Childhood Brain Cancer
ironjustice
brain cancer
http://www.physorg.com/news189782701.html
April 6, 2010 Src (short for sarcoma) is a family of proto-oncogenic
tyrosine kinases active in many cancer tumors, including
medulloblastoma, the most common malignant cancer in children. Src
represents one of the most promising targets for cancer therapy.
A recent study shows that pyrazolo-[3,4-d]-pyrimidine-derivatives,
designed to target Src, may be effective in interfering with the cell
cycle and causing cancer cell death in medulloblastoma. The results
were published in FASEB (The Journal of the Federation of American
Societies for Experimental Biology) and were funded by the Sbarro
Health Research Organization Center for Biotechnology (www.shro.org),
a nonprofit group devoted to molecular and genetic research located at
the College of Science and Technology at Temple University in
Philadelphia, PA and the Human Health Foundation (www.hhfonlus.org), a
nonprofit biotechnology research organization located in Terni, Italy.
"Our aim was to investigate the inhibitory effects of new pyrimidine-
derivatives," said lead author Antonio Giordano, M.D. PhD, the Founder
and Director of the Sbarro Institute for Cancer Research and Molecular
Medicine and a 'Chiara fama' Professor at the Department of Human
Pathology and Oncology, University of Siena, Siena, Italy. "Our
findings show that, in medulloblastoma cells, pyrimidine derivatives
can downregulate Src activity and reduce cell proliferation and tumor
progression in vivo. This suggests that pyrimidine derivatives could
be an effective therapeutic strategy not only for the treatment of
medulloblastomas, but also for other Src expressing tumors."
Although better treatment regimens, including surgery, chemotherapy
and radiotherapy have substantially improved survival, medulloblastoma
remains incurable in about one third of patients and current
treatments can cause toxic neurocognitive side effects.
"Compared with conventional chemotherapeutic agents cisplatin and
etoposide that are presently used in medulloblastoma therapy, we found
that these pyrimidine derivatives show major inhibitory effects on
cell proliferation," said Alessandra Rossi, Ph.D, a co-author of the
study, a Research Fellow at the Sbarro Institute. "Using these
compounds with radiotherapy could allow the reduction of radiation
doses and, consequently, the avoidance of radiotherapy-related
cognitive and endocrine toxic effects. Moreover, our findings reveal
that the pyrimidine compounds showed synergistic effects when combined
with cisplatin and etoposide, suggesting their possible use in
association with chemotherapy."
Attempts to further reduce the morbidity and mortality associated with
medulloblastoma have been limited by the toxicity of conventional
treatments and the low permeability of the blood-brain barrier (BBB),
which restricts the entry of hydrophilic and large liphophilic
compounds into the brain.
"Other Src inhibitors, currently in clinical trials for the treatment
of other pathologies, showed low efficacy in the treatment of
metastasis to the brain," said co-author Silvia Schenone, Ph.D,
Associate Professor at the University of Genoa, Genoa, Italy, in
collaboration with Maurizio Botta, Ph.D, Adjunct Professor at Temple
University, Director, Drug Discovery Program, Professor Medical
Chemistry and Dean of the Faculty of Pharmacy at the University of
Siena, Siena, Italy. "But our pyrimidine derivatives have liphophilic
characteristics, which enable them to pass through the blood brain
barrier more easily, representing an other advantage of their use in
medulloblastoma therapy."
Besides the possible use of these pyrimidine derivatives in the
treatment of medulloblastoma, these compounds could be useful to
develop new pharmacologic inhibitors to study the physiological and
oncogenic functions of Src.
Provided by Sbarro Health Research Organization
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Mechanism of inhibition of iron corrosion in hydrochloric
acid by pyrimidine and series of its derivatives
H.S. Awad, S. Abdel Gawad
Anti-Corrosion Methods and Materials
Year: 2005 Volume: 52 Issue: 6 Page: 328 - 336
ISSN: 0003-5599
DOI: 10.1108/00035590510624668
Emerald Group Publishing Limited
Abstract: Purpose –
To investigate the capability of a series of nitrogen-based
heterocyclic organic compounds in inhibiting corrosion of
iron in HCl and elucidate the dominant active form of the
applied compounds during the adsorption process to explore
the mechanism of their action.
Design/methodology/approach –
The tested compounds were pyrimidine containing compounds,
which were selected, based on molecular structure
considerations.
Gravimetric method has been applied with various
electrochemical techniques (polarisation resistance,
polarisation curves and electrochemical impedance
spectroscopy) to investigate inhibition efficiency and
mechanism.
Findings –
The inhibiting action of the investigated pyrimidine
containing compounds depends primarily on their
concentration and molecular structure.
These compounds act as mixed type inhibitors and
function via adsorption on the surface, which follows
Frumkin adsorption isotherm.
The inhibition by the tested pyrimidine derivatives
could be attributed to their chemisorption on the
metal surface forming donor/acceptor type of bond
between the inhibitor molecules and the vacant d
orbitals of the surface iron atoms.
Contribution from electrostatic adsorption, via
interaction between the protonated form of the
inhibitor and the charged metal surface, is also
possible.
Research limitations/implications –
The applied inhibitors were tested in the presence
of chloride ions as a corrosive medium.
Whether these inhibitors will function well in the
presence of other ions that are typically present
in natural corrosive environment is unknown.
Originality/value –
This paper provides useful information regarding
inhibition effect of pyrimidine and series of its
derivatives.
The outcome of this work contributes to better
understanding of the mechanism of inhibition by
this class of N-based heterocyclic organic compounds.
Keywords: Corrosion inhibitors, Iron, Organic compounds
http :// www .emeraldinsight,com /10.1108/00035590510624668
© Emerald Group Publishing Limited
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