Lysozymes: key players in our mucosal immunity


Lysozymes are key enzymes that are naturally produced by the body’s secretory cells within the mucosal membranes of the body. These enzymes are found in the saliva, tears, mother’s milk, digestive system and reproductive organs. Lysozymes are considered the most important bactericidal proteins within the mucosal immunity.

lysozymes

Within the body, the mucosal surfaces of the digestive tract, eye conjunctiva, respiratory pathways and reproductive regions are the largest area of exposure to potential pathogenic microorganisms. The mucous membranes contain a sophisticated immunological system led by lysozymes that protects the body from pathogenic development in these regions.

Lysozymes are powerful anti-microbials:

Lysozymes were discovered in the culture of a chicken egg in 1922 by Nobel laureate Sir Alexander Fleming. Fleming first observed the antibacterial action of lysozyme when he treated bacterial cultures with nasal mucus from a patient suffering from a head cold.

This enzyme attacks the protective cell walls of bacteria. Bacteria build a very tough protective skin of carbohydrate chain, interlocked by short peptide strands, which brace their delicate membrane against the cell’s high osmotic pressure.

Lysozyme breaks these carbohydrate – peptide linked chains, destroying the structural integrity of the cell wall (1, 2, 3). Lysozymes act as anti-microbial agents, causing bacterial cell wall to burst under its own internal pressure. In addition to its effectiveness in lysing the bacterial cell wall, lysozyme also appears to be effective at damaging the cell walls of yeast, including C. albicans (4, 5).

Newborns naturally get their lysozyme from mother’s milk. Reduced lysozyme levels in newborns are associated with respiratory infections and bronchopulmonary dysplasia (6). Children who are fed a formula diet that does not contain lysozyme have a three time greater rate of irritable bowel symptoms (7).

Stressors deplete our lysozyme reserves:

The body is constantly producing lysozymes but certain factors deplete lysozyme reserves and reduce the ability to produce new enzymes. These limiting factors include the following:

  • Chronic mental/emotional stress
  • Chronic infections
  • Anti-biotic and NSAID usage
  • Nutritional deficiencies
  • Low stomach acid
  • Leaky gut syndrome
  • Smoking
  • Chronic exposure to air pollution
  • Major food sensitivities

When the body is chronically stressed through any of the above mechanisms all enzyme formation is negatively affected. In particular, the enzymes involved in the mucosal immunity can be severely altered. This increases the risk of digestive disorders, asthma, allergies, vaginal infections and chronic pulmonary dysfunction.

Lysozymes improve gastrointestinal health through the following:

  • They compete directly with the pathogenic microorganisms for epithelial attachment sites in the gastrointestinal tract, thereby preventing the attachment and colonization of the gastrointestinal tract by way of adhesion and clearance of bacteria.
  • Lysozymes bind to and destruct the cell walls of bacteria, triggering their autolysis and eventually cell death.
  • Lysozymes also potentiate the activity of other immune factors such as IgA and AMPs in the mucous membrane to further restrict the entry and attachment of bacteria and viruses.

 

Best ways to improve lysozyme content:

As we grow older, our bodies produce fewer enzymes which increases the importance of attaining enzymatic material through our diet and supplementation. Raw cow, goat and sheep milk are fantastic sources of lysozyme. These sources should ideally come from grass-fed, free-ranging animals and never from commercialized farms.

Fermented raw dairy such as kefir, yogurt, Indian lassi, raw cheeses and African amasi are the rich sources of lysozymes. Uncooked eggs (particularly the white portion) are particularly good sources of lysozyme as well. Undenatured grass-fed, whey protein or raw whey liquid are also outstanding sources of lysozyme.

One could also find good supplemental lysozymes which are most often sold in natural anti-microbial combinations.

Sources for this article include:
1) http://pubs.acs.org

2) http://www.ncbi.nlm.nih.gov

3) http://www.ncbi.nlm.nih.gov

4) http://www.ncbi.nlm.nih.gov

5) http://www.ncbi.nlm.nih.gov

6) http://www.jpeds.com

7) http://www.ncbi.nlm.nih.gov

8) https://enzymevitaminhealth.com/research/lysozymes/

Learn more: http://www.naturalnews.com/046844_lysozymes_anti-microbials_enzymes.html?utm_content=buffer26c86&utm_medium=social&utm_source=facebook.com&utm_campaign=buffer#ixzz3DCrTSPwW

The Moral Decision Regarding Your Child’s Vaccines Your Doctor Won’t Tell You About.


At the topic that started it all. Childhood Vaccination. The most highly debated of topics around. Just thinking about the topic invokes some strong emotions. As I’m sure it does for every parent no matter which side of the coin you’re on.

When I began this journey of health, I didn’t actually set out on it knowingly. It just kind of…happened. It happened because of an awakening I had as a result of research. Research on this very topic.

Before my pregnancy, I had no feelings one way or the other about vaccines. Like many, I had no idea what was really involved in the process nor what was actually occurring within the body. It was only by grace that I stumbled upon some information when looking into new parent decisions, that I came across vaccination. This information led me to start my long and in depth look into vaccines.

Unfortunately, I had no idea where to look or what to start researching. A simple google search for vaccines will not get you any real information apart from mainstream media and CDC recommendations. It was only through an old time friend that I was able to start my journey into researching and knowledge. This process turned into a real rabbit trail and has brought me out much more knowledgeable about not only vaccines but other health topics as well as completely unrelated knowledge about the world we live in. I’m your typical research junkie and I’m thankful I stuck with it until I found a peace with my decision.

No matter where you fall in your decision to vaccinate, I wholeheartedly encourage you to research, research, research until you feel completely confident in your decision and have no lingering questions holding you back- and remember once it’s done, you can’t un-vaccinate.

Now, there are plenty of things I found in researching that contributed to our decision as a family. We considered everything from the reliability of the CDC’s information, the way the human body works and the way vaccines work, risk versus benefits, and much more. Those are things I may address in future posts but right now I want to address something that isn’t so commonly discussed. Morals and ethics.

 

Perhaps you’ve done your research and you’re aware of some of the methods used to culture disease for human vaccines. Maybe you’ve read about monkey kidneys and bovine serum (cow’s blood) that are used to facilitate growth, and the fact that traces of those can be left in a vaccine. Maybe you’ve read the vaccine inserts and have seen it right from the company.

While those things are disturbing, I’d like to talk about something even more disturbing. Human Diploid cells. Have you heard of it? This refers to fetal cell based vaccine productions.

In an essay by Dr. Rene Leiva M.D. entitled A Brief History of Human Diploid Strains, He discusses culturing viruses in aborted fetus cells. This process started in the 1960′s and has continued to develop since.  He states that:

“Human diploid cell strains (HDCSs) are batches of cells that are currently used for different purposes, including culturing viruses for the manufacturing of vaccines. HDCS-derived human vaccines have been licensed worldwide for polio IVP and OVP, rabies, rubella, measles, varicella-zoster, mumps, and hepatitis A. Current vaccines contain extremely small traces of the original fetal DNA, while the cell strains contain the complete fetal Chromosomal set.”

Did you catch that last part? The vaccines contain traces of human DNA. So that means, each time you get a vaccine, in addition to the virus strain and all of the adjuvents, your also getting someone else’s DNA. How wonderful! That’s not bound to mess with our systems…..

He explains that:

“Even though there are many cell strains in use in research, the most well known are WI-38 and MRC-5. These two cell strains come from two deliberately aborted fetuses.”

Tuck that information away in your back pocket because it will come in handy later when we look at some vaccine inserts. 

He continues to discuss the Wistar Institute where these cell strains originated and a previous paper from the 60′s in which  Dr. Leonard Hayflick first published a paper describing twenty-five different fetal samples derived from the lung, skin, muscle,kidney, heart, thyroid, thymus and liver of nineteen separate, electively-aborted fetuses.

This was also when abortion was illegal in the U.S. so they had to get their fetal tissue from Stockholm, Sweden. Fortunately for them, Roe Vs. Wade coincidentally occurred shortly thereafter.

Under the origin of Rubella section, it states that:

“(the) virus strain was obtained from a female human fetus in a series of twenty-seven abortions in the United States…“This fetus was from a twenty-five-year-old mother exposed to rubella eight weeks after her last menstrual period….The fetus was surgically aborted seventeen days after maternal illness and dissected immediately… It was then grown on WI-38.”

This is where the Rubella vaccine virus originated. Meaning that if your vaccine is for Rubella and from the strain WI-38….that’s where it originated.

But wait! That’s not the same thing that’s in MY vaccine…is it? That was in the 60′s…..

Unfortunately, that is where the strain originated and that strain is still being used in vaccines today. Remember those vaccine inserts? Did you read yours before or during your vaccination? Let’s check out the Merk VARIVAX [Varicella Virus Vaccine Live] insert. You can find it here.

Right under the description section, it says this:

“The virus was initially obtained from a child with wild-type varicella, then introduced into
human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures and
finally propagated in human diploid cell cultures (WI-38). Further passage of the virus for varicella vaccine
was performed at Merck Research Laboratories (MRL) in human diploid cell cultures (MRC-5) that were
free of adventitious agents. This live, attenuated varicella vaccine is a lyophilized preparation containing
sucrose, phosphate, glutamate, and processed gelatin as stabilizers.”

Recognize those numbers? WI-38 and MRC-5 are those exact strains we looked at earlier and the insert clearly states they are human diploid cells.

What about that DNA? That can’t be in the vaccine, right? The insert goes on to say:

“The product also contains residual 7 components of MRC-5 cells including DNA and protein and trace quantities of sodium phosphate monobasic, EDTA, neomycin and fetal bovine serum (fetal cow’s blood).”

Well, there you have it….from MERK themselves…..

Just in case you’re not convinced, let’s look at another insert- MMR. You can find the insert here. Right at the beginning is the description where it discusses 3 different sources. Check out number 3:

(3) MERUVAX® II (Rubella Virus Vaccine Live), the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts.”

I don’t know about you, but I don’t feel comfortable putting someone else’s DNA and proteins into my body or my children’s! Our bodies weren’t made for that. It’s unnatural and it can only cause unwanted side affects. Not to mention that it is an unethical means of vaccine productions.

This is only the beginning of the story when it comes to vaccines. I hope you take the time to research this topic fully before coming to a decision for yourself and your family. Whatever decision you come to, make sure you and your family feel fully comfortable with it, confident, and educated. It’s not a decision to make lightly.

 

Sources: 

The information in this post was originally found in a documentary entitled Lethal Injection: The Story of Vaccination by Clint Richardson. I highly recommend looking it up on YouTube and watching the whole documentary. It’s a hard hitter and not for the closed minded. Happy researching!

http://www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_pi.pdf

http://www.merck.com/product/usa/pi_circulars/v/varivax/varivax_pi.pdf

http://www.wellnesscenter.net/resources/articles/History_of_Cell_Lines_NCBC_credit_line-1.pdf

 

Large geomagnetic solar storm hits Earth.


Earlier this week, the sun spat out two long, powerful streams of magnetically charged particles.

The first wave hit the Earth the night of Sept. 11 and caused a moderate “G2” geomagnetic storm, yielding beautiful aurora light shows in Canada, the northern U.S. and Europe. The second, larger stream began hitting the Earth “just before noon EDT” today, according to C. Alex Young, Associate Director for Science in NASA’s Heliophysics Division.

Last night’s light show is nothing compared to the light show scientists are predicting for Friday and Saturday. The space weather forecasting service run by NOAA and the U.S. Air Force predicts that: “The geomagnetic field is expected to be at unsettled to major storm levels on day one (12 Sep), active to severe storm levels on day two (13 Sep) and unsettled to minor storm levels on day three (14 Sep).”

auroramap140912.png
Aurora map for Sept. 12, 2014

 

Both moderate G2 and major G3 storms cause auroras, though a more severe electromagnetic disturbance makes the lights brighter and spread over more of the Earth’s surface. In an email today, Young noted: “the storm level is predicted to increase to G3 level into tomorrow. If the storm reaches G3, aurora could be seen down to areas like Illinois and mid-Atlantic states. G2 is more like Idaho and New York State.”

To see an aurora, find a dark, cloudless area within the “aurora oval” and get away from light pollution. You may see a sky flashing green, blue-violet, or perhaps a rarer red hue. Young told CBS News in a phone call that the light show could last as little as 45 minutes or could go on for hours.

jn-hall-37511410513980-660x439.jpg
Aurora taken by JN Hall on September 12, 2014 in Fairbanks, AK, US.
SPACEWEATHER.COM

 

The Earth’s magnetic storms began on Monday in an active sunspot called AR2158. That spot spat out a moderate solar flare, followed by a more extreme one Wednesday.

In a press conference, Thomas Berger, director of NOAA’s Space Weather Prediction Center, said that “sunspot AR2158 is about the size of between 10 and 20 Earths, but appears to be in the process of breaking up.” The huge solar flare may have been “its swan song as it breaks down.”

The particles are not harmful to people on the ground. If the geomagnetic storm is severe, airplanes are rerouted to avoid magnetic disturbances in the polar regions. Electrical and satellite communications systems could be effected, though operators around the world take special precautions to minimize any damage. NOAA expects no major disruptions, though they are monitoring the situation.

This Electronic Glove Can Make Your Heart Beat Forever


Heart Sleeve

Scientists have created an amazing electronic membrane that could replace pacemakers! It fits over your heart and can keep it beating regularly over an indefinite period of time.

This new cardiac device is a thin, stretchable membrane which has a spider-web like network of sensors and electrodes imprinted within that is custom designed to fit over the heart and contract and expand with it as it beats. Researchers from the University of Illinois at Urbana-Champaign and Washington University in St. Louis used computer modelling technology and a 3D-printer to create a prototype membrane and fit it to a rabbit’s heart, keeping the organ operating perfectly “outside of the body in a nutrient and oxygen-rich solution”. By using high-resolution imaging technology the thin, elastic membrane will be custom made to fit “snugly” over the real heart. “When it senses such a catastrophic event as a heart attack or arrhythmia, it can also apply a high definition therapy,” said Igor Efimov of Washington Universitysaid biomedical engineer, who helped design and test the device.“It can apply stimuli, electrical stimuli, from different locations on the device in an optimal fashion to stop this arrhythmia and prevent sudden cardiac death,”Efimov told local radio station KWMU-1.

You may have heard of similar products and “cardiac socks” have been around since the 1980s but they are very basic and made of crude, fabric sleeves with electrodes sewn into place. Making it almost impossible to keep the senors in full contact with the heart. John Rogers, a materials scientists from the University of Illinois has created this new device with the use of stretchable electronics. Although Rogers’ electronics use the same rigid materials found in normal electronics (eg silicon), the circuits are laid out in curved, s-shaped design that allows them to stretch and bend without breaking. Rogers has actually compared the silicon sleeve to the pericardium which is the heart’s own membrane, he told KWMU-1 that“this artificial pericardium is instrumented with high quality, man-made devices that can sense and interact with the heart in different ways that are relevant to clinical cardiology.”

Although you won’t be getting fitted for your own life-prolonging heart sack just yet. This revolutionary technology is available for research. For now, the device will be used as a research tool allowing scientists to study how heart rate changes in response to different conditions. But, one day it could be developed for use in humans who need cardiac monitoring and help prevent sudden heart attacks and save millions of lives!

 

Source: nature.com

Down’s Syndrome babies should be killed, urges top scientist


Top scientist Richard Dawkins isn’t interested in protecting life on Earth. He’s only interested in protecting a planet full of people that he approves of. To him, Down syndrome babies have no importance in the world and should be terminated before they take their first breath. With the right prenatal testing, Dawkins believes that Down syndrome can be detected early, and the baby can be discarded as medical waste so they won’t waste any space on planet Earth. In a way, Dawkins is like Adolf Hitler, preparing his preferred race with the perfect qualities. He has no patience to care and love people who are slower than him. His brilliance is the model to live by, and babies with Down syndrome are apparently not fit for the world that he wants.

life

Richard Dawkins recently stated publicly on Twitter that it’s the moral thing to abort babies with Down syndrome before they have a chance to be born. The Twitter conversation began with Dawkins displaying a picture of pro-life supporters in Ireland — a country that does not endorse abortion or subsidize it. Dawkins criticized Ireland for its pro-life stance, writing, “Ireland is a civilised country except in this 1 area.”

One woman questioned Dawkins’ tweet, asking, “994 human beings with Down’s Syndrome deliberately killed before birth in England and Wales in 2012. Is that civilised?”

Dawkins replied, endorsing mass pre-meditated death of children with Down syndrome, “Yes, it is very civilised. These are fetuses, diagnosed before they have human feelings.”

Another commenter chimed in, confused, “I honestly don’t know what I would do if I were pregnant with a kid with Down Syndrome. Real ethical dilemma.”

Dawkins reassured the man that it was the moral thing to take out children with Down syndrome before they are born. “Abort it and try again,” he wrote. “It would be immoral to bring it into the world if you have the choice.”

This brings up the following questions: What if Richard Dawkins was born with a chromosomal disorder? Is it then moral to terminate his life? Where does Dawkins draw the line when pre-engineering a perfect human race? Should all children with deformities or cognitive impairments be discarded?

Taking the gift of life for granted

The most passionate pro-life army would probably be the 54.5 million people and counting who were ripped out of the womb over the past 40 years in the US. What if Dawkins had been one of them? He could have seized to exist. These people, discarded as medical waste, never had a say in the matter of their own life and were never allowed to take their first breath outside their mothers’ wombs. They were never given a chance. If they were allowed to speak today, every one of them would say it’s the adult’s moral responsibility to protect life conceived in the womb.

These people, who were denied their entire life’s liberty and every single possible choice, represented a new beginning, a clean slate. They never posed a threat to society and could have changed the world in a positive way, yet they were discarded as fetuses without feelings.

Court rulings like the 1973 Roe vs. Wade decision never restored women’s privacy and freedom of choice. The ruling only encouraged and subsidized the deaths of millions of future women and men who could have helped build a more compassionate society.

When abortion became federally endorsed, the medical procedure was no longer a last-ditch option; it became encouraged, and death has multiplied since then. The ruling never really protected freedom of choice; it only encouraged the death of millions who will never get a single choice.

By not respecting life and protecting it at all costs, society begins to endorse relative morality. When people are encouraged to harm others and take life, lawlessness abounds, even while it is endorsed by the law itself.

When life is respected first, then liberty can abound. The so-called liberty that the court “granted” is only an illusion of choice.

At the same time, being for life doesn’t mean that one should condemn women who’ve undergone abortions in the past. Women and men are both greatly impacted emotionally and spiritually after going through with an abortion. The last thing that they need is some zealot waving a sign in their face and telling them they should go to jail or hell.

All men and women have an inherent choice to either protect life or discard it. It’s just sad to see a leading scientist like Richard Dawkins regard human life so flippantly. Instead of subsidizing abortion and encouraging the genocide of people with chromosomal disorders, we should be empowering men and women with hope, education and resources to raise their families. The world would become a better place if a conscious shift occurred — a heart change that values life and compassion for all human beings, no matter the cost.

Sources for this article include:

http://www.independent.co.uk

http://www.lifenews.com

http://science.naturalnews.com

 

An International Team of Researchers Led by MSK Creates a New Tool That Mimics the Structure of Tumor Tissue.


An international team of researchers led by Memorial Sloan Kettering has created a new tool that can be employed in the search for personalized cancer therapies in prostate cancer: tiny formations called organoids. The study of organoids — three-dimensional structures about a millimeter in size composed of cells grouped together and spatially arranged like an organ or tissue — is a rapidly growing field in biology.

Traditionally, cell lines have been one of the main resources for evaluating potential new cancer drugs in the lab. Cell lines are populations of cells derived from a patient — such as a cancer cell — that can be grown indefinitely in culture.

“Identifying the molecular biomarkers that indicate whether a drug will work or why a drug stops working is paramount for the precision treatment of cancer,” says Yu Chen, the study’s senior author and a physician-scientist in MSK’s Genitourinary Oncology Service and ourHuman Oncology and Pathogenesis Program (HOPP). “By developing these organoids from patient prostate cancer samples, we are able to study the tumors in greater detail and correlate the genetic mutations with the response to various drugs.”

Organoids are also expected to provide much more information than cell lines. Because organoids mimic the structure of tumor tissue, they will enable the study of how the cancer cells interact with each other and the effect of hormones on tumor growth, for example, in addition to providing genetic markers for targeted drug therapies.

A Need for Better Prostate Cancer Models

Despite prostate being the most common type of cancer in men after skin cancer, until now there have been only a handful of prostate cancer cell lines available for testing of new drugs. “Many of the mutations that cause prostate cancer occur in a small percentage of patients and are not represented at all in the cell lines currently available,” Dr. Chen explains. “And with so few lines, we haven’t had the statistical power to properly evaluate targeted therapies that may act against these mutations.”

In the new study, published in Cell, the researchers reported successfully growing organoids from the tumors of seven patients with metastatic prostate cancer. Each three-dimensional organoid is molecularly identical to the patient’s cancer from which it originated. With the addition of the seven organoid lines described in this paper, Dr. Chen’s team has effectively doubled the resources available for doing this kind of testing of new prostate cancer drugs.

A New Era of Personalized Medicine

The organoids are proving useful in learning more about the effectiveness of current and experimental prostate cancer therapies. The prostate cancer organoids can be used to test multiple drugs simultaneously, through a technique called high-throughput screening.

Eventually, the researchers say, they may be able to develop organoids that are derived from each patient’s tumor, allowing drugs to be tested on the organoid before being given to the patient to truly personalize and optimize each person’s treatment. Dr. Chen’s team is already retrospectively comparing the drugs given to each patient against the organoids for clues about why the patient did or didn’t respond to therapy.

An Exploding Field

The use of organoids in studying cancer is relatively new, but the field is exploding quickly, according to Dr. Chen. In 2009, Hans Clevers, a researcher at the Hubrecht Institute in the Netherlands, first demonstrated that intestinal stem cells could form organoids. Dr. Clevers is a co-author on the Cell study, along with HOPP Chair Charles Sawyers, Genitourinary Oncology Service Chief Howard Scher, and many other members of MSK’s prostate cancer team.

Organoids derived from patient tumor samples, sometimes also called tumoroids, are being studied at Memorial Sloan Kettering and elsewhere for many other tumor types, includingkidney, pancreas, and thyroid.

Targeted drugs get first test in early stage lung cancer


The National Cancer Institute (NCI) has launched an ambitious new nationwide clinical trial to find out if two molecularly targeted drugs that have improved outcomes in advanced lung cancer can increase survival of patients with early-stage lung cancer that has been surgically removed.

Dana-Farber Cancer Institute researchers Pasi Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology at Dana-Farber, andGeoffrey Oxnard, MD, are leading the screening phase of the trial, in which some 6,000 to 8,000 patients will have their tumors tested for uncommon genetic alterations that are associated with improved response to targeted cancer drugs. Those who have the alterations will randomly receive either a targeted drug or a placebo, and all patients will be followed for five years to determine if the drug treatment prolongs survival.

One of the genetic alterations, in the EGFR gene, is found in about 10 percent of patients with adenocarcinoma of the lung, and 5 percent have an alteration in the ALK gene.

The opening of the clinical trial, called ALCHEMIST, was announced Monday by the NCI and by two NCI organizations that coordinate clinical trials. One is the Alliance for Clinical Trials in Oncology, and the other is the ECGG-ACRIN Cancer Research Group. ALCHEMIST is an acronym for the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials.

Patients will be recruited at multiple centers across the country over the next five or six years. To be eligible, patients must already have had surgery to completely remove their lung tumors, and must have completed any adjuvant (follow-up) treatment such as chemotherapy and radiation. Samples of the removed tumor will be analyzed for the presence of EGFR and ALK mutations.

Patients found to have EGFR mutations in their tumors will be referred to a trial of the drug erlotinib (commercial name Tarceva®), while those with ALK mutations will enter a separate trial of treatment with crizotinib (Xalkori®). In each trial, patients will be randomized to the drug or a placebo. Trial leaders expect about 800 patients to receive a drug or placebo in the two treatment trials. All patients will be followed for five years, including the large number of patients who will be found to lack either mutation.

Although the Food and Drug Administration has approved erlotinib and crizotinib for treatment of advanced lung cancer, it’s not known whether the drugs will be effective in patients who have undergone complete removal of lung tumors with one of the mutations.

More than half of patients experience recurrences of lung cancer, even if it was completely removed, because tiny clumps of cancer cells invisible to the surgeon metastasize through the blood vessels to cause new cancers.

“We are excited to participate in this ambitious undertaking,” said Oxnard. “Through this large-scale collaborative effort to genotype thousands of early-stage lung cancer patients, ALCHEMIST allows us to test better adjuvant treatments while simultaneously teaching us important lessons about the genetic complexity of lung cancer.”

The trial will investigate, in addition to the potential survival benefit of the targeted drugs, each patient’s lung cancer risk characteristics, and will analyze tumor specimens when patients relapse to determine how their tumors become resistant to treatment.

New Immunotherapy Drug for Melanoma Wins Approval


The Food and Drug Administration has approved a new type of  immunotherapy drug that will provide a much-needed option for patients with advanced or inoperable melanoma who no longer respond to other drugs – including the immunotherapy agent ipilimumab (Yervoy).

The drug, pembrolizumab or MK-3745, will be marketed under the name  Keytruda. Based on impressive performance in clinical trials, the FDA had designated pembrolizumab a “breakthrough therapy” and placed it on a fast-tracked approval process.

“This drug is exciting because of its really striking response rate and good indications that these responses are durable” for a least a year, says Patrick Ott, MD, PhD, clinical director of the Center for Immuno-Oncology at Dana-Farber.  “And it is very well tolerated, with very manageable side effects,” he adds. The drug has been available, alone and in combination with other drugs, in clinical trials conducted at the center.

Both Keytruda and Yervoy unleash the search-and-destroy power of the body’s immune system against cancer cells. These drugs, as well as others in clinical trials, are arriving on the crest of a new wave of immunotherapy research, in which Dana-Farber scientists have played a prominent role.

Advanced melanoma is responsible for about 9,700 deaths a year in the United States, but the outlook for these patients is growing brighter with the remarkable outcomes brought about by immunotherapy.

The approval of Keytruda marks a first in the United States for a new class of immunotherapy drugs that block the PD-1 protein, which is commandeered by melanoma and other cancer cells to avoid detection and attack by the body’s immune system.

PD-1, along with a pair of partner molecules, PD-L1 (which was discovered by Dana-Farber’s Gordon Freeman, PhD and colleagues) and PD-L2, work together to protect normal cells from being mistakenly harmed by immune soldier cells that defend the body against foreign microbial invaders. Many cancers exploit the PD-1 pathway to hide from the immune response, and drugs like Keytruda inhibit PD-1, stripping the cancer cells of their shield against immune attack.

Keytruda is intended to be used following treatment with ipilimumab, which does not block PD-1 but instead targets another immune-suppressing protein, CTLA-4.

Stephen Hodi, MD, director of the Center for Melanoma Oncology and of the Center for Immuno-Oncology, called the new availability of pembrolizumab  “an important step forward that meets an unmet need” – that is, patients that don’t respond to ipilimumab or other treatments for advanced melanoma.

In an unusually large phase 1 trial of patients whose melanoma had spread throughout the body, Keytruda shrank tumors in about 30 percent of patients – including patients who had failed to respond to ipilimumab. After one year, 69 percent of patients were alive – a sharp improvement over the current outlook for such patients.

Higher thyroxine dose needed in patients with hypothyroidism and lactose intolerance


Lactose intolerance may increase the likelihood that patients with hypothyroidism will need oral thyroxine, according to research published in The Journal of Clinical Endocrinology & Metabolism.

In a cohort study at the University of Roma, Latina, Italy, Miriam Cellini, a student in endocrine immunopathology, Marco Centanni, MD, and colleagues, looked at 34 patients with hypothyroidism due to Hashimoto’s thyroiditis (HT) and lactose intolerance (LI).

“The dose of thyroxine required to reach target thyroid-stimulating hormone(TSH) was higher in hypothyroid patients with HT and LI than in patients with isolated HT,” the researchers wrote.

The patients, all non-compliant with their lactose-free diet, were treated in an outpatient endocrinology unit at the institution’s hospital. The researchers evaluated the replacement dose of oral thyroxine between 2009 and 2012 to gauge which was appropriate for individuals.

In all patients, target TSH (median=1.02 mU/l) was reached with a median dose of 1.31 mcg/kg per day. Only five of 34 patients with lactose intolerance reached the desired TSH (median=0.83 mU/l) with a similar dose of 1.29 mcg/kg per day.

With progressive thyroxine dose increases, the remaining 29 patients reached the target TSH (median=1.21 mU/l) with a median of 1.81 mcg/kg per day (+38%, P<.0001). Of these, six were diagnosed with other gastrointestinal disorders and had a higher median dose requirement of 2.04 mcg/kg per day (+55%; P=.0032).

The 23 patients with isolated LI required a median dose of 1.72 mcg/kg per day (+31% P<.0001) to attain pharmacologic thyroid homeostasis.

The pathogenic mechanism leading to the need for increased thyroxine dose in patients with LI remains unclear, the researchers wrote.

Pregnant women with subclinical hypothyroidism more likely to miscarry


Among pregnant women at low risk for thyroid dysfunction, the existence of subclinical hypothyroidism, thyroid autoimmunity or both prior to 8 weeks’ gestation increases the likelihood of miscarriage, according to recent findings.

In the prospective cohort study, researchers evaluated 3,315 women seen at the gynecology/obstetrics clinics of 13 hospitals and six prenatal clinics in three Chinese cities. The women were enrolled in the study between January and September of 2012 at the clinics, all of which were located in areas of China deemed iodine sufficient. Women identified for analysis were between 4 and 8 weeks’ gestation, and had lived in the area for more than 5 years.

Study participants completed questionnaires pertaining to demographic and obstetric history (maternal age, gestational age, previous pregnancies/births, and previous miscarriage). The questionnaires also elicited information about education level, income, smoking status, alcohol consumption, family history of thyroid disorders, history of type 1 diabetes, autoimmune diseases and treatments involving head or neck irradiation.

At baseline, all women were imaged by ultrasound to confirm ongoing pregnancy. The study’s primary outcome was miscarriage, which was characterized as sudden pregnancy loss before 20 weeks’ gestation. Participants underwent monthly thyroid function tests and ultrasound imaging at the clinics. The thyroid tests measured thyroid stimulating hormone, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody and urinary iodine.

On the basis of the thyroid test results, women were classified into four groups: euthyroidism (ET), isolated subclinical hypothyroidism (SCH), isolated thyroid autoimmunity (TAI) and subclinical hypothyroidism with TAI (SCH and TAI). Patients in the SCH cohort were further divided into two subgroups SCH1 and SCH2, based on TSH levels; as a result, the SCH and TAI group was also further stratified into two groups (SCH+TAI1 and SCH+TAI2).

The researchers found that compared with ET women (2.2%), those with SCH had a significantly higher risk of miscarriage (7.1%; adjusted OR=3.40; 95% CI: 1.62-7.15). Additionally, women with TAI alone were also at significantly increased risk of miscarriage (5.7%) vs. ET patients (2.2%; adjusted OR=2.71; 95% CI, 1.43-5.12), as were women in the TAI+SCH1 groups (10%; adjusted OR=4.96; 95% CI: 2.76-8.90) and the TAI+SCH2 groups (15.2%; adjusted OR=95% CI, 3.76-24.28).

Among 110 women who miscarried, the gestational ages were lower among those with subclinical thyroid disorders (11.3 weeks) vs. ET women (9.33 weeks; P =.024). The subgroup analysis also determined that higher TSH levels were associated with lower gestational age at miscarriage, in women with or without TAI.

The researchers said these findings may support the need to monitor thyroid function in pregnant women.

“To some extent, these finding support universal screening of women of reproductive age for thyroid function and thyroid autoimmunity early during pregnancy or during the preconception period,” the researchers wrote.