Researchers at the UC San Diego School of Medicine and the Moores UCSD Cancer Center have new evidence that a type of immune system cell thought to be part of the first line of defense against breast cancer may also help promote its spread. They have found that when these cells, known as lymphocytes, make an inflammatory protein called RANKL (RANK ligand), breast cancer is more likely to spread to the lungs.

They have also shown that blocking a cascade of cellular signals that follow RANKL's docking to its receptor (RANK) on tumor cells can halt cancer progression, or metastasis, and may be a possible target for drug therapy.

The scientists, led by first author Wei Tan, PhD, a postdoctoral fellow in the Department of Pharmacology at the UC San Diego School of Medicine and Michael Karin, PhD, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, say that the findings establish RANKL as a potential marker that can be used to help determine breast cancer prognosis and adds further proof to the potentially important role of inflammation in cancer development and spread. They reported their findings April 22, 2009 at the AACR 100th Annual Meeting 2009 in Denver.

According to Tan, the role of lymphocytes in breast cancer progression has been controversial for the last 20 years. Such cells are supposed to detect and eliminate cancer cells, but paradoxically, the infiltration of lymphocytes such as B cells and T cells into breast cancer is sometimes an indicator of poor prognosis, including cancer recurrence and metastasis. RANKL has been shown in previous studies to be an important inflammatory protein that can lead to bone loss by activating cells that help break down bone. Along with another protein, IKK alpha, it has been implicated both in tumor formation and metastasis.

The researchers created two types of mice that developed breast tumors. One group had lymphocytes in the tumors and expressed RANKL while the other group did not. They found that the group lacking RANKL had significantly fewer lung metastases than those mice with RANKL. They then took tumor cells from both types of mice and injected them into mice with the same genetic background to avoid rejection and monitored the ability of the mice to form tumors and metastases to the lung.

The researchers didn't find any lung tumor metastases in mice without lymphocytes. Yet, when RANKL was injected into the animals, the same potential for the cancer to spread was restored, indicating that the lymphocytes, which make RANKL, are critically important to the process.

"Without lymphocytes, there is no metastasis," said Tan. "If we treat the mice with RANK ligand, there are metastases, which indicate that RANK ligand can compensate for the function of lymphocytes."

The study establishes the role of RANKL-expressing lymphocytes as a promoting factor in breast cancer metastasis and provides a potentially good marker for breast cancer prognosis, the researchers said.

Tan noted that additional experiments showed that blocking both RANKL and IKK alpha in those breast tumor cells inhibited lung metastases. "More importantly," he said, "blocking the signaling pathway downstream of RANKL blocks primary metastasis and can potentially be developed as a treatment strategy."

Results such as these are helping to change the thinking about inflammation and cancer. "In general, we used to think that inflammation in the immune response is a part of the host defense against the tumor, but now we think that there are different kinds of inflammation," Tan said. "For example, T-helper cells can activate an anticancer response, but can also promote a separate tumor promoting response. In this study, if we target the host pro-tumor inflammation and immune response, we can also reduce tumor metastasis and are very likely to develop a therapy that is more effective."

People are continually on the lookout for ways to safeguard their family's health at home. However, some of the most likely sources of danger may not be the first that come to mind. The National Pest Management Association (NPMA) warns that rodents, cockroaches and stinging insects pose serious, but often hidden, health risks when they infest a home.

"Many people think pests are just an annoyance and often forget that there are real health dangers associated with the presence of these pests in and around the home," says Greg Baumann, senior scientist for NPMA. "People don't think of asthma, Salmonella, or severe allergic reactions, which is why infestations should not be taken lightly."

Rodents bring other pests including fleas, mites, ticks and lice indoors and contaminate food with feces that can transmit Salmonella and Hantavirus. Cockroaches spread 33 kinds of bacteria, six parasitic worms and more than seven other types of human pathogens. More, cockroach droppings and shed skins lead to allergen accumulation that can trigger asthma attacks, especially in children. Nearly $1B is spent on professional cockroach management services in the U.S. each year, making them one of the most prevalent and hazardous pests.

Stinging insects, including wasps and hornets send more than half a million people to the emergency room every year. And according to the Center for Disease Control, West Nile virus, a disease spread by mosquitoes, resulted in more than 1,300 human cases and 43 fatalities in 2008.

NPMA offers these tips to keep pests from becoming a hidden danger at home:

- Mosquitoes breed in stagnant water. Eliminate standing water and sources of moisture in or around the home, in flowerpots, pool covers and other objects that collect water.

- Keep food and garbage in sealed containers.

- Seal cracks and holes in your home's exterior and patch ripped screens.

- If you see signs of a pest infestation, contact a licensed pest professional.

As the number of cases and deaths from swine flu go up in Mexico, and the US, Canada and other countries also report cases of the disease, but so far no deaths, other countries begin to take measures to contain the outbreak amid fears that this could be the start of a new global flu pandemic.

According to El Norte, a leading daily Mexican newspaper, the Mexican government's latest announcement is that 103 have died of flu, which the authorities suspect was swine flu, but this has not yet been confirmed through lab tests. According to other media reports, 20 of the deaths so far have been confirmed as swine flu.

Mexico's health minister, José Angel Córdova told Televisa network on Sunday evening that the suspected death toll had gone up from 81 on Saturday, and suspected cases of swine flu has gone up to 1,600, with about 1,000 of those people now recovered and released from hospital.

Córdova said the government has declared a state of "sanitary alert". In Mexico City and some states the authorities have closed schools and day care centres. Businesses are still open but employers have been asked to be sympathetic about absences and latecomers because people will struggle with childcare.

Hundreds of public events were cancelled in Mexico City on Sunday: two First Division football matches played to empty stadiums, church services were suspended, and many entertainment and culture events were cancelled. Restaurants in the city are being asked to shut early and limit customers to 50.

People have started using surgical masks, many of which are being handed out by government officials. Mexico City Mayor Marcelo Ebrard said they would shut down the metro if cases continue to rise: it transports about 4 million people a day, said the Washington Post.

On Sunday, the US government declared a state of public emergency after reporting 20 laboratory confirmed human cases of swine influenza A/H1N1. 8 of them in New York, 7 in California, 2 in Texas, 2 in Kansas and 1 in Ohio.

Acting head of the US Centers for Disease Control, Richard Besser, said that while the virus appeared to be the same strain as that infecting people in Mexico, the effect has been milder, reported the Financial Times. All 20 people had mild flu-like symptoms and only 1 of them had to be kept in hospital.

According to the World Health Organization (WHO), preliminary lab tests on the 20 cases found that the viruses had the same genetic pattern, and the virus is being described as a new subtype of A/H1N1 not previously seen in pigs or humans.

The New York Times reported that Secretary for Homeland Security Janet Napolitano told a news conference in Washington on Sunday that the emergency declaration was a standard measure to make sure that funds can be released and emergency measures taken without delay. She likened it to getting ready incase a hurrican strikes, but hopefully it will not.

There are also reports of confirmed cases in Canada, and suspected cases in New Zealand, Spain and Israel. No deaths have been reported outside Mexico, and most of the patients have made a full recovery.

The WHO Emergency Committee, which was formed in 2005, met on Saturday for the first time to discuss the outbreak. Under the advice of the Committee, the Director General urged all countries to " intensify surveillance for unusual outbreaks of influenza-like illness and severe pneumonia".

The WHO Emergency Committee said that based on the evidence so far, the "current situation constitutes a public health emergency of international concern", although there are still many unanswered questions.

According to the Financial Times, Dr Keiji Fukuda, the WHO's assistant director-general for health security, said the committee will be reviewing the situation again on Tuesday, and will then decide whether to raise the current pandemic alert phase from 3 to 4. It has been at phase 3 for some years, but in response to a different virus, the much deadlier H5N1 Avian flu virus.

Under the WHO pandemic flu phase system, phase 3 means "an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people", but human to human transmission has not led to sustained community outbreaks. After that is phase 4, which indicates sustained human to human community level transmission, phase 5 means it has spread to sustained level in at least one other country in the WHO region and the world should prepared for global pandemic, and phase 6 is global pandemic is under way.

A BBC News report earlier this morning said that health officials are warning that the UK should expect to see cases of swine flu. Two people are still undergoing tests in Lanarkshire after they came back from Mexico with flu-like symptoms.

Health Protection Agency Chief Executive Justin McCracken told the BBC that because of the way the strain is spreading across America, it was sensible to prepare for it in the UK as well.

"We are already mobilising things in the UK in case the virus comes over here. I definitely think we have enough of the drugs," said McCracken, adding that he did not think at this stage it was necessary to declare a state of emergency.

The UK and France are rated by the WHO as the two countries that are best prepared for an outbreak, said the BBC report.

Health Secretary Alan Johnson said the UK has a stockpile of flu drugs ready. The drugs, believed to be mostly Tamiflu, deal with the virus very effectively, he said, because "we know from Mexico".

Also, as soon as the strain is confirmed, then the UK government can set in motion pre-existing arrangements to make vaccines, he added.

The Foreign and Commonwealth Office is not currently advising people against travelling to affected areas of Mexico and the US, said the BBC.

By declaring a state of emergency in the US, the government can now release a quarter of the national stockpile of 50 million courses of anti-flu medication, and also allow some unapproved tests and drugs to be given to children, said the New York Times.

In Hong Kong, where memories of the SARS outbreak are still strong, the government has implemented much stricter measures. Travellers have been told to avoid Mexico and anyone arriving with a high temperature who has been to any city with a confirmed case is being detained and sent to hospital for testing. They are only released if the test is negative.

According to the Associated Press, passengers coming off planes at Narita International Airport near Tokyo, Japan, are being scanned by thermographic devices that can detect a person's temperature from a few feet away.

Many other Asian countries are also using thermal scanners to screen out passengers with high temperatures, said a Reuters AlertNet report early this morning.

Although there is no evidence that swine flu can be caught from pig products, Russia has banned meat imports from Mexico and other Latin American countries, as well as several states in the US; while Thailand has banned all pork imports from the US and Mexico, reported the Washington Post.

Medical College of Wisconsin Cancer Center researchers in Milwaukee have learned that a protein, CXCL12, that normally controls intestinal cell movement, has the potential to halt colorectal cancer spreading. These studies represent a potential mechanism by which CXL12 may slow cancer spreading. Controlling this process could lead to new biological therapies for colorectal cancers.

"Colorectal cancer ranks third in cancer-related deaths in the United States in 2008," says principal investigator Michael Dwinell, Ph.D., professor of microbiology and molecular genetics. "Finding therapies to prevent its spread to secondary organs would increase patient prognosis considerably." Luke Drury, a graduate student in the interdisciplinary program for biomedical research at the Medical College, was his research associate. Their abstract will be presented at the American Association for Cancer Research meeting in Denver, April 21.

Normal intestinal cells stick to underlying proteins, which provide survival signals to maintain cell health. If they become unstuck, the floating cells undergo a programmed cell death. In cancer, cells have acquired genetic changes that allow them to survive during loss of attachment. Previously, the researchers found that colorectal cancer cells lacked CXCL12 expression. In these studies, they re-introduced CXCL12 expression in colorectal cancer cells which prevented their ability to adhere to underlying proteins. Plus, the floating cells underwent programmed cell death.

The calming neurological effects of nicotine have been demonstrated in a group of non-smokers during anger provocation. Researchers writing in BioMed Central's open access journal Behavioral and Brain Functions suggest that nicotine may alter the activity of brain areas that are involved in the inhibition of negative emotions such as anger.

Jean Gehricke led a team of researchers from the University of California who studied the effect of nicotine patches on the subjects' tendency to retaliate in response to anger provocation. The subjects played a computer game and could see a video screen of another player who they believed to be their opponent, although, in fact, they were playing alone. After each round, the victor could give his opponent a burst of unpleasant noise - at a duration and volume set by the winner. In some of the subjects, nicotine was associated with a reduced tendency to retaliate, even after provocation by the 'opponent'.

According to Gehricke, "Participants who showed nicotine-induced changes in anger task performance also showed changes in brain metabolism. Nicotine-induced reductions in length of retaliation were associated with changes in brain metabolism in response to nicotine in brain areas responsible for orienting, planning and processing of emotional stimuli".

The authors say that their findings support the idea that people of an angry disposition are more susceptible to nicotine's effects, and are therefore more likely to become addicted to cigarettes. They conclude, "Novel behavioral treatments that affect the cortical and limbic brain areas, like anger management training, may aid smoking cessation efforts in anger provoking situations that increase withdrawal and tobacco cravings".