Nature Medicine

Based on new data reported in the May issue of Nature Medicine, scientists are urging caution in proceeding to clinical trials with a potential anticancer agent because of its potentially toxic effects on the human liver. To date, studies in human and animals cells in vitro have shown that a molecule called TRAIL can destroy tumor cells by causing them to undergo apoptosis (programmed cell death). The advantage of TRIAL is that it affects only cancerous cells, leaving normal cells unaffected; thus, this compound is being moved forward to clinical trials to be tested against human cancers. However, scientists have now discovered that TRAIL kills normal human liver cells in vitro, an action that could potentially cause liver failure in patients.

Shigekazu Nagata and colleagues at Osaka University Medical School, Japan, tested the sensitivity of liver cells from rats, mice, rhesus monkeys and humans to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). Although TRAIL did not destroy normal cells form the animals tested, it did induce apoptosis and rapid cell death in 60% of the human liver cells-a striking species difference.

So although the compound has potential as a selective anticancer agent, its effects on the human liver must be investigated further. In an accompanying News & Views article, Stephen Strom from the University of Pittsburgh writes, “It may not be too late to delay clinical trials until we have a better understanding of why some cells but not others are resistant to TRAIL.”

Nature Medicine

Bone cancer pain, due to bone destruction by cancerous cells, is common among cancer patients and can have a devastating effect on their quality of life. Most cancer-induced bone destruction is due to cells called osteoclasts, which absorb bone material and are present in increased numbers in cancerous bone. Existing treatments for bone cancer pain involve surgery, radio and chemotherapy, and morphine. Now scientists at the University of Minnesota may have discovered an alternative therapy.

Based on the knowledge that osteoclast formation is blocked by a molecule called osteoprotegerin (OPG), Patrick Mantyh and colleagues injected OPG into a mice femora which model bone cancer, and found that the treatment eliminated destructive the osteoclasts from the site of the cancer and also reduced bone destruction and pain. If OPG works the same way in humans, it could enhance the quality of life of patients with bone cancer.

Steve Thompson and David Tonge of Guy's, King's & St. Thomas's School of Medicine describe the results as “exciting” in an accompanying News & Views article, and urge more study of why osteoclast activity causes pain.

Nature Medicine

Diabetes affects around 5% of the US population-almost 15 million people. It occurs when the pancreas produces insufficient amounts of insulin to meet the body's needs for converting cellular glucose into energy, or when cells are unable to use insulin produced by the pancreas (insulin resistance).

Thus, transplantation of insulin-producing pancreatic islet cells as a potential cure for the disease has become a subject of intense research interest over the past two decades. Now, scientists at Sheba Medical Center, Israel, have devised a gene therapy method of engineering liver cells to become insulin-producing pancreatic-like cells in the hope that these can replace defective pancreatic cells.

Homeobox genes are genes that control the positioning of tissue during development, and PDX-1 is a homeodomain protein that plays a central role in regulating insulin gene expression, pancreas development and islet cell function. In a ‘gain of function technique,’ Sarah Ferber and colleagues used an adenovirus to insert the gene for PDX-1 into liver cells of mice that had been made hyperglycemic. These cells were then able to produce insulin, thus correcting the diabetic condition of the mice. These results demonstrate that PDX-1 can reprogram non-pancreatic tissue to produce insulin, and such transformed cells may provide a valuable source for replacing damaged pancreatic cells if the technique can be transferred to humans.

Axel Kahn from INSERM discusses the study in a News & Views article, and writes, “…these results could constitute a breakthrough in the prospects of therapy for type I diabetes.”