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Researchers find prostate cancer stem cell

in.reuters.com

Researchers find prostate cancer stem cell

Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease.

Existing cancer treatments have mostly been developed based on animal models, where therapies able to promote tumor shrinkage were deemed effective. However, animals could not provide a complete model of human disease. In particular, in mice, whose life spans do not exceed two years, tumor relapse is exceptionally difficult to study.

The efficacy of cancer treatments is, in the initial stages of testing, often measured by the ablation fraction of tumor mass (fractional kill). As CSCs would form a very small proportion of the tumor, this may not necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate new cells. A population of CSCs, which gave rise to it, could remain untouched and cause a relapse of the disease.

Researchers have found a stem cell, a kind of master cell, that may cause at least some types of prostate cancer.

Their findings are only experimental — the stem cells were found in mice — but could explain at least some types of prostate cancer and eventually offer new ways to treat it, they reported on Wednesday in the journal Nature.

The findings also show a potential new source for prostate tumors — so-called luminal cells, which secrete various compounds used in the prostate.

“The role of stem cells in the development of prostate cancer has been a focus of speculation for many years,” Dr. Helen Rippon of Britain’s Prostate Cancer Charity said in a statement.

“Importantly, this new stem cell does not rely on androgens — the male sex hormones that control prostate growth — to survive and grow. This may give a clue as to why prostate cancer often becomes resistant to treatments designed to regulate these androgens in the later stages of the disease,” added Rippon, who was not involved in the research.

“This improved knowledge will also be a step forward in learning how we might help to prevent the disease from developing in men in the first place.”

Michael Shen of Columbia University Medical Center and colleagues named the new stem cells CARNs, for castration-resistant Nkx3.1-expressing cells.

They normally regenerate part of the tissue that lines the inside of the gland, which produces semen. But the cells can also form tumors if certain genes meant to stop out-of-control growth get turned off.

Shen said researchers had believed that tumors arise from a different layer of cells in the prostate, called basal cells.

“Previous research suggested that prostate cancer originates from basal stem cells, and that during cancer formation these cells differentiate into luminal cells,” Shen said in a statement. “Instead, CARNs may represent a luminal origin for prostate cancer.”

Prostate cancer is the second most common cancer in men worldwide after lung cancer, killing 254,000 men a year globally.

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Military experiment seeks to predict PTSD

11U.S. Marine Lance Cpl. Greg Rivers, 20, of Sylvester, Ga., waits to take psychological tests at the Marine Corps Air Ground Combat Center in Twentynine Palms, Calif. on Sept. 29, 2009.

Military experiment seeks to predict PTSD

Some Marine and Army units being tested to detect early signs of stress

TWENTYNINE PALMS, Calif. – Two days before shipping off to war, Marine Pfc. Jesse Sheets sat inside a trailer in the Mojave Desert, his gaze fixed on a computer that flashed a rhythmic pulse of contrasting images.

Smiling kids embracing a soldier. A dog sniffing blood oozing from a corpse. Movie star Cameron Diaz posing sideways in a midriff top. Troops cowering for safety during an ambush.

A doctor tracked his stress levels and counted the number of times he blinked. Electrode wires dangled from his left eye and right pinky finger.

Sheets is part of a military experiment to try to predict who’s most at risk for post-traumatic stress disorder. Understanding underlying triggers might help reduce the burden of those who return psychologically wounded — if they can get early help.

PTSD is a crippling condition that can emerge after a terrifying event — car accident, sexual assault, terrorist attack or combat. It’s thought to affect as many as one in five veterans returning from Afghanistan and Iraq.

Military doctors have been mystified as to why certain warfighters exposed to bombings and bloodshed develop paralyzing stress symptoms while others who witness the same trauma shake it off.

Studies on veterans and civilians point to some clues. Childhood abuse, history of mental illness and severity of trauma seem to raise a person’s risk. Having a social net and a coping strategy appear to offer some protection.

However, none of the factors explored so far are reliable predictors.

“Right now, we can’t determine with certainty who will and who won’t develop PTSD,” said Paula Schnurr, deputy executive director of the Department of Veterans Affairs’ National Center for Posttraumatic Stress Disorder. “Perhaps with better measures, we can get closer.”

Earlier this year, a quarterly publication from the national PTSD center found that studies to date have looked at only “a narrow band of the potential risk and resilience predictors” and that more work beyond surveys was needed.

Urgency to detect early signs
New PTSD studies are using technology to try to get at the answer. Select Marine and Army units are undergoing a battery of physical and mental tests before deployment including genetic testing, brain imaging and stress exams. They are followed in war zones and upon return.

There’s an urgency to detect early signs. Since the 2001 terrorist attacks, more than 1.8 million U.S. troops have fought in Afghanistan or Iraq. The Obama administration is weighing whether to increase forces in Afghanistan where violence has escalated in recent months.

Previously called shell shock, combat fatigue and post-Vietnam syndrome, PTSD was officially recognized as a mental disorder in 1980. Sufferers experience flashbacks, nightmares, sudden outbursts and social withdrawal and are sometimes haunted years after the trauma.

The ongoing wars have given scientists fresh opportunities to follow service members.

One autumn morning, a throng of Marines squeezed into a trailer at the Marine Corps Air Ground Combat Center in Southern California before deploying to Afghanistan. They belonged to the 3rd Battalion, 4th Marine Regiment — nicknamed the “Thundering Third.”

“We’re doing this not to make you better prepared to go do what you have to do in Afghanistan. We’re not doing this to make your health any better,” said Dr. William Nash, a retired Navy psychiatrist and study co-investigator. “We’re doing this so that we can learn more about how to protect Marines from stress injuries like PSTD.”

Nash asked how many have heard of PTSD. A half dozen raised their hands.

Who wants PTSD? “Right, nobody,” he answered rhetorically.

The trailer soon buzzed like a factory, with Marines rotating from one test station to another in an assembly line. They donated blood, urine and saliva samples so researchers can search for genetic biomarkers that might play a role.

Groundbreaking research published last year on adult survivors of child abuse suggests that specific variations of a gene increased their chances of developing PTSD. Scientists believe there may be many other gene variants that contribute to PTSD risk.

Marines also underwent a blink test to gauge their startle response and neuropsychological screening. They filled out questionnaires and were interviewed by psychiatrists with a checklist to diagnose PTSD.

The work is funded by the Marine Corps, Veterans Affairs and Navy Medicine. Last year, about 1,000 Marines were recruited before leaving for Iraq.

This latest batch of 673 Marines who were tested during a two-week period in the fall headed to Afghanistan where they’re sure to see more intense fighting. They will be followed up in the field by Navy corpsmen with special “stress first-aid” training to read early signals.

Researchers recently did six-month follow-up testing on some Marines who returned from Iraq. It will take time to analyze the results, said the study’s lead investigator, Dr. Dewleen Baker of the VA San Diego Healthcare System.

Cmdr. Bryan Schumacher, the 1st Marine Division’s top doctor, said the purpose of studying PTSD triggers is not to bar someone from service. If it turns out that something can be done to prevent it, those vulnerable could get special training to reduce their risk, he said.

Similar research is ongoing 1,300 miles away at the University of Texas at Austin where scientists have collected detailed health data from 178 soldiers from nearby Fort Hood who recently came back from Iraq. The base was the scene of a massacre on Nov. 5 when an Army psychiatrist opened fire, killing 13 people and wounding dozens more.

The shooting has not affected the research, which enrolled first-time deployed soldiers. Unlike the Marines, the soldiers filled out monthly questionnaires online while in combat that tracked their experiences such as whether they saw a roadside bomb go off or knew of a wounded buddy.

Before deployment, soldiers submitted a DNA sample, had an MRI scan of their brain and inhaled carbon dioxide as part of a stress reaction test.

Early results suggest soldiers who reacted more strongly to the CO2 test and who were exposed to more stress in the field showed greater PTSD symptoms, said chief researcher Michael Telch, of UT Austin’s Laboratory for the Study of Anxiety Disorders.

The decision to volunteer in the Marine experiment was personal for Lance Cpl. Jaecob Kyllo. His grandfather fought in Korea and Vietnam and two uncles served in Operation Desert Storm. They spoke less afterward and would get irritated easily.

Kyllo said his uncles were diagnosed with PTSD and suspects his grandfather had it too.

“I’ve seen it before and it’s not the most pleasant thing,” said the 20-year-old from Seattle, who previously served in Iraq.

Melvin Carter, a 27-year-old Marine sergeant who had done three tours in Iraq, noticed buddies who were once laid-back turn angry after coming home. The Oakland, Calif., native copes with stress by laughing and cracking jokes.

Navy corpsman Benjamin Reinhardt was recently trained to look for signs of PTSD in 20 Marines attached to a mortar platoon. He likened his job to a school nurse. Marines confide in him about their innermost struggles. He thinks he can spot when someone is not himself.

“I tend to be reasonably observant with people’s personalities. I can see changes,” said the 21-year-old from upstate New York.

He added: “I hope none of us become PTSD casualties.”

Sheets, a 22-year-old private first class from Newark, Del., has never seen combat before. Before joining the Marines, Sheets dabbled with college and was working a dead-end job hauling trash.

He enlisted after being inspired by a sermon from his pastor. While in infantry school, he met a sergeant who suffered from PTSD. He’s not exactly sure what it is, but has heard horror stories.

“A guy comes home from war and he’s freaking out. He’s beating his wife. He’s drinking. He’s doing everything he can. He’ll go off and he’ll hate the Marine Corps,” Sheets said. “And it’s just like, OK, is that going to be me when I come home?”

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Cancer

A young woman exhales cigarette smoke in Shanghai, China. The People’s Republic of China is both the world’s largest producer and largest consumer of tobacco, which has led to an impending cancer epidemic in the most populous country on Earth.

Cancer is a disease that begins as a renegade human cell over which the body has lost control. In order for the body and its organs to function properly, cell growth needs to be strictly regulated. Cancer cells, however, continue to divide and multiply at their own speed, forming abnormal lumps, or tumors. An estimated 6.7 million people currently die from cancer every year.

Not all cancers are natural-born killers. Some tumors are referred to as benign because they don’t spread elsewhere in the body. But cells of malignant tumors do invade other tissues and will continue to spread if left untreated, often leading to secondary cancers.

Cancers can start in almost any body cell, due to damage or defects in genes involved in cell division. Mutations build up over time, which is why people tend to develop cancer later in life. What actually triggers these cell changes remains unclear, but diet, lifestyle, viral infections, exposure to radiation or harmful chemicals, and inherited genes are among factors thought to affect a person’s risk of cancer.

Lung cancer is the world’s most killing cancer. It claims about 1.2 million victims a year. Most of those victims are smokers, who inhale cancer-causing substances called carcinogens with every puff. Experts say around 90 percent of lung cancer cases are due to tobacco smoking.

Breast cancer now accounts for almost one in four cancers diagnosed in women. Studies suggest the genes you inherit can affect the chances of developing the illness. A woman with an affected mother or sister is about twice as likely to develop breast cancer as a woman with no family history of the disease. Lifestyle may also have an influence, particularly in Western countries where many women are having children later. Women who first give birth after the age of 30 are thought to have a three times greater risk of breast cancer than those who became mothers in their teens.

Geographical Distinctions

There are also stark geographic differences, with incidence rates varying by as much as thirtyfold between regions. In much of Asia and South and Central America, for example, cervix cancer is the most deadly in females. However, in North America and Europe another kind of gynecological cancer, ovarian cancer, is a more serious threat.

Among males, southern and eastern Africa record the second and third highest rates of oesophageal, or gullet, cancer after China, but western and central regions of Africa have the lowest incidence in the world. Differences in diet may explain this.

Nevertheless, the reasons why many cancers develop remain elusive. Brain cancer, leukemia (blood cancer), and lymphoma (cancer of the lymph glands) are among types that still mystify scientists.

Treatments

Yet ever more people are surviving diagnosis thanks to earlier detection, better screening, and improved treatments. The three main treatment options are surgery, radiotherapy and chemotherapy. Radiotherapy, also called radiation therapy, involves blasting tumors with high-energy x-rays to shrink them and destroy cancerous cells. Chemotherapy employs cancer-killing drugs.

Even so, future cancer cases are predicted to climb, since the world’s population is aging. The proportion of people over age 60 is expected to more than double by 2050, rising from 10 percent to 22 percent. This will add an estimated 4.7 million to the cancer death toll by 2030.