Highlight HEALTH

As 2007 comes to a close, I would like to thank you for your readership. Just over one year ago, I launched two websites, Highlight HEALTH and the Highlight HEALTH Web Directory. Here at Highlight HEALTH, my goal was to write about biomedical research I found interesting and to make it easier for people to understand research findings, empowering them to have more productive discussions with their physicians and to make informed decisions about healthcare. The Highlight HEALTH Web Directory is my endeavor to catalog and make available health-related websites I find to be informative and useful. More recently, I’ve also started writing about Web 2.0 in Health, Fitness and Medicine, and plan to publish a series of review articles on a number of health-focused social networks.

This past month, I started the Highlight HEALTH Network, an aggregation of content from both sites to allow readers to keep up with the latest articles on Highlight HEALTH and the newest additions to the Highlight HEALTH Web Directory, all from a single source.

Here are the most popular articles for 2007 (top 20 based on the number of page views/number of days posted):

1. The Highlight HEALTH Network RSS Dashboard Widget
2. Smoking Cessation Timeline: What Happens When You Quit
3. Dichloroacetate Not Ready for Therapeutic Use
4. The Highlight HEALTH Network
5. New Common Cold Virus Variant Deadly
6. Common Therapy for Prostate Cancer May Promote Metastasis
7. Overweight Kids and TV: An Advertising Epidemic
8. Saline Nasal Irrigation More Effective than Spray for Chronic Sinus Symptoms
9. Pediatric Grand Rounds 2.8
10. The Genetics of Panic Disorder
11. Smoking Duration vs. Intensity and the Impact on Lung Cancer Risk
12. Social Networks and Health - The Research and the Reviews
13. Quercetin
14. American Obesity Rate Levels Off
15. Biodegradable Polymers for Drug and Gene Delivery
16. Individual Genetics, Coffee Consumption, BRCA1 and Breast Cancer
17. The Flu, Your Health and the Importance of Vaccination
18. SCHIP Funding and Fiscal Irresponsibility
19. DNA Amplification by Polymerase Chain Reaction (PCR)
20. Sinus Congestion

Thank you and Best of Health in the coming year!

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A study published in the journal Cancer Research last month suggests that the principle treatment for advanced prostate cancer may actually encourage prostate cancer cells to metastasize [1]. Researchers at The Johns Hopkins University School of Medicine focused on a gene called Nestin, which encodes an intermediate filament protein. Intermediate filaments are cytoskeletal or scaffolding structures found in cells that, in addition to maintaining cell shape, control a variety of cellular processes including proliferation, migration and survival [2]. Nestin gene expression also distinguishes stem cells from differentiated cells and has been shown to be activated in pediatric brain tumors and rhabdomyosarcomas (cancers that develop from skeletal muscle), central nervous system tumors and gastrointestinal stromal tumors [3-6].

The Prostate and cancer

The prostate is a small, walnut-sized gland that is located beneath the bladder and wrapped around the urethra in men. The urethra is a tube that carries urine from the bladder and semen from the epididymis. A male sex gland, the prostate secretes components of prostatic fluid, which forms part of the semen that carries sperm.

The prostate can be affected by a number of problems, including:

1. Prostatitis (inflammation of the prostate)
2. Benign Prostatic Hyperplasa (BPH, an enlarged prostate)
3. Prostate cancer

Prostate cancer is the most common male neoplasia (meaning abnormal proliferation of cells in a tissue or organ) and is the leading cause of cancer death in American men [7]. It is a heterogeneous disease (meaning that the disease consists of a wide spectrum of presentations with variable response to treatment) ranging from asymptomatic to a rapidly fatal systemic malignancy, and progresses from pre-cancerous lesions, termed prostatic intraepithelial neoplasia (PIN), to invasive adenocarcinoma and ultimately to metastatic disease [8-10].

Androgen is the generic term for a group of steroid hormones, including testosterone, that principally influence the growth and development of the male reproductive system. Androgens affect prostatic epithelial cell differentiation and proliferation. The mainstay of treatment for advanced prostate cancer is androgen deprivation therapy, i.e. surgical or medical castration (meaning the use of surgery or drugs to suppress androgen production). However, despite high initial response rates to androgen deprivation, virtually all men progress to androgen-insensitive or androgen-independent prostate cancer. Thus, while early detection and treatment are generally associated with favorable clinical outcomes, there are presently no curative interventions for patients with advanced disease.

Nestin expression is linked to androgen withdrawal and affects cell migration

In cell lines derived from metastatic prostate cancer, Johns Hopkins researchers found that Nestin gene expression was elevated only in androgen-independent cells. They then examined Nestin gene expression in prostate cancer samples from 254 patients that encompassed the entire clinical spectrum of the disease, from untreated localized tumors to lethal metastatic cases. Increased levels of Nestin gene expression were found exclusively in lethal cases following androgen deprivation therapy. No detectable Nestin was found in prostate cancers that had not been subjected to the therapy. In an androgen-independent cell line derived from metastatic prostate cancer, loss of Nestin expression had no effect on cell viability or growth rate but was shown to greatly reduce cell motility. In a mouse model of human prostate cancer, compared to control tumors, transplanted prostate cancer cells with reduced Nestin expression produced one fourth the number of metastatic deposits and the deposits were dramatically reduced in size. The study thus identifies a specific role for Nestin in cell motility and a novel pathway for prostate cancer metastasis.

In the same issue of Cancer Research, another study in a genetically engineered mouse model of human prostate cancer demonstrated that prolonged exposure of the mice to reduced levels of androgen accelerated prostate tumor development compared to mice exposed to physiologically normal levels of androgen [11]. The mice displayed a molecular profile similar to that of mice with androgen-independent prostate tumors. The finding is significant since the mouse model is based on the loss-of-function of genes known to be relevant for human prostate cancer and is consistent with the conclusions of the first study described above.

Taken together, these results suggest that androgen deprivation therapy encourages prostate cancer cells to accelerate tumor development, making them more likely to spread throughout the body. While these results are too preliminary to alter current clinical practice, the findings warrant further study. Although the effects of androgen deprivation therapy are temporary, it is an effective treatment for slowing prostate tumor growth and can boost the effect of neoadjuvant therapy (e.g. radiation therapy used to shrink a tumor prior to surgical removal).

References

1. Kleeberger et al. Roles for the Stem Cell–Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis. Cancer Res. 2007 Oct 1;67(19):9199-206.
   View abstract
2. Coulombe and Wong. Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat Cell Biol. 2004 Aug;6(8):699-706.
   View abstract
3. Almqvist et al. Immunohistochemical detection of nestin in pediatric brain tumors. J Histochem Cytochem. 2002 Feb;50(2):147-58.
   View abstract
4. Kobayashi et al. Pediatric rhabdomyosarcomas express the intermediate filament nestin. Pediatr Res. 1998 Mar;43(3):386-92.
   View abstract
5. Dahlstrand et al. Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res. 1992 Oct 1;52(19):5334-41.
   View abstract
6. Tsujimura et al. Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal. Am J Pathol. 2001 Mar;158(3):817-23.
   View abstract
7. Cancer Facts & Figures 2007. American Cancer Society. Atlanta, Ga. 2007.
8. DeMarzo et al. Pathological and molecular aspects of prostate cancer. Lancet. 2003 Mar 15;361(9361):955-64.
   View abstract
9. Isaacs et al. Focus on prostate cancer. Cancer Cell. 2002 Aug;2(2):113-6.
   View abstract
10. Nelson and Montgomery. Unconventional therapy for prostate cancer: good, bad or questionable? Nat Rev Cancer. 2003 Nov;3(11):845-58.
    View abstract
11. Banach-Petrosky et al. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Res. 2007 Oct 1;67(19):9089-96.
    View abstract

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