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Immune-related gene may predispose to HPV-related cancer

Thu, Oct 23, 2014

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Source: bcm.edu
Author: Julia Parsons
 

An international coalition of cancer specialists led by a researcher now at Baylor College of Medicine has identified an immune related gene called transforming growth factor beta receptor 1 (TGFBR1) that appears to play an important role in determining whether a person develops a cancer related to human papilloma virus (HPV). HPV is, in particular, associated with anal cancer and cancers of the cervix, and the head and neck.

Their findings appear in the journal Cancer Research.

Until recently, head and neck cancer has been found primarily in smokers, but there has been a rise in HPV-associated head and neck cancer in nonsmokers. The head and neck cancer most-associated with HPV is oropharyngeal cancer, involving the tonsils and base of the tongue.

HPV is also one of the most common sexually transmitted diseases, with certain strains known to cause head and neck and/or cervical cancer.

The National Cancer Institute predicts that HPV-positive oropharyngeal cancer will likely surpass cervical cancer as the most common HPV-associated cancer in the United States by 2020.

“The real mystery is that in western countries, pretty much everyone is exposed to HPV but only a small number of people get HPV-related cancers,” said Dr. Andrew Sikora, vice-chair for research in the Department of Otolaryngology Head and Neck Surgery at Baylor. “We are trying to figure out what makes the people who actually get the cancer different from those who don’t, given that so many people are exposed.”

Using data collected as part of a genome-wide association study of head and neck cancer performed by the INHANCE consortium, the researchers were able to associate alterations in a number of immune-related genes with oropharyngeal cancer. One of these genes, TGFBR1, was found to be deregulated in patients with both oropharyngeal and cervical cancer.

“The fact that we were able to independently replicate our findings in two-different HPV-related cancers is exciting because it suggests that we have found something that is critical to the biology of how HPV causes cancer,” said Sikora, also co-director of the head and neck cancer program in the NCI-designated Dan L. Duncan Cancer Center Baylor.

“We hope to learn more about this gene and how it affects cancer,” Sikora added. “In the future we hope to develop a tool to identify who is more susceptible to HPV-related cancers.”

Sikora conducted the study while on faculty at the Icahn School of Medicine at Mount Sinai in New York prior to joining the Baylor faculty in July 2014. Co-author, Paolo Boffetta, director of the Institute for Translational Epidemiology at ISMMS was one of the investigators for the original INHANCE study.

Others who took part in this study include:  Chaya Levovitz; John Finnigan; Sara Alshawish; Marshal R. Posner; Weija Zhang; Eric E. Schadt; Eric M. Genden and Paolo Bofetta; The Icahn School of Medicine at Mount Sinai in New York; Dan Chen and Emma Ivansson of Uppsala University, Uppsala, Sweden.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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Mandibular reconstruction using plates prebent to fit rapid prototyping 3-dimensional printing models ameliorates contour deformity

Thu, Oct 23, 2014

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Source: 7thspace.com
Authors: Masaki Azuma, Toru Yanagawa, Naomi Ishibash Kanno, Fumihiko Uchida, Takaaki Ito, Kenji Yamagata, Shogo Hasegawa, Kaoru Sasaki, Koji Adachi, Katsuhiko Tabuchi, Mitsuru Sekido and Hiroki Bukawa
 

Recently, medical rapid prototyping (MRP) models, fabricated with computer-aided design and computer-aided manufacture (CAD/CAM) techniques, have been applied to reconstructive surgery in the treatment of head and neck cancers. Here, we tested the use of preoperatively manufactured reconstruction plates, which were produced using MRP models.

The clinical efficacy and esthetic outcome of using these products in mandibular reconstruction was evaluated.

Methods: A series of 28 patients with malignant oral tumors underwent unilateral segmental resection of the mandible and simultaneous mandibular reconstruction. Twelve patients were treated with prebent reconstruction plates that were molded to MRP mandibular models designed with CAD/CAM techniques and fabricated on a combined powder bed and inkjet head three-dimensional printer.

The remaining 16 patients were treated using conventional reconstruction methods. The surgical and esthetic outcomes of the two groups were compared by imaging analysis using post-operative panoramic tomography.

Results: The mandibular symmetry in patients receiving the MRP-model-based prebent plates was significantly better than that in patients receiving conventional reconstructive surgery.

Conclusions: Patients with head and neck cancer undergoing reconstructive surgery using a prebent reconstruction plate fabricated according to an MRP mandibular model showed improved mandibular contour compared to patients undergoing conventional mandibular reconstruction.

Thus, use of this new technology for mandibular reconstruction results in an improved esthetic outcome with the potential for improved quality of life for patients.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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Potential link between breast cancer genes, salivary gland cancer

Thu, Oct 23, 2014

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Source: http://www.drbicuspid.com/
Author: Donna Domino, Features Editor

The risk of developing salivary gland cancer might be higher in people with mutations in either of two genes associated with breast and ovarian cancers, according to a new study in JAMA Otolaryngology — Head & Neck Surgery (September 25, 2014).

Although salivary gland cancer is rare in the U.S. (about three cases occurring annually per 100,000 adults in the general population [0.003%]), this retrospective study suggests it occurs 17 times more often in people with inherited mutations in the BRCA1 and BRCA2 genes than those in the general population. A link between breast cancer and salivary gland cancer has been suspected for decades, the study authors noted.

The finding, which must be verified, should be considered during genetic counseling for people with BRCA1 or BRCA2 mutations. However, as the study authors noted, unless there is a family history of breast or ovarian cancer, it is premature to offer genetic testing for these gene mutations to individuals with salivary gland cancer.

Individuals known to carry mutations in these genes and who have a salivary gland mass should be evaluated by a physician, according to researchers at the Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

“Further study is needed to confirm this preliminary result, but I believe that a BRCA-positive patient with a lump in a salivary gland should have that lesion evaluated as soon as possible,” said study co-author Theodoros Teknos, MD, a professor and the chair of otolaryngology and the director of head and neck oncologic surgery at OSUCCC – James, in a statement.

It has been established that women who inherit mutations in either of the two genes have a higher risk of breast and ovarian cancer than women without the mutation; men with the mutations also are at higher risk of breast cancer, the study authors noted. The two mutated genes are also linked to prostate, pancreatic, and other cancers.

The study’s principal investigator, Rebecca Nagy, a certified genetic counselor and clinical associate professor of human cancer genetics at OSUCCC – James, recommends that individuals who carry a BRCA mutation be made aware of this possible association.

“The findings should be considered during genetic counseling of families with inherited BRCA1 or BRCA2 mutations,” Nagy said. “In the future, patients with salivary gland cancer and their family members might be referred for BRCA testing, or carriers of BRCA mutations might undergo surveillance for salivary gland cancers.”

For this retrospective study, the researchers included pedigrees from patients with breast cancer in the Clinical Cancer Genetics Program at the Ohio State University Wexner Medical Center. A total of 5,754 individuals were identified from 187 pedigrees, and their medical histories were reviewed for diagnoses of salivary gland tumors and BRCA testing.

“The observed rate of 3 of 5,754 cases (0.052%) of head and neck cancers in BRCA-positive probands and likely carriers is significantly higher than the background incidence rate of 3 of 100,000 (0.003%) per year (p < 0.001),” the study authors wrote.

“I would like physicians and dentists to realize that BRCA mutations carry risks for salivary gland cancer as well as breast cancer, and to remember that salivary glands include not only the paired parotid glands and submandibular glands but also innumerable minor salivary glands in the oral cavity,” Dr. Teknos advised.

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Critical Outcome Technologies and MD Anderson Cancer Center to evaluate COTI-2 in treating head and neck cancers

Thu, Oct 23, 2014

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Source: www.marketwatch.com
Author: press release

Critical Outcome Technologies Inc. (“COTI”), the bioinformatics and accelerated drug discovery company, announced today that it recently executed a material transfer agreement (“MTA”) with Dr. Jeffery Myers, MD, PhD, FACS of The University of Texas MD Anderson Cancer Center for the continued evaluation of COTI-2 in the potential treatment of patients with head and neck squamous cell cancer (“HNSCC”).

There are approximately 500,000 new cases worldwide of HNSCC a year, making it the sixth leading cancer in terms of new cases. In the United States, HNSCC is considered to be a rare disease and therefore represents a second “Orphan Disease” opportunity for COTI-2.

If HNSCC is caught at an early stage, current therapies, which include surgery and radiation followed by chemotherapy, can be effective. Unfortunately, HNSCC tumors with p53 mutations tend to be more difficult to treat with such mutations occurring in 30-70% of HNSCC tumors. These mutations are associated with poorer patient outcomes as traditional chemotherapy, using the current first line chemotherapy, cisplatin, is often ineffective. The overall five-year survival rate of patients with HNSCC is 40-50%.

As a small molecule activator of misfolded mutant p53 protein, COTI-2 has demonstrated in preclinical studies its ability to restore p53 function and thus induce cancer cell death for many common p53 mutations. As previously announced, the Company is planning a Phase 1 study in gynecological cancers (ovarian, cervical and endometrial) at MD Anderson with Dr. Gordon Mills and his team and these studies in HNSCC with Dr. Myers will seek to extend the understanding of COTI-2′s ability to treat p53 mutations across multiple cancer types.

Dr. Jeffrey Myers, leader of MD Anderson’s Multi-Disciplinary Head and Neck Cancer Research Program, has been studying the impact of p53 mutation, a common event in HNSCC, on tumor progression and response to therapy. His group has evaluated a number of single agent and combination treatments for p53 mutant tumors, and his preliminary findings with single agent COTI-2 in HNSCC in vitro tumor models show tremendous promise. In addition to seeing sensitivity of HNSCC cells to COTI-2, his group has found that this drug sensitivity is associated with activation of p21, an important mediator of p53′s response to cellular DNA damage. This response is consistent with the p53-dependent mechanism of action studied by Dr. Mills in ovarian cancer. Dr. Myers and his colleagues are planning more extensive studies of COTI-2 and its dependence on p53 re-activation for its effects in both in vitro and in vivo HNSCC tumor models.

“We look forward to further exploring COTI-2′s impact on HNSCC tumors,” said Dr. Wayne Danter, President and CEO. “We continue to believe that COTI-2 represents a potential breakthrough treatment given the central importance of p53 gene mutations in many cancers, including HNSCC. This second indication would broaden the treatment opportunities for our lead oncology asset, which has already been granted the Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of ovarian cancer.”

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Supervised tooth-brushing programs proposed for UK schools

Thu, Oct 23, 2014

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Source: www.delhidailynews.com
Author: staff

London: More than one in ten three-year-old children have rotten teeth in England. The condition is worse in some parts of the country. Around half of five-year-old children have missing, filled or decayed teeth. According to NICE’s new guidelines, the nurseries and schools in England must consider introducing supervised tooth-brushing and fluoride varnishing programs.

“Children, as young as three, are being condemned to a life with rotten teeth, gum disease and poor health going into adulthood. Many children have poor diets and poor mouth hygiene because there is misunderstanding about the importance of looking after children’s early milk teeth and gums,” said the director of Centre for Public Health at NICE, Prof Mike Kelly.

The advisory body said that nurseries and primary schools should supervise tooth-brushing in areas where there is a high level of child tooth decay.

NICE informed that tooth decay in adults and children is pretty high in disadvantaged area, for vulnerable people and in some of the ethnic minorities.

It also advises that once the local authorities identify the areas that will benefit, free fluoride toothpaste and toothbrushes should be given to parents and carers for use at home as well as at school. NICE also added that if supervised tooth-brushing is scheme is not possible, children’s teeth must be painted with fluoride varnish at least two times a year in order to strengthen the teeth.

Mandy Murdoch, health consultant and a part of the team which developed the guidelines said that part of the issue is most parents don?t understand that they should take steps in order to protect against tooth decay. Not only are they painful, rotten teeth may also lead to higher incidences of oral problems in life later.

“Around 25,000 young children every year are admitted to hospital to have teeth taken out,” she said. Given that we know how to prevent dental disease this really should not be happening,” said Professor Elizabeth Kay, the foundation dean for Peninsula dental school in Plymouth.

In adults, poor oral hygiene had been linked with increased tooth loss, gum disease and oral cancer.

There were “still unacceptable inequalities which need to be tackled” in people’s dental health said the British Dental Association.

The NICE guidelines were welcomed by the chairman of BDA?s dental public health committee, Dr. Christopher Allen.

“It’s important that local authorities have access to specialist dental health advice to ensure that the interventions chosen are the most appropriate for the needs of the population? he said adding that water fluoridation programmes might prove to be more efficient means of strengthening people?s teeth.

The BDA informed that only about six million people in UK have access to fluoridated water.

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Image cytometry may have roll in oral cancer screening

Fri, Oct 17, 2014

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Source: http://cebp.aacrjournals.org
Author: Calum MacAulay, Martial Guillaud, Lewei Zhang, Catherine Poh, and Miriam Rosin
 

Abstract: Oral cancer like many epithelial cancers which are readily accessible are much more treatable if caught in their early pre-invasive/minimally invasive stages. The oral cavity is easily examined and sampled. In British Columbia we have established an Oral Cancer Prevention Program in which we are evaluating and investigating several technologies and their interactions for the screening and follow-up of oral cancer to be implemented into a population based screening program. These sensitive “field of view” image based screening technologies are generally sensitive for the detection of suspect OPLs (oral premalignant lesions), but can highlight areas who’s actual characteristics may be masked by inflammation/ulceration and other conditions. As part of a comprehensive management program we present our pilot data on the use of oral cytological samples collected by targeted brushing and analyzed by a fully automated high resolution image cytometry device (cyto-savant). For this study we collected 196 cytological samples using targeted brushing of select areas in the oral cavity from individuals with squamous cell carcinoma (SCC), carcinoma in situ (CIS), severe dysplasia, no areas of abnormality and subjects with areas of inflammation/infection etc. All of these samples were spun down onto slides and the DNA quantitatively labeled with a modified Feulgen-Thionin stain and the slides automatically scanned by the cyto-savant. For each object (cell/debris) imaged ~120 features were calculated and used by a cell recognition decision tree (originally trained for cervical cell recognition) to differentiate cells from debris. The 108 samples from known normal areas and 60 samples from (SCC, CIS and severe dysplasia) were used to determine the appropriate thresholds for the frequency of cells displaying characteristics previously known to be associated with cancer detection (in cervix and lung). Using these thresholds the system correctly identified 86% of the abnormal cases and 86% of the normal cases. When tested on the 28 inflammation/infection cases the system correctly identified 92% of the evaluable samples as non OPLs. These pilot results indicate that image cytometry may have a roll in oral cancer screening. Supported by grant RO1-DE017013-01, NIDCR

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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Cigarette smoking caused 14 million serious diseases in 2009

Tue, Oct 14, 2014

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Source: www.medscape.com
Author: Larry Hand

Cigarette smoking remains a major cause of preventable diseases in the United States, with at least 14 million serious medical conditions attributable to smoking in 2009, according to an article published online October 13 in JAMA Internal Medicine.

“These estimates demonstrate that smoking accounts for millions of serious medical conditions in the United States that could be avoided in the absence of cigarette use,” write Brian L. Rostron, PhD, from the Center for Tobacco Products, US Food and Drug Administration, Silver Spring, Maryland, and colleagues. “Our results also indicate that previous estimates may have substantially underestimated smoking-attributable morbidity in the United States.”

The researchers analyzed multiple sources of data from 2006 to 2012, including 2009 population data from the US Census Bureau, smoking prevalence and disease risk from the National Health Interview Survey of US adults for 2006 to 2012, and data from the National Health and Nutrition Examination Survey of US adults for 2007 to 2010.

Current and former smokers were significantly more likely to have at least one smoking-attributable disease and multiple smoking-related conditions compared with never-smokers. Specifically, almost half of surveyed men and women (47.5% and 44.9%, respectively) aged 65 years and older reported having one or more smoking-related disorder, and almost 17% of men and more than 14% of women reported having multiple such disorders. In contrast, among never-smokers, 34.9% of men and 33.2% of women reported at least one such condition and 9.1% and 7.5%, respectively, reported two or more conditions.

Rates of smoking-related conditions were also elevated among current and former smokers aged 35 to 64 years compared with never smokers. For example, almost 12% of adults at least 35 years old reported having diabetes. The adjusted prevalence ratio compared with never-smokers was between 1.17 and 1.30. The researchers also found high prevalence ratios for lung cancer (range, 4.45 – 9.35) and chronic obsessive pulmonary disorder (COPD; range, 2.02 – 4.00).

Extrapolating from National Health and Nutrition Examination Survey data on COPD prevalence, the researchers estimated 14 million “lifetime major medical conditions” could be attributed to the effects of cigarette smoking in 2009 (95% confidence interval, 12.9 – 15.1 million).

The Centers for Disease Control and Prevention previously published estimates of 8.6 million adults having 12.7 million smoking-attributable conditions in 2000.

The recent US Surgeon General’s report “concluded that previous estimates of the disease burden of smoking could be substantial underestimates, given the absence of several major medical conditions caused by smoking,” the researchers write.

Updated, Expanded
The current report is based on data from about 180,000 people surveyed between 2006 and 2012 compared with previous Centers for Disease Control and Prevention estimates based on data from about 20,000 adults surveyed between 1988 and 1994. The current report is also based on calculations for full variance, which is not generally done, the researchers write. The new report also corrects for underreporting of COPD in self-reported survey data, they add.

“Our study confirms that cigarette smoking remains a major cause of preventable disease in the United States,” the authors conclude. “The resulting estimate indicates that the number of major smoking-attributable medical conditions in the United States is larger than has been previously reported, demonstrating the need for vigorous smoking prevention efforts. The disease burden of cigarette smoking in the United States remains immense, and updated estimates indicate that COPD may be substantially underreported in health survey data.”

Work Remains
In an accompanying commentary, Steven A. Schroeder, MD, from the Division of General Internal Medicine at the University of California, San Francisco, writes that in general, the prevalence of smoking has declined, but that this “decline is excruciatingly slow, and there are still more than 40 million smokers in the United States.” Much of current smoking is among “hard-to-reach” populations, he adds.

He concludes, “Tobacco control has been called one of the most important health triumphs of the past 50 years. Yet, although we have come a long way, there is still much more to be done, with the number of smokers worldwide now just short of 1 billion people.”

Source: JAMA Intern Med. Published online October 13, 2014

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Hospital Cancer Program Confronts The Existential

Mon, Oct 13, 2014

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Source: huffingtonpost.com
Author: Sasha Bronner

 
People who battle stage 4 cancer are familiar with words like chemotherapy, radiation and metastasize. But words they may not hear at a hospital as often are existentialism, mindfulness, legacy and humor.
Dr. Arash Asher at Cedars-Sinai Medical Center in Los Angeles is dedicating his life to changing that.

Asher, 38, is a physiatrist — a rehab doctor. Before his new program, Asher focused his training on the physical aspects of cancer treatment — things like cogitative rehab, and the management of pain and nausea. But a good number of patients kept coming back to him to talk about their deep and persistent fears. “We can treat someone’s physical pain, but I just felt like we weren’t doing enough as a system,” Asher says. “An antidepressant will not solve the issue.”
So Asher decided to create a rehabilitation program that focuses on the emotional fallout of cancer treatment. He recruited patients for the first course that began in mid-July and is currently in the fourth cycle of the program, called Growing Resiliency and Courage with Cancer, or GRACE.

Two hours a week, for five weeks, seven to nine patients meet in a conference room at Cedars-Sinai with Asher and Jeffrey Wertheimer, a neuropsychologist who co-developed the program. The group focuses discussions on themes or lessons — like wisdom, gratitude, humor, courage and legacy-creation. Patients are assigned homework reading, learn meditation techniques and conclude class with a piece on mindfulness.

The emphasis on mindfulness has a basis in research: it lowers the stress hormone cortisol and helps the brain control pain and emotions. That makes mindfulness a perfect tool for sick patients. Gratitude, a hallmark pillar of any mindfulness practice, has even been said to make us feel happier. Much of the GRACE programming is experimental, based on Asher’s instinct and clinical experience.

A book Asher read at age 17, by Austrian neurologist and psychiatrist Viktor Frankl, who also was a Holocaust survivor, has been a guiding inspiration for the Cedars-Sinai program.

Asher holds up an old copy of the book he’s kept since he was a teenager, the pages dog-eared and the edges frayed. “Frankl noticed that the people who survived the Holocaust weren’t necessarily the strongest or the most physical. They had this capacity to say, ‘I’m going to endure this pain and endure this humiliation because I have to write my book or I have to tell my story or I have to go back to my art.’”

Asher says his greatest lesson from Frankl’s memoir was this: “Nobody can take away the last of the human freedoms — which is one’s ability to choose his or her attitude in any given set of circumstances.”

This is the premise of Asher’s work — helping people cope with the inevitable and often painful conclusion of their lives. There are certain things you can’t treat with medications, Asher explains bluntly.

“When people come to you with fear — and these aren’t psychologically abnormal fears — these are people with stage 4 cancer and they are facing their own mortality, there’s a deep sense of loss of control,” Asher says. “Because you have no control over what your next CT scan will show or your next tumor marker.”

Instead of relying solely on anxiety medications, Asher uses tools like meditation and mindfulness, looking at how to find gratitude as a way to regain perspective.

“We’re never trying to be Pollyannaish, like, ‘Thank goodness for cancer because now you’re not materialistic.’ Or, ‘Thank goodness for cancer because now you know who your friends are,’” Asher says. “That’s just crap. But to say, ‘Okay, cancer is here. We are making the best of our circumstances. Are there things that we could gain that you were not really focusing on before?’”

So far, 22 patients have participated in the program. By early November, the total will be 31. Asher is keeping the groups small so that everyone gets attention and all voices are heard.

“We are used to prescribing meds and ordering tests and having control. But human nature is unpredictable and these are perceivably cheesy, non-scientific topics that we are covering,” he says.

For that very reason, Asher wasn’t always so convinced the program would be a hit. It took him nearly five years just to present the idea to colleagues.

“These are people with advanced-stage illnesses and my worst fear was wasting someone’s time when they don’t have a lot of time,” he says.

Matthew Morgan, 51, recently completed the GRACE program with Asher. After being diagnosed with head and neck cancer at the end of 2012, Morgan, a former television producer for shows like “Saved By The Bell” and “California Dreams,” had surgery to remove a portion of his tongue where a tumor was found. Despite a successful surgery, the cancer metastasized to his lungs, which made him a stage 4 cancer patient.

“Cancer is such a big umbrella. It covers a lot of different illnesses, different symptoms, different treatments, different prognoses,” Morgan explained in a quiet corner of the expansive waiting room at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai. “But there’s [always] something existential about it that is frightening.”

Morgan has a little trouble speaking, but manages well considering his surgery, which involved partial reconstruction of his tongue. “Over time, you learn how to work with what you have,” he says. “I had no idea that the surgery was going to be as dramatic as it was.”

Morgan has been through surgery, radiation and chemotherapy, facing the unknown at every stage. As he spoke to HuffPost, he awaited new scans that would help show his prognosis. “I think it’s helpful to do more than just sit at home and scratch your head about it,” he says.

Morgan was an eager recruit when he first heard of the GRACE program in its nascent stage from Asher. He claims to have had no expectations, but was excited to participate.

GRACE is not a just a support group. It’s more than a venue for patients to share experiences with cancer. In fact, Asher asked GRACE patients if they would have participated if he had billed it as a support group. Almost no one said yes. “Most of these patients are tired of being in a situation where everyone is just kind of bitching,” he says.

The group discusses assigned poems and essays, watches “Seinfeld” clips to facilitate a conversation about humor, and learns meditation methods. With a lesson plan and structured discussion, the program is more college course than group therapy.

One of Asher’s favorite lessons is on legacy creation. He observes that people often have the idea that a legacy is something tangible to be handed down to children.

“But we really reframe it as, ‘What do you want to be known for?’ ‘What is your identity?’ Because if you know where you want to go, you can live your life now working towards those goals,” Asher says.

The GRACE program also is shorter than a support group — just five weeks. For some participants, that’s about all the time they have left.

“Several people who have done the class have already passed,” Asher says. “I think it gave them something to focus on and think about. It gave them a sense of control.”

Morgan says he identified most deeply with the concept that he can choose his response to his situation. “This can be a very powerful tool for dealing with something like cancer,” he says. “The notion that you’re not responsible for it, but you’re response-able to deal with it.”

The sense of ownership has larger implications for the larger conversation about cancer. When asked what he feels is missing from the national dialogue about cancer, Asher doesn’t hesitate. “The idea that it’s possible to heal even if you can’t be cured,” he says.

That feeling was echoed in a recent email from one of Asher’s patients who had reached the end of his treatment options. Asher was eager to share the note, albeit anonymously. It read:

“As someone expressed at our last class ‘we are as one.’ However anyone else responded to treatment, I responded differently. To hear ‘me too,’ from everyone in the group was unbelievably bonding.”

“So much of the focus tends to be on the cure. And our patients identify themselves with that: cured or not cured,” Asher says.

He recalls his original inspiration in Frankl, who was able to keep his full identity in mind, despite his circumstances in the concentration camp. This ability, Asher believes, allowed Frankl to persevere, cope — and find solace in others.

“For the first time in many years,” the dying patient concluded his email. “I did not feel alone.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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Proteomic analysis of oral/head and neck cancer

Fri, Oct 10, 2014

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Source: http://cancerres.aacrjournals.org
Author: Shen Hu, Lifeng Zhang, Jiang Jiang, Martha Arellano-Garcia, and David Wong
 

Abstract: The stagnant survival rates over the past few decades for patients with oral/head and neck squamous cell carcinoma (OSCC/HNSCC) emphasize the need for identifying novel diagnostic and therapeutic targets based on molecular profiling of the tumor. In this study, we have conducted patient-based proteomic analysis towards the discovery of potential serum and tissue protein targets associated with OSCC/HNSCC. First, we have utilized quantitative proteomics based on gel electrophoresis and stable isotope labeling/tandem mass spectrometry (MS/MS) to identify differentially expressed serum proteins between lymph-node metastatic and non-metastatic OSCCs. Proteins in PAGE gel bands were digested and the resulting peptides were labeled with iTRAQ reagents and subsequently quantified with liquid chromatography (LC) with quadrupole time-of-flight MS or linear ion trap MS (LTQ). The differentially expressed proteins included transthyretin, alpha-fibrinogen, tetranectin, hemopexin, ficolin, HGF activator, plasminogen, clusterin, etc. Second, we have performed comparative proteomic analysis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs because HPV has been recognized as an important risk factor for a subset of OSCC/HNSCC. Differentially expressed proteins were revealed by 2-D gel electrophoresis and then identified using in-gel tryptic digestion followed by LC-MS/MS (linear ion trap). Interesting targets associated with HPV-positive HNSCC included NHEJ1, PARK7 (oncogene DJ-1), superoxide dismutase, heat shock protein beta-1, fatty acid-binding protein, etc. NHEJ1 is a DNA repair protein involved in DNA nonhomologous end joining whereas PARK7 acts as a positive regulator of androgen receptor-dependent transcription and has cell-growth promoting and transforming activities. In addition, we have profiled the E6- and E7-binding proteins within HPV-positive and HPV-negative HNSCC tissues using immunoprecipitation and LC-MS/MS. Apart from helping us to understand the molecular mechanism of the cancer diseases, these protein targets may also have potential clinical applications such as biomarkers if further validated.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling

Fri, Oct 10, 2014

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Source: http://cancerres.aacrjournals.org

Authors: Faina Linkov, Alex Lisovich, Zoya Yurkovetsky, Adele Marrangoni, Lyudmila Velikokhatnaya, Brian Nolen, Matthew Winans, William Bigbee, Jill Siegfried, Anna Lokshin, and Robert Ferris

Abstract: Squamous cell carcinoma of the head and neck cancer (SCCHN) is an aggressive disease which has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multi-analyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients prior to treatment (active disease group), 103 patients who were successfully treated (no evidence of disease, NED, group), and 117 smoker controls without evidence of cancer. The multi-marker panel offering the highest diagnostic power was comprised of 25 biomarkers, including EGF, EGFR, IL-8, tPAI-1, AFP, MMP-2, MMP-3, IFN-α, IFN-γ, IP-10, RANTES, MIP-1α, IL-7, IL-17, IL-1Rα, IL-2R, G-CSF, mesothelin, IGFBP-1, E-selectin, cytokeratin (CK)19, V-CAM, and CA-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer.

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