Navigation Links
DFMO may affect Barrett's esophagus

"While there was a suggestion that DFMO may influence the extent of Barrett's dysplasia, this finding is very preliminary and further study of this agent in a larger number of patients is needed," said Frank A. Sinicrope, M.D., professor of medicine and oncology at the Mayo Clinic, Rochester, MN.

Sinicrope presented his findings here at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.

The single-arm study included 10 patients with Barrett's esophagus and low-grade dysplasia. The patients received 0.5 g/m2/d of DFMO for six months. Using an endoscope, the researchers examined esophageal biopsies at enrollment and at three, six and 12 months (where available). A gastrointestinal pathologist who was blinded to the clinical/biomarker data graded the dysplasia.

Sinicrope conducted this study while at The University of Texas M. D. Anderson Cancer Center. He collaborated with colleagues at the National Cancer Institute, and the Arizona Cancer Center, Tucson.

After six months of DFMO treatment, one patient's dysplasia regressed, one patient's progressed, and eight patients had stable disease. At six months, two patients in the stable group who started with extensive low-grade abnormal cells had only limited or focal dysplasia based on four or more biopsies. These improvements remained at 12 months.

DFMO lowered the level of the polyamine putrescine, a target of the drug and a possible cancer risk marker. The agent works by inhibiting an enzyme in polyamine synthesis called ornithine decarboxylase (ODC). "ODC activity in Barrett's mucosa has been shown to be significantly higher in Barrett's than in normal adjacent mucosa from the same patients," Sinicrope said. "Since DFMO inhibits polyamine synthesis, the fact that putrescine levels were decreased at six months and later returned to baseline after being off the drug for six months suggests that the drug is affecting its target."

Interestingly, DFMO also reduced expression of Kruppel-like factor 5 (KLF5) gene, an important marker of abnormal cell proliferation in the esophagus that may represent a novel drug target.

"The results are encouraging because they identify KLF5 as a potential target of DFMO, which suggests a potential mechanism contributing to the chemopreventive effects of DFMO," Sinicrope said. "KLF5 has been shown to regulate proliferation, apoptosis and invasion in esophageal cancer cells."

Generally, DFMO was well tolerated. One patient had hearing loss and balance-related problems related to treatment.

"DFMO warrants further evaluation as a chemopreventive agent in patients with Barrett's esophagus and mucosal dysplasia," Sinicrope said. Currently, the Mayo Clinic researcher and his colleagues are planning a placebo-controlled chemoprevention trial in this patient population.


Contact: Jeremy Moore
American Association for Cancer Research

Related medicine news :

1. American Academy of Dermatology: How You Feel on the Inside Could be Affecting How You Look on the Outside
2. Past gains in reducing risk of heart disease have flattened, women especially affected
3. Governor Mike Huckabee Discusses How President Elect Barack Obamas Approach to Health Care Will Affect the Nation
4. Gene Mutation May Cause Some Cases of Seasonal Affective Disorder
5. New Treatment Options for Seasonal Affective Disorder, from Harvard Mental Health Letter
6. Impulse control area in brain affected in teens with genetic vulnerability for alcoholism
7. Folic acid, B vitamins do not appear to affect cancer risk
8. ADHD Affects Movement More in Boys Than in Girls
9. Study finds ADHD affects motor skills of boys more than girls
10. Consuming small amounts of caffeine when pregnant may affect the growth of an unborn child
11. Media Affects Public Perception of Infectious Diseases
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... ... of the leading plastic surgery practices in Florida, is proud to announce that ... for surgical innovations giant Ethicon Inc., a Johnson & Johnson Company. , Ethicon ...
(Date:11/30/2015)... (PRWEB) , ... November 30, ... ... (AIS) is pleased to announce the speakers for “Value-Based Payer-Provider Partnerships: Three ... learned from three innovative value-based care arrangements: Essentia Health and UCare, MissionPoint ...
(Date:11/30/2015)... ... , ... Sikka Software announced today that they are showcasing the Sikka Software ... complex business decisions by providing the tools and information they need to grow their ... procedures customized by zip code. , The Sikka Software Ecosystem includes over 32 ...
(Date:11/30/2015)... ... November 30, 2015 , ... The successful filing of an Investigational ... it is so important to this key industry segment, Regis Technologies has decided to ... on December 4th at 11am EST. , Federal law does not allow new drugs ...
(Date:11/30/2015)... EMIGSVILLE, PA (PRWEB) , ... November 30, 2015 ... ... (CCMS) software provider, has verified that their Vasont Universal Integrator (VUI) extension unites ... handle creating, editing, and managing content as a continuous process with the latest ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)...  Hanger, Inc. (NYSE: HGR ) (the "Company") ... of its previously announced consent solicitation (as amended and ... principal amount 7⅛% Senior Notes due 2018 (the "Notes") ... payable pursuant to the Consent Solicitation, (ii) the proposed ... expiration date of the Consent Solicitation.    ...
(Date:11/30/2015)... 2015  Novartis will demonstrate the strength of its ... American Society of Hematology (ASH) Annual Meeting. Presentations will ... as supportive care, including key findings in rare and ... The ASH Annual Meeting will be held December 5-8 ... Novartis Oncology . "We will be presenting encouraging overall ...
(Date:11/30/2015)... , Nov. 30, 2015   VolitionRx Limited (NYSE ... diagnostic tests for a broad range of cancer types and ... LD Micro Conference, which will be held December 1 - 3 ... from VolitionRx will be David Kratochvil , Chief Financial ... of Investor Relations. ® blood-based tests for ...
Breaking Medicine Technology: