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Like to eat meat? Consider this unappetizing truth: When you gulp down a nice juicy steak or hamburger, you are contributing to tumor-fueling inflammation in your body.In fact, eating a diet rich in red meat has long been linked to a host of ills including an increased risk of several types of cancer. But what is it about meat consumption that could impact cancer growth? Now scientists at the University of California, San Diego School of Medicine, have found a mechanism that explains how eating red meat, as well as milk, could spur the growth of malignancies. The new study, headed by Ajit Varki, M.D., suggests that inflammation resulting from a molecule introduced through eating these foods could make cancer grow. The research is set for upcoming publication in the Proceedings of the National Academy of Sciences (PNAS).Dr.Varki, UC San Diego School of Medicine distinguished professor of medicine and cellular and molecular medicine and co-director of the UCSD Glycobiology Research and Training Center, and his research team studied a non-human glycan, or sugar molecule, known as N-glycolylneuraminic acid (Neu5Gc). Although this molecule is not produced naturally in the human body, it’s incorporated into human tissues if you eat red meat. The body then develops antibodies against Neu5Gc – and this immune response could potentially trigger a low-grade chronic inflammation, spurring the growth of cancer. In a statement prepared for the media, Dr. Varki explained it has been recognized by scientists for some time that chronic inflammation can stimulate cancer progression."We've shown that tumor tissues contain much more Neu5Gc than is usually found in normal human tissues. We therefore surmised that Neu5Gc must somehow benefit tumors,” Dr. Varki said in the press statement. So the scientists came up with this hypothesis: The fact that Neu5Gc accumulates in human tumors despite circulating anti-Neu5Gc antibodies suggests a low-grade, chronic inflammation has developed, and caused the tumor to grow. To test this idea, the researchers worked with specially bred mice. The animals lacked the Neu5Gc molecule , just as humans do before they eat red meat and the molecule is absorbed into their bodies, and they had tumors.Anti-Neu5Gc antibodies were given to half of the mice . In those animals, the antibodies induced inflammation and their cancers started growing faster. In the control group comprised of mice that were not treated with antibodies, their tumor growth was far less aggressive.Building on previous research that has shown that humans who take non-steroidal anti-inflammatory drugs (commonly known as NSAIDs) have a reduced risk of cancer, the researchers tried giving NSAIDs to the mice with cancerous tumors fueled by anti-Neu5Gc antibodies. The result? The anti-inflammatory treatment blocked the effect of the Neu5Gc antibodies and the tumors became smaller."Taken together, our data indicate that chronic inflammation results from interaction of Neu5Gc accumulated in our bodies from eating red meat with the antibodies that circulate as an immune response to this non-human molecule – and this may contribute to cancer risk," Varki said in the media statement.For anyone interested in reducing inflammation through natural, non-drug methods, here are seven top strategies to incorporate into your lifestyle:1. Stop eating meat and dairy products.2. Concentrate on a Mediterranean flavored style of eating with lots of fruits, vegetables, whole grains , olive oils and nuts. Research has shown these foods lower inflammation levels.3. Don’t smoke and avoid those who do – second hand smoke can contribute to inflammation.4. Know your oils. Avoid all inflammation-causing trans-fats, hydrogenated and partially hydrogenated oils as well as saturated animal fats. Instead, add inflammation-fighting omega-3 oils like flaxseed, canola and walnut oil to your diet.5. Lose weight if you need to. Research has shown that a waist that measures over 40 inches in a man or over 35 inches in a woman is a sign of probable high inflammation.6. Don’t skimp on sleep. Previous studies have concluded less than six hours of sleep can result in inflammation .7. De-stress. Try yoga, meditation, walking and other forms of exercise. Staying continually stressed out means your body is releasing excess, inflammation-promoting stress hormones . Schedule a minimum of 20 minutes a day to let your worries go.

Non-melanoma skin cancer linked with increased risk for other cancers


People who have previously had non-melanoma skin cancer appear to face a higher risk of other cancers, US scientists have found.
Researchers at the Medical University of South Carolina analysed data on 769 people with non-melanoma skin cancer - basal cell and squamous cell carcinoma - and a further 18,405 people with no previous history of cancer for 16 years.
They found that the rate of cancer in people with a history of non-melanoma skin cancer was 293.5 cases per 10,000 people per year, while in people with no previous history of cancer it was just 77.8 cases per 10,000 people per year.
This interesting study adds weight to the possibility that non-melanoma skin cancer may somehow increase a person's future risk of developing other types of cancer. - Dr Alison Ross, science information officer, Cancer Research UK
After other risk factors - such as age, sex, body mass index, smoking and education level - had been taken into account, people with a history of non-melanoma skin cancer were found to face a two-fold increase in the risk of subsequent cancers.
Previous research has suggested that non-melanoma skin cancer survivors are at increased risk of developing melanoma in the future, but the researchers found that the disease also increases the risk of other forms of cancer.
The association was strongest in young people between the ages of 25 and 44.
Commenting on the findings, which are published in the Journal of the National Cancer Institute, Dr Anthony Alberg of the Medical University of South Carolina said: "This pattern of associations, with earlier age of [non-melanoma skin cancer] diagnosis being linked more strongly to the risk of developing subsequent malignancies, is consistent with the pattern that one would expect for a marker of inherited predisposition to cancer."
Dr Alison Ross, science information officer at Cancer Research UK, said: "This interesting study adds weight to the possibility that non-melanoma skin cancer may somehow increase a person's future risk of developing other types of cancer.
"The next steps will be for scientists to investigate the biology behind this link, so they can piece together what's really happening in the body and how."

US scientists have found evidence suggesting that the 'cancer stem cell' theory may not apply to melanoma - the most deadly form of skin cancer.
The theory that cancers develop from 'rogue' stem cells was put forward in 1997, when evidence for such 'cancer stem cells' was published in Nature Medicine. Scientists found that only a tiny proportion of cells taken from a given tumour had the ability to grow into new tumours when transplanted into laboratory animals.
Since then, stem-like cells have been found in many types of cancer, including breast, bowel and prostate cancer.
This study shows how important it is that we continue to fund research into how cancers develop at a fundamental level. - Ed Yong, science information manager, Cancer Research UK
Further work on melanoma previously estimated that only about one in one million melanoma cells were able to grow into new tumours.
However, a new study by researchers at the University of Michigan, which appears as the cover article in Nature, has found that at least one quarter of melanoma cells have the ability to form new tumours.
When scientists updated and improved the laboratory tests used to detect cancer stem cells and applied them to human melanoma cells transplanted into mice, they found the cells to be quite common.
According to the researchers, the findings suggest that the stem cell model needs to be reassessed as it appears not to hold true in melanoma.
Ed Yong, Cancer Research UK's science information manager, said: "The idea that most types of tumour grow from a tiny population of 'cancer stem cells' is one of the most interesting ideas in current cancer research. But this study suggests that it may not be true for every type of cancer - in melanoma, a much larger proportion of cancer cells are able to give rise to a new tumour.
"This study shows how important it is that we continue to fund research into how cancers develop at a fundamental level."
Sean Morrison, director of the University Of Michigan's Centre for Stem Cell Biology, said that the test usually used to detect cancer stem cells "misses" most of them.
He commented: "I think the cancer stem cell model will, in the end, hold up for some cancers.
"But other cancers, like melanoma, probably won't follow a cancer stem cell model at all. The field will have to be reassessed after more time is spent to optimise the methods used to detect cancer stem cells."
Study co-author Dr Timothy Johnson, director of the university's Multidisciplinary Melanoma Programme, noted that the cancer stem cell model has been regarded by some people as an "exciting new source for the development of life-saving cures for advanced melanoma".
"Unfortunately, our results show that melanoma does not strictly follow this model," he revealed.
"So we'll need to redirect our scientific efforts and remain focussed on the fundamental biological processes underlying the growth of melanomas in humans. And as we pursue new treatments for advanced melanoma, we'll have to consider that a high proportion of cancer cells may need to be killed

Moh’s Micrographic Surgery More Effective than Excision for Recurrent Basal Cell Carcinoma of the Face


Moh’s micrographic surgery (MMS) for the treatment of recurrent basal cell carcinoma (rBCC) of the face results in fewer recurrences than surgical excision, according to the results of a study published in the December 2008 issue of the Lancet Oncology.[1]
Skin cancer is often divided into two broad categories: melanoma and nonmelanoma. Nonmelanoma skin cancer refers to several different types of skin cancer, but the most common types are basal cell carcinoma and squamous cell carcinoma. Each year in the U.S., more than one million people are diagnosed with basal cell or squamous cell skin cancers. Unlike melanoma, these types of skin cancer are rarely deadly.
Basal cell carcinoma accounts for roughly 80% of all cases of nonmelanoma skin cancer. It most commonly develops on sun-exposed skin, with the head (particularly the nose) and neck being the most common sites. This type of skin cancer very rarely metastasizes (spreads beyond the skin), but it can cause extensive local damage to the skin and surrounding tissues.
Basal cell carcinoma is typically treated with either surgical excision or Moh’s micrographic surgery (MMS). Surgical excision involves the use of a scalpel to remove the cancer and some surrounding normal tissue, which is then sent to the lab where the margins are checked for cancer. If the margins are clear, it’s likely that the cancer was completely removed. Moh’s micrographic surgery is a more complicated procedure, during which a doctor removes thin layers of skin one at a time and evaluates them for cancer while the patient waits. The doctor keeps removing layers of skin until he or she reaches a layer that is cancer-free. This procedure removes the least amount of normal tissue, and also has the highest cure rates for both primary and recurrent cancers. The procedure generally requires less than four hours to complete but can take longer if the cancer is extensive.
In a study performed in the Netherlands, 408 primary BCCs (pBCC) and 204 recurrent BCCs (rBCC) were randomly assigned to surgical excision or MMS. After five years of follow-up, the researchers found that MMS produced significantly lower recurrence rates than surgical excision in the rBCC group. (Two patients in the rBCC group treated with MMS experienced a recurrence of cancer, versus ten patients treated with surgical excision.) However, in the group of patients with pBCC, there was not a significant difference between the two surgical modalities.
The researchers concluded that MMS is preferred over surgical excision for the treatment of facial rBCC because it produces significantly fewer recurrences.
Reference:
[1] Mosterd K, Krekels GAM, Nieman FHM, et al. Surgical excision of Moh’s micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncology

Melanoma Research: Interleukin-12 Indicates Survival Prospects for Melanoma Patients

Higher blood levels of an immune system protein predict poor survival prospects for melanoma patients with advanced disease, researchers at The University of Texas M. D. Anderson Cancer Center report today at the annual meeting of the American Association for Cancer Research.Their finding that elevated levels of interleukin-12 (IL-12) are a marker of poor prognosis also points to a molecular explanation for a long-known risk factor for melanoma patients - older age.Among 150 patients with Stage III melanoma, the study found that the highest levels of IL-12 are associated with a nearly 5-fold risk of death. Although older stage III patients also had an elevated risk of death, age was not a prognostic factor independent of IL-12."Melanoma in some cases can be vulnerable to attack by a patient's immune system," said senior researcher Jeffrey Lee, M.D., professor in M. D. Anderson's Department of Surgical Oncology. "What we've found could be evidence of a dysfunctional immune response that actually fuels the growth of melanoma."Blood-born IL-12 provides both an accessible prognostic marker and a key connection to other signaling proteins; IL-12 as well as these related proteins already have been targeted by antibody therapies in certain autoimmune disorders, Lee said.The research team examined age, stage of disease, and IL-12 levels in 658 melanoma patients - 445 with stage I or II disease, 150 with stage 3 and 63 at stage IV."First, we found that IL-12 levels increase with age," says first author and study presenter Yun Shin Chun, M.D. The mean levels of the protein increased at every age level above age 40. (See Chart) Age, disease stage and IL-12 levels were then analyzed separately as prognostic factors. Increases in all three were associated with poor overall survival."When we analyzed these three factors together, only stage of disease and IL-12 levels were independent predictors of overall survival," Chun said. Age dropped completely out of the picture. Stage of disease was the most powerful prognostic factor. Both IL-12 and IL-23 are cytokines, proteins that tell cells and other proteins what to do. Cytokines like IL-12 and IL-23 are particularly vital to immune system function. The general level of a person's immune function declines with age, Lee said, as do the levels of most cytokines. The rise of IL-12p40 with age is a relative anomaly.Chun, Lee and colleagues are investigating IL-12's connection to the tumor promoting IL-23 and about 30 other cytokines in high-risk melanoma patients. Some of the suspect cytokines, including IL-12 and IL-23, already are targeted by therapies used autoimmune disease, Lee noted.Funding for the research was provided by The Marit Peterson Fund for Melanoma Research, and the M.D. Anderson's SPORE grant in melanoma from the National Cancer Institute.

Mohs Surgery for Skin Cancer

Mohs surgery is named after its developer, Dr. Frederic E. Mohs. In the 1930’s, Dr. Mohs developed a method that “fixed” (preserved) and stained tissue directly on the patient. A chemical paste was applied to the tumor and was allowed to penetrate to a few millimeters depth. This required 6-24 hours, after which, the area was surgically removed and the entire peripheral and deep margin was examined for residual tumor. This process was repeated over days until all margins were found to be free of tumor. Defects resulting from Mohs surgery were generally allowed to granulate (fill-in) on their own and not sewn closed. This method had the disadvantages of being painful and time consuming (only one “stage” could be done per day) and the granulated wound often produced an ugly scar. Today, this technique has been modified; no chemicals are applied directly to the patient, multiple stages can be performed in hours, and the defect can be closed immediately if desired. The original concept of examining the entire peripheral and deep margin of the excised specimen remains.Background:When a routine excision is done, the specimen is processed by “breadloafing.” Like a loaf of bread is sliced, sections are taken vertically through the specimen at 3-4mm intervals and these sections are examined under the microscope. For practical reasons, only a few sections or “slices” are examined. Most skin cancers grow like the roots of a tree with extension of the tumor to the sides and downward. With breadloafing, tumor roots can be missed if they happen to grow in the 3-4mm gap between sections. In fact, less than 1% of the true peripheral and deep margin is examined by this method. This limitation is addressed by Mohs surgery.Technique:It is beyond the scope of this article to explain the Mohs procedure precisely step-by-step. However, the following are critical points that lead to the examination of theoretically 100% of the peripheral and deep surgical margin and conservation of surrounding normal tissue. After a pre-operative consultation has been completed and informed consent obtained:- The lesion is numbed with local anesthesia.- Tumor that can be seen or felt is removed with a curette or scalpel.- A thin, saucer-like layer of tissue is excised just a few millimeters around and underneath the resulting defect.- This layer is divided into pieces and inked. - A map is drawn that shows each piece in relation to the patient. - Each piece is frozen, mounted in a waxy substance and very thinly sectioned horizontally starting from the underside of the specimen. This is done by the Mohs histotechnician.- The slides are processed and examined by the Mohs surgeon. If tumor roots are seen on the slide, they extend beyond the underside of the tissue that was excised, and therefore, more tumor remains in the patient. The tumor site on the slide is matched to the previously drawn map and the precise location on the patient is identified. The process is then repeated and another saucer-like layer is removed, but only from the area that showed residual tumor. In this way, surrounding normal tissue is conserved.When no residual tumor is seen, the tumor is deemed completely removed and the defect can be repaired if desired. Often, the Mohs surgeon can repair the defect immediately. Alternatively, when the defect is more complex, closure can be coordinated with other physicians who specialize in reconstructive surgery such as plastic surgeons, facial plastic surgeons, otolaryngologists, or ophthalmologists. Cancers treatable by Mohs surgery:Mohs surgery has been used to excise many different types of skin cancer. However, BCCs and SCCs, the two most common forms of skin cancer, are the cancers most often treated by Mohs surgery. The treatment of melanoma by Mohs surgery is controversial at this time.Indications:Mohs surgery is a specialized technique that is not indicated for the treatment of every BCC or SCC and is most appropriately used under certain, well-defined circumstances. The majority of BCCs and SCCs can be treated with very high cure rates by standard methods including electrodessication and curettage (ED&C), local excision, cryosurgery (freezing) and irradiation. These are fairly quick and easy and can often be performed in the local physician’s office. Large or recurrent lesions or those that arise at sites where recurrence is more likely or where tissue conservation is important are most aptly treated with Mohs surgery. This includes many areas of the face. Training:The Mohs surgeon must be proficient in all aspects of the procedure including anesthesia, anatomy, surgery, pathology and reconstruction. Knowledge of these and other aspects of the procedure and most importantly, surgical judgement, are usually not acquired during the course of residency training and often require additional specialized fellowship training. Summary:Mohs surgery is a specialized surgical technique that results in high cure rates when used to remove skin cancers such as BCCs and SCCs. It is especially useful in lesions that, due to their size, location or other factors are at higher risk of recurrence if treated by standard methods or arise in areas where tissue conservation is important. It is not indicated for use in all cancers of the skin. Mohs surgery is labor intensive and requires a large support staff and specialized training in the technique.

Skin Cancer Research Suggests Novel way of Preventing Disease


New insight into skin-tanning process suggests novel way of preventing skin cancerFindings from a study led by researchers at Dana-Farber Cancer Institute and Children's Hospital Boston have rewritten science's understanding of the process of skin tanning – an insight that has enabled them to develop a promising way of protecting fair-skinned people from skin cancer caused by exposure to sunlight. The study, to be published by the journal Nature in its Sept. 21 issue, involved giving tans to specially engineered mice, not by exposing them to ultraviolet rays in sunlight (the usual route to a tan), but by applying a cream that switched on the tanning machinery in their skin cells. Because people who tan easily, or have naturally dark skin, are far less likely to develop skin cancer than fair-skinned individuals – who tend to get sunburns rather than tan – the findings suggests that medicinally-induced tans can protect at-risk individuals from the disease. "The study involved using a small molecule to essentially mimic the process that occurs when skin cells are struck by ultraviolet light from the sun," says the study's senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston. While the compound used in the study has not yet been tested in humans, the results "demonstrate the principle that actual tanning can be 'rescued' by recognizing the normal pathway and the precise step where it is blocked in people who do not tan well," he remarks. Melanoma is the fastest-increasing form of cancer in the world, accounting for 62,000 new cases in the United States every year and nearly 8,000 deaths, according to the American Cancer Society. It occurs when pigment-making skin cells called melanocytes begin dividing rampantly as a result of damage to their DNA. If melanoma tumors are detected and surgically removed before their cells spread to other parts of the body, patients have an almost 100 percent chance of surviving. The odds drop sharply, however, if treatment doesn't begin until the disease has spread, or metastasized. One trigger for melanoma development appears to be ultraviolet (UV) light from the sun, which can damage the skin's DNA. For most of human history, fair-skinned people, who tan poorly, occupied regions with low sun exposure, such as Nordic areas with winter months of darkness. As human populations have scattered throughout the globe, increasing numbers of fair-skinned people have come to live in sunny climes, and melanoma and other skin cancer rates have shot up. The new Dana-Farber report grew out of efforts by Fisher's laboratory to study melanoma in mice whose fair skin stemmed from the same genetic roots as fair-skinned people. The researchers succeeded in generating red-haired mice whose light skin contained melanocytes, but when the mice were subjected to low levels of UV radiation, they did not tan. Nor did they tan when the UV levels were raised slightly; but when they increased slightly more, the animals got skin sunburns. "These animals couldn't tan," Fisher remarks, who is also a professor of pediatrics at Harvard Medical School. "We'd proven in a rigorous genetic system what people have known for hundreds of years: Redheads don't tan well." This suggested that the mice were a good model for fair-skinned humans. It also led researchers to propose a new theory about how sun exposure triggers pigmentation in people who tan easily. If the researchers' theory was correct, it should be possible to induce dark pigmentation in fair-skinned mice with specific, targeted drugs. The most common origin of red hair and pale skin in humans is found in a tiny pouch-like receptor, called MC1R, on the surface of melanocytes. When the hormone MSH — for Melanocyte Stimulating Hormone — drops into the pouch, it causes a surge in the melanocyte's production of the chemical cAMP. cAMP then stimulates melanocytes to turn on a large number of genes, causing a pigment called melanin to be produced. If cAMP levels are low, the melanocytes make red/blond melanin. If cAMP levels are high, they make brown/black melanin. The melanin is eventually discharged from melanocytes and taken up by keratinocytes. MC1R is shaped differently in red-haired people, so that MSH cannot stimulate it strongly. The result is that cAMP production stays at low levels. Less cAMP means less red/blond pigment production, which results in fair skin. Many scientists have theorized that tanning occurs when ultraviolet radiation strikes the nuclei of melanocytes, causing DNA damage that prompts the melanocytes to produce pigment. This supposition, however, conflicted with the results of Fisher's experiments. "Our work suggested that a peculiarity in the MC1R receptor on melanocytes is responsible for a failure to tan," Fisher relates. "But that sort of change on the cell surface shouldn't impede UV radiation from reaching the melanocyte's DNA." If Fisher's results were correct, the traditional picture of the biology of tanning was wrong. In a series of experiments, Fisher's team found evidence to bolster their theory, leading to a new model of how tanning occurs. The experiments demonstrated that, rather than acting directly on the nuclei of melanocytes, UV radiation acts on keratinocytes (the most abundant as well as superficial cells in the skin), causing them to produce and secrete MSH, which attaches to adjacent melanocytes and starts the pigment-making process. While Fisher's model adequately explains why redheads don't tan, it isn't the only possibility. "Suppose that during the embryonic or fetal period MC1R never activated cAMP production in developing melanocytes," Fisher proposes. "Would mature melanocytes then be permanently 'crippled,' unable to respond to UV, regardless of how its signals were transmitted?" One way to disprove that 'permanently crippled' scenario would be to see if melanocytes with abnormal MC1R receptors can be coaxed into producing pigment in adult mice. To attempt this, Fisher and his associates treated the skin of red-haired, fair-skinned mice with a compound known to increase cAMP levels. The compound, called forskolin, is derived from the root of the forskohlii plant found in India. The mice involved in the experiment turned dark, proving that melanocytes in redheads aren't inherently unable to make pigment if appropriately stimulated. Further experiments showed that not only can red-haired mice be given tans without exposing them to UV light, but this sunless tanning process is virtually indistinguishable from that in dark-haired mice that tan naturally."When keratinocytes absorb melanin pigment, the pigment isn't randomly distributed within them," Fisher explains. "It forms arcs that look like tiny umbrellas over the keratinocyte's nucleus. When we artificially caused our red-haired mice to tan, the pigment in their keratinocytes made the exact same umbrella-like pattern."The Dana-Farber researchers also showed that tans acquired through forskolin conferred significant protection against skin cancer caused by exposure to UV light. Fisher notes that while it is unknown whether forskolin will penetrate deeply enough in human skin to activate melanocytes, these results suggest that the search for other substances that do reach deep into the skin may well have the same pigmentation effects in people."These studies suggest that a drug-induced 'rescue' of the tanning mechanism may correspondingly rescue at least some aspect of skin cancer protection," Fisher observes. "Such sunless tanning may also dissuade sun-seeking behaviors, which undoubtedly contribute significantly to high skin cancer incidence."