Nature Medicine

Tumor cells hidden in a transplanted organ can cause Kaposi sarcoma (KS)—one of the most frequent transplant-related malignancies—in the organ recipient, Mario Luppi and colleagues report in the May issue of Nature Medicine.

KS affects 1 in 200 transplant patients in the United States, a rate that is 400–500 times higher than among the general population. The researchers investigated KS transmission in five female organ recipients, who developed the disease after receiving organs from male donors. Using various techniques, the researchers confirmed that the tumors in these patients originated from the donor.

While previous studies have suggested that transplanted organs can transmit harmful viruses, the researchers report that viruses and virus-infected tumor cells can both be passed on to an organ recipient. The results, while still preliminary, highlight the potential for transmitting harmful diseases through transplanted organs, and the need for organ pre-screening.

Nature Medicine

Small alterations in a gene required for responding to chemotherapy can result in drug-resistant ovarian cancer, Alan D'Andrea and his colleagues report in the May issue of Nature Medicine.

In the United States alone, there are approximately 23,000 new cases of ovarian cancer diagnosed per year, and more than 15,000 women die from the disease. Ovarian cancer cells are initially sensitive to chemotherapeutic drugs such as cisplatin but, by an unknown mechanism, become resistant to the drugs over time. Understanding how the cells become resistant could lead to new drugs to treat the cancer, the researchers say.

The researchers examined the Fanconi anemia–BRCA pathway, which regulates sensitivity to cisplatin, in ovarian tumor cells. They found that the pathway is disrupted in some ovarian tumors and identified an early event—the removal of methyl groups from a critical gene in the pathway—that causes cisplatin resistance.

Nature Medicine

Reinforcing the existing tuberculosis (TB) vaccine with new genes from the microbe that causes the disease makes the vaccine more effective, Stewart Cole and his colleagues report in the May issue of Nature Medicine.

There is no consistently successful vaccine for TB, which kills more than 2 million people each year. The most commonly used vaccine, Bacille Calmette-Guérin (BCG), is most effective against certain childhood forms of the disease. BCG is a live vaccine derived from a virulent strain of the microbe that causes TB. When scientists first created the vaccine in 1922, they passaged the microbe through several generations, losing several microbial genes in the process.

Cole and colleagues added back some of those genes, including two that prompt a strong immune response. While BCG has a strong safety record, adding the new genes could potentially induce side effects, the researchers caution. Douglas Young discusses the findings in an accompanying News & Views article.

Nature Medicine

Introducing pancreatic genes into cells in the adult liver directs those cells to produce insulin and reverses diabetes in a mouse model of the disease, Lawrence Chan and colleagues report in the May issue of Nature Medicine.

Diabetes can result from abnormal control over blood glucose levels, which are regulated by insulin and other hormones produced by the pancreas. One approach to replacing damaged pancreatic cells has been to transplant cells from healthy individuals—but the procedure is risky. Introducing genes that can redirect cells in the liver to become pancreatic-like cells is one alternative.

In their approach, the researchers inserted the two pancreatic genes into an adenovirus and introduced them into liver cells. Cells that resemble those in a normal pancreas then appeared in the liver. These cells produced insulin and other pancreatic hormones, normalizing levels of glucose in diabetic mice. Exactly how these genes deliver such a potent effect is still unclear. The technique may also have to be tested further before it can be applied in people.