Nature Medicine

After the news that Dolly the sheep has arthritis and that cloned mice may have a reduced life-span, Nature Medicine reports on a further abnormality of animals produced using the technique: cloned mice are also prone to adult-onset obesity.

Randall Sakai and colleagues at the University of Cincinnati College of Medicine used the technique of somatic cell transfer to produce cloned mice-that is placing the nucleus of an adult cell into an enucleated donor cell. They measured various parameters of obesity and found the cloned mice were heavier than controls after 10 weeks growth. The clones were not simply larger than controls, but displayed all the characteristics of obesity-increased body fat, increased leptin levels, and raised plasma levels of insulin. Importantly, the offspring of these mice were not obese, meaning that the abnormality was not passed on through the germline.

Ian Wilmut, a key member of the team that generated the first clone, Dolly the sheep, writes an accompanying News & Views article discussing the work. He asks whether any colored animals are normal, and writes that detailed observations of clones "...are important before large-scale use of the technology in medicine..." can take place.

Nature Medicine

New mechanism of cancer growth and inhibition identified Colon cancer tissue is known to contain increased levels of an enzyme called cyclooxygenase-2 (COX-2), and as a result compounds that block the action of this enzyme such as celecoxib and have been tested for their ability to treat colon cancer. Now, scientists at the University of California, Irvine, have discovered a new mechanism by which these drugs might be effective against colon cancer.

By examining cells from human colon cancer cell lines, Andrzej Tarnawski and colleagues discovered that the molecule prostaglandin E2, which is produced by the action of COX-2, activates epidermal growth factor receptor, which in turn causes cell proliferation. Understanding how prostaglandins cause cancer growth, and how their effects can be blocked, will pave the way for the development of new anti-cancer medicines.

Nature Medicine

As much as 50% of all human tumors carry a mutation in the gene for p53. This gene applies the brakes at the appropriate time to cells that are dividing, thus when p53 is mutated, or switched off, cells grow uncontrollably. The ability to reactivate p53 activity in tumor cells is an attractive target for anticancer drug development.

Klas Wiman and colleagues at the Karolinska Institute in Sweden have screened several compounds in the search for one that would restore p53 activity. They discovered PRIMA-1, which is able to trigger p53-dependent apoptosis in human tumor cell lines. Moreover, when injected into mice carrying human tumors, PRIMA-1 decreased tumor volume.

The team concludes that because of its ability to restore p53 function, PRIMA-1 may provide the basis for the design of new potent anticancer drugs.

Nature Medicine

Kaposi sarcoma (KS) is a malignant tumor of the blood vessels most commonly seen in IV patients. Now, a team of scientists from the Istituto Superiore di Sanità in Rome, Italy, has discovered how these tumors are affected by protease inhibitor drugs-a finding that may lead to better treatment for KS both in HIV and non-HIV patients.

Based on the knowledge that there is a reduced incidence of KS in HIV patients treated with highly active antiretroviral therapy (HAART), of which protease inhibitor drugs are one component, Barbara Ensoli and colleagues tested the ability of this particular class of drugs to inhibit angiogenesis (the growth of new blood vessels). They showed that administration of two protease inhibitor drugs, indinavir and saquinavir, greatly reduced the growth of KS lesions in mice. The data suggest that these drugs may be useful against a wider range of cancers than just HIV-related KS.