Press releases
Please quote Nature Medicine as the source of these items.
The October 2009 issue of Nature Medicine is available online.
October 2009
Preserving fertility during cancer treatment
Nature Medicine pp 1179 - 1185
A mechanism that accounts for the negative effects of chemotherapy on female fertility, and a potential way to prevent it with a well known drug, is reported online this week in Nature Medicine.
Infertility is a major side effect in young patients undergoing cancer treatment, owing to the sensitivity of germ cells to chemotherapy. Stefania Gonfloni and her colleagues report that cisplatin, a commonly used chemotherapeutic drug, activates a pro-cell death signaling pathway in female mouse germ cells. Cisplatin treatment ultimately induces germ-cell death by activating an enzyme known as c-Abl. When c-Abl is mutated, it causes chronic myeloid leukemia, which can be therapeutically targeted with imatinib, better known as Gleevec.
Crucially, the scientists also show that treatment with imatinib counteracts the cisplatin-induced cell death of the female germ cells. This raises the possibility of using imatinib to preserve germ cells and thus fertility during chemotherapy.
Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death pp 1179 - 1185
Stefania Gonfloni, Lucia Di Tella, Sara Caldarola, Stefano M Cannata, Francesca G Klinger, Claudia Di Bartolomeo, Maurizio Mattei, Eleonora Candi, Massimo De Felici, Gerry Melino & Gianni Cesareni
Published online: 27 September 2009 | doi 10.1038/nm.2033
Losing weight without too much energy
Nature Medicine pp 1195-1201
A pathway for how insulin signaling in the mouse hypothamalus -- a region of the brain known to control food intake -- is involved in obesity is presented in this week's Nature Medicine. The findings could lead to a new therapeutic model for obesity intervention and weight loss treatment.
In struggling with weight gain, one approach is to eat less food. However, reducing food intake leads to a natural decrease in the amount of energy used, and this consequently contributes to a relapse of obesity. Various hormones, such as insulin, play a key regulatory role in the process of food intake and energy expenditure.
Insulin is known to inhibit food intake through FoxO1, a transcription factor, in hypothalamic neurons. Domenico Accili and colleagues observed that by significantly reducing the amount of FoxO1 in the hypothalamus, mice would reduce their food intake without also decreasing their energy use. They also show that FoxO1 in the hypothalamus inversely impacts the local concentration of Cpe, an enzyme that is required for the proper maturation of key hormones that also regulate food intake. An independent experiment where Cpe was over-expressed showed that this enzyme protected mice from weight gain without changing energy use, confirming the relationship between FoxO1 and Cpe.
The separation of food intake from energy spending allows for new therapeutic possibilities in obesity.
The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake pp 1195-1201
Muge Yemisci, Yasemin Gursoy-Ozdemir, Atay Vural, Alp Can, Kamil Topalkara & Turgay Dalkara
Published online: 20 September 2009 | doi 10.1038/nm.2026
First Paragraph | Full text | PDF | Supplementary information
