Monthly Archives: December 2018

The US surgeon general just issued a rare advisory about e-cigs like the Juul — here’s why vaping is so dangerous

In a rare national advisory, the top US public health official warned Americans of the dangers of e-cigarettes like the Juul, a popular device that lets users inhale nicotine vapor without burning tobacco.

US Surgeon General Jerome Adams said in the advisory on Tuesday that e-cigs like the Juul are a particular danger to kids and teens and called for fresh measures to halt their rising popularity.

“We need to protect our kids from all tobacco products, including all shapes and sizes of e-cigarettes,” Adams said in a statement, adding, “We must take action now to protect the health of our nation’s young people.”

The advisory singles out Juul multiple times, saying the sleek devices are popular among teens because they’re easy to conceal and don’t emit much odor. It tells parents, health professionals, and teachers to be on the lookout for all forms of nicotine-delivery devices, including e-cigs.

Adams’ announcement comes on the heels of warnings from several other federal agencies about a rise in e-cig use, including from the Centers for Disease Control and Prevention and the Food and Drug Administration.

In November, after new CDC data pointed to a 78% increase in e-cig use among high-school students, FDA Commissioner Scott Gottliebannounced moves to further restrict sales of e-cigarettes to prevent them from getting into the hands of young people. That included a crackdown on flavored offerings, which researchers say appeal strongly to young people.

Several days before the FDA’s announcement, Juul Labs, the Silicon Valley startup behind the most popular e-cig in the US, temporarily halted sales of its flavored varieties in stores until they agreed to adopt the company’s new age restrictions and a stronger system for making sure customers are at least 21 years old.

‘E-cigarettes and youth don’t mix’

Though smoking conventional cigarettes is uniquely deadly, and vaping appears to be somewhat healthier (especially for adults looking to switch), public health experts are concerned about how e-cigarettes affect young people.

Because of their runaway popularity, e-cigs could create a new generation of Americans hooked on nicotine, one of the world’s most addictive substances and the key ingredient in e-cigs like the Juul, these experts warn. Their concern comes in part from a host of studies suggesting that teens who vape are significantly more likely to go on to smoke regular cigarettes than teens who never vape.

This finding could be related to the way nicotine affects the developing brains of young people. Though the research on e-cigs is still limited because the devices are so new, researchers have a wealth of data on the negative effects of nicotine on teens who start smoking early.

In brain-imaging studies of adolescents who started smoking in their teens, researchers have found signs of reduced activity in the prefrontal cortex, the part of the brain tied to planning and decision-making. The same teens performed worse on memory and attention tasks than teens who didn’t smoke.

Nicholas Chadi, a clinical pediatrics fellow at Boston Children’s Hospital, spoke about the Juul at the American Society of Addiction Medicine’s annual conference this spring. He described some anecdotal effects of nicotine vaping that he’d seen among teens in and around his hospital.

“After only a few months of using nicotine,” the teens “describe cravings, sometimes intense ones,” Chadi said, adding that “after only a few hundred cigarettes — or whatever the equivalent amount of vaping pods — some start showing irritability or shakiness when they stop.”

Most e-cigs contain toxic metals, and using them may increase the risk of a heart attack

Beyond the effects of e-cigs on the developing brain, a host of health issues related to e-cigs is beginning to emerge.

This spring, scientists looked at the compounds in several popular brands of e-cigs aside from the Juul and found some of the same toxic metals that are in conventional cigarettes, such as lead.

A study published this month found that people who vape tended to have high concentrations of some of these toxic chemicals in their bodies.

In another study published this summer, scientists concluded that there was substantial evidence tying daily e-cig use to an increased risk of a heart attack. And this fall, a small study with rats suggested that vaping could have a negative effect on wound healing that’s similar to the effect of regular cigarettes.

But many teens may not be aware of these health risks. Researchers say that could be because so little research has focused on the Juul, which has captured a nearly 80% market share in the US.

So for a study published in October, researchers from Stanford University’s School of Medicine surveyed young people who vaped and asked them whether they used the Juul or another e-cigarette.

From their sample of 445 high-school students, the researchers observed that teens who used the Juul tended to say they vaped more frequently compared with those who used other devices. Juul users also appeared to be less aware of how addictive the devices could be, compared with teens who used other e-cigs.

“I was surprised and concerned that so many youths were using Juul more frequently than other products,” Bonnie Halpern-Felsher, a professor of pediatrics who was a lead author of the study, said in a statement.

“We need to help them understand the risks of addiction,” she added. “This is not a combustible cigarette, but it still contains an enormous amount of nicotine — at least as much as a pack of cigarettes.”

December, 2018|Oral Cancer News|

HPV discovery raises hope for new cervical cancer treatments

Source: www.eurekalert.org
Author: press release – University of Virginia Health Syste

Researchers at the University of Virginia School of Medicine have made a discovery about human papillomavirus (HPV) that could lead to new treatments for cervical cancer and other cancers caused by the virus.

HPV is responsible for nearly all cases of cervical cancer and 95 percent of anal cancers. It is the most common sexually transmitted disease, infecting more than 79 million Americans. Most have no idea that are infected or that they could be spreading it.

“Human papillomavirus causes a lot of cancers. Literally thousands upon thousands of people get cervical cancer and die from it all over the world. Cancers of the mouth and anal cancers are also caused by human papillomaviruses,” said UVA researcher Anindya Dutta, PhD, of the UVA Cancer Center. “Now there’s a vaccine for HPV, so we’re hopeful the incidences will decrease. But that vaccine is not available all around the world, and because of religious sensitivity, not everybody is taking it. The vaccine is expensive, so I think the human papillomavirus cancers are here to stay. They’re not going to disappear. So we need new therapies.”

HPV and Cancer
HPV has been a stubborn foe for scientists, even though researchers have a solid grasp of how it causes cancer: by producing proteins that shut down healthy cells’ natural ability to prevent tumors. Blocking one of those proteins, called oncoprotein E6, seemed like an obvious solution, but decades of attempts to do so have proved unsuccessful.

Dutta and his colleagues, however, have found a new way forward. They have determined that the virus takes the help of a protein present in our cells, an enzyme called USP46, which becomes essential for HPV-induced tumor formation and growth. And USP46 enzyme promises to be very susceptible to drugs. Dutta calls it “eminently druggable.”

“It’s an enzyme, and because it’s an enzyme, it has a small pocket essential for its activity, and because drug companies are very good at producing small chemicals that will jam that pocket and make enzymes like USP46 inactive,” said Dutta, chairman of UVA’s Department of Biochemistry and Molecular Genetics. “So we are very excited by this possibility that by inactivating USP46 we’ll have a way to treat HPV-caused cancers.”

Curiously, HPV uses USP46 for an activity that is opposite to what the oncoprotein E6 was known to do. E6 has been known for more than two decades to recruit another cellular enzyme to degrade the cell’s tumor suppressor, while Dutta’s new finding shows that E6 uses USP46 to stabilize other cellular proteins and prevent them from being degraded. Both activities of E6 are critical to the growth of cancer.

The researchers note that enzyme USP46 is specific to HPV strains that cause cancer. It is not used by other strains of HPV that do not cause cancer, they report.

Notes:
(1) The researchers have published their findings in the scientific journal Molecular Cell. The team included Shashi Kiran, Ashraf Dar, Samarendra K. Singh, Kyung Yong Lee and Dutta. All are from UVA’s Department of Biochemistry and Molecular Genetics.

(2)The work was supported by the National Institutes of Health, grant R01 GM084465.

December, 2018|Oral Cancer News|

Tobacco 21 — its time has come

Source: vtdigger.org
Author: Nevin Zablotsky, DMD

As we approach the holiday season I am reminded of the gifts of love we share with our families, as well as the New Year’s resolutions we make and try to keep after Jan. 1 history.

I am a periodontist having practiced in Burlington and South Burlington for the past 40 years. In that time I have treated patients that have been severely compromised by tobacco. Some have lost teeth from advanced periodontal disease and some have lost parts of their tongue and jaw due to oral cancer, leaving them significantly compromised functionally as well as well as emotionally. I have had to advise teenagers and their families that their tobacco chewing habit had caused significant enough changes in their mouth to warrant a biopsy of the involved area. This caused great stress to them as they waited a week to find out the results. Some may think that it takes many years for tobacco use to compromise one’s health, but teenagers can die a horrible death from tobacco use if they are one of the unlucky ones who is genetically predisposed to oral cancer.

Over the years, I have traveled throughout Vermont teaching about tobacco and nicotine addiction to elementary, junior and senior high school students. I feel that I have a good sense of what kids are thinking about these subjects. The elementary school students seem to understand that cigarettes are bad for them. When one talks to the middle school kids, there are some that are beginning to think that cigarettes and smokeless tobacco use is cool, and when speaking to high school students, there is a larger percentage of them that have begun to use a variety of these products, ranging from cigarettes and cigars, to hookahs, to a variety of e-cigarettes, with the newest product, Juul, going viral. This product has become so much of a problem local schools have sent letters to parents warning them of its sudden increase in usage .

It is legal for anyone over 18 to purchase all of these tobacco and nicotine products. Here are some facts to chew on.

About 95 percent of adult smokers begin smoking before they turn 21. Two-thirds of 10th grade students and nearly half of eighth grade students say it is easy to get cigarettes. More 18- and 19-year-olds using in high school means younger kids have daily contact with students who can legally purchase tobacco products.

I am often told that when one reaches the age of 18 they are mature enough to vote, or join the military, so therefore they are mature enough to decide on using tobacco products.

Tobacco use costs the military about $1.6 billion annually in lost productivity and health care expenses tied to respiratory problems, cardiovascular disease and slower healing, according to the Department of Defense data. That’s expected to climb to $19 billion during the next 10 years and result in 175,000 premature deaths. The Air Force bans tobacco in recreation facilities, and the Navy banned tobacco on all submarines. The Vermont National Guard also stated that they would abide by Tobacco 21 legislation if it passed, again citing readiness and fitness.

An argument has been made that tobacco retailers’ businesses will be irreparably harmed if tobacco 21 is implemented. Studies show that its impact over the first 5-8 years will be between one quarter and one half of a percent.

Vermont law does not allow the sale of alcohol to anyone under 21, and the new marijuana law passed last year also restricts its usage to those over 21. Given the proven health risks of tobacco use, why does the present law allow tobacco usage at age 18?

It has been calculated that 10,000 kids now under 18 and alive in Vermont will ultimately die prematurely from the smoking habit they began in their teenage years.

Six states have passed tobacco 21 legislation. This includes Massachusetts and Maine, with New York likely to join this group. Do we really want kids coming from our surrounding states coming here to get their cigarettes or e-cigarettes?

Even Altria and R.J. Reynolds, two of the largest tobacco companies in the world have stated that the age of sale should be 21.

So as we approach the new year I want to appeal to our representatives, to resolve to pass tobacco 21 in the 2019 legislative session, and remind them about how much suffering they can prevent. The decisions they make will have major consequences for generations to come. What a great resolution to keep. What a great holiday gift for us all.

Note: This commentary is by Nevin Zablotsky, DMD, a retired periodontist who practiced in South Burlington and the Coalition for a Tobacco Free Vermont.

December, 2018|Oral Cancer News|

Oral cancer prognostic signature identified

Source: www.eurekalert.org
Author: press release

Researchers in Brazil have identified a correlation between oral cancer progression and the abundance of certain proteins present in tumor tissue and saliva. The discovery offers a parameter for predicting progression of the disease – whether cervical lymph node metastasis is present, for example – and points to a strategy for overcoming the limitations of clinical and imaging exams. It could also help guide the choice of an ideal treatment for each patient.

The study began in the discovery phase with a proteomic analysis of tissue from different tumor areas using 120 microdissected samples. In the verification phase, prognostic signatures were confirmed in approximately 800 tissue samples by immunohistochemistry and in 120 samples by targeted proteomics.

The study was supported by São Paulo Research Foundation – FAPESP and conducted at the National Energy and Materials Research Center (CNPEM) in partnership with the São Paulo State Cancer Institute (ICESP), the University of Campinas’s Piracicaba Dental School (FOP-UNICAMP), the Institute of Computing from the same university, the University of São Paulo’s Mathematics and Computer Science Institute (ICMC) in São Carlos, and the Dental School of the West Paraná University (UNIOESTE), in addition to other institutions in Brazil and abroad.

“The data led to robust results that are highly promising as guides to defining the severity of the disease. We suggested potential markers of the disease in the first phase of the study and verified these markers in the second phase, enhancing the reliability of the findings and showing that these markers are effective in classifying patients with cervical lymph node metastasis,” said Adriana Franco Paes Leme, a researcher at CNPEM’s National Bioscience Laboratory (LNBio) and the corresponding author of the article published in Nature Communications.

Mouth cancer, also known as oral squamous cell carcinoma (OSCC), is the most common type of malignant head and neck tumor. Prevalence and mortality are high, with some 300,000 new cases diagnosed per year worldwide and 145,000 deaths. Although it is relatively easy to detect, typically when a dentist notices an oral lesion, the disease is usually diagnosed when it is already at an advanced stage.

“We worked on the study for five years until we achieved this breakthrough,” Paes Leme told. “It was divided into two phases. In the first, we used discovery proteomics to identify and quantify tumor tissue proteins. The second phase of the study consisted of analyses using immunohistochemistry and targeted proteomics, for when you know precisely which proteins you want to quantify.”

Proteomics focuses on the identification, localization and functional analysis of the proteins in a sample, which may consist of tissue or cells, for example. The proteins are quantified, post-translational modifications are detected, and their activity and interactions are assessed.

Bioinformatics and machine learning
The study funded by FAPESP had two phases. In the first phase, the researchers used laser microdissection and proteomics to map the proteins in mouth cancer tissue and correlate them with the clinical characteristics of patients. This analysis permitted the identification of several proteins, such as CSTB, NDRG1, LTA4H, PGK1, COL6A1, ITGAV, and MB, with differing levels of abundance depending on tumor area and links to key clinical outcomes.

In the second phase, after identifying and quantifying proteins in the 120-odd tumor tissue samples, the researchers deployed two protein verification strategies.

“One strategy consisted of gauging the abundance of the selected proteins in independent tissue samples using immunohistochemistry with antibodies. The other consisted of monitoring the same preselected targets in patients’ saliva,” Paes Leme said.

Saliva was chosen because this cancer is located in the mouth, where proteins could be secreted by neoplastic cells. “Saliva is a promising source of markers, as well as being a fluid obtained by noninvasive collection,” she explained. “We verified the proteins in saliva from 40 patients. Technical triplicates were analyzed to achieve the highest possible confidence level for the results in this phase of the study.”

After analyzing the saliva samples, the researchers used bioinformatics and machine learning techniques to arrive at prognostic signatures, verifying which of the proteins or peptides selected in the first phase could distinguish between patients with and without cervical lymph node metastasis.

“In addition, we had valuable information about the clinical evolution of the patients who took part in the study as volunteers by donating samples of their saliva,” Paes Leme said.

From this result, it was possible to identify three specific peptides – LTA4H, COL6A1, and CSTB – that can be used as a signature to classify patients with and without cervical lymph node metastasis, offering the potential to help doctors overcome the limitations of clinical exams and guide personalized treatment strategies.

Affordable biosensors
The scientists are now working on a new study designed to use translational techniques to build affordable biosensors capable of detecting prognostic signatures in patients’ saliva.

Peptides currently have to be identified and quantified by mass spectrometry and proteomics, which are costly techniques and not often available in clinics and hospitals.

“We want to develop a simpler and cheaper method that can easily be used by health professionals to assess the progression of the disease on the basis of tests that can be performed in a dentist’s or doctor’s office, or in clinical labs. In the study we’ve just published, we were able to identify this prognostic signature by mass spectrometry. We now plan to develop a biosensor with a focus on the use of this signature so that it can be adopted for clinical use and help guide treatment decisions”, Paes Leme said.

December, 2018|Oral Cancer News|

Immunotherapy extends the life of head and neck cancer patients

Source: Pharmatimes.com
Date: 12/3/18
Author: Anna Smith

A new immunotherapy can greatly extend the lives of a proportion of people with advanced head and neck cancer, with some living for three years or more, reports a major new clinical trial.

The study, by The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, found that the drug – MSD’s Keytruda (pembrolizumab) – has been shown to have significant benefits for patients, with 37% of those who received it surviving for a year or more, compared with only 26.5% of those on standard care.

The drug was evaluated in a trial of nearly 500 patients with very advanced head and neck cancer that had spread around the body and already become resistant to platinum chemotherapy, the first-line treatment for the disease.

Some 247 patients were randomised to receive Keytruda and 248 to standard of care – chemotherapy or the targeted agent Erbitux (cetuximab).

When chemotherapy or targeted therapies stop working, treatment options for people with advanced head and neck cancer are limited, and they are normally expected to survive for less than six months.

Patients in the Keytruda arm survived for a median of 8.4 months, compared to 6.9 months with standard treatment. However, a minority of patients responded extremely well to Keytruda – 36 patients saw their cancer partially or completely disappear, and some are still cancer free three years after first receiving the drug.

“Our findings show that the immunotherapy pembrolizumab extends the life of people with advanced head and neck cancer overall, and in a group of patients has really dramatic benefits. It is also a much kinder treatment than those currently approved,” said Professor Kevin Harrington, professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and consultant at The Royal Marsden NHS Foundation Trust.

“I would like to see pembrolizumab approved for use in the clinic, so that people with advanced head and neck cancer can be offered the chance of a longer life and improved quality of life.

“There is also an urgent need to work out how we can identify in advance which patients are likely to benefit, given that some of these people may do much better than they do on standard treatment.”

The trial was sponsored and funded by MSD, and the results are published in The Lancet.

December, 2018|Oral Cancer News|

Australian doctor helps restore cancer patient’s jaw using 3D printed mandible

Source: neoskosmos.com
Author: staff

Anelia Myburgh, a 31-year-old woman from Melbourne who lost most over her upper jaw and teeth to cancer has been offered a second chance in life thanks to Maxillofacial Surgeon George Dimitroulis, who customised a 3D printed jaw.

The fitted 3D mandible featuring a titanium frame, has changed Ms Myburgh’s life who had been left embarrassed and self-conscious, let alone unable to experience basic functions like eating or talking normally.

It all starter in April 2017, when she was diagnosed with jaw cancer after she noticed a small bump above her teeth, which was causing them to move and decided to have it checked with the dentist.

While a team of specialists reassured her it was fine, the test results that came a week later proved it was cancer which resulted in Ms Myburgh undergoing immediate lie-saving surgery to remove most of her upper jaw and part of her lips.

The patient was then left with only two teeth at the back of each side of her mouth and a deformed face.

People’s reactions – who sometimes stopped to take photos of her – made her avoid leaving her home and covering her face with a surgical mask if she had to.

“We communicate with our mouths, we eat with our mouths, if you don’t have a mouth we can’t really live in a way a person takes for granted,” Ms Myburgh told Nine News.

It wasn’t until she started researching possible treatment online that she stumbled upon Dr Dimitroulis’ work and previous successful procedures he had performed on patients using 3D technology.

Dr Dimitroulis assessed the case and decided to move forward with creating a 3D mandible for Ms Myburgh that would also allow teeth to be implanted.

The surgery only lasted a few hours and as seen on Nine News, Ms Myburgh’s new teeth look and feel like normal.

The doctors also took skin from the her forearm to recreate her lip.

“I can now enjoy life and meals with my friends,” the finance worker told Nine News.

“I’m slowly gonna get that burger!”

December, 2018|Oral Cancer News|

Study: Immunotherapy better than chemotherapy for subtype of head and neck cancer

Date: November 30th, 2018
Source: Scienmag

A randomized clinical trial involving 97 medical centers in 20 countries, including Moores Cancer Center at UC San Diego Health, found that treating patients who have chemotherapy-resistant head and neck cancer with the immunotherapy drug pembrolizumab is more effective and less toxic than standard chemotherapy, reports an international team of researchers in the November 30 online issue of The Lancet.

Previous research had shown that pembrolizumab (Keytruda) was safe and effective for treating patients with recurrent or metastatic head and neck squamous cell carcinoma whose disease had progressed while on or after receiving standard chemotherapy. Data from this clinical trial called KEYNOTE-040, a phase III study sponsored by Merck & Co., the manufacturer of the drug, takes the research a step further by comparing the immunotherapy drug head-to-head to three go-to chemotherapy drugs currently used as standard treatment: methotrexate, docetaxel and cetuximab.

“We compared pembrolizumab against standard of care to see if it fulfilled the promise of early data for patients who are unlikely to do well on standard therapy,” said Ezra Cohen, MD, professor of medicine at University of California San Diego School of Medicine and corresponding author on the study.

“In this trial, patients who received pembrolizumab alone had a higher response rate compared to those receiving standard chemotherapy while those responses lasted, on average, one-and-a-half years. Furthermore, the median survival at one year was markedly better. I feel it is safe to say that these types of therapies should be the new standard therapy for people with cancer that recurs and is resistant to therapy.”

Pembrolizumab is an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on tumor cells, allowing the immune cells to activate and attack tumors. Similar results were recently published for another anti-PD-1 drug, nivolumab (Opdivo). Both drugs should be considered by treating physicians for patients with this disease, said Cohen.

The study also pointed to potential biomarkers that can guide oncologists to determine which patients are most likely to respond to these anti-PD-1 drugs.

“It’s fairly clear that patients whose tumors express PD-L1 are most likely to benefit from this type of immunotherapy drug,” said Cohen, associate director for translational science at Moores Cancer Center and an internationally recognized physician-scientist who specializes in novel cancer therapies. “In this trial, overall survival was driven by PD-L1 expression. Only patients whose tumors expressed PD-L1 had a response to pembrolizumab and those responses tended to be durable.”

Over a 17-month period, 247 patients were randomized to receive pembrolizumab and 248 patients were randomly selected by their physicians to receive one of the three standard therapies. The median overall survival for patients receiving immunotherapy was 8.4 months and 6.9 months for patients treated with standard care. Patients received treatment until their cancer progressed, they developed unacceptable toxicity, they withdrew or their physician removed them.

The median duration of response was 18.4 months in the pembrolizumab group, compared with five months in the standard therapy group.

Twelve months after initiating the trial, 37 percent of patients receiving pembrolizumab were alive compared to 26.5 percent of patients on standard therapy.

###

Co-authors include: Denis Soulières, Centre Hospitalier de l’Université de Montréal; Christophe Le Tourneau, Institut Curie, INSERM U900 Research Unit, Versailles-Saint-Quentinen-Yvelines University; José Dinis, Instituto Português de Oncologia do Porto Francisco Gentil; Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori; Myung-Ju Ahn, Samsung Medical Centre; Ainara Soria, Hospital Universitario Ramón y Cajal; Jean-Pascal Machiels, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; Nicolas Mach, Hôpitaux Universitaires de Genève; Ranee Mehra, Fox Chase Cancer Center; Barbara Burtness, Yale University School of Medicine and Yale Cancer Center; Pingye Zhang, Jonathan Cheng, Ramona F Swaby, Merck & Co; and Kevin J Harrington, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre.

This research was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. The funder contributed to study design, data collection, data analysis, data interpretation, and the writing of The Lancet paper. The funder maintained the study database. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure: Cohen reports grant support to the institution from Merck Sharp & Dohme for clinical research related to the submitted work and serving an advisory role for AstraZeneca, Bristol-Myers Squibb, Eisai, Merck, Human Longevity and Pfizer, all outside the submitted work.

December, 2018|Oral Cancer News|