Monthly Archives: July 2011

Secondhand smoke, not just loud music, may harm teens’ hearing

Author: staff

Teenagers may seem to be not listening but they actually may be having trouble hearing. And the reason may not always be their ubiquitous iPod earbuds, especially if they live in a home where someone smokes, new research has suggested.

A study in a recent issue of the Archives of Otolaryngology—Head and Neck Surgery recommended that pediatricians consider secondhand smoke exposure to be a risk factor for hearing loss in adolescents and screen accordingly.

Approximately 60% of American children are exposed to secondhand smoke, which may also have the potential to have an effect on auditory development, leading to sensorineural hearing loss, according to researchers.

Researchers examined the risk factors for sensorineural hearing loss among 1,544 nonsmoking participants aged 12 to 19 years in the 2005-2006 National Health and Nutrition Examination Survey.

Adolescents exposed to secondhand smoke had higher rates of low- and high-frequency hearing loss than peers with no secondhand smoke exposure—and the degree of hearing loss increased with the amount of cotinine (a biomarker for nicotine exposure) in the blood.

Because most teens do not have routine hearing exams, pediatricians may want to ask follow-up questions of “tuned out” teens, particularly because 82% of those who had hearing loss were unaware of it.

Monitoring the hearing of adolescents exposed to secondhand smoke may head off problems in development and functioning associated with early hearing loss.

Introduction of maspin in cancer cell nucleus ‘halts disease’

Author: Edward Bartel

Scientists in Canada believe the injection of maspin into the nucleus of aggressive cancer cells can dramatically halt the spread of the disease, reducing the chance of needing developed cancer treatment.

Studies on two types of aggressive cancer cell, an invasive head and neck cancer and a form of breast cancer, were tested by applying two forms of maspin into the nucleus of one set of cells, while another set was applied to the cytoplasm – the surrounding area of a cell’s centre.

It has long been assumed that maspin had some effect on the development of cancer. However, the study’s findings, published in the Laboratory Investigation journal, suggest that the application of maspin can reduce the instance of cancer metastasis.

“Metastasis is the cause of 90 per cent of cancer deaths,” said one of the authors of the study, Dr Ann Chambers, professor of oncology, pathology and medical biophysics at Schulich School of Medicine and Dentistry, Canada.

She added: “Our new work suggests that when maspin is located in the nucleus it blocks cancer spread and growth.”

In Britain, Cancer Research UK report that 309,500 people were diagnosed with the disease in 2008, with the possibility of women developing breast cancer now at one in eight.

1 Goulet, Brigitte, ” Nuclear localization of maspin is essential for its inhibition of tumor growth and metastasis.” Laboratory Investigation. Thursday July 28th 2011.
2 Statistical Information Team: Cancer Research UK, “CancerStats News“. May 2011.

Convergence in Head and Neck Cancer


Powerful new technologies that zoom in on the connections between human genes and diseases have illuminated the landscape of cancer, singling out changes in tumor DNA that drive the development of certain types of malignancies such as melanoma or ovarian cancer.

Now several major biomedical centers have collaborated to shine a light on head and neck squamous cell cancer. Their large-scale analysis has revealed a surprising new set of mutations involved in this understudied disease.

In back-to-back papers published online July 28 in Science, researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center have confirmed genetic abnormalities previously suspected in head and neck cancer, including defects in the tumor suppressor gene known as p53. But the two teams also found mutations in the NOTCH family of genes, suggesting their role as regulators of an important stage in cell development may be impaired.

“This adds a new dimension to head and neck cancer biology that was not on anyone’s radar screen before,” said Levi A. Garraway, a senior associate member of the Broad Institute, an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and a senior author of one of the Science papers. “Head and neck cancer is complex and there are many mutations, but we can infer there is a convergence on a cellular process for which we previously did not have genetic evidence. It shows that if you do a genome sequencing project of this size you can gain major new biological insights.”

“The mutational analysis of NOTCH clearly indicated the power of genetic changes determining the function of these genes,” said Kenneth W. Kinzler, professor of oncology and a molecular geneticist at Johns Hopkins, co-director of the Ludwig Center at Johns Hopkins, and an author of one of the Science papers. “It gives us an important clue to start studying their function.”

Head and neck cancer is the sixth most common non-skin cancer in the world, with more than half a million new cases each year. Smokers, drinkers, and people infected with the human papillomavirus (HPV) have the highest risk of developing head and neck cancer, which is the collective name for tumors found in the oral cavity, including the mouth, larynx, and pharynx.

Patients often seek medical care only once they are in the later stages of the disease, when they may be offered surgery, radiation, chemotherapy, or a combination. Treatments can be disfiguring and debilitating, leaving patients unable to speak or swallow. The five-year survival rate of 50 percent has improved little over the past 40 years.

Jennifer R. Grandis, a professor of otolaryngology and pharmacology and chemical biology at the University of Pittsburgh School of Medicine and a senior author of one of the Science papers, bemoaned the dearth of genetic information about head and neck cancer several years ago at a conference where Garraway had given a talk about the genomic landscape of melanoma.

“There was a really big gap in knowledge that was an obstacle to doing the right kind of research” about head and neck cancer, she said. “If we didn’t know the spectrum of the mutations that were in our patients’ tumors, we couldn’t begin to develop more appropriate therapies because we were sort of playing in the dark.”

Grandis and Garraway decided to study a University of Pittsburgh collection of 74 pairs of tumor and normal tissue samples using the Broad’s capacity to perform whole-exome sequencing. The exome represents the tiny fraction of the genome that encodes proteins. Focusing on just these protein-producing genes allows scientists to zero in on mutations that alter key proteins involved in cancer growth. Another collaboration was unfolding among the cancer geneticists, sequencing experts, clinical researchers, and surgical oncologists at Johns Hopkins, MD Anderson, and Baylor College of Medicine to study 32 pairs of head and neck tumor and normal tissue samples by whole-exome sequencing and validate the findings in an additional 88 samples.

Both teams found mutations in the p53 gene in a little more than half of the tumors they studied. The next most common mutation occurred in NOTCH1, which showed up in about 15 percent of tumors.

Normally, NOTCH1 controls how cells differentiate into other kinds of cells, mature, stop dividing, and ultimately die. In head and neck cancer, the scientists saw mutations that turn NOTCH1 off, blocking differentiation and trapping cells in a proliferative, pro-cancer state. Their maturation is arrested, leaving them stuck in an earlier stage, where other damage from smoking or alcohol or even p53 mutations can destabilize the genome.

NOTCH1’s inactivation in head and neck cancer was surprising because in other cancers, such as leukemia, too much NOTCH signaling leads to cancer.

“Our study suggests that a gene’s role can depend on the tumor type. In some cases, a gene can act as a growth promoter in cancer, and in other cases, such as head and neck cancer, the same gene behaves as a growth suppressor,” said Kinzler.

Efforts to combat the mutated p53 tumor suppressor gene with targeted drugs, for example, have so far been unsuccessful.

The next step based on these novel head and neck cancer discoveries, the scientists agree, is to tease out how the genes function in normal cells, whether they form the lining of the larynx, pharynx, or another anatomical site affected by head and neck cancer.

“Both of our studies reveal few clues to the significance of NOTCH mutations. Further studies will be necessary to define its role in prognosis, diagnosis, and/or treatment,” said Nishant Agrawal, a head and neck surgical oncologist at Johns Hopkins and a lead author of one of the Science papers. “The idea is to use these genetic alterations to predict a patient’s prognosis and define personalized treatment strategies tailored to their cancer’s genome.”

Both teams confirmed the role of HPV infection in head and neck cancer, particularly oropharyngeal cancer. Thought to be transmitted by oral sex, the infection has become more prominent. The studies reveal that HPV-positive tumors carried fewer mutations than HPV-negative tumors. Patients with HPV-positive head and neck cancers tend to fare better than patients whose cancers are not caused by the virus.

Translating these discoveries into therapies for patients will take more studies and more time, the scientists all said, but the revelations set a course for the future.

Jeffrey N. Myers, professor of head and neck surgery at M. D. Anderson, said both groups’ work highlights the complexity of the disease and its multiple gene abnormalities.

“It has told us new things that will give us both clinical and scientific opportunities to study in the near and long term,” Myers said. “I think that we’re also in a position to design very specific clinical studies to further understand the significance of these mutations, as well as to begin to think about potentially targeting some of the abnormalities.”

Those studies could include looking at patients with different mutations in addition to p53 and the NOTCH family to see how well they fare.

“The race will be on to figure out the function and particularly the therapeutically relevant function of these mutations,” Grandis said.

Agrawal said the collaborative effort is necessary.

“I think it’s great we are advancing head and neck cancer research this way,” he said. “Unfortunately, the cancer has been beating us. Now it’s time for us to take a permanent lead.”


The research reported by the Broad, Dana-Farber, and University of Pittsburgh group was supported by major funding from the Carlos Slim Health Institute as part of Project Sigma. The investigators also received funding for aspects of the work from the National Human Genome Research Institute, the National Cancer Institute, the Starr Cancer Consortium, the Novartis Institutes for BioMedical Research, and the American Cancer Society.

The research reported by the Johns Hopkins, MD Anderson, and Baylor group was funded by grants from the National Institutes of Health, the National Institute of Dental and Craniofacial Research, the Cancer Prevention Research Institute of Texas, the AACR Stand Up To Cancer-Dream Team Translational Cancer Research Grant, and the Virginia and D.K. Ludwig Fund for Cancer Research. Author disclosures related to royalty agreements may be found in the paper.

About the Broad Institute of Harvard and MIT

The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to

About the Dana-Farber Cancer Institute

Dana-Farber Cancer Institute ( is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women’s Hospital as Dana-Farber/Brigham and Women’s Cancer Center and it provides pediatric care with Children’s Hospital Boston as Dana-Farber/Children’s Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding.

About Johns Hopkins Kimmel Cancer Center

Since its opening in 1973, the Johns Hopkins Kimmel Cancer Center has led the world in deciphering the mechanisms of cancer and new ways to treat it. The strength of our research and treatment programs was recognized early on by the National Cancer Institute, becoming one of the first to earn comprehensive cancer center status and recognition as a “Center of Excellence.”

One of only 40 cancer centers in the country designated by the National Cancer Institute (NCI) as a Comprehensive Cancer Center, the Johns Hopkins Kimmel Cancer Center has active programs in clinical research, laboratory research, education, community outreach, and prevention and control. The Kimmel Cancer Center is the only Comprehensive Cancer Center in the state of Maryland.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.

About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine ( integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Prescription Drug Prices Will Soon Be More Affordable

Source: Stamford Advocate

The cost of prescription medicines used by millions of people every day is about to plummet.

The next 14 months will bring generic versions of seven of the world’s 20 best-selling drugs, including the top two: cholesterol fighter Lipitor and blood thinner Plavix.

The magnitude of this wave of expiring drugs patents is unprecedented. Between now and 2016, blockbusters with about $255 billion in global annual sales are set to go off patent, notes EvaluatePharma Ltd., a London research firm. Generic competition will decimate sales of the brand-name drugs and slash the cost to patients and companies that provide health benefits.

Top drugs getting generic competition by September 2012 are taken by millions every day: Lipitor alone is taken by about 4.3 million Americans and Plavix by 1.4 million. Generic versions of big-selling drugs for blood pressure, asthma, diabetes, depression, high triglycerides, HIV and bipolar disorder also are coming by then.

The flood of generics will continue for the next decade or so, as about 120 brand-name prescription drugs lose market exclusivity, according to prescription benefit manager Medco Health Solutions Inc.

“My estimation is at least 15 percent of the population is currently using one of the drugs whose patents will expire in 2011 or 2012,” says Joel Owerbach, chief pharmacy officer for Excellus Blue Cross Blue Shield, which serves most of upstate New York.

Those patients, along with businesses and taxpayers who help pay for prescription drugs through corporate and government prescription plans, collectively will save a small fortune. That’s because generic drugs typically cost 20 percent to 80 percent less than the brand names.

Doctors hope the lower prices will significantly reduce the number of people jeopardizing their health because they can’t afford medicines they need.

Dr. Nieca Goldberg, director of The Women’s Heart Program at NYU Langone Medical Center in Manhattan, worries about patients who are skipping checkups and halving pills to pare costs.

“You can pretty much tell by the numbers when I check the patient’s blood pressure or cholesterol levels,” that they’ve not taken their medications as often as prescribed, she says.

Even people with private insurance or Medicare aren’t filling all their prescriptions, studies show, particularly for cancer drugs with copays of hundreds of dollars or more.

The new generics will slice copayments of those with insurance. For the uninsured, who have been paying full price, the savings will be much bigger.

Daly Powers, 25, an uninsured student who works two part-time jobs at low wages, says he often can’t afford the $220 a month for his depression and attention deficit disorder pills. He couldn’t buy either drug in June and says he’s struggling with his Spanish class and his emotions. He looks forward to his antidepressant, Lexapro, going generic early next year.

“It’d make all the difference in the world,” says Powers, of Bryan, Texas.

Generic medicines are chemically equivalent to the original brand-name drugs and work just as well for nearly all patients.

When a drug loses patent protection, often only one generic version is on sale for the first six months, so the price falls a little bit initially. Then, several other generic makers typically jump in, driving prices down dramatically.

Last year, the average generic prescription cost $72, versus $198 for the average brand-name drug, according to consulting firm Wolters Kluwer Pharma Solutions. Those figures average all prescriptions, from short-term to 90-day ones.

Average copayments last year were $6 for generics, compared with $24 for brand-name drugs given preferred status by an insurer and $35 for nonpreferred brands, according to IMS Health.

Among the drugs that recently went off patent, Protonix, for severe heartburn, now costs just $16 a month for the generic, versus about $170 for the brand name. And of the top sellers that soon will have competition, Lipitor retails for about $150 a month, Plavix costs almost $200 a month and blood pressure drug Diovan costs about $125 a month. For those with drug coverage, their out-of-pocket costs for each of those drugs could drop below $10 a month.

Jo Kelly, a retired social worker in Conklin, Mich., and her husband Ray, a retired railroad mechanic, each take Lipitor and two other brand-name medicines, plus some generic drugs. Both are 67, and they land in the Medicare prescription “doughnut hole,” which means they must pay their drugs’ full cost, by late summer or early fall each year. That pushes their monthly cost for Lipitor to about $95 each, and their combined monthly prescription cost to nearly $1,100.

Generic Lipitor should hit pharmacies Nov. 30 and cost them around $10 each a month.

“It would be a tremendous help for us financially,” she says. “It would allow us to start going out to eat again.”

For people with no prescription coverage, the coming savings on some drugs could be much bigger. Many discount retailers and grocery chains sell the most popular generics for $5 a month or less to draw in shoppers.

The impact of the coming wave of generics will be widespread — and swift.

Insurers use systems that make sure patients are switched to a generic the first day it’s available. Many health plans require newly diagnosed patients to start out on generic medicines. And unless the doctor writes “brand only” on a prescription, if there’s a generic available, that’s almost always what the pharmacist dispenses.

“A blockbuster drug that goes off patent will lose 90 percent of its revenue within 24 months. I’ve seen it happen in 12 months,” says Ben Weintraub, a research director at Wolters Kluwer Pharma Solutions.

The looming revenue drop is changing the economics of the industry.

In the 1990s, big pharmaceutical companies were wildly successful at creating pills that millions of people take every day for common conditions, from heart disease and diabetes to osteoporosis and chronic pain. Double-digit quarterly profit increases became the norm.

But the patents on those blockbusters, which were filed years before the drugs went on sale, last for 20 years at most, and many expire soon.

In recent years, many drug companies have struggled to develop new blockbuster drugs, despite multibillion-dollar research budgets and more partnerships with scientists at universities and biotech companies. The dearth of successes, partly because the “easy” treatments have already been found, has turned the short-term prognosis for “big pharma” anemic.

“The profit dollars that companies used to reinvest in innovation are no longer going to be coming,” warns Terry Hisey, life sciences leader at consultant Deloitte LLP’s pharmaceutical consulting business. He says that raises “long-term concerns about the industry’s ability to bring new medicines to market.”

But pharmaceutical companies can save billions when they stop promoting drugs that have new generic rivals, and U.S. drug and biotech companies are still spending more than $65 billion a year on R&D.

The 20 new drug approvals in the U.S. this year, and other important ones expected in the next few years, eventually will help fill the revenue hole.

For now, brand-name drugmakers are scrambling to adjust for the billions in revenue that will soon be lost. Many raise prices 20 percent or more over the last couple years before generics hit to maximize revenue. Some contract with generic drugmakers for “authorized generics,” which give the brand-name company a portion of the generic sales.

Brand-name companies also are trimming research budgets, partnering with other companies to share drug development costs and shifting more manufacturing and patient testing to low-cost countries.

Pharmaceutical companies have cut about 10 percent of U.S. jobs in four years, from a peak of about 297,000 to about 268,000, according to Labor Department data. Nearly two-thirds of the cuts came in the last 1 1/2 years, partly because of big mergers that were driven by the need to shore up pipelines and boost profit in the short term by slashing overlap.

Drug companies also are trying to stabilize future sales by putting more sales reps in emerging markets such as China and India, and diversifying into businesses that get little or no generic competition. Those include vaccines, diagnostic tests, veterinary medicines and consumer health products.

As the proportion of prescriptions filled with generic drugs jumped to 78 percent in 2010, from 57 percent in 2004, annual increases in prescription drug spending slowed, to just 4 percent in 2010. According to the Generic Pharmaceutical Association, generics saved the U.S. health care system more than $824 billion from 2000 through 2009, and now save about $1 billion every three days.

The savings are only going to get greater as our overweight population ages. People who take their medicines regularly often avoid costly complications and hospitalizations, says AARP’s policy chief, John Rother, bringing the system even bigger savings than the cheaper drugs.

In addition, many patients taking a particular brand-name drug will defect when a slightly older rival in the same class goes generic.

Global sales of Lipitor peaked at $12.9 billion in 2006, the year Zocor, an older drug in the statin class that reduces bad cholesterol, went generic. Lipitor sales then declined slowly but steadily to about $10.7 billion last year. That still makes Lipitor the biggest drug to go generic.

For patients, it’s a godsend.

Douglas Torok, 59, of Erie, Pa., now spends nearly $290 every three months for insulin for his Type 2 diabetes, plus four daily pills, including Lipitor, Plavix and two generics, for his blood pressure and cholesterol problems. The $40,000-a-year foundry supervisor fears not being able to cover the out-of-pocket costs when he retires and doesn’t have a generous prescription plan.

In the meantime, once Lipitor and Plavix get generic competition his copayment will plunge from the current $1 per day for each.

“I will pay $16 for 90 days” for both, says Torok, who hopes to travel more. “It’s a big deal for me on my income.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

New Screening Program for Throat Cancer

Source: The Telegraph

Patients would swallow a pill on a string, that expands into a one-inch sponge at the bottom of the throat.

This is then draw slowly back up, gently scraping off cells from the wall of the oesophagus.

These are then tested for a condition known as Barrett’s oesophagus, which can develop into oesophagal cancer over time.

Oesophagal cancer is the sixth-most common type in Britain, killing 7,500 people a year.

It is often diagnosed when it has advanced, which means survival rates are low: just eight per cent live at least five years from diagnosis, compared to 82 per cent for breast cancer.

Researchers at Cambridge University, Cambridge University Hospitals NHS Foundation Trust and the Medical Research Centre are excited because the ‘cytosponge’ is both cheaper and less invasive than the current testing method, endoscopy.

In that, an ear nose and throat expert inserts a tiny camera down the throat to select and remove sample cells. It costs about £400 a time.

The team, supported by Cancer Research UK, is now hoping to recruit 1,400 volunteers to compare the accuracy of both methods.

Dr Rebecca Fitzgerald, who led the Cambridge-based team that developed the cytosponge test, said: “If this trial is successful it will provide a cheap, safe and highly effective method of identifying people with Barrett’s oesophagus, so they can take steps to reduce their risk of developing cancer.

“This would open the doors for a national screening programme, much like those offered for breast, cervical and bowel cancers, to help prevent oesophagal cancer among the one to two people in every 100 with Barrett’s oesophagus who go on to develop the disease.”

Persistent heartburn can be an early sign of Barrett’s oesophagus, which is where the cells lining the lower gullet come to resemble those in the small and large intestines, because of returning stomach acid.

Kate Law, director of clinical trials at Cancer Research UK, said: “Hopefully this trial will provide a simple means of screening people for Barrett’s oesophagus on a much larger scale.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Oral Cancer Prevention International alleges that thousands of cancers are likely to result from J&J’s actions to protect its sales of Listerine

Author: press release

A lawsuit was filed against Johnson & Johnson and its Consumer Products Companies in the United States District Court, District of New Jersey on behalf of Oral Cancer Prevention International, Inc. (OCPI). OCPI is the developer of OralCDx®, a patented, testing protocol that can prevent oral cancer by identifying precancerous (dysplastic) cells in the mouth while they are still harmless. OralCDx® testing can be performed by dentists in addition to otolaryngologists (ENT’s), family practitioners, dermatologists, and other physicians.

The complaint alleges that in order to protect sales of its mouthwash Listerine, which has been linked to oral cancer, Johnson & Johnson and its Consumer Products Companies intentionally interfered with a February 10, 2010 sales agreement between OCPI and OraPharma, Inc., a specialty oral healthcare company. OraPharma had agreed to obtain the exclusive sales rights for OralCDx® to US dentists.

According to Attorney James S. O’Brien, Jr. of Pryor Cashman LLP, who represents OCPI: “The effect of J&J’s behavior, based on OraPharma’s own projections, is that an estimated 7,300 cases of otherwise preventable oral cancer will occur in the United States over the term of the sales agreement.”

According to the National Cancer Institute, over 30,000 Americans are diagnosed with oral cancer each year. It kills approximately as many Americans as melanoma, twice as many as cervical cancer, and is now rapidly rising among women, young people, and non-smokers. In fact there has been a nearly five-fold increase in oral cancer incidence in patients under age 40, many with no known risk factors. The high mortality rate for oral cancer has not decreased over the past 50 years primarily because there was no accurate, painless test to detect oral pre-cancer and early oral cancer.

The complaint accuses J&J on three main counts: fraud, tortuous interference with contract, and civil conspiracy. While it seeks a minimum of $60 million, based on the written OralCDx sales projections provided by OraPharma to OCPI, the full scope of its compensatory damages for just the first half of the OraPharma sales agreement which J&J blocked are in excess of $400M.
“Our laboratory already has data on thousands of patients whose life was saved only because an OralCDx test was performed. It is an unspeakable tragedy that so many thousands of other patients will develop this devastating cancer as a result of a Company’s wrongful actions to defend their sales of a mouthwash,” said Mark Rutenberg, CEO of OCPI.

FDA approves REMS for Fentora, Actiq

Author: staff

FDA has approved the Risk Evaluation and Mitigation Strategy (REMS) for Fentora (fentanyl buccal tablet) [C-II] and Actiq (oral transmucosal fentanyl citrate) [C-II]. Both products, manufactured by Cephalon, are indicated for management of breakthrough pain in opioid-tolerant patients with cancer.

The goals of REMS are to ensure proper patient selection, to prevent accidental exposure and inappropriate conversion between fentanyl products, and to mitigate the potential risks of misuse, abuse, addiction, and overdose. The newly approved REMS will replace the existing risk management programs for Fentora and Actiq.

Under REMS, pharmacies and healthcare professionals who prescribe Fentora and Actiq will enroll by completing an education module and knowledge assessment focused on safety information that includes appropriate patient selection. Prescribers will also educate patients as part of the program. Cephalon expects that enrollment in the REMS program will begin in September.

“The (REMS) program provides education and systems to support safe use of Fentora and Actiq, preserving availability of the medicines to patients through retail pharmacies and using other systems already familiar to prescribers and pharmacists,” said Lesley Russell, MB,ChB, MRCP, Cephalon’s chief medical officer.

When implemented, the REMS will provide checks and balances within the distribution channel to provide safeguards that will help ensure that the medications are appropriately dispensing to qualifying patients. All stakeholders can enroll in the system any time beginning in September.

There will be a transition period of about 6 months following the launch of REMS after which no prescription may be dispensed, unless the prescriber and pharmacy are enrolled.

Cephalon will provide regular updates to FDA regarding the effectiveness of REMS. On the basis of these evaluations, Cephalon plans to open discussions with FDA about the company’s pending supplemental New Drug Application for Fentora as a treatment for opioid-tolerant patients with non-cancer breakthrough pain.

Are lozenges and other smokeless products safer alternatives to smoking?

Source: Pennsylvania’s Fox News

Tobacco company rep David Howard waxes enthusiastic when he talks about a new product his employer, R.J. Reynolds Tobacco Co., has developed: a pellet of finely cured tobacco, binders and flavoring that dissolves in the mouth in 10 minutes.

Under test market in two U.S. cities — Denver and Charlotte, N.C. — Camel Orbs will join two dissolvable tobacco lozenges already on the market if it graduates to broader distribution. And Howard is optimistic it will.

“These products provide smokers with an option to enjoy the pleasure of nicotine without bothering others,” Howard said. “No secondhand smoke. No spitting. No cigarette butt.”

Dissolvable tobacco consists of small pieces of compressed, finely ground tobacco powder, binders and flavorings that are shaped into pellets, sticks or strips. When placed in the mouth, they dissolve within minutes, providing a nicotine hit.

The tobacco industry says that the products contain far fewer cancer-causing chemicals such as tobacco-specific nitrosamines and are a “harm reduction” strategy that, like electronic cigarettes, might help people turn to less risky tobacco habits or eventually quit smoking.

But public health officials and anti-smoking advocates fear that the products will help initiate a new generation of smokers. The flavoring and packaging appeal to children, they argue, and teenagers will gravitate toward a product they can easily hide.

On Thursday, the Food and Drug Administration will take up the issue with an advisory committee hearing on the effect of dissolvable tobacco products on public health.

“Tobacco companies are always one step ahead of the sheriff,” said Sen. Sherrod Brown (D-Ohio), one of several senators who asked the FDA to review the products. “They have found ways to evade the rules and regulations and public health warnings.”

The first dissolvable tobacco product, a lozenge called Ariva, debuted in 2001. But in the last year the number of products on sale or in test marketing has jumped and major tobacco companies have entered the arena. Reynolds is market-testing two other products, Camel Strips and Camel Sticks, in addition to Camel Orbs. Philip Morris is test marketing a dissolvable tobacco stick.

At the same time, use of smokeless tobacco — snuff, chew, electronic cigarettes and, increasingly, dissolvable tobacco — is growing at a rate of about 7% per year, according to a 2010 report by Research and Markets, an international market research and data company.

In some states, use of smokeless tobacco products among men is almost as high as the national prevalence of cigarette smoking among adults, which stands at 20.8%, according to the Centers for Disease Control and Prevention. Across the U.S., 7% of U.S. adult males use smokeless tobacco, the CDC said.

Use among children is growing too. According to a 2010 survey by Monitoring the Future, an annual nationwide study funded by the National Institute on Drug Abuse, 8.5% of 12th-graders said they had used a smokeless tobacco product in the last 30 days compared with 6.7% in 2003.

“Because it has a mild taste, we’re concerned dissolvable tobacco will be a starter product for kids,” said Matthew Myers, president of the Washington-based anti-smoking group Campaign for Tobacco-Free Kids. “Traditionally, girls have not used smokeless tobacco products. But this product does not have a substantial smell or require spitting. There is a real concern that this product will appeal to adolescent girls, particularly those concerned about weight.”

Public health officials also have expressed concern about the effect on teeth and gums of holding the product in the mouth for 10 to 20 minutes and the effect on the stomach from swallowing the tobacco chemicals.

Few studies have been done specifically on the potential health risks of dissolvable tobacco.

One study, published in March in the Journal of Agricultural and Food Chemistry, tested four dissolvable tobacco products, three of which were being test-marketed, and found they contained mostly nicotine and a variety of flavorings, sweeteners and binders.

Some products contained coumarin, which has been banned as a flavoring agent in foods because of its link to liver damage, said study author John V. Goodpaster, an assistant professor in the forensic and investigative sciences program at Indiana University-Purdue University Indianapolis.

Studies on other smokeless tobacco products show they are considerably less risky than smoking cigarettes and cigars, which raises the risk of lung and a variety of other cancers, respiratory illness and heart disease. However, smokeless products still increase the risk of oral, pancreatic and esophageal cancer as well as heart disease. They can cause gum disease and can be unsafe for a fetus, health experts say.

The lowered risks of dissolvable products should be seen as a positive development, said Brad Rodu, a professor of medicine and chairman of tobacco harm reduction research at the University of Louisville in Kentucky.

“One cannot call any tobacco product absolutely safe,” said Rodu, who said he received funds from tobacco companies to do his research but had no personal ties to any company. “But the health risks of using smokeless tobacco products over the long term are so low that they are barely measurable by modern epidemiological evidence.”

Rodu added that smoking-cessation aids such as nicotine gum and the medication Chantix have limited success and that people who can’t quit should be urged to try safer products.

“We have 45 million smokers in the United States,” he said. “If we had almost any other activity in society that was this dangerous, we would welcome products that were safer.”

Sara Troy Machir, vice president of communications and investor relations at Star Scientific Inc., maker of Ariva and another dissolvable tobacco product called Stonewall, said the Glen Allen, Va.-based company is developing two new products, Ariva BDL and Stonewall BDL, with lower levels of tobacco-specific nitrosamines (BDL stands for “below detection limits”).

Machir said the company was founded with the mission of reducing harms associated with tobacco use and that “we have absolutely no interest in recruiting another generation of tobacco users.”

Star Scientific applied to the FDA last year for approval to market its two new products as “modified risk tobacco products.” To the chagrin of anti-smoking advocates, the FDA announced in March that the products were not subject to regulation under the 2009 Family Smoking Prevention and Tobacco Control Act, which gives the agency the authority to regulate tobacco products.

Twelve senators, including Brown, Jeff Merkley (D-Ore.) and Barbara A. Mikulski (D-Md.), have asked the FDA to reverse its decision.

In April, the FDA announced it was developing a strategy to regulate additional categories of tobacco products and that it would review information on dissolvable tobacco from published studies, manufacturers’ research and the advisory committee meeting this week. The agency is expected to eventually close any loopholes that might prevent dissolvable tobacco products from escaping its jurisdiction.

“It’s very clear dissolvable products are here to stay, and I believe the FDA will have to deal with them,” Rodu said.

Taking out a cancer’s co-dependency: novel compound selectively kills cancer cells by blocking response to oxidative stress

Author: public release

A cancer cell may seem out of control, growing wildly and breaking all the rules of orderly cell life and death. But amid the seeming chaos there is a balance between a cancer cell’s revved-up metabolism and skyrocketing levels of cellular stress. Just as a cancer cell depends on a hyperactive metabolism to fuel its rapid growth, it also depends on anti-oxidative enzymes to quench potentially toxic reactive oxygen species (ROS) generated by such high metabolic demand.

Scientists at the Broad Institute and Massachusetts General Hospital (MGH) have discovered a novel compound that blocks this response to oxidative stress selectively in cancer cells but spares normal cells, with an effectiveness that surpassed a chemotherapy drug currently used to treat breast cancer. Their findings, based on experiments in cell culture and in mice, appear online in Nature on July 13.

The plant-based compound piperlongumine (PL), derived from the fruit of a pepper plant found in southern India and southeast Asia, appears to kill cancer cells by jamming the machinery that dissipates high oxidative stress and the resulting ROS. Normal cells have low levels of ROS, in tune with their more modest metabolism, so they don’t need high levels of the anti-oxidant enzymes that PL stymies once they pass a certain threshold.

“Piperlongumine targets something that’s not thought to be essential in normal cells,” said Stuart L. Schreiber, a senior co-author and director of the Broad’s Chemical Biology Program. “Cancer cells have a greater dependence on ROS biology than normal cells.”

Sam W. Lee and Anna Mandinova, senior co-authors from the Cutaneous Biology Research Center (CBRC) at MGH, weren’t looking for a ROS inhibitor when they found PL. Their interest lay in the tumor suppressor gene p53, which is mutated in more than half of all cancer types. Teaming up with the Broad’s Chemical Biology Program and Platform to screen libraries of chemical compounds, they were looking for something that might increase levels of the properly functioning p53 gene.

When they saw a promising signal for PL, they assumed it worked by enhancing the p53 gene. But to their surprise, PL induced cancer cell death independent of the tumor suppressor gene’s activity. And when they tested PL in normal cells, the cells didn’t die.

“The novelty of this compound was that it was able to recognize cancer cells from normal cells,” said Mandinova, a Broad associate member and a faculty member at MGH and Harvard Medical School. “It has a mode of action that targets something especially important to the cancer cell.”

Their second surprise came after the Proteomics Platform’s quantitative analysis identified the target of PL. The researchers imagined that they might find a protein encoded by a cancer-causing gene was being inhibited in some way, but instead of an oncogene, they saw an indirect process on which cancer cells depend.

A small number of new cancer drugs target oncogenes directly, but this may not be the only promising new direction for treating cancers. Cancer genes do not act alone. PL exploits a dependency that develops after oncogenes transform normal cells into cancer cells.

“Our studies suggest that piperlongumine’s ROS-associated mechanism is especially relevant to the transformed cancer cell,” said co-author Andrew M. Stern, associate director of Novel Therapeutics at the Broad. “And this in part may underlie the observed selectivity of PL.”

The scientists tested PL against cancer cells and normal cells engineered to develop cancer. In mice injected with human bladder, breast, lung, or melanoma cancer cells, PL inhibited tumor growth but showed no toxicity in normal mice. In a tougher test of mice that developed breast cancer spontaneously, PL blocked both tumor growth and metastasis. In contrast, the chemotherapy drug paclitaxel (Taxol) was less effective, even at high levels.

“This compound is selectively reducing the enzyme activity involved in oxidative stress balance in cancer cells, so the ROS level can go up above the threshold for cell death,” said Lee, a Broad associate member and associate director of CBRC at MGH. “We hope we can use this compound as a starting point for the development of a drug so patients can benefit.”

While hopeful, the authors remain cautious. Much more work needs to be done to better understand how the ROS process differs between normal and cancer cells before clinical studies can even be launched. Further studies will focus on different forms of cancer and their genotypes, or genetic information.

“Our next set of goals is to learn if there are specific cancer genotypes that will be more sensitive to this compound than others,” said Alykhan F. Shamji, associate director of the Broad’s Chemical Biology Program. “We hope our experiments will help be predictive of whether patients with the same genotypes in their tumors would respond the same way. It would help us to pick the right patients.”

1. The research reported in Nature was funded by the National Cancer Institute and builds on work performed through the Initiative for Chemical Genetics and the Cancer Target Discovery and Development Network.

2. Paper cited: Raj L et al. Selective killing of cancer cells with a small molecule targeting stress response to ROS. Nature. Published online July 13, 2011. DOI: 10.1038/nature10167.

Head and Neck Cancer Study

Source: American Journal of Neuroradiology

BACKGROUND AND PURPOSE: Radiographic determination of viable disease in cervical adenopathy following RT for head and neck cancer can be challenging. The purpose of this study was to evaluate the utility of US, with or without FNA, in regard to the postradiotherapy effects on documented metastatic adenopathy in patients with oropharyngeal cancer.

MATERIALS AND METHODS: This study included 133 patients with node-positive oropharyngeal cancer who were irradiated from 1998 to 2004. Sonographic evaluation was performed within 6 months of completion of radiation. Posttreatment US results were compared with pretreatment CT images and were recorded as the following: progression, suspicious, indeterminate, posttreatment change, or regression (positive) versus nonsuspicious or benign (negative). FNAC was classified as nondiagnostic, negative, indeterminate, or positive. Results of US and US-guided FNAC were correlated with findings at neck dissection and disease outcome.

RESULTS: Of 203 sonographic examinations, 90% were technically feasible and yielded a nonequivocal imaging diagnosis. Of 87 US-guided FNAs, 71% yielded a nonequivocal tissue diagnosis. The PPV and NPV of initial posttreatment US were 11% and 97%. Sensitivity and specificity were 92% and 28%. The PPV and NPV of US-guided FNA were 33% and 95%, and the sensitivity and specificity were 75% and 74%. On serial sonographic surveillance, of 33 patients with nonsuspicious findings, only 1 (3%) had neck recurrence. Of 22 patients with questionable findings on CT and negative findings on US, none had a neck recurrence.

CONCLUSIONS: In experienced hands, serial US is an inexpensive noninvasive reassuring follow-up strategy after definitive head and neck RT, even when CT findings are equivocal.

Abbreviations: FNA, fine-needle aspiration • FNAC, fine-needle aspiration cytology • late recur, late recurrence, >6 months later • NOS, not otherwise specified • NPV, negative predictive value • MDACC, M.D. Anderson Cancer Center • PET, positron-emission tomography • PPV, positive predictive value • RT, radiation therapy • US, ultrasonography