Do cell phones cause brain tumors?

Simple answer: we still don't know.

The results from the INTERPHONE study were published in the May issue of the International Journal of Epidemiology. This is the world's largest study on cell phone use and brain tumors. The INTERPHONE study's main goal was "to determine whether mobile phone use increases the risk of brain tumors and, specifically, whether radiofrequency energy emitted by mobile phones is tumorigenic."

An additional question addressed was: "do mobile phones increase the risk of brain tumors within the first 10-15 years of use?"

Unfortunately, due to methods, biases inherent in any epidemiology study of this magnitude, changes in mobile phone usage patterns and technology, no clear conclusions can be drawn from this study.

The International Agency for Research on Cancer (IARC) sponsored this multicenter study among 13 nations.

The INTERPHONE study is a case control study. Investigators first identified cases of meningioma and glioma between 2000 and 2004. There were 2708 glioma patients and 2409 meningioma patients studied. A "matched" control patient was identified for each tumor patient. That is a patient without a brain tumor who was of the same sex, approximately the same age, and from the same geographic region. There were 2972 matched controls for the glioma group and 2662 for the meningioma group.

During face to face interviews, all participants were questioned in detail about their past cell phone use. If the patient had died or was too ill to be interviewed, a "proxy" was interviewed.

As you can see, the results are completely dependent on a person's precise recall of past cell phone use and may not be entirely accurate.

Additional data analysis is ongoing and a large, prospective study is underway. So for now, no specific guidelines can be given regarding cell phone use and brain tumor.

• However, common sense would tell us to limit a child's usage, use speaker phone and hands free methods, use text messaging (but not while driving), and don't always listen with the same ear.

Graduate Student Research at UMBTC

The research lab and graduate and undergraduate student education has been and is a top priority for the UMBTC. The UMBTC provides an opportunity for students to learn, contribute and excel. We have been fortunate to work with bright, talented and motivated students. This year, the tradition of excellence continues. I am pleased to report that for the third year running, one of our graduate students took first place honors at the Celebration of Student Research, April 15th at NMU. And for the second time in three years, our students place 1st and 2nd.

Danny LeBert received the top prize for his research, "Investigation of an Alternative Cancer Recurrence Model and Characterization of Murine Neural Stem Cell Migratory Capabilities." This work aims to determine the mechanisms that lead to GBM recurrence. Danny will defend his Master's thesis this summer and will hopefully complete a postgraduate year in our lab.

Vanessa Thibado came in a close second with her work, "PARP-1 Inhibition as Concomitant Therapy in Resistant Glioblastoma Multiforme." This work is evaluating alternative treatment targets to render GBM more sensitive to chemotherapy. Vanessa is completing her first graduate year and will continue her work over the summer and the next academic year.

Danny and Vanessa are also very active in the Graduate Student Association at NMU. Vanessa is currently serving as President. She and Danny travelled to Lansing as Ambassadors to the 2010 Michigan Graduate Education Day. They were the only two graduate students from NMU to attend. Overall, 71 grad students from 16 Michigan universities participated. Danny and Vanessa met with Steve Lindberg, State Representative for our district and were introduced by him to the State House of Representatives.

These opportunities are made possible through the generous support of our community to the UMBTC.

On May 8th, the UMBTC is hosting its once a year fundraising event, the Hope Starts Here Challenge. We'd love for you to participate and, if possible, make a tax deductible contribution to the UMBTC so that we can continue the programs that are making a difference in the lives of our patients and families.

Can a tomato plant provide a new treatment for GBM?

This recently published paper from Stockholm inserted a gene from a tomato plant into GBM cells and made them more susceptible to treatment.

How does this work?

It is called suicide gene therapy. And this is the concept: find a gene coding for an enzyme that human cells don't have. Insert that gene only into cancer cells--not normal cells. This enzyme works by taking a harmless "pro-drug" and converting it into a toxic compound. Early attempts at this therapy used the enzyme thymidine kinase from the herpes simplex virus. This enzyme converts the drug ganciclovir into a compound that stops DNA synthesis. If a cancer cell can't make new DNA, it will eventually die.

The current paper uses the thymidine kinase gene from the tomato plant. The gene is delivered to GBM cells by neural stem cells. The tomato thymidine kinase acts on the drug AZT and converts it into compounds that interfere with DNA synthesis.

AZT might sound familiar. It is a retroviral agent used to treat patients with HIV. Jerome Horwitz first created the compound in 1964 while at the Karmanos Cancer Center in Detroit. The drug works by preventing the RNA of the HIV virus changing itself into DNA.

While tomato gene therapy may or may not make it to clinical trial stage, it is important for you to know that throughout the world, creative and ingenious new treatments for GBM are being developed all the time.

New Clinical Research Project Now Enrolling Patients

The UMBTC is beginning another clinical research study at MGH.

The study is entitled, "Is the presences of cytomegalovirus (CMV) in tumor tissue a prognostic factor for patients with newly diagnosed glioblastoma multiforme (GBM)?"

Background: CMV is a member of the herpesvirus family. Other members of this family include the viruses that cause chicken pox and mononucleosis. Between 50% and 80% of adults in the United States are infected with CMV by age 40. Most CMV infections are silent, causing no symptoms.  CMV infection can be serious, especially when transmitted to an infant at birth or in a patient immunosuppressed because of medication (i.e. transplant patients) or HIV. Once CMV is in our body, it stays there, dormant, for life.  Currently, there is no treatment for CMV.

Is there a link between CMV and GBM?  In 2002, Charles Cobbs, a Neurosurgeon, first reported finding CMV DNA in GBM tumor samples.  This result was confirmed by other investigators, including Duane Mitchell at Duke University.

It is unlikely that CMV causes GBM. But because CMV related proteins have an effect on cell growth and survival, CMV may contribute to the aggressive behavior of GBM. For example, CMV might make tumor cells more resistant to chemotherapy and radiation therapy or it might help tumor cells evade the immune system.

Study objectives: 

1. Quantify the amount of CMV DNA that is present in tumor tissue. We plan to develop a test that will tell us how much, if any, CMV DNA is present in a specimen of tumor tissue. We will use a technique called real time polymerase chain reaction (PCR). For this test, DNA will be extracted from a  small amount of tumor tissue removed at the time of surgery.  

2. We will next determine if the presence of CMV DNA in GBM samples is an independent prognostic factor. That is, does a person whose tumor contains CMV DNA respond better or worse to treatment? We will also use statistical tests to determine if a particular level of CMV DNA can predict response to treatment.

3. If the results look promising, we hope to expand the study to include other brain tumor centers and pediatric patients.

4. If it turns out that CMV DNA has a negative impact on patients, new and specific treatments can be developed to target CMV.

This study has been approved by the Institutional Review Board at MGH and the HIPAA compliance officer at MGH. That means that this study meets federal guidelines to protect a patient from harm and to protect confidential medical information.

If you or your family have questions about this clinical research, please contact the UMBTC at 906-225-7739 or email us at info@hopestartshere.org.

Researchers at UCLA sequence a human brain cancer genome

Researchers at UCLA have unraveled the complete genome of the U87 human malignant glioma cell line. This cell line is used in virtually every lab studying gliomas, including ours.

The first breakthrough is technology. UCLA basically repeated the Human Genome Project 50 times faster and at least a thousand times cheaper.  This means that sequencing an individual patient's cancer is achieveable and foreseeable.

The second breakthrough regards diagnosis. In addition to looking at cells and tissues under the microscope, we will be able to look at the DNA and know if the biopsy contains tumor tissue or scar tissue resulting from treatment.

The third breakthrough regards treatment. By knowing every mutation that occurs in a cancer cell, we can develop never before thought of targeted treatments.

Kudos to UCLA for showing us that technology doesn't always have to trump reason.

Identifying Molecular Subtypes of GBM

The article, "Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1," was published yesterday in the journal Cancer Cell and it will revolutionize the way we diagnose and treat GBM. Using state of the art molecular and genetic research techniques, the investigators confirmed what we have believed clinically for some time: GBM is not one disease. Even though GBMs look the same under the microscope, there are significant differences in tumor behavior and response to treatment amongst people diagnosed with "GBM." 


The data was obtained through The Cancer Genome Atlas (TCGA). TCGA was developed in order to understand the molecular and genetic events that lead to cancer formation so that rational and novel therapies could be created. GBM was one of the first four cancers to be included in the TCGA project.


The article described four new subtypes of GBM as well as their molecular and genetic characteristics:

• Classical: amplification of EGFR gene, deletion of CDKN2A gene (codes for p16INK4A and p14ARF), lack of p53 mutation
• Mesenchymal:  deletion of NF1 gene and high expression of tumor necrosis factor family of genes
• Proneural:  high levels of PDGFRA expression, mutations in IDH1 and p53 genes
• Neural:  expression of neuron markers

The hope is that this information will lead to new treatments that target an individual tumor's particular set of genetic and molecular abnormalities, and new biomarkers that might lead to diagnostic tests.

The UMBTC is working with Moffitt Cancer Center in Tampa to study the molecular and genetic profile of brain tumor tissue.  Call is at 906-225-7739 to learn more about this program and ways you might be able to participate.

Research Update

Our lab is newly energized following the 2nd Hope Starts Here Cycling Challenge. This event is great for us because it refocuses our efforts, gives us a new sense of purpose and rekindles our passion to make a contribution to the fight against brain cancer.
The past year has been very productive. Our research has been published and presented at national meetings. And we were very suprised and humbled that our research was recognized nationally with the BrainLab Community Neurosurgery Research Award.
This summer,we are looking at ways to turn off two genes. One, MGMT, counteracts temzolomide chemotherapy. The other, ZBTB7, appears to be involved in the conversion of a normal cell to a cancerous one.
Check back here for updates