical Center, Israel; Giovanni Scarzello, M.D., from the Department of Radiotherapy at the University of Padova, Italy; and Isaac Koziol, M.D., Mathew Bassignani, M.D., and Taryn Torre, M.D., all from Virginia Urology; and Shmuel Cytron, M.D., from Barzilai Medical Center, Israel.

The full manuscript of the study is available online at: http://www.sciencedirect.com/science/article/pii/S0167814013000236

Educational videos help cancer patients become familiar with radiation therapy

Radiation_EquipmentEach year, approximately one million cancer patients undergo radiation therapy and yet many have very little understanding of how it works or what to expect. Now, a pilot study conducted at Virginia Commonwealth University Massey Cancer Center suggests that educational videos shown before the patients’ initial consultation with their radiation oncologist can significantly boost their understanding of the planning and treatment process.

The results of the 32-patient pilot study were recently published in the Journal of Cancer Education. Every patient in the study reported learning new information from the DVD and felt they were better prepared for radiation therapy than before they watched it. Interaction testing demonstrated that patients benefited, regardless of age, gender, ethnicity income or health literacy. When asked the three most important things that they learned, participants most often cited the importance of not missing any radiation therapy appointments, possible side effects from radiation therapy, asking questions during appointments, the need for a support system and the effects of radiation therapy on cancer cells – all very important knowledge for any patient undergoing radiation therapy for cancer.

RMatsuyama“Prior research suggests that more than half of radiation oncology patients perceive that they did not get adequate information prior to treatment, and over 83 percent of patients with treatment complications want more information,” says the study’s lead researcher Robin Matsuyama, Ph.D., member of the Cancer Prevention and Control research program at VCU Massey Cancer Center. “Patients give informed consent during their initial consultation, and we believe that anything that helps patients understand this complex process allows them to ask more informed questions and become better prepared for the road ahead.”

Participants’ knowledge of radiation therapy and cancer care was evaluated before and after the video using a series of multiple choice questions. Additionally, prior to watching the video they were asked to complete a baseline assessment where they rated their knowledge of cancer and radiation therapy on a Likert scale. Before watching the video, 78 percent of patients rated their understanding of radiation therapy as “a little bit” or “not at all,” 91 percent reported little to no understanding of the difference between external beam radiation and brachytherapy, 81 percent had little to no understanding of the purpose of radiation tattoos, 71 percent had little to no understanding of how radiation was administered and 63 percent had little to no understanding of the role of the radiation oncologist.

After watching the video, participants got an average of 2.3 more questions correct on the multiple choice test. The most improvement was seen in patients 18-45 years old, African Americans, individuals earning below the poverty level and those with higher levels of education. The most common feedback about the video was that it could be shortened by approximately 5 minutes.

“Our study demonstrates that an educational video such as ours can significantly improve patients’ understanding of how radiation therapy works,” says Matsuyama. “We feel this could be a cost-effective way to prepare patients for their treatments, and we plan to conduct future studies in a larger sample of patients.”

Moving forward, the researchers are proposing a randomized clinical trial that will better assess the long-term effects of the video on knowledge retention, patient satisfaction and adherence to their treatments.

Matsuyama collaborated on this study with Drew Moghanaki, M.P.H., M.D., member of the Radiation Biology and Oncology research program and radiation oncologist at VCU Massey; Laurie Lyckholm, M.D., member of the Cancer Prevention and Control research program and hematologist-oncologist at VCU Massey; and Anthony Molisani, a graduate student in the Department of Social and Behavioral Health at VCU School of Medicine.
Funding for this study was provided, in part, by VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059 and the American Cancer Society.

The full manuscript of this study is available online at: http://link.springer.com/article/10.1007%2Fs13187-013-0473-1