Research
To fight cancer, nanoparticles need a better disguise
In the search for better ways to deliver powerful chemotherapy drugs only to tumors, leaving healthy tissue unscathed, nanoparticles are emerging as a promising tool. These tiny particles can be loaded with powerful chemotherapy drugs that, ideally, can be delivered directly to the cancer site. But the delivery only can be completed if the packages avoid detection by healthy cells.
To deliver nanoparticles carrying chemotherapy drugs directly to the tumor, City of Hope researchers are suggesting a better disguise. Shown in this illustration from the cover of the Journal of Materials Chemistry B, gold nanoparticles are cloaked in a protective coating that allows them to bypass healthy cells. But, when the particles encounter tumor cells, a tumor enzyme is drawn to the peptide in the coating. The enzyme chops through the cloak, allowing the drug-carrying particles to be ingested by the cell.
City of Hope scientists may have found a way to ensure their packages arrive safely. They recently published a paper in the Journal of Materials Chemistry B outlining a new strategy for disguising these drug-carrying nanoparticles so that they will drop their therapeutic drugs directly at the tumors – escaping notice from cells that want to filter them to the liver.
In their study, researchers applied a coating to gold nanoparticles to shield them from being gobbled up – a tactic that’s been used before but that still results in most of the particles collecting in the liver instead of at the tumor sites. However, this time researchers used a more cunning disguise: They masked the particles in a coating marked with a specific molecule that triggered the tumor itself to attack the nanoparticles, break through their shield and ingest them.
Continue reading “To fight cancer, nanoparticles need a better disguise” »
Scientists identify gene that may suppress cancer development
Although researchers have long known that chronic inflammation is tied to a higher cancer risk, the exact mechanism connecting them remains a mystery. But City of Hope scientists have identified a gene, called Rrm2b, that may fill in a piece of that puzzle.
City of Hope scientists found that the RRM2b protein – whose structure is modeled above – helps repair DNA and prevent cancerous changes.
The findings were published in a Cell Reports article earlier this month. In the study, the authors found that RRM2b (the enzyme manufactured by the Rrm2b gene) is responsible for DNA damage repair, and that animal subjects with deficient Rrm2b genes are more prone to developing blood cancers.
The researchers also found that Rrm2b gene loss leads to chromosomal abnormalities and triggers the secretion of pro-inflammatory molecules, both contributing to cancerous changes in cells.
“Our previous clinical data suggested that RRM2b protein levels are inversely associated with cancer progression,” said Lufen Chang, Ph.D., assistant research scientist in the Department of Molecular Pharmacology and lead author of this study. “Based on this study’s findings, we concluded that Rrm2b deficiency may be a potential risk factor for hematologic malignancies.” Continue reading “Scientists identify gene that may suppress cancer development” »
Researchers await Supreme Court decision on gene patents
The genetic test for BRCA mutations can be a lifesaver for women at high risk for breast cancer; for Angelina Jolie, who wrote about her experience in a New York Times op-ed this week, the test and subsequent preventive measures shrank her lifetime risk of breast cancer from 87 percent to 5 percent.
In the coming weeks, the Supreme Court will decide whether genes can be patented – impacting future research and development of diagnostic tests, including those for cancer risks.
But not everyone can readily afford that screening.
The test, offered solely by Myriad Genetics in the United States, costs approximately $3,000. Further, health insurance may not cover the expense without justification, such as having a close relative diagnosed with breast or ovarian cancers.
Meanwhile, 23andMe can test for more than 200 genetically linked conditions for $99.
One reason the BRCA test is so expensive is that Myriad discovered the cancer risks associated with the BRCA genes and patented them, giving the company a 20-year monopoly on their use.
The patenting of this discovery is not without controversy, and a years-long lawsuit against Myriad will culminate in a Supreme Court decision later this year. Continue reading “Researchers await Supreme Court decision on gene patents” »
Tiny gold rods could be used to attack hard-to-reach cancers
Gold has been used for jewelry, to fill teeth and to garnish desserts. Now, the precious metal may also prove to be an important tool for fighting cancer.
Gold nanoparticles, exponentially smaller than these more traditional nuggets, could be embedded in neural stem cells and used in targeted cancer therapies, suggests research conducted at City of Hope.
Already, doctors have many ways to kill cancer cells. The trick is not damaging the rest of the body in the process, says Jacob Berlin, Ph.D., an assistant professor in the Department of Molecular Medicine at City of Hope.
Thermal ablation – zapping tumors with intense heat – is one strategy that has shown considerable promise. But like other physical strategies, it requires probes or other means to access the cancer site. And in some cases, the tumor cannot be reached or may have spread, creating stray malignant cells. In other cases, there may be many tumors.
Now, working with researchers in the laboratory of Karen Aboody, M.D., an associate professor in the Department of Neurosciences and the Division of Neurosurgery, Berlin and his colleagues believe they’ve found a method of delivering blasts of thermal ablation directly to tumor sites, using tiny gold rods embedded in neural stem cells.
Continue reading “Tiny gold rods could be used to attack hard-to-reach cancers” »
Angelina Jolie’s choice highlights individuality of cancer risk
Faced with the knowledge that she carries a gene mutation that drastically increases her risk of breast and ovarian cancer, Angelina Jolie chose to have her breasts removed. She shared her story earlier this week in a frank New York Times op-ed that underscores the difficult choice faced by women who have the mutation.
Mutations in specific genes give some women a dramatically higher risk of breast cancer. Once they know this, they face tough, personal decisions.
In revealing her story, Jolie called attention to the fact that women with BRCA1 or BRCA2 gene mutations are roughly five times more likely to develop breast cancer than women without such a mutation.
Most women with cancer do not carry one of the gene mutations, and the mutations account for only a small percentage of cancers. About 5 to 10 percent of all breast cancers are associated with a BRCA mutation, and only women with a specific family history need to consider testing for BRCA mutations, experts say.
But Jolie’s disclosure is a good opportunity for women to consider their own cancer risk, said Joanne Mortimer, M.D., director of City of Hope’s Women’s Cancers Program.
“One of the wonderful things about health care reform is women are not being treated as one homogeneous population,” Mortimer said. “Instead, it’s based on assessing each woman for her risk … Knowing your risk is what’s important.”
Continue reading “Angelina Jolie’s choice highlights individuality of cancer risk” »
Melanoma isn’t only skin cancer that carries the risk of death
Melanoma is the skin cancer that’s most associated with being lethal, but a study in JAMA Dermatology suggests a much more common skin cancer also carries a risk of metastasis and death.
A new JAMA study finds that the second most-common form of skin cancer - cutaneous squamous cell carcinoma – carries a small risk of metastasis and death.
The 10-year retrospective study, led by researchers at Brigham and Women’s Hospital, examined outcomes for cutaneous squamous cell carcinoma, or CSCC, diagnosed between Jan. 1, 2001, and Dec. 31, 2009 – the largest study of CSCC outcomes since 1968.
Squamous cell carcinomas are the second most-common skin cancer, according to the Skin Cancer Foundation. Although most cases of this type of cancer are easily cured with surgery or ablation, the study found that the cancer carries a low but significant risk of metastasis and death.
Continue reading “Melanoma isn’t only skin cancer that carries the risk of death” »
Nanomagnets could combat drug-resistant bacteria, researcher says
Drug-resistant bacteria have made headline after headline, created problem after problem. And yet, they’re still with us. One City of Hope researcher has a provocative aim, however: To remove multidrug resistant bacteria from our blood using nanomagnets as “nanobiotics.”
Anil Suresh, Ph.D., is a staff scientist in the City of Hope lab of Jacob Berlin, Ph.D. An expert on nanoparticles and their use in biomedical applications, Suresh has been especially focused on using nanoparticles to improve drug delivery.
Drug-resistant bacteria create the potential for significant health risks, but one researcher has a theory on how to remove them from the bloodstream. Researcher Anil Suresh plans to test his approach on E. coli, shown here.
One planned project, however, takes a different tack. Noting that current research often focuses on developing nanoparticles as drug delivery agents that target certain cells, Berlin and Suresh began to wonder if nanoparticles could be targeted to disease-causing organisms and then used to remove the harmful organisms from the bloodstream, specifically through magnetic force.
After all, recent research has shown that magnetic shifts can be used to concentrate iron oxide nanoparticles at cancer metastases. And other studies have shown they have the potential to remove heavy metals, steroids, proteins and even cancer cells from the blood.
So, building on his experience at City of Hope, Suresh proposes attaching extremely tiny magnets, referred to in research terms as “super paramagnetic iron oxide nanomagnets,” to the surface of E. coli bacteria using antibodies. He then intends to use a strong permanent magnet — outside the body — to remove the magnetically tied E. coli from the bloodstream completely.
Suresh said his project, still in the planning stages, would not introduce foreign materials into the bloodstream and would thereby avoid side effects. After testing his hypothesis on E. coli, he plans to then move to tests on malaria-causing Plasmodium, typhoid-causing Salmonella and black-fever-causing Lieshmania bacteria.
City of Hope researcher Anil Suresh theorizes that dangerous bacteria could be removed from the bloodstream using nanomagnets.
He wrote in a recent proposal: “This novel proposal will model, optimize and achieve novel targeting strategy using permanent magnets to control and remove multidrug resistant microorganisms labeled with nanomagnets and will improve the current therapeutics drastically, in particular it will enable new and immediate treatment for several dreadful multidrug resistant microbes.”
The plan is not only provocative, but also promising. So promising in fact that India’s Department of Biotechnology, part of the Ministry of Science and Technology, has awarded him the prestigious Ramalingaswami Re-entry Fellowship for 2012-2013. The fellowship is awarded to just 50 Indian citizens who are working overseas in various fields of biotechnology and life sciences and would like to take up a scientific research position in India.
Winners are able to work in any of the scientific institutions or universities in the country and are eligible for research grants for five years, with an appraisal for another five years based on the progress.
Suresh said bacteria-causing diseases are still a major threat; the emergence of multidrug resistance is a significant health concern and a challenging task.
“I strongly believe that my project will do some justice to the current therapeutics,” he said. ”If everything works as planned, we might not have to worry about drug resistance, side effects caused by the drugs, etc. The proposed nanoparticles-based ‘nanobiotics’ strategy would be the simplest and safest approach ever implemented for the treatment of blood-borne bacteria.”
Berlin called the award “well-deserved,” saying how he’s looking forward to seeing Suresh “bring the promising idea of ‘nanobiotics’ to life.”
“It is a joy to see Anil win such a prestigious award,” he said. ”Anil has made significant contributions to our work here at City of Hope developing new nanoparticles to target the delivery of cancer drugs. He is an incredibly creative and passionate scientist. India is lucky to have him returning home to tackle such a devastating problem.”
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Survivors, stem cell transplants – and a reason to celebrate
Neural stem cells could become delivery tool for cancer drugs
Prostate cancer cells in blood might suggest risk of recurrence
Survivors, stem cell transplants – and a reason to celebrate
The description is simple: Blood and marrow stem cell transplants replace a person’s faulty stem cells with healthy ones.
The reality is complex: High doses of chemotherapy and radiation must be used to destroy the disease and “make room” for the new, nondiseased stem cells. The immune system is then essentially kick-started to start producing healthy cells on its own.
Survivors and family at the City of Hope “Celebration of Life” Bone Marrow Transplant Reunion
City of Hope’s numbers belie both: Physicians here have performed more than 11,000 blood and marrow stem cell transplants. Based on a 2012 report from the Center for International Blood and Marrow Transplant Research, City of Hope is the only transplant program in the country to achieve eight consecutive reporting years of “over performance” in one-year overall patient survival.
Perhaps only those who have been there – and back – can truly understand the significance of this achievement; what’s it’s like to have gotten another chance at life, to have survived not just a life-threatening cancer but the ordeal of the transplant itself. So, once a year, they get a chance to celebrate with the only others who come close to understanding – their transplant doctors, nurses and caregivers. Continue reading “Survivors, stem cell transplants – and a reason to celebrate” »
Stem cell transplant experts gather to honor pioneer Karl Blume
Five world-class specialists in stem cell transplantation. One place.
On Thursday, hematology experts from around the country convened at City of Hope to discuss the impact of Karl G. Blume, M.D., the founder of City of Hope’s bone marrow transplant program.
Blume launched the program in 1975, when such procedures were at the forefront of current science, and regarded as novelties in many circles. Today, that program is a world leader in hematopoietic cell transplantation. Continue reading “Stem cell transplant experts gather to honor pioneer Karl Blume” »
Focusing sound on metastatic bone cancer pain, tumor cells
Breast, prostate, colon and other cancers that spread to other parts of the body often take root in bone. These metastatic tumors can be very difficult to eradicate and often create terrible pain for the patient. A new technique helps alleviate that pain — and it might one day eliminate the cancer, too.
Cancer that spreads to bone can cause significant pain. Magnetic resonance guided focused ultrasound, or MRgFUS, can alleviate bone cancer pain. City of Hope researchers hope it also will destroy tumors.
When treating metastatic bone cancer pain, surgery is seldom used. Radiation is the preferred choice, but not all patients can receive it, and others choose not to have it.
So some clinicians are now turning to magnetic resonance-guided focused ultrasound, or MRgFUS (as it is inelegantly abbreviated), specifically to provide care that reduces patients’ cancer-related bone pain.
“MRgFUS is for those select patients who cannot have radiation therapy because they have previously been irradiated or they do not want it,” said Jeffrey Wong, M.D., chair of City of Hope’s Department of Radiation Oncology.
MRgFUS, which first emerged as a noninvasive way to treat uterine fibroids, uses pinpointed high-energy sound waves to heat and destroy pain-causing nerves in the membrane surrounding bone. This lowers or eliminates pain, improving the patient’s quality of life for months, according to the Food and Drug Administration, which approved MRgFUS for metastatic bone cancer in October 2012.
Wong recently treated the first patient in Southern California to receive MRgFUS for metastatic bone cancer outside of a clinical trial.
Now, he and his colleagues are working to turn MRgFUS to an even higher purpose — eradicating cancer cells altogether. Continue reading “Focusing sound on metastatic bone cancer pain, tumor cells” »
