Looking to trees to treat rare eye cancer
- From: J <nexsw@nvalid,anon>
- Date: Fri, 16 Mar 2007 05:42:45 -0500
<http://www.iol.co.za/index.php?set_id=1&click_id=31&art_id=nw20070315232604432C604251>
March 16 2007 at 11:20AM
By Julie Steenhuysen
Chicago - An extract from the bark of a South American tree might lead to
better treatments for a rare but deadly childhood eye cancer called
retinoblastoma, US researchers reported on Friday.
Retinoblastoma affects 1 in 15 000 children, causing about 3 percent of
all cancers in children. It forms when developing cells in the retina -
the eye's main light sensor - go haywire and start reproducing out of
control.
"The great majority of the cases exist in the developing world, where it
is a fatal disease," said Dr. Joan O'Brien of the University of
California, San Francisco, who led the study.
The cancer usually develops in children under age 6 and kills within two
to four years after diagnosis if not treated.
If detected early and treated with a combination of chemotherapy agents or
radiation, 90 to 95 percent of children live. But conventional treatment
has significant side effects.
Combination chemotherapy can cause hearing loss, kidney failure and
leukemia. Radiation therapy, which is now less commonly used, disfigures
the child.
In children who have the cancer in only one eye, the eyeball is sometimes
replaced with an implant.
"We can cure them, but at cost," said O'Brien. "It's important to find a
cheap, easily administered, nontoxic therapy."
O'Brien and colleagues at UCSF wanted to see whether the tree bark extract
beta-lapachone could cause the abnormal cells to commit suicide -
something it has been shown to do in a number of cancer types, including
breast and prostate cells.
They tested the extract in the laboratory and found that beta-lapachone
significantly blocked rapid cell growth of human tumour cells and that low
doses could cause damaged cells to kill themselves in a process called
apoptosis, or programmed cell death.
Writing in the journal Eye, the scientists said their findings support
other studies of the extract in different human cancers and may lead to an
effective treatment.
"The nice thing about the agent is that it kills at very low doses and it
appears to be selective to cancer," O'Brien said.
Substances that zero in on cancer are less toxic because they do less harm
to healthy cells, O'Brien said. Her lab is now testing the extract in mice
with retinoblastoma to look for possible toxic side effects.
beta-lapachone
A naphthoquinone compound derived from bark of Tabebuia sp., with
antitumor, antibacterial, antifungal and antitrypanosomal activities.
Beta-lapachone exerts its anti-tumor effect by indirect actions of
inducing p53-independent apoptosis and cell cycle arrest mediated through
altered activities of cell cycle control regulatory proteins; including
down-regulating retinoblastoma protein (pRB), a transcriptional repressor
target at transcription factor E2F-1, as well as induces expression of
cyclin dependent kinase inhibitor 1A (CDKN1A or p21). Both E2F-1 and p21
are required for G1/S-phase transition during cell cycle. This agent also
inhibits DNA topoisomerase I by a mechanism distinct from that of
camptothecin, and thereby blocks the formation of a cleavable complex
leading to enzyme inhibition and prevent DNA repair. Furthermore,
beta-lapachone could induce reactive oxygen species in vivo, and result in
cytotoxicity. Check for active clinical trials or closed clinical trials
using this agent. (NCI Thesaurus)
Synonym: b-Lapachone
Code names: ARQ 501
ARQ 501
ARQ501
Chemical structure name:
3,4-Dihydro-2,2-dimethyl-2H-naphtho(1,2-b)pyran-5,6-dione
5 studies were found.
1. No longer recruiting ARQ 501 in Subjects With Cancer
Condition: Cancer
2. No longer recruiting ARQ 501 in Combination With Docetaxel in Patients
With Cancer
Condition: Carcinoma
3. No longer recruiting Safety and Efficacy Study of ARQ 501 in Adult
Patients With Leiomyosarcoma
Condition: Cancer
4. No longer recruiting ARQ 501 in Combination With Gemcitabine in
Subjects With Pancreatic Cancer
Conditions: Pancreatic Cancer; Adenocarcinoma
5. No longer recruiting A Study of ARQ 501 in Patients With Squamous Cell
Carcinoma of the Head and Neck
Conditions: Head and Neck Neoplasms; Carcinoma, Squamous Cell
.
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