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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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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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It’s been three months since an article on dichloroacetate (DCA), the chemotherapeutic agent that selectively inhibits cancer cell growth in lung, breast and brain tumor cells grown in culture and lung tumors grown in immunocompromised rats, was published on Highlight HEALTH. Since then, thousands of people have read the article. Indeed, the blogosphere has been buzzing about DCA, unfortunately focusing on a conspiracy theory accusing big pharma of suppressing a cure for cancer instead of recognizing the study for what it is — a preliminary study in cell culture and rats that cannot be translated to humans without further research and clinical trials.

Safe alternative to DCA?

I was curious to see if there were any new developments regarding DCA use in either cancer prevention or the treatment of cancer. A Google search for “dichloroacetate” returned 340,000 pages, but before I had a chance to start browsing, one of the Sponsored Links at the top of the page caught my eye. In addition to a site where you can buy DCA, another site advertised a “safe alternative” to dichloroacetate.

Intrigued, I clicked on the link. The alternative is a “new flavonoid cancer treatment protocol”, which involves nothing more than dissolving 1000 mg of vitamin C in 0.5 L of water and adding the contents of 1 — 2 quercetin (pronounced “kwer-see-tin”) capsules (500 mg — 1000 mg).

Quercetin

A polyphenol, quercetin is one of a number of water-soluble plant pigments called flavonoids (meaning class of plant secondary metabolites known for their antioxidant activity) and is largely responsible for the color of many flowers, fruits and vegetables. High concentrations of quercetin are found in apples, onions, tea and red wine [1]. Quercetin and other flavonoids (also referred to as bioflavonoids) cannot be produced in the human body.

Quercetin is a powerful antioxidant; from a range of dietary flavonoids, quercetin was found to be the most effective inhibitor of oxidative damage to LDL (bad) cholesterol in vitro [2]. In contrast, another study found that quercetin had mostly prooxidant effects [3]. However, when mixed with other phenolic compounds, significant antioxidant capacity was identified, indicating a synergistic effect.

A number of research studies have demonstrated that quercetin is a natural antihistamine and anti-inflammatory [4-6]. Indeed, quercetin is unique in its ability to inhibit TNF-alpha (a cytokine involved in systemic inflammation) gene expression [7]. Studies have also shown that quercetin exhibits anticancer effects [8].

Clinical trials

A number of phase I clinical trials have been performed with quercetin evaluating pharmacokinetics [9] and adenoma regression [10]. A combination of curcumin and quercetin was evaluated to regress adenomas in patients with familialadenomatous polyposis (FAP), an autosomal-dominant disorder characterized by the development of colorectal adenomas and eventual colorectal cancer. The study found that the combination appeared to decreased polyp number and size from baseline after 6 months of treatment [10].

Epidemiologic data indicates that reduction in colorectal cancer risk associated with the highest 25% of data vs. the lowest 25% was largest for quercetin and catechin [11]. Overall, flavonoids showed strong and linear inverse associations with colorectal cancer risk. Large-scale genomic studies in colon cancer cells suggest that quercetin affects the expression of genes involved in cell cycle control [12-13]. Flavonoids also modulate cell cycle progression in prostate cancer cells [14-15].

Antioxidants and cancer

In September 2005, an article published in CA: A Cancer Journal for Clinicians warned against the use of antioxidants in combination with radiotherapy and chemotherapy [16]. Indeed, quercetin may alter the effects of chemotherapy medications used to treat cancer [17]. However, this position has been refuted by others [18] and a recent meta-analysis suggests that antioxidant supplementation does not interfere with therapeutic modalities for cancer and instead enhances the killing of therapeutic cancer agents, decreases modality side effects and protects normal tissue [19-20]. Another meta-analysis reviewing the evidence from randomized controlled trials on the impact of antioxidant supplementation on chemotherapeutic efficacy, although limited by lack of statistical power, found that many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses or both, as well as fewer toxicities than controls [21].

A recent review assessing the contribution of dietary flavonoids to the total antioxidant capacity of plasma in humans concluded that the large increase in plasma total antioxidant capacity observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, but is likely the consequence of increased uric acid levels [22]. A potent antioxidant, uric acid is a normal constituent of the body and is the end product of purine (meaning the nucleotides adenine and guanine, two of the four building blocks of RNA and DNA) metabolism. Because the increased plasma concentration of uric acid is much greater than the concentration of flavonoids, the change in uric acid levels is thought to be responsible for the relatively large increase in plasma total antioxidant capacity after consumption of flavonoid-rich foods. Most uric acid produced in the body is excreted by the kidneys. However, it has been proposed that renal uric acid clearance is regulated by an unknown signal that is issued in response to the level of oxidative stress [23], allowing the kidneys to reabsorb the potent antioxidant when needed.

Flavonoids have been shown to induce detoxifying Phase II enzymes [24-25], indicating that they are recognized by the body as foreign compounds. Thus, it has been proposed that the ability of flavonoids to induce detoxifying enzymes may be a major mechanism by which flavonoids protect against mutagens and carcinogens, and act as cancer chemopreventive agents [22].

References

1. Sampson et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002 Oct;102(10):1414-20.
   View abstract
2. O’Reilly et al. Flavonoids protect against oxidative damage to LDL in vitro: use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex vivo? Free Radic Res. 2000 Oct;33(4):419-26.
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3. Cirico and Omaye. Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation. Food Chem Toxicol. 2006 Apr;44(4):510-6. Epub 2005 Oct 10.
   View abstract
4. Middleton and Drzewiecki. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol. 1984 Nov 1;33(21):3333-8.
   View abstract
5. Taguchi et al. Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin. Yakugaku Zasshi. 1993 Apr;113(4):327-33.
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6. Loggia Della et al. Anti-inflammatory Activity of Benzopyrones that are Inhibitors of Cyclo- and Lipo-oxygenase. Pharmacol Res Commun. 1988 Dec;20 Suppl 5:91-4.
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7. Wadsworth et al. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol. 2001 Oct 1;62(7):963-74.
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8. Morrow et al. Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation. Mutat Res. 2001 Sep 1;480-481:269-76.
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9. Ferry et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996 Apr;2(4):659-68.
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10. Cruz-Correa et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1035-8. Epub 2006 Jun 6.
    View abstract
11. Theodoratou et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):684-93.
    View abstract
12. van Erk et al. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. Epub 2004 Apr 30.
    View abstract
13. Murtaza et al. A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell-cycle arrest, apoptosis and xenobiotic metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray. Biotechnol Appl Biochem. 2006 Jul;45(Pt 1):29-36.
    View abstract
14. Kobayashi et al. Effect of flavonoids on cell cycle progression in prostate cancer cells. Cancer Lett. 2002 Feb 8;176(1):17-23.
    View abstract
15. Knowles et al. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 2000;38(1):116-22.
    View abstract
16. D’Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin. 2005 Sep-Oct;55(5):319-21.
    View abstract
17. Desai et al. Human liver microsomal metabolism of paclitaxel and drug interactions. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):417-24.
    View abstract
18. Moss RW. Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants? Integr Cancer Ther. 2006 Mar;5(1):63-82.
    View abstract
19. Simone et al. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1. Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8.
    View abstract
20. Simone et al. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med. 2007 Mar-Apr;13(2):40-7.
    View abstract
21. Block et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007 Mar 14; [Epub ahead of print].
    View abstract
22. Lotito and Frei. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic Biol Med. 2006 Dec 15;41(12):1727-46. Epub 2006 Jun 3.
    View abstract
23. Kirschbaum B. Renal regulation of plasma total antioxidant capacity. Med Hypotheses. 2001 Jun;56(6):625-9.
    View abstract
24. Kong et al. Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Drug Metab Rev. 2001 Aug-Nov;33(3-4):255-71.
    View abstract
25. Walle and Walle. Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Drug Metab Dispos. 2002 May;30(5):564-9.
    View abstract

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