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Hormones produced by the heart eliminated human pancreatic cancer in more than three-quarters of the mice treated with the hormones and eliminated human breast cancer in two-thirds of the mice, according to researcher David Vesely, a doctor at the James A. Haley Veterans Hospital in Tampa and a professor at the University of South Florida (USF).

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The treatment has not yet been tried in humans, but a private biotechnology company is raising money in the hope of beginning human trials. Vesely is the hospital’s chief of endocrinology, diabetes and metabolism and is also professor of medicine, molecular pharmacology and physiology at USF.

The discovery of cardiac hormones

For more than 350 years, scientists and physicians thought the heart was a pump, delivering blood and oxygen to the body. But that view changed dramatically in 1981 when Adolfo deBold discovered that the heart produces atrial natriuretic factor (ANF), so-named because it is produced in the atrium of the heart and stimulates the production of urine and the excretion of sodium.

Vesely later discovered three more hormones that are produced from the same gene as ANF. He called them:

* Long acting natriuretic peptide, which also stimulates urine production and sodium excretion.
* Vessel dilator which opens the blood vessels and lowers blood pressure
* Kaliuretic peptide which increases potassium excretion

The hormones, called peptide hormones because they are composed of amino acids, help regulate blood volume and blood pressure. Most hormones, including such well-known hormones as insulin, are peptide hormones.

Started with congestive heart failure research

Vesely began his research on cardiac hormones by looking at the role they can play in diagnosing and treating congestive heart failure. Following his wife’s death from breast cancer in 2002 — and as it became clear that the hormones controlled cell growth — he decided to place the hormones into cancer cell cultures.

Using colon, ovarian, breast, prostate and pancreatic cancer cells, among others, Vesely found that the hormones kill up to 97% of all cancers in cell cultures within 24 hours. He then turned to trials with mice, injecting some with pancreatic cancer cells and others with breast cancer cells. Once the mice developed tumors, he treated them with the hormones.

At the end of one month, the treatment had eliminated cancer in 80% of the mice injected with human pancreatic cancer and in 66% of the mice injected with breast cancer. The results with pancreatic cancer were particularly exciting because it is a fast-moving cancer with poor prognosis.

No side effects in mice

The pancreatic cancers that were not cured were reduced to less than 10% of their original size. Treatment with vessel dilator gave the best results: reducing the tumor to 2% of its largest size. None of the mice died of cancer – all died of old age – and none suffered any side effects.

None of the mice received any other course of treatment such as surgery, chemotherapy or radiation and they did not suffer any side effects. After the mice died at the end of a normal life span, the researchers found that the cancer had not spread. If the hormones act the same way in humans, cancer could become a chronic condition treatable with these hormones, Vesely said.

A private biotechnology company is raising money to begin human trials, Vesely said. The Haley hospital and University of South Florida hold the patents on the discoveries.

Vesely will present his research at a symposium April 9 at the Experimental Biology 2008 conference in San Diego. The American Federation for Medical Research sponsors the session, which takes place during the annual meeting of The American Physiological Society.

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Not a day goes by without a new story about the environment. Although we often consider the environment on a global scale, cells in our body also have to contend with environmental factors. New studies from a team of researchers from the Research Institute of the MUHC and McGill University show that the environment surrounding breast cancer cells plays a crucial role in determining whether tumor cells grow and migrate or whether they fade away. Their study is the first to identify the genes behind this environmental control and correlate them with patient outcome. Their findings are published in this week’s issue of Nature Medicine.

“A tumour can not exist on its own. It has to be supported and nourished by the cell types around it, the microenvironment,” says senior author Dr Morag Park, Director of the molecular oncology group at the Research institute if the MUHC. “When we began this study there was little known about the importance of this microenvironment on cancer initiation and progression. We now know that this environment is pivotal; different patients have distinct tumour microenvironments at a gene level. Our findings show that the gene profile of these distinct microenvironments can be used to determine clinical outcome — who will fare well and who will not.”

Dr Park, a professor of oncology, biochemistry, and medicine at McGill University, and her team analyzed tissue from 53 breast cancer patients. They used a unique technique, laser capture microdissection (LCM), to separate tumour cells from microenvironment tissue. They compared the gene expression between the microenvironment tissue and controls using micro-array analysis. From thousands of genes they identified 163, which correlated with patient outcome. A good outcome was defined as having no tumour metastasis and tumour migration and non-responsiveness to therapy was considered poor outcome.

From the original 163 genes, the team further identified a panel of 26 specific genes that could be used to accurately predict clinical outcome. This 26 gene-profile, called the stromal derived prognostic predictor (SDPP), was used to predict outcome from a second set of beast cancer patients.

“We were able to show that the SDPP effectively predicts outcome in a second group of patients,” says Dr Park, “This panel accurately forecasted patient status, suggesting that this may be a promising diagnostic tool.

“Our next steps are to develop this 26-gene predictor into a functional test. We are currently working on this and we anticipate a product for clinical trials within a year,” adds Park.

“This work takes tremendous dedication and collaboration from a number of people including pathologists, surgeons, oncologists as well as researchers. I would like to thank the outstanding work done by G. Finak from the laboratory of Dr M. Hallett of McGill’s Computer Science Department, the breast surgeons of the MUHC, including Dr S. Meterissian, and by the Department of Pathology at McGill, where Dr A. Omeroglu works.”

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Case Western Reserve University School of Medicine researchers published a study in The American Journal of Human Genetics identifying the hereditary components of colorectal cancer (CRC.) “Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study” is the first large linkage study of families with CRC and colon polyps in the country. Because only five percent of CRC cases are due to known gene defects, this NIH-funded study is designed to identify the remaining CRC-related susceptibility genes. The team built on a previous study which identified a specific region on chromosome 9q that harbors a CRC susceptibility gene. Upon review of a whole genome scan of all chromosome pairs in 194 families, the researchers were able to identify additional CRC gene regions on chromosomes 1p, 15q, and 17p.

While the overall Case Western Reserve University School of Medicine study looked at families with colon cancer and colon polyps, the study also analyzed families with different clusters of cancer, such as CRC with multiple polyps and CRC with breast cancer. These different phenotypes appeared to link to different chromosomal regions, which the study teams says supports the idea of multiple susceptibility genes causing different types of cancers. These links will be further investigated in the next phase of the study.

“The goal of our study is to identify the CRC genes in susceptible patients to better understand who may be prone to develop CRC and why,” said Georgia L. Wiesner, M.D., lead author of “Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study.” “This study is step towards future the of genetic CRC testing.”

The genome-wide scan used in this study will help physicians elucidate the genetic factors in CRC in the future. Once the genes are identified, physicians will be able to use these genetic markers to identify “at risk” patients and to develop better cancer screening strategies, such as colonoscopies well before standard screening begins at age 50. Currently, without new gene tests, family history is the only tool to determine a person’s risk for CRC. Knowing the exact gene will allow physicians to better take care of CRC patients and lead to earlier screening.

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Although fewer of them undergo surgery, lung cancer patients in their 80s fare equally well following surgery as their younger counterparts, researchers report. The findings offer doctors potentially valuable guidance in treatment options for elderly patients, according to researchers.

A research team from the Hoag Cancer Center in Newport Beach, California, observed 1,293 patients with lung cancer, 482 of whom underwent surgical treatment. The oldest patients were more likely to be male. Older patients were also more likely to have localized disease.

Overall, the rate of surgery did not differ by age group. However, when primary lung cancer was considered separately, only 31.7 percent of patients older than 80 underwent surgery for their primary lung cancer compared with 38.5 percent of patients younger than 80. For patients with non-small cell lung cancer, the rate of surgery was 64 percent for those older than 80 and 83 percent for those younger than 80. For patients with regionally advanced disease, the rate of surgery for patients age 80 or older was 35 percent compared with 49 percent for those younger than 80 years old.

The five-year survival rate following surgery was 62 percent for those patients older than 80 compared with 53 percent for those aged 70 to 79 years. Among patients age 60 to 69 years and 50 to 59 years, the survival rate was 63 percent. For the youngest patients, those younger than 50, the survival rate was 79 percent.

“Although a smaller proportion of patients over the age of 80 underwent this type of surgery, their survival rate was comparable to the younger age groups,” said lead author Robert O. Dillman, M.D., medical director of the Hoag Cancer Center in Newport Beach, California.

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