Chemical link to testicular cancer probed

Scientists hope to prove whether common environmental chemicals, such as those used to make plastics, are to blame for rising testicular cancer rates.

Experts suspect that exposure while in the womb might explain why the rate of this cancer has doubled in 35 years.

The Edinburgh team told Human Reproduction such a study was only now possible because they had made a model to study the disease in development.

They will use mice harbouring human cells to test the theory.

Testicular cancer occurs in young men, but doctors have known for some years that the abnormal changes that lead to testicular cancer happen in the first few months that the foetus is growing
But because these changes occur during early pregnancy, when there is no means of studying the foetal testes, doctors do not know how and why these changes occur.

Researchers are fairly certain there must be an environmental cause because the rate of the cancer has increased so rapidly.

According to Professor Richard Sharpe, of the Medical Research Council's Human Reproductive Sciences Unit, one theory is that the changes are caused by pregnant women being exposed to environmental chemicals such as phthalates, which are used in many different household items, including plastic furniture and packaging.

But because the cancers only develop 20-40 years after the patient is born, it has been hard for doctors to discover what happened in foetal development to cause this to happen, especially when trying to establish if their mothers were exposed to phthalates or other environmental chemicals to establish a causal relationship.

Mouse model

Now the MRC researchers have developed a model in which early human foetal testis development can be studied and manipulated experimentally to establish once and for all if exposure to environmental chemicals is a likely culprit.

Prof Sharpe's team has grafted testis tissue from aborted foetuses under the skin of mice. The germ cells in the testes are at the critical stage when any faults in their development can result in changes which make them pre-cancerous.

The researchers will expose the mice to phthalates or other environmental chemicals to see if this induces changes in the foetal germ cells that would predispose them to develop into a cancer.

Prof Sharpe said: "We are choosing to study phthalates first for several reasons, because we know that in the test-tube they can affect foetal human germ cells. They are also the most ubiquitous of environmental chemicals. We are all exposed to them."

Phthalates are used to make plastic flexible, and so can be found in carpets, wall boards, car upholstery and fittings and certain cosmetics and pharmaceutical drugs.

However, Prof Sharpe said that there was uncertainty about whether phthalate effects on the foetus in animal models were relevant to humans.

He said: "This is one of the critical unresolved questions as to whether phthalates pose a risk to human health or not.

"It's a huge industry. These compounds are literally part of the fabric of our modern society so they cannot easily be banned or removed without having widespread effects on everyday life. We need to know for sure if these compounds are harmful or not. The hope is that our studies can resolve this one way or another."

The researchers say that if phthalates do cause effects on human foetal germ cells they could know within a year. If the chemicals are not responsible it could take much longer to conclusively disprove any link.

Fit heart can slow brain ageing, US researchers say

Keeping your heart fit and strong can slow down the ageing of your brain, US researchers say.

A Boston University team found healthy people with sluggish hearts that pumped out less blood had "older" brains on scans than others.

Out of the 1,500 people studied, the team observed that the brain shrinks as it ages.

A poor cardiac output aged the brain by nearly two years on average, Circulation journal says.

The link was seen in younger people in their 30s who did not have heart disease, as well as elderly people who did.

Lead researcher Dr Angela Jefferson said: "These participants are not sick people. A very small number have heart disease. The observation that nearly a third of the entire sample has low cardiac index and that lower cardiac index is related to smaller brain volume is concerning and requires further study."

The participants with smaller brain volumes on magnetic resonance imaging did not show obvious clinical signs of reduced brain function.

But the researchers say the shrinkage may be an early sign that something is wrong.

More severe shrinkage or atrophy occurs with dementia.

Dr Jefferson said there were several theories for why reduced cardiac index - how much blood the heart pumps out relative to body size - might affect brain health.

For example, a lower volume of blood pumping from the heart might reduce flow to the brain, providing less oxygen and fewer nutrients needed for brain cells.

"It is too early to dole out health advice based on this one finding but it does suggest that heart and brain health go hand in hand," she said.

Experts say a person's cardiac index is fairly static - meaning it would be difficult to change it if it were low, without doing pretty intensive exercise training.

Dr Clinton Wright, a brain and memory expert from the University of Miami, said: "Whether lower cardiac index leads to reduced brain volumes and accelerates neurodegeneration on an eventual path to dementia is not yet clear.

"To address the health needs of our ageing population, a better understanding of the links between cardiovascular disease and brain structure and function will be required."

The Boston School of Medicine team will now continue to study the individuals in the trial to see if and how the brain changes affect memory and cognitive abilities over time.

Two Die in Florida From Eastern Equine Encephalitis

TAMPA, Fla. (Reuters) Jul 30 - Two Florida residents have died from Eastern equine encephalitis, a mosquito-borne disease that is rare among humans but has infected a rising number of horses in the state, health officials said on Friday.

Both deaths were in the Tampa area, where a woman died on July 1 and an infant died on Wednesday, the Hillsborough County Health Department said. There is no vaccine for humans.

"It's a fairly rare disease," said Steve Huard, spokesman for the Hillsborough health department.

Only a few human cases a year are reported in the United States, mostly in Atlantic and Gulf coast areas, according to the U.S. Centers for Disease Control and Prevention. But the disease kills 33% of its victims and survivors often have significant brain damage, the CDC said.

Hillsborough County has issued a mosquito-borne illness alert and sent a plane to spray pesticides to kill mosquitoes that breed in standing water, Huard said.

Eastern equine encephalitis outbreaks are not uncommon among horses in Florida during the wet summer months when mosquitoes proliferate.

Sixty cases have been reported among Florida horses this summer in several dozen counties, Florida Agriculture and Consumer Services Commissioner Charles Bronson said.

Two cases of West Nile disease, another mosquito-borne viral disease, have also been reported among horses in Florida, though the CDC said the state has reported no human cases.

West Nile disease is usually mild in humans and most who contract it have no symptoms, although it killed 32 people in the United States last year.

Mosquitoes carry the viruses that cause both diseases and can transmit them to both horses and humans, but horses do not transmit the viruses to people.

Bronson urged horse owners to get their animals vaccinated against both.

"In the vast majority of cases we have seen this year, the horses either had no vaccinations at all or they were not current," Bronson said.

"We are seeing increases in mosquito populations and, since mosquitoes are the carriers of both these diseases, it's likely the situation is going to get worse before it gets better."

Eastern Equine Encephalitis kills 90% of infected horses, while West Nile virus has a mortality rate in horses of about 30%. Signs of the viruses include fever, listlessness, stumbling, circling and coma.

While the incidence of both diseases is down from levels seen earlier in the decade, the toll for 2010 continues to rise among horses, Bronson said.

Florida has also seen a resurgence of dengue fever, another viral disease transmitted by mosquitoes, in southern Florida after a 75-year absence from the state.

Dengue is common in Central America and the Caribbean and the hemorrhagic form of the disease can kill humans, although no recent dengue deaths have been reported in the continental United States.

Health officials urged residents to use mosquito repellents, wear protective clothing and avoid being outside at dawn and dusk, when mosquitoes are most active.

Meat Preservatives Linked to Bladder Cancer?

High intake of ingredients known as nitrite and nitrate added to processed meats to aid preservation may be tied to bladder cancer -- but the relationship appears to be tentative, researchers say. In a study that followed more than 300,000 men and women for seven years, dietary nitrite and nitrate, as well as nitrite alone, were associated with an increased risk of bladder cancer among individuals with the highest consumption of processed meat -- but the connection was of borderline statistical significance, according to Amanda J. Cross of the National Institutes of Health and colleagues. In other words, the findings may have more to do with chance alone than with an actual causal link. Consumption of processed meat itself was not associated with an increased risk of bladder cancer, Cross and colleagues reported in the journal Cancer. "I think we should approach these modest results with caution," Dr. Shilajit Kundu, chief of urologic oncology at Northwestern Memorial Hospital, said in an interview with MedPage Today. Kundu was not involved in the study. Nathan Bryan of the University of Texas, who also was not involved in the study, had similar concerns. "There is not one single bit of data presented that is statistically significant by conventional statistical rules with 95 percent confidence," he said in an email to MedPage Today and ABC News. "With over 300,000 subjects, statistical significance should not be a problem if there is a clear and indisputable association." Researchers suspect that meat could be involved in bladder cancer due to compounds related to cooking and processing, including nitrates, nitrites, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). Nitrate and nitrite are added to processed meat for preservation as well as enhancement of color and flavor. PAHs and HCAs can form during cooking. These compounds and their metabolites are excreted through the urinary tract, which could lead to the development of cancer through contact with the cells lining the bladder or through systemic exposure, the researchers said. Yet evidence from prospective studies of meat and bladder cancer has been inconsistent. So the researchers looked at data 300,933 patients in the NIH-AARP Diet and Health Study, which included a food frequency questionnaire. Using various databases of nutritional information, they estimated intakes of nitrate, nitrite, HCAs, and PAHs. Over seven years of follow-up, there were 854 cases of transitional cell bladder cancer. The researchers found that, compared with those who ate the least amounts of red meat those who ate the most had a 22 percent higher risk of bladder cancer, though the finding was of borderline statistical significance. The researchers said the relationship was driven by consumption of processed red meats. However, there was no association between bladder cancer and white meat or processed meat itself. There was also no association between bladder cancer and beef, bacon, hamburger, sausage, or steak -- but the researchers did find a positive association for cold cuts made from red meat. While bladder cancer and nitrate were not linked, there was an association with dietary nitrite. Those with the highest nitrite consumption had an increased risk compared with those with the lowest intake -- but again this finding did not reach the traditionally accepted level of statistical significance. Still, Cross and colleagues said the findings "support the hypothesis of 'N-nitroso compounds' involvement in bladder carcinogenesis, as processed meat also provides amines and amides necessary for the endogenous formation of [these compounds]." The researchers said the findings "provide modest support" for an increased risk of bladder cancer associated with nitrite plus nitrate and PhIP, but acknowledged that the study was limited by a lack of information on urination frequency and bladder infections and limited data on beverage intake. The authors called for further research into different dietary sources of nitrate and nitrite to determine which may have the strongest association with bladder cancer. "Additional research is needed to confirm our findings of a possible increased risk of bladder cancer with intake of red meat and especially for PhIP, as prospective investigations of meat-related mutagens and this malignancy are lacking," they added. Kundu told MedPage Today that "a lot of work still needs to be done before we can say that red meats or processed meats should be cut out all together."

Cardiotoxicity of Childhood Cancer Treatments Affects Many Young Adult Survivors

August 2, 2010 — More than one fourth of childhood cancer survivors treated with potentially cardiotoxic therapies have an abnormal cardiac function as young adults, according to new research.

Helena J. van der Pal, MD, with the Department of Medical Oncology, at the Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands, and colleagues reported the findings in the June 26 issue of Archives of Internal Medicine.

According to Dr. van der Pal and colleagues, studies evaluating cardiovascular toxicity in this setting have produced variable results. "Several population based studies observed a 6- to 8-fold increased mortality owing to CVD [cardiovascular disease] among childhood cancer survivors compared with the general population," they note.

To evaluate the incidence of cardiovascular toxicity further, they conducted echocardiograms in 525 young adults who had survived at least 5 years after treatment with potentially cardiotoxic therapies (anthracyclines, cardiac irradiation, high-dose cyclophosphamide, or high-dose ifosfamide). Of those, 514 were assessed for left ventricular shortening fraction (LVSF).

Overall, the median LVSF was decreased by 33.1% (range, 13.0% - 56.0%), and 27% of patients were defined as having subclinical cardiac dysfunction, defined as LVSF of less than 30%.

On multivariate analysis, the strongest predictors of subclinical cardiac dysfunction were higher cumulative anthracycline dose, thoracic irradiation, and diagnosis at a younger age.

High-dose cyclophosphamide and ifosfamide were not associated with a reduction of LVSF, whereas vincristine sulfate was associated with a trend towards decreased cardiac function (P = .07). When adjusted for antitumor efficacy, epirubicin hydrochloride was comparable to doxorubicin in cardiotoxicity, and both seemed more cardiotoxic than daunorubicin hydrochloride.

"Continued monitoring of all childhood cancer survivors treated with potentially cardiotoxic therapy with or without subclinical cardiac dysfunction is necessary to identify (childhood cancer survivors) who could possibly benefit from early treatment, which could avoid further deterioration of cardiac function," the authors conclude.

The study was supported by the Foundation of Pediatric Cancer Research, Amsterdam, the Netherlands. The study authors have disclosed no relevant financial relationships.

Herpes virus used to treat cancer

Doctors say they have used a genetically engineered herpes virus to treat successfully patients with head and neck cancer.

A London hospital trial of 17 patients found that use of the virus alongside chemotherapy and radiotherapy helped kill the tumours in most patients.

It works by getting into cancer cells, killing them from the inside, and also boosting the patient's immune system.

Further trials are planned for later in the year.

Head and neck cancer, which includes cancer of the mouth, tongue and throat, affects up to 8,000 people every year in the UK.

Study leader Dr Kevin Harrington, who is based at the Institute of Cancer Research in London, said current treatments were effective if the cancer was picked up early but that many patients were not diagnosed until it was more advanced.

The herpes virus, which is also being tested in patients with skin cancer, is genetically manipulated so that it grows inside tumour cells but cannot infect normal healthy cells.

Once there it has a triple effect - it multiplies, killing tumour cells as it does so, it is engineered to produce a human protein that activates the immune system and it also makes a viral protein that acts as a red flag to immune cells.

'Potential weapon'

In the 17 patients injected with the virus, in addition to their standard treatment, at the Royal Marsden Hospital, 93% showed no trace of cancer after their tumour had been surgically removed.

More than two years later, 82% of patients had not succumbed to the disease.

Only two of 13 patients given the virus treatment at a high dose relapsed, the journal Clinical Cancer Research reported.

There were no safety concerns with use of the virus, the researchers said, and it is hoped the virus could one day be used to fight other types of cancer.

"Around 35 to 55% of patients given the standard chemotherapy and radiotherapy treatment typically relapse within two years, so these results compare very favourably," said Dr Harrington.

He is now planning a trial comparing the viral treatment with the standard treatment in people newly diagnosed with head and neck cancer.

Dr Alison Ross, senior science information officer at Cancer Research UK, said it would be some time before the treatment could be used in patients as it still needed to be tested directly against standard treatment.

But she added: "This small study highlights the potential of using genetically modified viruses as a weapon to fight cancer."

Family, Friends Help You Live Longer

Humans are social animals, and most of us treasure our relationships with family and friends.

An emerging line of research suggests that relationships can keep us healthier. And a new study finds those social connections may also help us live longer.

This new study combined a large number of previous studies and concluded that a lack of social interactions ranks right up with smoking, obesity, and alcoholism as a risk factor for death.

Researchers from Brigham Young University analyzed 148 studies with a total of some 300,000 participants, tracking their social relationships and whether they survived to the end of their particular study, which averaged about seven years.
"Those who scored higher on those measures of social relationships were 50 percent more likely to be alive at that follow-up than people who scored low on those measures," said Professor Julianne Holt-Lunstad, one of the authors of the study.

She pointed out several ways relationships can affect our health. They can help us cope with stress. They can help us maintain healthy habits like eating well, exercising or seeing a doctor. And there's increasing research that shows a direct but poorly-understood link between relationships and physiological processes in the body.

"So for instance, our relationships have been linked to lower blood pressure, better immune functioning, and even inflammatory processes that are implicated in a number of diseases," said Holt-Lunstad. "And so our relationships can influence our health in a variety of ways that are all very important."

Even though Holt-Lunstad and her colleagues looked at almost 150 different scientific studies, most of them didn't assess the quality of the relationships.

"And certainly relationship quality matters, and not all relationships are entirely positive," she conceded. "And so it's possible that the effects that we have reported may be a conservative estimate, and that the odds of survival associated with high-quality relationships may actually be larger."

Speaking via Skype, Julianne Holt-Lunstad said her research suggests that policy makers need to consider relationships as a health issue. So just as no-smoking zones have expanded over the years, she suggests that city planners, for example, should consider whether their decisions might promote or hinder the development of personal relationships.
Julianne Holt-Lunstad's study is published in the journal PloS Medicine.