Study Suggests How Cancers Spread to Lungs

Cancers typically spread -- or metastasize -- to specific, predictable locations. Now researchers have a deeper molecular understanding of why, at least for lung metastases in mice.

The finding might someday lead to drug therapies that curb lung cancer metastasis in humans, experts say.

Dr. Yoshiro Maru of the Tokyo Women's Medical University and colleagues report that primary tumors transmit a series of signals throughout the body to "prepare the soil" in the lungs to accept the "seed" of a metastatic cell from solid tumors located elsewhere.

The key players in this process are signaling proteins, which pass back and forth like text messages between the tumor and the premetastatic lung, and then from the premetastatic lung to the tumor and the bone marrow.

"I think the important part of the paper is that it's putting molecules on these pathways between different cells ... and between the primary tumor and the soil," said Mikala Egeblad, an assistant research anatomist at the University of California, San Francisco.

Just as important, the new study suggests that blocking these signaling interactions could inhibit the ability of tumors to metastasize to the lungs.

The findings were published online Sept. 28 in the journal Nature Cell Biology.

According to Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, much has been learned about what differentiates a benign growth from a more aggressive cancer, as well as the characteristics of cells that break off from a primary tumor and make their way to distant sites within the body -- that is, to metastasize. This study, however, examines how a tumor is able to colonize a particular tissue -- in this case, the lungs.

"This research takes a look at what allows the cancer cells to set up a home in the lungs of the mice," Lichtenfeld said. "By understanding that mechanism, they potentially could incorporate that theory into the treatment of patients and perhaps, by understanding those mechanisms, you may be able to take advantage of that to prevent that [metastasis] from happening."

Studying lung metastases in mice, Maru and his team investigated the cellular signals that accompany tumor migration to the lung. What they discovered was a sort of signaling cascade -- a series of protein messages flashing back and forth throughout the body.

According to their theory: Suppose a tumor in the colon or breast is preparing to metastasize. Before it does so, it sends out specific proteins called growth factors throughout the body.

In cancer-free lungs, local cells respond by producing a second signal: a pair of molecules called S100A8 and S100A9. Nearby lung monocytes respond to these messages by producing the third and final message, called SAA3. This causes immune cells called macrophages to amplify the signal even further, driving both immune cells and tumor cells to migrate to the lungs.

Both of those cell types express the receptor for SAA3 -- a protein called TLR4. According to Maru, "that's a big problem," because TLR4, in a healthier context, induces immune cells to get on the move. But in this case deadly cancer cells get moving, too.

In this way, "the tumor prepares the soil, the pre-metastatic site, prior to its settlement," Maru said.

According to Egeblad, this study suggests "how the tumor is preparing organs, and particularly lungs, so that when the cancer cells arrive, they have an easier time staying and growing."

Added Lichtenfeld, "If they can interfere with that mechanism, they can prevent that [metastasis] from happening, and this could then become an important part of cancer treatment in the future."

More information

For more on lung cancer, visit the U.S. National Cancer Institute.

Scams and Shams That Prey on Cancer Patients

Cancer patients often turn to the Internet as a source of information and hope. But all too often, those hopes are betrayed by purveyors of so-called cancer "cures" that are anything but, experts say.

Earlier this month, five companies were charged with making false and misleading claims for cancer cures, and settlements were reached with six other companies, the U.S. Federal Trade Commission announced. Products marketed by the companies included essiac teas and other herbal mixtures, laetrile, black salve (a corrosive ointment), and mushroom extracts.

"There is no credible scientific evidence that any of the products marketed by these companies can prevent, cure, or treat cancer of any kind," said Lydia Parnes, director of the FTC's bureau of consumer protection, the Associated Press reported.

In June, the U.S. Food and Drug Administration issued warning letters to two dozen companies peddling everything from cure-all teas to tablets and tonics. And earlier this year, more than 100 manufacturers of such products were issued similar letters.

According to the American Institute for Cancer Research, black salves are one of the most dangerous of these fake cures. The products, which supposedly "draw out" the disease from under the skin, can actually burn the skin and cause scarring.

Which is not to say that none of these compounds has potential as cancer fighters. But consumers need to be careful.

"Many of these compounds touted as having beneficial effects have lots of lab research, but it's more selling hope in a jar based on preliminary lab research," said Sarah Wally, a nutritionist with the American Institute for Cancer Research in Washington, D.C. "That's not fair to the consumer, particularly consumers with cancer who have a really strong motivation to try anything that might offer hope."

Many of these so-called cures or preventive treatments won't actually cause harm (except to your wallet), but some can interact with regular, supervised medical treatment, Wally said.

"Antioxidants can actually interfere with chemotherapy and radiation treatment," she said. "Some people think, 'I'm just drinking juice.' But they might be drinking two gallons of juice a day of super-antioxidant juice compound, not thinking to discuss it with their doctor."

And, some consumers may actually forego lifesaving conventional treatments in favor of shams.

Here's some advice from the experts:

• "If it sounds too good to be true, it probably is," said Dr. Ted Gansler, director of medical content for the American Cancer Society. Beware of claims that one treatment will cure all types of cancer or more than one type of disease. Also be leery of language such as "scientific breakthrough," "miraculous cure," "secret ingredient" and "ancient remedy," as well as claims that a product is "natural" and therefore safe. And take note of claims that the product has limited availability and that the company needs advance payment.
• Find out if the product has ever been tested in humans. Laboratory and animal research is fine, but only as a starting point, not as a basis for recommending the therapy in humans, Wally said.
• "Be careful about the credentials of the people promoting the treatment," Gansler said. "The possibility that someone with no medical or scientific treatment is going to come up with a cure for cancer or other diseases is not very likely." Reliable sources of information include the American Cancer Society, Memorial Sloan-Kettering Cancer Center in New York City, and the University of Texas M.D. Anderson Cancer Center. (All have Web sites.)
• "Watch out for evidence that is only testimonial," Gansler said. "In some of the most notorious alternative clinics, people will be diagnosed with cancer who don't even have cancer and, later on, they're 'cured.' " The "patient" may actually believe he or she was cured.
• Be on the lookout for obvious factual errors. If someone says their "Stage 7" cancer has been cured, be leery. There is no "Stage 7" cancer.
• Wally advised: "Before you wholeheartedly jump into these things, you need to really sit down and have a discussion with your physician." This is especially true in an age when alternative and complementary medicines are gaining acceptance. It can be tricky distinguishing between something bogus and something that may have a benefit, Wally added.

More information

The FDA has more on fake cancer cures to be avoided.

Mental Health and Global Burden of Disease

Definition

The World Health Organization (WHO) defines mental health as a 'state of well-being in which every individual realizes his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community'. The term 'Global Mental Health' refers to the international perspective on different aspects of mental health. Taking into account cultural differences and country-specific conditions, it deals with epidemiology of mental disorders in different countries, their treatment options, mental health education, political and financial aspects, the structure of mental health care systems, human resources in mental health and human rights issues among others. The overall aim of the field of Global Mental Health is to strengthen mental health all over the world by providing information about the mental health situation in all countries and identifying mental health needs in order to develop cost-effective interventions to meet those specific needs.

Mental Health and Global Burden of Disease

Mental disorders make a substantial contribution to the Global Burden of Disease. This is a global measure of so-called disability adjusted life years (DALY's) assigned to a certain disease, which is a sum of years lived with disability and years of life lost due to this disease. Neuropsychiatric conditions account for 14 % of the global burden of disease. Within non-communicable diseases, they account for 28% of the DALY's and thereby more than cardiovascular disease or cancer. The most important contributions to this number have unipolar depression, alcohol-use-disorder, schizophrenia, bipolar depression and dementia. However it is estimated that the real contribution of mental disorders to the global burden of disease is even higher, amongst others due to complex interactions and co morbidity of physical and mental illness.

Treatment gap

Up to 30% of all people worldwide has a mental disorder, and although interventions for the treatment of mental disorders are available, the proportion of those people with mental disorders who would need treatment but who do not receive mental health care is very high. This so-called treatment gap is estimated to reach about 76-85% for low and middle-income countries, and still 35-50% for high-income countries. Even those who are treated are often treated inefficiently or in an inhumane way.

Interventions

Information and evidence about cost-effective interventions to provide better mental health care is available. Although most of the research (80%) has been carried out in high-income countries, there is also strong evidence from low- and middle-income countries that pharmacological and psychosocial interventions are effective ways to treat mental disorders, with the strongest evidence for depression, schizophrenia, bipolar disorder and hazardous alcohol use.

Recommendations to strengthen mental health systems around the world have been first mentioned in the World Health Report 2001, which focused on mental health:

1. Provide treatment in primary care
2. Make psychotropic drugs available
3. Give care in the community
4. Educate the public
5. Involve communities, families and consumers
6. Establish national policies, programs and legislation
7. Develop human resources
8. Link with other sectors
9. Monitor community mental health
10. Support more research

Based on the data of 12 countries, assessed by WHO-AIMS (World Health Organization Assessment Instrument for Mental Health Systems), the costs of scaling up mental health services by providing a core treatment package for schizophrenia, bipolar affective disorder, depressive episodes and hazardous alcohol use have been estimated. Structural changes in mental health systems according to the WHO recommendations have been taken into account. For most countries, this model suggests an initial period of investment of $ 0.30 – 0.50 per person per year. The total expenditure on mental health would have to rise at least 10-fold in low-income countries. In those countries, additional financial resources will be needed, while in middle- and high-income countries the main challenge will be the reallocation of resources within the health system to provide better mental health service.

Barriers

Although awareness of the need for treatment of people with mental disorders has risen, there have not been substantial changes in mental health care delivery during the past years. Main reasons to this problem are public health priorities, lack of a mental health policy and legislation in many countries, a lack of resources – financial and human resources – as well as inefficient resource-allocation.



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Birth Size Linked to Breast Cancer Risk

Women who are heavier and longer at birth are at increased risk of developing breast cancer later in life, British researchers report.

In fact, as birth weight and length increases, so does the risk for breast cancer, according to the results of a study published in the Sept. 30 online edition of PLoS Medicine.

"These researchers have documented in unequivocal terms that larger birth size is associated with increased breast cancer risk several decades later," said Dr. Dimitrios Trichopoulos, the Vincent L. Gregory Professor of Cancer Prevention at Harvard University School of Public Health Department of Epidemiology and author of an accompanying journal editorial.

Birth size reflects, to a considerable extent, the effects of the intrauterine environment on the fetus, Trichopoulos noted. "To this day, they had not been sufficiently appreciated by the scientific community, because each individual study could not provide conclusive evidence. We are facing now a new reality: that breast cancer has its origins several decades before its clinical appearance," he said.

For the study, a research team led by Dr. Isabel dos Santos Silva, a professor of epidemiology at the London School of Hygiene and Tropical Medicine, collected data on more than 600,000 women, 22,058 of whom had breast cancer. The data came from 32 studies.

The researchers found that women who were heavier and longer at birth had increased risk for breast cancer as adults. An analysis of birth records, among these women, found that for every 17.6 ounces of birth weight, the risk for breast cancer increased 7 percent.

In addition, birth length and head circumference were also associated with an increased risk of breast cancer. The strongest association between size at birth and an increased risk for breast cancer was seen for birth length, the researchers reported.

"Recognition of early life influences are critical in the etiology of breast cancer and helps to explain why several adult life primary prevention practices -- as distinct to secondary prevention ones focusing on early detection -- have been of limited effectiveness," Trichopoulos said.

"Prevention of breast cancer needs to take into account the very long natural history of the disease," he added.

Expert reaction to the new research was fairly guarded.

"There's good evidence for these findings, but there is really no clinical relevance for them," said Debbie Saslow, director of breast and gynecologic cancer at the American Cancer Society.

"There is nothing that women should do differently to try to have smaller babies, or women who were born with a longer length or larger head circumference should do anything differently when they grow up or get screened differently, or consider themselves at high risk -- it's really just a research issue," Saslow said.

More information

For more on breast cancer, visit the American Cancer Society

Gene Could Link Obesity, Colon Cancer

Researchers have uncovered a genetic link between obesity and the risk for colon cancer. The discovery could lead to greater accuracy in predicting who is at risk for the disease, experts say.

Research has suggested that colon cancer risk rises with increasing weight, but this finding points to a genetic reason for the link.

"We have discovered that a genetic variant of the adiponectin gene, called ADIPOQ, is associated with colon cancer risk," said lead researcher Dr. Boris Pasche, director of the division of hematology and oncology at the Comprehensive Cancer Center of the University of Alabama at Birmingham. "This genetic variant may identify individuals who have a higher risk to develop colorectal cancer," he said.

The report was published in the Oct. 1 issue of the Journal of the American Medical Association.

For the study, Pasche's team focused on ADIPOQ. This gene promotes the formation of a fat hormone called adiponectin. People who inherit a common variant of the gene have up to a 30 percent lower risk of colon cancer compared with people without this gene variant, the study found.

On the other hand, the researchers believe that people who do not have this gene variant, or those who have high levels of adiponectin in their blood, may be at a slightly increased risk for colon cancer and could benefit from early screening for the disease.

"Adiponectin, a hormone exclusively secreted by the adipose [fat] tissue, is now genetically linked with colorectal cancer," Pasche said. "This is the first evidence that genetic variants of a 'fat hormone' affect risk of colorectal cancer," he said.

Whether people without this gene variant can reduce their risk of colon cancer through diet and exercise isn't clear, the researchers noted.

"This adds a little bit more to our understanding of one place where genetics plays a role in colon cancer development," said Dr. Durado Brooks, director of colon and prostate cancer prevention programs at the American Cancer Society. "It helps point us in some more specific directions; it adds another piece to the puzzle," he said.

Brooks does not believe that the finding is definitive, however. "It supports some of the other work that has already been done, identifying this particular gene region with colorectal cancer," he said.

The finding does help clarify one element linking obesity and colon cancer, but "there is no clinical application to this finding in the immediate future," Brooks said. "I don't think we would alter any recommendation, other than encouraging people to maintain a healthy weight."

Dr. Georgia Wiesner, a cancer geneticist at University Hospitals' Case Medical Center in Cleveland, agreed.

"I'd love to say that any time we find a new gene that identifies risk or alters risk we would be able to put that into a new drug treatment or at least identify people who are more at risk," Wiesner said. "But in this study, it might just tease out the pathogenesis of disease," she said.

It's already known that people who are obese have a higher risk for colon cancer, Wiesner said. "I don't know that telling somebody they might have a specific marker is really going to alter what they are going to do," she said. "It doesn't mean that these people don't need regular screening."

More information

For more on colon cancer, visit the American Cancer Society

Hyperthermia

Hyperthermia in general means a body temperature that is higher than normal. High body temperatures are often caused by illness such as fever or heat stroke. But hyperthermia can also refer to heat treatment -- the carefully controlled use of heat for medical purposes. This document focuses on how heat is used to treat cancer.

When cells in the body are exposed to higher than normal temperatures, changes take place inside the cells. These changes can make the cells more likely to be affected by radiation therapy or chemotherapy. Very high temperatures can kill cancer cells outright.

The idea of using heat to treat cancer has been around for some time, but early attempts to treat cancer with heat had mixed results. And it was hard to maintain the right temperature in the right area while limiting the effects on other parts of the body. Today, newer tools allow better control and more precise delivery of heat, and hyperthermia is being studied for use against many types of cancer.

How can hyperthermia be used to treat cancer?

There are 2 main ways in which hyperthermia can be used:

* Very high temperatures can be used to destroy a small area of cells, such as a tumor. This is commonly referred to as local hyperthermia or thermal ablation.

* The temperature of a part of the body (or of the whole body) can be raised to a higher than normal level. Although it isn't hot enough to kill the cells directly, it can allow other types of cancer treatments such as radiation therapy, immunotherapy, or chemotherapy to work better. This is known as either regional hyperthermia or whole body hyperthermia.

Local hyperthermia

Local hyperthermia (or thermal ablation) is used to heat a very small area, such as a tumor. It involves creating very high temperatures that destroy (ablate) the cells that are heated. Radio waves, microwaves, ultrasound waves, or other forms of energy can be used to heat the area. The heat may be applied using different methods:

* External: High energy waves are aimed at a tumor near the body surface from a machine outside the body.

* Internal: A thin needle or probe is inserted directly into the tumor. The tip of the probe releases energy, which heats the tissue around it.

Radiofrequency ablation

Radiofrequency ablation (RFA) is probably the most commonly used type of local hyperthermia. It uses high-energy radio waves for treatment. A thin, needle-like probe is placed into the tumor for a short time, usually about 10 to 15 minutes. Placement of the probe is guided by ultrasound or CT scans. The probe releases a high-frequency current that creates heat (between 122° and 212 °F) and destroys the cancer cells within a certain area.

RFA may be repeated for tumor recurrence, regrowth, or incomplete treatments. It can also be added to any other treatment, like surgery, radiation therapy, chemotherapy, hepatic arterial infusion therapy, alcohol ablation, or chemoembolization. RFA is most commonly used to treat tumors in the liver, and is being studied for use in several other areas of the body. Long-term RFA treatment outcomes are not yet known.

Regional hyperthermia

Regional hyperthermia heats a part of the body, such as an organ, limb, or body cavity (a hollow space within the body). It is usually combined with chemotherapy or radiation therapy. In one approach, called regional perfusion, the blood supply to a part of the body is isolated from the rest of the circulation. The blood in that part of the body is pumped into a heating device and then pumped back into the area (perfused) to heat it. This technique is being studied as treatment for certain cancers in the arms or legs, such as sarcomas and melanomas.

A related technique is being tested along with surgery against cancers in the peritoneum (the space in the body that contains the intestines and other digestive organs). During surgery, heated chemotherapy drugs are circulated through the peritoneal cavity. This is called continuous hyperthermic peritoneal perfusion, or CHPP.

Another approach to regional hyperthermia is deep tissue hyperthermia. This treatment uses devices that are placed on the surface of the organ or body cavity and produce high energy waves directed at a specific area. These devices give off radiofrequency or microwave energy to heat the area being treated.

Whole-body hyperthermia

Whole-body heating is being studied as a way to make chemotherapy more effective in treating cancer that has spread (metastatic cancer). Body temperature is raised by using warm-water blankets, inductive coils (like those in electric blankets), or thermal chambers (much like large incubators).

Pros and cons of hyperthermia

A major advantage of regional and whole body hyperthermia is that they seem to make other forms of cancer treatment work better. Heating cancer cells to temperatures above normal (up to as high as 113° F) makes them easier to destroy using radiation and certain chemotherapy drugs. And local hyperthermia, such as RFA, can use very high temperatures to destroy tumors without surgery.

Scientists agree that hyperthermia works best when the area being treated is kept within an exact temperature range for a certain period of time. But this isn't always easy to do. Keeping an area at a constant temperature without affecting nearby tissues can be tricky, too. To add to this, not all body tissues respond the same way to heat -- some are more sensitive than others. Another problem is monitoring the temperature at a specific site within the body. Small thermometers on the ends of probes are often placed in the treatment areas to be sure the temperature stays within the desired range.

Side effects

The possible side effects of hyperthermia depend on the technique being used and the part of the body being treated. Most side effects are short-term, but some can be serious. Localized or regional hyperthermia can cause pain at the site, infection, bleeding, blood clots, swelling, burns, blistering, and damage to the skin, muscles, and nerves near the treated area. Whole-body hyperthermia can cause nausea, vomiting, and diarrhea. More serious, though rare, side effects can include problems with the heart and blood vessels and other major organs. Experience, improved technology, and better skills in using hyperthermia treatment have led to fewer complications, and the problems that people do have are less serious.

The future of hyperthermia

While hyperthermia is a promising way to improve cancer treatment, it is largely an experimental technique at this time and is not commonly used. Many clinical trials of hyperthermia are now being done to better understand and improve this technique, and also look at how it is best used along with other cancer treatments. Current studies are looking at its usefulness in treating many types of cancer, including the following:

* breast
* cervical
* colorectal (with spread to liver)
* endometrial
* kidney
* liver
* lung
* ovarian
* pancreas
* prostate
* sarcomas (soft tissue cancers)
* thyroid

For more information about clinical trials of hyperthermia, contact the National Cancer Institute (NCI) at 1-800-4-CANCER or visit the NCI Web site at www.cancer.gov/clinicaltrials.

The Search for Better Cancer Drugs

Today cancer is a more treatable disease than at any time in the past. More than half of all people with cancer now live at least 5 years after being diagnosed. This progress is the result of better ways to find cancer early and better ways to treat cancer once it is found.

But cancer treatment is still far from ideal. Many cancers cannot be cured, and some are still very hard to treat effectively. And treatments like chemotherapy can sometimes cause severe side effects that can affect a person's quality of life. Patients and doctors have long hoped for cancer treatments that would work better than (or at least as well as) the ones we use now but with fewer side effects.

Scientists have learned a great deal in recent years about what makes cancer cells different from normal cells in the body. This has helped them find 'targeted drugs' - drugs that focus more on the cancer itself without having major effects on normal cells in the body. The American Cancer Society has funded the search for such treatments for many years.

One promising new cancer treatment to come from this research is called anti-angiogenesis (an-tee-an-jee-oh-jen-uh-sis) treatment.

Immunotherapy

Immunotherapy is also called biologic therapy or biotherapy. It is treatment that uses certain parts of the immune system to fight disease, including cancer. This can be done in a couple of ways:

• stimulating your own immune system to work harder or smarter
• giving you immune system components, such as man-made immune system proteins

Immunotherapy is sometimes used by itself to treat cancer, but it is most often used along with or after another type of treatment to boost its effects.

For a long time doctors suspected that the immune system had an effect on certain cancers. Even before the immune system was well understood, William Coley, MD, a New York surgeon, first noted that getting an infection after surgery seemed to help some cancer patients. In the late 1800s, he began treating cancer patients by infecting them with certain kinds of bacteria, which came to be known as Coley toxins. Although he had some success, his technique was overshadowed when other forms of cancer treatment, such as radiation therapy, came into use.

Doctors have learned a great deal about the immune system since that time. This has led to research into how it can be used to combat cancer, with many different approaches being explored. In the last few decades immunotherapy has proven useful in treating several types of cancer.

The idea of using one's own immune system to fight cancer is tempting, but immunotherapy still has a fairly small role in treating most cancers. So far, in most cases, it hasn't been shown to clearly be better than other forms of treatment. For instance, it seems most likely to be effective when treating smaller, early stage cancers, and it may be less helpful for more advanced disease. Its main role at this time is making other forms of treatment better or providing cancer patients with another, often less toxic, treatment option.

But researchers have made important progress in this field in recent years. Newer, more effective treatments are now being tested that will have a greater impact on the outlook for people with cancer in the future.