NEWLY DISCOVERED ANTIBIOTIC KILLS PATHOGENS WITHOUT RESISTANCE

For years, pathogens resis­tance to antibi­otics has put them one step ahead of researchers, which is causing a public health crisis. But in new research, led by the researchers at the present study discloses that  a newly dis­cov­ered antibi­otic has been identified  that elim­i­nates pathogens without encoun­tering any detectable resistance -- a finding that chal­lenges long-​​held sci­en­tific beliefs and holds great promise for treating chronic infec­tions like tuber­cu­losis caused by Mycobacterium tuberculosis, diseseases caused by Streptococcus sp.

The work is mainly carried out by the North­eastern researchers led by Lewis along with the northeastern biology professor Slava Epstein and in association with NovoBiotic Pharmaceuticals in Cambridge and Selcia ltd. UK. They played an important role in   developing a novel method for growing uncul­tured bac­teria led to the dis­covery of the antibi­otic, called teixobactin, and also ana­lyzing and testing the com­pound for resis­tance from pathogens. It is supposed to be the first discovery of an antibi­otic to which resis­tance by muta­tions of pathogens have not been identified.

The research team says teixobactin's dis­covery presents a promising new oppor­tu­nity to treat chronic infec­tions caused by staphy­lo­coccus aureus, that are highly resis­tant to antibi­otics, as well as tuber­cu­losis, which involves a com­bi­na­tion of ther­a­pies with neg­a­tive side effects.

The screening of soil microor­gan­isms has pro­duced most antibi­otics, but only 1% of them will grow in the lab, and this lim­ited resource was over­mined. The reserachers  spent years seeking to address this problem by tap­ping into a new source of antibi­otics beyond those cre­ated by syn­thetic means: uncul­tured bac­teria, which make up 99% of all species in external envi­ron­ments. The scientists have devel­oped a novel method for growing uncul­tured bac­teria in their nat­ural envi­ron­ment. The approach of developing the same  involves the iChip, a minia­ture device Epstein's team cre­ated that can iso­late and help grow single cells in their nat­ural envi­ron­ment and thereby pro­vides researchers with much improved access to uncul­tured bac­teria.

The antibi­otic was dis­cov­ered during a rou­tine screening for antimi­cro­bial mate­rial using the above method. Lewis then tested the com­pound for resis­tance devel­op­ment and did not find mutant       Mycobac­terium tuber­cu­losis resis­tant to teixobactin, which was found to block sev­eral dif­ferent tar­gets in the cell wall syn­thesis pathway.

In 2013, Lewis revealed ground­breaking research in a sep­a­rate paper pub­lished byNature that pre­sented a novel approach to treat and elim­i­nate tuberculosis and other non resistant disease.

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Study show that reprogramming stem cells can prevent cancer following full body radiation

The body has evolved ways to get rid of faulty stem cells. A study conducted in the University of Colorado Cancer Center shows that one of these ways is a "program" that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. Radiation makes a stem cell lose its "stemness."

The study also shows that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, we may be able to prevent cancer in the aftermath of full body radiation.

Our body is not evolve to deal with leaking nuclear reactors and CT scans. It is evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA .

The team that carried out the research in the same explored the effects of full body radiation on the blood stem cells of mice. In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. Only, while most followed this instruction, a few did not. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their "stemness". Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it's not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation.

Usually in the healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. But when radiation reduces the heath and robustness  of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over.

These studies not only tell us why radiation makes hematopoietic stem cells (HSCs) differentiate but it also states that they also show activating a stem cell maintenance pathway. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again - restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.

When researchers tried to activate NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.

The scientist who carried out the research said "If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their "programmed mediocrity" (increased differentiation) and even HSC with cancer-causing mutations.

But there's also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation.

GINGER FOR OSTEOARTHRITIS

Arthritis is the common disease of old age people whose age is above 40. Arthritis is more common in women than in men. Basically, arthritis is a common group of disease that involves the damaged body joints. There are many types and form of arthritis, of which the most common form of is the Osteoarthritis which is affecting millions of people around the globe. Osteoarthritis occurs when the protective cartilage on the ends of the bones degenerates over time. Obesity may also lead to the major cause of osteoarthritis. Osteoarthritis may be also referred to as wear-and-tear arthritis.

Signs and Symptoms

Osteoarthritis often affect slowly but it gets worsen over time. The main symptoms observed in the osteoarthritis include pain in various body joints, the joints become tender or very sensitive, or stiffness of the joints which can be easily observed when the patient wake up in the morning.

Treatment

Various medications and drugs are available for the treatment of osteoarthritis, of which one of the best and proven natural remedy is the use of ginger for the treatment of the same.

Zingiber officinale which is commonly known as ginger by the common people have great medicinal values and is used for treatment therapy for curing wide range of diseases. Through various research it has been proved that ginger contains various anti-inflammatory compounds called gingerols that plays the major role in treating osteoarthritis to a great extent.

The scientific studies that were generally conducted used powdered ginger roots, fresh ginger roots at an equivalent dosage which proved to have given better results against osteoarthritis. These ginger extracts reduces the production of various chemical substances (for e.g. Leukotrienes) that are the main substances that promote joint pain and inflammation.

An example of chemical trial that was conducted from Australia’s Edith Cowan University to confirm the use of ginger for the treatment of osteoarthritis is mentioned below.

In this research 20 patients were recruited who were suffering from osteoarthritis. Each patients were under the observation period for 24 weeks where they were given ginger patch for treatment. Improvements started showing within 2 weeks of the treatments where the patients experienced reduced joint pain and increased mobility of the joint.

Most of the studies utilizes 1 gm of powdered ginger root or fresh ginger roots or an equivalent dosage of both have also been proven effective.

Ginger tea have also proved to be effective against osteoarthritis.

OMEGA-3 FATTY ACIDS RHEUMATOID ARTHRITIS

Rheumatoid Arthritis (RA) is an autoimmune disorder that causes systematic inflammation of the joints. Autoimmune disorder is the disorder that occur when the body’s tissues are mistakenly attacked by their own immune system.

    A joint is where two bones meet to allow movement of body parts. Arthritis means joint inflammation. The joint inflammation of rheumatoid arthritis causes swelling, pain, stiffness, and redness in the joints. The inflammation of rheumatoid disease can also occur in tissues around the joints, such as the tendons, ligaments, and muscles.₍₁₎

Although Rheumatoid Arthritis can occur at any age, but it usually occurs after the age of 40. According to the recent studies it has been seen that the disorder is more common in women than in men.

SYMPTOMS

Signs and symptoms of rheumatoid arthritis may include:

Ø  Tender, warm, swollen joints

Ø  Morning stiffness that may last for hours

Ø  Firm bumps of tissue under the skin of the arms

Ø  Fatigue, fever and weight loss.

Over time, rheumatoid arthritis can cause joints to deform and shift out of place.₍₂₎

CAUSES

Doctors still have no clue what exactly causes Rheumatoid Arthritis, although genetic components are most likely to be involved. Smoking is the most significant non-genetic risk.₍₃₎

TREATMENTS

OMEGA- FATTY ACIDS FOR RHEUMATOID ARTHRITIS

There is no proper cure for rheumatoid arthritis. Medications can reduce the inflammation in the joints in order to get relief from pain and prevent or slow down the joint damage. The drugs mainly given as a medication for rheumatoid arthritis have several side effects.

However, a 2012 systematic review concluded that the omega-3 fatty acid found in seafood and fish oil may be modestly helpful in relieving symptoms of rheumatoid arthritis. In the studies included many participants reported that taking fish oil containing omega-3 fatty acid had less joint swelling and pain, and less need for anti-inflammatory drugs to control the rheumatoid arthritis symptoms.₍₄₎

Omega-3 fatty acids exist in two forms namely;

Ø  Long-chain forms (DHA) which is found in higher levels in oily fish

Ø  Short chain forms mainly found in rapeseed oil, walnuts etc.

Amongst the classic inflammatory conditions, fish oil have been extensively used as a topic of research for treating rheumatoid arthritis. Animal models have been demonstrated that omega-3 fatty acids can delay the onset of arthritis, reduce its severity and improve joint pathology.

Omega-3 fatty acids are considered essential fatty acids. They are very much essential for the human health, but the body can’t make them and hence it is given as the supplement with the food an individual take. Omega-3fatty acid have turned out to be best supplement that can be used as the supplement to treat rheumatoid arthritis. Omega-3 fatty acids can be found in fish, such as salmon, tuna, sardines, anchovies, mackerel, other sea food including algae and krill, some plants and nut oils. Also termed as Polyunsaturated Fatty acids (PUFAs). Omega-e fatty acids play an important role in proper functioning of the brain, as well as the normal growth and development. The American Heart Association recommends eating fish at least twice a week. The most widely studied omega-3 fatty acids namely eicosapentaenoic acid (EPA) and docosaxaenoic acid (DHA) have various effects in the body. In the immune systems, EPA is a precursor for eicosanoids, which are messenger molecules that are less inflammatory. EPA and DHA also produces inflammatory molecules called resolvins ( Norling and Peretti), and reduce the expression of gene that produces inflammatory components (Calder). As rheumatoid arthritis is caused by inflammatory molecules attacking healthy cells, reducing inflammation can treat the cause of the disease.₍₅₎

Laboratory studies of University of Maryland suggests that diets rich in omega-3 fatty acids (and low in the inflammatory omega-6 fatty acids) may help people with osteoarthritis, although more study is needed for the same. New Zealand green lipped mussel (Perna canaliculus), another source of omega-fatty acids, has been reported to reduce joint stiffness and pain, increase grip strength, and improve walking pace in a small group of people with rheumatoid arthritis. Exceptionally, in some cases the symptoms got worse before they are improved.

An analysis of 17 randomized, controlled clinical trials looked at the pain relieving effects of omega-3 fatty acid supplements in people with rheumatoid arthritis or joint pain caused by inflammatory bowel disease and painful menstruation. The results suggests that omega-3 fatty acids, along with conventional therapies such as Non-Steroidal anti-inflammatory drugs (NSAIDs), may help relieve joint pain associated with these condition.₍₆₎

The influence of omega-3 fatty acids on the functional responses of various cell types involved in inflammation and on the production of the rage of chemical mediators produced has been a favorite topic for research of many. Various reports have been found over the year which states the effects of omega-3 fatty acids acts in anti-inflammatory manner, with more recent studies suggesting that they may be involved in the resolution of inflammation. The anti-inflammatory effects of omega-3fatty acids are widely reviewed round the globe. The ability of omega-3 fatty acid to down-regulate several aspects of inflammation suggests that these fatty acids might be important in determining the development and severity of inflammatory diseases and further they may be used as a useful component of therapy.

The main mechanism underlying the anti-inflammatory actions of omega-3 fatty acid include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor ˠ) and binding to the G-protein.

For e.g., Cleland et al. found that patients with RA who use fish oil supplements were more likely to reduce the use of non-steroidal anti-inflammatory drugs (NSAIDs) with respect to those patients that did not use fish oil as the supplement. The dose of omega-3 fatty acids used in these trials has typically been high, between about 1 and 7g/day and averaging about 3.5g/day. This dose would equate to 50mg per kg body wt. per day which is quite difficult to get it achieved through supplement diet or liquid oil.₍₇₎

However, in the current studies that are been conducted recently used a low dose of 0.4 gms per day, which is able to be obtained from diet and a high dose of 5.5 gms per day. Patients who had been diagnosed with rheumatoid arthritis over many years were asked for the participation in the clinical trials that were conducted. The progression of rheumatoid arthritis, including joint deformities can be delayed if the treatment is started early to reduce the excessive amounts of inflammatory molecules in the body. The fish oil treatment was additional to the use of a single first-line disease-modifying anti-rheumatic drug (DMARDs). The patients were guided by the physicians during the one-year study. After one year of supplementation, the researchers found that the patients in the high dose had a lower failure rate of first-line treatment. In the high-dose group, only 10% reported failure of DMARDs, while in a low-dose group, 32% reported DMARD failure. This meant that for around one quarter patients, fish oil supplementation and the first-line treatment were enough to stabilize rheumatoid arthritis, and for a further two-thirds, the first-line treatment was likely sufficient.

Various other meta-analyses results are also conducted for eg., Lee, Bae and Song analyzed ten clinical trials in rheumatoid arthritis patients and found that omega-3 supplements significantly reduced the use of common pain killers. Trials also found a non-significantly reduction in the number of tender and swollen joints, improvements in physical function, and less joint stiffness in the morning. The dose should be at least 2.7 gms per day, and the supplements should be taken for longer than 3 months.₍₈₎

However, omega-3 fatty acid intake do have some side effects in the human body. While conducting various research studies it has been found that the patients who were undertaking the omega-3 fatty acid as the supplement had mild stomach upsets and diarrhea. Recently, there have been concerns about the possible link between high levels of omega-3 fatty acid and prostate cancer.  It is also often dangerous to take fish liver oil in large doses because of the risk of overdosing with vitamin A. this is particularly important for the pregnant women, or women who are likely to get pregnant, because vitamin A can harm the newborn baby. Hence, it is always recommended to consult the dose of omega-3 fatty acids before intake.

 Unlike prescription medications, fish oil does not appear to slow progression of rheumatoid arthritis, only to treat the symptoms. Joint damage still occurs.

DOSE OF INTAKE

Researchers suggest that one need at least 2.7 gm per day of the long chain omega-3 fatty acids. Fish oil act quite slowly so it is recommended that one must have at least 3 months supplements of fish oil for having effective results. It is always recommended to have omega-3 fatty acid along with the diet that a person is having to reduce the risk of cardiovascular diseases.

REFERNCES;

1.      www.mayoclinic.org/disease-conditions/rhematoid-arthritis/basic/definations/con-20014868

2.      www.medicinenet.com

3.      www.wikipedia.org

4.      Omega-3 fatty acids- university of Maryland medical Centre

5.      Marine omega-3 fatty acids and inflammatory process: effects, mechanisms and clinical relevance: Calder PC

6.      Omega-3 fatty acids, rheumatoid arthritis, and inflammation: Julia Bird

7.      The benefits of omega-3 fatty acids: Linda Richards

8.      www.arthritisresearchchuk.org

9.      Omega-3 fatty acids and inflammatory processes: nutrition or pharmacology? : Philip C Calder

10.  Rheumatoid arthritis: William C Shiel Jr. MD, FACP, FACR

Apple boosts sexual pleasure in women

A new study reportedly has linked daily apple use with an enhanced sexual function in healthy women. Apples contain polyphenols and antioxidants that can stimulate blood flow to the genitals leading to better arousal. Researchers have performed the experiments on various women. They found that women who had one-two apples had beter lubricaton and sexual function.  The study says, apple contain phloridzin, that is structurally similar to estradiol, a female sex hormones linked with arousing sexuality

Source- hyderabad times.

Can smelling herbs help you sleep better?

Herbs are known to have sevral benefits. One of them, lavender, is said to aid sleep. Put a few drops on the pillow eac night will help one to reduce anxiety, stress and mood swings and calms the nerves. There are some other herbs which are beneficial as well, namely,
1. Cilantro helps to improve bone strength
2. Basil have anti bacterial properties. It is also anti inflammatory and cures mouth ulcers. Basil leaves are boiled in water which helps to cure sore throat.
3. Parsley is a power house of antioxidants, minerals and vitamins which helps to regulate blood cholesterol levels and prevents constipation.
4. Apart from imparting flavour to food, lemon grass also have antifungal properties and its stems are said to have folic acid content.

Sources- hyderabad times.

CARBOHYDRATE DIGESTION AND OBESITY STRONGLY LINKED

New research indicates that obesity in the general population may be genetically linked to how our bodies digest carbohydrates. The study investigated the relationship between body weight and a gene called AMY1, which is responsible for an enzyme present in our saliva known as salivary amylase. This enzyme is the first to be encountered by food when it enters the mouth, and it begins the process of starch digestion that then continues in the gut.

People usually have two copies of each gene, but in some regions of our DNA there can be variability in the number of copies a person carries, which is known as copy number variation. The number of copies of AMY1 can be highly variable between people, and it is believed that higher numbers of copies of the salivary amylase gene have evolved in response to a shift towards diets containing more starch since prehistoric times.

Researchers from Imperial College London, in collaboration with other international institutions, looked at the number of copies of the gene AMY1 present in the DNA of thousands of people from the UK, France, Sweden and Singapore. They found that people who carried a low number of copies of the salivary amylase gene were at greater risk of obesity.

The chance of being obese for people with less than four copies of the AMY1 gene was approximately eight times higher than in those with more than nine copies of this gene. The researchers estimated that with every additional copy of the salivary amylase gene there was approximately a 20 per cent decrease in the odds of becoming obese.

Professor Philippe Froguel, Chair in Genomic Medicine in the School of Public Health at Imperial College London, and one of the lead authors on the study, said: "I think this is an important discovery because it suggests that how we digest starch and how the end products from the digestion of complex carbohydrates behave in the gut could be important factors in the risk of obesity. Future research is needed to understand whether or not altering the digestion of starchy food might improve someone's ability to lose weight, or prevent a person from becoming obese. We are also interested in whether there is a link between this genetic variation and people's risk of other metabolic disorders such as diabetes, as people with a low number of copies of the salivary amylase gene may also be glucose intolerant."

Previous studies have found rare genetic variations causing extreme forms of obesity, but because they occur in only a small number of people, they explained very little of the differences in body weight we see in the population. On the other hand, research on more common genetic variations that increase risk of obesity in the general population have so far generally found only a modest effect on obesity risk. This study is novel in that it identifies a genetic variation that is both common and has a relatively large effect on the risk of obesity in the general population. The number of copies of the salivary amylase gene is highly variable between people, and so, given this finding, can potentially have a large impact on our individual risk of obesity.

The first step of the study involved the analysis of genetic data from a Swedish family sample of 481 participants, recruited on the basis of sibling-pairs where one was obese and the other non-obese. The researchers used these data to short-list genes whose copy number differences influence body mass index (BMI), and identified the gene coding for the enzyme salivary amylase (AMY1) as the one with the greatest influence on body weight in their analysis. They then investigated the relationship between the number of times the AMY1 gene was repeated on chromosome 1 in each individual and their risk of obesity, by studying approximately 5,000 subjects from France and the UK.

Story Source:

The above story is based on materials provided by Imperial College London. Note: Materials may be edited for content and length.

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Journal Reference:

1. M. Falchi et al. Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics, 2014 DOI: 10.1038/ng.2939

Sugar: time bomb....

New sugar limits: 26 'mini health time bombs' http://www.telegraph.co.uk/health/healthnews/10680467/New-sugar-limits-26-mini-health-time-bombs.html

Project Work in Medical Biochemistry and Microbiology 2013/2014 - Uppsala University, Sweden

Project Work in Medical Biochemistry and Microbiology 2013/2014 - Uppsala University, Sweden

Early tumor response from stereotactic radiosurgery predicts outcome

The response of a patient with metastatic brain tumors to treatment with stereotactic radiosurgery in the first six-to-twelve weeks can indicate whether follow-up treatments and monitoring are necessary, according to research conducted at the University of North Carolina School of Medicine.

          The study of 52 patients with metastatic brain legions, found that the tumors whose sizes decreased significantly after treatment with stereotactic radiosurgery (SRS) did not resume growth or require additional treatment. The research, conducted by a team led by Matthew G. Ewend, MD, chair of the UNC Department of Neurosurgery and member of the UNC Lineberger Comprehensive Cancer Center, could reduce the need to continually monitor patients who respond well to SRS.

 The volume of the tumors over time was measured to see the outcome, based on what happened in the beginning, what would happen long term.It was that tumors that did not shrink in the beginning were more likely later to be correlated to a patient having a neurological problem or needing steroids. If they did shrink, they were more likely to stay under control long term."

The advent of SRS systems allows physicians to target tumors with precise, high-dose beams of radiation. While the technique is in widespread use, current practice requires repeated check-ups to determine its effectiveness. The results of this study indicate that this monitoring may only be necessary for patients who do not respond favorably within the first six to twelve weeks after SRS treatment.

 few MRIs  scans are necessary afterwards for a good response.

Between 20 and 40 percent of adults with cancer develop brain tumors, which metastasize from cancers elsewhere in the body. The number of brain tumors treated by physicians has increased, as better treatments for the cancers that spawn them increase patient survival. Because of the systemic nature of these cancers, the survival implications of positive early response depend largely on how patients respond to therapy for their initial cancer.

"This is not in a vacuum. Even if you control the brain disease, they can still die of their other disease. With better control of the brain disease, the patients have a better chance of living longer, but it will take both improvements in systemic therapy and brain therapy," said Dr. Ewend.

The UNC study included patients with lung, breast, melanoma and renal cell cancers. It builds on prior research that indicated a similar response in patients with clear cell renal cancer. Dr. Ewend said that future research will need to increase the number of patients to reinforce the results and determine what factors influence positive early response. One possibility for future research is to determine the genetic factors behind tumor response, which will allow researchers to develop a genetic test to help predict a patient's outcome.

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Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.

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Journal Reference: Suzanne R. Sharpton, Eric K. Oermann, Dominic T. Moore, Eric Schreiber, Riane Hoffman, David E. Morris, Matthew G. Ewend. The Volumetric Response of Brain Metastases After Stereotactic Radiosurgery and Its Post-treatment Implications. Neurosurgery, 2014; 74 (1): 9 DOI: 10.1227/NEU.0000000000000190

DIFFERENT CANCER SAME MUTATION

 

An astounding variety of genetic abnormalities can cause healthy cells to turn cancerous. Few of these are shared among cancers of the same tissue, and fewer still are shared among cancers of different tissues. Nevertheless, scientists searching for such common genetic needles in an array of cancer.

“For the first time we have been able to analyze, across the board, large numbers of tumor samples . . . and also systematically look across different tumor types,” said Chris Sander, chair of the computational biology program at the Memorial Sloan-Kettering Cancer Center in New York, and senior author on one of the new papers. The main aim was to learn about principles of cancer biology that might not have been obvious from previous studies examining one tumor type in isolation.

“TCGA is all about analyzing each tumor type separately,” said Josh Stuart, a professor of biomolecular engineering at the University of California, Santa Cruz, who was not involved in either study. ON every time a new experiment is carried out in cancer, we always wanted to compare it to the previous one and it has been analyzed that there is some kind of  similarities.

One benefit of looking at cancer samples from all tissue types is that the pool of data becomes larger, offering more statistical power. .

A scientist team examined DNA copy number alterations—common features in cancer—at roughly 1.5 million loci across the genome. They found approximately 200,000 copy number alterations in total, which worked out to about 39 alterations per cancer sample.

To determine which of these alterations might be causing cancer, the researchers looked for only those that recurred across various cancer types. By doing so, they whittled down the 200,000 or so loci to just 140. Only 35 of these loci contained known oncogenes or tumor suppressor genes, meaning the remaining 105 contained new cancer-causing candidates to investigate.

Another scientist  team—which studied gene mutations and DNA methylation changes in addition to copy number alterations—similarly whittled down many thousands of such genetic aberrations to just 479 that were recurrent across multiple cancer types.

The team then asked which of these 479 genetic events occurred in each cancer sample, paving the way for new categories of cancer based on the particular constellations of aberrations they possessed. Interestingly, the team found that cancers with abundant single gene mutations tended not to have many copy number alterations and vice versa.

The two team  come to in conclusion is that they have a spectrum of tumors that are driven by copy number abnormalities  and then another set of tumors that are driven primarily by a series of mutational events. The two papers provided a very cogent argument that these are two of the major driving events.

Beyond learning more about the mechanisms behind the disease’s origins, such cancer studies might lead to a new kind of clinical trial. Sander described such studies as basket or matrix trials, in which patients with different tumor types—for example, breast, ovarian, or colorectal—but similar constellations of genetic alterations, would be treated with the same drug or drugs.

 It’s possible that the same mutation in different cancer types could indicate different responses to drugs.

REFERNCE-

G. Ciriello et al., “Emerging landscape of oncogenic signatures across human cancers,” Nature Genetics, doi:10.1038/ng.2762, 2013.

T. I. Zack et al., “Pan-cancer patterns of somatic copy number alteration,” Nature Genetics,doi:10.1038/ng.2760, 2013.

HOW VITAMIN D HELPS PREVENT LUNG CANCER?
Increasing vitamin D may now be a matter of life or death, as recent studies have shown that it may play a vital role in the fight against lung cancer. To date, lung cancer is one of the three most common cancers that kill men and women in developed countries with a statistic of one million deaths every year.
Researchers from the University of California at San Diego discovered a correlative relationship between higher rates of lung cancer and less exposure to the sun.
Cancer and vitamin D
The study compared data from national and international databases and compared the lung cancer rates in 111 countries. It found a correlation with smoking, lung cancer and significant lower UVB exposure. Although the current study focused only on lung cancer, research conducted on other cancers have pointed to the fact that most cancer cases are seen in subjects living far from the equator, suggesting that lower levels of vitamin D also account for a high risk of colon and other cancers.
Traditionally, vitamin D was thought to be mostly responsible for bone health and was the medical answer to the rickets phenomenon decades ago. More recent findings have shown that the body has cells and tissues which contain vitamin D receptors necessary for its proper functioning, spurring a lot of interest in the potential of what it can do. The fact that it has just been discovered to prevent a spectrum of chronic diseases, cancer included, has stimulated a debate about whether it is the answer to the cancer problem that has plagued the world.
What is vitamin D?
Curiously, vitamin D is not a vitamin but a hormone that, as earlier mentioned, affects a lot of physiological processes.
The body needs sufficient sun exposure to produce vitamin D . It can even be stored in the skin until the time when body needs it again. Strangely, it is impossible to get an overdose from sun exposure since the body has a mechanism that controls the amount it needs.
Getting vitamin D from dietary sources may not be enough, as there are not many foods naturally containing vitamin D. This leaves supplementation, which can be an option for those who may not get enough sun exposure.
Vitamin D controls cancer cells
The likely explanation for this is that vitamin D locally controls genes that help keep cancer at bay by keeping cellular proliferation in check. It has also been suggested that it can induce cell death and regeneration, reducing the potential for malignant cells to survive. Once it has done its job, it initiates its own destruction to guarantee that it does not enter circulation to influence calcium metabolism.
Andreas Moritz, a practitioner of alternative medicine and author of "Cancer is not Disease - It's a Survival Mechanism," describes cancer as the body's healing attempt when all other measures of self-preservation have failed. According to him, the reason the body allows some of its cells to become abnormal is because it attempts to heal itself. Thus, blocking its healing attempt can destroy the body while supporting it in its healing mechanisms can save it.
. The present treatment of cancer involves procedures such as chemotherapy, invasive procedure and use of pharmaceuticals. This narrow-minded focus on finding a cure practically ignores other options which have been around far longer than conventional medicine - such as the concept of a nutritional cure.
A look at the current trend in cancer treatments has seen such debilitating side effects in a patient's quality of life that it may appear to hasten a patient's decline rather improve his or her health. A patient may as well not undergo chemotherapy, as his chances of surviving without the procedure may well be higher than when he is undergoing treatment.
Nutritional care, on the other hand, seeks to work with the body's needs by providing the necessary vitamins and minerals needed to properly function. It is actually the natural way of keeping the body in balance and the best way to prevent diseases. In the event that the body's system is compromised due to illness, the body's immune system may be strengthened by taking food that naturally boost its immune system.
REFERENCE--
NATURAL NEWS JOURNAL
Learn more: http://www.naturalnews.com/035282_vitamin_D_lung_cancer_prevention.html#ixzz2fvBkc5oj

UNMASKING THE ROLE OF MAST CELLS IN DENGUE


Immune cells called mast cells can hinder rather than help the body's response to dengue virus, which suggests that mast cell products could be used as biomarkers to identify severe forms of the disease.

Every year, millions of people become infected with dengue virus: a mosquito-borne pathogen that poses an increasingly serious threat to global health. While the majority of individuals either experience no symptoms or mild dengue fever—a flu-like illness with headache, rash, and muscle and joint pain—a small percentage go on to develop a life-threatening condition called dengue hemorrhagic fever (DHF). This can result in hemorrhage, shock, organ failure and even death (World Health Organization, 1997).DHF is marked by the leakage of plasma proteins and fluid out of capillaries so that the blood becomes more concentrated. This vascular leakage is accompanied by a decrease in the number of platelets—cell fragments that help the blood to clot—and abnormalities in liver function. At present, there is neither a vaccine nor any specific therapy for severe dengue infection, and progress on both these fronts has been hampered by an incomplete understanding of disease pathogenesis. Now, in recent research by, Soman Abraham of Duke University and co-workers from the National University of Singapore reveals a pathogenic role for immune cells called mast cells in the response to dengue infection (St John et al., 2013). The study also reveals a potential biomarker that could identify patients at risk of DHF, as well as novel therapeutic targets.

Mast cells are part of the innate immune system—the body’s first line of defense against pathogens—and reside in tissues surrounding blood vessels and lymphatic vessels. They can be activated by the binding of specific antibodies to receptors on their surface, and can also recognize pathogens and inflammatory proteins directly. Mast cells contain large numbers of granules, which are enriched in substances such as histamine, tryptase, chymase and tumor necrosis factor, and within seconds of the mast cells being activated, these substances are released in a process called degranulation. The activated mast cells also begin to synthesize leukotrienes, prostaglandins, cytokines, and other inflammatory mediators. The release of these substances/mediators increases the permeability of blood vessels and recruits immune cells to the site of the infection. It also leads to activation of various non-immune cells, such as smooth muscle cells and mucous glands, which help to remove allergens and pathogens from the body.

Several lines of evidence are consistent with a protective role for mast cells in the host response to pathogens (Abraham and St John, 2010). Dengue virus is known to infect mast cells, particularly in the presence of pre-existing antibodies from an earlier infection (King et al., 2000). Mast cells also contribute to immunosurveillance, responding to dengue virus by activating host anti-viral responses and releasing signaling molecules that recruit additional immune cells (St John et al., 2011). By contrast, other recent work suggests that mast cells may sometimes have a pathogenic role. When infected with dengue virus in vitro, they trigger activation of endothelial cells (Brown et al., 2011). These line the inside of blood vessels and their activation can promote inflammation and blood clotting. Moreover, levels of certain mast cell proteins are elevated in patients with DHF compared to those with milder dengue fever (Furuta et al., 2012).

To begin to decipher the pathogenic role of mast cells, St John et al. injected dengue virus under the skin of the mouse ear. Local activation of mast cells (degranulation) and signs of capillary leakage were observed in the mice, which suggests that mice can be used to study dengue virus.

To delineate the role of mast cells in systemic dengue infection, the Duke-NUS team then introduced a clinical isolate of dengue virus directly into the mouse abdominal cavity. This induced a number of responses similar to those seen in patients with DHF, and which are consistent with increased vascular permeability. The mice also showed evidence of the virus in their bloodstream, as well as viral replication in the liver and spleen—the two primary organs affected in humans—and expressed a marker for mast cell activation, MCPT1. Similar findings were obtained in immunocompromised mice in which dengue virus can replicate more efficiently over a longer period. By contrast, genetically modified mice that were deficient in mast cells did not show vascular leakage in response to dengue virus, but began to do so when they were supplied with mast cells. Moreover, treatment with clinically approved mast-cell stabilizing compounds inhibited both mast cell activation and vascular leakage, in normal as well as immunocompromised mice.

To verify the mouse data, levels of chymase—the human equivalent of mouse MCPT1—were measured in a cohort of infected adults. The early clinical presentation of dengue fever and DHF are similar, but St John et al. found that chymase levels were consistently elevated in DHF patients compared to those with dengue fever. These findings point to a role for chymase (or mast cell activation) in the blood vessel pathology associated with dengue infection, and suggest that it could be a useful biomarker for DHF. Further studies are required to investigate the sensitivity, specificity, and predictive value of the test at various time points, and to determine whether it would also work in children.

The work of St John, Abraham and co-workers has revealed mast cells to be another deleterious player in dengue pathogenesis, despite their previously reported protective function. However, the factors that determine whether the mast cell response is beneficial or harmful are still unclear. The type and location of infected cells is likely to be important as different groups of mast cells can release distinct mediators. Whether the cells are activated by the virus itself or by pre-existing antibodies could also influence the response outcome, as could viral dosage. Lastly, the activity of other immune system components could influence the response of mast cells, as could the patient's genetic background and whether they have allergies.

Download figureOpen in new tabDownload powerpointFigure 1.

The response of mast cells to dengue virus can be beneficial or detrimental. When a mosquito injects dengue virus (brown hexagons) into the skin, the viruses are detected by specific antibodies (green) or unidentified receptors (blue) on the surface of resting (i.e., non-activated) mast cells. These can then trigger an anti-viral response (left) by releasing the contents of their granules (degranulation) and by upregulating intracellular anti-viral molecules (RIG-I and MDA5). The activated mast cells also secrete signaling molecules called chemokines, which recruit other immune cells including natural killer cells (NK), natural killer T cells (NKT) and T cells, which help to clear the virus. However, if local control mechanisms fail, the virus will enter the bloodstream and be carried to other organs (right). This activates the mast cells in these organs so that they undergo degranulation, releasing ready-made proteases such as chymase and tryptase, and synthesizing inflammatory mediators (leukotrienes and vascular endothelial cell growth factor [VEGF]). These increase the permeability of capillaries, leading to vascular leakage. Mast cells in these organs can also be activated by endogenous inflammatory mediators (such as C3a and C5a) that help the body to remove pathogens. Blocking mast cells (or their mediators) with drugs such as cromolyn, ketotifen and montelukast reduces pathogenic vascular leakage, but might also hamper viral clearance. Anti-mast cell therapy could thus be a double-edged sword.

Medications that block mast cells or their mediators have long been used to treat allergy and asthma, albeit with modest efficacy (Boushey, 2012). However, the use of these drugs in dengue infection must wait until we have a better understanding of how mast cells are regulated. It will be essential to find out how we can block vascular leakage without impeding viral clearance, and achieve overall control of infection without triggering an unwanted immune reaction. Nevertheless, the work of St John et al. offers new hope that it will be possible to treat or prevent DHF using readily available drugs, just as soon as we can identify which patients will benefit, and when

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IMMUNOLOGY eLife journal