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Common virus linked to deadly brain cancer.

Few people would ever suspect that one of the most deadly forms of brain cancer is caused by a common virus carried by the majority of people. Yet that's exactly the case, according to a number of new studies in prestigious medical journals.

In the same way that cervical cancer and head and neck cancer has been linked to certain strains of the HPV virus, the most common and deadly type of brain cancer, glioblastoma, has been linked to a virus in the herpes family called CMV (short for cytomegalovirus). (6), (7)

A diagnosis of glioblastoma means certain death, with population studies indicating typical overall survival rates of less than a year. (8) And unfortunately, this deadly form of brain cancer is the most common malignant brain tumor in the US. (8)

Establishing a link between this deadly cancer and a common virus is an enormous step in understanding how to treat, and potentially to prevent, early and unnecessary deaths. And more importantly, it led to the discovery of a drug that can quadruple the life span of those who have already been diagnosed with this deadly disease! (1)

The Dangers Of The CMV Virus

Cytomegalovirus, or CMV, may be the most impor-tant virus you've never heard of. The prevalence of latent CMV infection is up to 100% in most popula-tions of adults worldwide with increasing prevalence in the elderly, and is now considered to play multiple roles in immunosenescence, the gradual fading of immune function with age. (9), (10)

This is a serious problem. Latent CMV infections are strongly associated with frailty in the elderly and dramatically increases mortality risk. (11), (12) CMV has also been associated with accelerated aging in general, and even with shortening of telomeres (the age-regulating bits of DNA that govern each cell's lifespan). (13) Indeed, a 2013 study found disturbing early signs of immunosenescence in young people who tested positive for CMV, compared with their CMV-negative peers. (14)

And of course, waning immune function also opens the door for cancers to develop, freed of the ever-present surveillance carried out by a younger, more robust immune system.

And that's just with the latent form of the virus; the active form is far worse. Active CMV disease in older patients or in those with compromised immune systems is a devastating disease. It can cause hepatitis leading to liver failure, retinitis leading to blindness, severe colitis (large bowel inflammation), pneumonitis (viral pneumonia), esophageal inflammation, and disorders of the central and peripheral nervous systems. (15), (16)

But unlike other herpes viruses, CMV rarely produces detectable symptoms in otherwise healthy people. (16) That makes it difficult to diagnose, and dangerously easy to spread. Diagnosing CMV often requires two separate blood tests, several weeks apart, as well as a high index of suspicion by both patient and provider (see sidebar on the next page for an understanding of test results). (17) CMV spreads the way other herpes viruses do: by contact with bodily secretions, especially saliva. (18)

The ease of spread and the absence of symptoms in healthy adults accounts for the very widespread prevalence of CMV. (18) Estimates vary, depending on geography, socioeconomic status, and other variables, but at least 35%, and up to 100% of people in some communities, will test positive for CMV. (19-21)

CMV: The Cancer Connection

Over the past decade, scientists have become increasingly concerned at the growing association of CMV with certain cancers. While it is too early to label CMV a true cancer-causing virus, (22) evidence implicating CMV as a contributor to cancer comes from several observations:

* Studies show a strong correlation between cancer incidence and the percentage of adults who test positive for CMV.(23), (24)

* CMV proteins and DNA have been found in 90-100% of malignant cells from a variety of cancers, especially those of the brain, breast, prostate, liver, lung, and colon.(1), (25-33)

* CMV genes, once inserted into the host's own DNA, increase inflammation-generating genes that promote cancer growth.(34), (35)

* CMV genes are known to induce mutations in host tumor-suppressor genes, increasing the risk that a new cancer will develop. (36)

* CMV may help cancer cells avoid detection by the immune system by several mechanisms including increased secretion of immune suppressive cytokines. (22)

* CMV-infected cells produce more of the growth factors and chemical receptors needed for tumor development and invasion, compared to non-infected cells.(32), (33), (37)

The evidence for a direct connection between CMV and malignancy is by far the greatest in the case of the deadly brain tumor called glioblastoma multiforme (often simply "glioblastoma"). This tumor is the most common and aggressive brain cancer, and it carries a dismal prognosis.(38), (39)

Most patients die within the first 15 months of diag-nosis, with few surviving past 3 years.(40-42)

Glioblastomas occur most commonly in the frontal and temporal (side) lobes of the brain, where they produce disturbing symptoms that include persistent headaches, double or blurred vision, vomiting, changes in mood and personality, changes in cognition, seizures, and speech difficulty. (42)

In addition to their aggressive growth, glioblasto-mas are notoriously difficult to treat because of their location within the brain, where efforts to extract them are complicated by their deep invasion of healthy brain tissue and the brain's limited ability to repair itself.(10), (42) Patients with glioblastomas frequently experience a number of clinical complications including seizures, blood clots, fluctuating neurological symptoms as well as side effects from powerful corticosteroids and chemotherapeutic drugs. (43)

Glioblastomas leak fluid, increasing the pressure on brain tissue; they also disrupt the blood supply, making it difficult for anti-cancer drugs to reach them. (42)

All of this accounts for the fact that, despite three decades of research, we have managed to increase overall survival in cases of glioblastoma by only about 3 months.(42), (44) Making matters worse, the tumor strikes at the prime of life, occurring mainly in adults between 45 and 70, with a median age at death of 64 years. (42)

The high incidence of glioblastoma, coupled with the difficulty of its treatment, has made the search for causes and preventive measures paramount. That's why this emerging evidence about the link between CMV and malignant brain tumors is exciting to so many researchers. (34)

Strong Link Between CMV And Brain Cancer

There are a number of lines of evidence closely linking CMV with glioblastomas specifically, as well as to cancer in general. Virtually all glioblastomas have been found to contain CMV particles, proteins, and DNA (in one study of 250 patients, only one was CMV-negative).(1), (2), (45) In fact, the amount of CMV in a glioblastoma is closely correlated with the tumor stage: More advanced tumors contain more CMV.22 Recent studies show that the amount of CMV in a tumor can accurately predict survival time in glioblastoma victims, with those carrying the most virus dying significantly earlier (average 13 months) than those with lower viral burden (average 33 months).(45), (46)

Ironically, and tragically, further evidence of CMV involvement in glioblastoma comes from treatment misadventures with the cancer chemotherapy drug temozolomide. This drug, one of the few approved for treating glioblastoma, is powerfully immunosuppres-sive.47 In glioblastoma patients being treated with temo-zolomide, reports are now appearing of the emergence of active and devastating CMV disease, indicating that the virus had lain dormant until the patients' immune systems were suppressed by this chemo drug. (47), (48)

There's a glimmer of hope on the horizon, however, the direct result of our understanding of the CMV/glio-blastoma connection.

Antiviral Drug Quadruples Life Span!

Researchers at the internationally acclaimed Karolinska Institute in Sweden recently made medical headlines with their findings about the use of an antiviral drug quadrupling the lives of patients with glioblastomas. (1) The drug, valganciclovir, is widely used in treatment of active CMV infection in immunocompromised patients.

Beginning with an animal model, the researchers found that they could reduce the growth of medullo-blastomas (the main group of brain tumors to which glioblastomas belong) by 72% using a drug combination including valganciclovir to combat CMV infection. (34)

Next, they wanted to determine how effective valganciclovir would be as an add-on to chemotherapy. In a double-blind clinical trial, researchers gave valganciclovir to 42 glioblastoma patients already receiving standard chemotherapy. (49) Although tumor sizes were smaller in treated than in non-treated patients, the difference was not statistically significant. There were no significant differences in survival over the 6 months of the study period.

However, that all changed when patients were allowed to continue taking the drug after the study phase. Analyses showed that patients taking valganciclovir for longer than 6 months had an overall survival of 24.1 months, compared with just 13.1 months (a typical survival time) in patients taking the drug for 0 to 6 months. (49) By 4 years (an eternity for glioblastoma patients), 27.3% of long-term valciclovir patients survived, compared with just 5.9% of controls.

Encouraged by these results, the researchers immediately undertook another study, again providing valganciclovir as add-on to regular chemotherapy--but this time, extending the study period beyond the original 6-month time frame. (1) Fifty patients were treated and compared with controls who received only standard care. In the authors' own words, "The rate of survival of treated patients was remarkably high"--an understatement considering the facts. Take a look:

* At 2 years, 62% of all treated patients were still alive, compared with just 18% of controls with comparable cancers. (1) Median over-all survival was 25 months, vs. 13.5 months in controls (Figure 1A).

* Among those who received at least 6 months of valganciclovir, the 2-year survival rate was 70% and median overall survival was 30.1 months (Figure 1B). (1)

* And, among the 25 patients who received continuous valganciclovir treatment after the first 6 months, 90% of patients were alive at 2 years, and median overall survival was an incredible 56.4 months--that's more than 4 1/2 years, or a 4.2-fold increase over the 13.5 months in control patients.(1) (Figure 1C)

In other words, even short-term treatment with valganciclovir nearly doubled overall survival time; medium-term therapy nearly tripled survival time, and long-term, continuous therapy more than quadrupled it.

These are compelling results. At this point, anyone with a diagnosis of glioblastoma and a desire to extend their lives as much as possible should demand therapy with oral valganciclovir, at 900 mg/day twice daily, followed by a maintenance dose of 450 mg twice daily, with adjustments as needed for impaired kidney function and bone marrow suppression.

What About The Rest Of Us?

As exciting as the results of this study were for those battling glioblastoma, valganciclovir is prohibitively expensive to use as a preventive drug. It can cost upwards of $50,000/year and has myriad side effects, including plummeting white blood cell counts. (50)

There are no known drugs or supplements that can prevent primary infection with CMV in humans. However, if you are CMV-positive (like so many Americans), there are a number of ways you can protect yourself against the effects of the virus, including protecting against immunosenescence, the immune aging that triggers CMV activation.

Fight CMV-Related Immunosenescence Naturally

Although no human data exist yet, there's striking evidence that certain natural compounds can inhibit the replication and spread of CMV in animal and basic lab studies.

These include Urtica dioica (stinging nettle), garlic extract, Terminalia chebula (an Asian tree), ginger extracts, flavones from ginger-like Kaempferia parvi-flora, a variety of seaweed extracts, and oil from Nigella sativa (black cumin seed).(51-58) Black cumin seed oil in particular was so effective in mice that, after 10 days of treatment, no virus was detected in treated animals, while it was readily detectable in control mice.(55)

Other nutrients can fight the CMV that may already be in your body by enhancing your immune system's resources to fight CMV, as well as other infections that arise when immunosenescence sets in. These include the following:

* Probiotics and prebiotics, by balancing the intestinal microbial population, have powerful immune-stimulating properties. (59), (60) Studies show that probiotic/prebiotic therapy produces improvements in natural killer cell activity, activated T-lymphocytes (including "memory" cells responsible for recognizing old enemies), and cell signaling molecules called cytokines. (61-64)

* Elderly people are more likely to be deficient in zinc, a trace element absolutely required for normal immunity.(65) Zinc supplementa-tion fights immunosenescence by enhancing the appropriate immune response to stress in older humans and by increasing appropriate cytokine signaling to mobilize response to infection.(66), (67)

* Sulfur-containing antioxidants such as N-acetylcysteine help replenish the body's normal stores of natural antioxidants, which helps keep immune system cells fresh and vigorous. These supplements improve white blood cell function, increasing their ability to track and attack invaders, and increas-ing white cell proliferation in response to invasion. (68) Aged mice fed a diet rich in N-acetylcysteine and thioproline for 5 weeks showed an improvement in all immune func-tions, with values becoming close to those of young adult animals. (69)

* Spirulina, a blue-green algae, increases the microbe-eating activity of white blood cells called macrophages, while stimulating anti-body production and activating killer T-cells that destroy viruses and fungi. (70-72)

* Finally, the prescription drug metformin (which is in fact a natural derivative of the French lilac) has shown great promise in reducing immunosenescence and fighting CMV and CMV-related cancers. (73) Metformin has shown surprisingly beneficial results in combination with standard treatments for breast cancer, (74) and is now being closely investigated as an additional treatment for glioblastoma. Similar studies showed that metformin inhibits growth and migration of glioblastoma cells, a property that would reduce the tumor's invasiveness in patients' brains. (75) Excitingly, metformin has now also been shown to promote differentiation of Glioblastoma-initiating cells into non-cancer-producing cells in lab cultures.(76)

Summary

Recent research has established a surprising con-nection between a common virus, CMV, and a deadly brain tumor, glioblastoma. This relationship opens the door to a variety of forms of treatment and prevention of brain and other cancers.

At present, even with chemotherapy, survival in glioblastoma patients is rarely more than 15 months after diagnosis. (42)

But CMV proteins and DNA are found in the vast majority of glioblastomas removed at surgery, and the amount of CMV has been found to correlate closely with the severity of the tumor. (1), (2), (22), (45) This suggests that anti-CMV treatment might ameliorate glioblastoma and improve prognosis.

Indeed, treatment with valganciclovir, a specific anti-CMV drug, has been shown to dramatically increase overall survival in two studies of glioblastoma patients--as much as quadrupling life span! (1), (49)

However, for those with the CMV virus, but without glioblastoma, there are a few supplements that may help fight CMV infection and can mitigate its impact on your body.(51), (58)

You should consider being tested for CMV, by means of a blood test described in the sidebar on page 87. If you test positive, then start some of the recommendations made in this article.

The comforting news for Life Extension[R] members is that they have been supplementing with immune boosting nutrients for many decades.

If you have any questions on the scientific content of this article, please call a Life Extension[R] Health Advisor at 1-866-864-3027.S

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Title Annotation:cytomegalovirus
Author:Antone, Lisa
Publication:Life Extension
Article Type:Report
Geographic Code:1USA
Date:Feb 1, 2014
Words:4710
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