Wednesday, September 14, 2005

By Daniel J. DeNoon

Can removing a breast cancer cause rapid growth of tumors elsewhere in the body?

Yes, according to indirect evidence from a new analysis of clinical trial data. The controversial theory comes from Michael Retsky, PhD, of Children’s Hospital/Harvard Medical School in Boston, and colleagues.

“We say this is indirect evidence; we think this is a key to understanding the biology of breast cancer,” Retsky tells WebMD. “We certainly do not suggest any changes in clinical practice based on this. We hope this will entice clinical and experimental people to test these hypotheses.”

However, the theory is extremely controversial. A spokesman for the American Cancer Society says the findings are based on a misreading of existing data.

Big Tumors Fighting Little Tumors

Retsky and colleagues looked at long-term data on breast cancer patients treated in Italy. They saw two peaks in breast cancer relapse among premenopausal women whose cancer had spread to their lymph nodes. One relapse peak came very early — just 18 months after cancer diagnosis. The other started nearly five years after diagnosis.

This led them to a hypothesis. Cancers that relapse five or more years after cancer surgery, they suggest, come from single cancer cells in the body that grow slowly over time. Early relapses, they suggest, come from tiny, dormant cancers about 1 millimeter in size.

What makes these tiny cancers grow?

Animal studies show that big tumors give off chemical signals that keep smaller cancers from growing. When these big tumors are removed, the smaller cancers quickly grow blood vessels and become deadly.

The same thing may happen in some women after breast cancer surgery, Retsky says. And it’s seen only in younger women, he suggests, because reproductive hormones boost the cancer-enhancing effect.

Breast Cancer Screening Paradox

For more evidence, Retsky’s team looked at what some call the breast cancer screening paradox. It comes from observations in clinical trials comparing regular mammogram screening with no screening. In the first few years, women in their 40s who have mammograms — but not those in their 50s — have a higher risk of death than those not offered screening.

Over time, breast cancer screening shows a benefit for all women. But why the early increase in risk? Could it be due to women with node-positive breast cancer who suffer early relapses after surgery? Retsky suggests that it is.

Looking at data from studies of breast cancer screening, Retsky and colleagues saw about one excess death per 10,000 screened young women in the third year of screening. That, he says, is just what one would expect if his hypothesis is correct.

“It looked like surgery accelerated the disease by two years on average, which is the usual dormancy of this [blood vessel-free] tumor state,” Retsky says. “All the data show this.”

Even so, Retsky stresses, younger women with breast cancer still need surgery. He strongly advises women to continue to seek breast cancer screening — and, when a cancer is found, to have it removed.

“We don’t have all the answers,” Retsky says. “We think our work has pointed out that the mammography paradox is real. We are confident we understand what causes it. We have identified a problem — a mechanism that is testable. We have not found a solution. But identifying the problem is a major step in the right direction.”

Retsky and colleagues report their findings in the current issue of the International Journal of Surgery.

American Cancer Society Says It Isn’t So

Don’t believe any of this, says Robert A. Smith, PhD, director of cancer screening for the American Cancer Society.

“The data don’t add up to Dr. Retsky’s conclusion,” Smith tells WebMD. “The idea that surgical interruption of the tumor bed will cause death this rapidly just does not make sense.”

Smith, a strong proponent of early and regular breast cancer screening, says the apparent screening paradox does not exist.

“You do not expect mammograms to be instantly beneficial,” he says. “When you first invite women to screening, you get some with tumors that are already advanced. And not all of the women will respond to the invitation to screening. They may die next year or the year after, and because they were invited, they will be counted as a death in the screening group. So you really can’t look at this pattern and make any sense out of it.”

Young women, Smith says, tend to get more aggressive breast cancers.

“So the idea these women became worse after surgery may stem from the fact that their prognosis may have been poorer to begin with,” he says.

And Smith notes that Retsky’s data are based on observations from long ago, when breast cancer screening was in its infancy.

“The interesting thing is how beneficial modern, high-quality mammography can be,” he says. “Mammograms are quite a bit better today than in the clinical trials that proved they saved lives.”

By Daniel J. DeNoon, reviewed by Michael W. Smith, MD

SOURCES: Retsky, M.W. International Journal of Surgery, published online, Sept. 12, 2005. Michael Retsky, PhD, Children’s Hospital/Harvard Medical School, Boston. Robert A. Smith, PhD, director of cancer screening, American Cancer Society.

The kindness of strangers

On the fourth anniversary of 9/11, Americans find themselves once again counting the cost of an unimaginable catastrophe. This time though, the world has looked on not in awe at the human spirit arising from the ashes of the Twin Towers, but in shock and shame at the sight of the world’s richest country doing so little so late for its poorest people. The fallout from Hurricane Katrina will be weighed in thousands of lives lost and many more thousands wrecked (pp 526, 531, 582), and in further damage to America’s reputation around the world.

When the US government finally accepted offers of help from the United Nations last week, secretary general Kofi Annan might have been forgiven for feeling a certain degree of schadenfreude. This is after all also the UN’s 60th anniversary, an opportunity for the UN’s critics to crank up pressure to reform. Few would disagree that the UN is inefficient, bureaucratic, and encumbered with an impossibly broad mandate. In this week’s BMJ, Kelly Lee calls it “a management consultant’s worst nightmare” (p 525). But in the build up to next week’s UN summit, US criticism of the UN—embodied in the form of US ambassador, John Bolton—has moved beyond these well worn gripes to questioning key aspects of the UN’s strategy. Most significantly, Bolton has called for the removal from next week’s agenda of all reference to the millennium development goals (MDGs).

Whatever one’s view of the MDGs (seen by some as reflecting the priorities of donors rather than recipient nations and by most people as probably unachievable), they do focus attention in the rich world on the health needs of the poor. Targets give the international community a stick with which to beat itself when it falls short on commitments, as it is clearly doing (p 536).

The US government wants the world’s attention to shift elsewhere, but the UN must resist this, whatever threats its largest donor makes to withdraw funding. America’s own recent experience shows the dangers of diverting funds from routine public health initiatives to perceived, and probably overestimated, threats to homeland security. Erica Frank estimates that on 11 September 2001, and on every day since then, over 5000 people died in the US from 10 leading causes, including heart disease, cancer, and stroke (p 526). “Predictable tragedies happen every day,” she says, but funds are being diverted to prevent bioterrorism, leaving health departments in the US without money for basic disease surveillance. The most recent effects of the diversions of funds can be seen in the disastrous flooding after Hurricane Katrina.

The neglected levees will be repaired, the flood waters will recede, and street cars will again ply their routes to New Orleans’ sunken districts of Desire and Cemetery. But how much will America’s leaders be willing to learn from their unfamiliar and uncomfortable experience of having had to depend on the kindness of strangers?

Fiona Godlee, editor

Reported by www.longevinex.com:

For over a decade researchers have debated whether red wine produces health benefits because of its alcohol content, or because of other molecules in red wine. Now researchers at Nanjing Medical University in China report on the use of de-alcoholized red wine and cardiovascular health. Animals were fed alcohol, red wine, de-alcoholized red wine and pure research-grade resveratrol, a molecule found in red wine. Animals were then fed a high cholesterol diet and the human equivalent of 210 milligrams of resveratrol, or 280 millilters of red wine or alcohol-free red wine.

The results of the study are surprising. After 12 weeks the animals actually experienced a rise in circulating levels of total cholesterol, LDL cholesterol, and “good” HDL cholesterol regardless of whether they were fed alcohol, red wine, alcohol-free red wine or resveratrol.

However, while cholesterol plaque formed in the arteries (thoracic aorta) of the cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques were significantly reduced in rabbits given de-alcoholized red wine, red wine, or resveratrol. Resveratrol prevents cholesterol plaque from forming within artery wall regardless of whether circulating levels of cholesterol are high or low!

Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels.
International Journal Molecular Medicine 16:533-540, 2005
Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM.
Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, P.R. China.

Moderate consumption of red wine is associated with a reduced risk of coronary heart disease (CHD). This phenomenon is based on data from epidemiological observations known as the French paradox, and has been attributed to CHD-protective phytochemicals, e.g. resveratrol in red wine. Since red wine also contains alcohol, it is conceivable that alcohol interacts with resveratrol to elicit the observed cardioprotective effects.

To determine whether resveratrol has alcohol-independent affects, we compared cardioprotective properties of dealcoholized Chinese red wine with alcohol-containing Chinese red wine having comparable amounts of resveratrol, using a hypercholesterolemic rabbit model and resveratrol as a reference. Animals fed a high cholesterol (1.5%) diet were simultaneously given water containing resveratrol (3 mg/kg/day) or red wine (4 ml/kg/day) containing 3.98 mg/l and 3.23 mg/l resveratrol for regular and dealcoholized red wine, respectively, for a 12-week duration. Total, HDL- and LDL-cholesterol and triglyceride levels in the plasma were measured before and after the cholesterol challenge. Atherosclerotic plaques in the thoracic aorta were evaluated using histochemical methods. Vascular and endothelial functions in the femoral artery were also assessed by ultrasonographic image analysis.

High cholesterol-fed animals showed a significant increase in plasma levels of total, HDL- and LDL-cholesterol, but not triglycerides, compared to those fed a regular diet. Dietary cholesterol-elicited lipid changes were similarly observed in animals concurrently fed dealcoholized red wine, red wine or resveratrol. In contrast, whereas atherosclerotic lesions were clearly evident in specimens prepared from the thoracic aorta of high cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques, and thickness of the intima layer were significantly reduced in rabbits given dealcoholized red wine, red wine, or resveratrol.

These results were in agreement with data obtained by an ultrasound analysis of endothelial function, which showed a 25% reduction in flow-mediated dilation (FMD) in rabbits fed a high cholesterol diet compared to animals on control diet. This decrease was effectively prevented by the simultaneous exposure to dealcoholized red wine, red wine, or resveratrol. Our study shows that animals given dealcoholized red wine exhibited cardio-active effects comparable to those of animals orally administered resveratrol, and suggests that wine polyphenolics, rather than alcohol present in red wine, suffice in exerting cardioprotective properties. The results also provide support for the notion that resveratrol and phytochemicals in red wine can suppress atherosclerosis without affecting plasma lipid levels.

Olive oil reveals its hidden virtue
New Scientist, Sep 2005

EXTRA-virgin olive oil has a similar anti-inflammatory effect to ibuprofen. That may help explain why the Mediterranean diet, rich in olive oil, protects against heart disease, cancer and Alzheimer’s disease.

Paul Breslin and his team at the Monell Chemical Senses Center in Philadelphia have discovered that olive oil contains the compound oleocanthal which, like ibuprofen, turns out to be a COX-1 and COX-2 inhibitor (Nature, vol 437, p 45). “Structurally it’s not similar, but pharmacologically it’s very similar,” says Breslin.

About 50 millilitres of olive oil a day effectively amounts to a low-dose anti-inflammatory, the researchers say.

Am J Physiol Regul Integr Comp Physiol (July 14, 2005). doi:10.1152/ajpregu.00834.2004

Vitamin E at high doses improves survival, neurological performance and brain mitochondrial function in aging male mice

Ana Navarro^1*, Carmen Gomez¹, Maria-Jesus Sanchez-Pino¹, Hipolito Gonzalez¹, Manuel J Bandez¹, Alejandro D , and Alberto ²

¹ Department of Biochemistry and Molecular Biology, School of Medicine, University of Cadiz, 11003-Cadiz, Spain
² Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD-Buenos Aires, Argentina
E-mail: [email protected]

Male mice receiving vitamin E (5.0 g alpha-tocopherol acetate/kg of food) from 28 wk of age showed a 40 % increased median lifespan, from 61 ± 4 wk to 85 ± 4 wk, and 17 % increased maximal lifespan, whereas female mice equally supplemented exhibited only 14 % increased median lifespan.

The alpha-tocopherol content of brain and liver was 2.5-times and 7-times increased in male mice, respectively. Vitamin E-supplemented male mice showed a better performance in the tightrope (neuromuscular function) and the T-maze (exploratory activity) tests with improvements of 9-24 % at 52 wk and of 28-45 % at 78 wk. The rates of electron transfer in brain mitochondria, determined as state 3 oxygen uptake and as NADH-cytochrome c reductase and cytochrome oxidase activities, were 16-25 % and 35-38 % diminished at 52-78 wk. These losses of mitochondrial function were ameliorated by vitamin E supplementation by 37-56 % and by 60-66 % at the two considered time points. The activities of mtNOS and Mn-SOD decreased 28-67 % upon aging and these effects were partially (41-68 %) prevented by vitamin E treatment. Liver mitochondrial activities showed similar effects of aging and of vitamin E supplementation, although less marked. Brain mitochondrial enzymatic activities correlated negatively with the mitochondrial content of protein and lipid oxidation products (r² = 0.58-0.99, p < .01) of respiration and of complex I and IV activities correlated positively (r² = 0.74-0.80, p < .01) behavioral tests and with maximal lifespan.

A 2-month-old mouse deficient in the Klotho protein, center, shows signs of aging, compared with a normal mouse, left. A 3-year-old mouse with an overabundance of the protein, right, has lived beyond the normal life span. (By Aline Mckenzie — University Of Texas Southwestern Medical Center At Dallas)

Life-Lengthening Hormone Found in Mouse Research
By Rob Stein
Washington Post Staff Writer
Friday, August 26, 2005; Page A01

Scientists have identified a hormone that significantly extends the life span of mice, a discovery that could mark a crucial step toward developing drugs that boost longevity in people.

The hormone is the first substance identified that is produced naturally in mammals, including humans, and can extend life span — a long-sought goal in the intense effort to help people live longer.

Much more work is needed to study the substance, and investigate whether the hormone or a similar compound would be effective and safe in people, experts cautioned. But the discovery opens highly promising avenues for research and provides tantalizing new clues toward deciphering the basic biology of aging.

“This is a significant discovery. It’s an exciting paper,” said Anna McCormick of the National Institute on Aging, which helped fund the new research, published online yesterday by the journal Science. “It’s definitely the way you would go about designing molecules that would promote healthy aging and longevity in people.”

Makoto Kuro-o of the University of Texas’s Southwestern Medical Center at Dallas, who led the research, said, “This could provide a key to understanding the molecular mechanisms of aging and opens up new areas to the potential therapy for multiple age-related diseases in humans.”

The discovery was triggered by a study Kuro-o and his colleagues published in 1997. That study identified a gene in mice that, when damaged, caused the animals to experience all the hallmarks of aging in humans — hardening of the arteries, thinning bones, withered skin, weak lungs — and to die prematurely. They dubbed the gene Klotho, for the Greek goddess who spins the thread of life.

Suspecting the gene may play a role in regulating life span, Kuro-o and his colleagues genetically engineered mice with overactive Klotho genes. In the latest experiments, they found that these animals lived an average of 20 to 30 percent longer than normal — 2.4 to 2.6 years vs. a normal life span of about two years — without any signs of ill effects, according to the new report.

Dr. Jeff Sutherland and Dr. Dick Loyd will discuss their latest findings in identifying frequencies for balancing the body and improving health, well-being and longevity.

Many people have asked for help in using the Cameron Aurameter and saliva testing to identify frequencies. New ways to use the FSCAN for scanning the body, the Advanced Biophoton Analyzer for remote transmission of frequencies, and the new F165 frequency generator will be discussed. Hardware and cabling for enhancement of these devices will be explained along with plate zapping techniques to target specific organ systems and enhance their function. The workshop will be as hands on as possible given space and time constraints.

It will be held at the Doubletree Guest Suites Seattle-Southcenter about 15 minutes from the Seattle airport (not the SeaTac Doubletree). Discounts on rooms are available by talking to Doubletree manager Karen Dodge at 206-575-8220.

The workshop will be held from 9am to 5pm on Saturday, 20 August 2005 and the early bird registration fee is $295 until 15 August. Late registration will be $350. There will be a reception on Friday evening prior to the workshop at 5:30-6:30pm followed by presentations and discussion with Dr. Sutherland and Dr. Loyd. The fee for the reception is $25 for workshop participants and $50 for those only attending the reception.

All questions on the workshop should be directed to Dale Fawcett at (360) 598-6585. You can sign up for the workshop by clicking on the link below – Paypal or credit cards.

Seattle Workshop, Early Bird Registration – $295
Seattle Workshop plus Reception, Early Bird Registration – $320Seattle Reception Only – $50

Frequency research is going on in labs all over the world and new technology is often first used by the military. Deriving positive uses of military technology in medicine typically takes decades due to systemic suppression of innovation. See comments from the Harvard Business Review in a previous posting.

Israelis unleash Scream at protest
New weapon knocks crowds off feet
Sound blast triggers nausea, dizziness
Mitch Potter
MIDDLE EAST BUREAU

JERUSALEM—The knees buckle, the brain aches, the stomach turns. And suddenly, nobody feels like protesting anymore. Such is the impact of the Scream, the latest weapon in the Israeli army’s high-technology toolkit.Launched Friday afternoon near the West Bank village of Bil’in, after another in the almost daily demonstrations against Israel’s controversial security barrier turned violent, Israel’s secret weapon lived up to its billing, by most accounts.

Witnesses describe a minute-long blast of sound emanating from a white Israeli military vehicle. Within seconds, protestors began falling to their knees, unable to maintain their balance. An Israeli military source, speaking on the customary condition of anonymity, confirmed the existence of the Scream, or Tze’aka in Hebrew, in an interview yesterday.

“The intention is to disperse crowds with sound pulses that create nausea and dizziness,” the Israel Defence Force spokesperson told the Toronto Star. “It is probably the cleanest device we have ever had, when you compare it to rubber bullets or tear gas. It is completely non-lethal. It has no adverse effects, unless someone is exposed to the sound for hours and hours.”

IDF officials said the technology was researched and developed over a span of five years as a result of “lessons learned” during the Israeli army’s withdrawal from Lebanon.

Aspartame induces lymphomas and leukaemias in rats
Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Luca Lambertini
Eur. J. Oncol., 10 (2), 00-00, 2005

Aspartame, a widely used artificial sweetener, was administered with feed to male and female Sprague-Dawley rats (100-150/sex/group), 8 weeks-old at the start of the experiment, at concentrations of 100,000; 50,000; 10,000; 2,000; 400; 80 and 0 ppm. Treatment lasted until spontaneous death of the animals. In this report we present the first results showing that aspartame, in our experimental conditions, causes a statistically significant, dose-related increase in lymphomas and leukaemias in females. No statistically significant increase in malignant brain tumours was observed
among animals from the treated groups as compared to controls.