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Gen kanker dimatikan dalam kanker otak yang mematikan

Para ilmuwan telah mengidentifikasi molekul RNA kecil yang dapat menekan gen penyebab kanker pada tikus dengan glioblastoma mulitforme , jenis yang mematikan dan tidak dapat disembuhkan dari tumor otak . Sementara obat-obatan kemoterapi standar merusak DNA untuk menghentikan sel-sel kanker berkembang biak , metode baru menghentikan sumber yang menciptakan sel-sel kanker . Pendekatan ini juga bisa berpotensi digunakan untuk membungkam gen pada kanker dan penyakit asal genetik lainnya ....read more

Cancer genes
turned off in deadly brain cancer

Date:

April 3, 2015

Source:

Northwestern
University

Summary:

Scientists have
identified a small RNA molecule that can suppress cancer-causing genes in mice
with glioblastoma mulitforme, a deadly and incurable type of brain tumor. While
standard chemotherapy drugs damage DNA to stop cancer cells from reproducing,
the new method stops the source that creates those cancer cells. The approach
could also potentially be used for gene silencing in other cancers and diseases
of genetic origin.

...........................

northwestern Medicine
scientists have identified a small RNA molecule called miR-182 that can
suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a
deadly and incurable type of brain tumor.

While standard chemotherapy drugs damage DNA to stop cancer cells from
reproducing, the new method stops the source that creates those cancer cells:
genes that are overexpressing certain proteins.

"Our study identified miR-182 as a glioblastoma tumor suppressor that
reduces the expression of several oncogenes that promote cancer
development," said senior author of the study Alexander Stegh, an
assistant professor in the Ken and Ruth Davee department of neurology and of
medicine at Northwestern University Feinberg School of Medicine.

The study, published April 2 in Genes and Development, used a
nanostructure called spherical nucleic acids (SNAs) to safely deliver miR-182
across the blood-brain barrier to reach tumor cells. There it directly targeted
multiple oncogenes at once, increasing cancer cell death and reducing cancer
cell growth. SNAs are composed of multiple strands of DNA and RNA densely
arranged around a nanoparticle center.

"We demonstrate a more specific, more personalized approach to
therapy," Stegh said. "SNAs are a very promising platform to silence
the particular genes that drive or contribute to cancer progression in
individual patients."

There are 16,000 new cases of the deadly brain tumor reported in the U.S.
every year. Patients have a very poor prognosis, with median survival of just
14 to 16 months.

The molecule miR-182 is a microRNA, a type of short non-coding RNA that can
bind to hundreds of genes to reduce their protein expression in cells. Looking
at large-scale genomic datasets, Stegh and colleagues saw that patients with
higher levels of miR-182 had a better chance of surviving glioblastoma
mulitforme longer.

In the study, they found that miR-182 suppressed Bcl2L12, a cancer gene
that blocks cancer cell death in response to chemo- and radiation therapy. The
microRNA also impeded two other oncogenes, c-Met and HIF2A. The next challenge
was establishing a way to get miR-182 to those specific targets.

The solution was in SNAs, a structure invented by Northwestern colleague
and co-author Chad Mirkin, the George B. Rathmann Professor of Chemistry at the
Weinberg College of Arts and Sciences and a professor of medicine at Feinberg.

"We designed a novel delivery method for miR-182 using SNAs,"
Stegh said. "Small gold nanoparticles are conjugated with miR-182
sequences. They cross the blood-brain/blood-tumor barrier, and accumulate
within brain tumor sites, where they target oncogenes, regulate cell growth and
differentiation, reduce tumor burden and prolong survival in our mouse
models."

SNAs have unique properties that allow them to reach cells safely without
causing toxicity or activating the immune system.

"Our approach to gene silencing has not been demonstrated before in
such a powerful way for the treatment of brain cancers," Stegh said.
"These particles, microRNA based SNAs, could also potentially be used for
gene silencing in other cancers and diseases of genetic origin."

Additional studies will be needed to test miR-182 and the nanoparticle
delivery before it becomes an option for patients with glioblastoma mulitforme.
But first, Stegh and colleagues want to hone the particle design and to
investigate treatments that combine miR-182 with established chemotherapy drugs
in mouse models.







Story Source:

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







Journal Reference:

1.    Fotini M. Kouri, Lisa A. Hurley, Weston
L. Daniel, Emily S. Day, Youjia Hua, Liangliang Hao, Chian-Yu Peng, Timothy J.
Merkel, Markus A. Queisser, Carissa Ritner, Hailei Zhang, C. David James, Jacob
I. Sznajder, Lynda Chin, David A. Giljohann, John A. Kessler, Marcus E. Peter,
Chad A. Mirkin, Alexander H. Stegh.miR-182 integrates apoptosis, growth, and
differentiation programs in glioblastoma. Genes & Development,
2015; 29 (7): 732 DOI:10.1101/gad.257394.114

http://www.sciencedaily.com/releases/2015/04/150403095933.htm

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