TeloVac vaccine trial for Pancreatic Cancer

It is a common knowledge that pancreatic cancer is one of the most dangerous known types. It has the worst survival rate of all common cancers, mostly because patients are usually diagnosed with the disease too late for an efficient treatment, when the cancer is inoperable. In many cases, patients often have less than six months to live, and unlike other cancers, there has been very little improvement in long-term survival in the past 40 years.

However, there are some, potentially good, news for the new vaccine which may turn out to be breakthrough in the pancreatic cancer treatment and prevention. Actually, if successful, the vaccine will open a way to treat and prevent other cancers as well, revolutionizing the mere approach to the disease.

The TeloVac vaccine is part of a new generation of drugs that use the body’s own defenses to fight the disease, stopping tumors in their tracks. Yes, most vaccines are used to prevent infection, but therapeutic cancer vaccines mark a different approach by aiming to treat disease, stimulating the immune system to recognise and target the cancer.

The TeloVac trial involves more than 50 hospitals, is funded by Cancer Research UK and coordinated by Royal Liverpool University Hospital. It is a Phase 3 trial, which involves comparing the new treatment to standard therapy, and is essential before any new therapy is licensed.

The vaccine, also named GV1001, contains small sections of telomerase -- a protein that is over-produced by cancer cells. The injection of the vaccine, therefore, presents the immune system with telomerase, helping T-cells to recognize and target the cancer cells more effectively. Found at high levels in many cancer cells, telomerase effectively makes them immortal, allowing them to live on when healthy cells would die – easing the growth and spread of the tumor

Telomerase is a ribonucleoprotein enzyme which is involved in the DNA replication of the cell cycle. The enzyme is over expressed in majority of human cancers including 90% of advanced pancreatic cancer patients and therefore is a natural therapeutic target in the treatment of cancer. 

The over-expression of Telomerase enables the cancer cells to overcome mortality and therefore be a major contributing factor to progression of cancer. Telomerase is one of the body’s own proteins and therefore not recognized or attacked by the immune response.

The scientists and doctors involved in the TeloVac trial are keen not to raise the expectations of patients. In earlier small-scale trials, some patients did have a prolonged life-expectancy of several months (three months in average). But until the results of this major trial are known it won't be clear whether this was anything to do with the vaccine.

In the largest trial of its kind in the UK, more than 1,000 men and women in the late stages of pancreatic cancer are either being given the vaccine alongside their normal drugs or treated as usual. The results from the 53 hospitals taking part will not be available until next year but, anecdotally, some patients credit their participation in the trial with giving them an extra year or two of life.

Professor John Neoptolemos from Royal Liverpool University Hospital, who is co-coordinating the large-scale British trial, said: “When you have got pancreatic cancer, it is like a time bomb in people.” Pancreatic cancer cells are normally invisible to the immune system but the vaccine ‘spots’ the telomerase spilling out from them and kick-starts the fight back. “The problem is tumors are clever and are able to turn the immune cells into traitors which help to guard the tumor,” said Professor Neoptolemos. “The vaccine takes away the masking effect of the tumor.” Healthy cells escape the attack because their levels of telomerase are too low to bother the immune system. This cuts the risk of side-effects such as nausea and hair loss normally seen with cancer drugs.

If TeloVac passes the current trial successfully, it would be available for treating advanced forms of pancreatic cancer by the end of 2013. However, more studies would be underway to assess its effectiveness in preventing pancreatic cancer and treating patients suffering from earlier stages of the disease.

Scientists hope the method could work on other types of cancers as well and therefore have planned a trial on patients with lung tumor for later this year.

“We strongly believe this has the potential to overcome the limits of other current cancer vaccines and become part of the standard of care not only for pancreatic cancer but for various other types of cancers,” said Jay Sangjae Kim, the founder of GemVax, the Korean company developing the TeloVac vaccine.  “In other words, a truly 'universal' vaccine will be available in the near future,” he added.

Sources and Additional Information:

http://www.presstv.ir/detail/175280.html

http://www.bbc.co.uk/blogs/thereporters/ferguswalsh/2011/04/pancreatic_cancer_vaccine_trial.html

http://www.dailymail.co.uk/health/article-1377069/Universal-cancer-vaccine-TeloVac-arrive-years.html

http://www.lctu.org.uk/docs/Leaflets/telovac.pdf

Dental Problems Linked to Increased Risk of Pancreatic Cancer

In January 2007, a group of Harvard investigators published some research suggesting that periodontal disease—as a marker of a susceptible immune system—may indicate an increased risk for pancreatic cancer.

Investigation of this possible association is still ongoing, but preliminarily it appears that periodontal disease and pancreatic cancer may be linked by an underlying mechanism that is inflammatory driven. An understanding of this potential relationship may help dental practitioners to better educate their patients on the potential ramifications of systemic inflammation in the oral cavity relative to diseases of the digestive tract.

Encouraged by previous studies that suggests gum inflammation (periodontal disease) and tooth loss may also be associated in some way with an increased risk of pancreatic cancer, researchers from Harvard University and the University of Puerto Rico looked at a large database of information to find out whether there was any evidence of such a connection.

In 16-year, questionnaire-based, study of 51,529 predominately Caucasian male health professionals between ages 40 and 75, 216 men were diagnosed with pancreatic cancer. Researchers reported that periodontal disease was associated with a 64% increase in the risk of pancreatic cancer, after adjusting for smoking and other risk factors. The researchers also found that within this study population, periodontal disease with recent tooth loss (within the previous four years) was associated with a 2.7-fold increase in the risk of pancreatic cancer. Furthermore, they found that the timing and severity of periodontal disease, as manifested by recent tooth loss, may have a joint effect.

Age, smoking, and obesity did not appear to influence the association between periodontal disease and pancreatic cancer. When men with a history of diabetes were excluded from the analysis, a statistically significant association between periodontal disease and pancreatic cancer was still observed. The investigators suggested that several mechanisms may explain the biological plausibility of the associations observed in this study.

Possible Explanations

One of the hypotheses of why the dental problems might be a substantial risk factor for the pancreatic cancer development is that periodontal disease may promote pancreatic carcinogenesis through inflammation. The investigators cite earlier reports that plasma C-reactive protein (CRP) levels—an important biomarker of systemic inflammation—were consistently higher in subjects with a history of periodontal disease than those with no history.

"People with periodontal disease have higher levels of blood levels of C-reactive protein, an inflammatory marker that has been associated with heart disease," noted Dominique S. Michaud, an assistant professor of epidemiology at the Harvard School of Public Health in Boston. "Periodontal disease is also linked to heart disease in some studies." The inflammation may somehow contribute to the promotion of cancer cells, she added.

An alternative hypothesis is that periodontal disease may influence pancreatic carcinogenesis through increased generation of ­carcinogens, specifically nitrosamines. Nitro­samines are known to induce pancreatic cancer in animals and are considered potential carcinogens in human pancreatic cancer. Approximately 45% to 75% of nitrosamine formation is endogenously formed by salivary and gastrointestinal bacteria. The formation of nitrosamines in the oral cavity of individuals with poor oral hygiene is eight times higher than in individuals with good oral hygiene.  Also, periodontal disease and poor oral hygiene are associated with higher levels of oral bacteria and elevated nitrosamine levels within the oral cavity. As such, this relationship may place certain individuals at greater risk because nitrosamines and gastric acidity may play important roles in pancreatic cancer.

Individuals afflicted with chronic pancreatitis are at greater risk for developing pancreatic adenocarcinoma. Research published by Wheatley-Price and colleagues suggests that inflammation plays a role in the disease etiology of pancreatic cancer through the different forms of several inflammatory pathway genes. The same genotype is associated with an increased risk of coronary artery disease, raising the possibility that inflammatory processes may be important etiologically in pancreatic cancer. Accordingly, the chronic, low level inflammation associated with periodontitis may convey a greater risk of pancreatic cancer.

Stolzenberg-Solomon and colleagues examined the association between dentition history and pancreatic cancer on a prospective group of 29,133 Finnish men who smoked. They found that tooth loss was significantly associated with pancreatic cancer and that this trend was consistent across all categories of tooth loss. The researchers also reported that compared with those with less tooth loss, the edentulous subjects were more likely to have ulcers, which is linked to Helicobacter pylori infection.

Stolzenberg-Solomon and colleagues  discussed several mechanisms that may explain the increased risk associated with tooth loss and pancreatic cancer, including the contribution of poor oral hygiene to more deleterious gastrointestinal flora, and consequently, increased nitrosation. Another theory raised by these researchers is that tooth loss may be an indicator of a less healthy lifestyle or of health status in general. For instance, tooth loss reduces masticatory ability thereby leading to consuming a less healthy diet. Edentulous individuals in the study had greater intake of total and saturated fat and diminished intake of folate, both dietary factors that are associated with a greater risk of pancreatic cancer. The analysis of the data controlled for these dietary factors and the factors did not modify the association that Stolzenberg-Solomon and colleagues found between tooth loss and pancreatic cancer.

What Causes Periodontal Disease?

Our mouths are full of bacteria. These bacteria, along with mucus and other particles, constantly form a sticky, colorless "plaque" on teeth. Brushing and flossing help get rid of plaque.  Plaque that is not removed can harden and form "tartar" that brushing doesn't clean.  Only a professional cleaning by a dentist or dental hygienist can remove tartar.

The longer plaque and tartar are on teeth, the more harmful they become. The bacteria cause inflammation of the gums that is called "gingivitis."  In gingivitis, the gums become red, swollen and can bleed easily.  Gingivitis is a mild form of gum disease that can usually be reversed with daily brushing and flossing, and regular cleaning by a dentist or dental hygienist. This form of gum disease does not include any loss of bone and tissue that hold teeth in place.

When gingivitis is not treated, it can advance to "periodontitis" (which means "inflammation around the tooth.")  In periodontitis, gums pull away from the teeth and form spaces (called "pockets") that become infected. The body's immune system fights the bacteria as the plaque spreads and grows below the gum line. Bacterial toxins and the body's natural response to infection start to break down the bone and connective tissue that hold teeth in place. If not treated, the bones, gums, and tissue that support the teeth are destroyed.  The teeth may eventually become loose and have to be removed.   

Daily Oral Hygiene Measures to Prevent Periodontal Disease

• Brushing properly on a regular basis (2 times a day), with the patient attempting to direct the toothbrush bristles underneath the gum-line, so as to help disrupt the bacterial and plaque growth that may occur there.

• Use fluoride toothpaste. Using toothpaste with fluoride helps to prevent decay.
• Flossing daily and using interdental brushes if there is sufficient space between teeth and behind the last tooth in each quarter.
• There are some instances that typical brushing is not just enough. There are still some parts of your gums as well as oral cavity that are left non-brushed. In a typical dental consultation, you will be advised to use an electric toothbrush that will provide you with perfect cleaning angle for your teeth. In using this type of toothbrush, you will first feel some pain or discomfort. In most cases, your gums might bleed also. So in using this, you have to set the time, for example, 30 seconds first then gradually increase it when you can already tolerate the after brushing effects.
• Using an antiseptic mouthwash. Chlorhexidine gluconate based mouthwash or hydrogen peroxide in combination with careful oral hygiene may cure gingivitis, although they cannot reverse any bone loss due to periodontitis. (Alcohol based mouthwashes may aggravate the condition).
• Regular dental check-ups and professional teeth cleaning as required. Dental check-ups serve to monitor the person's oral hygiene methods and levels of bone around teeth, identify any early signs of periodontitis, and monitor if it has responded to treatment.

Sources and Additional Information:

http://abcnews.go.com/Health/CancerPreventionAndTreatment/story?id=2800201&page=2

http://www.dimensionsofdentalhygiene.com/ddhright.aspx?id=1426

http://ndri.com/article/dental_hygiene_practice_also_important_for_possible_risk_of_pancreatic_cancer_from_periodontal_or_gum_disease-206.html

http://www.nidcr.nih.gov/OralHealth/Topics/GumDiseases/PeriodontalGumDisease.htm

http://www.tonehealth.org/How-to-Prevent-Periodontal-Disease.htm