Navigation Links
Several FDA-approved anti-cancer drugs induce stem cell tumors, perhaps thwarting therapy
Date:3/10/2014

AMHERST, Mass. Using a new approach to systematically test chemotherapy drugs in an unusual animal model, a research team led by University of Massachusetts Amherst molecular biologist Michele Markstein, with Norbert Perrimon at Harvard Medical School, report that several have a serious side effect: Inducing hyper proliferation in stem cells that could lead to tumor recurrence.

Markstein says, "We discovered that several chemotherapeutics that stop fast growing tumors have the opposite effect on stem cells in the same animal, causing them to divide too rapidly. This was a surprise, because it showed that the same drug could have opposite actions on cells in the same animal: Suppressing tumor growth on one cell population while initiating growth in another. Not only is the finding of clinical interest, but with this study we used an emerging new non-traditional tool for assessing drugs using stem cells in the fruit fly gut."

She adds, "We did these experiments in the fly because Drosophila stem cells, in the intestine, are very much like the stem cells in our intestine, and it's a lot easier to do experiments in flies than humans or even mice."

Further, Markstein explains, "When it comes to stem cells, it is important to conduct studies in living animals because stem cells are acutely attuned to the other cells in their microenvironment. Indeed the side effect that we observed is caused by damage that the chemotherapy drugs to cells in the stem cell microenvironment. The stem cells respond to this damage by hyper proliferating."

Markstein and Samantha Dettorre at UMass, with Perrimon and colleagues at Harvard Medical School, pioneered large-scale chemical screening in adult fruit flies that they feel will be useful for testing other chemicals. Conventional in vitro cell screens can identify drugs that act directly on stem cells, the authors note, but they cannot test and identify drugs that act on the all-important microenvironment, which provides cues for stem cell division, differentiation, and death.

The flies provide "ready-made stem cell microenvironments" that are "difficult-to-impossible" to create in petri dishes, Markstein notes. Specifically, she and her colleagues inserted a human cancer-causing gene in the fly genome, turned on that gene in its intestinal stem cells, and found that it did form fast-growing tumors.

To take full advantage of Drosophila's ready-made microenvironments, they developed new technology to determine the size of tumors inside each fly gut. The previous standard in the field was to dissect flies to visualize tumors, which are typically labeled green with green fluorescent protein. In the new method, the researchers decided to use a different label, an enzyme from fireflies called luciferase. This allows them to measure tumor size simply by crushing the flies en masse, rather than dissecting them one-by-one.

They asked the National Cancer Institute for chemotherapy drug samples and received a library of 88 currently in clinical use. After demonstrating that flies are sensitive to human chemotherapy drugs, they obtained a library of over 6,000 small molecules from the Harvard Institute of Chemistry and Cellular Biology, to screen for novel drugs. The screen identified new compounds, three of which are from Chinese medicinal extracts that can inhibit tumors without causing the side effect.

Markstein recalls, "We systematically fed the FDA-approved drugs to the flies and found that 14 suppressed tumor growth in the intestine. This was a great result, validating the relevance of flies as a clinical model. It was also very interesting, however, that we found that half these tumor-suppressing drugs had the opposite effect on the non-tumor stem cells, causing them to over-proliferate. This resulted in small growths or 'tumors,' that with the right genetic background could potentially become cancerous."

These results in the fly may seem surprising. But recent work by others reported a similar effect of the drug doxorubicin in mice, Markstein points out. In mice, doxorubicin induced cells to overgrow by triggering the TNF-alpha pathway, but in flies several chemotherapy drugs including doxorubicin triggered a different pathway called JAK-STAT which has been conserved through evolution in both flies and humans. Both pathways trigger the inflammatory response, which is generally associated with cancer.

Overall, the authors conclude that screening in whole animals such as flies pays off, and is necessary to detect effects that involve more than one cell type. Indeed, Markstein argues that the impact of a chemotherapy drug on the stem cell microenvironment is just as important as its impact on the stem cell itself.


'/>"/>
Contact: Janet Lathrop
jlathrop@admin.umass.edu
413-545-0444
University of Massachusetts at Amherst
Source:Eurekalert  

Related medicine news :

1. Producers of the TV series In View Hosted by Larry King Announce the Posting of Several Videos to the Show’s YouTube Channel
2. The Maercks Institute Reports An Increasing Desire for Natural Looking Breast Augmentations, Launches Several New Websites To Increase Awareness
3. HUMAN Healthy Vending Wins Several School District Accounts, Lands 60+ School Machine Contracts in Past 120 Days
4. Tools4ever Identity and Access Management Solutions Implemented at Several Healthcare Facilities
5. Japantown Dental Offers Several Different Teeth-Whitening Options
6. Prion-like proteins drive several diseases of aging
7. Plastic Surgeon Finally Releasing First Solo Music Artist Song in September and Several Charities Await the Results
8. New Diabetic Drink Option FlavorVIA Comes in Several Natural Flavors to Enjoy
9. Several Korein Tillery Lawyers Nominated as Finalists for the Public Justice “Trial Lawyer of the Year” Award
10. Tools4ever Adds Several More Educational Entities to Its Roster by Providing Secure, Efficient Identity and Access Management Solutions for Employee and Student Use
11. The Chris Elliott Fund Celebrates National Brain Tumor Awareness Month with Several New Education and Awareness Programs
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Several FDA-approved anti-cancer drugs induce stem cell tumors, perhaps thwarting therapy
(Date:5/2/2016)... ... 2016 , ... Atlantic Information Services, Inc. (AIS) is pleased to announce its ... the Pharma Landscape .” CMS recently proposed a test of alternate payment models for ... preserving care provided to beneficiaries. The webinar will review the details of this model, ...
(Date:5/2/2016)... ... May 02, 2016 , ... The Evolve Paddle Board Company- which specializes ... today the outcome of their partnership with Yoloha Yoga- producers of high quality cork ... , SUP yoga has seen a dramatic rise in popularity throughout the last few ...
(Date:5/2/2016)... TN (PRWEB) , ... May 02, 2016 , ... ... and behavioral health services, today announced the opening of Twin Lakes Recovery Center. ... will be Summit’s first in the state. The residential facility is set ...
(Date:5/2/2016)... CA (PRWEB) , ... May 02, 2016 , ... ... offering regenerative therapy, which includes amniotic fluid/“stem cells” and Platelet Rich Plasma (PRP) ... athletes and celebrities,” said Dr. James Baranski, D.C., of Advanced Spine & Sport ...
(Date:5/1/2016)... ... May 01, 2016 , ... Women’s Excellence ... new mothers a better understanding of what to expect after they deliver. The ... baby postpartum, · The blues and depression, · Breastfeeding beyond postpartum · Baby ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... , April 29, 2016 ... glyco-biology expertise, today announces the appointment of Dr. ... Dr. Zurlo is an oncologist with many years clinical ... and biotechnology industries. His last role was at Mologen ... of the Executive Board. Previously Dr. Zurlo held various ...
(Date:4/28/2016)... BURLINGAME, Calif. , April 28, 2016 /PRNewswire/ ... first-ever widely accessible breast and ovarian cancer risk ... cancer panel analyzing 30 genes that highly impact ... and women. Available today, the Color Test analyzes ... pancreatic, prostate, stomach, and uterine cancers. The Color ...
(Date:4/28/2016)... April 28, 2016 Dr. Vivek ... and Ste phen Schmidt ... a leading provider of cloud-based software solutions for life sciences, today ... to bring a wealth of insight to a growing business.  This ... George Phillips joined ArisGlobal in the position ...
Breaking Medicine Technology: