By far, chemotherapy is the best cancer therapy used in the medical field. Since cancer cells rapidly divide, traditional chemotherapy mechanism is based on attacking cancer cells by detecting any abnormal cell growth and damaging the DNA responsible for their replication. However, this therapy method also causes the death of normal fast-growing cells that are essential for human’s health. Recent research showed that during cancer cell activity, Ras-signaling that are released by cancer cells promote unusual type of viruses named Mammalian reovirus. These benign viruses attain abilities in inducing reversion of different types of cancers specifically by following certain signalling that are released by cancerous cells. Therefore, due to its promising potential as a better alternative for chemotherapy, reovirus has been going under extensive clinical trials that focus on discovering new cancer treatments (Harrington, et al., 2010). Moreover, p53 gene, a tumor suppressor, plays a major role in regulating the cell cycle, hence supressing rapid cancerous cell growth. For cancer treatment, specific drugs that activate the p53 gene in the cell are used in chemotherapeutic pathways. According to previous studies, the death of reovirus- induced cancer cells were enhanced by specific p53 gene stabilizer (Forsyth, et al., 2008). In this study, cells infected with reovirus were treated with and without anti-cancer drugs, Etoposide, Doxorubicin, and Actinomycin D, in order to examine the virus’s effect on enhancing the death of cancer cells. The main questions in this study are: What is the best anti-cancer drug that should be combined with reovirus in order to achieve the maximum positive outcome of a cancer treatment? What kind of effect does the status of p53 gene in a cancer cell have on the achieved outcome? Does reovirus-induced therapy play a role in reducing chemotherapy negative side-effects? Can Reovirus function alone?
Summary:
In this study, the main objective was to reduce the side-effects caused by chemotherapy agents. In order to accomplish this favoured outcome, the cancerous cells were treated with minimum drug concentrations, while attempting to acquire most of their ability in accumulating high levels of p53 gene. Yet, following this method did not result in cancer cells death, and p53 gene levels revealed absolutely no effect. Following the same method with reovirus-induced cells resulted in different outcomes. It was observed that the level of cell death was notably enhanced in cells regulated by p53 gene once they were combined with Etoposide and Actinomycin, but not with Doxorubicin. These findings revealed that Doxorubicin is not p53-dependant and it interacts with other macromolecules with great complexity. Instead, Etoposide and Actinomycin are p53-dependant and both follow similar mechanism in promoting cancer cells death. Next, to further prove the previously obtained results, higher concentrations of the drugs were used to test whether drug type has an effect on reovirus-induced cell death. Similar results were observed indicating that certain chemotherapy agents are more efficient compared to others, such as Doxorubicin, in enhancing reovirus-induced cell death. This is clinically useful for selecting suitable drugs that are the most effective treatment, yet with optimal dosages needed by the patients. Importantly, the cell death caused by the combination of reovirus and these chemotherapy agents are p53 dependent, and regulate p53-taget genes (Pan, et al., 2011). Furthermore, a transcription factor named NF-kB was discovered as a major mediator to chemotherapy resistance (Chang and Miyamoto, 2006), and the addition of either Etoposide or Actinomycin to reovirus-induced cells enhanced its activity. However, NF-kB activation might be beneficial to increase the reovirus-induced cancer cell death level, and its inhibition displayed a reduction in the death levels. In other words, cancer cells that are chemotherapy-resistant due to high levels of NF-kB factor are likely approachable by reovirus and anti-cancer drugs combination therapy. Noteworthy, 50% of cancer cells have p53 gene mutations, and cells that harbored p53 gene achieved the highest levels of reovirus-induced cancer cells death. Finally, based on observations, the combination of reovirus and anti-cancer agents restore p53 gene function, improving cancerous cells death.
Critique:
The article begins with an introduction about Mammalian reovirus as an alternative pathway for cancer treatment. It goes further to discuss the various studies that focused on the ability of reovirus in inducing regression of different types of cancer cells in vivo and in vitro, then clearly explaining the benefits this virus present when combined with anti-cancer drugs. In turn, this establishes the background upon which the researchers introduce various possible pathways in which this newly discovered virus could be combined with cancer treatments. The questions which the researchers were trying to address in this study were clearly represented. However, the challenges that were faced by the researchers during this study are not clearly stated in the introduction section.
The researchers have organized the materials and methods section well by grouping various sections under subheadings followed by a description of what was involved or obtained. Moreover, context is provided for all experiments preformed since the researchers provided comprehensive explanations for the purpose of each experiment conducted. All these factors helped the reader to follow how this study was performed.
The result section is well-organized with subheadings that explored the main findings from the experiments conducted. The data was presented using different representations including different types of graphs and high-quality images, making it easier for readers to follow and interpret. This article, however, lack the use of tables to organize the data collected throughout the study. All data collected were accounted for in the conclusion and assisted in supporting the results. The researchers also offered an explanation regarding the interpretation of the results, and how they are related to the main study questions.
The article was novel and ground-breaking because it led to the discovery of possible, less detrimental therapeutic methods in treating cancer. The researchers concluded that the combination of reovirus and anti-cancer agents is dependent on p53 gene. However, in one of the results, the researchers displayed disagreement with the results of another study in which they presented NF-kB transcription factor as a mediator to chemotherapy resistance. Controversially, based on the data, NF-kB factor resulted in the enhancement of reovirus-induced cancer cell death. This could be puzzling for an average reader, therefore, this article in intended to audience with high level of education. Overall, Although the experiment was well-conducted, the researchers should more refined to result in less conflicting findings.