| Natalie Raso - Weapons of Targeted Destruction: Using Viruses to Kill Cancer | Discussion |
| Project
Information Abstract Project Summary Background Purpose Scientific Thought Hypotheses Apparatus and Materials Genetically Engineered KM110red Herpesvirus Methodology Procedure for Cell-Line Splitting Procedure for KM110r Infection Procedure for Immunofluorescent Microscopy Imaging Statistical Analyses Proliferation Assay Analyzed Data Major Results Graphed Results Discussion of Statistics Controls and Variables Conclusions Discussion Discussion of KM110r Efficacy Successes and Failures Sources of Error and Data Limitations Future Research Applications Glossary Bibliography Acknowledgements |
The results of this experiment have
confirmed that KM110r is an effective and safe oncolytic virus therapy
because of its ability to successfully terminate cancer cells and to
ignore non-cancerous cells. This result substantiates KM110r as an
effective cancer therapy and worthy of being developed into an oncolytic
virus. In the 34°C temperature trial all
U2OS cells were 100% dead by time period 4, and in the 37°C temperature
trial all U2OS cells were 100% dead by time period 3 in the first trial,
and by time period 2 in the second. However in the 39°C trials by time
period 4, an average of 26% lysis of U2OS cells occurred. These findings
demonstrate that 34°C conditions delay cell death, and 39°C conditions
either do not permit complete cell death or may simply delay cell death.
Therefore, it appears that KM110r optimally kills cancerous cells at 37°C.
However this makes sense, given that HSV-1 (from which KM110r was
developed) is a virus that has evolved in a human host environment.
Therefore the virus has adapted to human conditions, one if which is the
human physiological (body) temperature of 37°C, thus making it its optimal
temperature condition. This investigation did not support
identification of a point during in
vitro cell differentiation at which hFOB cells become permissive to
KM110r. Consequently, it is still unclear why the virus is safe in normal
cells. However, this reveals a very advantageous quality of the virus from
a gene therapeutics perspective. The differentiation that occurred in the
hFOB cells at 39°C are changes that would generally occur in a normal
precursor bone cells. Thus it is clear that the virus is able to
distinguish between normal cell differentiation and cancer, and is able to
ignore normal cell differentiation. At each temperature trial, hFOB
cells grew at equal rates regardless of their viral infection status.
Standard error and t-probability statistical analyses showed that the
difference between hFOB infected and hFOB uninfected growth rates was not
statistically significant. This continues to verify the resistance of
normal cells to KM110r. The U2OS infected growth trends were
determined to be significantly different at each temperature range, as
confirmed by standard error and ANOVA tests. These results demonstrate the
distinct variations in U2OS growth at different temperature conditions.
This implies that irregular changes are occurring in the U2OS cells as a
result of temperature changes, which may alter the efficacy of the virus.
Although further experimentation and
interpretation is required in extrapolating the data from an in vitro to an in vivo setting (i.e. humans), the
present findings of this experiment are highly indicative of the efficacy
of KM110r to terminate cancer cells and to ignore non-cancerous cells.
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