Featured Research

from universities, journals, and other organizations

Clinical waste may be valuable for monitoring treatment response in ovarian cancer

Date:
December 6, 2013
Source:
Massachusetts General Hospital
Summary:
A microchip-based device developed may greatly simplify the monitoring of patients' response to treatment for ovarian cancer -- the most lethal form of gynecologic cancer -- and certain other malignancies. The team reports using their device to isolate and identify tumor cells from ascites, an accumulation of fluid in the abdomen that often occurs in abdominal cancers.

Ascites fluid from ovarian cancer patients is introduced through a filter into an inlet (left) where magnetically labeled benign cells are trapped. The remaining fluid passes through a microchip containing microwells where antibody-labeled tumor cells are captured (inset) for collection, imaging, and additional analyses.
Credit: Hakho Lee, PhD, and Jaehoon Chung, PhD, MGH Center for Systems Biology

A microchip-based device developed by Massachusetts General Hospital (MGH) investigators may greatly simplify the monitoring of patients' response to treatment for ovarian cancer -- the most lethal form of gynecologic cancer -- and certain other malignancies. The team from the MGH Cancer Center and the Center for Systems Biology reports using their device to isolate and identify tumor cells from ascites, an accumulation of fluid in the abdomen that often occurs in abdominal cancers. The PNAS Early Edition paper also describes development of a panel of four protein markers to accurately identify ovarian cancer cells in ascites.

"We were able to demonstrate that simply squirting small amounts of otherwise discarded ascites fluid into our device allowed us to quantify tumor cells and explore mechanistic markers of tumor progression without the need to process liters of ascites with advanced instrumentation not readily available in many community hospitals," says Cesar Castro, MD, MMSc, MGH Cancer Center and Center for Systems Biology, co-lead author of the PNAS paper. "Moreover, achieving point-of-care readouts of tumor cell markers from repeatedly collected ascites at different time points, could allow for frequent monitoring of treatment response without having to wait for the next imaging scan."

The ability to reliably track treatment response essentially lets caregivers know whether a particular anticancer drug should be continued or if another option should be tried. Tumor recurrence begins before metastases become visible on imaging studies, so several options for non-invasive "liquid biopsies" are being investigated, including analysis of circulating tumor cells and other factors found in the blood. Since ovarian cancer metastases are usually confined to the abdominal cavity and ascites commonly form in advanced disease, the research team theorized that ascites fluid could be an alternative, if not better, option than blood for treatment monitoring.

Isolation of ascites tumor cells (ATCs) has been challenging, since they constitute less than 1 percent of the cells in ascites fluid. ATCs themselves vary greatly in size, and other fluid contents -- inflammatory and blood cells, cells from the abdominal lining and additional debris -- often form large clumps that would clog typical microfluidic devices. Along with removing the non-tumor-cell components of ascites fluid, the team also needed a way to accurately identify ovarian cancer cells and analyze their molecular properties.

Through a lengthy process that involved laboratory work comparing ovarian cancer cells with benign cells and ascites samples from ovarian cancer patients with those from individuals with noncancerous conditions like cirrhosis, the investigators uncovered a panel of four protein markers that specifically identified ATCs from ovarian cancer patients. They confirmed the accuracy of the panel, called ATCDX, in two separate sample sets, comparing ascites fluid from ovarian cancer patients with either noncancerous fluid or with ascites from patients with other types of cancer.

Prior to the passage of ascites fluid through the MGH team's device -- called the ATC chip -- the sample is first labeled with magnetic nanoparticles that bind to noncancerous inflammatory cells. The sample is introduced into the three-inch-long ATC chip through a filter that screens out clumps of debris and then passes by a magnet that traps the magnetically labeled benign cells. Also added to the device is a mixture of antibodies to the ATCDX proteins, which label the markers for imaging detection. After the magnetic sorting, the sample passes over a series of microwells of successively smaller size, which collect ATCs while even smaller leukocytes pass through the device. The concentration of ATCs captured on the chip is 1,000 times greater than it was in the original fluid sample.

The investigators tested the device initially by analyzing ascites samples repeatedly collected from a single ovarian cancer patient over a 14-week course of treatment, first with standard chemotherapy and then with antiangiogenic therapy when disease progression resumed. The ATC chip revealed that the number of ATCs dropped during initial treatment response, rose with progression and fell again as antiangiogenesis relieved the patient's symptoms. They also found that analysis of the molecular properties of ATCs from 46 ovarian cancer patients could distinguish those whose tumors responded to treatment from nonresponders.

"This device far exceeded our expectations," says Ralph Weissleder, MD, PhD, director of the Center for Systems Biology and senior author of the PNAS report. "Coupled with our diagnostic panel, we were able to clearly distinguish between tumor cells and the extensive cellular debris commonly found in ascites. The ATC chip and the set of protein markers we uncovered, which reliably identified ovarian cancer cells floating in ascites, provide a novel platform for extending ATC analysis to settings where the expensive equipment and labor-intensive techniques that ATC isolation previously required would not be feasible."

The research team notes that large-scale production of the ATC chip is already being planned, and if future studies confirm their results, the device's low cost -- estimated at less than $1 each -- and ease of use would make ATC analysis a practical and valuable tool for both treatment of and research into ovarian cancer and possibly for other tumors that induce the formation of ascites, including pancreatic cancer.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. V. M. Peterson, C. M. Castro, J. Chung, N. C. Miller, A. V. Ullal, M. D. Castano, R. T. Penson, H. Lee, M. J. Birrer, R. Weissleder. Ascites analysis by a microfluidic chip allows tumor-cell profiling. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1315370110

Cite This Page:

Massachusetts General Hospital. "Clinical waste may be valuable for monitoring treatment response in ovarian cancer." ScienceDaily. ScienceDaily, 6 December 2013. <www.sciencedaily.com/releases/2013/12/131206163059.htm>.
Massachusetts General Hospital. (2013, December 6). Clinical waste may be valuable for monitoring treatment response in ovarian cancer. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2013/12/131206163059.htm
Massachusetts General Hospital. "Clinical waste may be valuable for monitoring treatment response in ovarian cancer." ScienceDaily. www.sciencedaily.com/releases/2013/12/131206163059.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins