Friday, August 15, 2014
Wednesday, August 13, 2014
Synthetic molecule uses salt to trigger self-destruction of cancer cells
By Nick Lavars
August 13, 2014
A team of international researchers has developed a molecule capable of triggering cancer cell death by carrying chloride into cancer cell membranes. The molecule flushes the cells with salt and causes them to self-destruct, potentially paving the way for new types of anti-cancer drugs.
The international effort involves researchers from the UK, Texas and South Korea who have collaborated to develop a synthetic ion transporter with a chloride payload. Once it reaches the cancer cells, the chloride interacts with the sodium in the cell membranes and leads to its demise.
"This work shows how chloride transporters can work with sodium channels in cell membranes to cause an influx of salt into a cell," says the University of Southampton's Professor Phillip Gale, one of the study's co-authors. "We found we can trigger cell death with salt.”
The survival of cells in the human body is reliant on the regulation of ions inside their membranes. Upsetting the balance causes them to self-destruct through what is known as apoptosis, a mechanism the body uses to dispose of dangerous or damaged cells.
We have seen apoptosis form the basis of a number of cancer researchefforts. The most recent being a cloaked DNA nanodevice that evades the body's immune system to hone in on leukemia and lymphoma cells to activate the suicide switch. The chloride-carrying molecule is the first to demonstrate the effects of salt on cancer cells, however, with the researchers also claiming it could bring benefits to sufferers of cystic fibrosis.
The molecule works by binding to the chloride ions in the cell's membranes. It then draws on the membrane's sodium channels, creating a blanket surrounding the ion and causing it to dissolve. The researchers first found this to be effective in a model with an artificial membrane, a team from South Korea's Yonsei University then tested its efficacy in cultured human cancer cells. An important finding was that the cell's ion balance was disrupted prior to the death of the cell, rather than resulting from the apoptotic process, indicating it was indeed the chloride payload causing its death.
"We have thus closed the loop and shown that this mechanism of chloride influx into the cell by a synthetic transporter does indeed trigger apoptosis," said Professor Jonathan Sessler from the University of Texas and one of the study's co-authors. "This is exciting because it points the way towards a new approach to anticancer drug development."
One complication the researchers will have to overcome for its molecule to be used in cancer treatments is limiting it to cancerous cells. As it stands, the molecule triggers the death of both cancerous and healthy cells so the team will need to modify the synthetic transporter to bind only to the more cancerous ones.
The team's research was published in the journal Nature Chemistry.
Source: University of Southampton
Love What You See — These Women Reveal What They Feel When They Look In The Mirror
When Gary Hinze began coughing up blood after working out, his doctor sent him to an oncologist near his home in Grass Valley, California. The diagnosis: Stage IIIA lung cancer. "He pretty much told me I was a goner," says Hinze, then 62. A recommendation from another local doctor sent Hinze and his wife, Sandie, to the UC-Davis Comprehensive Cancer Center in Sacramento, a couple hours away. "The team at UC-Davis didn't give up," says Hinze. An unusual combination of chemotherapy and radiation shrank the tumor to the point that "the doctors had trouble finding it on an x-ray," and the diseased part of his lung could be removed. Today, the part-time musician and local TV variety show host has been cancer-free for three years. "Those doctors saved my life," he says.
Hinze tapped into the type of state-of-the-art expertise available at the nation's major cancer centers -- and not just to people who live nearby. In particular, the 68 hospitals designated as national cancer centers by the National Cancer Institute (cancer.gov), which are supported by taxpayer dollars, are a rich resource for patients everywhere. Someone diagnosed with a particularly complex or advanced cancer may benefit greatly by traveling for treatment to a team that has had a wealth of experience with that tumor and is on the cutting edge of research. Each facility's website makes it easy to request an appointment. "Most people who come to our hospital are not referred," says Mark Kris, chief of thoracic oncology at Memorial Sloan Kettering Cancer Center in New York. "They come on their own."
[Read: Can You Afford Your Cancer Care? ]
Even if your health insurance won't cross the distance, or if you have access to high-quality cancer care near home, it can be reassuring (if not lifesaving) to at least pick all those brains. Many oncologists have a relationship with one of the major centers, or are willing to form one. "It's realistic to do as much stuff as you are able within your community," says Mark Fesen, a medical oncologist in Salina, Kansas, and author of "Surviving the Cancer System." But he advises patients to look for this willingness to cooperate, so there should be no resentment when you seek a second opinion, and it becomes a simple matter for you and your local physician to pick up the phone for a quick consult about your pathology reports or latest scans, or which drug cocktail is the best to try after the first one stops working. With straightforward cancers, a local second opinion may be all the assurance you need. But given the supersonic pace of discovery, getting the most expert possible input can add peace of mind if not change the course of treatment.
"With something like that you want the best of the best," says Jody Cross, 47, a psychotherapist from Sag Harbor, New York, who successfully completed surgery, chemotherapy and radiation for Stage IIB breast cancer at her local hospital but was not satisfied with advice she got locally about reconstructive surgery. An opinion that it would be okay to get an implant after 33 rounds of radiation on her breast conflicted with her own research indicating that there would be an increased risk of infection and other complications. So she went to Memorial Sloan Kettering for guidance. "They told me not to open that can of worms," she says. Cross's health plan paid for the second opinion; some plans will not. Discuss your options with your insurer early in treatment, advises Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. "And get the information in writing."
[Excerpted from U.S. News' 'Best Hospitals 2015,' the definitive consumer guidebook to U.S. hospitals. Order your copy now.]
Cross's consultation took place face-to-face, but technology is making it possible for patients to tap a leading specialist remotely. When a patient two and a half hours away was diagnosed with a metastatic melanoma not long ago, Gary Doolittle, an oncologist specializing in melanomas at the University of Kansas Medical Center in Kansas City, provided his expert input via interactive video. Doolittle explained the risks and benefits of the best option, interleukin2, an especially toxic chemotherapy that had to be administered in an intensive care unit with qualified nursing on hand. The University of Kansas Cancer Center was the only hospital in the region with the ability to administer it.
"The patient did have to come to Kansas City for two treatments," Doolittle says, "but the initial consultation and a checkup between the two treatments were done by video." His treatments completed, the patient can now be monitored by his local physician.
Long-distance consultations may glean insights from a whole team of experts. "Tumor boards" that include surgeons, oncologists, radiologists and pathologists meet regularly to discuss particular cases, often linking in doctors elsewhere. At the UNC Lineberger Comprehensive Cancer Care Center in Chapel Hill, North Carolina, for example, the melanoma tumor board meets every Thursday morning. An oncologist in a different part of the state or country could see a patient with melanoma on Monday, get all the records to UNC Lineberger by Thursday, and log on to participate in what Thomas Shea, associate director for outreach programs at Lineberger, calls a "freewheeling" discussion. "The patient gets the benefit of five or six opinions instead of just one, all without leaving home," he says.
[Read: The Doctor Will Skype You Now .]
As cancer increasingly is understood as a disease driven by gene mutations, and drugs are developed to address them, these opinions will more often focus on an individual's genetic information rather than the location of the cancer. So-called targeted therapies work like precision bombs, foiling the cancer-friendly behavior of aberrant genes while preserving healthy tissue. Herceptin, for example, treats an overproduction of the protein HER2 in breast cancer. Gleevec, which inhibits an enzyme in a certain form of leukemia and has raised the seven-year survival rate to nearly 90 percent from less than 50 percent a decade ago, has also been found to work against the same mutation in gastrointestinal cancer. Some lung cancer patients benefit from crizotinib, a drug that blocks a tumor-promoting protein created by a mutated form of the anaplastic lymphoma kinase gene. By inhibiting a protein made by a particular form of the BRAF gene, vemurafenib attacks melanoma tumors.
The research into such personalized medicine includes targeted immunotherapy, too -- that is, teaching a patient's own immune system to fight the cancer. "I wanted to find a hospital that deals with glioblastomas, that is doing research and has other options to offer," says Ryan DeGrand of St. Louis, Missouri, who chose to have surgery locally 10 years ago when he was diagnosed with one of the deadliest forms of brain cancer but then looked at his broader options. That search led to a vaccine treatment at Duke Cancer Institute in Durham, North Carolina. "My local hospital was honest," he says. "They said, 'You may live 18 months. You may live two years. We just don't know.'" DeGrand was 32 at the time with two young children, and that prognosis wasn't acceptable.
The Duke team started him off with standard chemotherapy and radiation, which could be administered in St. Louis. Then DeGrand entered a clinical trial at Duke. His cancer was found to express a protein that encourages cancer cells to grow. For the past 10 years, DeGrand has been going to Duke once a month for a shot of Rindopepimut, a vaccine that stimulates his immune system to produce antibodies that fight the protein. He has been cancer-free since beginning the treatment.
Other immunotherapies show promise in the fight against melanoma and leukemia. In 2011, the FDA approved ipilimumab, a drug that blocks the action of a molecule that keeps immune cells, called T-cells, from attacking melanoma cells. At Memorial Sloan Kettering, T-cells from patients with B-acute lymphoblastic leukemia were genetically modified in the lab so they would attack cancer cells containing a certain protein. Eighty-eight percent of the leukemia patients who were infused with their own "re-educated" immune cells achieved complete remission.
Almost 100 drugs have so far been approved to target specific genes or proteins. Taking advantage of these targeted therapies depends on knowing the genetic makeup of the tumor, and for that reason, some top cancer hospitals now consider genetic testing a standard of care. Memorial Sloan Kettering, Massachusetts General Hospital in Boston, MD Anderson in Houston and Vanderbilt-Ingram in Nashville, Tennessee, now regularly screen patients for certain mutations. Sloan Kettering recently announced an expanded genetic screening program that is expected to be looking for mutations in over 340 genes by next year.
Do You Need to Ask for Genetic Testing After a Cancer Diagnosis?
Experts say that depends. Some of the more common genetic tests performed today are so-called reflex tests for known diagnostic markers, says Lichtenfeld. These include the HER2 protein for breast cancer; EGFR, a protein, and ALK for lung cancer; the fusion gene BCR-ABL for chronic myeloid leukemia; the KRAS gene for colon cancer and BRAF for melanoma. "If you have one of these cancers, you're going to get that test," he says.
Advanced genetic screening, in which hundreds of genes are tested, may not be currently necessary for common or early-stage tumors, says Richard Haspel, assistant professor of pathology at Beth Israel Deaconess Medical Center in Boston. These tests may be useful if the "tumor is advanced or rare and the oncologist has limited treatment options," Haspel says. The important question for a patient to ask, he says, is "Does my doctor understand what genetic testing is available and when it's appropriate?"
The rush is on to find more biomarkers. The National Institutes of Health's Cancer Genome Atlas project, launched in 2006, aims to identify all the mutations in more than 20 cancers. The Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston have launched an extensive research project into cancer genomics. The Moffitt Cancer Center in Tampa, Florida, is collecting tissue and biological samples from patients in a network of hospitals in 11 states. And Memorial Sloan Kettering's new screening program should be a rich source of information.
[Read: 16 Health Screenings All Women Need .]
All the research efforts may not result in clinical success stories immediately, or even soon. But as Ryan DeGrand discovered, the opportunity to participate in the research through a clinical trial is another potential benefit of connecting with a national cancer center. Kym Sinclair, 30, a nurse from Santa Cruz, California, who was diagnosed with Hodgkin's lymphoma in August 2011, spent six months getting one blood test after another and one chest x-ray after another to determine the cause of her extreme fatigue, chronic cough and weight loss. The ongoing diagnosis -- or misdiagnosis as it turned out -- was a lung infection and the effects of stress from working in a busy emergency department. Finally, after losing 43 pounds, Sinclair went to UC-Davis. At her first appointment after the biopsy, a team from the clinical trials department joined the oncologist, and she was recruited for a trial in which participants were given the standard treatment, but with more frequent PET scans to determine whether the drug was working. Patients who did not respond could be switched to a more aggressive therapy. Sinclair was one of the lucky ones. "My tumor shrank after four infusions of chemo," she says. She continued to go to Davis every other week until all 12 infusions were completed, although sometimes trial participants may be able to get the treatment locally. The cost of an experimental treatment is typically covered by the institution sponsoring the trial, as has been the case for DeGrand and Sinclair.
[Read: 10 Lessons From Empowered Patients .]
The rapid advances in cancer care mean more patients are surviving, which brings its own set of issues. Many of the major centers, including UC-Davis and Vanderbilt-Ingram, provide assistance for any cancer survivor no matter where treated. These support services can connect you with a peer who knows firsthand about the challenges of your particular cancer treatment, for example, or with a professional who can advise you on nutrition and physical therapy. "It's not 'high-five,' and you're out of here," says Sinclair. "You're a cancer patient for life."
"We're at a tipping point," says the American Cancer Society's Lichtenfeld. "We're close to making expert cancer care available to anyone anywhere." Thanks to partnerships and advancing technology, patients can be more sure than ever of getting the very best care possible at home.
Saturday, August 9, 2014
So as I'm stumbling upon another birthday that also marks the anniversary of discovering my own breast cancer, I've decided to embark on a journey over the next year to explore exactly what it is about this new normal that isn't so normal -- one detail at a time. Let's kick off this adventure with those beautiful creatures who center my world - yep, my kids.