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مجال
التميز
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تميز دراسي وبحثي
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البحوث المنشورة
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البحث (1):
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عنوان البحث:
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Metabolomic Profiling Of The
Effects Of Melittin On Cisplatin Resistant And Cisplatin Sensitive Ovarian
Cancer Cells Using Mass Spectrometry And Biolog Microarray Technology
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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13/10/2016
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موجز عن البحث:
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In the present study, liquid
chromatography-mass spectrometry (LC-MS) was employed to characterise the
metabolic profiles of two human ovarian cancer cell lines A2780
(cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their
exposure to melittin, a cytotoxic peptide from bee venom. In addition, the
metabolomics data were supported by application of Biolog microarray
technology to examine the utilisation of carbon sources by the two cell
lines. Data extraction with MZmine 2.14 and database searching were applied
to provide metabolite lists. Principal component analysis (PCA) gave clear
separation between the cisplatin-sensitive and resistant strains and their
respective controls. The cisplatin-resistant cells were slightly more
sensitive to melittin than the sensitive cells with IC50 values
of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited
the greatest metabolic perturbation upon treatment. The changes induced by
melittin in the cisplatin-sensitive cells led mostly to reduced levels of
amino acids in the proline/glutamine/arginine pathway, as well as to
decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and
nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism
were supported by the data from the Biolog assays. The lipid compositions of
the two cell lines were quite different with the A2780 cells having higher
levels of several ether lipids than the A2780CR cells. Melittin also had some
effect on the lipid composition of the cells. Overall, this study suggests
that melittin might have some potential as an adjuvant therapy in cancer
treatment.
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البحث (2):
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عنوان البحث:
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Metabolomic Profiling Of The Synergistic
Effects Of Melittin In Combination With Cisplatin On Ovarian Cancer Cells
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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14/04/2017
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موجز عن البحث:
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Melittin, the main peptide present in bee
venom, has been proposed as having potential for anticancer therapy; the
addition of melittin to cisplatin, a first line treatment for ovarian cancer,
may increase the therapeutic response in cancer treatment via synergy, resulting
in improved tolerability, reduced relapse, and decreased drug resistance.
Thus, this study was designed to compare the metabolomic effects of melittin
in combination with cisplatin in cisplatin-sensitive (A2780) and resistant
(A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass
spectrometry (MS) was applied to identify metabolic changes in A2780
(combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR
(combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells.
Principal components analysis (PCA) and orthogonal partial least squares
discriminant analysis (OPLS-DA) multivariate data analysis models were
produced using SIMCA-P software. All models displayed good separation between
experimental groups and high-quality goodness of fit (R²) and goodness of
prediction (Q²), respectively. The combination treatment induced significant
changes in both cell lines involving reduction in the levels of metabolites
in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and
pyrimidine metabolism, and the arginine/proline pathway. The combination of
melittin with cisplatin that targets these pathways had a synergistic effect.
The melittin-cisplatin combination had a stronger effect on the A2780 cell line
in comparison with the A2780CR cell line. The metabolic effects of melittin
and cisplatin in combination were very different from those of each agent
alone.
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البحث (3):
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عنوان البحث:
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Liquid Chromatography Mass
Spectrometry (LCMS) And Phenotype Microarray Profiling Of Ovarian Cancer
Cells After Exposure To Cisplatin
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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26/01/2017
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موجز عن البحث:
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Background:
Despite cisplatin’s effectiveness against ovarian cancer, these cancer cells
have shown the ability to resist chemotherapy – a resistance that represents
a major obstacle to current therapeutic strategies.
Objective: The
objective of the study was to determine whether or not cellular resistance
could be linked to changes in metabolites.
Methods: Liquid
chromatography-mass spectrometry (LC-MS) hydrophilic interaction
chromatography was used to analyze the intracellular metabolomic profile of
ovarian cancer cell line A2780 and the cisplatin resistant cell line A2780CR,
before and following treatment with cisplatin at inhibitory concentration
(IC50) concentrations. Phenotype MicroArray™ (PM) experiments were also
applied in order to test carbon substrate utilization or sensitivity in both
cell lines after exposure to cisplatin. Data extraction was carried out with
MZmine 2.10 with metabolite searching against an in-house database. The data
were analyzed using univariate and multivariate principal component analysis
(PCA) and orthogonal projections to latent structures discriminant analysis
(OPLS-DA) methods.
Results: There
was clear discrimination between the controls and the cisplatin treated
samples on the basis of PCA and OPLS-DA. The cisplatin-sensitive cells were
as expected more sensitive to cisplatin than the resistant cells with IC50
values of 4.9 and 10.8 μg/mL, respectively. The results demonstrated that the
intracellular metabolomic changes induced by cisplatin in the
cisplatin-sensitive cells led to reduced levels of acetylcarnitine,
phosphocreatine, arginine, proline and glutathione disulfide (GSSG) as well
as to increased levels of tryptophan and methionine. While PM experiments
showed lowered glucose metabolism in the sensitive cells following treatment
which was reflected in decreased levels of ATP.
Conclusions:
Overall the metabolic changes induced in A2780CR cells by cisplatin were much
fewer than those induced in A2780 cells. The sensitive cells had a much
quicker onset of apoptosis than the resistant cells as judged by measurement
of caspase 3. Increased resistance to oxidative stress in the resistant cells
was consistent with higher levels of proline, due to less induction of
proline dehydrogenase, and elevated levels of glutathione (GSH) and GSSG
following cisplatin treatment.
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المؤتمرات العلمية:
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المؤتمر (1):
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عنوان المؤتمر:
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Scottish Metabolomics Network
Inaugural Meeting
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تاريخ الإنعقاد:
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30/11/2015
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مكان
الإنعقاد:
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Edinburgh,
UK
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طبيعة المشاركة:
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Poster
presentation
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عنوان المشاركة:
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The Metabolomic Effects Of
Melittin On Ovarian Cancer Cells Using High Resolution Mass Spectrometry
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ملخص المشاركة:
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Melittin
is a peptide that is the principal component of honey bee venom. It has been
proposed to have potential for anticancer therapy. Untargeted metabolomic
profiling is a powerful tool in biomarker discovery. In the present study,
liquid chromatography (LC) coupled with mass spectrometry (MS) was used to
characterize metabolic profiles of A2780 human ovarian cancer cell lines in
response to exposure to the melittin.
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المؤتمر (2):
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عنوان المؤتمر:
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Metabolic Profiling
Forum-Metabomeeting 2015
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تاريخ الإنعقاد:
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07/12/2015
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مكان
الإنعقاد:
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Cambridge,
UK
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طبيعة المشاركة:
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Poster
presentation
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عنوان المشاركة:
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Metabolomic Profiling Of The
Effects Of Melittin On Cisplatin Resistant And Cisplatin Sensitive Ovarian
Cancer Cells
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ملخص المشاركة:
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Cancer
is a destructive disease that changes the metabolism of a cell and the
surrounding milieu. Worldwide, more than 230,000 women are diagnosed with
ovarian cancer each year, and this disease is responsible for an estimated
140,000 deaths per year worldwide. Melittin is a peptide that is the
principal component of honey bee venom. It has been proposed as to have
potential for anticancer therapy. Metabolomics is a new field of “omics”
research concerned with the high-throughput identification and quantification
of the small molecule metabolites in the metabolome. Untargeted metabolomic
profiling is a powerful tool in biomarker discovery. In the present study,
liquid chromatography (LC) coupled with mass spectrometry (MS) was used to
characterize metabolic profiles of human ovarian cancer cell lines A2780 and
the cisplatin resistance cell line A2780CR in response to exposure to the
melittin.
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