Overcoming the odds

  • 12/25/2007
  • Regina,Saskatchewan,Canada
  • Tim Switzer
  • Regina Post Leader (www.canada.com/reginaleaderpost)

“Live strong” is more than just a yellow bracelet on Dale Bloom’s wrist. It’s how the Regina man has been forced to approach his life for the last three years.

Bloom was diagnosed with advanced stage oral cancer on Jan. 10, 2005. On Oct. 7 of this year, he finished the Chicago Marathon.

“It’s like night and day,” said Bloom, 46. “I never gave up any hope. Even though the odds weren’t that great — I was told it was a one-in-three shot — it never crossed my mind that I wasn’t the one.”

As he stood among 44,999 other runners in the starting area of the marathon, Bloom’s mind couldn’t help but wander to the previous 21/2 years.

“There were a lot of people that helped me get to that point,” Bloom said, fighting back tears. “It was crazy, but that’s who I thought about. I thought about my co-workers, who set up a dance card to each take an hour out of their schedules to come and sit with me at chemotherapy just to take my mind off things. I thought about my son’s friends parents, who got together and all organized days of cooking where they brought us food each and every day. My sisters were there from beginning to end. In 2005, I lost my mother and in 2006, I lost my father so I thought about them a lot.

“And then I thought about my wife and kids, who were the reason why I wanted to get through this.”

There were times in those first few months when it looked like running would never be an option again. By April 2005, Bloom had lost 45 pounds and was bedridden. He only got up to go to the Allan Blair Cancer Centre for radiation and chemotherapy treatments. The effect of the treatments left him unable to speak or create saliva, forcing him to use a feeding tube. He eventually underwent four surgeries to remove the muscles on the left side of his neck.

But it was during those low times that Bloom decided what he wanted most.

“We would communicate in writing and one of his goals very early on was he wanted to be able to run again,” said Bloom’s wife, Dawn. “That meant normalcy to him. I remember the day he told me all he wanted to do was run around the lake.

“I thought, ‘OK, were going to set that as a goal.’ But privately I just wanted him to live. I knew running was his passion and it would make him happy if he could run just a little bit.”

But with two radiation treatments per day, Bloom’s health started to improve. By June 30, he made his trek around Wascana Lake.

“There’s no doubt in any of our minds or from his cancer team that the key reason he is still alive is because when he couldn’t fight anymore, his body was so strong from being in shape before, that it started fighting again,” said Dawn. “That’s why it’s important for him to keep running because if that cancer comes back, he knows his body can fight for him again.”

As the months wore on, Bloom steadily improved. In September 2005, he was back at work at Crown Investments Corporation, where he is a corporate secretary, and was into a regular running routine the following spring.

The normalcy Bloom craved was evident this year in Chicago. When he woke up the morning of the race, the temperature outside was already 27 C with 100-per-cent humidity. Midway through the race, the temperature had risen to 33 C and people started dropping out of the race left and right.

“All you heard were sirens, constant sirens,” recalled Bloom. “There were gurneys and stretchers and people getting taken to hospitals. The emergency rooms in Chicago got so full that they applied the pressure to stop the race.”

At the 35-kilometre mark, runners were told to stop and that buses would be coming to pick them up.

Bloom soon realized no buses were imminent and picked up the pace. That continued until the 40-kilometre mark, where race officials stood in his way and wouldn’t let him finish unless he started walking.

Once you stopped running you realized, ‘Geez, it’s really hot!’ ” Bloom said with a laugh.

Meanwhile, Dawn and two of the couple’s three children, son Connor and daughter Morgan (their other daughter, Katie, couldn’t make the trip), were waiting at the finish line, wondering what was taking Dale so long. No one had informed them that marathoners were being asked to stop running.

That didn’t make the moment Bloom crossed the finish line any less emotional.

“It was so overwhelming for him to finish because it was like we could start living our new normal life again after that day,” said Dawn. “It was very, very different from all the other marathons and our family knew it. Everyday is different than it was a couple years ago, but that moment was like a new beginning.”

They understood that even more when touring Chicago a week later. While trying to get into Wrigley Field to take some photos, Dale and Connor ran into a man outside the stadium, who noticed the scars on Dale’s neck. As it turned out, that man, Joe, had gone through the same thing in 1998. He also made sure the family got the photos they wanted.

After that, the Blooms sat and talked with Joe about what each had been through.

“We had never met anyone who has survived this cancer for more than five years,” said Dawn. “I said something about that and Joe said, ‘Now you have.’ ”

Bloom is still going to regular checkups, but there hasn’t been any sign of cancer since his surgeries. And he’s shooting for either the New York or Chicago marathon in 2008.

“Things are good again,” said Dale.

2009-04-16T09:48:42-07:00December, 2007|Archive|

Machine ‘may speed up cancer treatment’

  • 12/25/2007
  • Melbourne, Australia
  • staff
  • news.theage.com.au

A state-of-the-art radiation machine being trialled in Australia could revolutionise cancer treatment, saving patients time and money, doctors said.

Doctors at Brisbane’s Princess Alexandra (PA) Hospital are confident the new $2.5 million linear accelerator, now in use for intermediate or phase two trials on early stage breast cancer patients, would be of particular benefit to women from rural and remote areas.

Dr Margot Lehman, a radiation oncologist conducting the trial, said women were being recruited at five centres in Australia, and two in New Zealand, under the Trans-Tasman Radiation Oncology Group (TROG).

“If we can prove this is a feasible treatment option, then we will be going to a full-blown phase three trial where we will be comparing this technique with the standard six-week course for women with early stage breast cancer who have had breast conserving treatment,” she said.

PA Hospital’s director of radiation oncology services Professor Bryan Burmeister said women in rural or remote areas often opted for a mastectomy rather than spending the time and money on travelling and accommodation needed for six weeks of treatment.

“Now they only have to spend a week and that is a huge difference, in terms of cost, in terms of quality of life and numerous other things,” he said.

Older machines only targeted tumours in relation to the nearest bones, he said.

But the new generation technology pinpointed tumours in soft tissue, enabling radiation treatment to be carried out on a smaller area and over a shorter period once the tumour had been surgically removed.

“If we can accurately position the tumour, we can minimise the radiation dose to surrounding normal tissues,” Prof Burmeister said.

“And if we can reduce the amount of tissue we have to treat in the body, we can certainly make the course of treatment shorter and that enables us to reduce our waiting lists and spare patients a long time away from their homes.”

Prof Burmeister said breast cancer made up a significant part of the oncology department’s workload at the PA Hospital, which was why the breast cancer trial was being conducted, comparing it with conventional six-week treatments.

But the machine also had applications for lung, prostate, head and neck cancers, he said.

“Once this technology becomes more streamlined and we are able to introduce it to other forms of cancer, it will have an impact on reducing the waiting list.”

Marjorie Anderson, 60, from Brisbane bayside suburb Thornlands, said the cancer treatment meant she could spend time with her family at Christmas after condensing six weeks of treatment into one.

“I wouldn’t have been able to go camping (with family),” Ms Anderson told reporters.

“Plus it’s good to get it over twice a day in one full-on week, rather than once a day for six weeks,” Ms Anderson said.

2009-04-16T09:48:19-07:00December, 2007|Archive|

p53 — Master and Commander

  • 12/25/2007
  • Boston, MA
  • William D. Foulkes, M.B., Ph.D.
  • New England Journal of Medicine Volume 357:2539-2541

The gene known variously as p53, TP53, and Trp53 is currently featured in nearly 45,000 published articles listed in PubMed — a remarkable number suggesting that the protein product of this gene, p53, is one of the most important molecules in biology. When it was discovered in 1979, the p53 phosphoprotein (molecular mass, 53 kD) was postulated to have “a crucial role in the modulation of the transformed state.”1 This idea has found support in innumerable studies, including the one reported on by Poeta et al. in this issue of the Journal (pages 2552–2561), in which somatic mutations in TP53 were associated with a poor outcome after surgical treatment of squamous-cell carcinoma of the head and neck. In particular, mutations that resulted in a shortened, and presumably malfunctioning, p53 protein or that interfered with the DNA-binding domain of p53 were independent predictors of a poor prognosis. So what is p53, and why is it important in cancer?

The p53 protein functions primarily as a multitarget transcription factor. This means that it controls the expression of a wide range of genes with disparate functions. Additional cancer-related functions continue to be discovered, but thus far, its known functions include cell-cycle regulation, senescence, apoptosis, repair of DNA damage caused by genotoxic agents, angiogenesis, and regulation of oxidative stress.2 Such a broad range of relevant functions places p53 in a controlling position with respect to many cancer-related processes. With such a long list of interacting partners, it is not surprising that alterations in TP53 are very often found in cancer3 — indeed, it is probably the mutated gene most frequently found in cancer cells.

The important question for clinicians is whether all this knowledge is useful in the management of cancer. Despite the abundance of data, it has been hard to show that TP53-mutation status can really have an influence. For example, the expert panel of the American Society of Clinical Oncology on the use of tumor markers in breast cancer recently concluded that the current data are insufficient to support a recommendation for using p53 measurements in the treatment of women with breast cancer.4 This is also true for other less thoroughly investigated cancers, such as head and neck cancer.

Of course, clinical recommendations must take into account what is happening in the real world of patient care, not just the results of randomized, controlled trials. For example, Poeta et al. used microarray technology to identify TP53 mutations. The use of this approach raises questions about the general applicability of the findings, but as the costs of these types of comprehensive genomic analyses continue to decrease, there will be an increasing demand to introduce the technology into the clinic. Indeed, the study by Poeta et al. and other recent investigations suggest that we are not too far from the era of molecularly tailored medicine,5 and it is reasonable to predict that knowledge of TP53 status will be central to this field.

In simple terms, oncologists want to know whom to treat and how to treat them. There are three ways in which oncologists could use knowledge of TP53. First, the choice of cancer treatment could be influenced by the status of TP53 in the tumor — patients with a tumor that bears a TP53 mutation would receive one type of treatment, whereas patients without such a mutation would receive a different treatment. But there are thorny details: changes in p53 function can render a tumor sensitive to one type of chemotherapy but resistant to another. Moreover, as shown by Poeta et al. and others, not all apparently deleterious TP53 mutations have the same effect; at the very least, mutations will have to be categorized into subgroups before physicians can decide how the information should be used. For these reasons, the design of the prospective studies that will be required to validate findings based on retrospective analyses will be complex.

Second, small molecules could be specifically designed to target p53 directly, or perhaps indirectly, using the technique of synthetic lethality, in which cells are killed only when two independent pathways are blocked. This approach is specific to cancer cells because only they will have abnormal p53; when a second pathway is interrupted by the chosen drug, cancer cells are killed but normal cells are not. This technique has been used successfully to kill cells deficient in the BRCA1 or the BRCA2 protein and is now being used in patients with germ-line mutations in the BRCA1 or the BRCA2 gene who have had a relapse after initial treatment for breast or ovarian cancer. It is an attractive approach, because TP53 mutations that result in a malfunctioning p53 protein are so common in cancer.

A third avenue is gene therapy using TP53 itself. Despite early enthusiasm, it has not proved easy to develop successful gene therapy, and recent well-publicized catastrophes have cast doubt on the whole field. Moreover, it has become apparent that TP53 not only is a cancer gene but also has a broad role in the functioning of the entire organism.2 Thus, altering the function or even the level of p53 protein may have profound effects on normal cells. For example, slight overexpression of p53 in all cells in a mouse resulted in premature aging. In humans, the Arg72Pro polymorphism in p53 results in a slight reduction in the activity of the protein. This change is associated with a small but probably significant increase in cancer risk but also appears to be associated with an increased life span. Perhaps p53, when functioning normally, acts to regulate stem-cell renewal and thus has opposing effects on cancer and longevity through the expansion or reduction of the stem-cell pool.

It thus appears that p53 touches on many parts of our lives — growth, health, longevity, and death. More, perhaps, than a “genome guardian,” p53 seems to be master and commander of key cellular processes that help to determine our fate. Controlling this molecule when it has gone awry may prove to be difficult. As has been widely observed, replacing malfunctioning commanders with new ones that are designed to work better is fraught with its own dangers.

Source Information

Dr. Foulkes is the director of the Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal.


1. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979;278:261-263. [CrossRef][Medline]
Vousden KH, Lane DP. p53 In health and disease. Nat Rev Mol Cell Biol 2007;8:275-283.

2. Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994;54:4855-4878.

3. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol (in press).
Varmus H. The new era in cancer research. Science 2006;312:1162-1165

2009-04-16T09:47:58-07:00December, 2007|Archive|

Researchers Train the Immune System to Deliver Virus that Destroys Cancer in Lab Models

  • 12/25/2007
  • web-based article
  • staff
  • Biocompare (www.biocompare.com)

An international team of researchers led by Mayo Clinic have designed a technique that uses the body’s own cells and a virus to destroy cancer cells that spread from primary tumors to other parts of the body through the lymphatic system. In addition, their study shows that this technology could be the basis for a new cancer vaccine to prevent cancer recurrence.

The technology combines infection-fighting T-cells with the vesicular stomatitis virus that targets and destroys cancer cells while leaving normal cells unharmed. The study, which has not yet been replicated in humans, is significant because it describes a potential new therapy to treat and prevent the spread of cancer in patients.

“We hope to translate these results into clinical trials. However, until those trials are done, it’s difficult to be certain that what we see in mouse models will clearly translate to humans. We’re hopeful that will be the case,” says Richard Vile, Ph.D., a Mayo Clinic specialist in molecular medicine and immunology and the study’s principal investigator.

In primary cancers of the breast, colon, prostate, head and neck and skin, the growth of secondary tumors often pose the most threat to patients, not the primary tumor. The prognosis for these patients often depends upon the degree of lymph node involvement and whether the cancer has spread.

Dr. Vile and colleagues theorized that they could control the spread of cancer through the lymphatic system (bone marrow, spleen, thymus and lymph nodes) by manipulating the immune system.

Researchers zeroed in on immature T-cells from bone marrow, programming them to respond to specific threats to the immune system while delivering a cancer-destroying virus to the tumor cells.

To deliver the virus, researchers removed T-cells from a healthy mouse, loaded them with the virus and injected the T-cells back into the mouse. Researchers found that once the T-cells returned to the lymph nodes and spleen, the virus detached itself from the T-cells, found the tumor cells, selectively replicated within them and extracted tumor cells from those areas.

Cancer Vaccine
The procedure used in this study triggered an immune response to cancer cells, which means that it could be used as a cancer vaccine to prevent recurrence.

“We show that if you kill tumor cells directly in the tumor itself, you can get a weak immunity against the tumor, but if you use this virus to kill tumor cells in the lymph nodes, you get a higher immunity against the tumor,” Dr. Vile says.

The technique used in this study successfully treated the cells of three different diseases: melanoma, lung cancer and colorectal cancer. The results include:

– Two days after treatment, the presence of melanoma tumor cells in lymph nodes was significantly less, but not completely gone. There were no cancer cells in the spleen.

– Ten-to-14 days after a T-cell transfer, both the lymph nodes and spleen were free of melanoma tumor cells.

– Mice treated with a single dose of the T-cells transfer developed a potent T-cell response against melanoma tumor cells.

– Although the procedure was not intended to treat the primary melanoma tumor, significant reductions in tumor cells were observed.

– In mice with lung cancer metastasis, cancer cells were significantly reduced in one-third of mice and completely eradicated in two-thirds of mice. Efforts to clear metastases from colorectal tumors were similarly effective.

– Lung and colorectal tumor cells were purged from lymph nodes. Also, the spleens of mice that had lung cancer developed immunity to the cancer after the treatment.

The technology already exists to extract T-cells from patients, attach the virus and inject the cells back into the patients. Doctors currently use a similar process to attach radioactive tracers to T-cells when trying to find the source of an infection in patients.

“This is technology that is relatively easy to translate to humans because it involves taking T-cells from the patient — something routinely done today — loading them with this virus and then putting those T-cells back into patients whose cancer has spread to lymph nodes, are at high risk of the cancer spreading to other parts of the body or are at high risk of succumbing to the cancer,” Dr. Vile says.

Mayo Clinic
The study appeared in the Dec. 9 online issue of Nature Medicine.

2009-04-16T09:47:33-07:00December, 2007|Archive|

Smokebusters invite Young to give anti-smoking presentation

  • 12/25/2007
  • Moberly, MO
  • Janet Morales
  • Moberly Monitor (/www.moberlymonitor.com)

At age 14, Don Young’s parents divorced. He was naturally upset and turned to friends to help fill the void. Many of these friends were smokers so to fit in and be part of the cool crowd he took up the bad habit too. He told his “Smoker’s Story” and that of other smokers and tobacco chewers to the students at Westran High School with the aid of an electro-larynx since he no longer has a larynx (vocal chords) due to the cancer caused by years of smoking.

“I didn’t like it the first time,” said Young of his initial smoking experience. “It burned my tongue and throat. The doctor said that is a way the body tells you it doesn’t belong. But I didn’t listen to my body and my body got adjusted to it.”

At age 48, Young thought his sore throat was the result of a cold. After it persisted, his wife Kay urged him to see a doctor. A nodule was found in his throat and removed.

“Cigarettes were my best friend,” said Young. “I went everywhere with them. I smoked right up to the hospital to get my biopsy.”

Young was assured the cancer was completely removed. Young had tried to quit smoking before but “that was enough to scare me”. He and his wife both threw away all their cigarettes, never to smoke again.

But the doctor had been wrong.

Three months after the first procedure, Young found the cancer had returned and he underwent the removal of his right vocal chord. He was treated with radiation to keep the cancer from spreading.

It didn’t.

He went back and had a total laryngectomy but was given less than a year to live. It was then he realized he needed to seek a second opinion.

“If you get sick,” said Young, “get a second opinion. Don’t be afraid to ask for a second opinion. If I had, things might have been different but that’s in the past.”

He went to Barnes Hospital in St. Louis. There they performed a 19-hour surgery removing part of both sides of his neck. Six inches of his esophagus was removed. A portion of his small intestine was removed and transplanted in his neck to form a new esophagus. His chest muscle was used to wrap around the front of his neck and skin was grafted from the top of his leg to cover it. But that was still not the end of it.

“The skin graft failed, the intestine died and my neck blew out,’ said Young. “I lost so much blood I passed out. I was sure I was dying.”

Young was in the hospital for four months but he survived the ordeal. Eventually Young’s stomach was pulled up and attached to the back of his throat to make a new esophagus. Since the passage won’t stay open by itself, Young has to put a two-foot flexible tube down his throat for five minutes each morning to dilate the opening.

Since Young had a trachiostomy, he now has an opening in his throat, a stoma, that he breathes through. Since he no longer breathes through his mouth, he has difficulty when he catches a cold because he can’t blow his nose. He has to cover the stoma to take a shower but he cannot swim because of it. He cannot lie down to sleep since bending or lying flat interferes with breathing. Due to the laryngectomy, he must use the mechanical device in order to speak.

But Young is just one person and it is easy for students to think it won’t happen to them. That is why Young brought along photographs of others, including teenagers, who have had life-altering, sometimes life-ending, encounters with cancer due to smoking or chewing tobacco. He showed them pictures of teenagers with severe tongue cancer, a man who lost his nose from years of blowing smoke out through his nasal passages and other gruesome medical photos of people who have suffered from cancer due to the use of tobacco products. He warned girls that smoking effects their unborn children.

“Studies have shown,” said Young, “that a baby stops breathing for 11 seconds whenever the mother takes a drag on a cigarette. Three hundred to 400 babies die of respiratory failure from breathing second-hand smoke.”

Young, who once was told he had less than a year to live has been cancer free for 14 years.

“I’m a survivor, a fighter,” he said. “I don’t believe in giving up.”

Young has used this second chance to spread the word about the dangers of using tobacco products. He has been a volunteer for the American Cancer Society and named St. Louis Volunteer of the year in 1997. He was selected as Community hero and carried the Olympic torch in St. Louis in 1996, 2000 and 2004. He was named Coping magazine’s Cancer Survivor of the Year 2000.

“My fight against smoking has taken me into schools, colleges, churches, youth organizations, public forums, medical schools and corporations to speak with people about my experience,” said Young. “I documented the course of my illness with graphic pictures of my surgeries and treatment. I desired that the pictures would be used to demonstrate the horrors of my cancer treatment and the price I paid for my decisions. I am thankful that I was given a second chance at life to not only show the pictures, but to narrate the story.

“You don’t have to smoke, do drugs,” Young admonished the Westran High Schoolers. “You don’t have to drink alcohol either. Marry someone who doesn’t smoke so your children won’t smoke and your grandchildren won’t smoke. That’s how we can have a smoke-free society.”

2009-04-16T09:47:10-07:00December, 2007|Archive|

Cellphone Use Might Raise Mouth Cancer Risk

  • 12/22/2007
  • United Kingdom
  • staff
  • Cellular- News (www.cellular-news.com)

A new medical study is reporting that cell phone use raises the risk of mouth cancer. Five years of heavy use increased the chances of developing a tumor by around 50 percent compared with people who had never used a mobile phone.

Previous studies into the links between phones and cancer have generated conflicting results with the vast majority claiming to have found no evidence of serious health risks, although some have found increases in cancer rates around the ear.

The lifestyles of 402 people with benign mouth tumors and 56 with malignant tumors were compared to a control group of 1,266 people. Those who used mobile phones were more likely than normal to develop parotid gland tumors. The parotid is the largest of the salivary glands and sits at the back of the mouth not far from the ear. Long-term users of mobile phones tended to develop tumors on the same side of the head as the phone was normally held. People who used mobile phones in rural areas, where the phone has to work harder to make contact with the nearest base station, were found to be at greater risk. The cause of the heightened risk was not established.

Most studies have looked at the way the electromagnetic fields created by phones warm tissue; however, the levels of the fields are thought too small to have a heating effect. Instead, some researchers believe the fields have the power to disrupt chemical bonds within cells or damage DNA. The lead researcher – Dr. Siegal Sadetzki, from the Chaim Sheba Medical Centre in Tel Hashomer, Israel – urges caution regarding drawing conclusions.

The research, carried out in Israel, was published in the American Journal of Epidemiology.

2009-04-16T09:46:49-07:00December, 2007|Archive|

HPV May Cause Second Cancers

  • 12/22/2007
  • Augusta, GA
  • staff
  • www.wjbf.com

About 15 years ago we learned that HPV, the human papilloma virus, causes cervical cancer. Now, researchers say, that could be just the beginning. They’re looking into an HPV risk for other, or second cancers.

Camille Ragin, Ph.D., M.P.H., Epidemiologist, “We realized that these cervical cancer patients, when we looked at these second cancers, they were primarily at an increased risk of developing head and neck cancers and also lung cancer.”

Women aren’t the only ones at risk. Five years ago, Johns Hopkins researchers found HPV in oral cancer, and most of the patients were men.

Maura Gillison, M.D., Head & Neck Oncologist, “To our surprise, it turned out HPV was in a significant number of these cancers, and they seemed to have distinct characteristics that made them different from cancers that were, that didn’t have HPV in them.”

Most of the cancers started in the tonsils and were not associated with smoking or drinking.

Dr. Gillison, “What was critical was just the number of oral sexual partners you’ve had in your lifetime.”

Findings from the studies could raise new questions about the HPV vaccine used to prevent cervical cancer.

Dr. Gillison, “If the vaccine is shown to be effective in preventing oral HPV infection, then it would be indicated regardless of gender.”

Dr. Ragin, “That certainly cannot be ruled out because there are so many other cancers in men, anal cancers and other types of cancers, penile cancers that are in men, that are also driven by HPV.”

An earlier study for the HPV vaccine was conducted at the Medical College of Georgia.

According to the Centers for Disease Control, most people who have HPV infections don’t have symptoms and clear the infection on their own.

2009-04-16T09:46:00-07:00December, 2007|Archive|

Scientists Weigh Stem Cells Role as Cancer Cause

  • 12/22/2007
  • New York, NY
  • Gina Kolata
  • New York Times (nytimes.com)

Within the next few months, researchers at three medical centers expect to start the first test in patients of one of the most promising — and contentious — ideas about the cause and treatment of cancer.

The idea is to take aim at what some scientists say are cancerous stem cells — aberrant cells that maintain and propagate malignant tumors.

Although many scientists have assumed that cancer cells are immortal —that they divide and grow indefinitely — most can only divide a certain number of times before dying. The stem-cell hypothesis says that cancers themselves may not die because they are fed by cancerous stem cells, a small and particularly dangerous kind of cell that can renew by dividing even as it spews out more cells that form the bulk of a tumor. Worse, stem cells may be impervious to most standard cancer therapies.

Not everyone accepts the hypothesis of cancerous stem cells. Skeptics say proponents are so in love with the idea that they dismiss or ignore evidence against it. Dr. Scott E. Kern, for instance, a leading pancreatic cancer researcher at Johns Hopkins University, said the hypothesis was more akin to religion than to science.

At stake in the debate is the direction of cancer research. If proponents of the stem-cell hypothesis are correct, it will usher in an era of hope for curing once-incurable cancers.

If the critics are right, the stem-cell enthusiasts are heading down a blind alley that will serve as just another cautionary tale in the history of medical research.

In the meantime, though, proponents are looking for ways to kill the stem cells, and say that certain new drugs may be the solution.

“Within the next year, we will see medical centers targeting stem cells in almost every cancer,” said Dr. Max S. Wicha, director of the University of Michigan Comprehensive Cancer Center, one of the sites for the preliminary study that begins in the next few months (the other participating institutions are Baylor College of Medicine in Houston and the Dana-Farber Cancer Institute in Boston).

“We are so excited about this,” Dr. Wicha said. “It has become a major thrust of our cancer center.”

At the National Cancer Institute, administrators seem excited, too.

“If this is real, it could have almost immediate impact,” said Dr. R. Allan Mufson, chief of the institute’s Cancer Immunology and Hematology Branch.

The cancer institute is financing the research, he said, and has authorized Dr. Mufson to put out a request for proposals, soliciting investigators to apply for cancer institute money to study cancer stem cells and ways to bring the research to cancer patients. The institute has agreed to contribute $5.4 million.

“Given the current fiscal situation, which is terrible, it’s a surprising amount,” Dr. Mufson said. “We actually asked for less,” he added, but the cancer institute’s executive committee asked that the amount be increased.

Proponents of the hypothesis like to use the analogy of a lawn dotted with dandelions: Mowing the lawn makes it look like the weeds are gone, but the roots are intact and the dandelions come back.

So it is with cancer, they say. Chemotherapy and radiation often destroy most of a tumor, but if they do not kill the stem cells, which are the cancer’s roots, it can grow back.

Cancerous stem cells are not the same as embryonic stem cells, the cells present early in development that can turn into any cell of the body. Cancerous stem cells are different. They can turn into tumor cells, and they are characterized by distinctive molecular markers.

The stem-cell hypothesis answered a longstanding question: does each cell in a tumor have the same ability to keep a cancer going? By one test the answer was no. When researchers transplanted tumor cells into a mouse that had no immune system, they found that not all of the cells could form tumors.

To take the work to the next step, researchers needed a good way to isolate the cancer-forming cells. Until recently, “the whole thing languished,” said Dr. John E. Dick, director of the stem cell biology program at the University of Toronto, because scientists did not have the molecular tools to investigate.

But when those tools emerged in the early 1990s, Dr. Dick found stem cells in acute myelogenous leukemia, a blood cancer. He reported that such cells made up just 1 percent of the leukemia cells and that those were the only ones that could form tumors in mice.

Yet Dr. Dick’s research, Dr. Wicha said, “was pretty much ignored.” Cancer researchers, he said, were not persuaded — and even if they had accepted the research — doubted that the results would hold for solid tumors, like those of the breast, colon, prostate or brain.

That changed in 1994, when Dr. Wicha and a colleague, Dr. Michael Clarke, who is now at Stanford, reported finding cancerous stem cells in breast cancer patients.

“The paper hit me like a bombshell,” said Robert Weinberg, a professor of biology at M.I.T. and a leader in cancer research. “To my mind, that is conceptually the most important paper in cancer over the past decade.”

Dr. Weinberg and others began pursuing the stem-cell hypothesis, and researchers now say they have found cancerous stem cells in cancers of the colon, head and neck, lung, prostate, brain, and pancreas.

Symposiums were held. Leading journals published paper after paper.

But difficult questions persisted. One problem, critics say, is that the math does not add up. The hypothesis only makes sense if a tiny fraction of cells in a tumor are stem cells, said Dr. Bert Vogelstein, a colon cancer researcher at Johns Hopkins who said he had not made up his mind on the validity of the hypothesis.

But some studies suggest that stem cells make up 10 percent or even 40 percent or 50 percent of tumor cells, at least by the molecular-marker criterion. If a treatment shrinks a tumor by 99 percent, as is often the case, and 10 percent of the tumor was stem cells, then the stem cells too must have been susceptible, Dr. Vogelstein says.

Critics also question the research on mice. The same cells that can give rise to a tumor if transplanted into one part of a mouse may not form a tumor elsewhere.

“A lot of things affect transplants,” Dr. Kern, the Johns Hopkins researcher, said, explaining that transplanting tumors into mice did not necessarily reveal whether there were stem cells.

Other doubts have been raised by Dr. Kornelia Polyak, a researcher at the Dana-Farber Cancer Institute. Dr. Polyak asked whether breast cancer cells remain true to type, that is, whether stem cells remain stem cells and whether others remain non-stem cells? The answer, she has found, is “not necessarily.”

Cancer cells instead appear to be moving targets, changing from stem cells to non-stem cells and back again. The discovery was unexpected because it had been thought that cell development went one way — from stem cell to tumor cell — and there was no going back.

“You want to kill all the cells in a tumor,” Dr. Polyak said. “Everyone assumes that currently-used drugs are not targeting stem cell populations, but that has not been proven.”

“To say you just have to kill the cancer stem cell is oversimplified,” she added. “It’s giving false hope.”

The criticisms make sense, Dr. Weinberg said. But he said he remained swayed by the stem cell hypothesis.

“There are a lot of unanswered questions, mind you,” he said. “Most believe cancer stem cells exist, but that doesn’t mean they exist. We believe it on the basis of rather fragmentary evidence, which I happen to believe in the aggregate is rather convincing.”

Dr. Wicha said he was convinced that the hypothesis was correct, and said it explained better than any other hypothesis what doctors and patients already know.

“Not only are some of the approaches we are using not getting us anywhere, but even the way we approve drugs is a bad model,” he said. Anti-cancer drugs, he noted, are approved if they shrink tumors even if they do not prolong life. It is the medical equivalent, he said, of mowing a dandelion field.

He said the moment of truth would come soon, with studies like the one planned for women with breast cancer.

The drug to be tested was developed by Merck to treat Alzheimer’s disease. It did not work on Alzheimer’s but it kills breast cancer stem cells in laboratory studies, Dr. Wicha says.

The study will start with a safety test on 30 women who have advanced breast cancer. Hopes are that it will be expanded to find out if the drug can prolong lives.

“Patient survival,” Dr. Wicha said, “is the ultimate endpoint.”

2009-04-16T09:45:40-07:00December, 2007|Archive|

Cancer Surgery Switch

  • 12/22/2007
  • Torquay, England
  • staff
  • www.thisissouthdevon.co.uk

Life saving surgery for people with cancer of the head and neck is to move from Torbay Hospital to Exeter, it has been revealed. Around 50 people a year are currently treated at Torbay Hospital for the disease, Torbay Council’s Stronger Communities Scrutiny Board heard before giving the decision their blessing.

Under the plans being brought in patients will still have initial consultancy and follow up appointments at the Shiphay site, but the actual operation will take place at the Royal Devon and Exeter Hospital.

The scrutiny board heard there had been ‘widespread professional debate’ about the changes, along with future plans to have either Plymouth or Exeter as the one main centre for treatment.

Guidelines say head and neck cancer centre services should be concentrated in centres serving one million people and at least 100 newly-diagnosed cases a year.

2009-04-16T09:45:12-07:00December, 2007|Archive|

TP53 Mutations Associated with Decreased Survival in Head and Neck Cancer

  • 12/21/2007
  • Memphis, TN
  • staff
  • CancerConsultants.com

According to an article recently published in the New England Journal of Medicine, mutations in the TP53 gene result in lower survival rates for patients diagnosed with squamous-cell carcinoma of the head and neck. Patients with this genetic mutation may benefit from certain therapeutic approaches.

Head and neck cancers originate in the oral cavity (lip, mouth, tongue), salivary glands, paranasal sinuses, nasal cavity, pharynx (upper back part of the throat), larynx (voice box), and lymph nodes in the upper part of the neck. Worldwide, head and neck cancer is diagnosed in approximately 640,000 people annually and is responsible for approximately 350,000 deaths each year.

Squamous cell carcinoma of the head and neck is the most common type of head and neck cancer; it originates in squamous cells.

As more is understood about cancer, genetics has been recognized as a crucial factor in the disease’s development. One area of genetic research involves the p53 protein, which is produced by the TP53 gene. The p53 protein suppresses the abnormal growth of cancer cells. If mutations exist in the TP53 gene, abnormal p53 proteins are produced that often lack the ability to suppress the growth of tumors.

Researchers from the United States and Italy recently conducted a clinical trial to evaluate the potential effects of a mutated TP53 gene on outcomes among patients with squamous-cell carcinoma of the head and neck. This trial included 560 patients who underwent surgery in an attempt to cure their disease. Mutations of the TP53 gene were analyzed from samples of the cancer taken during surgery. Mutations were classified as either disruptive or nondisruptive, depending upon how the TP53 mutation affected the p53 protein. Patients were followed for approximately seven years.

– TP53 mutations were found in over 53% of patients.

– Overall, any type of mutation within the TP53 gene was associated with a 40% decrease in overall survival.

– Patients who had TP53 mutations classified as disruptive mutations were associated with a 70% decrease in overall survival compared with patients with no TP53 mutations.

The researchers concluded that mutations within the TP53 gene, particularly those that are classified as disruptive mutations, significantly decrease overall survival among patients with squamous-cell head and neck cancer. Future trials will undoubtedly continue to explore genetics’ role in cancer with the goal of individualizing therapy.

Poeta M, Manola J, Goldwasser M, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. The New England Journal of Medicine. 2007;357:2552-2561.

2009-04-16T09:44:52-07:00December, 2007|Archive|
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