Nature Medicine

Some forms of prostate cancer thrive on the male hormone, androgen and thus a form of prostate cancer treatment is to use compounds that block androgen’s effects to stop the growth of tumorous cells. However, there is presently no treatment available to extend the survival of men with prostate cancer that is androgen-refractory. And unfortunately, the doses of chemotherapeutic drugs required to overcome androgen-refractory prostate cancer are so large that they are prohibited by their toxicity.

Now, scientists at Merck Research Laboratories in Pennsylvania have devised a way to increase the dose of one chemotherapeutic drug, doxorubicin to such a level that it can be tolerated by prostate cancer patients and also be high enough to destroy cancerous cells.

Raymond Jones and colleagues attached doxorubicin to a peptide in such a way that the linking bond can be cleaved by prostate specific antigen (PSA), which is over-expressed in prostate cancer tissue.

When the doxorubucin conjugate was tested in mice, it was found to be 15 times more potent than ordinary doxorubucin at blocking the growth of human prostate cancer tumors. It was also less toxic to ordinary tissue because it is activated only in the presence of PSA, which is largely confined to the prostate gland. The authors conclude, “These experiments support the use of PSA-hydrolyzable peptide conjugation for the treatment of prostate cancer in man.”

Nature Medicine

One of the bacteria that causes food poisoning, Staphylococcus Aureus, can also cause nasty skin blisters-a condition known as bullous impetigo-through the release of the toxin, exfoliatin. Based on knowledge of a similar condition in which the skin also appears scalded, researchers at the University of Pennsylvania have discovered the mechanism by which exfoliatin causes bullous impetigo.

Desmoglein 1 (Dsg 1), is a cadherin adhesion molecule that helps to stick cells together. John Stanley and colleagues have shown that exfoliatin attacks both mouse and human Dsg 1, but leaves other cadherins in tact. The attack on Dsg 1 causes blistering just below the surface of the epidermal barrier, allowing S. Aureus to proliferate and spread beneath this barrier resulting in further blistering.

Current treatment for bullous impetigo relies on the antibiotics dicloxacillin and erythromycin, but understanding how the S. Aureus toxin causes blistering will mean that better therapies for the painful condition can be developed. Ervin Eptstein from USCF School of Medicine explains the value of the discovery in an accompanying News & Views article.

Nature Medicine

Malaria kills more than 1 million children in sub-Saharan Africa each year, making the disease a priority for the development of a vaccine. However, scientists are still trying to discover which antigen from the causative parasite, Plasmodium falciparum, is the most effective at inducing an immune response, and therefore the most useful for vaccination purposes.

P. falciparum has a complex life cycle and resides in different sexual and asexual forms in the blood and in the liver. Researchers at the Pasteur Institute in France believe that the liver-stage of the life cycle is an ideal target for immunization because it lasts for 5.5 days and is not associated with the pathology of malaria.

Based on the knowledge that people immunized with irradiated sporozoites-the infectious form of the parasite injected in the mosquito’s saliva into the bloodstream that take refuge in liver cells-are protected against infection, Perre Druihle and his team identified a sporozoite antigen that elicits a powerful immune response. They found that injection of this antigen, LSA-3, into chimpanzees protected them from infection by sporozoites.

Malaria expert, Stephen Hoffman of the Naval Medical Research Center in Baltimore, explains the potential value of the research in an accompanying News & Views article.