Norgine launches Lymphoseek in Italy

Source: www.prnewswire.co.uk
Author: press release

Norgine B.V. today announced the launch of Lymphoseek® (technetium Tc 99m tilmanocept) in Italy. Lymphoseek® is a radiopharmaceutical used for diagnostic purposes by nuclear medicine specialists and surgeons. It is specifically designed for a procedure called sentinel lymph node biopsy (SLNB) and represents a significant alternative to the current method of identifying sentinel lymph nodes in adult patients with breast cancer, melanoma, or localised squamous cell carcinoma of the oral cavity.

Lymphoseek® has been specifically designed to target, bind to and be retained in sentinel lymph nodes, the first lymph node (or group of nodes) to which cancer cells are most likely to spread from a primary tumour. Lymphoseek® has a false negative rate of 2.6% in T1-T4cN0 oral squamous cell carcinoma (OSCC). It detected sentinel lymph nodes in 98% of patients with Tis, Tx or T1-T4cN0 breast cancer and T1-T4cN0 melanoma

Lymphoseek® offers particular value in identifying lymphatic drainage from tumours in the floor of the mouth (underneath the tongue) which can prove especially difficult. Currently up to 70-80% of patients with early oral cancer receive elective neck dissection surgery, a major procedure which could be avoided by using sentinel lymph node biopsy (SLNB) for staging.

Peter Martin, COO at Norgine commented: “Making Lymphoseek® available to patients demonstrates our commitment to improving patients’ quality of life with access to new innovative specialist diagnostic tools and treatments. Norgine wants all eligible patients suffering from oral cancer, breast cancer or melanoma to have their cancers accurately staged using sentinel lymph node biopsy with Lymphoseek®. This will result in a reduction in unnecessary surgical interventions that can optimise the use of healthcare resources and improve patients’ outcomes.”

Head and neck cancer is the seventh most common type of cancer in Europe. It is about half as common as lung cancer, but twice as common as cervical cancer. There were more than 150,000 new patients diagnosed in Europe in 2012.

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September, 2017|Oral Cancer News|

Simple test can detect oral cancer in minutes

Source: www.click2houston.com
Author: Click2Houston.com Staff

Nearly 50,000 people will be diagnosed with oral cancer in the United States this year, and those numbers are expected to rise. Now, a simple, non-invasive test may soon be available to detect this deadly cancer early, with the hope of saving more lives.

Jeffrey Stanger was enjoying the good life when a trip to the dentist led to a frightening diagnosis. A biopsy revealed Jeffrey had oral cancer.

“When we refer to oral cancer, I’m talking about tumors involved in the mouth or the throat,” otolaryngologist, Dr. Elizabeth Franzmann explained.

Franzmann said cases of oral cancers are on the rise in this country due to the human papilloma virus or HPV. She says this type of cancer can be difficult to detect early on.

“So we are in better need of screening tools for this disease that are simple and inexpensive,” Franzmann added.

Franzmann and her team discovered that a molecule called CD44 plays an important role.

“We published a paper that showed that sure enough the levels in cancer patients were elevated compared to controls,” Franzmann said.

From there they developed a simple oral rinse test called OncAlert that can be used right in the dentist’s office.

Franzmann, showing the product, explained, “This protein pad here will turn a certain color of green.”

The green color means shows a person is at high risk. Jeffrey says this simple test can be a life saver.

“So you can detect it in very earlier stages,” he explained.

Jeffrey had surgery to remove the cancer, and is back smiling and enjoying life.

In spring of 2017 Vigilant Biosciences opened their FDA trial for the U.S. version of the OncAlert rapid test. A similar test that’s sent to the lab is already available here in the U.S. Both tests are made by Vigilant Biosciences, which recently received a federal grant from the National Institutes of Health for Oral Cancer Research.

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September, 2017|Oral Cancer News|

This Man Tried An ‘Alternative’ Cancer Treatment—and Ended Up Poisoning Himself

Source: Menshealth.com
Author: Alisa Hrustic
Date: September 12, 2017

Being diagnosed with cancer is one of the scariest things that can happen to you, but what follows can be even scarier. Treatment for the disease is expensive, painful, and extensive, so it’s not uncommon for people to ponder alternative solutions.

That’s all well and good, as long as it’s approved by your doctor. As for taking medicine into your own hands? That’s not always the best idea, since some alternative treatments can be extremely dangerous. Just recently, one Australian man learned that the hard way, according to a recent case report published in the British Medical Journal.

The 67-year-old man—who had been diagnosed with prostate cancer, which had gone into remission—consumed homemade apricot kernel extract daily for five years, since it’s typically marketed as a preventive medicine for cancer. He was also taking a fruit kernel supplement called Novodalin. While he was undergoing a routine surgery, his doctors noticed that his oxygen levels had severely dropped while he was under anesthesia, leading to a condition known as hypoxia, which can be deadly.

Once they performed blood tests on the patient, the doctors concluded that his blood contained 25 times the accepted level of cyanide, a potentially deadly chemical, according to the report.

That’s because apricot kernels contain amygdalin, also known as laetrile. Amygladin is a known cyanogenic glycoside, meaning it’s processed and converted into cyanide in your body, according to the Food and Drug Administration. While laetrile has been talked up for its anticancer properties, no human studies have actually proven its effectiveness in treating the disease. In fact, “no controlled clinical trial of laetrile has ever been conducted,” says the National Cancer Institute.

“Many extracts lack quality control in production and are not subject to extensive testing applied to standard medicines,” the authors of the report write, “hence efficacy and safety cannot be assured.”

Pits and seeds of several fruits—like apricots, apples, peaches, and cherries—can contain substantial amounts of cyanide. Just last July, a man in the U.K. suffered cyanide poisoning after eating cherry seeds.

If you’re exposed to small amounts of cyanide, you may experience dizziness, rapid breathing and heart rate, or headaches. If you consume a large amount, however, it can cause loss of consciousness and even respiratory failure, which can be fatal, according to the Centers for Disease Control and Prevention.

Luckily, the man described in the case report didn’t die, but his doctors quickly explained that the apricot kernel extract was slowly making him sick. He decided to continue taking it anyway.

Why? “He personally believes that the quality of evidence is sufficient for his purposes,” Alex Konstantatos, M.D., coauthor of the case report and head of pain medicine at Alfred Hospital in Melbourne told The Verge, “or maybe he cannot wait for the scientific proof to come through as it may take too long to prevent his cancer from recurring.” (Check out the video below to see how you may be approaching skin cancer all wrong, too.)

The thing is, people have actually died from ingesting too much cyanide. In 2011, a 2-year-old girl died after eating about 10 apricot kernels, according to a separate case report.

Konstantatos told The Verge that he wrote about this specific case because he wanted to bring awareness to the health implications of alternative medicine. Most doctors typically only ask about prescribed medications, and often aren’t aware of self-prescribed supplements, he says.

That means you should always check in with your doctor first before you consume any supplement, herb, or other popular “treatment”—it may just save your life.

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September, 2017|Oral Cancer News|

Alcohol industry ‘playing down’ risk of cancer by using tobacco industry tactics

Source: news.sky.com
Author: Paul Kelso, Health Correspondent

The alcohol industry is misleading the public by downplaying the risk of cancer through similar tactics to the tobacco industry, researchers say.

Liquor bottles in grocery store

A study led by the London School of Hygiene and Tropical Medicine (LSHTM) and Sweden’s Karolinska Institutet found the industry is using “denying, distortion and distraction” strategies to minimise evidence.

Researchers analysed information relating to cancer on the websites and documents of 28 alcohol industry organisations between September and December last year, finding that most showed “some sort of distortion or misrepresentation” of evidence.

The industry most commonly presented the relationship between alcohol and cancer as highly complex, implying there was no evidence of a consistent or independent link, according to the study.

Other tactics included denying that any relationship existed or claiming that there was no risk for light or moderate drinking, as well as presenting alcohol as just one risk among many.

Alcohol consumption is an established risk factor for a range of cancers, including oral cavity, liver, breast and colorectal cancers, and accounts for about 4% of new cancer cases annually in the UK.

The latest British government advice on alcohol, issued last year, makes an explicit link between cancer and alcohol.

It states: “The risk of developing a range of health problems (including cancers of the mouth, throat and breast) increases the more you drink on a regular basis.”

During the consultation phase the alcohol industry challenged the link with cancer.

The authors of the report, published in the Drug and Alcohol Review journal, said it was important to highlight that those who drink within the recommended guidelines – not more than 14 units a week for both men and women – “shouldn’t be too concerned when it comes to cancer”.

Mark Petticrew, Professor of Public Health at the LSHTM and the study’s lead author, told Sky News: “The information, on balance, across organisations we looked at seems to be quite extensively inaccurate or misrepresents the evidence.

“The evidence linking alcohol consumption and cancer is reasonably clear and has firmed up over recent years. The information on these websites, given out by alcohol bodies, appears to be not representing that evidence base, which is quite consistent.

“We know the tobacco industry attempted to confuse the relationship between lung cancer and smoking and put out a lot of very distracting information. We see similar types of argument use in these alcohol industry websites.”

Institute of Alcohol Studies chief executive Katherine Brown said: “This report shows that, like the tobacco industry before them, alcohol companies are misleading consumers about the evidence linking their products to cancer.

“We cannot rely on a profit-driven industry to promote public health. Consumers have a right to know the truth about alcohol and cancer, so they can make fully informed decisions about their drinking.”

The alcohol industry denied the report’s findings.

Glasses of light and dark beer on a pub background.

Drinkaware, a charitable trust funded by drinks manufacturers, said: “Its recent review of Drinkaware’s cancer information, which is extensive, has confirmed that the information we are providing accurately reflects the most recent research evidence.”

Henry Ashworth, president of the International Alliance for Responsible Drinking, said: “We do not agree with the conclusions reached in this paper. We believe in sharing the current state of the scientific evidence and stand by the information that we publish on drinking and health.”

Chris Snowdon, head of lifestyle economics at the Institute of Economic Affairs, said: “This is a diatribe disguised as a study that seeks to create a false narrative in which businesses always lie and anti-alcohol campaigners always tell the truth.

“We need to have sensible and evidence-based information about the risks of alcohol. The risks associated with cancer are not the biggest risks when it comes to drinking, the bigger risks are to do with violence, drink-driving and liver cirrhosis.

“It’s not cancer, so I’m not convinced that actually people understood fully what the risks associated with drinking are in terms of cancer when it doesn’t have an effect on people’s consumption of it at all.”

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September, 2017|Oral Cancer News|

World Trade Center responders might face greater risk of HPV throat and tongue cancer

Source: medicalxpress.com
Author: provided by Rutgers University

Firefighters at the World Trade Center were exposed to tons of toxic dust and debris that blanketed Manhattan on 9/11. Credit: Shutterstock

Researchers at Rutgers University – investigating the causes of head and neck cancers in World Trade Center rescue and recovery workers – will take the lead in a study to determine whether the responders are at a greater risk for human papillomavirus (HPV)-related throat and tongue cancer because of their exposure to toxic dust and debris.

“If we find that the prevalence of HPV is higher in World Trade Center exposed rescue workers it could mean that they have an increased likelihood of infection with HPV or have less of an ability to be able to clear this common infection naturally,” said Judith Graber, assistant professor of epidemiology in the School of Public Health.

HPV is the most common sexually transmitted infection in the United States, according to the Centers for Disease Control and Prevention, with most infections going away on their own. There is also now a vaccine to prevent HPV given to adolescents and teens. This is a new vaccine not given to adults and rates of vaccination have been low in the US.

While HPV-related oropharyngeal cancer, which includes throat, tonsils, back of tongue and soft palate, is relatively small, the number of HPV throat and tongue cancers are expected to increase and surpass HPV-related cervical cancers by 2020.

Graber said oropharyngeal cancer – which has a lower survival rate – is among the diseases which pose great risk for WTC rescue and recovery workers, who appear to have a greater incidence of throat and tongue cancer. Surviving patients, often left disfigured after treatments, are at a higher rate for depression, unemployment and suicide compared with other cancer patients, according to the study.

While the prevalence of HPV in the United States among people age 69 and younger is estimated at less than 10 percent, Graber said research indicates that 80 percent of all tumors found in this type of cancer are infected with HPV, some which can cause cancer.

“The symptoms, risk factors and exposure history could help in early prevention of this very devastating cancer,” said Graber.

The new Rutgers study will use tissue samples provided by the World Trade Center Biorepository at Mount Sinai from WTC workers diagnosed with oropharyngeal cancer and compare to tissue samples of people being treated for the disease at University Hospital in Newark.

This research is a spinoff of a two-year federally funded study examining risk factors for all head and neck cancers among WTC responders. Graber and her colleagues, including co-principal investigator, Mark Einstein, professor and chair department of OBGYN & Women’s Health at Rutgers New Jersey Medical School, are hoping to discover opportunities for early detection for these potentially debilitating diseases.

“HPV is very common, but cancers related to HPV are uncommon,” said Einstein. “Understanding the relationship between HPV and the development of oropharyngeal cancer is of critical importance so we can prevent and target this cancer better with novel therapies”.

What researchers need to determine in this new study, Graber said, is whether the higher incidence of the throat and tongue cancer is due to the fact that this group is being closely monitored, because of respiratory exposure after 9/11 or as a result of an HPV infection that creates a problem for a weakened immune system.

The information is critical, Graber said, in the quest to design a more definitive study to determine how and why these cancers are developing among those exposed during the rescue, recovery and clean-up efforts at the World Trade Cente

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September, 2017|Oral Cancer News|

What’s next after creating a cancer-prevention vaccine?

Source: www.scientificamerican.com
Author: Dina Fine Maron

A winner of this year’s Lasker Awards talks about his work with HPV

Imagine a vaccine that protects against more than a half-dozen types of cancer—and has a decade of data and experience behind it.

We have one. It’s the human papillomavirus (HPV) vaccine, and it was approved for the U.S. market back in June 2006. It can prevent almost all cervical cancers and protect against cancers of the mouth, throat and anus. It also combats the sexually transmitted genital warts that some forms of the virus can cause.

On Wednesday, two researchers who completed fundamental work on these vaccines received one of this year’s prestigious Lasker Awards, a group of medical prizes sometimes called the “American Nobels.” Douglas Lowy and John Schiller, whose research provided the basis for the HPV vaccine, were selected alongside a researcher who separately unraveled key aspects of metabolic control of cell growth. Planned Parenthood was also given an award, for its public service. Lowy and Schiller, who both work at the U.S. National Cancer Institute (NCI), received the Lasker for their research on animal and human papillomaviruses—work that enabled the development of a vaccine against HPV-16 type, a form of the virus that fuels many HPV malignancies. The duo’s experiments proved that the vaccine is effective in animals, and they also conducted the first clinical trial of an HPV-16 vaccine in humans. That gave pharmaceutical companies the evidence they needed to invest in their own vaccines designed to protect against multiple kinds of HPV, and ultimately led to the versions administered around the world today.

Yet HPV shots have had a difficult run. Despite overwhelming evidence of their safety and effectiveness, in some developed countries—including the U.S.—HPV inoculations face opposition from individuals and groups that fear the shots are still too new and unproved to use on their children. The HPV vaccine also faces another hurdle beyond other routine pediatric shots: the virus is transmitted via sexual contact—which some parents and communities believe teens should not or will not have, and thus that the shots should not be mandatory. (The U.S. Centers for Disease Control and Prevention [CDC] currently recommends administering two doses of the vaccines to children 11 to 12 years old, administered at least six months apart.)

Scientific American spoke with Schiller, a virologist, about his and Lowy’s award-winning HPV research, their future plans and how to combat anti-vaccine attitudes.

[An edited transcript of the interview follows.]

What’s the biggest hurdle to getting more coverage with the HPV vaccine?
The biggest problem is actually not in the West or most developed countries; it is in the lower- and middle-income countries because of availability there and vaccine prices that limit availability. In those settings vaccine acceptance is actually very high. But those settings present the biggest problem, since some 85 percent of cervical cancers occur in low-resource settings. In the more developed countries there are many different factors involved [in vaccine hesitancy], and they differ by country. In the U.S. it is more about fear of vaccines in general. And there are some issues with HPV vaccines specifically related to this being about a sexually transmitted disease.

So far, more than 270 million doses of HPV vaccines have been distributed worldwide. But in the United States, by 2015 only 28 percent of teen males and 42 percent of teen girls had received the full course of three shots then recommended by the CDC. How can the science community help combat HPV vaccine hesitancy?
There are quite a few studies that show one of the biggest issues is that the vaccine is not being promoted sufficiently by pediatricians and general practitioners. If you look at other vaccines like for meningitis and hepatitis B—which are also administered to adolescents and could be given in the same visit as HPV—they are given at greater rates than HPV. So, there is some disconnect in communication between pediatricians and parents there. Part of the problem here is that the HPV vaccine is a prophylactic vaccine to prevent a disease—cervical cancer—that those providers never see. Obstetrician-gynecologists see it, but pediatricians don’t, which is the opposite of most other childhood or pediatric vaccines. Right now it’s being singled out as something special instead of treated as a routine childhood or adolescent vaccine. But we’ve had this vaccine for 10 years now and it’s not the new kid on the block anymore.

Mounting evidence suggests that among people who feel vaccines are unsafe, any new data showing that they arereally safe does not move the needle to convince them. So, what can be done?
My feeling is that there is a certain percentage of people who, no matter what facts you present to them, they are just not going to be convinced. Quite frankly it doesn’t pay to spend a lot of resources trying to convince that relatively small fraction. What we need to focus on is a much larger fraction of the population who aren’t having their kids vaccinated for reasons like convenience—like it’s a hassle—or they just need a bit more information to make them comfortable. People against all vaccines, those people would not be convinced to get an HPV vaccine so it’s not worth spending a lot of resources on them. I think one of the things that would increase HPV vaccine coverage would be allowing people to get them at their local CVS. I’m not an expert on this, but I have a daughter who as a teen spent much more time at the local CVS than at her local Kaiser clinic. Different states have different laws about which vaccines can and can’t be delivered at pharmacies—but if someone could go get an HPV vaccine at the same place they get their flu vaccine, presumably it would lead to an uptick.

I see you studied molecular biology as an undergrad at the University of Wisconsin–Madison. Did you always want to work on vaccines?
No, absolutely not. When I first started out I was an academic purist and thought you should study knowledge for its own sake. I was fascinated by molecular biology. When I first heard about the way metabolism works in bacteria, plants and humans, that just wowed me because that was a common feature of all life. I just wanted to study that. I thought people who did translational work were sort of selling out to the man—this was in the 1970s. I didn’t get interested in vaccines until much later. Now, I’m very fascinated with translational research.

So, what changed?
It was a very gradual thing. To this day we still do basic research, and it’s still intrinsically valuable to do basic research because you don’t know when it will lead to a transformational breakthrough.

What led you to work on HPV?
When I had just joined the field, suddenly there was this discovery that made papilloma viruses important for human health as opposed to just an understanding of how cells become cancerous. I had joined Doug Lowy’s lab at the National Cancer Institute as a postdoc back in 1983, and the second lecture I went to there was by Harald zur Hausen—who later won the Nobel Prize—and his lecture was saying “eureka! We found a virus that seems to cause 50 percent of cervical cancers”—and that virus turned out to be a human papilloma virus strain, HPV-16. So basically we went from looking at a model about how a normal cell transforms to become carcinogenic to something probably involved in causing human cancer. It was somewhat serendipitous.

What are you working on now?
One thing we are doing at the NCI, and cosponsored by the Bill & Melinda Gates Foundation, is testing if one dose of HPV vaccine is enough to provide long-term protection. It would be transformative, especially in the developing country setting, if you could just have one dose at a younger age. This new trial is going to be done in Costa Rica in collaboration with the Costa Rican government. That’s the site where we had done a prior pilot trial that suggested one dose may be enough.

We are also looking into cancer immunotherapy work. It turns out that these virus-like particles that we work with for the HPV vaccine—these are typically the outer shell of a virus, like from the HPV-16 strain or other animal, or human papilloma virus particles—have a unique ability to infect tumor cells and bind to them specifically. So we are using that knowledge to develop cancer therapies that are broad-spectrum. It turns out these cancers, like melanoma, do bind these particles, specifically.

One other thing we are doing is trying to develop vaccines that would treat herpes simplex infections and HPV infections in the female genital tract. Again, this would take advantage of these virus-like particles’ structures.

Last year I interviewed Michael Sofia, who won a Lasker Award for his hepatitis C vaccine work. The name of that vaccine, sofosbuvir—brand name Sovaldi—is a nod to his last name. But the National Institutes of Health (NIH) do a lot of early-stage research, and then it’s passed off to private companies that develop it further. Your name isn’t part of the HPV vaccines Gardasil or Cervarix, for example. Is it frustrating doing a lot of that behind-the-scenes work?
It’s funny because I would never have thought of that. It would have never entered my mind to name a vaccine after ourselves. We are so used to doing this translational work. My job is to move a project along so it’s interesting enough for a company to invest hundreds of millions of dollars for the benefit of large numbers of people. NIH doesn’t have the money to do phase III trials for lots of drugs, and even if they did it wouldn’t lead to all the drugs we need—because NIH wouldn’t have the money to develop them. This translational and basic research is what NIH does best. That work is way too fraught with failure for companies to do it all. It has to be done in the public sector, and then when things look more promising companies can take it over.

What advice would you offer someone considering becoming a scientist now?

It’s got to be a passion because being a scientist—especially early in your career—is more a lifestyle than occupation. You have to really want to do it, because there is a lot of uncertainty—especially about running your own lab and getting funding. Success and failure can be on a knife’s edge sometimes. The other thing is that you need to be strategic about thinking of what you want to go into, and that’s hard for young people because they don’t have the perspective: There are some fields just opening up ripe for discoveries. And there are some areas that are very mature, that we have been working on for a long time, where there are a lot of scientists working already—so the chances of making a big impact are lower. From my own life, this is like when we started with human papilloma viruses. When I went into this field, we had just been given the tools to study them and so it seemed like a great opportunity to get involved. In some ways it’s best if you can pick an emerging field with new tools to answer big questions. But you have to pick something you are really interested in and go with it.

The other thing I’d say is read a lot. Now with PubMed and access to all these journals there is no excuse for not knowing the background in something that basically has already been done. Young people tend to want to get out and do experiments, but a few days searching PubMed may save someone years of work trying to reinvent the wheel.

Right now, what would you say is the biggest challenge—or one of the biggest challenges—that needs to be solved?
That’s a really tough one. I think as scientists we are all sort of locked into the things we study. I could say cancer, obviously. But Alzheimer’s is something we obviously need to solve. HIV infection. All these different things. One of the things that really needs to be solved in terms of the whole scientific enterprise now is stable funding. Right now we are in a situation where there are too many good scientists—especially young scientists—competing for a limited pot of money. So you lose some good people because there’s not enough money to go around. Also, people are forced to do relatively mundane things that are really a methodological extension of something they’ve done before instead of something truly transformative that would have a large chance of failure. Grant reviewers are looking at something likely to succeed and move the field incrementally, or something transformative that may have a high chance of failure, and have to make those decisions. This is an issue across the sciences. The obvious solution would be to have more funding, but then that raises the question about how to do that. And I’m not a politician.

What, if anything, does this Lasker Award do for your work?
Quite honestly, probably nothing, because one of the nice things about being part of intramural research [at NIH] is that I have stable funding. I’ve had six people in my lab for the last 25 years, so this won’t lead to more grants or me doubling the size of my lab, or anything like that. I’m happy with my moderate-sized lab and collaborations with a lot of great people. That’s why I’m here. Every four years we have a site visit, which is a retrospective review of “what have you done for us lately,” and if it’s reasonable I will continue to get funding. So the award won’t affect my research career much at all.

Right now, some in the scientific community fear amid this political climate that facts matter less than they once did and thus science matters less. What’s your take on that?
Obviously, my perspective is science matters a lot. I really can’t comment on what’s happening in the country overall—and whether this is something that is pervasive where science is really held in less esteem, or it’s that there is a vocal minority being heard a lot now. I would hope it’s the latter.

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September, 2017|Oral Cancer News|

Personalised cancer treatment

Source: medicalxpress.com
Author: University of Oslo

In Norway, more and more people are being affected by cancer of the mouth and throat. In recent years, the incidence has increased but the mortality has remained the same. Cisplatin is one of the most commonly administered cytostatics for this patient group. At the start of treatment, the drug works well. Gradually, though, most patients experience that the tumour develops resistance against this drug and the prognosis for survival then becomes very poor.

In her PhD thesis, Jian Gao wanted to find out how the cancer cells could protect themselves against this cytostatic i.e. what is the underlying mechanism of resistance.

She therefore cultured various cancer cell lines derived from oral cavity which were given differing doses of the cytostatic cisplatin. A cancer cell line is cultured from patients’ cancerous tumours and can live indefinitely in the laboratory. These types of cell lines are used to examine the biology and the changes that have resulted in the development of cancer. Because the cancer cell lines divide in the laboratory, they can also adapt to new growth conditions, for example by becoming resistant to the cytostatic cisplatin in the same way as the cancer tissue in the patients.

“First, I had to find those cancer cells that were sensitive to the cytostatic,” explains Jian Gao. By identifying the sensitive cancer cell lines that I could make resistant in the laboratory, I could then study which changes took place in the cells as they changed from being sensitive to being resistant,” clarifies Gao.

Cytostatic for cancer cell lines

“During this process I found two different cancer cell lines. At the beginning, I gave them a dose of cytostatic that was strong enough to kill half of the cancer cells. This dose was increased each week, and after eight months both types of cancer cells were resistant to the cytostatic, cisplatin,” explains Gao.

Next, these cells had a resting period from any type of treatment. Gao wanted to see whether this resistance could be reversed by the pause in cytostatic treatment. However, it became apparent that the pause did not have any effect and the cells were permanently resistant to cisplatin. The resistant cell lines had changed permanently.

“Since I have two cell types that I knew were resistant, and I could now compare these cell lines with the original sensitive cancer cell lines,” comments Gao.

To compare gene expression in the cells, Gao used a technique that studies the expression of about 21,000 genes, a so-called mRNA microarray. This technique was used to look at changes in gene expression in the resistant cancer cell lines and then compare them with the gene expression in the original sensitive cancer cell lines.

Up-regulated genes

Only three genes were found to be up-regulated in both of the resistant cell lines. Of these genes, Gao decided to look at a cytokin, interleukin 6 (IL-6), which is a signal molecule that is often up-regulated in cancer, and which is associated with a poor prognosis and cisplatin resistance in several types of cancer.

By investigating expression of the IL-6 gene in head and throat cancers in 399 patients and then comparing this with survival, Gao and her co-workers found that, after treatment with the cytostatic cisplatin, the patients with cancer tumours with the up-regulated interleukin 6 gene did not have a better prognosis for survival.

Apparently, such cancer tumours were resistant to cisplatin. However, detailed mapping of the resistant cancer cell lines revealed that IL-6 in itself did not make the cancer cisplatin resistant. The effect had to be exerted via currently unknown mechanisms, possibly in the interaction between the cancer and IL-6 stimulation in the surrounding connective tissue.

Growth factors

Connective tissue can produce growth factors which cause the cancer to grow. There are a number of different growth factors and, of the eight known epithelial growth factors, Gao and her co-workers could demonstrate a relationship between the tumour’s gene expression in four of these epithelial growth factors and survival. The four growth factors were: Amphiregulin, epidermal, heparin-binding EGF-like growth factor and betacellulin. Could increased production of these growth factors explain cisplatin resistance?

Jian Gao’s research showed that if these growth factors were up-regulated, there was a high probability that the patient would not survive. At the same time, no relationship was found between cisplatin resistance in the cancer cell lines and the production of these growth factors.

However, the researchers could demonstrate that the more of these four growth factors a tumour expressed, the poorer the prognosis for the patient. By quantifying the amount of mRNA in the tumour tissue, Gao and co-workers could predict the patient’s prognosis considerably more accurately than the TNM system, which is the traditional method used to determine the stage of a cancer. The level of these four growth factors could predict how long even the most ill patients with distant metastases would live.

These growth factors have a common receptor in the so-called EGF receptor family. Currently, there are a number of drugs in use in patient treatment that can block this receptor. For patients whose cancers demonstrate high expression of these growth factors, it could potentially be particularly appropriate to use these medicines to reduce the growth of the cancer and increase the patient’s chances of survival.

In the last part of her PhD thesis, Gao tried to find the various “inhibitors” that could affect cisplatin resistance. After several trials with various signal and receptor inhibitors, she finally found that a drug called AG825, which inhibits the activity of an EGF receptor family member (HER 2), could reduce cisplatin resistance in four different cancer cell lines. This occurred by increasing the ability of cisplatin to trigger the cells’ self-destruct programme (apoptosis).

These drugs are already in use to treat patients with other types of cancer and, even though the details of the mechanism must be investigated in more detail, Gao and co-workers have demonstrated the probability that treatment with a cytostatic combined with “inhibitors” of the cancer cells’ protective mechanism will be advantageous. This could considerably improve the effect of the cytostatic cisplatin and thereby improve the prognosis for survival for patients with cancer of the head or throat.

But a lot of work still remains, and the journey from cell line reactions in the laboratory to how cancer cells in patients react to the same type of combined therapy is often long. Only more research can provide the answer to whether this is a navigable route to a more effective, personalised treatment of cancer of the head and throat.

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September, 2017|Oral Cancer News|

Why HPV Vaccination Rates Remain Low in Rural States

Source: TechnologyReview.com
Author: Emily Mullin
Date: September 1, 2017

 

Mandi Price never thought she’d be diagnosed with cancer at age 24. She was a healthy college student finishing her senior year when, during a regular Pap smear, her gynecologist found abnormal cells in her cervix. It was stage II cervical cancer.

Even more devastating was the fact that her cancer was preventable. Doctors detected a strain of human papillomavirus, the most common sexually transmitted infection in the U.S., in Price’s cancer cells. That strain of HPV is targeted by a vaccine called Gardasil. But Price never got the vaccine. Her primary care doctor didn’t recommend it when she was a teenager growing up in Washington state. Had she received it before becoming infected with HPV, she wouldn’t have gotten cancer.

Price dropped out of her classes to get treatment. She needed surgery to remove the tumor from her cervix, then underwent chemotherapy and radiation to kill any remaining cancerous tissue. At her one-year follow-up appointment, doctors found that the cancer had spread. She endured chemotherapy for another six months. Now, at 29, Price is in remission and is working in Los Angeles. “Most of my 20s comprised being in a hospital. It was isolating,” she says.

Merck’s Gardasil vaccine was considered a breakthrough when it was approved by the U.S. Food and Drug Administration in June 2006. It was the first vaccine to protect against several cancers. But more than a decade after the vaccine came out, vaccination rates in many places in the U.S., especially in the South, Midwest, and Appalachian states, still remain much lower than rates for other childhood vaccines—too low to stop transmission of the most dangerous HPV strains.

In 2016, only about 50 percent of girls and 38 percent of boys had all the required doses of the HPV vaccine needed to be fully protected, according to data released last week by the U.S. Centers for Disease Control and Prevention. Those figures are up slightly from last year, but still not close to the 80 percent that public health experts want to achieve.

Gardasil is approved to protect against cervical, vulvar, and vaginal cancers in girls and women ages 9 through 26, as well as anal cancer for the same age group in both girls and boys. Recently, the vaccine has also been shown to protect against oral cancers in men. HPV causes about 32,000 cancers every year, with cervical cancer the most common for women and oral cancers the most frequent in men.

Electra Paskett, a cancer epidemiologist at Ohio State University, says she is still surprised that the vaccine’s uptake has been so slow. “It’s crazy that there’s not a line around the corner. If we said we have a vaccine for breast cancer, we’d be vaccinating day and night,” she says.

The problem the vaccine has faced is its link to a taboo in American culture: sexual activity among teenagers. About one in four people in the U.S., including teens, are currently infected with HPV. Health-care providers are the biggest hurdle to getting more children vaccinated. Some primary care physicians, like in Price’s case, may not recommend it at all.

For Merck, the world’s largest vaccine maker, Gardasil has been a profit generator even though the company admits the uptake of the vaccine has been surprisingly slow. The company says it’s trying to increase rates by educating health-care providers.

William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University, remembers the initial excitement in the medical community when Gardasil first came out. “I thought the advent of our first explicitly anti-cancer vaccine, and the fact that it was so incredibly successful and safe, would be immediately embraced with pizzazz and rose petals,” he says.

Regional differences
State vaccination rates were as high as 73 percent among girls in Rhode Island and as low as 31 percent in South Carolina for all three doses in 2016. Among boys, Wyoming had the lowest rate, with only 20 percent getting the full round of shots.

Overall, teens living in major metropolitan areas were far more likely to get the vaccine than those living in rural areas, which may be more socially conservative and lack access to certain health-care services. In some of these places, average household incomes are lower than the national average, and parents might not be able to afford to take their pre-teens or teens to get the vaccine.

In some states with low vaccination rates, HPV-caused cancers are the among the highest. In Mississippi, for example, only about 34 percent of girls and 25 percent of boys get all required doses of the vaccine. The state also has one of the highest rates of HPV-related cervical cancer in the country. Wyoming tells a similar story, with high rates of HPV-associated cancers in both men and women.

Of course, those cancer rates can’t yet be tied to the states’ low vaccination rates. Gardasil was introduced just over a decade ago, and many of these cancer cases are in people who were too old to get the vaccine when it came out. But it means that these disparities could grow if more people there don’t get the vaccine.

HPV vaccination for boys is especially lagging in some areas. Paskett, who has studied cancer in Appalachia, say there’s a perception that HPV only causes cancers in women. “A lot of parents don’t know that boys should be vaccinated,” she says. Boys and men not only carry HPV but can get HPV-related cancers, like anal, penile, throat, and tongue cancers.

Price says shortly after her cancer diagnosis, she urged her parents to get her two younger brothers vaccinated.

Doctor hesitancy
A 2015 study found that a little over a quarter of the 776 pediatricians and family physicians surveyed do not strongly endorse the HPV vaccine. About one-third of the total doctors surveyed also said that having to talk about a sexually transmitted infection makes them uncomfortable.

Nneka Holder, associate professor of adolescent medicine at University of Mississippi Medical Center, says she is frustrated that so many doctors don’t recommend the HPV vaccine because they think it means they have to talk to parents about sex.

“We don’t usually explain to patients how they get hepatitis or meningitis,” she says. “So why should HPV be different?” Instead, she says health-care providers should focus on the cancer prevention aspect of the vaccine, rather than how HPV is spread.

Even health-care providers who do talk to parents about the vaccine aren’t always effective at getting their message across. A study from 2014 found that 47 percent of Minnesota health-care physicians and nurses that did ask parents about their concerns with the vaccine said they lacked time to probe the issue further, and 55 percent felt they couldn’t change parents’ minds.

Schaffner says doctors that are most successful with getting parents on board with the HPV vaccine are the ones who don’t call special attention to it. He says the best tactic is for physicians to sandwich in the HPV vaccine with other recommended vaccines—as in, “It’s time for your son to get the meningococcal, HPV, and Tdap vaccines.”

Parent concerns
Since the vaccine is just over 10 years old, it’s too early to know how many cases of cancer it has prevented so far. But clinical trials have showed that the vaccine provides nearly 100 percent protection against cervical infections caused by certain strains of HPV. These infections have fallen by 64 percent among teen girls in the U.S. since 2006, when the vaccine was introduced. Large clinical trials of the HPV vaccine have also shown it’s safe for both boys and girls.

These benefits have led Virginia, Rhode Island, and Washington, D.C., to adopt public school mandates for HPV vaccination. But some parents are still uncomfortable about the HPV vaccine’s association with sex and think their children don’t need it because they’re not sexually active. That has led parents to form groups in opposition to such mandates.

Aimee Gardiner, director of one such group called Rhode Island Against Mandated HPV Vaccine, says she doesn’t see HPV as the “epidemic” she thinks the CDC has made it out to be. “For me the risk of developing a cancer from any HPV is so insignificantly small that I do not feel like the vaccine is a necessity,” she says. Gardiner has two children, one of whom isn’t old enough to receive the vaccine and the other who hasn’t received it. She says she doesn’t plan to vaccinate them with Gardasil.

It’s true that for most people, the immune system clears the virus from their systems naturally. But for a small number of people, HPV persists and can turn cancerous. For those patients, like Price, cancer can be a major life ordeal, not to mention much more expensive than a vaccine that costs about $150 per dose.

Looking ahead
HPV vaccination rates continue to increase steadily, but the problems associated with its uptake could spell trouble for other vaccines in the future. For example, researchers for years have been working on a vaccine that would protect people from contracting HIV, the virus that causes AIDS. If a vaccine for HIV were ever to be successful, it could run into the same problems. HIV’s risk factors—unprotected sex and intravenous drug use—make it even more taboo.

Another worry is that rising anti-vaccine sentiments causing parents to opt out of vaccinating their children will hurt efforts to expand HPV vaccine coverage.

One factor that may increase vaccination rates is a new guideline from the CDC announced in October 2016. Children ages 11 to 14 now only need two doses of the HPV vaccine at least six months apart instead of three, which was previously recommended. Teens 15 and older still need to complete the three-dose series. This change may increase uptake of the vaccine, as vaccination rates drop off after each dose.

For Price and other cancer patients, the thought of not getting a vaccine that could prevent something so terrible is unimaginable. “I am a huge proponent of it,” she says. “If you had the chance to prevent cancer in your son or daughter, why wouldn’t you do that?”

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September, 2017|Oral Cancer News|

FDA Approves First Gene Therapy For Leukemia

Source: npr.org
Author: Rob Stein
Date: August 30, 2017

The Food and Drug Administration on Wednesday announced what the agency calls a “historic action” — the first approval of a cell-based gene therapy in the United States.

The FDA approved Kymriah, which scientists refer to as a “living drug” because it involves using genetically modified immune cells from patients to attack their cancer.

The drug was approved to treat children and young adults up to age 25 suffering from a form of acute lymphoblastic leukemia who do not respond to standard treatment or have suffered relapses.

The disease is a cancer of blood and bone marrow that is the most common childhood cancer in the United States. About 3,100 patients who are 20 and younger are diagnosed with ALL each year.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb said in a written statement.

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses,” Gottlieb said.

The treatment involves removing immune system cells known as T cells from each patient and genetically modifying the cells in the laboratory to attack and kill leukemia cells. The genetically modified cells are then infused back into patients. It’s also known as CAR-T cell therapy.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials,” Marks said in the FDA statement.

The treatment, which is also called CTL019, produced remission within three months in 83 percent of 63 pediatric and young adult patients. The patients had failed to respond to standard treatments or had suffered relapses. Based on those results, an FDA advisory panel recommended the approval in July.

The treatment does carry risks, however, including a dangerous overreaction by the immune system known as cytokine-release syndrome. As a result, the FDA is requiring strong warnings.

In addition, the treatment will be initially available only at 32 hospitals and clinics that have been specially trained in administering the therapy.

Novartis, which developed the drug, says the one-time treatment will cost $475,000 for patients who respond. People who do not respond within a month would not be charged, and the company said it is taking additional steps to make sure everyone who needs the drug can afford it

But some patient advocates criticized the cost nevertheless.

“While Novartis’ decision to set a price at $475,000 per treatment may be seen by some as restraint, we believe it is excessive,” says David Mitchell, founder and president of Patients For Affordable Drugs. “Let’s remember, American taxpayers invested over $200 million in CAR-T’s discovery.”

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August, 2017|Oral Cancer News|

Gliknik announces dosing of first patient in phase 2 trial targeting prevention of recurrence of high-risk oral cavity cancer

Source: www.prnewswire.com
Author: press release

Gliknik Inc. today announced that clinicians have enrolled and dosed the first of 80 patients in the company’s phase 2 clinical trial assessing the efficacy and safety of biropepimut-S (GL-0817), an immunomodulatory therapeutic targeting the prevention of recurrence of squamous cell cancer of the oral cavity in patients at high risk of recurrence after surgery, chemotherapy, and radiation.

“We are pleased to enroll the first patient in this phase 2 trial of biropepimut-S, which will further our understanding of the potential role of this advanced-design cancer vaccine with immune enhancing adjuvants in high-risk oral cavity cancer,” said Jeff Herpst, Senior Director of Clinical Development at Gliknik.

High-risk oral cavity cancer is associated with a recurrence rate of approximately 70% within three years of the time of surgical resection despite adjuvant chemoradiotherapy. Unfortunately, only a small percent of patients respond to the clinical options currently available for physicians to use in treating such patients who recur.

“With recurrent oral cavity cancer being so difficult to treat, now is an opportune time to assess how useful and safe biropepimut-S may be in protecting individuals from recurrence of high-risk oral cavity cancer,” said David Block, CEO of Gliknik. “The goal of the study is to see if we can activate the individual’s immune system to eliminate residual cancer cells that cannot be seen by current imaging methods, thereby avoiding clinical recurrence. We are finding that physicians and patients are interested in clinical trials addressing this significant unmet medical need.”

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August, 2017|Oral Cancer News|