tumor

An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression

Source: www.nature.com
Author: A E Rice, Y E Latchman, J P Balint, J H Lee, E S Gabitzsch and F R Jones
 

We have investigated if immunotherapy against human papilloma virus (HPV) using a viral gene delivery platform to immunize against HPV 16 genes E6 and E7 (Ad5 [E1-, E2b-]-E6/E7) combined with programmed death-ligand 1 (PD-1) blockade could increase therapeutic effect as compared to the vaccine alone. Ad5 [E1-, E2b-]-E6/E7 as a single agent induced HPV-E6/E7 cell-mediated immunity. Immunotherapy using Ad5 [E1-, E2b-]-E6/E7 resulted in clearance of small tumors and an overall survival benefit in mice with larger established tumors. When immunotherapy was combined with immune checkpoint blockade, an increased level of anti-tumor activity against large tumors was observed. Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8+ tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1+ TILs. When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8+ TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1+ TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials.

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

September, 2015|Oral Cancer News|

Cancer patient has his mouth and tongue rebuilt using tissue from arm

Source: www.dailymail.co.uk
Author: Madlen Davies

When David Barwell was diagnosed with the advanced mouth cancer, he feared he would never speak or eat again. But now, British surgeons have rebuilt his entire oral cavity using tissue from his arm, in a 15-hour operation.
Screen Shot 2015-07-07 at 12.02.05 PM
They had to remove a tumour the size of a plum from his throat, forcing them to cut away the bottom of his mouth and tongue. But medics were able to use skin and blood vessels from his arm to rebuild the oral cavity, and re-model his tongue.

The operation will allow him to eat, drink and one day speak again, they hope. British-born Mr Barwell, who was living in Poland when he was diagnosed, travelled across Europe in a campervan to come back to Britain for treatment. Now recovering from the operation, he and his wife of 28 years, Barbara, have praised the NHS and its staff as ‘incredible’. Mrs Barwell, a 67-year-old mother-of-one, was fought back tears as she thanked the NHS for its work.

She said: ‘These people are amazing. After working for 15 hours to save David’s life and rebuild his mouth the surgeon, Mr McVicar, called me personally to tell me the operation had worked, and I could not believe it. I have never seen treatment so good, not anywhere in Europe.’

Mrs Barwell, who grew up in Poland but moved to Nottingham in the 1980s to study, added:
‘We used to make plans, both as a family and a business, but now we just can’t. We just want to take one day at a time and build a new life and start again. It will be different but we just have to hope that the cancer in his mouth will be totally gone and won’t come back. Usually people give cards to staff, and I will, but these wards are so incredible that I want to say more to thank them. The whole team are the best; it’s a very special world in here, one of hope and kindness.’

‘David writes me a note every day saying he loves me and thanking me for my devotion to him. We are so happy together and I am so thankful to the staff.’

Now recovering from the operation, Mr Barwell is fed through a tube into his stomach and uses a suction pipe to control his saliva. He is not yet able to speak properly, but he has expressed his thanks to staff at Nottingham’s Queen’s Medical Centre in a heartfelt note.

He wrote: ‘I am very grateful to Mr McVicar and his team for their help and support during this terrible illness. The treatment I have received has been first-class.’

Mr Barwell, who owns a Nottingham packaging company with his wife, began feeling unwell in October last year. But his illness initially misdiagnosed by doctors in Spain and Poland, where the couple had been living for nine years, and he was treated for an infection and given antibiotics. Finally, he was diagnosed with T4 mouth cancer in Poland in March, after losing almost four stone (25kg) in less than three months.

A T4 tumour is the most serious and hard-to-treat stage of the disease, because the cancer has spread from the mouth into nearby muscles, bones or skin. When doctors in Poland were unable to treat the disease, Mr Barwell drove back to Nottingham in a campervan to receive NHS care. Mr Iain McVicar, consultant maxillofacial surgeon for Nottingham University Hospitals, who operated on Mr Barwell, said: ‘It was a complicated situation with him living in Poland.

‘It might have been a much smaller procedure if it had been six or eight months before.
‘It [the tumour] would have got bigger and would have killed him.’

He added: ‘When you wake up you are just grateful you are alive because this kind of surgery carries a risk of death.

‘But he’s made the first leap and he’s done very well.’

Doctors are currently assessing whether Mr Barwell will need any further treatment or surgery.

Screen Shot 2015-07-07 at 12.07.29 PM
‘This is only the first part of the treatment, he’s probably going to need radiotherapy. It’s quite a complicated problem,’ said Mr McVicar.

‘It’s a very big operation and he’s not out of the woods yet but, hopefully, the tumour has been completely removed.
‘Hopefully he will ultimately be able to eat, drink and talk freely.’

It is also hoped he will be able to speak again with the help of therapists. Both Mr Barwell’s family and hospital staff say people need to be more aware of any changes in their mouths and more willing to go to a doctor or dentist to get help.

Mrs Barwell said: ‘I want people to be more forceful, and not just sit back and take antibiotics and ignore it. If it’s worrying you should see a doctor.

‘They need to be aware of what is wrong with them and look after themselves.’

Mr McVicar agreed, saying: ‘If people have something not right in their mouth for more than two weeks they should get it looked at.’

DNA shed from head and neck tumors detected in blood and saliva

Source: www.medicalexpress.com
Author: Wang et al., Science Translational Medicine (2015)
 
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Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and human papillomavirus DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location. Credit: Wang et al., Science Translational Medicine (2015)

 

On the hunt for better cancer screening tests, Johns Hopkins scientists led a proof of principle study that successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. A report on the findings is published in the June 24 issue of Science Translational Medicine.

“We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers,” says Nishant Agrawal, M.D., associate professor of otolaryngology—head and neck surgery—and of oncology at the Johns Hopkins University School of Medicine. “In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions.”

Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don’t generally occur in normal cells have long been considered good targets for screening tests.

In the case of head and neck cancers associated with HPV—tumors on the rise among Americans—Agrawal and his colleagues searched patients’ blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS and NRAS.

The major risk factors for head and neck cancers are alcohol, tobacco—including chewing tobacco—and HPV infection.

For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76 percent) and in the blood of 41 of the 47 (87 percent). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96 percent).

When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47 percent), seven of 10 larynx cancers (70 percent) and two of three hypopharynx cancers (67 percent).

The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.

“One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn’t ask patients to gargle; we only asked them to rinse their mouths to provide the samples,” says Agrawal, a member of Johns Hopkins’ Kimmel Cancer Center and Ludwig Center.

Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91 percent), six of seven larynx cancers (86 percent) and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx and hypopharynx cancers and 20 of 22 oropharynx cancers (91 percent).

Agrawal says the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100 percent. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.

“Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.

The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.

In addition, Agrawal says: “We don’t yet have definitive data on false positive rates, and won’t until there are more studies of the tests in healthy people.” However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable results.

False results in gene tests arise when DNA are copied many times, sequenced and analyzed. The scientists used a method they developed and tested previously in cervical fluid to find ovarian and cervical cancers. Specifically, they attach a kind of genetic bar code—a random set of 14 DNA base pairs—to trace each copied DNA fragment to its original one. DNA copies lacking the bar code are suspected to be an artifact of the process, and any mutation found in it is disregarded.

Agrawal says that tests like the one his team used, if used commercially, likely would cost several hundred dollars, and “our long-term goal is to create a test that costs less than $50 so it can be administered by physicians or dentists.”

To screen for head and neck cancers, which occur in more than 50,000 people in the U.S. each year, doctors conduct physical examinations. Biopsies are taken of suspicious-looking lesions, but “this method is not ideal, as evidenced by the fact that most head and neck cancers are rarely found at very early stages, when they are most curable,” says Agrawal.

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

Study finds the prognosis of HPV positive tumors in head and neck cancer patients to vary depending on site

Source: sciencecodex.com
Author: Staff

 

Vienna, Austria: Patients with cancer of the throat and who are positive for the Human Papilloma virus (HPV+) have a good prognosis, but until now the effect of being HPV+ on the prognosis of tumours located elsewhere in the head and neck was unknown. Danish researchers have now shown that HPV status appears to have no prognostic effect on the outcome of primary radiotherapy in head and neck cancer outside the oropharynx (the part of the throat located behind the mouth, and which contains the soft palate and the base of the tongue), the ESTRO 33 congress will hear today (Sunday).

Presenting her results to the congress, Dr Pernille Lassen, MD, PhD, from the Aarhus University Hospital, Aarhus, Denmark, will say that head and neck cancers located outside the oropharynx should probably not be treated with the less intensive treatment strategies that are currently being investigated in clinical trials for HPV+ oropharyngeal tumours.

“HPV status has a very potent prognostic impact in radiotherapy for oropharyngeal cancer, and DNA from HPV has been found in all types of head and neck cancer, although it is far more common in oropharyngeal tumours. We decided to investigate the impact of HPV status in non-oropharyngeal cancers in the DAHANCA database, which includes all Danish head and neck cancer patients,” Dr Lassen will say.

The researchers searched the database to identify patients with locally advanced cancers who had been treated primarily with radiotherapy, and identified 1606 patients with larynx and pharynx carcinomas. Overall, 40% of the tumours were HPV positive, and the frequency was significantly higher in oropharyngeal cancer (57%), than in non-oropharyngeal (13%).

Being positive for HPV significantly improved tumour control (81% as opposed to 55%), as well as survival from the cancer (89% and 55% respectively), and death from any cause (82% and 38% respectively), after five years.

“In non-oropharyngeal cancers we found no prognostic impact of being HPV positive in any of these endpoints,” Dr Lassen will say. “This indicates that HPV status does not help us in predicting response to treatment, and hence the outcome of these cancers.

“We know from laboratory studies that HPV positive tumour cells are much more sensitive to radiation therapy than HPV negative cells, so until now we believed that they would behave similarly irrespective of site,” Dr Lassen will say. “However, these data indicate that this is not the case, and at present we do not understand why this should be, though it probably can be ascribed to other biological/genetic differences between the tumours rather than the HPV status. We would now like to try to elucidate the underlying mechanisms behind these different outcomes.”

There could be, for example, biological and/or genetic differences between the tumours other than the HPV status, the researchers say; for example, genetic changes caused by smoking tobacco, differences due to tumours of mixed make-up (for example, a combination of HPV+ and tobacco), or perhaps simply differences due to the site. “Such tumours with a combination of causes represent a challenge in our clinical daily practice,” Dr Lassen will say.

“We have started following up our work by analysing all the tumour samples using polymerase chain reaction, a way of amplifying DNA in order to be able to analyse changes in genetic information. We hope this will enable us to understand more about why the role of HPV in non-oropharyngeal tumours is so different. There are few data available on this subject at present, so finding out will be an important step towards optimising treatment for these patients.”

President of ESTRO, Professor Vincenzo Valentini, a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, commented: “These findings will have an important impact on the treatment of HPV+ head and neck cancers, and are likely to lead to a change in current practice.”

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

April, 2014|Oral Cancer News|

Michael Douglas: It took doctors nine months to figure out walnut-sized tumor at the back of my tongue was throat cancer

Source: www.nydailynews.com
Author: Corky Siemaszko

Michael Douglas said the tumor at the back of his tongue was the size of a walnut, but it still took doctors nine months to figure out it was throat cancer.

“I knew something was wrong,” he said. “My tooth was really sore, and I thought I had an infection.”

But the ear-nose-and-throat doctors and periodontists he consulted kept giving him antibiotics.

“And then more antibiotics, but I still had pain,” he said.

Finally, in 2010, a doctor in Montreal figured out that thing on his tongue was tumor.

“Two days later, after the biopsy, the doctor called and said I had to come in,” Douglas recalled in a wide-ranging interview with New York magazine. “He told it me it was stage-four cancer. I said, ‘Stage four. Jesus.’

“And that was that. After complaining for nine months and them not finding anything, and then they told me I was stage four? That was a big day.”

Douglas not only talked about his brush with mortality, he also chatted about his Hollywood comeback. He plays flamboyant piano tickler Liberace in an HBO biopic, “Behind the Candelabra,” that airs May 26.

“Liberace loved sex,” he said.

But the “Wall Street” star’s revelation that he had cancer sent a scare through Hollywood, where the words “stage four” were looked at as a death sentence. And for a time, Douglas looked like hell — losing 45 pounds as he subsisted on mostly on matzo ball soup as he healed.

douglas

Weakened by chemotherapy and radiation treatments, Douglas said he spent hours lying on a couch. Douglas looked like hell while recovering from cancer — losing 45 pounds as he subsisted on mostly on matzo ball soup.

“I watched a lot of sports, anything where I didn’t know the ending,” he said.

But Douglas was lucky to have a curable kind of cancer and now he’s back at work feeling a “new rejuvenation.”

Douglas said he believe his illness was “karmic retribution” for his decades of success, including two Academy Awards and four Golden Globes.

“That’s life,” said Douglas, 68. “I was ready for some karmic retribution.”

Douglas may be on the mend, but he’s hit other bumps in the road. His glamorous wife, actress Catherine Zeta-Jones, remains in rehab, where she has been fighting depression.

His troubled 34-year-old son by his first wife is doing time for distributing crystal meth — and recently had nearly five years added to his sentence after he was caught doing drugs in prison.

“I have gone from being a very disappointed but loving father who felt his son got what was due him to realizing that Lady Justice’s blindfold is really slipping,” he said. “I’m not defending Cameron as a drug dealer or drug addict, but I believe, because of his last name, he’s been made an example.”

Douglas, who has two kids with Jones, has expressed regrets in the past about being a lousy dad to Cameron. And he has spoken about growing up in the shadow of his famous father, actor Kirk Douglas.

“Success is expected, and yet the track record of the second generation is not great,” he said. “Only a small group of us, like Jane Fonda, have succeeded.” Fonda’s dad was actor Henry Fonda.

“The good and the bad of being second generation is: There are no illusions,” he said. “I always knew that this was a business. It can be wonderful, but it is a business.”

New research reveals genetic mutations of HNC

Source: www.drbicuspid.com
Author: DrBicuspid Staff

New findings regarding the genetic mutations that cause head and neck cancer (HNC) may lead to new therapies, according to collaborative research presented in November at the 2012 Chemotherapy Foundation Symposium in New York City.

Aaron Tward, MD, PhD, and colleagues analyzed tumor samples provided by the University of Pittsburgh from 92 patients with head and neck squamous cell carcinoma (HNSCC), according to an article on onclive.com.

Patient samples were chosen to reflect the normal distribution of patients with these cancers — that is, mostly men and smokers, noted Dr. Tward. Of these patients, 89% reported a history of tobacco use and 79% alcohol use; 14% of all tumors and 53% of oropharyngeal tumors were found to be positive for human papillomavirus (HPV).

Tumor sites also were selected to be roughly representative of the general HNSCC patient population — that is, most were oral cavity cancers, followed by a substantial proportion of oropharynx cancer samples and a few from patients with hypopharyngeal or laryngeal tumors.

Investigators used hybrid capture sequencing to compare tumor tissue and nontumor tissue from the same patient. They also compared the total number of mutations in the HNSCC samples with samples from previous tumor studies.

The analysis yielded a large number of mutations. For example, 5,000 genes had at least one mutation, and 1,300 had at least two, the researchers reported. Dr. Tward emphasized, however, that most of these are not implicated either in promoting or maintaining the cancer. He said the vast majority are “passengers” — that is, mutations alongside another mutation that acts as a “driver.”

December, 2012|Oral Cancer News|

The effect of treating institution on outcomes in head and neck cancer

Source: medicalxpress.com

Patients with head and neck cancer receiving radiation treatment at an academic center have a higher survival rate than those receiving treatment at a community center, according to a study in the December 2012 issue of Otolaryngology–Head and Neck Surgery.

“Despite similar rates of treatment completion and rate of treatment breaks between groups, patients treated in academic centers had more advanced cancer but better survival,” the authors state in their conclusion.

The study evaluated differences in patient characteristics, treatment, and cancer outcomes in the head and neck cancer population at the University of Minnesota from 2002 through 2008. Data were gathered on demographics, general medical data, tumor variables, insurance type, marital status and health behaviors.

The study analyzed 355 patients with mucosal head and neck cancer treated with radiation therapy from 2002 to 2008. One hundred forty-five (41%) received radiation treatment at community hospitals, and 210 (59%) were treated at academic hospitals. Within the academic hospitals group, 197 underwent radiation at the University of Minnesota, and 13 received radiation at an alternative academic center.

Both treatment groups shared similar characteristics in regard to sex, comorbidity, marital status, work status, insurance, and alcohol use. However, the community group had more current smokers and slightly older patients on average. Patients in the academic group were more likely to live in an urban location and had a higher median income. Patients undergoing radiation treatment at university centers had significantly more advanced cancer. After adjusting for these differences in patient characteristics, patients in the academic hospitals had about two-thirds the risk of dying compared with the community hospitals. The five-year survival rate was 53 percent for patients treated in academic centers compared with 33 percent for patients treated in community settings.

As a result of the study, the authors conclude that “more subtle differences in treatment administration and support at academic centers need to be investigated to understand the survival differences.” In addition, the authors note, “Potential disparities in care related to income, socioeconomic status, and geography should be further explored.”

Source: American Academy of Otolaryngology

December, 2012|Oral Cancer News|

No ref’s return as special as Corrente’s

Source: sportsillustrated.cnn.com
Author: Peter King

The voice of Tony Corrente was ebullient, as ebullient as a man who stared down his own mortality within the past few months and lived to tell about it.

“How are you doing?” I asked Corrente an hour after he refereed his first game — Niners-Jets at the Meadowlands Sunday — since his tongue and throat cancer eradication of last winter.

“Wonderful, fantastic, perfect!” he practically shouted into the phone. “Never been better, and I mean that. I am elated. I have a new lease on life.”

Corrente checked into the M.D. Anderson Cancer Center in Houston the day after his final game of the 2011 season — the Detroit-New Orleans Wild Card game — for treatment of a thumb-sized malignant tumor at the base of his tongue, where it connects with the back of his throat. He had 13 chemotherapy treatments and 33 zaps of radiation in a short period, to attack the tumor aggressively. Doctors told him if the tumor had been discovered as little as three weeks later the news would have been very dark for him. But they began treatment in time, and in the spring, they found that the tumor was under control. He’s had two thorough checkups since, and both have given him a clean bill of health.

This is why, as the National Anthem played Sunday in New Jersey, Corrente said a long prayer of thanks for his doctors and for those who supported him during the ordeal.

“I did not ever in my wildest dreams think I’d be back on the field,” Corrente said, his voice catching.

Corrente looks a little slim still. He’s having trouble putting weight on. And he said, “I still carry some of the fatigue with me. But I’m ahead of the curve in physically rebounding from this, so I consider myself lucky in that regard.”

In many regards. It’s good to see Corrente back

October, 2012|Oral Cancer News|

Growing ‘mini tumors’ from patient’s cancer could lead to custom treatments

Source: www.huffingtonpost.com
Author: Marilynn Marchione

It’s a medical nightmare: a 24-year-old man endures 350 surgeries since childhood to remove growths that keep coming back in his throat and have spread to his lungs, threatening his life. Now doctors have found a way to help him by way of a scientific coup that holds promise for millions of cancer patients.

The bizarre case is the first use in a patient of a new discovery: how to keep ordinary and cancerous cells alive indefinitely in the lab.

The discovery allows doctors to grow “mini tumors” from each patient’s cancer in a lab dish, then test various drugs or combinations on them to see which works best. It takes only a few cells from a biopsy and less than two weeks to do, with materials and methods common in most hospitals.

Although the approach needs much more testing against many different types of cancer, researchers think it could offer a cheap, simple way to personalize treatment without having to analyze each patient’s genes.

“We see a lot of potential for it,” said one study leader, Dr. Richard Schlegel, pathology chief at Georgetown Lombardi Comprehensive Cancer Center in Washington. “Almost everyone could do it easily.”

An independent expert agreed.

For infections, it’s routine to grow bacteria from a patient in lab dishes to see which antibiotics work best, Dr. George Q. Daley of Children’s Hospital Boston and the Harvard Stem Cell Institute said in an email. “But this has never been possible with cancer cells because they don’t easily grow in culture,” he said.

The new technique may reveal in advance whether a person would be helped by a specific chemotherapy, without risking side effects and lost time if the drug doesn’t work. “Pretty nifty,” Daley wrote.

In the case of the 24-year-old, described in Thursday’s New England Journal of Medicine, lab-dish tests suggested that a drug used to treat a type of blood cancer and some other unrelated conditions might help.

It’s not a drug that doctors would have thought to try, because the man technically does not have cancer. But his lung tumor shrank after a few months of treatment, and he has been stable for more than a year. He still has to have operations to remove throat growths that keep coming back, but only about once every five months.

The man, an information technology specialist in suburban Washington who asked to remain anonymous to protect his privacy, has recurrent respiratory papillomatosis, or RRP. It’s usually due to infection at birth with certain types of a virus, HPV, that causes genital warts.

The condition causes wartlike growths in the throat, usually around the voice box. These growths usually are noncancerous but can turn malignant, and even benign ones can prove fatal if they spread to the lungs. The main treatment is surgery, usually with lasers to vaporize the growths and keep them from choking off the airway or making it hard to talk.

About 10,000 or more people in the U.S. have the disease, said Jennifer Woo, president of the RRP Foundation. Woo, 29, is a medical student at Georgetown and one of the researchers on the study. She also has the condition but said it is confined to her throat and has required only about 20 surgeries so far.

The man in the study has a much more serious case.

“I was diagnosed when I was 3 or 4. At first, I had to have surgery every 7 to 10 days,” the man said in a phone interview. “I get short of breath and my voice will get more hoarse.”

Two years ago, the growths to his lungs became extensive and life-threatening, and his physician, Dr. Scott Myers, described the condition at a meeting of Georgetown hospital specialists. “It’s crushing the airway,” Myers said.

Doctors suggested that the new lab method pioneered by Schlegel and others might help. It borrows an idea from stem cell researchers: adding mouse cells for nourishment, plus a chemical that prevents cell death to an ordinary lab culture medium. That enabled healthy and cancerous cells to keep growing indefinitely.

Researchers grew “mini tumors” from the man’s lung mass and from healthy tissue and screened various drugs against them. One proved ineffective. Another worked against the tumor but at too high a dose to be safe. The third did the trick.

A similar approach could let doctors screen drugs for cancer patients.

“What could be more personalized than taking this person’s cell, growing it in culture, finding a drug to treat them and then treat them?” said Doug Melton, co-director of the Harvard Stem Cell Institute. The Georgetown method gives an answer quickly enough that it could save lives, he said.

Tyler Jacks, a cancer researcher at the Massachusetts Institute of Technology and former president of the American Association for Cancer Research, said the next step is to show that this could work for many different cancers and that it leads to better outcomes in patients.

“It seems to have worked in this one instance, but other tumors might prove to be more challenging,” he said.

The National Institutes of Health paid for much of this work and has already sent research teams to Georgetown to learn the method. About a dozen other universities have done the same, Schlegel said. So far, his lab has grown prostate, breast, lung and colon cancer cells. Georgetown University is seeking a patent on the method.

September, 2012|Oral Cancer News|

Demystifying the immortality of cancer cells

Source: http://medicalxpress.com/
Author:

In cancer cells, normal mechanisms governing the cellular life cycle have gone haywire. Cancer cells continue to divide indefinitely, without ever dying off, thus creating rapidly growing tumors. Swiss scientists have discovered a protein complex involved this deregulated process, and hope to be able to exploit it to stop tumor formation in its tracks.

The telomeres can be seen as white dots on these chromosomes © National Institute of Health

All our cells come equipped with an automatic self-destruct mechanism; they are programmed to die after a certain number of divisions. This internal clock is of great interest to cancer researchers, because most forms of cancer exhibit a defect in this innate timing mechanism. Cancer cells continue to divide indefinitely, long past the moment at which a normal cell would self-destruct. A team of researchers from professor Joachim Lingner’s laboratory at EPFL has learned how this defect is regulated in a tumor. Post-doctoral researcher Liuh-Yow Chen led the team in publishing an article appearing in the journal Nature on the 4th of July 2012. Their hope is that the discovery will provide new targets for drug therapies to combat the deadly disease.

Cellular immortality, which is responsible for cancer formation, hearkens back to a critical function of the cells of the developing embryo. At the ends of every chromosome there is a special sequence of DNA known as a telomere, whose length is governed by the telomerase enzyme. This sequence represents the lifespan of the cell. Every time the cell divides, it is shortened, and when the telomere finally runs out, the cell dies. This reserve allows most cells to divide about 60 times – sufficient for the cell to play its given role in the organism, without succumbing to inevitable genetic mutation.

Cellular immortality, cancer’s common denominator
Normally, once the embryonic stage is completed, our cells stop producing telomerase – with the notable exception of somatic stem cells. But occasionally, a cell will mutate and reactivate production of the enzyme, so that when the cell divides, the telomere gets longer instead of shorter. This is what gives cancer cells their immortality.

“This mutation, on its own, is not enough to cause cancer,” explains Joachim Lingner, co-author and head of the lab. “But cellular immortality is a critical element in tumor formation in 90% of known cancers.” Researchers the world over hope to be able to stop the runaway growth of cancer cells by targeting this mechanism with drug therapy.

But interestingly enough, even in a cancer cell the telomere doesn’t grow indefinitely long. With each cell division it loses some 60 nucleotides, like most cells, but then the activated telomerase causes it to gain just as many back. The internal clock is reset to zero, and the cell becomes immortal. But there’s one interesting question here: What is stopping the telomere from getting indefinitely long?

Stopping the clock with three proteins
The EPFL team was able to provide an answer to this question; they identified three proteins that join together and then attach themselves to the telomere. A bit like a lid on a pot, this protein complex prevents telomerase from acting on the telomere. But in the cancer cell, their timing is off – their involvement takes place too late.

“If we could cause these proteins to act earlier, or if we could recreate a similar mechanism, the cancer cell would no longer be immortal,” explains Ligner. The cancer cells would die a normal death. Clinical applications are still a long way off, however, he insists. “Our discovery may allow us to identify potential targets – for example, a secondary protein to which these three proteins also attach. But right now our work is still in the basic research stages.”

Source: Cancer July 5, 2012