The research identifies a transporter, encoded by the gene, as a potential target for drugs to boost oxalate secretion in the gut and help prevent kidney stones, said Peter Aronson, M.D., professor of internal medicine and physiology and senior author of the research.

The most common type of kidney stones are composed of calcium oxalate. The transporter, known as SLC26A6, normally secretes oxalate into the intestine and prevents absorption of too much of the oxalate from the diet.

"When this gene is knocked out in the mouse, more oxalate from the diet is absorbed, the plasma level of oxalate is increased, more oxalate is excreted in the urine by the kidney, and kidney stones are formed," Aronson said.

In addition to pinpointing a potential drug target, he said the research raises the possibility that abnormal expression or regulation of the anion transporter encoded by the gene could cause kidney stones in humans, although this has not yet been tested directly.

info.med.yale/ysm/

Still, he says a significant response rate represents "a vast improvement" in the care of these pre-cancers, which are a group of diseases in which the bone marrow progenitor cells that normally morph into red and white blood cells and platelets, fail to respond to normal growth controls. That results in too many progenitor cells (also known as blasts) and too few mature blood cells, and in about 30 percent of patients, the disease progresses to acute myeloid leukemia (AML). About three-fourths of MDS patients succumb to either MDS or to AML within about 2-3 years from diagnosis.

MDS is difficult to treat, especially since it usually strikes the elderly. Ten years ago, there was little to offer patients other than blood transfusions and supportive care, Kantarjian says, and newer treatments, which include the use of stem cell transplants, are not for every patient.

Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.

It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous. Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Decitabine prevents the methylation process, enabling the gene to become active again.

In addition to increased survival and time-to-progression in some patients, decitabine improved quality of life in patients who responded and eliminated the need for frequent transfusions, Kantarjian said.

mdanderson