that might save

big problems of

diabetes, cancer

Nicky Phillips

February 18, 2011

Then and now … members of the group of 99 Ecuadorians with dwarfism who took part in a 22-year study, pictured at the start of the study in 1988, above, and in 2009.

A GROUP with dwarfism from a province in Ecuador could hold clues to preventing cancer.

Of the 99 individuals, who are in perfect proportion except for a genetic mutation that stunts their growth, only one developed cancer during a 22-year study.

Scientists researching the group believe this growth mutation is the key to their disease immunity, and suggest drugs could give a similar degree of protection to full-grown adults.

An Ecuadorian endocrinologist and co-author of the study, Jaime Guevara-Aguirre, said researchers first noticed the lack of chronic disease in the community while they were investigating their growth defect.

”[We] were more in search of problems than solutions,” he said.

After more than two decades of following those with Laron dwarfism, which is caused by a mutation in their growth hormone receptor gene, Dr Guevara-Aguirre and his American colleague Valter Longo found no cases of diabetes and only one non-lethal case of cancer.

When they looked at the group’s normal-sized relatives, who lived in the same town over the same period, around17 per cent had been diagnosed with cancer and 5 per cent had diabetes – the same rate found among other Ecuadorian adults.

The researchers concluded that growth hormone must have a downside in normal size adults. ”The growth hormone receptor-deficient people don’t get two of the major diseases of ageing,” said Associate Professor Longo, a biologist at the University of Southern California.

To understand how this mutation could protect against cancer and diabetes, the researchers studied the effects of compounds in the participants’ blood.

They found low levels of IGF-1 could reduce DNA damage and promote cell death when DNA damage did occur – two processes that decrease cancer-promoting behaviour in cells.

The Laron group also had lower blood insulin levels, which accounted for the absence of diabetes.

People with Loran dwarfism were instead more likely to die from accidents, cardiovascular disease or alcohol-related causes, the researchers found.

Drugs that reduce growth hormone are readily available and are used to treat people with gigantism. The risks and benefits of giving adults these or similar drugs to reduce growth hormones would need to be weighed up against the side-effects of drugs used to treat diabetes and cancer, said Professor Longo, whose findings are published in the journal Science Translational Medicine.

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Natives use for cancer treatments

Medium sized shrubby tree with soft cork-like bark. Small flowers are followed by little orange tomato-like fruits. Plant is used for its anti-cancer properties.

Description: Small or medium sized shrubby tree to 10-20ft. Small orange fruits are very popular with birds, but have little taste and may not be palatable for humans. Despite its name, it does not contain any nicotine compounds. The common name Wild Tobacco is a misnomer.

Hardiness: Subtropical, will survive brief frosts

Uses: Plant contains Withaferin A and Withacnistin, both having anti-tumor properties. Extracts from this plant have historically been used by natives as an herbal treatment for cancer. Can also be used as a diuretic.

Native Range: Native to Central and South America and the Caribbean.

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Dec 17 – Video of tumor growth in zebrafish is providing clues that could lead to new cancer treatments. Images from scientists in the UK and Italy show how new cancer cells co-opt the immune system into helping the disease spread. Rob Muir reports

View video here

Cure clues from cancer cell close-up

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Could Improve Gene Therapy

for Brain Cancer

Science (Aug. 11, 2010) — An ingredient in the venom of the “deathstalker” scorpion could help gene therapy become an effective treatment for brain cancer, scientists are reporting. The substance allows therapeutic genes — genes that treat disease — to reach more brain cancer cells than current approaches, according to the study in ACS Nano.

Miqin Zhang and colleagues note that gene therapy — the delivery of therapeutic genes into diseased cells — shows promise for fighting glioma, the most common and most serious form of brain cancer. But difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients.

The scientists describe a new approach that could solve these problems. Key ingredients of their gene-delivery system are chlorotoxin, the substance in deathstalker scorpion venom that can slow the spread of brain cancer, and nanoparticles of iron oxide. Each nanoparticle is about 1/50,000th the width of a human hair. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient. “These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers,” the article notes.

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Saving Eyes

Ocular Oncologists Inject Drug Into Eye

To Starve Tumors And Save Sight

October 1, 2008 — Ocular oncologists adopted a drug originally intended to treat colon cancer as a treatment for cancers in the eye as well as macular degeneration. The drug reduces abnormal blood vessel growth, which starves tumors and stops blood vessels from leaking. This interrupts the processes that would, if not stopped, greatly damage patients’ vision.

Whether it’s cancer or macular degeneration, many times patients must face the reality that they will go blind. Now, a new treatment is helping save their sight.

The first thing everyone notices about Dove Karn is her beautiful blue eyes — and it was in Central Park where she came to terms with the fact that she had melanoma in one of those very eyes.

Her tumor was treated with radiation — but the side effects could destroy her vision. Ocular oncologist Paul Finger turned to a new drug to stop Dove’s vision from slipping away.

“It’s a real paradigm shift — like antibiotics were for infections,” says Paul Finger, M.D., an ocular oncologist at the New York Eye Cancer Center in New York City. “This anti-blood-vessel drug is saving people’s vision.”

Avastin is a shot given directly into the eye. It starves the tumor by stopping the growth of abnormal blood vessels that normally would feed the tumor.

“Avastin stops new blood vessels from growing, but it also prevents new and old blood vessels from leaking — and the leaking is what takes away most of the patient’s vision,” Dr. Finger said.

Dove will need to get shots every 6 to 8 weeks, indefinitely — but she says it’s worth it.

“This year was the year that I could say I’m in remission,” Karn said. “I have a full-time teaching job. My children are fabulous — life is wonderful right now.”

ABOUT CANCER IN THE EYE: Ocular melanoma — eye cancer — is a particularly rare and aggressive form of cancer that attacks the pigment cells in the retina. There are essentially two types of intraocular melanoma: low-grade tumors, which grow slowly and rarely metastasize, and high-grade tumors, which grow more quickly and metastasize at a very early stage. Once a tumor metastasizes, the cancer spreads quickly to the liver and other organs, and a patient has only 6 to 12 months to live in the worst cases, although some can survive for as long as 5 years. The National Eye Institute estimates some 2,000 newly diagnosed cases of ocular melanoma occur per year in the United States and Canada –roughly seven in one million people. It affects people of all ages and races, and is not hereditary. Ocular melanoma kills nearly half of those who develop it.

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Study Suggests

Science (July 28, 2010) — Current research suggests that taking morphine can block new blood vessel and tumor growth. The related report by Koodie et al, “Morphine suppresses tumor angiogenesis through a HIF1?/p38MAPK pathway,” appears in the August 2010 issue of the American Journal of Pathology.

Morphine is currently the gold standard of analgesics used to relieve severe pain and suffering. Angiogenesis, or new blood vessel growth, is critical for tumor progression from dormant to malignant. Morphine is commonly used to treat cancer pain, but the effects of morphine use on new blood vessel and tumor growth remain controversial.

Using a clinically relevant morphine dose in a mouse model of Lewis lung carcinoma, researchers led by Dr. Sabita Roy of the University of Minnesota Medical School in Minneapolis, MN examined the effect of morphine use on new blood vessel growth in tumors. They found that chronic morphine use decreased levels of tumor angiogenesis in a manner dependent on the opioid receptor. This effect was mediated by suppression of signaling induced by low oxygen concentrations, leading to a reduction in the levels of pro-angiogenic factors. Therefore, morphine may not only serve as an analgesic for cancer patients, but may also inhibit tumor angiogenesis and growth.

Koodie et al conclude that “morphine is a potential inhibitor of tumor growth, through the suppression of tumor cell-induced angiogenesis and hypoxia-induced p38 MAPK activation of HIF-1. In addition to its analgesic potential, morphine can be exploited for its anti-angiogenic potential in cancer pain management; these findings support the use of morphine for cancer pain management.”

This work was supported by the National Institutes of Health

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The Cancer-Causing Sex Virus

Matthew Herper, 07.21.10, 04:15 PM EDT

HPV–known for causing cervical cancer–is

emerging as the leading cause of throat cancer in

men. Should they get the vaccine too?

Nine Things You Need To Know About HPV

Martin Duffy, a Boston consultant and economist, thought he just had a sore throat. When it persisted for months, he went to the doctor and learned there was a tumor on his tonsils.

Duffy, now 70, had none of the traditional risk factors for throat cancer. He doesn’t smoke, doesn’t drink and has run 40 Boston marathons. Instead, his cancer was caused by the human papilloma virus (HPV), which is sexually transmitted and a common cause of throat and mouth cancer.

HPV tumors have a better prognosis than those caused by too many years of booze and cigarettes. But Duffy “is in the unlucky 20%” whose cancer comes back–despite rounds of chemotherapy and radiation that melted 20 more pounds off a lean 150-pound frame. Now the cancer has spread throughout his throat, making eating and talking difficult. “I made my living as a public speaker,” he says. “Now I sound like Daffy Duck.” Duffy believes he has only a few months left. “How do you tell the people you love you love them?” he asks.

Nine Things You Need To Know About HPV

Most strains of the HPV virus are harmless, but persistent infections with two HPV strains cause 70% of the 12,000 cases of cervical cancers diagnosed annually in the U.S. Other forms of the sexually transmitted virus can cause penile and anal cancer, and genital warts. The HPV throat cancer connection has emerged in just the last few years and is so new that the government doesn’t track its incidence. Researchers believe it is transmitted via oral sex. But top researchers estimate that there are 11,300 HPV throat cancers each year in the U.S.–and the numbers are growing fast as people have been having more sexual partners since the 1960s. By 2015 there could be 20,000 cases. For more surprising discoveries about HPV, read here.

These big numbers have some top researchers arguing that drug makers should test whether HPV vaccines now used to prevent cervical cancer in women can also prevent throat infections in boys. Two vaccines, Gardasil from Merck ( MRK – news – people ) and Cervarix from GlaxoSmithKline ( GSK – news – people ), are approved for preventing cervical cancer. Gardasil is approved for use in boys only to prevent genital warts.

Vaccinating boys could stop this meteoric increase in throat cancer. “Clearly, boys need to be vaccinated,” says Marshall Posner, the incoming medical director of head and neck cancer at Mt. Sinai Medical Center in New York. “I want my kids to be vaccinated. I don’t see a downside to these vaccines.”

There’s only one problem: The vaccine manufacturers aren’t terribly hot on the idea. GlaxoSmithKline says it has no plans to study throat cancer. It adds that it is “committed to providing a vaccine specifically designed to protect against cervical cancer in girls and young women.”

Merck, the maker of Gardasil, seemed more interested a couple of years ago. In 2008 it funded Maura Gillison, the Ohio State University researcher who established the HPV-throat-cancer link in 2000, to do a pilot study to show that test could reliably detect HPV infection in the throat. The pilot study was successful. By early 2009 Gillison says that a larger study of the vaccine in throat cancer looked close to being green lit.

But after Merck agreed to buy rival Schering-Plough ( SGP – news – people ) for $41 billion in March 2009, interest in a big study seemed to evaporate, Gillison says. In a statement, Merck says that “due to competing research and business priorities, we decided not to move ahead with an efficacy study at this time.”

The drug makers’ reticence probably stems from a fear that a throat-cancer vaccine would be hard to get approved. Papilloma viruses usually cause cancer slowly, causing pre-cancerous lesions that take many years to blossom into full-fledged malignant tumors. Papilloma viruses cause the horn-like growths in rabbits that probably gave rise to myths of “jackalopes” in the American West. In the cervix, early abnormal growths can be picked up with a diagnostic test, the Pap smear. Clinical trials of Gardasil and Cervarix took advantage of this, measuring the number of pre-cancerous growths prevented by the vaccines.

But there are no easy-to-detect pre-cancers in the throat. Adolescent boys would have to be followed for decades to to see if the vaccine prevented throat cancer, an unlikely scenario. Short of this, studies could only look at the prevention of HPV throat infections, not cancer or cancer precursors directly. Approving a vaccine for wide use based on this type of short-term data would require a leap of faith that the Food and Drug Administration might not be willing to take.

Top researchers say the federal government needs to step in and fund the long study if drug companies cannot be persuaded to do it themselves. “I’m sorry Merck decided not to do it,” says Posner. “But in the end, this is a federal responsibility. It’s a public health issue.”

For his part, Martin Duffy thinks that drug companies’ complacent attitude toward throat cancer would be different if more of their employees were in his situation. “It will change real fast,” he says, “if one of their executives comes down with this disease.”

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Inflammatory Bowel Disease

Science (July 11, 2010) — A South Dakota State University scientist’s research shows an extract made from a food plant in the Brassica family was effective in alleviating signs of ulcerative colitis, an inflammatory bowel condition, in mice.

The ongoing study by associate professor Moul Dey in SDSU’s Department of Health and Nutritional Sciences — funded by the National Institutes of Health — moves on now to examine the potential use of the plant extract against colon cancer.

“There is an established link between ulcerative colitis and colon cancer. People who have ulcerative colitis are at significantly higher risk to have colon cancer,” Dey said. “Whether this plant extract might help with colon cancer symptoms directly or perhaps delay the onset of colon cancer in ulcerative colitis patients, we don’t know the answers to those questions, but it is something we would like to look into.”

Dey and her team will carry out that research over the next two and a half years as she continues her work on a Pathway to Independence award for promising young scientists. That National Institutes of Health grant of nearly $900,000 over five years was awarded to Dey for work she began as a researcher at Rutgers University.

As a researcher at Rutgers starting in 2004, Dey developed a mammalian cell-based screening platform and screened nearly 3,000 plant extracts for potential anti-inflammatory activity. A plant-derived compound called Phenethylisothiocyanate, or PEITC, was one among others that showed potential anti-inflammatory activities. The NIH funded Dey’s proposal to study it further.

PEITC is found in the Brassica genus of plants, which includes cabbage, cauliflower, watercress and broccoli. Barbarea verna, also known as upland cress or early wintercress, a herb that is used in salads, soups, and garnishes, is one of the richest sources of dietary PEITC in Dey’s study.

Scientists had already studied the compound for its anticarcinogenic properties prior to Dey’s investigation on its anti-inflammatory activities.

“I tested this substance in a mouse model that is already established and widely used. What we found is that it not only alleviates several clinical signs of ulcerative colitis — for example, it attenuates the damage that occurs in the colon tissues and colon epithelium, as well as the clinical signs like diarrhea and blood in stool. The weight loss is a major sign in colitis and that was alleviated, too.” However, she noted that although mammalian animal models are routinely used for an initial test of biological effects of compounds targeted for potential human use, obtained results may not always repeat in humans.

Inflammatory bowel disease, or IBD, is a set of chronic and relapsing inflammatory disorders of the intestine that affects an estimated 2 million people annually in the United States. Two common forms of IBD are Crohn’s disease and ulcerative colitis.

When Dey and her colleagues looked into the mechanism by which the compound might be working against IBD, they found that it downregulates many of the genes that are known to be upregulated in human patients with colitis. That means the compound acts on cells to decrease the quantity of cellular components such as specific proteins that are produced abundantly in colitis patients. One such protein is a novel transcription factor. Transcription factors are one of the groups of proteins that read and interpret the genetic “blueprint” in the DNA.

“We are excited about these findings and our next step would be to see how this plant and the compounds from this plant may be effective against colon cancer, alleviating colon cancer or preventing the onset of colon cancer,” Dey said.

“I am not a cancer biologist per se. My interests are really in cellular mechanisms of inflammatory diseases. The only reason we are going to study colon cancer in this particular project is because ulcerative colitis is very closely linked to colon cancer.”

Colon carcinogenesis is highly preventable, yet colon cancer has one of the highest death rates among all cancers due to typical late diagnosis.

Since people already eat vegetables containing PEITC, there is a long history of human consumption with no adverse effects.

“Obviously the dose we are testing is significantly higher than what we eat in a vegetable, but we have done multiple safety tests and found that this dose is safe in animals,” Dey said.

Dey has no plans to test the extract in humans as part of the current project, but said additional tests would be required if the extract leads to new drugs or treatments in humans.

Dey’s co-authors are Peter Kuhn of Phytomedics Inc., of Jamesburg, N.J.; David Ribnicky, Kenneth Reuhl and Ilya Raskin of Rutgers University, and VummidiGiridhar Premkumar, who is currently at University of Cincinnati

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COLUMBUS, Ohio (UPI) — A substance produced when eating broccoli and Brussels sprouts may block the growth of cancer cells, U.S. researchers say.

Scientists at the Ohio State University Comprehensive Cancer Center say study evidence suggests the substance, indole-3-carbinol, known as I3C, may have anti-cancer effects, a university release said Tuesday.

The laboratory study discovered a connection between I3C and a molecule called Cdc25A, which is essential for cell division and proliferation, the release said.

“Cdc25A is present at abnormally high levels in about half of breast cancer cases, and it is associated with a poor prognosis,” says study leader Xianghong Zou, assistant professor of pathology at the Ohio State University Medical Center.

The study, published in the journal Cancer Prevention Research, said I3C destroyed the molecule and blocked the growth of breast cancer cells.

The molecule also occurs at abnormally high levels in cancers of the prostate, liver, esophagus, endometrium and colon, in non-Hodgkin lymphoma, and in other diseases such as Alzheimer’s disease, Xianghong noted.

“I3C can have striking effects on cancer cells,” he said, “and a better understanding of this mechanism may lead to the use of this dietary supplement as an effective and safe strategy for treating a variety of cancers and other human diseases.”

Copyright 2010 by United Press International

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Drug boosts survival

in major skin cancer study