Yale Bulletin and Calendar

May 7, 2004|Volume 32, Number 29|Two-Week Issue

Chemotherapy agent called cisplatin effectively transmits 'death signal' to other cells

One of the most widely used cancer chemotherapy agents not only kills cells directly, but also appears to cause cells to transmit a "death signal" to neighboring cells, according to a Yale researcher.

The agent, cisplatin, has been used in cancer chemotherapy for over 30 years and is effective in the treatment of testicular, lung, head, neck, cervical and ovarian cancers, among others. It played a major role in the recent recovery from testicular cancer of champion cyclist Lance Armstrong.

However, the response to cisplatin varies from patient to patient and many tumors develop resistance over time. The study was intended to understand how cisplatin kills cancer cells.

The senior author of the study, Dr. Peter Glazer, professor and chair of the Department of Therapeutic Radiology at the School of Medicine, says the "death signal" is only active when the cells are at high density, touching each other. The cells then communicate between gap junctions, which are small tunnels where cell molecules pass between cells.

"By careful attention to cell growth conditions, we found that treatment of monolayer cells at high density with cisplatin results in greater cell killing than when the same cells are treated at low density with the same dose of the drug and then handled in the same way. This is consistent with a cell-interdependent mechanism of cell death," he says. "Right now we think this action is unique to cisplatin."

The new pathway appears to require the activity of DNA-dependent protein kinase, an enzyme already known to play a role in the DNA damage response. Glazer says he and his co-author, Ryan Jensen, also of Yale, discovered the new pathway for cisplatin while studying tumor cells cultured at different densities and treated with various cancer therapy agents.

Glazer says he will now look at actual tumors and try to identify the molecular pathways to exploit this discovery in order to enhance the effectiveness of cisplatin.

-- By Jacqueline Weaver

T H I SW E E K ' SS T O R I E S

Alpern named as new medical school dean

Sixteen honored for strengthening town-gown ties

Author Fadiman named first Francis Writer in Residence

Yale counselor helped ease grief of war-torn families in Kosovo and Iraq

Media failed to 'connect the dots' before 9/11, journalist says

With a hoisting of tentacles, giant squid returns to Peabody

Alumni delegates explore issues . . .

Threatened nation-state is topic of two-day YCIAS conference

Event showcasing medical students' original research . . .

New center offers treatment for primary immunodeficiencies

The letters of literary figures are featured in Beinecke exhibit

In elderly, recovery from injuries often good . . .

Study: For-profit hospices offer fewer services than non-profits

Chemotherapy agent called cisplatin effectively transmits . . .

Scientists learn more about bond of water molecules, protons

New fund will support YSN faculty's initiatives to improve health care

Juniors are recognized for scholarship and character

'Modernist Voices' will explore themes in American and British literature

Dr. Terri Fried lauded for her work in geriatric patient care and research

Event explores new advances in chemical biology

Yale Books in Brief

Campus Notes