Oral gel contains cancer-preventing compounds derived from black raspberries

Author: Maria Perno Goldie, RDH, MS, with the assistance of Allison Walker

Maria Perno Goldie (MPG): I had the opportunity to interview Dr. Susan Mallery, who is a humble as she is intelligent. I had the assistance of Allison Walker, a freelance journalist who has been involved in dental publishing for more than 20 years.

Dr. Susan Mallery (SM) is a Professor in the Division of Oral Surgery, Oral Pathology, and Anesthesiology at The Ohio State University, College of Dentistry, in Columbus, Ohio. Her research interests include oral cancer initiation, AIDS-related oral cancer and chemoprevention. Dr. Mallery has published articles in journals such as Cancer Research, Cancer Prevention Research, Molecular Pharmaceutics, Carcinogenesis and Clinical Cancer Research, to name a few.

She graduated from The Ohio State University with her DDS and later returned to receive her oral pathology specialty training and a PhD in Pathology. Dr. Mallery is licensed by the Ohio State Dental Board and board certified by the American Board of Oral Pathology and American Academy of Oral Pathology. She belongs to the American Academy of Oral Pathology, American Board of Oral Pathology, American Association for Cancer Research, and is a Fellow of the American Association for the Advancement of Science. She is a consultant at The Ohio State University and James Cancer hospitals.

MPG: Oral squamous cell carcinoma (OSCC) will be diagnosed in more than 36,000 Americans this year and has a particularly high mortality rate—as it will kill approximately 8,000 patients this year. As excisional surgery is the primary treatment for OSCC—even those patients who are cured suffer loss of tissues critical for esthetics, speech and eating. Due to OSCC’s high rates of morbidity and mortality and its high socio-economic impact, a strategy to prevent progression of precancerous oral lesions to OSCC is more appealing.

Currently, precancerous oral lesions are surgically removed—with either a blade or laser—and the tissues evaluated microscopically. Discouragingly, approximately 30% of lesions that are completely removed as confirmed by microscopic evaluation recur and some progress to OSCC. Dr. Mallery has dedicated her nearly 30-year career to studying new strategies to preventing oral cancer. Her research has been supported by funding from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and The Ohio State University (OSU) Center for Clinical and Translational Science. It is also funded by the Fanconi Anemia Research Fund, a grassroots organization whose mission is to find effective treatments and a cure for Fanconi anemia and to provide education and support services to affected families worldwide. Dr. Mallery stresses that she is a part of a team, and that the research is truly a team effort.

Fanconi anemia (FA) is one of the inherited anemias that leads to bone marrow failure (aplastic anemia). It is a recessive disorder: if both parents carry a defect (mutation) in the same FA gene, each of their children has a 25% chance of inheriting the defective gene from both parents. When this happens, the child will have FA. Fanconi anemia patients have an extremely high risk of developing squamous cell cancers in areas of the body in which cells normally reproduce rapidly, such as the oral cavity, esophagus, the gastrointestinal tract, the anus, and the vulva. FA patients may develop these cancers at a much earlier age than people without Fanconi anemia.

Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problems associated with FA, still must have regular examinations to watch for signs of cancer. Head and neck squamous cell carcinoma (HNSCC) is a significant threat for people with FA, regardless of bone marrow transplantation status. Not only is the incidence of HNSCC considerably higher than in the general population (500-700 times higher), patients with FA present with these types of cancers at a younger age than those without FA – the median age is 27 years. Regular screenings are critically important.

MPG: Dr. Mallery, you have been investigating a number of agents to identify new therapeutics that can suppress the conversion of pre-cancerous to cancerous cells (chemoprevention), in particular, anthocyanins. Can you explain this to us?

SM: Chemoprevention is a way to prevent or delay the development of cancer by taking medicines, vitamins, or other agents. My colleagues and I are using a bimodal approach. Our first breakthrough was the creation of an oral gel containing high concentrations of anthocyanins, powerful cancer-preventing compounds found in black raspberries. Study results showed that the gel, when applied to the mouth, selectively removed atypical epithelial cells for the population through either preprogrammed cell death (apoptosis) or causing terminal differentiation (making the protective keratin covering).

MPG: Can you explain the mechanism of action of these anthocyanins?

SM: As briefly mentioned above, anthocyanins—and likely other black raspberry (BRB) compounds—are capable of modulating epithelial cell growth by affecting intracellular signaling and gene expression. Also apparent from our pilot study was that some patients derived more benefit from gel application. These inter-patient differences prompted a later study to help identify the cause.

Analyses of saliva samples collected after BRB rinses were conducted to assess local pharmacokinetics and compare the capacities of three different BRB rinse formulations to provide sustained intraoral levels of anthocyanins. Not surprisingly, these studies showed that BRB metabolism was affected by three intraoral enzymatic components, i.e. (1) oral tissues, (2) saliva, and (3) oral bacteria (“microflora”).

As all three components affected BRB bioactivation and local retention, it is likely inter-patient differences in these three areas that contribute in large part to BRB gel responsiveness. We are currently conducting the logical extension study of the pilot trial, which entails inclusion of a gel-placebo and multicenter testing. Results to date have confirmed therapeutic efficacy is limited to the BRB gel formulation and not the placebo. More complex analyses—which assess the gel’s effect at the molecular level—are ongoing.

One of the largest challenges with oral cancer chemoprevention is to develop an effective, yet nontoxic strategy. Efficacy speaks for itself—the need for nontoxic is tied to the fact that many to most of these treatments will be necessary for the life of the patient. The lifelong need is tied to the fact that persons who develop precancerous oral lesions have genetic mutations in the cells that are key for future epithelial generations, i.e., epithelial stem cells. When stem cells divide (which is not very often), they make perfect copies of themselves. Consequently, if the stem cells are mutated, their daughter cells faithfully carry forward this mutation. Our BRB gel data imply that locally applied black raspberry constituents can re-direct appropriate epithelial cell growth by removing mutated cells from the overall cell population. Consistent with a food-based approach, no systemic or local toxicities occurred.

Local delivery allows for better therapeutic concentration at the site with fewer systemic side effects. With oral cancer chemoprevention given systemically, the liver, in first-pass metabolism, makes the agent less active than the parent compound. The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption that is generally related to the liver and gut wall. We must have a compliant patient population with local delivery, it is vital. In some cases the decision involves having multiple biopsies or applying a gel a number of times per day. Not having frequent biopsies can be a good motivator.

MPG: Dr. Mallery, you have been investigating alternatives to the surgical removal of pre-cancerous oral lesions. Can you explain what you have found in this area?

SM: We have turned our attention to identifying alternatives to the surgical removal of pre-cancerous lesions. However, we are not “there” yet. Close clinical follow up is critical. If we suspect a malignant lesion, we must first biopsy, and if it is an active lesion, place the gel to prevent recurrence.

MPG: Dr. Mallery went on to tell a story about her passion and her work in one of the studies. She related that one third of the patients in the pilot trial were “super” responders, lesions resolved clinically and histologically, and biochemical and molecular markers returned to normal after treatment. There was an intermediate group of about one third, and the last third did not respond in either a negative or positive way. The researchers wanted to determine what caused the “super” responders to react as they did. The study was done with normal, healthy people, and it was found that there is a large difference in variability in enzyme levels to recycle the product. Best responders bioactivate the product and keep it in place for a long time. Enzyme profiles are being done.

SM: Because BRB components alone are insufficient to regress some patients’ precancerous oral lesions, we have decided to introduce a second chemopreventive, the synthetic vitamin A compound, fenretinide. Fenretinide is a “bench” chemopreventive star capable of causing either differentiation or apoptosis in transformed epithelial cells. Previous fenretinide oral cancer chemoprevention trials, which relied on systemic fenretinide delivery, were unsuccessful. Although none of these studies assessed drug levels at the target site, the pill-based delivery format could not even achieve treatment-relevant blood levels. Furthermore, large systemic doses of fenretinide resulted in toxicities including night blindness and changes in blood lipid profiles.

The objective of this study was to enhance oral mucosal permeation of fenretinide by co-incorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Co-incorporation PG or menthol in fenretinide/Eudragit RL PO patches led to significant ex vivo fenretinide permeation enhancement. Addition of PG above 2.5 wt% in the patch resulted in significant cellular swelling in the buccal mucosal tissues. These alterations were ameliorated by combining both enhancers and reducing the PG level.

After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa was greater relative to permeation obtained from the enhancer-free patch. In vitro and in vivo release of fenretinide from the patch was not significantly increased by co-incorporation of permeation enhancers, indicating that mass transfer across the tissue, and not the patch, largely determined the permeation rate control in vivo. As a result of its improved permeation and its lack of deleterious local effects, the mucoadhesive fenretinide patch co-incorporated with 2.5 wt% PG + 5 wt% menthol represents an important step in the further preclinical evaluation of oral site-specific chemoprevention strategies with fenretinide.

Fenretinide was studied in pill form, where there was more drug in the blood versus at the site. There were also toxicity problems. My team and I always thought that fenretinide would be a good drug if delivered in a different manner.

I worked with Peter Larsen, DDS, Chair of Division, Oral Maxillofacial Surgeon, Gary Stoner, PhD, and Kashappa Goud Desai, PhD, in both trials. Steven P. Schwendeman, PhD, is a pharmaceutical chemist, Professor and Chair Department of Pharmaceutical Sciences, College of Pharmacy, at the University of Michigan. His lab developed the fenretinide patch with Kashappa-Goud Desai, PhD. Fenretinide is lipophillic, and they needed the formulation to be stable, for the patch to stick on the site, deliver drug, and allow the drug to penetrate in an aqueous environment into keratinized tissue. It is great science! These two researchers are involved with patent application for the fenretinide patch, to be placed on active or recently excised lesions.

A combination approach with these two chemotherapeutics may someday be achieved and they may be complementary or synergistic. They have different mechanisms of action and if delivered at the same time could be antagonistic. The dosing must be staggered, with initial application, and perhaps 12 hours later, delivery of the next drug. When the patch is applied to lesions, pharmacokinetic studies show no drug in the saliva. The hypothesis is for targeted delivery and uptake of fenretinide, followed by field coverage with the raspberry rinse. A published study stated that the objective was to develop fenretinide oral mucoadhesive patch formulations and to evaluate their in vitro and in vivo release performance for future site-specific chemoprevention of oral cancer. The gel was used topically at the site of the lesion or after excision.

Our goal is to create complementary oral cancer chemoprevention strategies that would permit targeted delivery directly to visible lesions as well as address the need for field coverage throughout the mouth. My colleagues and I are optimistic that optimized delivery formulations and dosing schedules for BRB and fenretinide will help make appreciable clinical progress. We aim to prevent cancerization, which is transformation of cells into cancer, or from a normal to a cancerous state.

The concept is that being exposed to toxins and metabolic enzymes can activate toxins and cause the mutated cells to become active. There is now a multi-centered NCI trial of the raspberry product in patients, based on the pilot study. There are two manuscripts, one published and one pharmacokinetic study in rabbits ready to be published. The patch is considered a device by the FDA and they must apply as an Investigational New Device (IND). It is a very safe drug.

MPG: Dr. Mallery, what is your advice about prevention of oral cancers?

SM: I recommend not using tobacco in any form, using alcohol in moderation, visiting an oral healthcare provider at least every six months, practicing good oral hygiene, living a healthy lifestyle, having good nutrition, and providing immunization against the human papillomavirus (HPV) for sons and daughters. Precancerous lesions (oral dysplasia) tend to be on the floor of mouth, lateral border of the tongue, etc. The raspberry gel is sticky, and we are trying to get the adherent patch dosage as a “burst delivery” every 15 minutes. Patients are told not to eat or drink for 30 minutes, and the patch is designed for use multiple times throughout the day. It will be a prescription agent. Research has been conducted in Dr. Schwendeman’s lab on oral cancer patients with polyglycolic acid and polylactic acid implants (properties similar to resorbable sutures) that can deliver drug in the former cancer site. We know our patient population, they may not apply something four times a day. Polymeric implants for cancer chemotherapy may be one of the answers.

MPG: I want to thank Dr. Mallery for her time and expertise. I also wish to thank Allison Walker for her assistance with this interview.

March, 2012|Oral Cancer News|

Video: What You Need to Know About Oral Cancer: Surgical Management of Oral Cancer


March, 2012|Oral Cancer News|

Erlotinib dose doubled for smokers with head/neck cancer

Author: Miriam E. Tucker

Giving smokers a higher, short-course dose of erlotinib before definitive surgery for squamous cell carcinoma of the head and neck resulted in favorable responses for the first patients evaluated in a small pilot study.

Investigators gave 300 mg of erlotinib (Tarceva) to smokers daily and 150 mg daily to nonsmokers who had a waiting period of more than 14 days before scheduled surgery for head and neck cancer. Seven of the 10 patients evaluated so far had partial responses and 3 had stable disease, according to a poster presented at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology. The study was based on recent data in non–small cell lung cancer

(NSCLC) patients showing that smokers metabolize erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, twice as quickly as do nonsmokers (J. Clin. Oncol. 2009;27:1220-6), said lead author Dr. Mercedes Porosnicu of Wake Forest Baptist Medical Center in Winston Salem, N.C. That study established the maximum tolerated dose of erlotinib at 300 mg daily in NSCLC patients who smoke.

Dr. Poroniscu’s presentation included the case study of a smoker with a very large oral cavity tumor protruding through his lips. He was described as being in significant pain and unable to eat or chew. The first CT scan showed a tumor of at least 8 cm and there was “significant metabolic activity” on PET scan.

“At 6 days of erlotinib treatment, his tumor was obviously smaller and he could chew, eat, and talk. Metabolic activity on PET scan dropped to 44% compared to initial tumor metabolic activity,” Dr. Porosnicu said. “At the end of 14 days’ treatment, his tumor was at least 20% smaller, and he had gained 5 pounds. His surgery wasn’t delayed, and the only treatment-related toxicity was a minimal skin rash.”

A total of 12 patients have been treated to date, for an average of 18.2 days, she reported. Nine were smokers and three were nonsmokers. All patients, smokers and nonsmokers, tolerated the erlotinib dose well with no serious adverse events and no delays in the scheduled time of surgical intervention. There were no grade 3 or 4 toxicities.

Of 10 evaluable patients (including 8 smokers who received 300 mg), 7 (including 5 smokers) showed a partial response, as defined by at least a 20% reduction in maximum tumor diameter. The other three patients (all smokers) showed stable disease. Two of the 12 treated patients received shorter duration treatment but nonetheless displayed good responses.

January, 2012|Oral Cancer News|

What accounts for racial differences in head/neck cancer?

Author: DrBicuspid Staff

Why are African-Americans more likely than Caucasians not only to be diagnosed with head and neck cancer, but also to die from the disease? While the answer isn’t a simple one, differences in lifestyle, access to care, and tumor genetics may be partly to blame, according to a new study from Henry Ford Hospital.

The study, which was presented September 14 at the American Academy of Otolaryngology – Head and Neck Surgery Foundation’s annual meeting in San Francisco, also found that African-Americans are more likely to be past or current smokers, one of the primary risk factors for head and neck cancer.

“We’re really trying to understand why African-Americans with head and neck squamous cell carcinoma do so poorly,” said lead author Maria Worsham, PhD, director of research in the department of Otolaryngology – Head and Neck Surgery at Henry Ford, in a news release. “Using a comprehensive set of risk factors that are known to have some bearing on the disease, we’re able to gain a better understanding of what contributes to racial differences and work to help improve patient care.”

This year alone, it’s estimated that 52,140 new cases of head and neck cancer will be diagnosed, and roughly 11,460 will die in 2011 from oral cavity and pharyngeal and laryngeal cancers, she and her team members noted.

African-Americans are more likely to be diagnosed with late-stage head and neck squamous cell carcinoma (HNSCC) and have a worse five-year survival rate than Caucasians. It’s unknown whether significant biological rather than socioeconomic differences account for some of the disparities in outcomes.

To get at the root of these differences, Worsham and her team used a large Detroit multiethnic group of 673 patients with HNSCC. Most notably, 42% of the study group was African-American.

The researchers took a broad approach to the study, examining many of the intertwined variables influencing health and disease to look for differences among African-Americans and Caucasians. In all, the study focused on 136 risk factors, including demographics (age, race, gender), smoking and alcohol use, access to care, and type of cancer treatment (radiation and/or surgery). Tumor characteristics, including stage, biology, and genetics, also were examined.

Among the study findings:

  • While 88% of African-Americans in the study had medical insurance, the majority had Medicare or Medicaid instead of private health insurance.
  • African-Americans also were more likely to be unmarried or living alone, both of which previous studies suggest have a negative impact on quality of life and survival.
  • In terms of cancer treatment, African-Americans in this study were more than two times more likely than Caucasians to receive radiation therapy. The study showed fewer African-Americans (43%) opted for surgery than Caucasians (49%).
  • African-American tumors were six to seven times more likely to present with lymphocytic response.
  • Compared to Caucasian tumors, African-American tumors were almost two times more likely to have loss of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and gain of the small inducible cytokine A3 (SCYA3) gene. CDKN2A is important to cell cycle regulation, and the SCYA3 gene product has dual roles of tumor lymph node metastasis and local host defense against tumors in HNSCC.
September, 2011|Oral Cancer News|

Aerosmith’s Bassist is Treated for Tongue Cancer with Laser Surgery


Aerosmith will be performing in Mexico and South America this fall and one of the band members will be along for the tour thanks to a radical medical procedure. In one Aerosmith song, bassist Tom Hamilton sends a message to his throat and tongue cancer with the lyrics “you’ve got no business with me.”

Five years ago, Hamilton underwent chemotherapy and radiation for tongue-base cancer, but it came back and extended into his voice box. That is when he turned to Dr. Steven Zeitels. “This is not your classic way, or even traditional way, to try and remove a cancer from the tongue base,” Zeitels said.

Radical surgery was now Hamilton’s only option. But that could leave his voice and breathing passage permanently damaged.

“I was just terrified,” Hamilton said. “I really though, ‘Oh, I am looking at not being able to talk.'”

Zeitels has treated vocal cord cancer with the green-light KTP laser, so Hamilton agreed to be the first person treated that way for tongue base cancer.

The laser emits a green light, which is concentrated in the extra blood running through the cancer.

“Where there is a lot of cancer, there will be a lot of blood,” Zeitels said. “Where there is a lot of blood, there will be a lot of combustion so that you are actually watching the tissues burn completely different”

But not everyone is a candidate for this surgery.

“The second I had a tiny bit of consciousness, the first thing I did was make a sound, and it felt normal, and it sounded normal.” Hamilton said.

A major advantage of the laser is that it can be done repeatedly as new benign or malignant lesions are found.

In this case the patient feels the doctor saved his voice and his life.

Hamilton will be hitting the road this fall as part of the ‘Aero Force One’ tour to Mexico, South America and Japan.

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

August, 2011|Oral Cancer News|

Michael Douglas Continues to Put Oral Cancer in the Spotlight


Actor Michael Douglas’ recent revelation that he had stage IV oropharyngeal cancer has highlighted the growing incidence of oral cancer, and experts say dentists can help stem the alarming increase of the disease by checking for it during routine examinations.

The actor’s cancer included a walnut-sized tumor at the base of his tongue,  requiring radiation therapy, chemotherapy, and surgery. Douglas says his doctors told him he had an 80% survival rate if it hadn’t spread to his lymph nodes.

While tobacco was the prime cause of oral cancer in the past, recent studies have attributed the steady increase of the disease to the human papillomavirus (HPV16). There are approximately 130 versions of HPV but only nine cause cancers, and the HPV16 version causes almost half of the oral cancers in the U.S., said Brian Hill, executive director of the Oral Cancer Foundation.

“Tobacco is no longer the only bad guy,” he told “HPV16 is increasing in incidence as the causative etiology, and if it continues on this trend line, it will replace tobacco as the primary cause of oral cancers.”

Dentists can play a key role in catching the disease in its early stages if they check for it during examinations, Hill pointed out. “But many dentists think it’s such a rare disease that they don’t bother to screen for it,” he said. “Most Americans have never even heard of oral cancer, but it’s not as rare or uncommon as people would like to think it is. This is why an opportunistic screening by the dental community is so important.”

Hill, a nonsmoker, got the same diagnosis as Douglas in 1998 and underwent radiation therapy, chemotherapy, and surgery. Since Hill’s oral cancer had metastasized to both sides of his neck by the time it was discovered, surgeons removed the right side of his neck to remove the lymph nodes there. He has been cancer-free for 10 years and said there are a lot of stage IV survivors out there.

“I’m on this side of the grass and that’s all that’s important,” he said, adding with a laugh, “I’m not pretty, but I’m still here.”

Changing demographics

In the last decade, the demographics of oral cancer have changed dramatically, according to Hill and other experts, pointing to the sexual revolution and accompanying increase in the prevalence of oral sex. Today almost half of those diagnosed with the disease are younger than 50 years old — with some as young as 20, according to Hill — and they are usually nonsmokers. According to the American Cancer Society, oral cancer occurs almost as frequently as leukemia and claims more lives than melanoma or cervical cancer. The incidence in oral cancer patients younger than age 40 has increased nearly fivefold, with many patients with no known risk factors, according to the ADA.

“Social and sexual behaviors have changed,” Hill said. “Oral sex is more common. The virus is spreading, especially among young people because sexual contact is more common, and this virus is not only ubiquitous in our society, but the mechanism of transfer is very simple.”

Until 2000, scientists were unsure if HPV caused oral cancer, Hill said, but definitive research in 2000 revealed it as a distinct etiology for the disease, and more recent studies have supported this finding.

The disease is dangerous because often there are no symptoms in the early stages that a person might notice. “It’s a very insidious disease,” Hill explained. He recalled that it was not until a lymph node became swollen that Hill realized something was wrong. Even then, it was not painful, he said.

But an alert dentist will notice subtle signs and symptoms in a simple three to five minute visual and tactile exam, Hill noted. “There will be things he’ll pick up on, and that’s why we’re urging that the dental community to become more involved in oral cancer screening,” he said.

Approximately 37,000 new cases of oral cancer are diagnosed each year in the U.S., according to OCF, and some 43% of those people will die of the disease. Only 57% of all diagnosed oral cancer patients (considering all stages at time of discovery) will be alive five years after their diagnosis, Hill said. Approximately 100 people in the U.S. will be diagnosed with oral cancer every day, he added, and one person will die every hour from it.

And when celebrities get oral cancer, it helps bring about much needed public awareness about the disease, said Hill, noting that, in addition to Michael Douglas, such luminaries as Sigmund Freud, Babe Ruth, Beatle George Harrison, and Ulysses S. Grant have been among its victims.

“When somebody famous gets the disease, it finally gets the world’s attention,” he noted.

Oral cancer screening tips

According to the Oral Cancer Foundation, an oral cancer screening includes a systematic visual examination of all the soft tissues of the mouth, including manual extension of the tongue to examine its base, a bimanual palpation of the floor of the mouth, and a digital examination of the borders of the tongue, and a tactile examination of the lymph nodes surrounding the oral cavity and in the neck.

“Any sore, discoloration, induration, prominent tissue, irritation, or hoarseness that does not resolve within a two-week period on its own, with or without treatment, should be considered suspect and worthy of further examination or referral,” the foundation’s website states.

The website also offers a more complete oral cancer screening protocol and a photo gallery showing various forms oral cancer can take. It can be accessed at

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

Matthew Algeo’s ‘The President is a Sick Man’ vindicates an old story, and its reporter

Author: teve Weinberg

Stephen Grover Cleveland, born in 1837, would become one of the most unusual U.S. presidents, in multiple ways. Living in the east, he planned to make his way to the boomtown of Cleveland, in 1854, seeking riches. His prospects looked good, given the influence of his distant relative, Moses Cleaveland, often credited with founding the city.

The young man never made it past Buffalo, N.Y., however, where an uncle made him an employment offer. The rest of his life, Grover Cleveland (he dropped Stephen in favor of his middle name) would be bound up in New York state politics, except when he spent two nonconsecutive terms in the White House, 1885-1889 and 1893-1897.

Matthew Algeo, a historian and radio journalist, focuses on a dramatic, little-known event in his new book, “The President Is a Sick Man.” Algeo, a strong writer, nevertheless saddles his work with a ponderous subtitle “Wherein the Supposedly Virtuous Grover Cleveland Survives a Secret Surgery at Sea and Vilifies the Courageous Newspaperman Who Dared Expose the Truth.”

Suffering from mouth cancer in 1893, Cleveland disappeared to undergo surgery on the yacht of a friend. The president, his doctors and political advisers feared that news might exacerbate a financial recession and trigger panic.

Cleveland’s popular wife, Frances, young enough to be his daughter, lied to journalists about the president’s whereabouts. Cleveland’s press aide lied, too. Reporters accepted the falsehoods, misleading the citizenry into believing the nation’s leader vanished for five days to undergo dental work — painful, to be sure, but rarely fatal.

The truth did not begin to leak until about two months later. E.J. Edwards broke the story in The Philadelphia Press, only to be vilified as a spinner of falsehoods by a rival Philadelphia newspaperman, Alexander McClure of The Philadelphia Times, who convinced a lot of readers that President Cleveland had been treated shabbily.

Proud of his reporting and his skepticism, Edwards felt stung.

In this fascinating, rarely acknowledged saga, Edwards’ reputation would not be restored until 1917, when W.W. Keen, one of the physicians aboard the yacht, decided to set history straight. He wrote a compelling, credible account in the widely circulated Saturday Evening Post magazine. As Algeo notes, Edwards was able to bask in the glow of vindication for seven years, until his death during 1924.

Cleveland had emphasized truth-telling during his presidencies, so the secrecy and unfair attacks on Edwards sullied the president’s reputation. Algeo is a first-rate researcher and offers readers context aplenty, perhaps none so relevant today as the perception of cancer in the celebrity political realm.

“The public’s perception of cancer has changed dramatically since 1893,” Algeo notes. “No longer is the word itself avoided in polite company. Nor is cancer considered an automatic death sentence. But the disease has not been conquered, and in some ways it remains the same ‘dread and mysterious enemy’ that E.J. Edwards wrote of in his story about the secret operation on Grover Cleveland.”

1. Steve Weinberg is a biographer and a member of the National Book Critics Circle. He lives in Columbia, Mo.

Certain head and neck cancer patients benefit from second round of treatment

Author: press release

A new study has determined predictors that can better identify patients who will benefit from a potentially toxic second course of treatment, which offers a small but real chance of cure in select patients with head and neck cancer. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the findings could help guide treatment decisions for head and neck cancer patients.

Radiation is often used to treat patients with head and neck cancer. If their cancer reappears, they have limited treatment choices: chemotherapy is not curative, and surgery can be curative but is often not possible. Chemotherapy and a second course of radiation have previously been shown to be another option. Joseph Salama, MD, formerly of the University of Chicago, and his colleagues conducted an analysis of prior studies to determine how patients tolerate this second round of treatment and which patients benefit the most from it.

The investigators analyzed data from 166 patients with head and neck cancer who received a first round of radiation followed by a second round plus chemotherapy because their cancer recurred or they developed a new tumor. The second course of treatment could cure approximately 25 percent of patients at two years, but it was quite toxic. (Some patients lost the ability to speak or swallow. In addition, approximately 20 percent of patients died from treatment-related complications.)

Certain patients benefited from the treatment over others. Those who were cancer-free for a longer period of time, did not have chemotherapy with their first course of radiation, were treated with a higher dose of radiation in the second round, and had surgery prior to the second course of radiation were more likely to be cured at two years than those who had none or only one of these features. “These can help doctors determine which patients are best suited for a second course of radiation with chemotherapy for head and neck cancer,” said Dr. Salama.

The authors concluded that for patients with recurrent head and neck cancer in a previously irradiated area, concomitant chemotherapy with reirradiation is a treatment option that offers a small but real chance of cure in select patients; however, due to the risk of severe toxicity, the treatment should be limited to investigational studies and experienced medical centers.

Targeting Cancer Treatment

Source: Medical News Today

Cancer treatment is depending more and more today on specific factors of a patient’s tumor, including gene mutations, or proteins that are commonly typical of certain cancer cells, rather than focusing on where in the body the cancer started. Before, treatment was based on finding where in the body the cancer originated, such as the breast or lung.

Targeted therapy is all about the cancer’s genes, tissue environment that contributes the tumor’s growth and survival, and its proteins. Nowadays, cancer therapy is designed to interfere with a signal that tells the cancer cells not to die or tells it to divide, while before, chemotherapies had the goal of interfering with cancer cells as division was already underway, when the cells were dividing into new ones.

The human body is made of various types of cells, including skin cells, brain cells, or blood cells. Each one has a specific function.

Cancer occurs when healthy cells change and start growing out of control; they eventually form a tumor – a mass. A benign tumor is noncancerous, whereas a malignant one is cancerous, it can spread to other parts of the body.
Cancer cells either divide too quickly or do not die when they should do
Specific genetic mutations within a cell change the way it behaves.

When the genes that control cell division mutate (change), they can multiply too quickly; the cell has become cancerous.
Cells are genetically programmed to die, when the specific genes that tell the cell to die mutate, and the cell does not die, it has become a cancerous cell.

Put simply, cancerous cells either divide too rapidly or do not die when they should, in both cases because their genes have changed.

Researchers study cancer cells and how they respond to their environment; by doing this they are finding that particular gene mutations are linked to the development of certain cancers. They are then able to develop medications that modify the alterations that had occurred in the cancer cell to stop the erroneous instructions of either dividing too fast or not dying – the effect can be to destroy the tumor, or at least to slow down its progression.

One example is a type of breast cancer that has too much HER2 (human epidermal growth factor receptor 2), a type of protein. The drug Herceptin (trastuzumab) blocks HER2. 25% of breast cancers are of this type. Herceptin only works for this specific type of breast cancer.

A tumor is part of a network of blood vessels, lymph and tissues. Without this network the tumor would not exist. Cancer spreads when a bit breaks off from the tumor and travels through the bloodstream or lymph system. Blood vessels nearby help feed the growing tumor.

Targeting the new blood vessel growth around a tumor is an effective way of treating some cancers. The process of growing new blood cells is known as angiogenesis. Bevacizumab (Avastin), sunitinib (Sutent), sorafenib (Nexavar), lenalidomide (Revlimid), and thalidomide (Thalomid) are drugs that interfere with angiogenesis – they stop blood vessels being formed and growing around the tumor.

Targeted therapies can be classified as:

Monoclonal antibodies – these are designed to block a specific target on the outside of cancer cells. A bit like trying to prevent electricity from flowing by placing a plastic plug into an electrical socket. As they are generally made up of large compounds which the body cannot absorb very well, they are administered intravenously. Examples include pertuzumab (Omnitarg), alemtuzumab (Campath-1H), panitumumab (Vectibix), bevacizumab, cetuximab (Erbitux), rituximab (Rituxan), and trastuzumab.
Oral small molecules – the patient swallows a pill, as the molecules are much smaller than those in monoclonal antibodies the body can absorb them well. This type of medication usually interferes with cancer processes within the cancer cell, inside it. Examples include nilotinib (Tasigna), lapatinib (Tykerb), imatinib (Gleevec), sorafenib, dasatinib (Sprycel), erlotinib (Tarceva), gefitinib (Iressa), sunitinib, and temsirolimus (Torisel).
Proteasome inhibitors – these are specialized proteins that interfere with enzymes (proteasomes) that break down other proteins within the cell when they are no longer needed. Bortezomib (Velcade), an injection that is used for treating multiple myeloma is an example.

Not all tumors have the same targets, though, recent studies have shown. A targeted treatment might not work for each patient. As these treatments may have side effects, and can be very costly, doctors have to try hard to match each patient to the most effective treatment whenever possible.

Sometimes targeting a medication to a tumor is not as simple as it sounds. What was targeted might turn out to be of no importance, or what worked before has no effect after a while – the cancer becomes resistant to the treatment. Targeted therapies may have serious side effects. Angiogenesis inhibitors are frequently linked to hypertension (high blood pressure).

Scientists and oncologists see targeted treatments as a major breakthrough in medicine. However, except in very few cases, these medications are not used on their own. Patients usually also undergo a combination of chemotherapy, radiation therapy, hormonal therapy or surgery.

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

Study findings may change surgical practice

Author: press release

Currently, about 30 per cent of patients who receive oral surgery have their cancer recur. But a new, Canada-wide surgical trial using a new approach to remove tumours and pre-cancerous cells from the mouths of those diagnosed with early-stage oral cancer offers new hope for patients.

The Terry Fox Research Institute (TFRI) announces the launch of a $4.7 million Pan-Canadian Phase III clinical trial aimed at improving outcomes for patients undergoing surgery for oral squamous cell cancers. The Canadian Optically Guided Approach for Oral Lesions Surgical Trial (The COOLS Study) has the potential to revolutionize clinical practice here and around the world for this kind of cancer.

“Our investment in this promising study is our response to a serious clinical concern expressed by head and neck surgeons across Canada and it has the potential to change surgical practices for cancer of the mouth nationally and internationally,” said Dr. Victor Ling, TFRI President and Scientific Director.

Using a new surgical approach guided by an existing hand-held light tool, the surgeons, pathologists, and scientists involved in this nine-centre study will determine whether recurrence is reduced when they shift the surgical field for the removal of tumours or pre-cancerous cells in the mouth.

The surgeons will use fluorescence visualization (FV) or “blue light” provided by the optical aid rather than traditional white light to determine the tissue to be removed. Under the blue light, normal tissue generates a fluorescence which is absent in tumour or pre-cancerous tissue. The study will aim to spare normal healthy tissue from surgery while catching high-risk, pre-cancerous tissue identified through FV.

“This study will have an immediate impact on practice if the study turns out the way we hope,” says TFRI COOLS Study principal investigator Dr. Miriam Rosin, a senior scientist with the BC Cancer Agency who holds joint appointments at the University of British Columbia and Simon Fraser University. “If the study is successful, it will help to reduce the number of deaths from oral cancer as well as to improve the quality of life for people living with this disease. Working with scientists, we will have this new approach ready to disseminate to the surgical community at large and even globally.”

“In work we’ve conducted to date in Vancouver, there has been almost no recurrence where surgery followed the contour of the lesion shown by using FV-guided surgery. Working together with surgeons, pathologists, research staff and scientists, this TFRI-funded study will enable us to test the approach on a broader cohort of patients at sites across the country and obtain the evidence required to change current practice.” remarks principal investigator Dr. Catherine Poh, a senior scientist with BC Cancer Agency and oral pathologist and associate professor, University of British Columbia and oral pathologist and consulting dentist, Vancouver General Hospital.

This is the first Canadian study ever to bring together this group of clinicians to address a surgical challenge in oral cancer. “Our surgical community has expressed great interest in participating in this trial which provides an unique and important opportunity to assess a surgical intervention in a controlled prospective manner across many sites,” says principal investigator Dr. Scott Durham, an ear, nose and throat surgeon and clinical professor and head, division of otolaryngology, Vancouver General Hospital. The study aims to build a network of clinicians, pathologists and research staff across the country to fight oral cancer.

About The Terry Fox Research Institute:
Launched in October 2007, The Terry Fox Research Institute is the research arm of The Terry Fox Foundation. TFRI seeks to improve significantly the outcomes of cancer research for the patient through a highly collaborative, team-oriented, milestone-based approach to research that will enable discoveries to translate quickly into practical solutions for cancer patients worldwide. TFRI collaborates with over 50 cancer hospitals and research organizations across Canada as MOU partners. TFRI headquarters are in Vancouver, BC.