OMPI Seminar: Hamid Moradi and Richard Richardson

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Thursday, March 24, 2016

Time: 3:30-5:00 pm - Thursday 24 March 2016. Refreshments start at 3:15

Location: The Ottawa Hospital Auditorium, 2nd floor, main hospital, 501
Smyth Road

Webcast link:


1. Characterization of radioresistance in human ovarian cancer cells

By Hamid Moradi, Carleton University

Abstract: "The development of a radiosensitivity predictive assay is an
attractive goal in radiation Oncology. Since there is a high degree of
inter-patient variability in the inherent sensitivity or resistance to
therapy, it is crucial to have the ability to identify molecular markers
that correlate with sensitivity or resistance to radiation treatment. We
have applied Raman micro-spectroscopy (RMS) in vitro to discriminate
between the ovarian carcinoma cell lines A2780s (parental wild type) and
A2780cp (cisplatin cross radio-resistant variant). These two cell lines
represent a good model of tumor tissues of similar origin but with
different intrinsic chemo- and radio-sensitivities. Moreover, their
radiobiological behavior has been extensively studied and their survival
curves under different irradiation schemes are known.
The Raman spectra collected from individual cells undergo initial
preprocessing (background subtraction, normalization and noise
reduction) to yield true Raman spectra representative of the cells. The
mean of these spectra are analyzed with Principal Component Analysis
(PCA) followed by Linear Discriminant Analysis (LDA) to yield a strong
separation between the cell lines. The objective of this ongoing work is
to characterize the spectral differences between the two cell types in
order to determine the underlying biochemical basis for this separation.
The multivariate classification model constructed using such Raman
spectra of ovarian cancer cells could potentially be utilized for early
prediction of tumor response."

Talk on 2016 paper by Richard Richardson and Mary-Ellen Harper, University of Ottawa: "Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy"

By Richard Richardson, Canadian Nuclear Laboratories, Chalk River

Abstract: It has been more than 60 years since the discovery of the
oxygen effect that empirically demonstrates the direct association
between cell radiosensitivity and oxygen tension, important parameters
in radiotherapy. Yet the mechanisms underlying this principal tenet of
radiobiology are poorly understood. Better understanding of the oxygen
effect may explain difficulty in eliminating hypoxic tumor cells, a
major cause of regrowth after therapy. Our analysis utilizes the
Howard-Flanders and Alper formula, which describes the relationship of
radiosensitivity with oxygen tension. Here, we assign and qualitatively
assess the relative contributions of two important mechanisms. The first
mechanism involves the emission of reactive oxygen species from the
mitochondrial electron transport chain, which increases with oxygen
tension. The second mechanism is related to an energy and repair
deficit, which increases with hypoxia. Following a radiation exposure,
the uncoupling of the oxidative phosphorylation system (proton leak) in
mitochondria lowers the emission of reactive oxygen species which has
implications for fractionated radiotherapy, particularly of hypoxic
tumors. Our analysis shows that, in oxygenated tumor and normal cells,
mitochondria, rather than the nucleus, are the primary loci of
radiotherapy effects, especially for low linear energy transfer
radiation. Therefore, the oxygen effect can be explained by
radiation-induced effects in mitochondria that generate reactive oxygen
species, which in turn indirectly target nuclear DNA.