Highlight HEALTH

Welcome to the 7th edition of the Cancer Research Blog 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 Blog 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.
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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.
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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.
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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.
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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.
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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.
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10. Hüsemann et al. Systemic spread is an early step in breast cancer. Cancer Cell. 2008 Jan;13(1):58-68.
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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].
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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.
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13. Johns and Houlston. A systematic review and meta-analysis of familial prostate cancer risk. BJU Int. 2003 Jun;91(9):789-94.
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14. Straif et al. Carcinogenicity of shift-work, painting, and fire-fighting. Policy Watch, The Lancet Oncology. 2007 Dec;8(12):1065-1066.

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!

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.
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2. Coulombe and Wong. Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat Cell Biol. 2004 Aug;6(8):699-706.
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3. Almqvist et al. Immunohistochemical detection of nestin in pediatric brain tumors. J Histochem Cytochem. 2002 Feb;50(2):147-58.
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4. Kobayashi et al. Pediatric rhabdomyosarcomas express the intermediate filament nestin. Pediatr Res. 1998 Mar;43(3):386-92.
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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.
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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.
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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.
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9. Isaacs et al. Focus on prostate cancer. Cancer Cell. 2002 Aug;2(2):113-6.
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10. Nelson and Montgomery. Unconventional therapy for prostate cancer: good, bad or questionable? Nat Rev Cancer. 2003 Nov;3(11):845-58.
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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.
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