Cancer Screening Rates Have Fallen In US

Despite evidence that earlier diagnosis and improved treatment increases survival, rates of people seeking preventive cancer screening have fallen in the US in the last ten years. Failure of leading bodies to agree screening guidelines, plus reductions in workers with insurance cover could be among reasons for the decline, suggest researchers from the University of Miami Miller School of Medicine.
They write about their NIH-funded study in a paper published 27 December in the online open-access journal Frontiers in Cancer Epidemiology.

In the US, although numbers of cancer survivors have gone up as a result of improved diagnosis and treatment, cancer is still one of the most prominent chronic diseases that in 2011 killed more than 570,000 people.

Alongside a fall in rates of advanced cancer diagnoses in the US in the last ten years, has been an increase in the number of cancer survivors returning to work. The researchers suggest, in their background information, that keeping to a cancer screening schedule could be an important factor (as this helps detect secondary tumors early and reduce potentially limiting side effects).

However, their analysis reveals that although cancer survivors tend to show much higher rates of screening adherence, their numbers too have started falling off in the last three years.

Lead author Tainya Clarke, a research associate in the School's Department of Epidemiology and Public Health, says in a statement:

"There is a great need for increased cancer prevention efforts in the US, especially for screening as it is considered one of the most important preventive behaviors and helps decrease the burden of this disease on society in terms of quality of life, the number of lives lost and insurance costs."

"But despite this, our research has shown that adherence rates for cancer screenings have generally declined with severe implications for the health outlook of our society," she adds.

In January 2012, a new report by the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) showed that the percentage of people screened for cancer in the US remains below national targets for 2020, with rates lower among Asian and Hispanic Americans than other groups.

The NIH Study Also Looks at Workforce

For this latest study, Clarke and colleagues examined cancer screening adherence rates of the general public and cancer survivors and compared them to government-recommended "Healthy People" screening goals.

They looked at screening rates for colorectal, prostate, breast and cervical cancers. Not only did they compare rates between the general population and cancer survivors, but they also looked at rates among workers.

The data on screening rates came from National Health Interview Surveys conducted between 1997 and 2010 that in total covered nearly 174,400 people aged 18 and over. These annual surveys randomly sample the US population by household, and collect demographic and health information, including cancer history and cancer-related health behaviors such as cancer screening.

The Results

When they analyzed the data, Clarke and colleagues found that the general population did not meet the government's "Healthy People" screening goals for any type of cancer, apart from colorectal cancer (for this cancer, 54% of the general population underwent screening: the government's 2010 goal is 50%).

But among cancer survivors, who have a higher risk for cancer, the pattern was quite different. Their screening rates, for all types of cancer except cervical (this fell to 78% over the last ten years), exceeded the government goals.

However, the researchers also noticed a decline in the number of cancer survivors who went for cancer screening in the last three years.

Disparities Among Workers

The NIH Survey results also enabled the researchers to include data on working adult Americans with and without a history of cancer: including more than 7,500 with a history of cancer (representing 3.8 million working cancer survivors), and over 119,300 workers with no history of cancer (representing more than 100 million).

They found that among survivors, white collar workers on the whole had higher cancer screening rates than blue collar workers.

Clarke says this was a key finding that she hopes will lead to changes in employment policies to eliminate disparities among different groups of the working population of cancer survivors.

She hopes it will also spur researchers to look more closely at factors influencing screening rates so as to design better workplace interventions and encourage more workers in all occupations to take up screening.

She and her colleagues speculate that ongoing disputes over screening guidelines among bodies like the United States Preventive Services Task Force, American Cancer Society and others, plus reductions in rates of workers covered by insurance that have occurred in the past decade, may lie behind the trend.

Rice University Scientists Turn Soy Mash Into Succinic Acid

The humble soybean could become an inexpensive new source of a widely used chemical for plastics, textiles, drugs, solvents and as a food additive.

Succinic acid, traditionally drawn from petroleum, is one focus of research by Rice chemists George Bennett and Ka-Yiu San. In 2004, the Department of Energy named succinic acid one of 12 "platform" chemicals that could be produced from sugars by biological means and turned into high-value materials.

Several years ago, Rice patented a process by Bennett and San for the bio-based production of succinic acid that employed genetically modified E. coli bacteria to convert glucose into succinic acid in a way that would be competitive with petroleum-based production.

The new succinate process developed by Bennett, San and Chandresh Thakker and reported recently in Bioresource Technology promises to make even better use of a cheap and plentiful feedstock, primarily the indigestible parts of the soybean.

"We are trying to find a cheaper, renewable raw material to start with so the end product will be more profitable," said Thakker, a research scientist in the Bennett lab at Rice's BioScience Research Collaborative and lead author of the study. "The challenge has been to make this biomass process cost-competitive with the petrochemical methods people have been using for many years."

Bennett feels they have done that with soybean-derived feedstock as an inexpensive source of the carbon that microorganisms digest to produce the desired chemical via fermentation. "A lot of people use plant oils for cooking - corn or soybean or canola - instead of lard, as they did in the old days," he said. "The oils are among the main products of these seeds. Another product is protein, which is used as a high-quality food.

"What's left over is indigestible fiber and small carbohydrates," said Bennett, Rice's E. Dell Butcher Professor of Biochemistry and Cell Biology. "It's used in small amounts in certain animal feeds, but overall it's a very low-value material."

The Rice researchers are changing that with the help of E. coli bacteria engineered to process soy meal that generally gets discarded. Certain microbes naturally produce succinic acid from such feedstock, but manipulating E. coli's metabolic pathways (by eliminating pathways that produce other chemicals like ethanol, for instance) can make it far more efficient.

Expanding on their success in producing succinic acid from glucose, the new microbes are engineered to metabolize a variety of sugars found in soybean meal. The theoretical ideal is a 1:1 ratio of feedstock (the extracted sugars) to product, which they feel is achievable by industry. In the lab, under less controlled conditions, they still found the process highly efficient. "We're demonstrating a very high yield," Thakker said. "We're achieving in a flask a non-optimized formation of succinate that is close to the theoretical goal."

Bennett said his lab has been looking at soybeans for nearly three years. "We're always interested in low-cost feedstock," he said. "We were able to get a connection with a soybean group that is very interested in technologies to make better and more profitable use of their crop.

"There's a fair amount of oilseed residuals available, including cottonseed carbohydrates, that are not used for any high-value product, and we're in the space of microbial engineering to enable these sorts of materials to be used in a good way," he said.

Enzyme PRSS3 Linked To Aggressive Prostate Cancer

An enzyme, known as PRSS3, is specifically associated with aggressive prostate cancer risk, researchers from the Mayo Clinic, Florida reported this week in the journal Molecular Cancer Research.
The scientists, who claim they are the first to link the enzyme to prostate cancer, added that they have developed a compound that can stop PRSS3 from encouraging metastasis - when cancer spreads beyond its point of origin to other parts of the body.

Senior investigator, Evette Radisky, Ph.D., a cancer biologist, said:

"This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells - perhaps by freeing them from surrounding tissue - to promote malignancy and invasiveness.

I don't think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer - the kind that is potentially lethal."

Dr. Radisky and team had set out to determine, from data on previous clinical trials which had information on molecules that are irregularly switched on in cancer, which enzymes encouraged metastasis.

In a previous study they had identified a link between the protease and the initial stages of breast cancer.

They wanted to find out whether any other cancer abnormally expresses this protease, and when. They gathered and analyzed data from several sources.

A protease is an enzyme that breaks down proteins and peptides.

Dr. Radisky said:

"The link between PRSS3 activity and aggressive prostate cancer jumped out at us. We found a definitive trend of increasing PRSS3 expression with cancer progression."

In an animal experiment using mice with prostate cancer, they showed that protease expression was vital for prostate cancer metastasis. When PRSS3 was silenced, the cancer did not spread.

The team had previously crystallized the structure of the PRSS3 protease, and identified a place on the enzyme where a small protein therapeutic could bind to plug up the "scissoring" action of the molecule.

Dr Radisky said "The protease has an active site that breaks down other proteins, and our inhibiting agent sticks to the site, shutting it down."

The authors believe their breakthrough could pave the way for "several possible future clinical applications".

Prostate cancer patients could be tested for the presence of the enzyme, so that doctors could identify which ones had the highest risk of metastasis, Dr Radisky added.

The team have developed a "prototype drug", which they say provides a template upon which an agent could be used to treat patients with aggressive prostate cancer. Dr. Radisky said:

"Our inhibitor does not have the characteristics we need for a clinically useful drug. But it puts us on the right path to develop one."

Unhealthy Behavior Common Among University Students

An analysis of student lifestyles was carried out by researchers at the University of Vigo to evaluate how much students drink, whether or not they take illegal drugs, their diet and how much exercise they do. The results of the study published by the Journal of Environmental Research and Public Health indicates that a surprising number of students engage in unhealthy behavior, especially excessive drinking.
One of the main authors, Jose M. Cancela said: The amount drunk per unit of time is higher among women. In other words, even though male students drink more often, females do so more intensively in shorter periods of time, which is known as binge drinking."

A total of 985 students of various different courses at the University of Vigo were randomly selected to be interviewed. The results were slightly shocking and highlighted the extent of alcohol and substance abuse among students, especially women.

Of the men interviewed 41.7% admitted to living a sedentary lifestyle compared to 51.2% women. Women were also found to do a lot less exercise than men with only 20.9% of women doing physical exercise compared to 38.6% of men. Men took illegal drugs more often than women.

The researchers note:





"We were also surprised by the high consumption of illegal drugs among university students - 44.9% of men and 30.9% of women - which we understand could lead to significant future health problems, mainly related to the nervous system."

An irregular attitude to food was apparent in 8.8% percent of men and 16.6% of women. Students who took subjects like education were more likely to have an irregular attitude to food than students who took subjects such as health (19.2% vs 6.3%).

In 2008 universities across Spain set up a Healthy University Network which promoted healthy living for students across the country. The researchers believe that this was just a first step and that healthy habits should be encouraged as part of study plans.

Cancela concludes, "In the light of the results, training and information courses are required in these areas, together with healthy leisure - not just sports facilities - to set up university guidance services for a healthy student lifestyle


 The reason why some people are more vulnerable to alcohol than others was identified in a study published in PNAS. The gene called RASFR2 was found to regulate the predisposition to drink and influence the activity of mesolimbic dopamine neurons. This along with environmental factors, and other genes, is thought to be the reason why some people drink a lot more than others.

The affects of drinking alcohol as a student have been identified in a previous study published in Alcoholism: Clinical & Experimental Research. They found that students who binge drink have worse attention and visual working memory processes than those who don't and require much more effort to carry out certain tasks.

What is Acne? What Causes Acne? How to Get Rid of Acne

The word acne comes from the word acme meaning "the highest point", which comes from the Greek akme meaning "point" or "spot" - it was originally mispelt, with an 'n' rather than an 'm' in 1835.

Acne is a disease that involves the oil glands of the skin. It is not dangerous, but can leave skin scars. Your skin has pores (tiny holes) which connect to oil glands located under the skin. The glands are connected to the pores via follicles - small canals. Sebum, an oily liquid, is produced by these glands. The sebum carries dead skin cells through the follicles to the surface of your skin. A small hair grows through the follicle out of the skin. Pimples grow when these follicles get blocked.

In humans, when pimples appear they tend to do so on the patient's face, back, chest, shoulders and neck. Acne develops when follicles get blocked and infected.

Simply put - skin cells, sebum and hair can clump together into a plug, this plug gets infected with bacteria, resulting in a swelling. A pimple starts to develop when the plug begins to break down.

There are various types of pimples

• Whiteheads - remain under the skin and are very small.
  
• Blackheads - clearly visible, they are black and appear on the surface of the skin. Remember that a blackhead is not caused by dirt. Scrubbing your face vigorously when you see blackheads will not help.
  
• Papules - visible on the surface of the skin. They are small bumps, usually pink.
  
• Pustules - clearly visible on the surface of the skin. They are red at their base and have pus at the top.
  
• Nobules - clearly visible on the surface of the skin. They are large, solid pimples. They are painful and are embedded deep in the skin.
  
• Cysts - clearly visible on the surface of the skin. They are painful, and are filled with pus. Cysts can easily cause scars.

How common is acne?

Dermatologists (skin specialists) say that approximately three-quarters of 11 to 30 year-olds will get acne at some time. Acne can affect people of all races and all ages. It most commonly affects adolescents and young adults. There are people in their fifties who still get acne. According to Brown University, USA, approximately 17 million Americans are estimated to have acne at any one time.

Although acne affects both men and women, young men suffer from acne for longer - probably because testosterone, which is present in higher quantities in young men, can make acne worse.

What causes acne?

Nobody is completely sure what causes acne. Experts believe the primary cause is a rise in androgen levels - androgen is a type of hormone. Androgen levels rise when a human becomes an adolescent. Rising androgen levels make the oil glands under your skin grow; the enlarged gland produces more oil. Excessive sebum can break down cellular walls in your pores, causing bacteria to grow.

Some studies indicate that susceptibility to acne could also be genetic. Some medications which contain androgen and lithium may cause acne. Greasy cosmetics may cause acne in some susceptible people. Hormone changes during pregnancy may cause acne to either develop for the first time, or to recur.

Treatment of acne

How your acne is treated may depend on how severe and persistent it is.

Treating mild acne

The majority of people who get acne will develop mild acne. This can usually be treated with OTC (over-the-counter) medications. OTC medications can be bought at a pharmacy without a doctor's prescription. They are usually applied to the skin - topical medicines.

Most acne OTC products may contain the following active ingredients:

• Resorcinol - helps break down blackheads and whiteheads. It is a crystalline phenol and comes from various resins. Resorcinol is also used for treating dandruff, eczema and psoriasis.
  
• Benzoyl Peroxide - kills bacteria and slows down your glands' production of oil. Benzoyl peroxide is a white crystalline peroxide used in bleaching (flour or oils or fats) and as a catalyst for free radical reactions. It works as a peeling agent, accelerating skin turnover and clearing pores, which in turn reduces the bacterial count in the affected area.
  
• Salicylic Acid - helps break down blackheads and whiteheads, also reduces shedding of cells which line the follicles of the oil glands, effective in treating inflammation and swelling. Salicylic acid is a white crystalline substance which is also used as a fungicide, or in making aspirin or dyes or perfumes. It causes the epidermis to shed skin more easily, prevents pores from becoming blocked while at the same time allowing room for new cells to grow. It is commonly added to shampoos used for treating dandruff.
  
• Sulfur - helps break down blackheads and whiteheads. Sulfur, in its native form, is a yellow crystalline solid. Sulfur has been used for centuries for treating acne, psoriasis and eczema. Scientists are not sure how sulfur works to help skin diseases. We do know that elemental sulfur does oxidize slowly to sulfurous acid which is a mild reducing and antibacterial agent.
  
• Retin-A - helps unplug blocked pores. Retin-A contains Tretinoin, an acid from of vitamin A, also known as all-trans retinoic acid (ATRA). Tretinoin is also used for the treatment of acute promyelocytic leukemia. Retin-A has been used widely to combat aging of the skin, it also acts as a chemical peel.
  
• Azelaic Acid - strengthens cells that line the follicles, stops oil eruptions, reduces bacteria growth. It is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Azelaic acid also mops up free radicals, which reduces inflammation. It is useful for patients with darker skin who have dark patches on their face (melasma), or whose acne spots leave persistent brown marks.

You can buy acne medications in the forms of gels, soaps, pads, creams and lotions. If your skin is sensitive you may prefer a cream or lotion. Gels, which are usually alcohol based and tend to dry the skin, are better for people with oily skin. OTC medications will have these ingredients in different concentrations. It is advisable to start with the lowest strengths. You may experience skin irritation, redness, and/or burning when you first try them. These side effects usually go away after continued use. If they don't you should see your doctor.

Virus may be possible acne cure - researchers from the University of Pittsburgh believe that a virus that lives on our skin might one day be used to effectively treat acne.

Treating more severe cases of acne

If your acne is more severe you should consider seeing a dermatologist - a skin specialist. The specialist may prescribe a treatment that contains some of the active ingredients mentioned above, such as benzoyl peroxide, azelaic acid, as well as adabalene. Prescription medications for acne are presented in many forms, such as creams, lotions, etc. Your dermatologist will decide what is best for you.

You may be prescribed an oral or topical antibiotic. Antibiotics can combat the growth of bacteria and reduce inflammation. Most commonly Erythromyocin and Tetracycline are prescribed as antibiotics for the treatment of acne.

• Treating a cyst with interlesional corticosteroid injection
  If an acne cyst becomes severely inflamed there is a high risk of rupturing. A rupturing acne cyst can often result in scarring. The specialist may inject a diluted corticosteroid to treat the inflamed cyst and to prevent scarring. The injection will lower the inflammation and speed up healing. The cyst will "melt" within a few days.
  
• Isotretinoin
  This is a strong oral retinoid, used for the treatment of severe cystic acne, as well as severe acne that has not responded to other medications and treatments.
  
• Oral antibiotics
  Oral antibiotics are frequently prescribed for patients with severe acne and some patients with moderate acne too. The aim of such oral antibiotics is to lower the population of Propionibacterium acnes (P. acnes), a bacterium commonly found on the skin, which will multiply rapidly in blocked follicles. The dosage will be initially high, and then as the acne reduces so will the dosage. Antibiotics are not taken for more than six months. As time passes the P. acnes can become resistant to the antibiotic and another antibiotic is needed. Some American studies have indicated that it is better to use oral broad-spectrum antibiotics.
  
• Oral contraceptives
  The majority of women with acne find that taking certain oral contraceptives clears it up. Oral contraceptives suppress the overactive gland and are commonly used as long-term treatments for acne in women. If the woman has a blood-clotting disorder, smokes, has a history of migraines, or is over 35, she should not take this medication without checking with a gynecologist first.
  
• Topical antimicrobials (topical = applied to the skin or mucus membranes)
  As with oral antibiotics, the aim of topical antimicrobials for the treatment of acne is to reduce P. acnes populations. Topical antimicrobials are used for patients with moderate to severe acne. Examples may be clindamycin, erythromycin, and sodium sulfacetamide
  The dermatologist may prescribe a topical retinoid. Topical retinoids are a derivative of Vitamin A and are very popular for the treatment of acne. They unclog the pores and prevent whiteheads and blackheads from developing. Examples of topical retinoids prescribed in the USA are adapalene, tazarotene, and tretinoin.


Looking after your skin if you have acne (or are prone to acne)

• Wash your face about twice each day. Do not wash it more often. Use a mild soap made especially for people with acne, and warm water. Do not scrub the skin. Experts advise the use of an OTC lotion which contains benzoyl peroxide.
  
• Don't try to burst the pimples. You may push the infection further down, causing more blocking and worse swelling and redness. Popping pimples makes scarring more likely.
  
• If you have to get rid of a pimple for some event, such as a wedding, or public speaking occasions, ask a specialist to treat it for you.
  
• Try to refrain from touching your face with your hands. When you are on the phone try not to let the receiver touch your face - there may be sebum and skin residue on it.
  
• Keep your hands clean, wash them regularly.
  
• Always wash your hands before touching your face. This includes before applying lotions, creams or makeup.
  
• Glasses should be cleaned regularly. They will collect sebum and skin residue.
  
• You skin needs to breathe. If your acne is on your back, shoulders or chest try wearing loose clothing. Tight garments, such as headbands, caps and scarves should be avoided - if you have to wear them make sure they are cleaned regularly.
  
• Don't go to sleep with makeup on. Only use makeup that is nonceomedogenic or nonacnegenic - you should be able to read this on the label. If you cannot find it, ask the shopkeeper or pharmacist. You should use makeup which does not have oil and does not clog up the pores.
  
• Hair collects sebum and skin residue. Keep your hair clean and away from your face.
  
• Too much sun can cause your skin to produce more sebum. Several acne medications make it more likely that you will be sunburned.
  
• If you shave your face, do it carefully. Use either an electric shaver or safety razors. If you use a safety razor make sure the blade is sharp. Soften your skin/beard with warm soapy water before applying the shaving cream.

Other articles about skin conditions/diseases

What is psoriasis? What causes psoriasis?

What are skin tags? What causes skin tags?

What are pimples? How to get rid of pimples

What are blackheads? How to get rid of blackheads

What Are Hives? What Is Urticaria? What Causes Hives?

What are warts? What causes warts?

What are genital warts? What causes genital warts?

What is dandruff? What causes dandruff?

What is nail fungal infection? What causes nail fungal infection?

What is skin cancer? What is melanoma?

What can make acne worse?

• Menstrual cycle - Girls and women with acne tend to get it worse one or two weeks before their menstrual period arrives. This is probably due to hormonal changes that take place. Some people say they eat more chocolate during this time and wonder whether there may be a connection. However, experts believe the worsening acne is not due to chocolate, but rather to hormonal changes.
  
• Anxiety and stress - mental stress can affect your levels of some hormones, such as cortisol and adrenaline, which in turn can make acne worse. Again, stress can make some people binge-eat. Experts believe the culprits are most likely the hormone levels, rather than the binge-eating.
  
• Hot and humid climates - when it is hot and humid we sweat more. This can make the acne worse.
  
• Oil based makeups - moisturizing creams, lubricating lotions, and all makeup that contain oil can speed up the blocking of your pores.
  
• Greasy hair - some hair products are very greasy and might have the same effect as oil based makeup. Hair products with cocoa butter or coconut butter are examples.
  
• Squeezing the pimples - if you try to squeeze pimples your acne is more likely to get worse, plus you risk scarring.

Establishment Of New Blood Supply In Patients With Blood-Based Diseases Improved By Pre-Transplant Umbilical Cord Blood Expansion

Donated umbilical cord blood establishes a new blood supply in patients more quickly after transplantation when it is first expanded in the lab on a bed of cells that mimics conditions in the bone marrow, researchers report in the New England Journal of Medicine.

The phase 1/2 study led by scientists at The University of Texas MD Anderson Cancer Center addresses the main difficulty with using umbilical cord blood stem cells to replace the blood supply of patients who have had theirs destroyed by chemotherapy or radiation to treat leukemia, lymphoma and other blood-based diseases.

"You get fewer cells - blood stem cells, immune cells - from two umbilical cords than you do by collecting from a donor's bone marrow or peripheral blood," said senior author Elizabeth Shpall, M.D., professor in MD Anderson's Department of Stem Cell Transplantation and Cellular Therapy.

That lengthens the time between infusion of the cord blood cells and establishment, or engraftment, of the new blood supply. "It's a high-risk time, patients don't have white blood cells to fight infection, they don't have platelets to keep them from bleeding," Shpall said.

More cells transplanted, faster recovery

By taking blood from one of the two donated umbilical cords and growing it in the laboratory on a bed of mesenchymal precursor cells, the researchers greatly increased the number of cells transplanted, reduced recovery time and increased the proportion of patients whose new blood became established.

"Expansion achieved a median 12-fold increase in total cells transplanted and a 40-fold increase in the number of CD34+ cells, which are crucial for engraftment," Shpall said. "This led to faster engraftment of white blood cells and platelets, which we believe enhances patient safety."

"Pre-transplant cord blood expansion on mesenchymal stromal cells could become the new standard of care if our findings are confirmed in a randomized clinical trial," Shpall said.

Shpall notes that readily available mesenchymal precursor cells provided by Australian regenerative medicine company Mesoblast Limited reduced the time it takes to expand the cord blood cells from more than a month to a few weeks.

Australian scientist and study co-author Paul Simmons, Ph.D., executive vice president for research at Mesoblast, led the research team that originally identified mesenchymal precursor cells and discovered a way to extract mesenchymal cells from the bone marrow for use in other settings.

Only about 25 percent of those needing a blood stem cell transplant have a matching donor - the ideal situation for a transplant. Double-cord blood transplant is one of the main options for the rest, which includes a higher proportion of those with African, Asian or Latino heritage, who are underrepresented among blood stem cell donors.


Patients who receive peripheral blood from a matched donor, the main method used in blood stem cell transplants, on average have their infection-fighting white blood cells (neutrophils) engraft in 11 days and their platelets in 13 days. For a double-cord blood transplant, the same cells engraft in 26 days and 53 days, respectively.

"That isn't good enough," Shpall said. She and other researchers have long sought optimal ways to expand cord blood. The key cells are blood stem cells, which can differentiate into any type blood cell - platelets, white cells or red cells.

Expansion hastens white cell, platelet engraftment

In 31 high-risk patients, the team expanded blood cells from one of the two cords transplanted. They compared outcomes to 80 cases of standard double-cord blood transplant reported to the Center for International Blood and Marrow Transplantation.

The study's composite endpoint of neutrophil engraftment within 26 days, platelet engraftment within 60 days and survival at 100 days was reached by 63 percent of the expanded cord blood group compared with 24 percent among controls.

Patients with expanded cord blood had:

• Median time to neutrophil engraftment of 15 days, compared to 24 for controls.
• Median time of platelet engraftment of 42 days, compared with 49 for controls.
• Cumulative neutrophil engraftment rate of 88 percent at 26 days, compared with 53 percent in control cases.
• Cumulative platelet engraftment rate of 71 percent at 60 days, compared with 31 percent in controls.

"In addition to the faster engraftment of neutrophils and platelets, the quality of engraftment was better than anything we've seen," said first author Marcos de Lima, M.D., who led the study while on MD Anderson's faculty and is now professor of medicine at Case Western Reserve University School of Medicine in Cleveland.

Goals: Less bleeding, fewer infections, hospital stays and transfusions

"Cord blood transplant patients often need platelet transfusions for months," de Lima said. "Most of the control group did not start making their own platelets, while in the study group, 70 percent of patients engrafted within 60 days."

"From patients' perspective, these are things you want to see going forward: less bleeding, less infection, fewer trips to hospital and less dependence on transfusions," de Lima said.

Mesoblast is sponsoring a prospective, randomized Phase 3 trial led by Shpall in 15 centers that will compare 120 patients who receive one expanded and one regular cord blood transplant to 120 others who get the standard double cord transplant.

Recreating bone marrow environment in lab flasks

Shpall and Ian McNiece, Ph.D., also a professor in Stem Cell Transplantation and Cellular Therapy, have been working on cord blood expansion for 15 years. They thought mesenchymal precursor cells, which form a supportive network in the bone marrow that allows blood cells to grow, would enhance cord blood cell expansion. The stromal cells do not provoke an immune response when donated.

They developed a technique to take mesenchymal stromal cells from a relative of the patient, cultivate those cells, and then expand cord blood on a layer of the cells in the lab. The logistics and time involved in this procedure limited enrollment in the clinical trial. They evaluated Mesoblast's cells, found them to be superior to donor cells in terms of expansion of blood-forming precursors, and switched to the off-the-shelf cells.

"This really recapitulates what happens in our bone marrow, where mesenchymal stromal cells provide the optimal environment for blood stem cells to proliferate and differentiate," McNiece said. "We also supplement growth factors to the media the cells are grown in to drive them in a direction of differentiation we think is optimal for patient treatment."

Child's Leukemia Cured By Her Own Re-Engineered Immune Cells

Thanks to an experimental new therapy, a seven-year-old girl in the US with an aggressive form of childhood leukemia has been cured with her own re-engineered immune cells. After the treatment, her doctors could find no evidence of cancer.
Pediatric oncologist Stephan A Grupp, of The Children's Hospital of Philadelphia (CHOP), and his team, were able to help Emily Whitehead by recruiting her as the first child patient on a clinical trial he is leading called CTL019, which is testing T cell therapy to treat acute lymphoblastic leukemia (ALL) and other B cell cancers.

On the trial, Emily (also known as Emma), who had relapsed twice following standard chemotherapy for ALL, received a custom-designed version of her own T cells which rapidly multiplied and destroyed the leukemia cells.

Grupp is the director of Translational Research for the Center for Childhood Cancer Research at CHOP, and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

He and his team from CHOP and the University of Pennsylvania presented the updated trial results at the 2012 annual meeting of the American Society of Hematology (ASH), which took place in Atlanta from 8 to 11 December.

How T Cell Therapy Works on the Clinical Trial CTL019

The T Cell Therapy Clinical Trial CTL019 (formerly CART19) is testing the effect of T cell therapy for patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL).

Dr. Stephan Grupp, M.D., Ph.D. of The Children's Hospital of Philadelphia examines first pediatric patient Emma six months after T Cell therapy. Emma had relapsed B cell leukemia.

In the trial, researchers took immune system T cells from each patient's own blood. These cells are often called the "workhorses" of the immune system, they do the "heavy work" of recognizing and attacking invading disease cells.

The team then genetically modified the extracted T cells to express a protein that binds to a target called CD19, a protein found on the surface of B cells, a type of white blood cell that becomes cancerous in certain leukemias and lymphomas, such as ALL, NHL and CLL.

When they become cancerous, B cells are capable of "flying under the radar" of the T cells and evade them. The genetic modification makes T cells capable of detecting and then destroying the cancerous B cells. The genetically reengineered T cells are referred to as "chimeric antigen receptor T cells".

After reengineering, the modified T cells are then put back into the patient where they disperse and go in search of the cancerous B cells. They also multiply in the body at a rate that enables them to kill the rapidly dividing cancerous B cells. And they also stay in the body and continue to fight any new cancerous B cells.

Initial Results Show Promise

Only 12 patients have been treated so far: 10 adults with chronic lymphocytic leukemia (CLL), and 2 children with acute lymphoblastic leukemia (Emily being one of them). But researchers say the early results show great promise.

For instance, the modified T cells can survive for many months in the patient's body, and have the ability to grow into large quantities. And they have killed large quantities of ALL or CLL cells in 9 of the 12 patients.

The team hopes CTL019 will prove an effective therapy for patients with B cell cancers. But because only a few patients are on this phase of the trial, there now needs to be a big push to enrol many more adult and pediatric patients, to see if the same results are seen in a larger group.

Emily's Story

85% of children with ALL, the most common childhood cancer, are cured after two years of treatment with standard chemotherapy. But there is a 15% minority that has a type of ALL that resists even the most intense chemo regimens.

At first Emily's doctors thought she would be among the 85% with the type of ALL that would respond to chemo, but a relapse proved she had the more resistant variety.

After a second relapse following a second course of chemo, Emily was enrolled on the CTL019 clinical trial.

Unfortunately, Emily got very ill during the trial. While flu-like symptoms were expected, Emily developed cytokine release syndrome: the effect of T cells growing in Emily's body caused high levels of a certain protein that is involved in rheumatoid arthritis.

After administering a drug to counteract the protein, Emily's condition improved dramatically: almost overnight her breathing improved, her fever dropped, and her blood pressure went back to normal.

In the weeks that followed, Emilly recovered completely from the cytokine release syndrome, but her doctors weren't sure if the T cell therapy was working. So they did a bone marrow test to check for results.

Grupp takes up the story:

"Three weeks after receiving the treatment, she was in remission. Emily completely responded to her T cell therapy."

"We checked her bone marrow for the possibility of disease again at three months and six months out from her treatment, and she still has no disease whatsoever. The cancer-fighting T cells are still there in her body," he adds.

Who Else Might Benefit from the Treatment Emily Received?

The team points out that CTL019 is designed for children and teenagers with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas only.

It is for cancers that have not responded to standard chemotherapy: it is not for people with newly diagnosed disease.

The researchers warn that these results are still preliminary, and that not all children who qualify for the trial will have the same result.

In the long term, Grupp sees cell therapies like CTL019 as potential replacements for bone marrow transplants.

"I've been meeting with families to discuss bone marrow transplant for 20 years," he says.

"In almost every meeting, I say that bone marrow transplant is very hard and that if we had an alternative for children at that point in treatment, I would be delighted to put myself out of business. And for the first time, we're seeing how that might actually happen."

Drug Shortage Linked To Cancer Relapse

A drug shortage appears to have caused a higher rate of relapse among children, teens and young adults with Hodgkin lymphoma, researchers form St. Jude Children's Research Hospital reported this week. The scientists say this is the first example of the tragic consequences of the current drug shortage. They emphasized that protecting patient access to lifesaving treatment must always be the number one priority in any health care system.
Children, adolescents, and young adults with Hodgkin lymphoma in a national clinical trial showed an estimated two-year cancer-free survival rate that dropped from 88 to 75 percent due to a drug shortage.

The study began before any reported drug shortages, however, the change started in 2009 after a shortage of mechlorethamine became apparent. The drug mechlorethamine was replaced by cyclophosphamide for treatment of patients with middle or high risk Hodgkin lymphoma.

No study patients are deceased, but those who relapsed had more rigorous therapy that was linked with higher risks of infertility and other health issues later.

The results of comparing these two groups two years after their cancer diagnoses are published in the New England Journal of Medicine. The outcomes demonstrate the first available evidence of a drug shortage that resulted in disadvantages in specific patients.

History Of Drug Shortages

Recently, many caregivers and patients have had their medical treatments compromised by drug shortages, like mechlorethamine and other injectable drugs. Available since the 1960's for cancer treatment, mechlorethamine just became obtainable again.

Cyclophosphamide is a safe and effective substitute for mechlorethamine, used for decades for treatment of children and adults with Hodgkin's lymphoma.

Monika Metzger, M.D., an associate member of the St. Jude Department of Oncology and the study's principal investigator, said:

"This is a devastating example of how drug shortages affect patients and why these shortages must be prevented. Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available."

Previous shortages have most frequently been solved using substitutions. This study has given a real face to the drug shortage problem, showing that it is real. There are actual therapies that are unable to be given because drugs are just not available.

Michael Link, M.D., the senior author and professor of pediatrics in hematology-oncology at Stanford, as well as a member of the pediatric hematology-oncology service at Packard Children's Hospital, explains:

"Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed."

Results of Drug Substitutions

Hodgkin lymphoma is cancer that attacks the lymph system and makes up approximately six percent of childhood cancers. Around 90 percent of patients in the United States with this cancer will become long-term survivors.

In 2002, the five institutions collaborating on this study worked as the Pediatric Hodgkin Consortium and accepted a seven-drug chemotherapy treatment course, which included mechlorethamine, to treat high risk child patients. The researchers aimed to avoid infertility and other issues and maintain high cure rates.

In 2006, a companion study started for patients with intermediate-risk disease. The risk groups are defined by how far the cancer has spread, the location and number of lymph nodes involved, as well as the experience of negative symptoms like night sweats, fever, and weight loss.

Patients underwent 12 weeks of the seven-drug chemotherapy treatment course. They also received radiotherapy with their dose given in accordance to their chemotherapy response. Once mechlorethamine was no longer available, the substitution cyclophosphamide was allowed in its place.

Results for cancer patients are calculated in terms of cancer-free survival, also known as the number of years patients live disease-free. When investigators looked at the substitution's influence, they saw that approximate disease-free survival was 88 percent for the 181 patients whose treatment included mechlorethamine.

For the 40 patients who were given cyclophosphamide, the rate was 75 percent. The variation prompted researchers to stop enrolling new patients in the trials.

As a whole, patients who had the cyclophosphamide experienced less negative symptoms and were more inclined to have intermediate-risk, rather than high-risk Hodgkin lymphoma. The authors note that there is no valid explanation for the significant difference in event-free survival besides the drug substitution.

The patients in the study were between the ages of 3 and 21, with half being under 14 years. Relapsed patients underwent additional therapy. Extra treatment included extensive chemotherapy and a stem cell transplant using the patient's own blood-creating stem cells.

The investigators said it is too early to determine whether these patients will experience the same long-term survival rates as those who did not get their cancer back.

Whooping Cough Cases Remain High, UK

Cases of whooping cough in England and Wales have remained high through November, says the Health Protection Agency (HPA).

New figures released by the agency on Friday show 1,080 confirmed cases for November, down from October's 1,631, bringing the total so far for 2012 to 8,819, the highest for any year since the 1990s.

No deaths were reported for November, says the agency, who at the end of October said 13 infants had died in the current outbreak which began in the middle of 2011.

Although the slight fall in cases from October to November is the first downturn in the current outbreak, it does not necessarily mean it is coming to an end, as Gayatri Amirthalingam, HPA's consultant epidemiologist for immunisation, explains:

"The November figures show a welcome decrease of whooping cough cases since October. However, it is very important to note that we usually see a reduction in cases of whooping cough at this time of year so this decrease is in line with normal seasonal patterns."

Whooping Cough

Whooping cough, also known as pertussis, is a highly contagious bacterial infection of the lungs and airways. The illness can last for three months.

The first signs of infection are usually a dry and irritating cough. This progresses to intense bouts of coughing followed by a "whooping" noise, which is how the illness got its name.

Other symptoms include raised temperature, runny nose, and vomiting after coughing.

Although whooping cough affects all ages, young babies are most at risk. Until they complete their vaccination around four months old, they are the ones most likely to have severe complications that can lead to death.

Older children and adults who get whooping cough usually get mild, unpleasant symptoms that rarely lead to complications.

Nevertheless, whooping cough is highly infectious. When infected people cough, they shed bacteria that can then be inhaled by others.

Vaccination for Pregnant Women

In order to protect newborn babies, who do not start receiving the whooping cough vaccine until they are two months old, the Department of Health is offering pregnant women the whooping cough vaccination. They announced this at the end of September.

The vaccine being offered to pregnant women is called Repevax, which has been used to immunize children in the UK since 2004.

The aim of the campaign is to boost the short term immunity mothers pass on to their babies while they are still in the womb.

Although it is too early to see if this is having an effect on the current figures, the Department of Health recently reported a take up rate of around 40% in pregnant women.

While encouraged by the take up rate, Amirthalingam urges:

"We would like to remind pregnant women how serious this infection can be in young babies and how it can in some cases cause death. Vaccination between 28 and 38 weeks of pregnancy should offer babies the best protection against whooping cough before they receive their own vaccines."

It is also important, says Amirthalingam, that parents make sure children receive their vaccinations on time, even babies of women who were vaccinated in pregnancy, in order to ensure their continued protection through childhood.

And parents should also be alert to the signs and symptoms of whooping cough, "which include severe coughing fits accompanied by the characteristic 'whoop' sound in young children but as a prolonged cough in older children or adults", says Amirthalingam.

More information on the whooping cough vaccine for pregnant women is available on the NHS Choices website.

Affecting Whole Country

The current outbreak is affecting the whole country, but the south west and south east have seen more cases than the north east and Wales, according to a report in the Telegraph.

The outbreak is not due to parents stopping their children being immunized, say experts. The illness tends to come in waves, as immunity provided by vaccination weakens over time, allowing small outbreaks to occur.

The United States is facing a similar surge in whooping cough cases, thought to be the highest in half a century.

'Exhausted' T Cells Lead To Chronic Viral Infection

When you get an acute infection, such as influenza, the body generally responds with a coordinated response of immune-cell proliferation and attack that rapidly clears the pathogen. Then, their mission done, the immune system stands down, leaving a population of sentinel memory cells to rapidly redeploy the immune system in the event of reinfection.

This is why vaccination works, and it's why, in theory at least, people who have had the chicken pox once will never get it again.

But what about chronic infection? In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become "exhausted" and the immune system can collapse, giving the pathogen the edge.

Now, a new study by researchers at the Perelman School of Medicine, University of Pennsylvania, is showing just how that happens. The findings also suggest a novel therapeutical approach that might be used to shift the balance of power in chronic infections. The study appears in Science.

The team, led by E. John Wherry, PhD, associate professor of Microbiology and Director of the Institute for Immunology, used a mouse model of chronic viral infection to map the T-cell response that arises when the immune system is on an extended war footing. They found that two distinct classes of virus-specific CD8+ T cells - one expressing high levels of the protein T-bet, the other expressing high levels of the protein Eomes, work together to keep the infection in check.

Specifically, they found that the two cell populations appear to have a progenitor-mature cell relationship. The T-bet-expressing cells appear to function as the progenitor cells - that is, stem cells. These cells divide both to regenerate and maintain the pool of virus-specific T cells. But they also divide and differentiate to form mature, terminally differentiated Eomes-expressing cells. These cells are more effective at fighting the virus itself, but cannot replicate.

"There's a balance, an equilibrium, which allows you to maintain control over the infection but is insufficient to give you complete clearance," Wherry explains.

These two cell subpopulations tend to confine themselves to different anatomic regions in the infected animals, the researchers found. T-bet-positive cells were found in the blood and spleen, whereas Eomes cells were found in the liver, bone marrow, and gut.

Loss of either subpopulation, which the researchers modeled by deleting one or the other protein, reduces the immune system's ability to fight the infection, leading to a shift in favor of the pathogen.

According to Wherry, these data can help explain the gradual loss of virus-specific T cells observed in such chronic infections as hepatitis C.

"Our data suggest the reason for loss of immune control during some chronic infections is that the long-term pressure on this progenitor-mature cell relationship depletes the progenitor pool," he says.

What's more, the study suggests new therapeutic avenues that can be used to fight, or at least better control, chronic infections. For instance, he says, "If we can maintain these progenitor cells longer, or coax the terminal progeny to divide further, we may be able to shift the balance and maintain control of the infection," he says.

Wherry's lab is now studying candidate molecular pathways to determine their efficacy in controlling, and perhaps modulating, these two T-cell populations.

Hepatitis C Drug May Cause Fatal Skin Reactions

The oral hepatitis C drug telaprevir (Incivek) will now come with a boxed warning regarding the potentially fatal severe skin reactions that may occur in patients.
Vertex Pharmaceuticals stated that there have been reports of fatal cases in patients with a continuous rash and systemic symptoms who kept taking INCIVEK combination treatment after recognizing a severe skin reaction.

It has been known that receiving INCIVEK combination treatment may cause a person to develop a rash and serious skin reactions, as the adverse side effects were previously listed in the warnings and precautions section of the drug label.

The alert has been given a greater significance via a boxed warning, due to the reported fatalities that have occurred and the importance of discontinuing INCIVEK combination treatment if any skin conditions are experienced.

Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex, explained:

"The safety of people taking our medicines is our first priority, and we are committed to ensuring that patients and physicians are aware of the label update to help them use INCIVEK properly. We will continue to educate physicians to follow the rash management plan developed while INCIVEK was in clinical trials and the information contained in the updated label."

Less than 1% of the patients who received INCIVEK combination treatment in Phase 3 clinical trials developed a severe skin reaction. A hospital visit was needed to treat the skin reactions, but all of the patients recuperated.

The fatality reports that were linked to skin reactions appeared after post marketing observation. However, the number of deaths was not reported by the company.

Anyone who is receiving INCIVEK combination treatment should stop immediately if any severe skin reactions occur and should seek medical assistance, Vertex Pharmaceuticals said.

Further information was also added onto the label regarding the time period leading to onset of anemia and management of the condition.

Aspirin Tied To Lower Risk For Liver Cancer And Death From Liver Disease

A new study from the US finds that use of aspirin is tied to a reduced risk for hepatocellular carcinoma, the most common type of primary liver cancer, and also to a reduced risk of death from chronic liver disease.
Vikrant V. Sahasrabuddhe, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and colleagues, write about their findings in the 28 November online issue of the Journal of the National Cancer Institute, JNCI.

Hepatocellular carcinoma occurs mainly in people with chronic liver disease. Some studies suggest the cancer could be a result of the chronic inflammation in liver disease affecting cellular processes.

NSAIDs as Cancer Preventers

Because of their anti-inflammatory properties, and their widespread use to prevent heart problems and cerebrovascular diseases like stroke, researchers are investigating the potential of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) as cancer preventers.

However, a recent study published in JNCI in August, suggests while the evidence is encouraging, the cancer-protective effect of NSAIDs is not as large as previously thought, and not enough to outweigh the risks (primarily of serious bleeding in the gut), and concludes it is too early to recommend people start taking them to ward off cancer.

What the Researchers Did

In the meantime, although more studies are looking at the potential anti-cancer effect of NSAIDs, the link to risk for liver cancer and death from chronic liver disease remains unclear, say the authors of this new JNCI paper, where they describe how they carried out an observational study of 300,504 men and women aged 50 to 71 years.

The participants, who were enrolled in the National Institutes of Health-AARP Diet and Health Study, had reported their use of aspirin and other NSAIDs and were followed for 10 to 12 years.

The researchers were able to link the NSAID use data from these participants to registered diagnoses of 250 cases of hepatocellular carcinoma and 428 cases of chronic liver disease.

What They Found

When they analyzed the links they found participants who used NSAIDs had a lower risk of hepatocellular carcinoma and a reduced risk of death from chronic liver disease compared to participants who did not use the drugs.

But when the researchers differentiated between aspirin and non-aspirin NSAIDs, there were some marked differences.

Participants who used aspirin showed a 41% reduced risk for hepatocellular carcinoma and a 45% reduced risk of death from chronic liver disease.

Whereas participants who used non-aspirin NSAIDs showed no reduced risk for for hepatocellular carcinoma, and a 26% reduced risk of death from chronic liver disease.

Sahasrabuddhe and colleagues write:

"Aspirin, in particular, when used exclusively or with other non-aspirin NSAIDs showed a consistent protective effect related to both HCC [hepatocellular carcinoma] incidence and CLD [chronic liver disease] mortality, regardless of the frequency or exclusivity of use."

If confirmed, these associations with the use of aspirin "might open new vistas for chemoprevention of HCC and CLD," they conclude.

Experts Say Fine to Look at NSAIDs, But Also Need to Improve Established Approaches

In an accompanying editorial, researchers from the Department of Epidemiology and Community Medicine at the University of Ottawa in Canada, note that the known causes of chronic liver disease and primary liver cancer are use of alcohol, and hepatitis B and C virus infections, and there have also been suggestions of a link with diabetes and obesity.

"We already have cheap, readily available interventions," they write, citing examples such as vaccines for hepatitis B and C virus, although "effective strategies for reduction of HBV and HCV are not always available or fully applied."

"Also, alcohol abuse and obesity are complex and multifactorial challenges that require interventions at the individual and system levels," they add, concluding that while we should continue to explore the potential for new drug strategies like NSAIDs, we should not lose sight of the need to improve established practices and interventions.

Brain Tumors Respond To Diet And Radiation Therapy

Brain cancer researchers have successfully treated mice with malignant gliomas, a type of aggressive and deadly brain tumor, with a unique combination of radiation therapy and ketogenic diet, a high fat, low carbohydrate and minimal protein regime that forces the body to use fat instead of sugar for energy. Should the approach succeed in human trials, they say the diet could quickly and easily be added to current human brain tumor treatments.
The researchers, led by Adrienne C. Scheck, from Barrow Neurological Institute at St. Joseph's Hospital and Medical Center in Phoenix, Arizona, in the US, reported the results of using the combination therapy on mice in PLoS ONE.

Theirs is thought to be the first study of its kind to look at the effects of the ketogenic diet with radiation.

In a press statement released this week, Scheck says their study shows promise for treating human malignant gliomas:

"We found that the ketogenic diet significantly enhances the anti-tumor effect of radiation, which suggests that it may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas," she explains.

Ketogenic Diet

The ketogenic diet is a high fat, low carbohydrate, controlled protein diet that has been used since the 1920s to treat epilepsy. The word ketogenic means the body produces ketones (keto = ketone, genic = producing).

Usually the body converts carbohydrates (from foods like sugar, bread, pasta) into glucose (a type of sugar) to use for energy. In the ketogenic diet, because of the restriction in carbohydrate intake, the body can't use glucose and is forced to use fats as its source of energy: a process known as "ketosis".

In a recent study, scientists showed it may be possible to use specific fatty acids from the ketogenic diet to make a pill, so epilepsy patients can have the benefit of the diet without its side effects, which include constipation, hypoglycaemia, retarded growth and bone fractures.

There is also evidence that the diet's effect on brain regulation or homeostasis has potential for treating other brain disorders.

Increased Survival

For their study, Scheck and colleagues used two groups of mice with high-level malignant gliomas. They kept one group on a standard diet and the other group on a ketogenic diet.

The ketogenic diet they used was KetoCal (KC) a nutritionally complete, commercially available formula used in the treatment of epilepsy in children. The formula has a 4:1 ratio of fat to carbohydrate plus protein.

Both groups received radiation therapy and regular brain scans to monitor tumor growth.

The results showed that the median survival for the mice on the ketogenic diet was about five days longer than the mice on the standard diet, and the vast majority of them survived with no sign of tumor recurrence, even when they switched back to a standard diet, for over 200 days.

None of the mice on the standard diet survived more than 33 days.

Adjuvant Therapy in Human Brain Tumor Treatment

The authors conclude that the ketogenic formula "significantly enhances the anti-tumor effect of radiation".

They suggest the changes to cell metabolism induced through the diet may make it a useful "adjuvant to the current standard of care for the treatment of human malignant gliomas".

Speculating on the reason why the ketogenic diet is effective when combined with radiation therapy, they suggest it stops tumor growth by reducing the stimulation of growth factor hormones, and it may also reduce inflammation and edema around the tumors.

Sheck is currently planning to set up clinical trials in humans.

She says the diet could easily and quickly be incorporated as an adjuvant therapy in current human brain tumor treatments without having to seek approval from regulators.

Coffee Drinking May Halve Risk Of Mouth And Throat Cancer

A new study from the US finds people who drink more than 4 cups of caffeinated coffee a day have half the risk of dying from oral/pharyngeal (mouth and throat) cancer as people who drink it either occasionally or not at all. However, the researchers say their findings need to be confirmed by more research, and for now should just be received as good news for coffee drinkers and not be used as a reason to recommend everyone should drink 4 cups of coffee a day.
Lead author Janet Hildebrand and colleagues from the American Cancer Society (ACS) in Atlanta, Georgia, write about their findings in a paper published online first on 9 December in the American Journal of Epidemiology.

Oral/Pharyngeal Cancer

Oral/pharyngeal or mouth and throat cancer is rarely diagnosed in the early stages because symptoms usually do not appear until the cancer is advanced. Also, the symptoms can be mistaken for something else, such as toothache.

The cancer can sometimes be spotted early during a routine exam by a doctor, dentist, or dental hygienist, and some dentists and doctors suggest you look at your mouth in a mirror at least once a month to check for symptoms.

The most common symptoms are a mouth sore that fails to heal, or a pain in the mouth that doesn't go away.

The biggest risks for developing oral/pharyngeal cancer are tobacco and alcohol use. Most people who have it are tobacco users.

Infection with the human papillomavirus (HPV) is also a risk factor, especially in people who do not use tobacco. The number of cases of oral/pharyngeal cancer tied to HPV has risen sharply in the last thirty years.

Researchers Examine Link with Coffee

Previous epidemiological studies have suggested coffee drinking is linked to a reduced risk for mouth and throat cancer.

It has also been suggested that it may not be the caffeine in coffee, but the fact it is rich in antioxidants, polyphenols, and other compounds, that help prevent or slow the development of cancer.

For their study, Hildebrand and colleagues used data from the Cancer Prevention Study II, a prospective US cohort study that the ACS started in 1982.

That study gathered a wealth of lifestyle and health information on 968,432 men and women, including their tea and coffee consumption. When they enrolled on the study, none of the participants had cancer, but over the 26 years of follow up, 868 died from oral/pharyngeal cancer.

When they analyzed the tea and coffee consumption in relation to deaths from oral/pharyngeal cancer, the researchers found those participants who reported drinking more than 4 cups of caffeinated coffee a day had a 49% lower risk of death from oral/pharyngeal cancer compared to those who reported not drinking coffee at all or only an occasional cup.

The link was not affected by gender, tobacco and alcohol use.

The researchers found an insignificant link with decaffeinated coffee, and none at all with tea.

Conclusion and Next Step

The researchers conclude:

"In this large prospective study, caffeinated coffee intake was inversely associated with oral/pharyngeal cancer mortality. Research is needed to elucidate biologic mechanisms whereby coffee might help to protect against these often fatal cancers."

Hildebrand says in a press statement:

"We are not recommending people all drink 4 cups of coffee a day. This is just a little bit of good news for those of us who enjoy coffee."

"There may be some other effects of coffee that may prevent people with certain conditions from drinking a lot of caffeine," she cautions, noting that:

"This study is about just one cancer site among many. There needs to be much more consistent research before we can support the conclusion that coffee should be consumed for cancer prevention."

The team is now planning to analyze links between coffee consumption and cancer in a more diverse population in the ACS's new Cancer Prevention Study - 3 (CPS-3).

The Society hopes to recruit at least 300,000 adults from a range of ethnic and racial backgrounds across the US to take part in CPS-3, which aims to increase knowledge of how to prevent cancer.

There has been a lot of debate recently about the benefits and harms of coffee drinking, with more recent news suggesting the benefits probably outweigh the harms.

But researchers spreading the good news are all saying the same thing, as Hildebrand and colleagues themselves point out in this latest study: while there appear to be some health perks from drinking coffee, there are also a few cautions, and the evidence is not solid enough to actively encourage people to go out and drink coffee.

One In Two Men Will Develop Cancer

New figures for the UK predict a man's risk of developing cancer during his lifetime will rise to one in two by 2027, largely because more people are living longer.
The figures, released by Cancer Research UK on Wednesday, show that in the next 15 years, 50 men out of every 100 in the UK will be diagnosed with cancer at some point during their lives, compared with 44 out of 100 in 2010.

They also show the risk for women developing cancer will rise from 40 to 44 out of every 100 over the same period.

The backdrop to these new figures is age: the biggest risk factor for cancer. Living longer means a higher risk of developing cancer. And in the UK, as in other developed nations, more people are reaching an age where they are more likely to develop cancer.

Harpal Kumar, chief executive of Cancer Research UK, says in a statement that their figures are a "glimpse into the future".

"On the plus side our life expectancy is increasing but this also means more of us are likely to be diagnosed with cancer," he says.

But there is also another backdrop: thanks to research, cancer diagnosis and treatment is improving all the time, so while the risk of developing cancer is going up, so is the chance of surviving it.

Experts say prostate cancer, bowel cancer and melanoma are among those most likely to rise in the next 15 years.

Prostate Cancer

Prostate cancer remains a huge challenge: cases are growing and there is no reliable way to identify the ones that are life-threatening.

"Prostate cancer needs research," says Professor Malcolm Mason, prostate cancer expert at Cancer Research UK.

Mason says there are many questions that research still needs to answer. As the population ages, more and more men will be diagnosed with prostate cancer.

"Over the last 40 years prostate cancer incidence rates in Great Britain have tripled, and three-quarters of cases are diagnosed in men aged over 65 years," says Mason.

However, there are some glimmers of hope, such as a paper published recently in Molecular Cancer Research where scientists at the Mayo Clinic in Florida report finding an enzyme called PRSS3, or mesotrypsin, that may help drive aggressive prostate cancer. They believe the discovery could lead to a test and better treatment.

Another promising area of research is that being carried out by Cancer Research UK scientists. They are studying a protein called microseminoprotein-beta (MSMB) that may help identify men at greater risk for prostate cancer. They suggest this could be a more accurate marker than the one currently used in screening tests, the prostate specific antigen (PSA).

 

For instance, in a paper published in 2010 in the journal PLoS ONE, Cancer Research UK scientists conclude that "urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades."

Mason says it's men at higher risk for prostate cancer who are likely to benefit most from screening, and it might be better to target those men that to try and screen all men.

However, it is "only through continued research that we'll be able to offer improved tests to reduce the number of men who die from the disease," he adds.

Bowel Cancer

Research into bowel cancer has already improved diagnosis and prevention. Researchers have shown how a one-off flexi-scope (single flexible sigmoidoscopy) test could reduce new cases and deaths from bowel cancer in those who take it up.

For example, one study published in 2011 in the Journal of the National Cancer Institute, shows how a single flexible sigmoidoscopy screening reduced bowel cancer incidence and deaths.

In that study, disease incidence was lowered by 18% and deaths by 22%. Among screened patients, incidence was reduced by 31%, and by 46% for advanced cases. And deaths in screened participants were reduced by 38% compared to controls.

Cancer Research UK also ran a 16-year trial that showed deaths from bowel cancer fell by 43% and cases by a third, in participants who had just one flexi-scope test.

"Our research showed for the first time that we could dramatically reduce the incidence of bowel cancer, and the number of people dying from the disease, by using this one-off test," says Professor Wendy Atkin, Cancer Research UK's bowel cancer screening expert who led the research.

Atkin describes their work as a "fantastic example" of the benefits research brings; "there is no other way we would be able to develop new treatments, know whether a new treatment is better or worse and know who should receive it," she adds.

Melanoma

Researchers by Cancer Research UK and others around the world has led to promising new treatments for advance melanoma, bringing hope to patients.

However, it is also essential that efforts to prevent the disease continue.

Most cases of melanoma are due to over-exposure to the sun's UV rays, and sunbeds. One study published recently shows how sun damage causes newly discovered melanoma-driving genetic changes.

Other areas where research is making inroads, is finding out how melanoma cells circumvent the immune system, and also fighting the cancer's resistance to chemotherapy.

Public Generosity

"It's only through research that we will be able to beat cancer. We need to do more work to understand what drives cancer and how we can prevent it, as well as developing new treatments to reduce the number of people who will die from it," urges Kumar.

"Understanding the biology of cancer is rather like completing a complex jigsaw puzzle. Many pieces have already fallen into place but we need more research before we can complete the picture. And thanks to the generosity of the public, our world class scientists are playing a leading role in beating this devastating disease," he adds.

Cancer Research UK has released the figures ahead of a UK television advertising campaign that launches on Boxing Day whose message is cancer will only be defeated through research.

UK charities are facing tough times. A recent report compiled by the Charities Aid Foundation and the National Council for Voluntary Organisations finds that charity giving in the UK fell by 20% in real terms in 2011-2012.

Extended Use Of Zytiga Approved By FDA For Late-Stage Prostate Cancer

Today the U.S. Food and Drug Administration (FDA) lengthened the approved use of Zytiga (abiraterone acetate) as treatment for men with late-stage, castration-resistant prostate cancer (metastatic) before undergoing chemotherapy.
First approved in 2011, Zytiga is used in patients whose prostate cancer developed further after treatment with docetaxel, a chemotherapy drug. Zytiga is a pill that reduces the production of testosterone, the male sex hormone.

This drug is known to preserve quality of life, reduce the spread of cancer, as well as slow the development of pain and the decline of an individual's overall health, according to a study released earlier this year.

A separate study also recommended Zytiga in combination with prednisone for late-stage, castration-resistant prostate cancer, and showed that Zytiga is being used successfully in over 40 different countries.

Tumor growth during prostate cancer is triggered by testosterone. Surgery or drugs are used to decrease the effects or block creation of testosterone.

Castration-resistant prostate cancer is when the prostate cancer cells keep growing even without large amounts of testosterone.

Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, says,

"Today's approval demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment."

The FDA examined the application for this altered use of Zytiga under the agency's priority review program. This specific program gives an accelerated six-month examination for drugs that may give major benefits in treatment or offer a treatment when no current therapy exists.

A clinical study was conducted using 1,088 men with late-stage, castration-resistant prostate cancer who had not yet undergone chemotherapy which established the successfulness and safety of Zytiga.

The study was developed to calculate the length of time a patient existed before death as well as the amount of time a patient lived without further tumor development. These two time periods were measured by imaging known as radiographic progression-free survival, or rPFS.

Patients who took Zytiga had a medical survival rate of 35.3 months, while those taking a placebo had a 30.1 month survival rate. Results showed that Zytiga enhanced rPFS. The median rPFS was 8.3 months in the placebo group, while in the other group had not been achieved yet at the time of calculation.

Side effects that were seen included:

• joint swelling or discomfort
• hot flush
• diarrhea
• vomiting
• fatigue
• swelling caused by fluid retention
• cough
• urinary tract infection
• bruising
• shortness of breath
• high blood pressure

The most frequently documented laboratory abnormalities were:

• high levels of the enzyme alkaline phosphatase
  -this could be a sign of other medical problems
• low levels of potassium, lymphocytes, and phosphorous in the blood
• high levels of fatty acids, liver enzymes, and sugar in the blood

Written by Kelly Fitzgerald

View drug information on Zytiga.

Trojan Horse" Cancer Treatment Eliminates Cancer In Mice

An experimental treatment that uses white blood cells like "Trojan horses" to carry a tumor-busting virus, completely abolished prostate cancer spread after chemo or radiotherapy in mice. The researchers hope clinical trials in human patients with prostate cancer can start in early 2013.
Claire Lewis, a professor at the Department of Oncology in the University of Sheffield, and colleagues, write about their findings in a recent issue of the journal Cancer Research.

Using immune cells to carry viruses to treat cancer is an emerging field. In June 2012, researchers reported discovering how when a cancer-killing virus is injected in the bloodstream it hitches a ride on blood cells and evades attack from the immune system, allowing it to reach cancer tumors, and start destroying cancer cells.

Lewis and her team have also been investigating this approach, and discovered that the challenge is to get enough of the virus deep into the tumor.

After chemotherapy or radiotherapy, the immune system floods the tumor with white blood cells called "macrophages" that mop up the debris caused by the therapy.

UK researchers have suggested that a "Trojan Horse" cancer therapy has completely eliminated the spread of prostate cancer in mice.

Lewis and colleagues found that injecting macrophages carrying a tumor-busting or "oncolytic virus" (OV) into the bloodstream at the exact moment when this surge occurs, they "surf the wave" of white blood cells and inundate the tumor in large numbers.

"... we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the post-treatment regrowth of primary prostate tumors in mice, and their spread to the lungs for up to 27 or 40 days respectively," they write.

The treatment also "significantly increased the lifespan of tumor-bearing mice compared to those given docetaxel or irradiation alone," they add.

In a statement released last week, Lewis says:

"Our "Trojan horse" can convert a patient's own white blood cells into tiny tumor-killing machines which fight to prevent tumor regrowth after the end of chemo or radio therapy treatment."

"This is very empowering for patients who have been undergoing rounds and rounds of chemotherapy or radiotherapy because treatment means it is their own white blood cells doing the work and blasting the cancer," she explains.

First author Munitta Muthana, from Sheffield's Department of Infection and Immunity, adds:

"With the initial support of the Yorkshire Cancer Research (YCR) and latterly Prostate Cancer UK, our new therapy has been developed to treat prostate cancer; however, it has the potential to be used to treat patients with any form of cancer."

Kate Holmes, Head of Research at Prostate Cancer UK describes the study as an "exciting development" in the "Trojan Horse" approach.

"It demonstrates that this innovative method of delivering a tumor-killing virus direct to the cancer site is successful at reducing the development of advanced prostate tumors in mice which have been treated with chemotherapy and radiotherapy."

"If this treatment goes on to be successful in human trials, it could mark substantial progress in finding better treatments for men with prostate cancer which has spread to the bone, and ensuring the impact of more traditional therapies is maximised," she adds.

Meanwhile, across the Atlantic in the US, researchers at the Mayo Clinic have discovered th an  enzyme called PRSS3, or mesotrypsin, may help drive aggressive prostate cancer. They suggest their finding will lead not only to more effective treatment of advanced prostate cancer, but may also help identify those at high risk for the aggressive form.

Prostate cancer is the most common cancer in men in the UK, where rates have tripled in the last 40 years.

In 2009, about 40,800 men in the UK were diagnosed with the disease, or around 112 a day.

High-fat diets: Addiction that's hard to break

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Eating unlimited amounts of high-fat food for just six weeks before resuming a more reasonable diet is enough to cause anxiety, intense cravings and other withdrawal-like symptoms in mice.
The rodents also experienced chemical changes in their brains that suggested parallels between the ways they respond to fatty and sugary foods and the ways they respond to harder drugs, like cocaine.
Together, the new findings add to a growing body of research into the addictive qualities of junk food.
"What this means from my interpretation is that it's important to prepare oneself for the low that can be experienced from changing the diet and removing palatable high-fat, high-sugar rewards," said Stephanie Fulton, a neuroscientist at the University of Montreal. "We can try to plan for the low and replace food with other things that give us pleasure, whatever that might be."
Sugar's Power Over Human’s Traced
Over the last decade or so, a growing number of studies have begun to suggest that certain kinds of food can truly be addictive, said Nicole Avena, a neuroscientist at the University of Florida, Gainesville.
Rats that are cyclically deprived of sugar or fat and then given free access to sweet or rich foods, for example, binge on those foods when they're available, and they show intense signs of craving. Once they're addicted, rats will go to great lengths to get fat-and-sugar filled foods like Oreos, including crossing a grid that zaps them with electric shocks.
Some of the first studies in the field showed simply that, when sugar is taken away from rats, the animals go through withdrawal symptoms, including anxiety, depression and tremors. Follow-up work found that those symptoms accompany changes in dopamine and opioid systems -- two types of neurotransmitters that are involved in cravings and withdrawal.
In more recent, detailed and nuanced research, Avena's group and others have documented specific changes in the behavior and brain chemistry of rodents after a period of overeating junk food that mimic what happens when the animals abuse drugs.
Food Obsession Similar to Drug AddictionFor the new study, Fulton and colleagues wanted to see what would happen to mice that ate a tasty but less-than-healthful diet for a relatively short period of time.
After six weeks on chow that was rich in saturated fats, the rodents in her study had gained just 11 percent of their body weight, making them far from obese.
But when half of the mice were put back on a low-fat diet, the researchers reported in the International Journal of Obesity, the animals acted increasingly anxious. In a maze test, for example they chose to spend more time sitting still in the darkness than exploring exposed areas.
After being taken off the high-fat diet, mice also showed increased signs of craving -- with more motivation to get a high-sugar solution.


At the same time, the researchers measured changes in brain chemicals, including dopamine and a molecule called CREB, which have been linked in previous work to both food cravings and drug addictions.
"Even periods of high-fat feeding that don't leave to obesity can produce several important biochemical and behavioral changes that make it hard to give up," Fulton said.
The new study is one of many that are adding up to demonstrate how high-fat, high-sugar foods affect not just our waistlines, Avena said, but also our brains.
"It's important that people know these types of studies are going on and that the findings that are being discovered are relatively consistent," she said. "It might make people think twice about the kinds of foods they eat and why they are eating them and whether there might be some kind of addition-like compulsion to eat certain kinds of foods."
"It's a new way to think about food," she added. "It's about us having to eat foods as opposed to us wanting those foods."

 

Jagaricin and antifungal drugs: an interview with Prof Christian Hertweck

Please can you give a brief introduction to human fungal infections?

Most people have already experienced a fungal infection (mycosis) of the outer layer of the skin, athlete’s foot or ringworm. Whereas such infections may be cumbersome and often difficult to cure, usually they are not dangerous. However, in cases where a fungus causes a systemic infection, this is, it infects internal organs such as lungs orbrain, the infection may turn into a life-threatening disease. Of course, only pathogenic fungi cause problems and the degree of virulence varies.

There is a particular risk of severe fungal infections for individuals with a weak or compromised immune system, for example patients suffering from AIDS, diabetes,chemotherapy or who have undergone organ transplantation. We are exposed to airborne fungal spores entering the respiratory system, but in immunocompromised individuals these spores may germinate and the fungus may spread within the body and destroy affected organs.

The major causes for human fungal infections are Candida and Aspergillus species, yet there are many other ones that can cause infections. In any case, these infections inflict sever suffering, both physical and mental.

Please can you outline what antifungal drugs are currently available?

For treating systemic fungal infections, most often so-called polyene macrolides (e.g. amphotericin) and lipopeptides (e.g. echinocandins) are clinically used. These therapeutics efficiently target the fungal cell wall. However, when given intravenously, the drugs cause severe side effects, for example, amphotericin is nephrotoxic (poisonous for the kidney). There is an urgent need for new and improved antiinfectives.

Please can you explain what jagaricin is?

Jagaricin is produced by a bacterium that infects mushrooms such as white button. The compound belongs to the group of lipopeptides. Besides aiding in the infestation of the mushroom, it is active against a variety of other fungi including human pathogens such as Aspergillus fumigatus and Candida albicans.

How did your research into jagaricin originate?

We became aware of less investigate bacteria that can infect mushrooms and assumed that the bacteria likely employ small compounds that weaken or kill the fungus. We then reasoned that such compounds would be potentially active against other fungi and thus perhaps also useful for treating mycoses.

Sequencing the genome of the bacterium proved to be very helpful because with the genomic inventory at hand we were able to predict its potential for metaboliteproduction. We noted that the candidate genes were silent under standardized culture conditions in the laboratory. Thus, we wanted to catch the bacterium in action and monitored how it infects the mushroom.

Using a modern method to visualize the production of metabolites (imaging mass spectrometry) we discovered that a compound with a particular molecular mass accumulates in lesions of the mushroom tissue.

Finally, we succeeded in finding growth conditions to produce sufficient amounts of the antifungal agent for a full structural elucidation and biological testings.

What impact do you think your research will have on antifungal drugs?

I believe that our work is the proof of principle that mushroom pathogens are a promising source of novel antifungal agents. Furthermore, the combination of genome data and imaging techniques will be most useful for the discovery of potential therapeutics that are only produced in a particular biological context. Very likely, jagaricin would have been overlooked using a classical approach.

How long do you think new antifungal drugs will take to develop?

The discovery of a new anti-infective agent does not at all imply that this compound will soon be available at the pharmacy. In the case of successful clinical trials, the development of a new drug typically takes around ten years. Notably, only a tiny fraction of the potential drugs will make it into clinical trials, and the development of a new drug is extremely cost-intensive.

Do you think these new antifungal drugs will be better than current antifungal drugs?

It is a bit too early to speculate on that. We hope that a pharmaceutical company will be interested in evaluating the therapeutic potential of jagaricin.

What plans do you have for further research into this field?

We have various on-going projects that focus on the discovery of antibiotics from so far neglected sources, including bacteria and fungi, combining the strengths of chemistry and biology.

What do you think the future holds for antifungal drugs?

To answer that we may ask ourselves how would our future look like without antifungal drugs. Unfortunately, considering the immense costs for drug development, for pharmaceutical companies it is far more lucrative to develop other drugs such as lipid reducers, antidepressants, drugs many individuals take over a long time – rather than a few doses of an antibiotic. General programs in this area of research and translational measures are urgently needed.

Where can readers find more information?

 

About Prof Christian Hertweck

Christian Hertweck (*1969) gained a Ph.D. in Organic Chemistry at the University of Bonn and at the Max Planck Institute for Chemical Ecology.

He was Feodor Lynen postdoctoral fellow at the University of Washington, Seattle, before starting his own research group at HKI Jena.

Since 2006 he has been full professor at the Friedrich Schiller University, Jena, and head of the Department of Biomolecular Chemistry at the Leibniz Institute for Natural Product Research and Infection Biology (HKI).

His research interests encompass bacterial and fungal natural products, with a focus on biosynthesis, pathway engineering, and microbial interactions.