Broccoli Reduces the Incidence of Bladder Cancer

A Biocompare news story entitled 'Broccoli Packs Powerful Punch To Bladder Cancer Cells' cites a study conducted by both Harvard and Ohio State Universities resulting in a finding that men who consumed two or more half-cup servings of broccoli per week enjoyed 44 percent less bladder cancer incidence than men who ate less than a serving per week. From the article:


“We're starting to look at which compounds in broccoli could inhibit or decrease the growth of cancerous cells,” said Steven Schwartz, a study co-author and a professor of food science and technology at Ohio State University .

“Knowing that could help us create functional foods that benefit health beyond providing just basic nutrition.”

Some 63,000 people will be diagnosed with bladder cancer this year, according to the American Cancer Society. And more than 13,000 with the disease will die.

The researchers isolated compounds called glucosinolates from broccoli sprouts. During chopping, chewing and digestion, these phytochemicals morph into nutritional powerhouses called isothiocyanates – compounds that the scientists believed play a role in inhibiting cancer.

Their hunch was right, at least in the laboratory experiments. There, isothiocyanates hindered the growth of bladder cancer cells. And the most profound effect was on the most aggressive form of bladder cancer they studied.

The researchers presented their findings on July 18 in New Orleans at the annual Institute of Food Technologists meeting.

They first extracted and measured the levels of glucosinolates from broccoli sprouts. They then used a process that uses enzymes to convert the glucosinolates to isothiocyanates.

While young sprouts naturally have higher concentrations of these phytochemicals than full-grown broccoli spears, eating the spears also provides health benefits, Schwartz said.

He and his colleagues treated two human bladder cancer cell lines and one mouse cell line with varying amounts of glucosinolates and isothiocyanates. Even though glucosinolates are converted to isothiocyanates, the researchers wanted to know if the former would have any effect on controlling the growth of cancer cells.

It didn't.

However, the isothiocyanates decreased proliferation in all three cell lines. The strongest effect was on the most aggressive of these lines – human invasive transitional cell carcinoma.

The researchers aren't sure what caused this effect, or exactly how these compounds keep cancer cells from proliferating. But they are looking into it.

“There's no reason to believe that this is the only compound in broccoli that has an anti-cancer effect,” said Steven Clinton, a study co-author and an associate professor of hematology and oncology at Ohio State. “There are at least a dozen interesting compounds in the vegetable.

“We're now studying more of those compounds to determine if they work together or independently, and what kind of effects they have on cancer cells,” he added.

Broccoli isn't the only cruciferous veggie with health benefits, the researchers say. The plant's kin, which include cabbage, cauliflower, Brussels sprouts and kale, may all contain similar disease-fighting phytochemicals.

It's too early to suggest just how much broccoli or other cruciferous vegetables should be eaten to stave off or slow down the progression of bladder cancer. Still, they are an important part of the diet.

“Cruciferous veggies have an effect on other types of cancer, too,” Schwartz said. “We already know that they contain compounds that help detoxify carcinogens. We're thinking more along the lines of progression and proliferation, such as once cancer starts, is there a way to slow it down?”

More on Cellular Garbage

A new website called 'Week in Science' published a blog item containing information about the connection between Alzheimer's disease and a cellular garbage disposal function. From the website article:

A Biocompare news story entitled 'Enzyme Shreds Alzheimer's Protein' provides information about an enzyme that may have significance in the battle against Alzheimer's disease. The story is of interest on several levels. The italicized article is interspersed with my comments in bold print.


"An enzyme found naturally in the brain snips apart the protein that forms the sludge called amyloid plaque that is one of the hallmarks of Alzheimer's disease (AD), researchers have found. They said their findings in mice suggest that the protein, called Cathepsin B (CatB), is a key part of a protective mechanism that may fail in some forms of AD. Also, they said their findings suggest that drugs to enhance CatB activity could break down amyloid deposits, counteracting one of the central pathologies of AD.

An enzyme, whose function entails cutting up a protein known to form amyloid plaque, may protect against some forms of Alzheimer's disease. If this is so then drugs enhancing the function of the enzyme could be used to treat the disease. Illustrated are some general approaches to the cause and treatment of disease. Frequently diseases can be traced to malfunctions of cellular mechanisms. The deadly amyloid plaque may accumulate for a variety of reasons one of which could be the breakdown of a mechanism designed to prevent its formation. A single enzyme malfunction could be the culprit.

Li Gan and colleagues published their findings in the September 21, 2006, issue of the journal Neuron, published by Cell Press.

Their experiments were prompted by previous studies showing that the cysteine protease CatB--an enzyme that snips apart proteins--closely associated with the amyloid-ß (Aß) protein that forms the amyloid plaques, a hallmark of AD. However, those studies had not determined whether CatB was "good" or "bad"--that is, whether it acted to produce Aß from a longer protein, called amyloid precursor protein (APP), or whether it broke down Aß.

In their experiments, Gan and colleagues determined that CatB was the latter--breaking down Aß, apparently to enable other enzymes to further degrade the protein for the cell's protein "garbage deposal" system.

Cells need to break down and dispose of proteins. Specific enzymes are part of this system. Because of its essential nature enzymes associated with the function are said to have evolved early in natural history. What sort of cellular life would be viable in the absence of such functions? Presumably the generation of enzymes enabling the degradation and disposal of proteins would occur after proteins and a mechanism enabling their synthesis already existed. Then how would such "life forms" avoid self-destruction amidst a garbage strewn environment?

They found that knocking out the CatB gene increased plaque deposition in a mouse model of AD in which mice expressed the human form of APP. They also found that CatB tended to accumulate within amyloid plaques and that it acted to reduce Aß levels in neurons. And they found that introducing a pathological form of Aß, called Aß1-42, into neurons increased CatB in young and middle-aged mice with human APP, but not old mice. "Thus, upregulation of CatB may represent a protective mechanism that fails with aging," wrote the researchers, and such failure may play a role in late-onset sporadic AD.

Their test tube studies showed that CatB biochemically degrades Aß by snipping one end of the protein, called the C-terminal end. What's more, the enzyme also degrades the long strings of Aß that form amyloid plaque, they found.

Finally, they found that increasing levels of CatB in aging mice with human APP markedly reduced plaque deposits in the animals' brains.

Gan and colleagues concluded that "our findings suggest that inhibition or loss of CatB function could interfere with its protective function and promote the development of AD, whereas overexpression of CatB could counteract Aß accumulation and aggregation. Thus, pharmacological activation of CatB could downregulate Aß1-42 assemblies through C-terminal truncation, offering an approach to the treatment of AD."

This looks promising.

Is Laser Surgery Safer than Contacts?

A news release of Oregon Health & Science University (OHSU) entitled 'Eye Doctor Says Laser Surgery Safer Than Contacts' indicates that laser surgery may be safer than the use of contact lenses. This is a surprising conclusion for some however, there have been instances when those who wear contact lenses lose their eyes as a result of infection connected with the lenses. A part of the article follows. The entire article can be accessed at the link.


The risks associated with laser surgery versus contact lenses can not be compared directly, partly because complications from contact lenses accumulate over years of use, and complications from surgery occur soon after the surgery.

Data extrapolated from a study in Lancet shows the lifetime risk of bacterial keratitis to be 1 in 100 for contact lenses worn daily. Bacterial keratitis is an infection that causes an inflammation of the cornea and can lead to vision loss. Wearing contact lenses overnight or improper care or cleaning further increases the risk of infection from contacts. The risk of bacterial keratitis has changed little over the years for contact lens wearers and is the same worldwide.

Vision loss from laser surgery is easier to calculate. Mathers looked at a large study of military personnel who had laser surgery and found results similar to those of the OHSU Casey Vision Correction Center.

A study of more than 32,000 U.S. Armed Forces members receiving laser surgery published in the journal Ophthalmology found a loss of vision of one line on an eye chart was 1 in 1,250. A loss of two or more lines of vision, which would be more significant, but less frequent, was not reported. Data from the OHSU Casey Vision Correction Center showed no cases of vision loss greater than two lines in 18,000 procedures performed over 10 years.

"Even with perfect care of your contacts, the risks for infection and vision loss are still there," said Mathers. "Our long-term results at OHSU confirm the experience of the U.S. military: Laser surgery is as safe, and probably safer, than long-term use of contact lenses."

The calculated risks of vision loss from contact lenses and laser surgery are approximate and subject to change. Highly oxygen-permeable contact lenses and advances in laser surgery should make both even safer. There are approximately 20 million to 25 million contact lens wearers in the United States, and approximately 1 million people in the United States have laser surgery every year.

"Data from these studies strongly suggest our intuition regarding these risks needs to be reassessed," Mathers said. "I, for one, look forward to further investigations of these risks."

Black Tea: A Stress Recovery Aid

This press release from University College London has some good news for tea drinkers about stress recovery:


"Daily cups of tea can help you recover more quickly from the stresses of everyday life, according to a new study by UCL (University College London) researchers. New scientific evidence shows that black tea has an effect on stress hormone levels in the body.

The study, published in the journal Psychopharmacology, found that people who drank tea were able to de-stress more quickly than those who drank a fake tea substitute. Furthermore, the study participants – who drank a black tea concoction four times a day for six weeks – were found to have lower levels of the stress hormone cortisol in their blood after a stressful event, compared with a control group who drank the fake or placebo tea for the same period of time.

In the study, 75 young male regular tea drinkers were split into two groups and monitored for six weeks. They all gave up their normal tea, coffee and caffeinated beverages, then one group was given a fruit-flavoured caffeinated tea mixture made up of the constituents of an average cup of black tea. The other group – the control group – was given a caffeinated placebo identical in taste, but devoid of the active tea ingredients. All drinks were tea-coloured, but were designed to mask some of the normal sensory cues associated with tea drinking (such as smell, taste and familiarity of the brew), to eliminate confounding factors such as the ‘comforting’ effect of drinking a cup of tea.

Both groups were subjected to challenging tasks, while their cortisol, blood pressure, blood platelet and self-rated levels of stress were measured. In one task, volunteers were exposed to one of three stressful situations (threat of unemployment, a shop lifting accusation or an incident in a nursing home), where they had to prepare a verbal response and argue their case in front of a camera.

The tasks triggered substantial increases in blood pressure, heart rate and subjective stress ratings in both of the groups. In other words, similar stress levels were induced in both groups. However, 50 minutes after the task, cortisol levels had dropped by an average of 47 per cent in the tea drinking group compared with 27 per cent in the fake tea group.

UCL researchers also found that blood platelet activation – linked to blood clotting and the risk of heart attacks – was lower in the tea drinkers, and that this group reported a greater degree of relaxation in the recovery period after the task.

Professor Andrew Steptoe, UCL Department of Epidemiology and Public Health, says: “Drinking tea has traditionally been associated with stress relief, and many people believe that drinking tea helps them relax after facing the stresses of everyday life. However, scientific evidence for the relaxing properties of tea is quite limited. This is one of the first studies to assess tea in a double-blind placebo controlled design – that is, neither we nor the participants knew whether they were drinking real or fake tea. This means that any differences were due to the biological ingredients of tea, and not to the relaxing situations in which people might drink tea, whether they were familiar with the taste and liked it, and so on.

“We do not know what ingredients of tea were responsible for these effects on stress recovery and relaxation. Tea is chemically very complex, with many different ingredients. Ingredients such as catechins, polyphenols, flavonoids and amino acids have been found to have effects on neurotransmitters in the brain, but we cannot tell from this research which ones produced the differences.

“Nevertheless, our study suggests that drinking black tea may speed up our recovery from the daily stresses in life. Although it does not appear to reduce the actual levels of stress we experience, tea does seem to have a greater effect in bringing stress hormone levels back to normal. This has important health implications, because slow recovery following acute stress has been associated with a greater risk of chronic illnesses such as coronary heart disease.”

Flesh Eating Bacteria

The website of the Howard Hughes Medical Institute published an interesting report related to so called flesh-eating baceria. The article is entitled 'Solved: The Mystery of Flesh-Eating Bacteria's Relentless Attack.' The article revealed an enzyme called ScpC, produced by the bacteria Streptococcus, degrades interleukin-8; an immune system signaling molecule. From the article:



Emanuel Hanski, a microbiologist at Hebrew University in Jerusalem, and colleagues have found that the success of group A Streptococcus is due in part to a protein that blocks the immune system's distress calls. The findings, published in the October 4, 2006, issue of the EMBO Journal, could lead to new strategies for treating necrotizing fasciitis and halting its rapid destruction of tissue. The paper was published in advance online.


“There are different avenues you could explore for treatment, all based on reducing the amount of ScpC the bacteria produces.”
Emanuel Hanski

The bacterium, group A Streptococcus, wreaks destruction on muscle and skin tissue in the form of necrotizing fasciitis, which kills roughly 30 percent of its victims and leaves the rest disfigured. Antibiotics and surgical interventions, the known treatments, often fail. Necrotizing fasciitis is a serious but rare infection of the skin and the tissues beneath it.

The work began two years ago, when Hanski developed a mouse model for necrotizing fasciitis. After injecting the mice with a virulent strain of Streptococcus of a type known as M14, isolated from a necrotizing fasciitis patient, the team noticed that unlike most strep infections, in which white blood cells swarm invading bacteria to clear them from the body, few white blood cells appeared at the M14 infection site. A similar phenomenon had been observed in patients with necrotizing fasciitis but did not receive sufficient attention at the time.

“We knew that the pathology of the disease in people was typified by various degrees of a lack of white blood cells," said Hanski. After publishing their findings in the British medical journal The Lancet in 2004, the team began to search for the factor that blocked the recruitment of white blood cells during M14 infection.

They focused on the gene for a Streptococcus peptide called SilCR, after finding that the gene product was turned off in the M14 strain. “This gene is supposed to produce a peptide that acts as a signaling molecule that the Streptococcus bacteria use to communicate with each other,” said Hanski. “Since the bacteria were not producing the peptide, we decided to synthesize it ourselves and give it to mice infected with M14.”

The mice receiving this peptide survived at a much higher rate than mice that did not receive it. The team also observed many white blood cells at the infection site in mice receiving the peptide.

Next, the team turned its attention to an important human immune system signaling molecule, interleukin-8. In healthy people, an infection triggers the production of interleukin-8(IL-8), which acts as a distress call. “When the body senses an infection, it creates interleukin-8 to recruit white blood cells to the infection,” said Hanski.

In a laboratory culture, the M14 strain of Streptococcus destroyed IL-8. But when the team added the SilCR protein to the growing bacteria, the IL-8 survived.

“The amount of IL-8 that survives is inversely related to how much SilCR there is in the culture,” said Hanski. This may be one reason why some strains are less virulent than others; they might make more SilCR. “It would be interesting to study the amount of SilCR produced by the other strains and to determine their degree of tissue invasiveness.” said Hanski.

The link between SilCR and a healthy immune response still did not explain the underlying mechanism. The team knew that SilCR itself did not degrade IL-8, so they began to search for the missing link in the chain of events. They expected to find an enzyme that degrades IL-8. Drawing on a database of enzymes and using advanced techniques that measure the levels of gene transcription products in a cell, they soon identified the culprit: an enzyme called ScpC.

The team then created a mutant variation of the M14 strain of Streptococcus that could not produce ScpC. As expected, this strain was much less virulent than the original M14. Only three of 28 mice receiving the mutant strain succumbed to infection, a death rate much lower than that of mice who received the original strain. Mice receiving the original bacteria developed lesions that grew until the mice died; while mice receiving the mutant strain developed only small lesions that spontaneously healed.

“The experiments show that SilCR down-regulates the production of ScpC, and ScpC is what destroys the IL-8,” said Hanski. “In our strain, M14, SilCR is missing completely, which explains why it is so virulent.”

He said the work points to more effective strategies for treating Streptococcus infection. “There are different avenues you could explore for treatment, all based on reducing the amount of ScpC the bacteria produces,” Hanski said. “You could look for a specific inhibitor of ScpC, or you could explore the activity of SilCR more fully and try to boost its action.”

Cancer and p53

In the blog 'Intelligently Sequenced' there appears a post entitled 'The Notorious p53.' The post, most of which is quoted below, refers to an article appearing at the website of St. Jude Children’s Research Hospital. The focus of the article is a protein known as p53 which has a function related to damaged DNA. Mutations involving the gene coding for this protein are common among cancer patients. The article:


"The website for St. Jude Children’s Research Hospital features an article about p53 levels. P53 is associated with responses to damaged DNA occasioned by radiation and chemicals. More than any other gene, the gene that codes for the p53 protein is found mutated in cancer patients.

As the article entitled 'Mechanism controlling DNA damage response has potential novel medical applications' indicates, p53 is associated with cellular responses to stress. Research connected with it is linked to efforts to improve cancer therapies. A cause of cancer is believed to be damage to DNA brought about through radiation and chemical reactions.

An impact of the St. Jude study was a finding thatDNA damage led to an increase in p53 protein synthesis. This finding ran counter to a previously held notion that enhanced p53 levels resulted from a decrease in the rate in which the protein is broken down. A practical benefit to the discovery is apparant namely, a potential to manipulate the synthesis rate to occasion positive results following damage to DNA.

Following damage to DNA p53 can either prevent cellular division or trigger apoptosis or cellular suicide. In so doing p53 inhibits the proliferation of damaged cells which in turn can inhibit cancer.

The specifics of the mechanism controling the rate of p53 synthesis involve an untranslated region of mRNA coding for p53. This UTR acts as a control switch. A protein known as nucleolin suppresses synthesis of p53 by binding to the UTR of p53 mRNA. When DNA damage occurs however, another protein known as RPL26 binds the UTR and causes accelerated translation of the mRNA resulting in more p53.

Researchers were able to document the link between the regulating proteins and synthesis levels by inhibiting RPL26 production which short circuits an increase in p53 following damage to DNA. The p53 functions of halting cellular proliferation or apoptosis were correspondingly compromised. Likewise reduced nucleolin levels increase p53 production in response to DNA damage.

The article goes on to indicate a general approach to the phenomenon of protein synthesis shutdown which can result from damaged DNA or other factors like hypoxia- too little oxygen. By utilizing specific regulatory binding proteins a bypass strategy might be realized."