In this exciting Editor’s Picks collection, our Science Editor, Dr. Jaydev Upponi, offers a glimpse into the world of nanoparticles—the novel delivery system of anti-cancer therapeutics.
Jaydev Upponi, PhD.
Dr. Upponi: Currently, there is a new variety of chemotherapeutic agents available to treat cancer. These chemotherapeutic agents pose potential disadvantages, such as toxicity to normal cells and premature drug degradation owing to their poor solubility.
To overcome these limitations, scientists must solubilize and increase the amount of an anti-cancer drug at the area of concern and reduce the toxicity to normal cells. This is achieved by embedding drugs into what are called nanoparticles.
Prepared using various polymers, a variety of these novel drug delivery systems are currently being used (to name a few, there are synthetic polymers, microcapsules, cell ghosts, lipoproteins, liposome and micelles). Read more…
Let’s face it, Google rules the world. With over 300 million people worldwide using Google daily, not to mention all of the other Google products like Android (the smartphone operating system), Google Scholar, Google docs, and Gmail to name a few, the search engine company provides some of the most powerful tools available to the public to increase productivity and deliver the information we all consume. However, Google isn’t generally associated with the data analysis sector of scientific research, particularly when offering a prognosis for a cancer patient.
That is, until recently. Using an algorithm called NetRank – based on Google’s PageRank algorithm – scientists at the Dresden University of Technology ranked nearly 20,000 proteins by their relevance in pancreatic cancer. The labs of Dr. Michael Schroeder, Dr. Christian Pilarsky, and Prof. Robert Grützman published their work in PLos Computational Biology on May 17.
For cancer diagnosis, scientists frequently use biomarkers such as cancer cell metabolites or intracellular proteins to determine what type of cancer a patient has, with nearly 100% accuracy (as claimed in the work cited above). These biomarkers can also be used to help predict a patient’s prognosis, though with lower accuracy (50-70% accuracy, depending on the type of cancer). Using NetRank, these scientists aimed to correlate biomarkers detected in cancer patients with their cancer stage and prognosis. NetRank improved upon current prediction methods, such as the Pearson correlation statistical method, by up to 7%. The authors claim that as the sample size increases, this percentage will increase, just like Google improves their search results as more search data is collected.
These tools are invaluable because they are automatable, unbiased and scalable, as more genetic data is found. The authors claim that using biomarkers to determine the clinical outcome of a patient are superior to established clinical techniques like grade, tumor size and nodal status. Ultimately, NetRank is a fascinating, outside-of-the-box approach to a practical problem.
Approximately 71,500 women in the United States are diagnosed with gynecological cancer every year, according to the Centers for Disease Control. Researchers from University Hospitals Case Medical Center have developed a more effective way to treat gynecological cancers, shortening radiation treatment time from five weeks to three days.
The new method, stereotactic body radiotherapy (SBRT) has been used on other types of cancer, but Case Medical Center is the first treatment facility to apply it to gynecological cancers. Dr. Charles Kunos, who co-authored the article, said the radiation therapy machine “looks like a robot you would make cars with, and targets specific cancer cells.”
Unlike traditional radiation therapy, SBRT uses focused radiation beams and targets well-defined tumors. In order to focus in on the region, the tumors need to be imaged and marked (using fiduciary markers) in advance. During treatment with the Cyberknife system (from Accuray), patients need to be immobilized, and even the patient’s breathing needs to be taken into account.
The highly specific nature of the procedure not only shortens treatment time, it limits the effect of the radiation on healthy tissues.
“SBRT holds great promise for treating persistent or recurrent gynecological cancers,” said JoVE Science Editor, Dr. Nandita Singh. “SBRT can deliver radiation with high precision and is particularly effective in delivering reduced radiation to cancer targets that are refractory to chemotherapy and conventional radiation.”
Dr. Kunos said he is very pleased with his article, and felt that it was critical to high-quality video of the protocol for people to see when he and his team launch a nationwide clinical trial. To learn more about how a video in JoVE Medicine can help you, please click here.
This post was co-authored by JoVE Editorial Director, Dr. Beth Hovey.
The JoVE team is back in Cambridge, MA after a successful trip to the annual AACR meeting in Chicago last week. We set up camp in the exhibitor’s hall at booth 4821, and a steady stream of you came by to visit. It was great to meet you all!
We also attended a wide range of posters, symposia and other special sessions, and got to hear about novel research on the cancer field.
Closely associated with the meeting was the Stand Up To Cancer (SUTC) campaign, for which AACR is the sole scientific partner. SUTC funds “Dream Teams”—collaborative, multi-disciplinary teams of scientists whose aim is to ultimately translate cutting edge scientific discoveries into advances in cancer prevention and treatment.
At this year’s AACR meeting, Dr. Bert Vogelstein, SUTC’s Genomics Advisory Committee Leader, announced the publication of his work on the use of whole genome screens for the prediction of disease. While he noted that whole genome sequencing is important and informational following diagnosis of disease, he suggested that clinicians do not use this technology as a risk assessment tool.
JoVE author, Dr. Charles Sawyers and his colleague Dr. Arul Chinnaiyan were named as the leaders of the latest SUTC’s list of Dream Teams. The Prostate Cancer Dream team will first focus on finding a cure for advanced (metastatic) prostate cancer.
If you aren’t familiar with Nobel Prize winner, Dr. Elizabeth Blackburn‘s work with telomeres and telomerase, I suggest looking her up. To give some background information, telomeres are a repetitive sequence of DNA at the end of chromosomes that depletes naturally over time. They have been likened to the protective plastic at the end of a shoelace.
The telemores are at the ends of the chromosomes, shown here in red.
Dr. Blackburn gave a fascinating talk on Sunday at the AACR annual meeting about the relationship of telomere maintenance in aging and cancer. She has shown that low levels of the enzyme telomerase results in shorter telomeres which in turn correlates with diseases such as pulmonary fibrosis, cardiovascular disease, impaired immune function, cancer, and even obesity.
Telomere length and telomerase levels are intricately entwined with major age-related diseases and “healthspan,” the length of time one lives without disease. Dr. Blackburn’s work promises to hold insight into our constant battle against cancer and aging.
This post was co-written by JoVE Science Editor, Dr. Claire Standen.
The JoVE booth is packed up and on its way to Chicago for the annual meeting of the American Association for Cancer Research (AACR). On March 31st the JoVE team will be joining the conference, along with over 18,000 other registered attendees. We are looking forward to an exciting program full of the most current cancer-related research!
We are particularly eager to learn more about some of the advancements in cancer diagnostics, immunotherapy and cancer model systems. It looks like there are some remarkable talks and posters this year across the spectrum of basic, translational and clinical cancer research.
Immunofluorescent image of interstitial cells of Cajal (ICC) from Dr. Sawyer's JoVE publication.
So, if you are attending the AACR conference, come and visit the JoVE booth (#4821) in the Exhibit Hall. You can sign up for a one-month personal subscription to all sections of JoVE and the chance to win an iPad. Also, if you have tips for things to do in the Windy City, we’d love to hear from you. See you there!
If you can’t make it this year, watch this space for updates on some of the JoVE editor’s favorite research at the meeting.
From a health care perspective, the best cigarette is no cigarette, but for the millions of people who try to quit every year, researchers from Cornell University may have found a way to make smoking less toxic.
Using natural antioxidant extracts in cigarette filters, the scientists were able to demonstrated that lycopene and grape seed extract drastically reduced the amount of cancer-causing free radicals passing through the filter. The research will be the 1500th article published in JoVE.
“The implications of this technique can help reduce the hazardous effects of tobacco smoke,” said Dr. Boris Dzikovski, who co-authored the paper, “because free radicals are a major group of carcinogens.”
Scientists have tried to make safer cigarettes in the past. Haemoglobin (which transports oxygen in red blood cells) and activated carbon have been shown to reduce free radicals in cancer smoke by up to 90 percent, but because of the cost, the combination has not been successfully introduced to the market.
JoVE Content Director, Dr. Aaron Kolski-Andreaco, is very excited to be publishing this article as the journal’s landmark 1500th article.
“Practically, this research could lead to an alternative type of cigarette filter with a free radical scavenging additive,” said Kolski-Andreaco. “It could lead to a less harmful cigarette.”
Visualizing the structure and function of living organisms has always been an important part of cell biology, and the ASCB video contest “Celldance” is giving researchers a chance to show their cell’s best moments.
The seven winning videos, which were announced on December 3, show everything from chromosome alignment to mechanosensing. The first-place prize went to Tsutomu Tomita of Timelapse Vision for “Cancer Dance: The Plasma Membrane in Normal and Transformed Cells.” The video was unveiled at the ASCB Annual Meeting yesterday afternoon. Click here to see it.
Though the winning entry came from a company, most come from academic labs, like Bin He’s “Animation of Chromosome Alignment and the Spindle Assembly Checkpoint,” which won in the Public Outreach category. What do PI‘s think of their student submitting videos?
“People in the lab started joking that I was his producer,” said Dr. Daniela Cimini, who accepted the award on behalf of He, “because I was paying his salary while he was making this video instead of doing experiments.”
Since she showed up to give the acceptance speech, she probably doesn’t mind adding “Award-winning video producer” to her list of accomplishments.
The small molecule ligand (red) binds to a unique site on the Ras oncoprotein (brown) and blocks the Ras activation by SOS1 (cyan). (c) Genentech
Dr. Guowei Fang and his colleagues at Genentech have discovered a potential new target for drug cancer therapies. He presented his research yesterday at the ASCB Annual Meeting in Denver, Colorado.
The target is a small molecule-binding pocket on Ras, the most commonly mutated oncogene in humans. The oncogene (a gene that can mutate to cause cancer) is found in approximately a quarter of all tumors, and is a marker for a poor prognosis.
“It had been considered to be undruggable,” said Dr. Fang, “because it’s a protein and it’s intracellular.”
Using nuclear magnetic resonance spectroscopy, Dr. Fang and his drug-discovery team sorted through 3,300 small molecule compounds and found 25 compounds that bind to Ras oncoproteins. All of the proteins bound to Ras in the same location, making it a promising target.
So far, because all of the compounds have such a low affinity for the protein, all of the research has been done in vitro. The next logical step in the effort to create a medicinal compound is to increase the affinity of the binding compounds.
Dr. Fang’s manuscript is currently under review, and the team hope to have it published soon.