Urologists use optics, chemistry to catch small tumors

Tuesday 22 October 2013

Islamabad, Oct 23 (Newswire): Some bladder cancer tumors are so small, surgeons can't see them. Urologist Edward Messing is using a new liquid dye that reacts to light to help him see all the small bladder tumors that might have been missed in conventional biopsies. 
The earlier the better, when it comes to detecting cancer. Now, doctors are shedding new light on detecting the deadly disease. Currently, 400-000 people suffer from it while 60,000 more will find out they have it, and bladder cancer usually strikes more than once.

Larry Sylvan, a cancer survivor, says, "At nine months it was back." He knows what it's like to battle bladder cancer. Sylvan's doctor, Edward Messing, says, "The surgery was successful; I got everything I could see." The doctor's key word -- see; some bladder cancer tumors are so small, surgeons can't see them.

Dr. Messing, a urologist at the James P. Wilmot Cancer Center in Rochester, N.Y., says, "Before it was sort of blind guessing." A new photo-sensitizer, a liquid dye inserted into the bladder, improves detection of those small tumors. Under ordinary light, everything looks fine, but when the florescent light is turned on, the entire background looks blue, except where the tumor is -- that shows up bright red.

Jerry Gulette was one of the first patients to use the dye. He's battled bladder cancer time and time again. Dr. Messing says, "I had seen maybe four, five tumors when I cystoscoped him with the white light. And when we turned on this pink light there were 12 or 13."

More than 94 percent of the people diagnosed with bladder cancer will survive it if it's caught in the early stages. That's why this new procedure is so critical for those diagnosed.

Urologists use a liquid dye to more easily find tiny cancers in the bladder that could grow after surgery.

The liquid dye helps identify all the tiny tumors in the bladder that can remain after a major surgery is done. The dye, called a photosensitizer, reacts with light to make the cancerous tissue look bright red during an examination. The photosensitizer even detects a rare form of bladder cancer that is hard to detect because it lies almost flush against the walls of the bladder.

The bladder stores urine, which is produced when the kidneys filter urea, a waste product of proteins, from the blood. The bladder is a hollow organ made of muscle, connected to the kidneys by the ureters, and empties through the urethra. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing.

About 90 percent of bladder cancers begin in the cells lining the bladder. Cancer that is confined to the lining of the bladder is called superficial bladder cancer and is sometimes removed by scraping away the cancerous cells with a small wire loop.

In some cases, cancer that begins in the transitional cells spreads through the lining of the bladder and invades the muscular wall of the bladder. This is known as invasive bladder cancer. Invasive cancer may grow through the bladder wall and spread to nearby organs.

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Molecular biologists devise strategy to starve brain tumors

Islamabad, Oct 23 (Newswire): Brain tumor researchers have found that brain tumors arise from cancer stem cells living within tiny protective areas formed by blood vessels in the brain. Killing those cells is a promising strategy to eliminate tumors and prevents them from re-growing.

The researchers have found that drugs that block new blood vessel formation can destroy the protected areas and stop cancer from developing.

Brain tumors are often deadly. Figuring out a way to wipe them out has been a mystery for scientists. But now, a new discovery may offer clues and hope for those with even the most hard-to-treat tumors.

In the last two months, Will Pappas has had three surgeries, chemo and radiation.

"You hold out hope that well, it's just something little, and they can get it all. And then it wasn't. Then you think, well, at least it's not cancerous, and then it is," Cayce Pappas, Will's mom, says.

"It" is a brain tumor -- the stubborn kind that's hard to treat. In fact, doctors gave this seven-year-old only a 20 percent chance of surviving. Stories like Will's have molecular biologists determined to find a way to destroy brain tumors.

"It's what makes us all come to work in the morning," Richard Gilbertson, a molecular biologist from St. Jude Children's Hospital, says.

For years, researchers thought all cells inside a tumor were the same. But recently, they've discovered something different -- a small group of cancer stem cells.

"They give rise to all the cells that make up the cancer," Dr. Gilbertson explains.

Dr. Gilbertson's research shows those cancer stem cells live close to blood vessels, which fuel them. In lab experiments, he's proven drugs that target the blood vessels also destroy the cancer stem cells and can ultimately wipe out the tumor.

"So, if you can target those cells, you can have a devastating effect on the disease," Dr. Gilbertson says. Drugs like Avastin and Tarceva are now being tested in humans to see if they can target the cancer stem cells. "It's this tangible way of actually getting at the heart of the disease," Dr. Gilbertson says.

Will is taking the drug Tarceva. His mom is hoping it will work a miracle.

"That would be amazing. We would jump at the opportunity to increase our odds. He's still got a lot left to do," Cayce says.

Dr. Gilbertson says other cancers, like those of the blood, breast and colon, also contain cancer stem cells and may be treated in a similar way in the future.

Researchers at St. Jude Children's Hospital have found that brain tumors appear to arise from cancer stem cells that live inside tiny protective 'niches' formed by blood vessels in the brain. Breaking down these niches is a promising strategy for eliminating the tumors and preventing them from regrowing.

Scientists previously believed that tumors are lumps of cancerous tissue that must be completely removed or destroyed to cure a patient. But over the last five years, cancer researchers have learned that not all cancer cells are created equal. In the same way that normal tissue in the body is generated from stem cells, so is cancer.

CSCs are the ultimate source of the tumor, consistently supplying it with new cells. Researchers have identified the CSCs for acute myeloma leukemia, four types of brain cancer, and breast cancer. So it is possible that we need not kill all cancer cells to rid a patient of the disease. Targeting the CSCs specifically might be much more efficient.

To find a weakness for CSCs, neurobiologists at St. Jude compared them to noncancerous neural stem cells. These neural tissue generators are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cells survive. CSCs, they discovered, required similar conditions to flourish: in over 70 human brain tumors, the CSCs were frequently located close to tiny vessels called capillaries.

When the researchers injected mice with a mix of stem and endothelial cells from human brain tumors, those animals sprouted larger tumors than the mice that received stem cells alone.

The new findings from St. Jude indicates that it is possible to kill the cancer by disrupting the shielded compartments in the small capillaries of the brain where CSCs reside. Anti-angiogenic drugs, such as Avastin, block the formation of new blood vessels.

In tests with mice, those same drugs cause a significant drop in cancer stem cells and slow tumor growth. Human clinical trials are currently in progress at St. Jude to determine the effectiveness of Avastin and another anti-angiogenic drug in eliminating tumors and preventing their recurrence in children with brain cancers.

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Skin cancer linked to loss of protein that hooks skin cells together

Islamabad, Oct 23 (Newswire): In a study to be published in PLoS Genetics, researchers at the Stanford University School of Medicine have implicated the lack of a protein important in hooking our skin cells together in the most common variety of skin cancer.

Depletion of this protein, called Perp, could be an early indicator of skin cancer development, and could be useful for staging and establishing prognoses.

These findings' significance may extend beyond skin cancer, as Perp is found in the linings of many of our internal organs, where it plays the same role it does in the skin: maintaining cell-to-cell adherence.

This suggests that Perp could be a useful tool for classifying tumors in these internal organs, which are often diagnosed too late to be effectively treated.

Skin is the largest organ in the body by weight, consisting of several sheets of cells layered one atop the next. The bottom layer is composed of basal cells, which, after proliferating for a while, migrate upward toward the skin surface, differentiating from one cell type to another several times along the way.

Skin's outermost layer consists mainly of closely knit squamous cells. Perp is a critical player in maintaining this cell-cell adhesion in these cell types, which makes our skin such an effective barrier against pathogens and toxic and allergenic substances.

Skin belongs to a class of tissues known collectively as epithelium. Epithelial tissue also lines many internal organs such as the lungs, colon, breast, esophagus and pancreas. Several organs' epithelial linings, like skin, are multilayered.

"A good 90 percent of all human cancers originate in epithelial tissue," noted Laura Attardi, PhD, senior author of the study and associate professor of radiation oncology and of genetics at the medical school. "Epithelial tissues are constantly regenerating, creating ample opportunities for errors to occur during DNA replication that can promote tumor growth.

Also, these tissues are particularly exposed to the environment -- the skin to UV radiation, the colon to dietary carcinogens, the lungs to inhaled toxins, and so forth."

Perp, first identified by Attardi in the late 1990s, is a key protein in desmosomes, multi-protein structures found on the surfaces of epithelial cells. Desmosomes are one kind of so-called adhesion junction, cell-surface features that bind fiercely to one another from one cell to the next. Adhesion junctions cause cells to stick together and form a barrier.

Perp, a desmosomal component, weaves in and out of a cell's surface like a thread through fabric. The protein's intercellular tail wraps around structures in the cell, firmly anchoring the desmosome on the membrane. The desmosome's outward-facing features bind strongly to their counterparts on neighboring cells, creating a tight seal.

"People have long assumed that this was desmosomes' only function," said Attardi, who is also a member of the Stanford Cancer Center. The new study shows not only that desmosomes are crucial to maintaining epithelial tissues' integrity, but that the loss of Perp, which is crucial to desmosomes' function, promotes cancer. Disrupted function of another kind of adhesion junction has, indeed, been implicated in late-stage cancers. But desmosome disturbances may occur earlier on, during tumors' initial development.

In 2005, in a study published in Cell, Attardi first showed that Perp is integral to desmosomes. She and her associates produced mice lacking Perp, allowing them, unexpectedly, to identify a role that Perp plays in the skin.

Mice whose skin was deficient in Perp exhibited desmosome loss as well as blistering and increased skin-cell proliferation. In these mice, moreover, so-called p53 tumor suppression -- a mechanism widely acclaimed for its importance in shutting down cell division when genetic damage can't be properly repaired -- fails to function normally, implying that Perp played some as-yet-unspecified role in that pathway. (The p53 protein has been found to be mutated in at least half of all human tumors.)

"In this new study, we attempted to mimic the way skin cancers originate in people," said Attardi. She and her colleagues exposed both normal mice and the bioengineered Perp-deficient mice to UVB light -- a range of ultraviolet wavelengths known to induce the great majority of human skin cancers -- and compared the incidence of squamous-cell carcinoma in the two groups. In the mice lacking Perp, skin tumors arose faster, and were both more abundant and aggressive, than in normal mice.

"Perp loss promotes cancer in three different ways," Attardi said. The scientists observed the overproduction of inflammatory molecules (known to promote cancer), the increased survival of cells that should have committed suicide in response to excessive UVB and a loss of cell-cell adhesion commensurate with the loss of desmosomes.

At the same time, the mice with early stages of skin cancer continued to retain normal function of another variety of adhesion junction complex that has been observed to be dysfunctional in advanced cancer stages, such as metastasis. What the researchers have shown in this study is that the earlier loss of desmosome function is enough, by itself, to promote tumor growth.

The investigators also observed a substantial disappearance of Perp in biopsied human squamous-cell carcinoma samples. Once again, the alternative adhesion junction complexes that have been implicated in later stages of cancer appeared to be present and functioning normally in almost all of these samples, further supporting the idea that desmosome loss due to Perp inactivation can be an early, defining event in cancer progression.

Squamous-cell cancer is the second-most common of all human skin cancers after basal-cell carcinoma, striking hundreds of thousands per year in the United States. The Attardi lab findings could be applicable to basal-cell carcinoma, too. On the order of 1 million new cases of basal-cell carcinoma, by far the most common skin cancer, are reported in the United States each year. Fortunately these cancer types have very high cure rates -- largely because they're so easily spotted that tumors can be removed long before they advance to a dangerous state.

But epithelial tissues at many far less accessible sites (for example, internal organs such as esophagus and pancreas) develop cancers that are caught late -- often too late for effective treatment. Most healthy epithelial cells harbor desmosomes on their surfaces, suggesting that these ubiquitous structures' depletion or dysfunction may factor into a number of different tumor types.

"We think our study may also be relevant to other cancers, such as head-and-neck cancer, which is much deadly than skin cancer," she said. More than 35,000 new head-and-neck cancer cases are diagnosed each year in the United States.

A tumor-progression marker that could be detected early might prove useful not only in diagnosing and staging tumors but also in enhancing physicians' treatment decisions. "You might use more aggressive treatment on tumors lacking Perp, but spare patients with tumors that have Perp from the most-aggressive treatments," said Attardi. "Understanding this protein's role better may also point to new therapeutic approaches."

The study, whose first author was Veronica Beaudry, a graduate student in Attardi's laboratory, was supported by funding from the National Institutes of Health. Other Stanford co-authors were Dadi Jiang, PhD, and Rachel Dusek, PhD, postdoctoral researchers in Attardi's lab; research associate Eunice Park; Hannes Vogel, MD, professor of pathology; and Stevan Knezevich, MD, PhD, Vogel's former associate in pathology.

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