Survivor's story highlights cancer event
APPLETON - Steve Maufort received a hero's welcome on Saturday, landing at the 6th annual "Journey of Hope" fundraiser and walk in Appleton in the ThedaStar Air Medical helicopter.
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Vitro Builds Its Product and Technology Base for Cancer Stem Cell Therapy
Vitro Diagnostics, Inc. , dba Vitro Biopharma, announced advances in its adult stem cell products and technology with application to cell-based therapy of cancer.
Cancer stem cells are thought to generate cancerous tumors, and while some of these tumor cells| |
Vitro’s proprietary stem cell technology and products, now subject to pending patent protection, may lead to novel cell therapy for cancer.
The Company is pursuing suitable strategic partners to commercialize these novel therapeutic products. Furthermore, the Company has also commercialized various modified stem cell lines and related products to support cancer stem cell research including the development of new methods to target the selective eradication of cancer stem cells, which is essential to therapeutic efficacy. These products and other tools for use in stem cell research are now commercially available ( www.vitrobiopharma.com/ :
).Dr. Rice, a member of Vitro’s SAB and a University of Colorado cancer researcher said, “Cellular-mediated destruction of cancer stem cells represents a promising new avenue for the development of effective treatments that specifically target cancer stem cells. Vitro has developed an exciting portfolio of products to advance research in this field, which is one of the few approaches to show promise against intractable cancers such as most forms of brain cancer. Additionally, Vitro’s patent pending technology for cancer therapy represents an exciting and novel approach to the selective eradication of cancer stem cells that could usher in new promise in the fight against cancer.”
Why Don't Brain Tumors Respond To Medication?
ScienceDaily (2009-09-02) -- Malignant brain tumors often fail to respond to promising new medication. Researchers in Germany have discovered a mechanism and a tumor marker for the development of this resistance. A "death receptor" can possibly provide information as to how great the chances of success are for chemotherapy. At the same time, it offers a new approach for promising brain tumor therapy.
Glioblastoma, the brain tumor that killed Senator Ted Kennedy, still mostly untreatable, say docs Read more: http://www.nydailynews.com/lifestyle/hea
Tuesday, September 1st 2009, 11:00 AM
Ted Kennedy waged a battle against one of the most lethal of all brain tumors -- and at first, as the Massachusetts senator kept active seeing friends and going on his beloved sailboat, he almost seemed to have the upper hand.
But despite his access to the best medical treatment available, Kennedy lost the fight of his life just 15 months after his diagnosis.
Kennedy and others unlucky enough to learn they have glioblastoma receive a grim prognosis: about a year or a little more is the average life expectancy.
The outlook hasn’t changed all that much in the last 40 years, according to Dr. Eugene S. Flamm, chairman of neurosurgery at Montefiore Medical Center.
“It is a rapidly growing tumor that does not respond to treatment,” he says. “Even if you remove it surgically, the outcome is the same. The transformation of normal brain cells into tumor cells continues even after surgery.”
Despite the gloomy outlook, some doctors are more optimistic.
“It depends how you measure success,” says Dr. Alan Hirschfeld, chairman of neurosurgery at St. Vincent’s Hospital Manhattan. “If you measure it by extending life for two or three months, it’s successful. If you measure it in terms of curing the patient, no, we haven’t succeeded.”
“Survival time has increased very definitely,” says Dr. Michael Gruber, an oncologist at NYU Langone Medical Center. “How well a patient does depends on four indicators. Age is one. If you are over 50, your prognosis is worse than someone who is under 50. It also depends on the grade of tumor, whether it can be taken out, and a patient’s neurological status.”
In 2005, a drug called temozolomide was added to radiation therapy as the treatment for this type of tumor, and the median survival time was 14.6 months, according to the New York Times. Temozoliomide, which is taken orally and has fewer side effect than older drugs that were given intravenously, is now the go-to drug for treating glioblastoma.
Unfortunately, this rapidly growing tumor is virtually impossible to completely remove, says Hirschfeld.
“Although you can see something that looks very well defined on the MRI, the tumor extends well beyond those borders,” he says. “Even if you get 99.9 percent of it, you could still be left with 10 million cells that can grow and cause a recurrence.”
The cost of treating such a brain tumor is high -- from $100,000 to $500,000 is the figure experts at various medical centers tossed out, according to the New York Times.
When Kennedy was undergoing treatment, his own doctors couldn’t agree on whether he should have surgery, the Times reported. The senator flew to Duke for a three-plus hours operation in June that his doctors billed as “successful." But he lived just a few months longer.
Though there are no known risk factors for this type of tumor, it seems to strike people between the ages of 50 and 70 the most frequently, says Hirschfeld. It’s about equally common in men and women.
While new findings continue to extend the lives of patients with glioblastoma, for the moment, it remains one of the most dreaded diagnoses. For those who receive it, putting up a fight against the tumor may help.
“If you go to the Internet and do a search on outcomes in glioma, everyone will call it a terminal illness,” Dr. Henry Friedman, co-director of Duke’s brain tumor center, told the Times. “Your outcome is ‘dead on diagnosis.’ If you don’t have the philosophy that you can win, you have lost before you started.”
Sen. Kennedy’s Death Puts Focus On Brain Cancer
The recent death of Senator Ted Kennedy has focused new attention on brain cancer. Glioblastoma multiforme (GBM), the aggressive brain tumor that took Sen. Kennedy’s life, is one of the deadliest brain tumors that can occur in both adults and children.
It is also one of the most difficult tumors to treat. Oral drugs can’t cross the blood-brain barrier, and tumor removal surgery has limited effectiveness. Malignant gliomas are prone to infiltrating healthy tissue. Small pieces of tumor, invisible during surgery, may later take root and grow back into other tumors. Patients generally live less than a year after diagnosis.
Like many other companies in the field, NeoPharm of Lake Bluff, Ill. has encountered challenges in its efforts to develop a treatment for GBM. NeoPharm’s drug candidate, IL 13-PE38QQR (IL-13), is designed to kill malignant glioma cells while preserving healthy tissue. The company uses a method called convection-enhanced delivery to deliver IL-13 through catheters inserted in the brain tissue. Further trials for IL-13 were put on hold in late 2006 after the drug candidate failed to meet its primary endpoint in a Phase III clinical trial. The company went head-to-head with the current standard-of-care treatment, the Gliadel Wafer, developed by MGI Pharma. The NeoPharm study found that IL-13 was just as effective, but not more so, than the Gliadel Wafer.
In the meantime, NeoPharm is exploring other options for IL-13. The company recently signed a Comparative Research and Development Agreement (CRADA) with the National Institute of Neurological Diseases and Stroke (NINDS), a division of the National Institutes of Health (NIH) to start a Phase I trial for various brain diseases. As part of the agreement, NeoPharm will be starting a Phase I trial for brain stem cancer. The trial will combine NeoPharm’s IL-13 with NINDS’ convection-enhanced delivery, which the agency had previously licensed to NeoPharm.
Other companies developing treatments for brain cancer include Boneca, ZGene, and ImmunoCellular Therapeutics.
Gene Vital To Brain's Stem Cells Implicated In Deadly Brain Cancer
ScienceDaily (2009-08-17) -- Researchers have identified a protein that activates brain stem cells to make new neurons -- but that may be hijacked later in life to cause brain cancer in humans. The protein called Huwe1 normally functions to eliminate other unnecessary proteins and was found to act as a tumor suppressor in brain cancer.
Marijuana compound fights brain cancer
Guillermo Velasco and a team of researchers at Complutense University in Spain have shown that the psycho-active chemical in marijuana, delta-9-tetrahydrocannibinol (THC), encourages brain cancer cells to begin a process called autophagy, in which the cell basically dissolves itself.
The team noted that cannabinoids such as THC showed cancer-fighting effects in mice implanted with human brain cancer cells and in human patients with brain tumors. When mice implanted with human brain cancer cells that received the THC, showed significant reduction of tumor growth.
Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme, a highly aggressive brain tumor. A comparison of biopsies taken before and after treatment showed that that tumors showed increased autophagy activity after receiving the THC.
None of the patients showed toxic effects from the treatment. Earlier assessments of THC in cancer treatment have also shown the therapy to be well tolerated. The researchers say that these findings might lead to new approaches for fighting tumor growth in brain cancer.
The findings appear in the April issue of the Journal of Clinical Investigation.
Discovering the Secrets of Brain Tumors
Physicians decide how to treat brain cancer in part based on what a patient’s tumor looks like under the microscope. But while the microscope can help classify a tumor, it cannot always reveal the molecular changes that drive the disease. And in an era of molecularly targeted therapies, this is what physicians and patients increasingly want to know.
Molecular markers have been identified and even genomic tests have been developed for breast and other common cancers, but progress has been slower in brain cancer. Obtaining the tumor tissue needed for molecular studies is difficult, and hundreds, if not thousands, of samples are needed to capture the genetic diversity of brain cancer.
Nonetheless, there is reason for optimism. Some of the first genomic studies of cancer included surveys of brain tumors, and for the first time, several clinical trials are enrolling patients based on tumor markers, such as combined deletions on chromosomes 1 and 19.
A database being developed by NCI and its partners around the country could also help move the field toward more individualized care. The Glioma Molecular Diagnostic Initiative (GMDI) is collecting and integrating molecular, genetic, and clinical data on hundreds of patients with gliomas, the most common type of brain tumor.
Changing the System
The March 1 issue of Cancer Research includes one of the first publications using the study’s database. The researchers propose a new classification system for gliomas based on tumor gene activity. While the results are considered preliminary, they illustrate the promise of an approach that seeks to integrate different types of information from patients with the disease, the researchers said. “Unlike the standard classification system for gliomas, we came up with a system that is based purely on biology,” said lead investigator Dr. Howard A. Fine, chief of NCI’s Neuro-Oncology Branch in the Center for Cancer Research. “The results confirm and extend the findings of smaller glioma classification studies published previously,” he added. Collectively, these studies show that there are subtypes of brain tumors defined not by their appearance under the microscope, but rather by the molecular pathways that are altered in tumors, said Dr. Mark Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center, who was not involved in the research. “These studies all have the same goal,” Dr. Gilbert continued. “For a hundred years we’ve made treatment decisions on the basis of looking at brain tumor tissue under the microscope. Yet we know that two patients can have very different outcomes even though their tumors look identical, so it would be helpful if we could figure out the pathways that made the cancers different.”
Clinical Genomics
Created to help attain that goal, GMDI has enrolled more than 800 patients with gliomas at 14 institutions around the country. A tumor sample collected during surgery for each patient is sent to NCI for molecular analysis. Clinical information on each patient is then linked to molecular and genetic descriptions of the tumor in a public database called REMBRANDT (Repository of Molecular Brain Neoplasia Data). “We have built the largest cancer clinical genomics database for any tumor type, let alone an uncommon type such as glioma,” said Dr. Fine. In the Cancer Research study, the researchers used 159 gliomas from GMDI to develop an algorithm that assigns gliomas to six subtypes under two groups, glioblastomas and oligodendrogliomas. They validated the algorithm in three additional data sets, totaling nearly 700 gliomas. The results confirm what physicians have always known—that some patients will do better than others for reasons that may not be understood, said Dr. Michael Prados, director of translational research in neuro-oncology at the University of California, San Francisco Comprehensive Cancer Center. He also leads a consortium that provided some of the annotated tumor samples used in the analysis. “If we really want to change the outcomes for patients, then we need therapies that address changes in particular pathways,” added Dr. Prados. “We don’t have those therapies now, so the challenge going forward is: How will we use this information to make a difference in patients therapeutically?”
Exploring the Biology
As a next step, Dr. Fine’s group is characterizing the biology of the tumors to inform the development of new therapies. Until very recently, most patients with brain cancer received the same toxic drugs. But with a growing pipeline of molecularly targeted cancer drugs, physicians can start to evaluate these agents rationally in clinical trials.
Given that the most common subtypes may include only about 10 percent of all tumors, the selection of patients for these trials will be critical. A drug may perform poorly in a trial of unselected patients, and therefore could be discarded, even though it may be very effective for a specific subset of patients. “For prognostic purposes, for drug development, and for the design of future clinical trials, we really need to be able to group brain tumors according to their underlying biology,” said Dr. Fine.
The genome surveys published last year and a recent follow-up report about relatively common mutations in brain tumors have set the stage for more individualized approaches to the disease. And while much more work remains to be done, everyone in the field seems to be moving in the same direction. “Information is power, and these studies are all expanding the knowledge base,” said Dr. Prados. “This will let us develop therapies for patients in a more specific way.” —Edward R. Winstead
Newly Discovered Gene Could Be a Prime Target in the Most Lethal Brain Cancer
2/20/09
Duke Medicine News and Communications
Scientists at Duke University Medical Center and Johns Hopkins University have discovered mutations in two genes that could become therapeutic targets in malignant glioma, a dangerous class of brain tumors.
"The fact that the defective genes code for metabolic enzymes found only in malignant glioma, and not in normal tissue, could make the gene products therapeutic targets," says Hai Yan, MD, PhD, lead author, an assistant professor in the Duke Department of Pathology. The findings are published in the Feb. 19 issue of the New England Journal of Medicine. 
These genetic flaws might also help distinguish between primary and secondary glioblastoma multiforme (GBM), two subtypes of especially deadly malignant gliomas, with survival of only months after their diagnosis. Patients that have mutation of the genes, isocitrate dehydrogenase 1, gene 1 and 2 (IDH1 and IDH2), also had a longer survival time.
Because the researchers found this genetic mutation in several different stages of glioma development, "the results suggested that the IDH mutations are the earliest genetic changes that start glioma progression," said Darell Bigner, MD, PhD, a co-author and director of the Preston Robert Tisch Brain Tumor Center at Duke University. Yet, patients with GBM or anaplastic astrocytoma who had the IDH mutations also were found to live longer than patients with those two cancers who lacked the mutations.
CMV: A virus in search of a vaccine
With the exception of the so-called cervical cancer vaccine, no shots have been approved specifically to prevent malignant tumors. But cervical cancer, which is caused by the sexually transmitted human papillomavirus (HPV), isn't the only tumor linked to a virus; another is cytomegalovirus (CMV), a usually harmless form of herpes that's the target of a possible therapeutic cancer vaccine for brain tumor patients.
As Scientific American reports this month, CMV has been found in the most common type of brain tumor, glioblastoma multiforme (GBM) — the cancer Massachusetts Democratic Sen. Edward Kennedy is battling. Duke University is recruiting 20 patients with these types of tumors for a combined phase 1/2 clinical trial (an early stage of testing that checks the safety and usefulness of a product) of an experimental vaccine treatment for these patients. It's also testing a similar version in another trial.
Duane Mitchell, the Duke University neuro-oncologist heading up the GBM vaccine treatment trials, is optimistic about them, telling Scientific American that creating a shot that goes after CMV "may be a radically new way to consider treating these tumors."
Pharma giant Novartis, meanwhile, is working on a CMV vaccine that would prevent infection with the virus. The company, headquartered in Basel, Switzerland, announced late last month that it expected to begin a phase 2 trial (which tests efficacy) of a preventive CMV vaccine this year. While CMV isn’t dangerous to most people, it infects 30,000 newborns in the U.S. annually, causing severe disability such as vision or hearing loss, seizures and cognitive problems in 8,000, according to the Centers for Disease Control and Prevention (CDC). It can also be deadly in people with weakened immune systems, such as AIDS patients.
Still, there are challenges. One researcher who tested a preventive CMV vaccine, University of Pennsylvania emeritus professor Stanley Plotkin, came up short when he found that it seemed to produce an immune response without actually preventing infection. "Is antibody sufficient, or do you need cellular immune responses? Or, are cellular immune responses sufficient and you don't need antibody? Those are unresolved issues," Plotkin told The Scientist in 2006, "that have somewhat hindered CMV vaccine development."
Salk researchers develop novel glioblastoma mouse model
| La Jolla, CA th Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma-the most common and deadly brain cancer in humans-that closely resembles the development and progression of human brain tumors that arise naturally. |
| (Media-Newswire.com) - La Jolla, CA – Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma—the most common and deadly brain cancer in humans—that closely resembles the development and progression of human brain tumors that arise naturally. "Mouse models of human cancer have taught us a great deal about the basic principles of cancer biology," says Inder Verma, Ph.D., a professor in the Laboratory of Genetics. "By definition, however, they are just that: approximations that simulate a disease but never fully capture the molecular complexity underlying disease in humans." Trying to mimic randomly occurring mutations that lie at the heart of all tumors, the Salk researchers used modified viruses to shuttle cancer-causing oncogenes into a handful of cells in adult mice. Their strategy, described in the Jan. 4, 2009 issue of the journal Nature Medicine, could not only prove a very useful method to faithfully reproduce different types of tumors but also to elucidate the nature of elusive cancer stem cells. The most frequently used mouse cancer model relies on xenografts: Human tumor tissue or cancer cell lines are transplanted in immuno-compromised mice, which quickly develop tumors. "These tumors are very reproducible, but this approach ignores the fact that the immune system can make or break cancer," says first author Tomotoshi Marumoto, Ph.D., a former postdoctoral researcher in the Verma lab and now an assistant professor at the Kobe Medical Center Hospital in Kobe, Japan. Other animal models either express oncogenes in a tissue-specific manner or shut down the expression of tumor suppressor genes in the whole tissue. "But we know that tumors generally develop from a single cell or a small number of cells of a specific cell type, which is one of the major determinants of the characteristics of tumor cells," explains postdoctoral researcher and co-author Dinorah Friedmann-Morvinski. To sidestep the shortcomings of currently used cancer models, the Salk team harnessed the power of lentiviral vectors to infect nondividing as well as dividing cells and ferry activated oncogenes into a small number of cells in adult, fully immunocompetent mice. After initial experiments confirmed that the approach was working, Marumoto injected lentiviruses carrying two well-known oncogenes, H-Ras and Akt, into three separate brain regions of mice lacking one copy of the gene encoding the tumor suppressor p53: the hippocampus, which is involved in learning and memory; the subventricular zone, which lines the brain's fluid-filled cavity; and the cortex, which governs abstract reasoning and symbolic thought in humans. He specifically targeted astrocytes, star-shaped brain cells that are part of the brain's support system. They hold neurons in place, nourish them, digest cellular debris, and are suspected to be the origin of glioblastoma. Within a few months, massive tumors that displayed all the histological characteristics of glioblastoma multiforme preferentially developed in the hippocampus and the subventricular zone. The ability of adult stem cells to divide and generate both new stem cells ( called self-renewal ) as well as specialized cell types ( called differentiation ) is the key to maintaining healthy tissues. The cancer-stem-cell hypothesis posits that cancers grow from stem cells in the same way healthy tissues do. Known as tumor-initiating cells with stem like properties these cells have many characteristics in common with normal stem cells in that they are self-replicating and capable of giving rise to populations of differentiated cells. To test whether the induced glioblastomas contained bona fide cancer stem cells, Marumoto isolated cultured individual tumor cells in the lab. These cells behaved and looked just like neural stem cells. They formed tiny spheres—often called tumor spheres—and expressed proteins typically found in immature neural progenitor cells. When given the right chemical cues, these brain cancer stem cells matured into neurons and astrocytes. "They displayed all the characteristics of cancer stem cells, and less than 100 and as few as 10 cells were enough to initiate a tumor when injected into immunodeficient mice," says Friedmann-Morvinski. Most xenograft models for brain tumors using tumor cell lines require at least 10,000 cells. "These findings show that our cancer model will not only allow us to start understanding the biology of glioblastoma but will also allow us to answer many questions surrounding cancer stem cells," says Verma. Although the work described to date pertains to glioblastoma, Verma and his team are currently using this methodology to investigate lung, pancreatic, and pituitary cancers. Authors who also contributed to the work include Ayumu Tashiro, Ph.D., at the Kavli Institute for Systems Neuroscience at the Medical Technical Research Center in Trondheim, Norway; Miriam Scadeng, Ph.D., at the UCSD Center for Functional MRI in La Jolla; Yasushi Soda, Ph.D.; and Fred H. Gage in the Laboratory of Genetics at the Salk Institute. This work was supported by the National Institutes of Health and in part by the H. N. and Frances C. Berger Foundation. The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health, and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes. For information on the commercialization of this technology, please contact Dave Odelson at 858-453-4100, x 1223 ( dodelson@salk.edu ) in of the Salk Office of Technology Management and Development. |
