Highlight HEALTH

Last Sunday, 60 Minutes profiled John Kanzius, an inventor who may have come up with one of the most promising breakthroughs in cancer research in years. It’s still in the experimental stage and much research needs to be done, but if future clinical trials are successful, the Kanzius Machine will destroy cancer cells throughout the body without need for drugs or surgery.

John Kanzius was diagnosed with terminal leukemia six years ago. Watching children endure difficult chemo treatments while he was undergoing his own chemotherapy motivated him to come up with an alternative. At the start of his interview with 60 Minutes correspondent Lesley Stahl, he said [1]:

I have no business being in the cancer business. It’s not something that a layman like me should in, it should be left to doctors and research people.
[Lesley Stahl: But sometimes it takes an outsider.]
Sometimes it just — maybe you get lucky.

And lucky he has been. Kanzius is a retired radio technician and station owner. As an alternative to chemotherapy, his idea was to build a radio-wave machine that focused radio waves to destroy cancer cells. Kanzius knew that strong radio waves could heat metal and wondered if metal injected in a tumor would heat up when placed in a radio-wave field, thereby killing the cells. Following initial experiments with a garage-built prototype, he spent about $200,000 to have an advanced version of his radio-wave machine built. Using hotdogs injected with copper sulfate (an aqueous metal solution), Kanzius found that he could heat up small regions injected with the metal by placing them in a radio-wave field, leaving surrounding areas unharmed.

Dr. Steven Curley and colleagues at the MD Anderson Cancer Center have begun testing Kanzius’ radio-wave technology on animals. Instead of copper sulfate, the researchers are using single-walled carbon nanotubes — molecular-scale tubes of graphitic carbon that, among other unique properties, are efficient conductors of heat. The nanoparticles are so small, thousands of them can fit inside a single cell. In a paper published in the December 2007 issue of the journal Cancer, the researchers demonstrated that, when exposed to a non-invasive radiofrequency (RF) field, an aqueous suspension of carbon nanotubes injected in malignant liver cancer tumors in rabbits produced lethal thermal injury to cancer cells [2]. The controls, tumors exposed only to the RF field or only to the nanotubes, were undamaged. However, some healthy liver tissue surrounding the cancerous tissue sustained heat damage due to nanotube leakage from the tumor.

Thus far, the technique has only been used on solid, localized tumors in animals by injection. The next step is to evaluate methods for targeting the nanotubes so they attach to and are taken up by cancer cells and not normal cells. According to Curley, the targeting of nanotubes to cancer cells and not to normal cells is a major challenge in advancing the therapy [3]. Researchers are looking to bind the nanotubes to antibodies, peptides or other agents that would target molecules expressed exclusively on cancer cells.

Gold nanoparticles have also been shown recently to enhance non-invasive RF thermal destruction of human gastrointestinal cancer cells in vitro [4].

Dr. Curley estimates that human clinical trials are at least three to four years away [3]. Using physics-based concepts, the Kanzius Machine is a potential new cancer treatment that may one day replace chemotherapy and surgery. That said, remember that many cancer therapies that have been promising in vitro and in animal models didn’t work in humans. There is zero evidence this will work in humans and targeting is a major issue that has to be overcome first.

References

1. The Kanzius Machine: A Cancer Cure? 60 Minutes. 2008 Apr 13.
2. Gannon et al. Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field. Cancer. 2007 Dec 15;110(12):2654-65.
   View abstract
3. Radio Waves Fire Up Nanotubes Embedded in Tumors, Destroying Liver Cancer. M.D. Anderson News Release. 2007 Nov 1.
4. Gannon et al. Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells. J Nanobiotechnology. 2008 Jan 30;6:2.
   View abstract

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Neurofibromatosis (NF) is a set of genetic disorders that can cause tumors to develop and grow along various types of nerves. The tumors may also affect the development of non-nervous system tissues such as skin and bone.

There are three types of NF tumors that result from mutation or loss of different tumor suppressor genes:

• Neurofibromatosis type 1 (NF1) is the most frequent inherited cause of brain and nerve tumors. One in every 3,000 children is born with NF1, making it also one of the most common inherited human diseases worldwide. Enlargement and deformation of bones may also occur. Approximately 50% of people with NF1 also have learning disabilities. NF1 is caused by a mutation or loss of the tumor suppressor gene NF1.

• Neurofibromatosis type 2 (NF2) is much rarer, occurring in one in 25,000 births. NF2 is characterized by the development of multiple tumors on the cranial and spinal nerves. The hallmark of NF2 is the formation of tumors that affect auditory nerves. Hearing loss beginning in the teens or early twenties is typically the first symptom of NF2. NF2 is caused by a mutation or loss of the tumor suppressor gene NF2.

• Schwannomatosis is even rarer than NF2, affecting one in 40,000 individuals. SImilar to NF1 and NF2, Schwannomatosis tumors can develop on cranial, spinal and/or peripheral nerves. Although patients with Schwannomatosis do not have learning disabilities, they experience chronic pain and occasionally numbness, tingling and weakness. The candidate Schwannomatosis tumor suppressor gene is named INI1.

The National Institutes of Health (NIH) is the primary source of federal funding for biomedical research. However, other agencies also support research initiatives. In 1996, Congress added Neurofibromatosis to the Congressionally Directed Medical Research Program (CDMRP-NFRP). This program has been responsible for many advances in NF research, including NF mouse models, learning disabilities and nerve signaling pathways. In 2005, the Neurofibromatosis Research Program (NFRP) established the NF Clinical Trials Consortium, which is comprised of 10 major hospitals nationwide. The Consortium was established, not for drug discovery, but as a pipeline to test drugs repurposed to treat NF, including rapamycin (a relatively new immunosuppressant drug) and lovastatin (a statin used for lowering cholesterol). The Consortium will initially focus on NF1 for proof of concept. Once established, it will have the option of expanding to encompass NF2 and Schwannomatosis studies.

NF research program funding in jeopardy

The U.S. House and Senate included an $8 million appropriation for the CDMRP-NFRP in the FY2008 Defense Bill. This is a decrease of $2 million from 2007 and is over a 66% decrease from the high-water mark of $25 million in FY2005. Recently, I wrote about Flat Funding of Biomedical Research and The Threat to America’s Health. Separate from the NIH, the CDMRP is another funding source that supports research initiatives. The drastic funding cuts in the CDMRP-NFRP, specific to NF studies, endanger the research investment made to date, particularly with the NF Clinical Trials Consortium described above.

The Children’s Tumor Foundation (CTF), a non-profit medical foundation dedicated to improving the health and well being of individuals and families affected by the neurofibromatoses, is the largest non-government funder of NF research in the world. In 1991, the CTF began a formal advocacy and lobbying program for federal funding of NF research. Recently, the CTF announced an advocacy campaign to increase federal funding of the CDMRP-NFRP [1]:

We are all aware of the budget pressures our country faces, and understand that the $25 million funded in 2005 is not realistic in the current environement. However, this small program has accomplished so much, and as we enter what we believe will be a period of rapidly increasing clinical trials, this is a particularly important time for continued support of this funding. We are asking all of you to contact your Congressman and Senators to seek their support. There is much discussion of earmark reform in Washington. It is important to note that this funding is not an earmark. It is not directed to any one institution, state or district. It is a long standing program that makes grants solely on a peer review basis. Further, this is not a partisan issue - this funding has benefited over the years from strong support from both Democrats and Republicans. The accomplishments and return on investment from the CDMRP are a shining example of what the federal government can achieve when legislators work with the scientific community and non-profit organizations.

Indeed, the CDMRP-NFRP is a small program. Congressional appropriations for NF from 1996 to 2008 totaled just $190.3 million. By comparison, CDMRP funding for breast cancer totaled $2222.7 million, for prostate cancer, $890 million [2]. Nevertheless, CDMRP funding for NF research in 2008 is critically important to address the needs of translational research (meaning to connect basic research to patient care), complications of NF with high morbidity and mortality, and refinement and standardization of imaging techniques and biomarkers for use in future clinical trials.

You can read more on the Children’s Tumor Foundation and Neurofibromatosis here at Highlight HEALTH. Additional non-profit organization resources are listed in the Highlight HEALTH Web Directory.

I’m actively involved in neuro-oncology, specifically NF research, and can attest to the importance of CDMRP-NFRP funding. I encourage you to take a moment and email your Senator and Representative and urge them to support increased Neurofibromatosis research funding through the CDMRP. You can find your legislators contact information by visiting the House and Senate websites. For the House website, simply enter your zip code in the box in the upper left corner; for the Senate website, select your state from the pulldown menu in the upper right corner. Use the contact information provided to email, fax or mail your request for support.

UPDATE: April 1st, 2008

Sample letters are now available (in MS Word format) for download, making it that much easier to email, fax or mail your Senator and Representative.

References

1. The Children’s Tumor Foundation: Advocacy. Accessed 2008 Mar 30.
2. Congressionally Directed Medical Research Programs: Funding History. Accessed 2008 Mar 30.

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Welcome to the 7th edition of the Cancer Research Carnival, a blog carnival devoted to cancer research. This edition includes some great articles on cancer research ethics, cancer therapeutics, cancer stem cells, cancer genetics and cancer biology.

I believe it’s important to maintain perspective on the significance of cancer research and the impact it has on patients. As such, this months edition of the Cancer Research Carnival includes narratives from some people affected by the disease. I think their stories will inspire us all with their determination and courage, and serve as motivation to continue searching for therapies to combat cancer.

How is research progressing on the battle against cancer?

The latest American Cancer Society (ACS) annual cancer statistics report finds that cancer deaths have decreased by 18.4% in men and 10.5% in women since mortality rates began to decline in the early 1990s [1]. However, despite a declining death rate, there was an increase in the number of cancer deaths in 2005 compared to 2004. The ACS says that it’s [2]:

… important to understand that for the number of cancer deaths to decrease, the decline in the overall cancer mortality rate must be large enough to offset the increasing numbers due to growth and aging of the population.

Over the last 15 years, researchers have been making progress. Although the rate of decline in cancer deaths in 2005 wasn’t enough to exceed population factors, cancer mortality rates continue to decrease. Indeed, between 1990/1991 and 2004, over a half million deaths from cancer were averted [2].

With these statistics in mind, let’s get to the research highlighted in this months edition of the Cancer Research Carnival.

Cancer Research Carnival #7

Adventures in Ethics and Science

A recent New York Times essay by Andrew Vickers ponders why cancer researchers are so reluctant to share their data [3]. Dr. Janet Stemwedel discusses the essay, asking Should Researchers Share Data?.

Bayblab

Autophagy, the self-removal of cellular components, is frequently observed in tumor cells following radiotherapy. Researchers have found that inhibition of genes associated with autophagy results in enhanced cytotoxicity of radiotherapy to otherwise resistant carcinoma cells [4]. Kamel talks about Autophagy and Radiation Resistance.

Mark’s Daily Apple

Increased body-mass index (BMI) is associated with the risk of some types of cancer. A systematic review and meta-analysis published in the Lancet journal last month assess the strength of associations between BMI and different sites of cancer [5]. Mark’s Daily Apple reports there’s a Higher Cancer Risk if You’re Fat and questions whether public education on the risks of obesity is truly enough.

The Pink Tee Shirt

Beep Beep - Emmy describes what it’s like to be living with breast cancer.

Stage 4 cancer is like a hungry coyote out there, watching, setting traps.
I wonder when he will catch me.

Cancer and Your Genes

Two papers in the February 28th issue of Nature provide understanding into a subset of breast and ovarian cancers, the action of drugs used to treat them and a novel mechanism of drug resistance to chemotherapy [6-7]. Dr. Matt Mealiffe reviews the articles and their significance, describing the Mechanism of Cisplatin-Resistance in BRCA2-Related Ovarian Cancers.

Cancer Genetics

SNPs (pronounced “snips”) are DNA sequence variations that occur when a single nucleotide in the genome is altered, producing different alleles (meaning sequences that code for the same gene). Two papers in the March issue of Nature Genetics identify multiple new SNPs associated with prostate cancer [8-9]. Ramunas breaks it down, describing Prostate Cancer — Old & New SNPs and deCODEPrCa.

Eye on DNA

As research identifies more disease-associated SNPs, new genetic tests allow consumers to test themselves for disease susceptibility. Dr. Hsien-Hsien Lei discusses this competitive market, reporting that deCODE Launches PrCa Prostate Cancer DNA Test.

Mystery Rays from Outer Space

Although it’s widely accepted that metastasis is a late event in cancer progress, a recent study demonstrated that tumor cells can spread systemically from early alterations in breast cancer [10]. Dr. Ian York deliberates Early Metastasis.

Z-Mail 101

David’s daughter Beth presents her thoughts on the situation her Aunt Wendy is in as she battles colon cancer.

You have to live life day by day and for each moment. Enjoy what you have in front of you and not take for granted the little things. We’re all going to die at some point; cancer patients just have more information.

Terra Sigillata

The internet is increasing used as a source of health information. A current study of quality criteria for online content, specifically for breast cancer information, finds that most resources are accurate [11]. However, websites that contain information on complementary and alternative medicine (CAM) were likely to contain inaccurate statements. Abel Pharmboy suggests we Beware of Alternative Medicine Sites Offering Breast Cancer Advice.

Doctor David’s Blog

An investigation examining the role of BRCA1 in human mammary stem cell fate found that BRCA1 plays a critical role in the differentiation of ER-negative stem/progenitor cells to ER-positive luminal cells [12]. Dr. David Loeb reviews study and discusses Cancer Stem Cells and Familial Cancer Risk for Breast Cancer.

Gene Sherpas: Personalized Medicine and You

Men with a family history of prostate cancer have a much greater risk of developing the disease than men with no family history. A systematic review and meta-analysis demonstrated that the risks are greatest for relatives of those diagnosed when they were young and those with more than one affected relative
[13]. The Dr. Steve Murphy evaluates the study and its shortcomings, discussing the New England Journal, Prostate Cancer and Babel.

Britannica Blog

The World Health Organization’s International Agency for Research on Cancer (IARC) has been conducting research on the increased risk of cancer in night-shift workers as well as the increased cancer risk in painters and firefighters [14]. Kara Rogers reviews the biology of melatonin secretion and disruption of circadian rhythm, writing about Cancer on the Night Shift: Why Night Workers Are at Risk.

Chrysalis Angel

Chrysalis Angel worries when she hears the word “cured” and reminds us all to Remain Vigilant.

Stay on top of your check ups, follow the recommendations of your doctors, do your own breast self exams. Take back your life and your health. You can only do that by remaining vigilant. Then, get out, enjoy your life and loved ones. Make your life as much of what you want it to be as you can, and maybe someday soon – there will be an absolute cure for cancer.

Conclusion

Thanks to everyone that contributed articles — it’s been a pleasure to host this months edition of the Cancer Research Carnival. Be sure to take a moment and let your fellow bloggers know this issue is available so that everyone’s hard work can be appreciated and enjoyed by all. You can find more information about the carnival as well as the hosting schedule and past editions at the Cancer Research Blog Carnival.

References

1. Cancer Facts & Figures 2008. American Cancer Society. Atlanta, Ga. 2008.
2. Report Says Half a Million Cancer Deaths Have Been Averted Since Death Rate Drop. American Cancer Society Press Release. 2008 Feb 20.
3. Vickers A. Cancer Data? Sorry, Can’t Have It. The New York Times. 2008 Jan 22.
4. Apel et al. Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res. 2008 Mar 1;68(5):1485-94.
   View abstract
5. Renehan et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008 Feb 16;371(9612):569-78.
   View abstract
6. Edwards et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008 Feb 28;451(7182):1111-5. Epub 2008 Feb 10.
   View abstract
7. Sakai et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008 Feb 28;451(7182):1116-20. Epub 2008 Feb 10.
   View abstract
8. Eeles et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008 Mar;40(3):316-21. Epub 2008 Feb 10.
   View abstract
9. Thomas et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008 Mar;40(3):310-5. Epub 2008 Feb 10.
   View abstract
10. Hüsemann et al. Systemic spread is an early step in breast cancer. Cancer Cell. 2008 Jan;13(1):58-68.
    View abstract
11. Bernstam et al. Commonly cited website quality criteria are not effective at identifying inaccurate online information about breast cancer. Cancer. 2008 Feb 11;112(6):1206-1213 [Epub ahead of print].
    View abstract
12. Liu et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1680-5. Epub 2008 Jan 29.
    View abstract
13. Johns and Houlston. A systematic review and meta-analysis of familial prostate cancer risk. BJU Int. 2003 Jun;91(9):789-94.
    View abstract
14. Straif et al. Carcinogenicity of shift-work, painting, and fire-fighting. Policy Watch, The Lancet Oncology. 2007 Dec;8(12):1065-1066.

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