Monthly Archives: February 2011

Curing Cancer with Dwarfism, Down syndrome, and Vegetables

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With the world abuzz about dwarfism preventing cancer, we wondered: what other sorts of genetic tinkering can, unexpectedly, prevent or cure cancer?

Dwarfism

Laron syndrome is a genetic disorder that causes dwarfism. Individuals with Laron syndrome possess a mutation on the GHR gene, rendering the gene defective and body insensitive to human growth hormone—hence stunted growth.

In a study recently published in Science Translational Medicine,1 scientists studied 100 Ecuadoreans with Laron syndrome and compared them to 1,600 relatives who were normally proportioned. Over the 22-year course of the study, none of the subjects with Laron syndrome were diagnosed with diabetes, and only one individual reported any tumorous growth (a benign ovarian tumor). Comparatively, of relatives living under the same conditions over the same timeframe, 5 percent were diagnosed with diabetes and 17 percent with cancer.

The Food and Drug Administration has already approved growth-hormone-blocking drugs to treat acromegaly, a type of gigantism, and in the future, these sorts of drugs may be used to prevent cancer or diabetes in high-risk populations.

Down Syndrome

Individuals with Down syndrome possess an extra 21st chromosome. According to a recent study published in Nature,2 this extra chromosome could decrease an individual’s risk of cancer.

One particular gene on the 21st chromosome, Dscr1, regulates blood vessel growth, or angiogenesis. Researchers found that in mice, an extra 21st chromosome—and therefore, an extra copy of the Dscr1 gene—kept abnormal angiogenesis (and resulting tumor growth) in check. To verify that the Dscr1 gene affects humans in the same way, the researchers generated stem cells from skin cells taken from an individual with Down syndrome. They then injected one group of immunocompromised mice with these Down syndrome-derived cells, and another group with cells derived from a chromosomally normal human. In the “normal” group, the mice’s tumors generated networks of blood vessels to feed themselves, but in the “Down syndrome” group, the tumors hardly formed any blood vessels at all.

With this discovery, researchers are looking for ways to target the Dscr1 pathway, starve tumors of blood vessels, and not just treat, but prevent cancer.

Cruciferous Vegetables

What do broccoli, cauliflower, cabbage, turnip, and watercress all have in common? Sure, they are all vegetables, but they could all also help reduce the incidence of cancer.

As members of the cruciferous vegetable family, these foods contain isothiocyanates (ITCs), phytochemicals that fight cancer by working on the tumor suppressor gene p53. When the gene is functioning properly, its proteins play a role in keeping cells healthy and preventing them from starting abnormal growth. When the gene is mutated, p53 fails to provide this protection.

According to a study recently published in Journal of Medicinal Chemistry,3 scientists found that ITCs can remove defective p53 proteins while leaving normal p53 proteins alone. This means that not only was your mother right—you really should finish all your broccoli—but because half of all human cancers include mutated p53 genes, the future of cancer treatment may very well include ITC-based drugs.

Resources from Wiley on This Topic
Cancer: Basic Science and Clinical Aspects

by Craig A. Almeida and Sheila A. Barry
Cancer: An Interdisciplinary View

Wiley Interdisciplinary Reviews (WIREs) Collection
Tumor Microenvironment

by Dietmar W. Siemann
Anticancer Therapeutics

by Sotiris Missailidis

1. Guevara-Aguirre, J., Balasubramanian, P., Guevara-Aguirre, M., Wei, M., Madia, F., Cheng, C., Hwang, D., Martin-Montalvo, A., Saavedra, J., Ingles, S., de Cabo, R., Cohen, P., & Longo, V. (2011). Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans Science Translational Medicine, 3 (70), 70-70 DOI: 10.1126/scitranslmed.3001845

2. Baek, K., Zaslavsky, A., Lynch, R., Britt, C., Okada, Y., Siarey, R., Lensch, M., Park, I., Yoon, S., Minami, T., Korenberg, J., Folkman, J., Daley, G., Aird, W., Galdzicki, Z., & Ryeom, S. (2009). Down’s syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1 Nature, 459 (7250), 1126-1130 DOI: 10.1038/nature08062

3. Wang, X., Di Pasqua, A., Govind, S., McCracken, E., Hong, C., Mi, L., Mao, Y., Wu, J., Tomita, Y., Woodrick, J., Fine, R., & Chung, F. (2011). Selective Depletion of Mutant p53 by Cancer Chemopreventive Isothiocyanates and Their Structure−Activity Relationships Journal of Medicinal Chemistry, 54 (3), 809-816 DOI: 10.1021/jm101199t

Probiotics and Health Claims

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This month, Wiley will release Probiotics and Health Claims, a book that investigates the food, feed, and pharmaceutical applications and assessment procedures of probiotics around the world. We sat down with the book’s two editors, Wolfgang Kneifel and Seppo Salminen, to pick their brains about what, exactly, the term “probiotics” means, and how they predict probiotics will be used in the future.

  • What are probiotic microorganisms?
    The scientific definition has undergone some revision during the last decades. Briefly, probiotics are live microorganisms which exert certain beneficial properties to the host (human or animal) depending on their activity and cell density. The spectrum of effects seems to be increasing, and the mechanisms of action are not fully investigated so far, consequently opening up interesting perspectives for future research.
  • What are some of the most common ways probiotics are used in commercial products?
    In principle, there are three types of probiotic vehicles: food products (of which fermented dairy products can be regarded as the dominating segment), pharmaceutical preparations and dietary supplements (which come in different formats, ranging from capsules to tablets, drops and powders), and probiotic feeds.
  • How are probiotics developed?
    Usually, the development process of probiotics is a multidisciplinary one, where microbiologists, medical experts, nutritionists and technologists are cooperating. When formulating a defined product, these scientists start with an extensive screening of isolate candidates and then consider individual properties (e.g. identity and taxonomy, safety, stability, resistance, functional and technological criteria). Often, probiotics have been selected out of hundreds of possible candidates. They are assessed not only in laboratory tests and models, but also in dynamic models, followed by clinical trials under double-blind placebo-controlled conditions. Further in-depth information is contained in our book.
  • Are probiotics ever used for harm instead of health?
    Never. If so, they would not carry the name “probiotic”.
  • What do you think the future holds for companies and products which seek to make health claims?
    There is some evidence that both sides—i.e. the applicant (industry) as well as the assessing bodies—are undergoing a demanding period of progress and development. Very few probiotic claims worldwide have been officially endorsed. As discussion is still ongoing on this subject, it is difficult to foresee to what degree food product development, in general, will be affected health claim regulation in the future.
  • What is the most important piece of advice you can offer to non-scientists regarding probiotics?
     Advice of scientists to non-scientists needs to be simple and meaningful. In this context, scientists should be able to produce these sorts of statements, such as the following: “Probiotics can be regarded as the most prominent pacesetters bridging the two areas health and food like no other product. Probiotic foods are not to be seen necessarily as therapeutics, but they are a proper and attractive way of improving well-being, preventing discomfort, and reducing the risk of diseases.”
  • What inspired you to study Food Science?
     It was mainly the challenge of this topic’s inherent interdisciplinary nature.
  • In your lifetime, what would you consider to be the most significant scientific discovery in Food Science?
    Different milestones can be seen in the development of Food Sciences during the last 20-30 years, e.g. the invention of new processes guaranteeing maximum preservation of important nutrients and maintaining product quality and shelf-life. However, one particularly notable development is the advance of international networking for food safety issues. There is no doubt that food crises have shaken consumers as well as producers; however, the number of food crises has not increased. Rather, food crises have become more easily and readily recognizable due to global monitoring and control mechanisms, which causes them to appear to have become more numerous.

    Related work from these authors
    Handbook of Probiotics and Prebiotics, 2nd Edition
    by Yuan Kun Lee and Seppo Salminen

Stopping HIV in the Macrophage

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HIV is an elusive virus. Affecting more than 30 million people worldwide, the virus thrives in the human immune system by adapting in a number of ways, which makes effective treatments and an eventual cure exceedingly difficult. However, scientists at the University of Rochester and Emory University recently unveiled one of the mechanisms by which HIV is able to replicate itself inside the human immune system: dNTP substitution in macrophages.1 With this discovery, it is possible that new treatments are on the horizon.

HIV drugs typically target helper T Cells (CD4+ T cells)—the white blood cells that are eventually depleted by the virus. However, HIV also infects macrophages2—a derivative of monocytes—but until recently, scientists were unable to determine how the virus was able to thrive inside this kind of cell.

To replicate, HIV ordinarily uses the host’s own protein machinery—specifically the nucleoside dNTP (deoxynucleoside triphosphate), which is broken down to become a building block for DNA and RNA. However, dNTP is absent in macrophages, because macrophages don’t replicate. In lieu of dNTP, researchers Baek Kim and Raymond Schinazi found that the virus recruits a closely related molecule, rNTP (ribonucleoside triphosphate), to replicate. Kim and Schinazi then confirmed their findings by showing that when they blocked the ability of the virus to interact with rNTP, they reduced HIV’s ability to replicate in macrophages by more than 90%.

The ability to thwart HIV reproduction in macrophages could be a more effective than existing treatments at limiting the ravages of the virus for several reasons:

  1. Macrophages appear to be the first cells infected by HIV.
  2. Once helper T cells become depleted, macrophages may serve as the source of HIV production.
  3. Infected macrophages eventually spreads HIV to the central nervous system.

Some drugs that are already being tested for other purposes also happen to offer rNTP-targeting potential. Cordycepin, a compound derived from wild mushrooms, is one such drug; currently it is being tested as an anti-cancer drug, but it has also been shown to efficiently inhibit HIV-1 replication in macrophages.

Resources from Wiley on This Topic
Antiviral Drugs: From Basic Discovery Through Clinical Trials

by Wieslaw M. Kazmierski
HIV-1 Integrase: Mechanism and Inhibitor Design

by Nouri Neamati, Binghe Wang
AIDS and Tuberculosis: A Deadly Liaison

by Stefan H. E. Kaufmann and Bruce D. Walker

1. Kennedy EM, Gavegnano C, Nguyen L, Slater R, Lucas A, Fromentin E, Schinazi RF, & Kim B (2010). Ribonucleoside triphosphates as substrate of human immunodeficiency virus type 1 reverse transcriptase in human macrophages. The Journal of biological chemistry, 285 (50), 39380-91 PMID: 20924117

2. Benaroch, P., Billard, E., Gaudin, R., Schindler, M., & Jouve, M. (2010). HIV-1 assembly in macrophages Retrovirology, 7 (1) DOI: 10.1186/1742-4690-7-29