Symposium speakers 2015: Martin Pomper

Neuro X is the title and theme for the May 1 symposium hosted by Johns Hopkins Institute for NanoBioTechnology. The event kicks off with a continental breakfast at 8 a.m. in the Owens Auditorium, between CRB I and CRB II on the Johns Hopkins University medical campus. Talks begin at 9 a.m. Posters featuring multidisciplinary research from across many Hopkins divisions and departments will be on display from 1 p.m. to 4 p.m.

One of this year’s speakers is Martin G. Pomper, MD, PhD.

Martin Pomper, MD, PhD

Martin Pomper, MD, PhD

Martin Pomper is the William R. Brody Professor of Radiology at the Johns Hopkins School of Medicine, with a joint appointment in Chemical and Biomolecular Engineering at the Whiting School of Engineering. He received his undergraduate, graduate (organic chemistry) and medical degrees from the University of Illinois at Urbana-Champaign. His postgraduate medical training was at Johns Hopkins and included an internship (Osler Medical Service), residencies (diagnostic radiology and nuclear medicine) and fellowship (neuroradiology). He is board-certified in diagnostic radiology and nuclear medicine. He has been on the Radiology faculty at Johns Hopkins since 1996. He is currently the director of the Johns Hopkins Small Animal Imaging Resource and associate director of the In Vivo Cellular and Molecular Imaging Center, both funded by the National Cancer Institute to support molecular imaging research.

Dr. Pomper is director of the Johns Hopkins Center for Translational Molecular Imaging. He is co-director of the Johns Hopkins Center of Cancer Nanotechnology Excellence and the Positron Emission Tomography Center. His interests are in the development of new radiopharmaceuticals, optical probes and techniques for molecular imaging of cancer and central nervous system disease. His research group consists of chemists, physicists, molecular biologists and clinicians working together toward clinical molecular imaging. He is Editor-in-Chief of Molecular Imaging and a past President of the Society of Nuclear Medicine’s Molecular Imaging Center of Excellence. He has numerous patents related to medical imaging, many of which have been licensed, as well as several imaging agents in clinical trials.

Additional speakers will be profiled in the next few weeks. To register your poster and for more details visit http://inbt.jhu.edu/news/symposium/

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

New eyes for diagnostics

Initial medical diagnoses are done based on physical examination by a health care professional. However, as the technology of optics, computing, and biology continues to advance, engineers have essentially developed “enhanced eyes” for health care professionals to see beyond the limits of our natural vision to diagnose patients. For example, with the advent of ultrasound, doctors are able to see into a pregnant mother’s womb to monitor the health of a developing baby.

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source: http://www.upmc.com/patients-visitors/education/tests/pages/petct-scan.aspx

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source: http://www.upmc.com/patients-visitors/education/tests/pages/petct-scan.aspx

New imaging techniques and machines are combining existing modalities. This improves diagnoses and combines the strengths of each imaging modality. For example, cancer diagnosis can now be achieved by scanning a patient with a dual PET/CT machine (Fig. 1). In this method, imaging specialists combine the strength of CT scans, which shows high resolution of organ location and tissue distribution, and PET scans, which determines molecular/cellular activity by introducing a radioactive molecule into the body.

These technologies have also increased our understanding of diseases and are used frequently in research to develop new theories for disease mechanisms. Nevertheless, because of the amount of technology and engineering that has gone into developing these machines, they are still very costly both to patients and researchers.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

How firefly research helped gene therapy

Sometimes on a calm summer or fall night, one is able to observe the beautiful dance of blinking fireflies. Scientists began to explore mechanisms to describe this unique natural phenomenon as early as the late 1800’s. After a series of experiments with solutions at different temperature with ground up abdomens of fireflies, Raphael Dubois named the enzyme luciferase and the substrate luciferin that were the cause of the light-producing reaction (1).  But it wasn’t until recently in 1985 that scientists were able to clone the gene for luciferase and express it in bacteria to produce the luciferase.

firefly

Figure 1: Picture of firefly. Source: http://www.fireflyexperience.org/photos/

Once the gene was cloned, genetic researchers realized the importance of the findings and started to use it as a reporter gene for experimental gene therapy. Gene therapies involve transfection of new genetic material into the host’s DNA and can be applied not only for therapies for diseases of genetic origin, but can be used for cancer therapy and diagnostic purposes.

By incorporating the gene for luciferase along with the gene of interest, the Hai-Quan Mao lab in the Department of Materials Science and Engineering at Johns Hopkins University can detect whether or not their nanoparticles used for gene delivery have been successful simply by adding luciferin to the cells. If the gene transfer was successful, then the luciferase will act on the substrate luciferin to emit light.

Sources

1)     Fraga, Hugo. “Firefly luminescence: A historical perspective and recent developments.” Photochemical & Photobiological Sciences 7.2 (2008): 146-158.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

 

Drug-chemo combo destroys challenging breast cancer stem cells

Gregg Semenza

Gregg Semenza

Researchers affiliated with Johns Hopkins Physical Sciences-Oncology Center (PS-OC) have shown that combining chemotherapy with an agent that blocks a certain cancer survival protein holds the key to fighting one of the the toughest forms of breast cancer.

Only 20 percent of patients with what are known as “triple-negative” breast cancer cells respond to chemotherapy. PS-OC associate director and Johns Hopkins professor of  medicine Gregg Semenza demonstrated in a recent study that chemotherapy actually enhances triple-negative cancer stem cell survival by switching on proteins called hypoxia-inducible factors (HIF). But when combined with currently available and FDA-approved HIF-inhibiting drugs, such as digoxin, Semenza said, chemotherapy shrank tumors.

Mice with implanted triple-negative breast cancer stem cells were treated with a combination therapy comprised of the HIF-inhibiting drug plus the chemotherapeutic drug paclitaxel. That combo treatment decreased tumor size by 30 percent more than treatment with chemotherapy. Furthermore, Semenza’s study showed that combining digoxin with the a different chemotherapeutic agent called gemcitabine “brought tumor volumes to zero within three weeks and prevented the immediate relapse at the end of treatment that was seen in mice treated with gemcitabine alone,” a press release on the study stated. Clinical trials will be needed to verify these results.

Debangshu Samanta, Ph.D., a postdoctoral fellow in the Semenza lab, was the lead author on this research published online in the Proceedings of the National Academy of Sciences. Additional authors include Daniele Gilkes, Pallavi Chaturvedi and Lisha Xiang of the Johns Hopkins University School of Medicine.

Read the PNAS article here.

Visit the PS-OC website here.

For all press inquiries regarding INBT, its faculty and programs, contact INBT’s science writer Mary Spiro, mspiro@jhu.edu or 410-516-4802.

 

Podcast: Artificial blood vessel visualizes cancer cell journey

Researchers from Johns Hopkins Institute for NanoBioTechnology are visualizing many of the steps involved in how cancer cells break free from tumors and travel through the blood stream, potentially on their way to distant organs.  Using an artificial blood vessel developed in the laboratory of Peter Searson, INBT director and professor of materials science and engineering, scientists are looking more closely into the complex journey of the cancer cell.

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue). (Wong/Searson Lab)

INBT’s science writer, Mary Spiro, interviewed device developer Andrew Wong, a doctoral student Searson’s  lab, for the NanoByte Podcast. Wong is an INBT training grant student. Listen to NANOBYTE #101 at this link.

Wong describes the transparent device, which is made up of a cylindrical channel lined with human endothelial cells and housed within a gel made of collagen, the body’s structural protein that supports living tissues. A small clump of metastatic breast cancer cells is seeded in the gel near the vessel while a nutrient rich fluid was pumped through the channel to simulate blood flow. By adding fluorescent tags the breast cancer cells, the researchers were able to track the cells’ paths over multiple days under a microscope.

VIDEO: Watch how a cancer cell approaches the artificial blood vessel, balls up and then forces its way through the endothelial cells and into the streaming fluids within the channel of the device. (Video by Searson Lab)

The lab-made device allows researchers to visualize how “a single cancer cell degrades the matrix and creates a tunnel that allows it to travel to the vessel wall,” says Wong. “The cell then balls up, and after a few days, exerts a force that disrupts the endothelial cells. It is then swept away by the flow. “

Wong said his next goal will be to use the artificial blood vessel to investigate different cancer treatment strategies, such as chemotherapeutic drugs, to find ways to improve the targeting of drug-resistant tumors.

Results of their experiments with this device were published in the journal Cancer Research in September.

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Check out this gallery of images from the Searson Lab. The captions are as follows:
Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).
Figure 2. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a vessel with dual-labeled MDA-MB-231 breast cancer cells on the periphery.
Figure 3. Phase-contrast and fluorescence overlays depicting a functional vessel comprised of human umbilical vein endothelial cells (HUVECs) with dual-labeled MDA-MB-231 breast cancer cells on the periphery (green in the nucleus, red in the cytoplasm).

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

 

Jordan Green named to PopSci’s Brilliant Ten

Jordan Green, Johns Hopkins University associate professor of biomedical engineering and executive committee member for the Johns Hopkins Institute for NanoBioTechnology, was named one of Popular Science magazine’s Brilliant Ten. The magazine recognized “inspired young scientists and engineers … whose ideas will transform the future.”

Jordan Green (Photo by Marty Katz)

Jordan Green (Photo by Marty Katz)

Green’s work focuses on using nanoscale particles made in the shape of footballs that can train the body’s own immune system to tackle cancer cells. Turns out, particles with the elongated ovoid shape have a slightly larger surface area, which gives them an edge over spherical particles. The football-shaped particles did a better job of triggering the immune system to attack the cancer cells.

Green collaborated with Jonathan Schneck, M.D., Ph.D., professor of pathology, medicine and oncology at Johns Hopkins School of Medicine. Both are affiliated faculty members of Johns Hopkins Institute for  NanoBioTechnology. Their work was published in the journal Biomaterials on Oct 5, 2013.

Read more about their research here.

Congratulations to Dr. Green for the recognition of your interesting and promising work!

Watch a video where Green explains his work in simple terms using toys.

Three-way brain tumor therapy sparks immune system with radiation

Johns Hopkins researchers have found that combining radiation with two therapies that activate the immune system allow mice with brain tumors (glioblastoma) to survive longer than mice who did not receive the combo treatment. INBT affiliated faculty member Michael Lim, M.D., an associate professor of neurosurgery, oncology at the Johns Hopkins University School of Medicine, said the radiation may act “as kind of kindling, to try to induce an immune response.”

brainRead the full press release from Johns Hopkins regarding the publication in PLoS One journal below:

A triple therapy for glioblastoma, including two types of immunotherapy and targeted radiation, has significantly prolonged the survival of mice with these brain cancers, according to a new report by scientists at the Johns Hopkins Kimmel Cancer Center.

Mice with implanted, mouse-derived glioblastoma cells lived an average of 67 days after the triple therapy, compared with mice that lasted 24 days when they received only the two immunotherapies. Half of the mice who received the triple therapy lived 100 days or more and were protected against further tumors when new cancer cells were re-injected under the animals’ skins.

The combination treatment described in the July 11 issue of PLOS One consists of highly focused radiation therapy targeted specifically to the tumor and strategies that lift the brakes and activate the body’s immune system, allowing anti-cancer drugs to attack the tumor. One of the immunotherapies is an antibody that binds to and blocks an immune checkpoint molecule on T cells called CTLA-4, allowing the T-cells to infiltrate and fight tumor cells. The second immunotherapy, known as 4-1BB, supplies a positive “go” signal, stimulating anti-tumor T cells.

None of the treatments are new, but were used by the Johns Hopkins team to demonstrate the value of combining treatments that augment the immune response against glioblastomas, the most common brain tumors in human adults. The prognosis is generally poor, even with early treatment.

“We’re trying to find that optimal balance between pushing and pulling the immune system to kill cancer,” said Charles Drake, M.D., Ph.D., an associate professor of oncology, immunology and urology, and medical oncologist at the Johns Hopkins Kimmel Cancer Center.

The researchers speculate that when radiation destroys tumor cells, the dead tumor cells may release proteins that help train immune cells to recognize and attack the cancer, said Michael Lim, M.D., an associate professor of neurosurgery, oncology at the Johns Hopkins University School of Medicine and member of Johns Hopkins’ Institute of NanoBiotechnology.

“Traditionally, radiation is used as a definitive therapy to directly kill cancer cells,” said Lim, who also serves as director of the Brain Tumor Immunotherapy Program and director of the Metastatic Brain Tumor Center at Johns Hopkins Medicine. “But in this situation we’re using radiation as kind of kindling, to try to induce an immune response.”

Lim says if further studies affirm the value of the triple therapy in animals and humans, the radiation could be delivered a few days before or after the immunotherapies and still achieve the same results. Lim said this leeway “could make applications of this therapy in patients possible.”

The researchers say they were also encouraged to see that the triple therapy created “immune memory” in mice that were long-term survivors. When brain tumor cells were re-introduced under the skin of the animals, their immune systems appeared to protect them against the development of a new brain tumor.

Drake said since the immune system usually doesn’t generate a memory when foreign (tumor) cells are still present in the body. “But the idea that this combination treatment was successful at generating immunological memory really suggests that we could do this in patients and generate some long-term responses.”

The researchers are developing a variety of clinical trials to test combination therapies against brain tumors.

Other researchers on the study include Zineb Belcaid, Jillian A. Phallen, Alfred P. See, Dimitrios Mathios, Chelsea Gottschalk, Sarah Nicholas, Meghan Kellett, Jacob Ruzevick, Christopher Jackson, Xiaobu Ye, Betty Tyler, and Henry Brem of the Department of Neurosurgery at Johns Hopkins University School of Medicine; Jing Zeng, Phuoc T. Tran, and John W. Wong of the Department of Radiation Oncology and Molecular Radiation Sciences at the Johns Hopkins Kimmel Cancer Center;  and Emilia Albesiano, Nicholas M. Durham, and Drew M. Pardoll at the Kimmel Center’s Department of Oncology and Medicine, Division of Immunology.

Funding for the study was provided by the WW Smith Charitable Foundation and individual patient donations.

Michael Lim is a consultant for Accuray and receives research funding from Accuray, Bristol-Meyers Squibb, Celldex and Aegenus. Charles Drake has served as a consultant for Amplimmune, Bristol-Meyers Squibb, Compugen, Dendreon, ImmunExcite and Roche/Genentech and is on the Scientific Advisory Board of Compugen. He receives research funding from Bristol-Meyers Squibb, Aduro and Janssen and has stock ownership in Compugen. Drew Pardoll is a consultant/advisor for Jounce Therapeutics, Bristol-Meyers Squibb, ImmuneXcite and Aduro and receives research funding from Bristol-Meyers Squibb. Jing Zeng, Michael Lim, Charles Drake and Drew Pardoll hold a patent for the work related to this study.

The authors declare that they have a patent relating to material pertinent to this article; this international patent application (PCT/US2012/043124) is entitled “Use of Adjuvant Focused Radiation Including Stereotactic Radiosurgery for Augmenting Immune Based Therapies Against Neoplasms.” These relationships are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

From bacterial intelligence to a cyber-war on cancer

Screen Shot 2014-03-18 at 11.40.42 AMINBT will host a special seminar, “From bacterial intelligence to a cyber-war on cancer,” on April 17 at 2 p.m. in Room 160 of the Mattin Center. The guest speaker is Eshel Ben-Jacob, PhD, professor and Maguy-Glass Chair in Physics of Complex Systems from Tel Aviv University. This event is free and open to the university community.

ABSTRACT: Cancer continues to elude us. Metastasis, relapse and drug resistance are all still poorly understood and clinically insuperable. Evidently, the prevailing paradigms need to be re-examined and out-of-the-box ideas ought to be explored. Drawing upon recent discoveries demonstrating the parallels between collective behaviors of bacteria and cancer, Dr. Ben-Jacob shall present a new picture of cancer as a society of smart communicating cells motivated by the realization of bacterial social intelligence. There is growing evidence that cancer cells, much like bacteria, rely on advanced communication, social networking and cooperation to grow, spread within the body, colonize new organs, relapse and develop drug resistance. Dr. Ben-Jacob shall address the role of communication, cooperation and decision-making in bacterial collective navigation, swarming logistics and colony development. This will lead to a new picture of cancer as a networked society of smart cells and to new understanding of the interplay between cancer and the immune system. Dr. Ben-Jacob shall reason that the new understanding calls for “a cyber-war” on cancer – the developments of drugs to target cancer communication and control.

Related Links:

Bacterial linguistic communication and social intelligence

Bacterial survival strategies suggest rethinking cancer cooperativity

 

 

Cancer spreads through ‘Rock’ and ‘Rho’

n low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red). Credit: Daniele Gilkes

In low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red).
Credit: Daniele Gilkes

ROCK1 and RhoA genes found partly to blame for cancer metastasis. Gregg Semenza, co-director of the Johns Hopkins Physical Sciences-Oncology Center (PS-OC), led a team that made the discovery. The following comes from a Johns Hopkins press release:

Biologists at The Johns Hopkins University have discovered that low oxygen conditions, which often persist inside tumors, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationary to mobile and invasive. Their evidence, published online in Proceedings of the National Academy of Sciences on Dec. 9, underlines the importance of hypoxia-inducible factors in promoting breast cancer metastasis.

“High levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and senior author of the article. “We now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.”

To move, cancer cells must make many changes to their internal structures, Semenza says. Thin, parallel filaments form throughout the cells, allowing them to contract and cellular “hands” arise, allowing cells to “grab” external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.

Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers. In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.

What the study showed is that low oxygen conditions, which are frequently present in breast cancers, serve as the trigger to increase the production of RhoA and ROCK1 through the action of hypoxia-inducible factors.

“As tumor cells multiply, the interior of the tumor begins to run out of oxygen because it isn’t being fed by blood vessels,” explains Semenza. “The lack of oxygen activates the hypoxia-inducible factors, which are master control proteins that switch on many genes that help cells adapt to the scarcity of oxygen.” He explains that, while these responses are essential for life, hypoxia-inducible factors also turn on genes that help cancer cells escape from the oxygen-starved tumor by invading blood vessels, through which they spread to other parts of the body.

Daniele Gilkes, Ph.D., a postdoctoral fellow at the PS-OC and lead author of the report, analyzed human metastatic breast cancer cells grown in low oxygen conditions in the laboratory. She found that the cells were much more mobile in the presence of low levels of oxygen than at physiologically normal levels. They had three times as many filaments and many more “hands” per cell. When the hypoxia-inducible factor protein levels were knocked down, though, the tumor cells hardly moved at all. The numbers of filaments and “hands” in the cells and their ability to contract were also decreased.

When Gilkes measured the levels of the RhoA and ROCK1 proteins, she saw a big increase in the levels of both proteins in cells grown in low oxygen. When the breast cancer cells were modified to knock down the amount of hypoxia-inducible factors, however, the levels of RhoA and ROCK1 were decreased, indicating a direct relationship between the two sets of proteins. Further experiments confirmed that hypoxia-inducible factors actually bind to the RhoA and ROCK1 genes to turn them on.

The team then took advantage of a database that allowed them to ask whether having RhoA and ROCK1 genes turned on in breast cancer cells affected patient survival. They found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.

“We have successfully decreased the mobility of breast cancer cells in the lab by using genetic tricks to knock the hypoxia-inducible factors down,” says Gilkes. “Now that we understand the mechanism at play, we hope that clinical trials will be performed to test whether drugs that inhibit hypoxia-inducible factors will have the double effect of blocking production of RhoA and ROCK1 and preventing metastases in women with breast cancer.”

Other authors of the report include Lisha Xiang, Sun Joo Lee, Pallavi Chaturvedi, Maimon Hubbi and Denis Wirtz of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Cancer Institute (U54-CA143868), the Johns Hopkins Institute for Cell Engineering, the American Cancer Society and the Susan G. Komen Breast Cancer Foundation.

Picture this: Transcription ‘twists’ toward metastasis

Mol Cancer Res Cover (1)

Molecular Cancer Research Cover

Researchers associated with Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins School of Medicine and School of Public Health have published “The Twist Box Domain Is Required for Twist1-induced Prostate Cancer Metastasis,” in a recent issue of the journal Molecular Cancer Research. An illustration related to the work graced the cover.

Authors on the paper include co-lead authors Rajendra P. Gajula and Sivarajan T. Chettiar,  as well as Russell D. Williams, Saravanan Thiyagarajan, Yoshinori Kato, Khaled Aziz, Ruoqi Wang, Nishant Gandhi, Aaron T. Wild, Farhad Vesuna, Jinfang Ma, Tarek Salih, Jessica Cades, Elana Fertig, Shyam Biswal, Timothy F. Burns, Christine H. Chung, Charles M. Rudin, Joseph M. Herman, Russell K. Hales, Venu Raman, Steven S. An and corresponding author Phuoc T. Tran

Here is an abstract of their paper and caption for the cover:

“Twist1 plays key roles during development and is a master transcriptional regulator of the epithelial-mesenchymal transition that promotes cancer metastasis. We demonstrated three important findings in prostate cancer cells that overexpress Twist1: (1) Twist1 leads to elevated cytoskeletal stiffness and traction forces at the migratory edge of cell collections; (2) The Twist box domain is required for Twist1-induced pro-metastatic in vitro properties and in vivo metastases; and (3) Hoxa9 is a novel Twist1 transcriptional target that is required for Twist1-induced pro-metastatic phenotypes. Targeting the Twist box domain and Hoxa9 may effectively limit prostate cancer metastatic potential.”

Visit the journal here: Molecular Cancer Research