July 10, 2007, 5:30 AM CT

How Cancer Drug Works

The annoying bulges of an over-wound telephone cord that shorten its reach and limit a callers motion help to explain why drugs called camptothecins are so effective in killing cancer cells, as per researchers at St. Jude Children's Research Hospital and Delft University of Technology.

Using a type of nanotechnology called magnetic tweezers as well as yeast cells, researchers showed that a camptothecin drug called topotecan kills cancer cells by preventing an enzyme, called DNA topoisomerase I, from uncoiling double-stranded DNA in those cells. Instead, the DNA becomes locked in tight twists, called supercoils, which bulge out from the side of the over-wound DNA moleculemuch like the bulges in an over-wound telephone cord. If these supercoils accumulate and persist while the cell is trying to separate the two strands of DNA to make exact copies of the chromosomes during cell division, the cells will die.

Nanotechnology studies work at a scale of about 100 nanometers or less. For comparison, one nanometer is approximately 10 times the size of an atom; and 10 nanometers is one-thousandth of the diameter of a human hair.

In this first-of-its-kind study, scientists used the microscopic magnetic tweezers to monitor changes in the length of an individual DNA molecule caused by the action of a single topoisomerase I enzyme; and to study how the binding of a single topotecan molecule to this enzyme-DNA complex alters DNA uncoiling. Based on the results of those studies, researchers developed the supercoil theory to explain the drugs ability to kill cancer cells, and then tested that theory in yeast cells. Their conclusionthat accumulation of DNA supercoiling kills the cellsprovides a novel model for how topotecan works; and it provides insights into the drugs action that could help researchers in the clinical development of these agents. A report on this work appears in the advanced, online issue of Nature......... Posted by: Andria      Read more         Source

July 10, 2007, 5:06 AM CT

More Lethal Subtype Of AML

A new study shows that the activity of a particular gene can identify people who have a more lethal form of acute myeloid leukemia, singling out those patients who should receive more intense treatment.

The gene, called ERG (for ETS-related gene), has also been associated with chronic leukemia and to breast and prostate cancer.

The findings apply to acute myeloid leukemia (AML) patients with leukemia cells that have normal-looking chromosomes, a feature that occurs in about half of AML patients.

Among these patients, those with leukemia cells showing high ERG activity are almost six times more likely to relapse or die within five years than are patients with low ERG expression following standard treatment.

The Cancer and Leukemia Group B study was initiated by scientists at the Ohio State University Comprehensive Cancer Center, and their findings were published online in the Journal of Clinical Oncology.

"Our study shows that high ERG activity predicts a poor prognosis in these patients, even when other molecular markers are taken into consideration," says first author Guido Marcucci, associate professor of internal medicine and an AML specialist at Ohio State's James Cancer Hospital and Solove Research Institute.

"The findings mean that these patients require a stem-cell transplant or other aggressive treatment, and that patients with low ERG activity can be treated using standard treatment."........ Posted by: Andria      Read more         Source

July 8, 2007, 10:14 PM CT

genes associated with colon cancer

A 10-year study involving thousands of Israeli Jews and Arabs, led by scientists from American and Israeli institutions, has yielded important new information in the search for the genes that make a person more likely to develop colon cancer.

In a paper would be reported in the recent issue of Cancer Biology and Therapy, the international research team reports finding a significant link between genetic variation in a single region of human chromosome 8 and the risk of colorectal cancer.

The link was found by detailed comparisons of genetic material from thousands of patients with colon cancer and non-patients, and by evaluating the occurence rate of colon cancer among the immediate family members of patients with colon cancer.

In all, people who carry the specific genetic variation, called a marker, were found to be 23 percent more likely to have colon cancer than individuals without the marker. The scientists estimate that this single genetic variation might account for 14 percent of colorectal cancer cases in Israel, where colon cancer is the leading cause of cancer deaths. The specific marker is called the C allele of rs10505477.

Three other research teams are reporting similar findings today in the journal Nature Genetics, having simultaneously found their way to the same small area of chromosome 8, called 8q24, in the search for colon cancer genetic links. The fact that these studies were performed among other populations around the world suggests that this one genetic marker is highly influential across ethnic groups......... Posted by: Andria      Read more         Source

July 5, 2007, 9:40 PM CT

Electric Pulses To Destroy Cancer Cells

A team of biomedical engineers at Virginia Tech and the University of California at Berkeley has developed a new minimally invasive method of treating cancer, and they anticipate clinical trials on individuals with prostate cancer will begin soon.

The process, called irreversible electroporation (IRE), was invented by two engineers, Rafael V. Davalos, a faculty member of the Virginia TechWake Forest University School of Biomedical Engineering and Science (SBES), and Boris Rubinsky, a bioengineering professor at the University of California, Berkeley.

Electroporation is a phenomenon known for decades that increases the permeability of a cell from none to a reversible opening to an irreversible opening. With the latter, the cell will die. What Davalos and Rubinsky did was apply this irreversible concept to the targeting of cancer cells.

IRE removes tumors by irreversibly opening tumor cells through a series of short intense electric pulses from small electrodes placed in or around the body, said Davalos, who is the 2006 recipient of the Hispanic Engineer National Achievement Award for Most Promising Engineer or Scientist. This application creates permanent openings in the pores in the cells of the undesirable tissue. The openings eventually lead to the death of the cells without the use of potentially harmful chemotherapeutic drugs......... Posted by: Andria      Read more         Source

Tue, 03 Jul 2007 04:25:59 GMT

DNA Discoveries in Science and Art

Here is a great video about Rosalind Franklin who made the first clear X-ray images of the structure of DNA. She died of ovarian cancer at the age of 37! So artists Wyllie O Hagan try to “use their art to support awareness raising missions for ovarian cancer”. Posted by: Bertalan      Read more     Source

July 2, 2007, 10:03 PM CT

How Cancer Evades The Immune System

One of the fundamental traits of a tumor how it avoids the immune system might become its greatest vulnerability, as per scientists from the University of Southern California. Their findings, demonstrated in human breast and colorectal cancers, indicate that a technique for determining a tumors immune signature, could be useful for diagnosing and treating specific cancers.

In the July 1 issue of Clinical Cancer Research, a publication of the American Association for Cancer Research, the scientists describe a means for determining which genes have been altered in a tumor to allow it to evade the bodys natural defenses. In time, the scientists believe such analysis could become a standard practice in cancer diagnosis and therapy.

The implication is that once you know the mechanism by which tumors evade the immune system, you can match that tumor to available therapies, said senior author Alan L.Epstein, M.D., Ph.D., professor of Pathology at USCs Keck School of Medicine. First, we find the genetic changes that allow a tumor to defeat the immune system, then we can apply therapies that compensate for these genetic alterations.

As per Epstein, tumors are notorious for demonstrating a broad array of genetic and biological variations. Their differences vary widely between cancer types, even between subcategories within a particular type of cancer. However, while the genetic variations that comprise an immune signature are complex, the scientists discovered that a small subset of genes is integral in explaining immunological behavior......... Posted by: Andria      Read more         Source

June 28, 2007, 11:38 PM CT

Key To Understanding Cancer Development

A research team including University of Central Florida Microbiology Professor Keith Ireton is using the bacterial pathogen Listeria Monocytogenes to understand the mechanisms of cell growth and cancer development.

In research published this month in the Journal of Biological Chemistry, the team observed that a Listeria protein called InlB induces internalization and degradation of a human receptor known as Met. Met has been implicated in the development of some cancers.

Lisa A. Elferink at the University of Texas Medical Branch led the team. She and Ireton observed that the ability of InlB to induce Met internalization and degradation requires a human protein called Cbl. If researchers could figure out how to control Cbl, such knowledge might lead to the development of drugs that induce the destruction of Met and are useful in treating Met-related cancers.

Ireton is an expert on Listeria monocytogenes, a cause of food poisoning. He has long studied how it enters into cells of the human body, and explains the mechanism in this months issue of the journal Cellular Microbiology.

We observed that Listeria actually provokes human epithelial cells (cells lining the small intestine) into ingesting bacteria, Ireton said. When Listeria contacts an epithelial cell, the bacterium causes changes in the cells cytoskeleton that allow the cell to swallow up the bacterium. We discovered that a human protein called CrkII plays a critical role in stimulating internalization of Listeria by somehow controlling the cytoskeleton......... Posted by: Andria      Read more         Source

June 27, 2007, 6:39 PM CT

Support for chromosomal theory of cancer

Berkeley Thirty-six years into the war on cancer, researchers have not only failed to come up with a cure, but most of the newer drugs suffer from the same problems as those available in the pre-war days: serious toxicity, limited effectiveness and eventual resistance.

This is no surprise to University of California, Berkeley, genetics researcher Peter Duesberg, professor of molecular and cell biology. As per his novel yet controversial "chromosomal" theory of cancer, which is receiving increased attention among cancer researchers, each cancer is unique, and there is no magic bullet.

"The mutation theory of cancer says that a limited number of genes causes cancer, so cancers should all be more or less the same," Duesberg said. The chromosomal theory, which he laid out in an article in the May 2007 issue of Scientific American, implies instead that, "even if cancers are from the same tissue, and are generated with the same carcinogen, they are never the same. There is always a cytogenetic and a biochemical individuality in every cancer".

The most that can be expected from a drug, he said, is that it is less toxic to normal cells than cancer cells, and that as a result a cancer detected early can be knocked back by chemotherapy. His chromosomal theory offers hope of early detection, however, since it ascribes cancer to chromosomal disruption, called aneuploidy, that can be seen easily through a microscope......... Posted by: Andria      Read more         Source

June 26, 2007, 10:34 PM CT

Bisphosphonates And Osteonecrosis Of Jaw Bone

Treatment with intravenous bisphosphonates drugs used to reduce harm done to bones by cancer or cancer treatment increases the risk of jaw or facial bone disease or infection, a large-scale comparative study by scientists at the University of Texas Medical Branch at Galveston (UTMB) has found.

Drawing on the National Cancer Institutes Surveillance, Epidemiology and End Results (SEER) database associated with Medicare insurance claims, researchers from the UTMB Center for Population Health and Health Disparities compared more than 14,000 cancer patients treated with two types of intravenous bisphosphonates (pamidronate and zoledronic acid) with nearly 27,000 cancer patients who did not receive the drugs. After six years, about 5.5 percent of bisphosphonate users had undergone facial or jaw bone surgery or been diagnosed with inflammation of the jaw bone, compared with 0.3 percent of non-users.

This study is based on a much larger population than earlier investigations of this phenomenon, and while those studies gave rise to a lot of speculation, this one definitely implies that something serious is going on, said Gregg S. Wilkinson, professor of preventive medicine and community health at UTMB and lead author of a paper published online June 26 by the Journal of the National Cancer Institute. We havent proven causation, but we found a very strong association between these drugs and disease involving the face and jaw bones......... Posted by: Andria      Read more         Source

June 25, 2007, 7:55 PM CT

Characterizing Aggressiveness Of Cancer Cells

Levels of a small non-coding RNA molecule called let-7 appear to define different stages of cancer better than some of the "classical" markers for tumor progression, scientists from the University of Chicago report in the June 25, 2007, early online edition of the Proceedings of the National Academy of Sciences.

By suppressing genes that are active in the developing embryo, silenced just before birth, and re-activated years later in a number of advanced cancers, the let-7 family of "microRNAs"tiny snippets of RNA that can put the brakes on expression of selected genesappears to prevent human cancer cells from reasserting their prenatal capacity to divide rapidly, travel and spread.

Since they were first discovered in 1993, there had been growing interest in microRNAs and their role in gene regulation. Hundreds of these tiny molecules, about 20 nucleotides in length, have been discovered, scattered throughout the human genome. They act in most cases by attaching themselves to specific sites on messenger RNA, where they block ribosome access and thus prevent production of that protein.

"There may be no human cancer that is not regulated by microRNAs," said study author Marcus Peter, professor in the Ben May Department for Cancer Research at the University of Chicago, "and among microRNAs, let-7 appears to be a key player in preventing a cancer from becoming more aggressive"......... Posted by: Andria      Read more         Source