https://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&feed=atom&action=historyViral Oncology - Revision history2024-03-28T12:00:02ZRevision history for this page on the wikiMediaWiki 1.39.6https://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123976&oldid=prevDitmarsf: /* Adenovirus */2016-05-17T18:47:36Z<p><span dir="auto"><span class="autocomment">Adenovirus</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Adenojpg.gif|thumb|300px|right|Structure of Adenovirus. [http://microbewiki.kenyon.edu/images/8/81/Adenojpg.gif].]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Adenojpg.gif|thumb|300px|right|Structure of Adenovirus. [http://microbewiki.kenyon.edu/images/8/81/Adenojpg.gif].]]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Adenoviruses are a class of nonenveloped (Without a lipid bilayer) viruses with a double stranded DNA genome<del style="font-weight: bold; text-decoration: none;">. Adenoviruses enter </del>the cell through endocytosis. Once <del style="font-weight: bold; text-decoration: none;">in </del>the virus enters the cell <del style="font-weight: bold; text-decoration: none;">the </del>capsid breaks apart and ruptures the endosome releasing its DNA into the host cell <del style="font-weight: bold; text-decoration: none;">and </del>eventually <del style="font-weight: bold; text-decoration: none;">attaching </del>to histone proteins <del style="font-weight: bold; text-decoration: none;">to enable </del>transcription and translation of viral genes. [8]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Adenoviruses are a class of nonenveloped (Without a lipid bilayer) viruses with a double stranded DNA genome <ins style="font-weight: bold; text-decoration: none;">that enters </ins>the cell through endocytosis. Once the virus enters the cell <ins style="font-weight: bold; text-decoration: none;">its </ins>capsid breaks apart and ruptures the endosome releasing its DNA into the host cell<ins style="font-weight: bold; text-decoration: none;">. The DNA </ins>eventually <ins style="font-weight: bold; text-decoration: none;">attaches </ins>to histone proteins <ins style="font-weight: bold; text-decoration: none;">and enables </ins>transcription and translation of viral genes. [8]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>For an adenovirus to successfully replicate in a host cell a number of processes must be completed in succinct order. The most important of these events being the repression genes which lead to apoptosis or programmed cell death which if active would hinder the viruses ability to replicate within the cell. The adenovirus accomplishes this through 2 major gene products; E1B-19K and E1B-55K. E1B-19K does two major things in the host cell. [9] The first and most important function of this protein is its ability to bind and sequester BAK. BAK when activated induced apoptosis by binding to BAX and forming pores in the mitochondrial wall. Apoptogenic proteins then leech from the mitochondria ultimately releasing capase and lysing the cell. In addition, this protein works to stabilized viral and cellular DNA.[10] <br> </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>For an adenovirus to successfully replicate in a host cell a number of processes must be completed in succinct order. The most important of these events being the repression genes which lead to apoptosis or programmed cell death which if active would hinder the viruses ability to replicate within the cell. The adenovirus accomplishes this through 2 major gene products; E1B-19K and E1B-55K. E1B-19K does two major things in the host cell. [9] The first and most important function of this protein is its ability to bind and sequester BAK. BAK when activated induced apoptosis by binding to BAX and forming pores in the mitochondrial wall. Apoptogenic proteins then leech from the mitochondria ultimately releasing capase and lysing the cell. In addition, this protein works to stabilized viral and cellular DNA.[10] <br> </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>E1B-55K functions on a p53 dependent pathway. p53, also known as the “Guardian of the Genome”, works to regulate the cell cycle, check for mutations in genes and initiate apoptosis. E1B-55K binds to p53 and adds a repression domain to the protein. This results in p53 acting as a repressor instead of an activator for the various apoptotic genes it would normally bind. Additionally, p53 with this repression domain has a binding affinity ten times higher than p53 alone. This repression domain effectively eliminates all p53 dependent apoptosis pathways allowing adenovirus to replicate without programmed cell death.[11]<br> </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>E1B-55K functions on a p53 dependent pathway. p53, also known as the “Guardian of the Genome”, works to regulate the cell cycle, check for mutations in genes and initiate apoptosis. E1B-55K binds to p53 and adds a repression domain to the protein. This results in p53 acting as a repressor instead of an activator for the various apoptotic genes it would normally bind. Additionally, p53 with this repression domain has a binding affinity ten times higher than p53 alone. This repression domain effectively eliminates all p53 dependent apoptosis pathways allowing adenovirus to replicate without programmed cell death.[11]<br> </div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123975&oldid=prevDitmarsf: /* Oncolytic Viruses */2016-05-17T18:45:45Z<p><span dir="auto"><span class="autocomment">Oncolytic Viruses</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Oncolytic Viruses=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Oncolytic Viruses=</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Oncolytic viruses are viruses that specifically target and kill cancer cells. This process usually relies on genetically modified viruses that <del style="font-weight: bold; text-decoration: none;">are only able </del>to replicate within <del style="font-weight: bold; text-decoration: none;">cancer </del>cells. <del style="font-weight: bold; text-decoration: none;">This selection is typically accomplished through </del>the <del style="font-weight: bold; text-decoration: none;">knockout </del>of genes that <del style="font-weight: bold; text-decoration: none;">repress cellular apoptosis</del>. <del style="font-weight: bold; text-decoration: none;">These cells then kill cancer cells through </del>the lytic cycle.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Oncolytic viruses are viruses that specifically target and kill cancer cells. This process usually relies on genetically modified viruses that <ins style="font-weight: bold; text-decoration: none;">have lost their ability </ins>to replicate within <ins style="font-weight: bold; text-decoration: none;">somatic cells but maintain virulence in cancerous </ins>cells. <ins style="font-weight: bold; text-decoration: none;">Many of these cells are no longer able to infect somatic cells due to </ins>the <ins style="font-weight: bold; text-decoration: none;">loss or inactivation </ins>of genes that <ins style="font-weight: bold; text-decoration: none;">can suppress apoplectic mechanisms within the cell</ins>. <ins style="font-weight: bold; text-decoration: none;">Without these repression mechanisms the virus is only able to undergo </ins>the lytic cycle <ins style="font-weight: bold; text-decoration: none;">within cancer cells making them a potent and efficient method of cancer treatment</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td></tr>
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</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123974&oldid=prevDitmarsf: /* Introduction */2016-05-17T18:42:26Z<p><span dir="auto"><span class="autocomment">Introduction</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Introduction=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Introduction=</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Oncolytic.jpg|thumb|300px|right|Cartoon of the typical pathway in which an oncolytic virus infects a cancerous cell and destroys it. [http://www.nature.com/nrclinonc/journal/v4/n2/fig_tab/ncponc0736_F1.html nature]]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Oncolytic.jpg|thumb|300px|right|Cartoon of the typical pathway in which an oncolytic virus infects a cancerous cell and destroys it. [http://www.nature.com/nrclinonc/journal/v4/n2/fig_tab/ncponc0736_F1.html nature]]]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Viral oncology is a subsection of oncology concerned with the treatment of tumors with viral particles. While this field has gotten a lot of press in recent years, the idea of using viruses as oncolytic agents has been around since the early 1920’s, and the correlation between viruses and remission has been around singe the mid-to-late 1800s [1]. Most of the patients studied in the 1800s had blood-based cancers such as leukemia or lymphoma with significant immune suppression [3]. The most famous report of this type was made by Dr. Dock [2] in which a 47 year old woman with myelogenous leukemia went into remission after a flu infection. Another more shocking case is that of a 4 year old boy with lymphatic leukemia who contracted chickenpox. Before his contraction of chickenpox, his liver, spleen and lymph nodes were all severely swollen and his leukocyte count was greatly elevated (200 cells/ul). After contracting chicken pox his liver and spleen returned to normal size and his white count fell back into normal levels (4.1 cells/ul). However, in both cases the remission was short lived and the cancer soon returned. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Viral oncology is a subsection of oncology concerned with the treatment of tumors with viral particles. While this field has gotten a lot of press in recent years, the idea of using viruses as oncolytic agents has been around since the early 1920’s, and the correlation between viruses and remission has been around singe the mid-to-late 1800s [1]. Most of the patients studied in the 1800s had blood-based cancers such as leukemia or lymphoma with significant immune suppression [3]. The most famous report of this type was made by Dr. Dock <ins style="font-weight: bold; text-decoration: none;">in 1904 </ins>[2] in which a 47 year old woman with myelogenous leukemia went into remission after a flu infection. Another more shocking case is that of a 4 year old boy with lymphatic leukemia who contracted chickenpox. Before his contraction of chickenpox, his liver, spleen and lymph nodes were all severely swollen and his leukocyte count was greatly elevated (200 cells/ul). After contracting chicken pox his liver and spleen returned to normal size and his white count fell back into normal levels (4.1 cells/ul). However, in both cases the remission was short lived and the cancer soon returned. </div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br> The first attempt to use viruses <del style="font-weight: bold; text-decoration: none;">in oncology </del>was the treatment of chronic joint disease with hepatitis in <del style="font-weight: bold; text-decoration: none;">the 1897’s </del>[1]. <del style="font-weight: bold; text-decoration: none;">Then</del>, in 1949 a clinical trial took place in which 22 patents with Hodgkin's lymphoma were treated with tissue samples from hepatitus positive individuals. While some did achieve remission for a short time many in the study also contracted hepatitis B, and the study was discontinued [4]. A number of similar experiments were run throughout the 1950’s and 1960’s with minimal success. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br> The first attempt to use viruses <ins style="font-weight: bold; text-decoration: none;">a curative </ins>was the treatment of chronic joint disease with hepatitis in <ins style="font-weight: bold; text-decoration: none;">1897, with minimal success </ins>[1]. <ins style="font-weight: bold; text-decoration: none;">Despite the lack of success in the 1897 trials</ins>, in 1949 a clinical trial took place in which 22 patents with Hodgkin's lymphoma were treated with tissue samples from hepatitus positive individuals. While some did achieve remission for a short time<ins style="font-weight: bold; text-decoration: none;">, </ins>many in the study also contracted hepatitis B, and the study was discontinued [4]. A number of similar experiments were run throughout the 1950’s and 1960’s with minimal success. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost 50 years after the failed experiments of the 1950's and 60's a breakthrough came in the form of oncolytic adenovirus H101. This virus was approved by the Chinese Government for cancer treatments in 2005 and works by targeting p53 deficient cells (most cancers are p53 deficient)[5]. Today, thanks in large part to H101, a number of viral pathways are being investigated by medical researchers in an attempt to increase our cancer fighting toolbox.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost 50 years after the failed experiments of the 1950's and 60's a breakthrough came in the form of oncolytic adenovirus H101. This virus was approved by the Chinese Government for cancer treatments in 2005 and works by targeting p53 deficient cells (most cancers are p53 deficient)[5]. Today, thanks in large part to H101, a number of viral pathways are being investigated by medical researchers in an attempt to increase our cancer fighting toolbox.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Why Viruses?==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Why Viruses?==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br> While the medical community has been aware of the correlation between remission and viral infection since the mid-1800s, medical professionals were unsure as to why this correlation existed<del style="font-weight: bold; text-decoration: none;">, </del>until we began to understand the molecular and genetic mechanisms behind cancer and cancer replication. Cancer cells are the product of small scale evolution, which is to say that the accumulation of point mutations and chromosomal shifts, along with chromosomal instability, have resulted in a phenotype drastically different from its ancestor. Typically, in cancer cells, we see a selection for growth advantages over somatic cells. These increased growth factors include immunity to density and anchorage dependence as well as up and down regulation of certain genes such as telomerase or p53.[6]<br> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br> While the medical community has been aware of the correlation between remission and viral infection since the mid-1800s, medical professionals were unsure as to why this correlation existed until we began to understand the molecular and genetic mechanisms behind cancer and cancer replication. Cancer cells are the product of small scale evolution, which is to say that the accumulation of point mutations and chromosomal shifts, along with chromosomal instability, have resulted in a phenotype drastically different from its ancestor. Typically, in cancer cells, we see a selection for growth advantages over somatic cells. These increased growth factors include immunity to density and anchorage dependence as well as up and down regulation of certain genes such as telomerase or p53.[6]<br> </div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>While these genetic and molecular changes result in <del style="font-weight: bold; text-decoration: none;">a massive </del>increase in fitness when compared to somatic cells, often times certain defensive mechanisms are sacrificed. For example in many cancer cells a number of genetic repair enzymes are shut off as well as proteins that defend against mutations in the genome and foreign DNA.<br></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>While these genetic and molecular changes result in <ins style="font-weight: bold; text-decoration: none;">an </ins>increase in fitness when compared to somatic cells, often times certain defensive mechanisms are sacrificed. For example in many cancer cells a number of genetic repair enzymes are shut off as well as proteins that defend against mutations in the genome and foreign DNA.<br></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Without the ability to defend against foreign DNA many cancer cells are left vulnerable to viral attacks. By exploiting the innate viral sensitivity of most cancer cells scientists have been able to engineer viruses that can not only selectively kill cancer cells but also generate an cancer specific immune response within the patients body. [7]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Without the ability to defend against foreign DNA many cancer cells are left vulnerable to viral attacks. By exploiting the innate viral sensitivity of most cancer cells scientists have been able to engineer viruses that can not only selectively kill cancer cells but also generate an cancer specific immune response within the patients body. [7]</div></td></tr>
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</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123973&oldid=prevDitmarsf: /* Introduction */2016-05-17T18:37:00Z<p><span dir="auto"><span class="autocomment">Introduction</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Introduction=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Introduction=</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Oncolytic.jpg|thumb|300px|right|Cartoon of the typical pathway in which an oncolytic virus infects a cancerous cell and destroys it. [http://www.nature.com/nrclinonc/journal/v4/n2/fig_tab/ncponc0736_F1.html nature]]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Oncolytic.jpg|thumb|300px|right|Cartoon of the typical pathway in which an oncolytic virus infects a cancerous cell and destroys it. [http://www.nature.com/nrclinonc/journal/v4/n2/fig_tab/ncponc0736_F1.html nature]]]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Viral oncology is a subsection of oncology concerned with the treatment of tumors with viral particles. While this field has gotten a lot of press in recent years, the idea of using viruses as oncolytic agents has been around since the early 1920’s, and <del style="font-weight: bold; text-decoration: none;">since as early as </del>the mid-to-late <del style="font-weight: bold; text-decoration: none;">1800’s doctors noticed that certain viral infections would cause remission in cancer patients </del>[1]. <del style="font-weight: bold; text-decoration: none;">These </del>patients <del style="font-weight: bold; text-decoration: none;">usually </del>had blood-based cancers such as leukemia or lymphoma with significant immune suppression [3]. The most famous report of this type was made by Dr. Dock [2] in which a 47 year old woman with myelogenous leukemia went into remission after a flu infection. Another more shocking case is that of a 4 year old boy with lymphatic leukemia who contracted chickenpox. Before his contraction of chickenpox, his liver, spleen and lymph nodes were all severely swollen and his leukocyte count was greatly elevated (200 cells/ul). After contracting chicken pox his liver and spleen returned to normal size and his white count fell back into normal levels (4.1 cells/ul). However, in both cases the remission was short lived and the cancer soon returned. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Viral oncology is a subsection of oncology concerned with the treatment of tumors with viral particles. While this field has gotten a lot of press in recent years, the idea of using viruses as oncolytic agents has been around since the early 1920’s, and <ins style="font-weight: bold; text-decoration: none;">the correlation between viruses and remission has been around singe </ins>the mid-to-late <ins style="font-weight: bold; text-decoration: none;">1800s </ins>[1]. <ins style="font-weight: bold; text-decoration: none;">Most of the </ins>patients <ins style="font-weight: bold; text-decoration: none;">studied in the 1800s </ins>had blood-based cancers such as leukemia or lymphoma with significant immune suppression [3]. The most famous report of this type was made by Dr. Dock [2] in which a 47 year old woman with myelogenous leukemia went into remission after a flu infection. Another more shocking case is that of a 4 year old boy with lymphatic leukemia who contracted chickenpox. Before his contraction of chickenpox, his liver, spleen and lymph nodes were all severely swollen and his leukocyte count was greatly elevated (200 cells/ul). After contracting chicken pox his liver and spleen returned to normal size and his white count fell back into normal levels (4.1 cells/ul). However, in both cases the remission was short lived and the cancer soon returned. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br> The first attempt to use viruses in oncology was the treatment of chronic joint disease with hepatitis in the 1897’s [1]. Then, in 1949 a clinical trial took place in which 22 patents with Hodgkin's lymphoma were treated with tissue samples from hepatitus positive individuals. While some did achieve remission for a short time many in the study also contracted hepatitis B, and the study was discontinued [4]. A number of similar experiments were run throughout the 1950’s and 1960’s with minimal success. </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br> The first attempt to use viruses in oncology was the treatment of chronic joint disease with hepatitis in the 1897’s [1]. Then, in 1949 a clinical trial took place in which 22 patents with Hodgkin's lymphoma were treated with tissue samples from hepatitus positive individuals. While some did achieve remission for a short time many in the study also contracted hepatitis B, and the study was discontinued [4]. A number of similar experiments were run throughout the 1950’s and 1960’s with minimal success. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost 50 years after the failed experiments of the 1950's and 60's a breakthrough came in the form of oncolytic adenovirus H101. This virus was approved by the Chinese Government for cancer treatments in 2005 and works by targeting p53 deficient cells (most cancers are p53 deficient)[5]. Today, thanks in large part to H101, a number of viral pathways are being investigated by medical researchers in an attempt to increase our cancer fighting toolbox.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost 50 years after the failed experiments of the 1950's and 60's a breakthrough came in the form of oncolytic adenovirus H101. This virus was approved by the Chinese Government for cancer treatments in 2005 and works by targeting p53 deficient cells (most cancers are p53 deficient)[5]. Today, thanks in large part to H101, a number of viral pathways are being investigated by medical researchers in an attempt to increase our cancer fighting toolbox.</div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123972&oldid=prevDitmarsf: /* Possible Solutions */2016-05-17T18:34:50Z<p><span dir="auto"><span class="autocomment">Possible Solutions</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Possible Solutions==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Possible Solutions==</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br>As discussed earlier a major problem facing oncolytic viruses is the inability of the virus to move thorough the connective tissue surrounding the target tumor. Recently, doctors have begun experimenting with pre-treatments before dosing someone with a virus, such as hyaluronidase or collagenase, which would work to break up the connective tissue allowing the virus to attach to the cancer cell and infect it.[39]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br>As discussed earlier a major problem facing oncolytic viruses is the inability of the virus to move thorough the connective tissue surrounding the target tumor. Recently, doctors have begun experimenting with pre-treatments before dosing someone with a virus, such as hyaluronidase or collagenase, which would work to break up the connective tissue allowing the virus to attach to the cancer cell and infect it.[39]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Doctors are also thinking about employing a “viral cocktail” much like those used in chemotherapy or in treating retroviruses. These would contain a number of different types of viruses that function using different pathways <del style="font-weight: bold; text-decoration: none;">hopefully, </del>making it <del style="font-weight: bold; text-decoration: none;">more </del>difficult for the <del style="font-weight: bold; text-decoration: none;">cells </del>to develop an immunity.<br> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Doctors are also thinking about employing a “viral cocktail” much like those used in chemotherapy or in treating retroviruses. These would contain a number of different types of viruses that function using different pathways making it <ins style="font-weight: bold; text-decoration: none;"> </ins>difficult for the <ins style="font-weight: bold; text-decoration: none;">cancers </ins>to develop an immunity.<br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">Most importantly, due to the diversity within viruses and our ability to manipulate them at a genetic level, modern medicine can create a diverse pool of oncolytics and immunoviruses that should be able to combat even the most potent cancers.</del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=References=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=References=</div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123971&oldid=prevDitmarsf: /* Problems Still Facing Viral Oncology */2016-05-17T18:23:00Z<p><span dir="auto"><span class="autocomment">Problems Still Facing Viral Oncology</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Problems Still Facing Viral Oncology=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Problems Still Facing Viral Oncology=</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>While viruses are certainly promising as a cancer fighting tool there are still a number of <del style="font-weight: bold; text-decoration: none;">problems with the use of viruses in treating cancer</del>. The first and most obvious of these problems is that <del style="font-weight: bold; text-decoration: none;">ultimately </del>viral oncology involves injecting a person with a live virus which carries with it a risk of contracting disease. While almost all viruses are attenuated significantly or genetically modified to the point where they should be totally non-pathogenic to somatic cells there is still a risk, especially as many cancer patients are immunocompromised. Additionally<del style="font-weight: bold; text-decoration: none;">, because these are ultimately viruses</del>, the patient’s body often mounts a defense against the virus itself <del style="font-weight: bold; text-decoration: none;">resulting in an </del>immune <del style="font-weight: bold; text-decoration: none;">response </del>and <del style="font-weight: bold; text-decoration: none;">the destruction of many </del>circulating <del style="font-weight: bold; text-decoration: none;">viruses within the body </del>before they can infect <del style="font-weight: bold; text-decoration: none;">any cancer </del>cells[34,35]. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>While viruses are certainly promising as a cancer fighting tool there are still a number of <ins style="font-weight: bold; text-decoration: none;">challenges still facing viral oncology</ins>. The first and most obvious of these problems is that viral oncology involves injecting a person with a live virus<ins style="font-weight: bold; text-decoration: none;">, </ins>which carries with it a risk of contracting disease. While almost all viruses are attenuated significantly or genetically modified to the point where they should be totally non-pathogenic to somatic cells there is still a risk, especially as many cancer patients are immunocompromised. Additionally, the patient’s body often mounts a defense against the virus itself <ins style="font-weight: bold; text-decoration: none;">causing the </ins>immune <ins style="font-weight: bold; text-decoration: none;">system to attack </ins>and <ins style="font-weight: bold; text-decoration: none;">destroy </ins>circulating <ins style="font-weight: bold; text-decoration: none;">viral particles </ins>before they can infect <ins style="font-weight: bold; text-decoration: none;">target </ins>cells[34,35]. </div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br><del style="font-weight: bold; text-decoration: none;">The real </del>problems facing viral oncology have to do with the way cancer exists inside of the human body. Most cancers <del style="font-weight: bold; text-decoration: none;">exist in </del>a large mass of cells called a tumor. This tumor is surrounded by connective tissue that differs significantly from the cell membrane. This <del style="font-weight: bold; text-decoration: none;">means that </del>many viruses that enter the cell by binding to specific proteins <del style="font-weight: bold; text-decoration: none;">are not able to penetrate this wall of connective tissue. This ultimately results in an inefficient spread </del>of viral particles and incomplete infection of the cancerous mass<del style="font-weight: bold; text-decoration: none;">, this </del>problem gets exponentially worse as the cancerous tumor becomes larger. <del style="font-weight: bold; text-decoration: none;">Additionally, while </del>direct injection of viral particles into the tumor coupled with increased dose does reduce this effect <del style="font-weight: bold; text-decoration: none;">large </del>tumors still <del style="font-weight: bold; text-decoration: none;">end up with and incomplete infection</del>.[36] </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br><ins style="font-weight: bold; text-decoration: none;">While the </ins>problems <ins style="font-weight: bold; text-decoration: none;">intrinsic to using a virus are significant, the majority of the ptoblems </ins>facing viral oncology have to do with the way cancer exists inside of the human body. Most cancers <ins style="font-weight: bold; text-decoration: none;">form </ins>a large mass of cells called a tumor. This tumor is surrounded by connective tissue that differs significantly from the cell membrane. This <ins style="font-weight: bold; text-decoration: none;">connective tissue blocks </ins>many viruses that enter the cell by binding to specific proteins<ins style="font-weight: bold; text-decoration: none;">, significantly reducing the efficiency </ins>of <ins style="font-weight: bold; text-decoration: none;">the </ins>viral particles and <ins style="font-weight: bold; text-decoration: none;">resulting in an </ins>incomplete infection of the cancerous mass<ins style="font-weight: bold; text-decoration: none;">. This </ins>problem gets exponentially worse as the cancerous tumor becomes larger. <ins style="font-weight: bold; text-decoration: none;">While </ins>direct injection of viral particles into the tumor coupled with increased dose does reduce this effect <ins style="font-weight: bold; text-decoration: none;">larger </ins>tumors still <ins style="font-weight: bold; text-decoration: none;">prove difficult to fully infect</ins>.[36] Another problem with viral oncology stems from the <ins style="font-weight: bold; text-decoration: none;">necrotic region contained within many </ins>cancerous tumors<ins style="font-weight: bold; text-decoration: none;">. This </ins>necrotic region <ins style="font-weight: bold; text-decoration: none;">is made up of cancerous cells </ins>that <ins style="font-weight: bold; text-decoration: none;">have died and lysed due to increased cellular density and inefficient distribution of nutrients</ins>. As the tumor continues to expand <ins style="font-weight: bold; text-decoration: none;">and grow </ins>the necrotic region <ins style="font-weight: bold; text-decoration: none;">also expands. This expansion can kill cancer cells in the interior of </ins>the <ins style="font-weight: bold; text-decoration: none;">tumor </ins>before the virus is able to adequately replicate<ins style="font-weight: bold; text-decoration: none;">. Premature cell death </ins>coupled with <ins style="font-weight: bold; text-decoration: none;">many cancers </ins>accelerated division rate often means that the virus simply cannot replicate fast enough to keep up with the tumor.[37]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Another problem with viral oncology stems from the <del style="font-weight: bold; text-decoration: none;">fact that </del>cancerous tumors <del style="font-weight: bold; text-decoration: none;">oftentimes contain a </del>necrotic region <del style="font-weight: bold; text-decoration: none;">within the tumor </del>that <del style="font-weight: bold; text-decoration: none;">maintains an equilibrium with the surface tumor cells</del>. As the tumor continues to expand the necrotic region <del style="font-weight: bold; text-decoration: none;">does as well often times killing </del>the <del style="font-weight: bold; text-decoration: none;">cancer cell </del>before the virus is able to adequately replicate<del style="font-weight: bold; text-decoration: none;">, that </del>coupled with <del style="font-weight: bold; text-decoration: none;">the </del>accelerated division rate <del style="font-weight: bold; text-decoration: none;">seen in cancer cells </del>often means that the virus simply cannot replicate fast enough to keep up with the tumor.[37]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Lastly, due to the inherent instability of a cancer cell’s genome<ins style="font-weight: bold; text-decoration: none;">, </ins>cancer cells <ins style="font-weight: bold; text-decoration: none;">are </ins>rapidly <ins style="font-weight: bold; text-decoration: none;">able to </ins>develop defenses against <ins style="font-weight: bold; text-decoration: none;">viruses</ins>. While oncolytic viruses are designed to exploit innate defensive shortcomings <ins style="font-weight: bold; text-decoration: none;">within the </ins>cancer cells most of these shortcomings concern genome regulation and internal defense not external defense. In some trials doctors have observed cancer cells becoming totally resistant to a certain strain of virus by no longer producing surface binding proteins that the virus needs to enter the cell.[38]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Lastly, due to the inherent instability of a cancer cell’s genome <del style="font-weight: bold; text-decoration: none;">often times </del>cancer cells <del style="font-weight: bold; text-decoration: none;">will </del>rapidly develop defenses against <del style="font-weight: bold; text-decoration: none;">a virus</del>. While oncolytic viruses are designed to exploit innate defensive shortcomings <del style="font-weight: bold; text-decoration: none;">in </del>cancer cells most of these shortcomings concern genome regulation and internal defense not external defense. In some trials doctors have observed cancer cells becoming totally resistant to a certain strain of virus by no longer producing surface binding proteins that the virus needs to enter the cell.[38]</div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Possible Solutions==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Possible Solutions==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>As discussed earlier a major problem facing oncolytic viruses <del style="font-weight: bold; text-decoration: none;">today </del>is the inability of the virus to move thorough the connective tissue surrounding the target tumor. Recently, doctors have begun experimenting with pre-treatments before dosing someone with a virus, such as hyaluronidase or collagenase, which would work to break up the connective tissue allowing the virus to attach to the cancer cell and infect it.[39]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>As discussed earlier a major problem facing oncolytic viruses is the inability of the virus to move thorough the connective tissue surrounding the target tumor. Recently, doctors have begun experimenting with pre-treatments before dosing someone with a virus, such as hyaluronidase or collagenase, which would work to break up the connective tissue allowing the virus to attach to the cancer cell and infect it.[39]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Doctors are also thinking about employing a “viral cocktail” much like those used in chemotherapy or in treating retroviruses. These would contain a number of different types of viruses that function using different pathways <del style="font-weight: bold; text-decoration: none;">that would, </del>hopefully, <del style="font-weight: bold; text-decoration: none;">overwhelm the cancer </del>making it more difficult for the cells to develop an immunity.<br> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Doctors are also thinking about employing a “viral cocktail” much like those used in chemotherapy or in treating retroviruses. These would contain a number of different types of viruses that function using different pathways hopefully, making it more difficult for the cells to develop an immunity.<br> </div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">Lastly</del>, <del style="font-weight: bold; text-decoration: none;">because we are able </del>to <del style="font-weight: bold; text-decoration: none;">design these </del>viruses <del style="font-weight: bold; text-decoration: none;">to target very specific surface proteins </del>and <del style="font-weight: bold; text-decoration: none;">shape the treatment </del>to <del style="font-weight: bold; text-decoration: none;">make more infectious for the patients specific type </del>of <del style="font-weight: bold; text-decoration: none;">cancer resistance is something the field is largely able to circumvent. The diversity and malleability of viruses means that doctors have an arsenal of vectors with distinct methods of infection </del>and <del style="font-weight: bold; text-decoration: none;">attack </del>that should be able to <del style="font-weight: bold; text-decoration: none;">overpower </del>even the most <del style="font-weight: bold; text-decoration: none;">aggressive forms of cancer</del>.<del style="font-weight: bold; text-decoration: none;"><br></del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">Most importantly</ins>, <ins style="font-weight: bold; text-decoration: none;">due </ins>to <ins style="font-weight: bold; text-decoration: none;">the diversity within </ins>viruses and <ins style="font-weight: bold; text-decoration: none;">our ability </ins>to <ins style="font-weight: bold; text-decoration: none;">manipulate them at a genetic level, modern medicine can create a diverse pool </ins>of <ins style="font-weight: bold; text-decoration: none;">oncolytics </ins>and <ins style="font-weight: bold; text-decoration: none;">immunoviruses </ins>that should be able to <ins style="font-weight: bold; text-decoration: none;">combat </ins>even the most <ins style="font-weight: bold; text-decoration: none;">potent cancers</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=References=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=References=</div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123970&oldid=prevDitmarsf: /* HIV */2016-05-17T17:57:35Z<p><span dir="auto"><span class="autocomment">HIV</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:HIV.png|thumb|300px|right|Cartoon of the structure of an HIV viron. [https://en.wikipedia.org/wiki/HIV wikipedia]]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:HIV.png|thumb|300px|right|Cartoon of the structure of an HIV viron. [https://en.wikipedia.org/wiki/HIV wikipedia]]]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br> <del style="font-weight: bold; text-decoration: none;">The </del>Human Immunodeficiency Virus is a retrovirus that causes progressive immunodeficiency in the form of AIDS. HIV only infects cells that play a role in the human immune response, most famously the CD4+ T cell but also macrophages and dendritic cells. HIV contains 2 RNA “chromosomes” chat code for 9 total proteins. The HIV capsid is surrounded by a lipid bilayer made up of its previous host cell’s cell membrane. This membrane makes the virus difficult to detect in the body and increases HIVs infectivity. HIV enters its host cell by fusing its cellular membrane to the cellular membrane of its host cell and injecting its viron into the cytoplasm. Once there the capsid falls apart and the viral RNA is turned into double stranded DNA using reverse transcriptase, this segment of DNA is then integrated into the host cells genome where it can sit in perpetuity. [29]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br> <ins style="font-weight: bold; text-decoration: none;">HIV or </ins>Human Immunodeficiency Virus is a retrovirus that causes progressive immunodeficiency in the form of AIDS. HIV only infects cells that play a role in the human immune response, most famously the CD4+ T cell but also macrophages and dendritic cells. HIV contains 2 RNA “chromosomes” chat code for 9 total proteins. The HIV capsid is surrounded by a lipid bilayer made up of its previous host cell’s cell membrane. This membrane makes the virus difficult to detect in the body and increases HIVs infectivity. HIV enters its host cell by fusing its cellular membrane to the cellular membrane of its host cell and injecting its viron into the cytoplasm. Once there the capsid falls apart and the viral RNA is turned into double stranded DNA using reverse transcriptase, this segment of DNA is then integrated into the host cells genome where it can sit in perpetuity. [29] <ins style="font-weight: bold; text-decoration: none;"><br></ins></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>HIV immunotherapy focuses on dendritic cells. Dendritic cells are antigen presenting cells <del style="font-weight: bold; text-decoration: none;">that are </del>typically found in regions of the body most likely to be exposed to foreign invaders, i.e. the lungs, skin, nose and stomach. These cells are designed to recognize and present foreign antigens. When a dendritic cell recognizes a foreign antigen it moves to the lymph nodes and attaches to T <del style="font-weight: bold; text-decoration: none;">cells </del>and B cells where the antigen is attached to MHC proteins<del style="font-weight: bold; text-decoration: none;">, triggering </del>a targeted immune response. HIV <del style="font-weight: bold; text-decoration: none;">typically </del>uses these cells as a transportation system, infecting a dendritic cell then lysing it when it moves into the lymph nodes.[30,32]<br> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>HIV immunotherapy focuses on dendritic cells. Dendritic cells are antigen presenting cells typically found in regions of the body most likely to be exposed to foreign invaders, i.e. the lungs, skin, nose and stomach. These cells are designed to recognize and present foreign antigens. When a dendritic cell recognizes a foreign antigen it moves to the lymph nodes and attaches to T and B cells where the antigen is attached to MHC proteins<ins style="font-weight: bold; text-decoration: none;">. The MHC protiens trigger </ins>a targeted immune response <ins style="font-weight: bold; text-decoration: none;">against that antigen and whatever is producing it</ins>. HIV uses these cells as a transportation system, infecting a dendritic cell then lysing it when it moves into the lymph nodes.[30,32]<br> Dendritic cells are of special importance to cancer immunotherapy <ins style="font-weight: bold; text-decoration: none;">as </ins>they seem to be able to effectively create a tumor specific immune response when compared with direct presentation of the antigen to a T or B cell. This <ins style="font-weight: bold; text-decoration: none;">means there is </ins>a stronger response to the cancer cells and a greater likelihood for remission.[31]<br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Dendritic cells are of special importance to cancer immunotherapy <del style="font-weight: bold; text-decoration: none;">is because </del>they seem to be able to <del style="font-weight: bold; text-decoration: none;">more </del>effectively create a tumor specific immune response when compared with direct presentation of the antigen to a T or B cell. This <del style="font-weight: bold; text-decoration: none;">creates </del>a stronger response to the cancer cells <del style="font-weight: bold; text-decoration: none;">with these antigens </del>and a greater likelihood for remission<del style="font-weight: bold; text-decoration: none;">. HIV presents these antigens when its RNA genome is transcribed inside of the dendritic cell. The HIV viron has been genetically engineered to contain a copy of a cancer antigen that when transcribed can bind to the antigen presenting proteins within the dendritic cell</del>.[31]<br></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>HIV is used as the vaccine vector for a number of reasons. HIV as discussed earlier, is selective and only infects certain cell types, including the dendritic cell. This means that the vaccine will be more effective per unit than a non-specific virus. Additionally, because HIV is a retrovirus it is able to be engineered as a lentiviral vector. A lentiviral vector is a modified retrovirus that has been given a new series of genes to transcribe within a cell. These vectors <ins style="font-weight: bold; text-decoration: none;">are </ins>very effective in gene therapy <ins style="font-weight: bold; text-decoration: none;">because </ins>the genes <ins style="font-weight: bold; text-decoration: none;">encoded within the lentiviral factor </ins>can continue to transcribed and translated long after the original dose. HIV is especially effective as its genes actually integrate into the host’s genome.<br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>HIV is used as the vaccine vector for a number of reasons. <del style="font-weight: bold; text-decoration: none;">First off and most importantly, </del>HIV as discussed earlier, is selective and only infects certain cell types, including the dendritic cell. This means that the vaccine will be more effective per unit than a non-specific virus. Additionally, because HIV is a retrovirus it is able to be engineered as a lentiviral vector. A lentiviral vector is a modified retrovirus that has been given a new series of genes to transcribe within a cell. These vectors <del style="font-weight: bold; text-decoration: none;">have been shown to be </del>very effective in gene therapy <del style="font-weight: bold; text-decoration: none;">as </del>the genes can continue to transcribed and translated long after the original dose. HIV is especially effective as its genes actually integrate into the host’s genome.<br></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>There have been a number of cases of modified HIV being used to treat cancer most of which were performed by Dr. Carl H. June. He is currently working on using the virus in treating pancreatic cancer.[33]<br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>There have been a number of cases of modified HIV being used to treat cancer most of which were performed by Dr. Carl H. June. He is currently working on using the virus in treating pancreatic cancer.[33]<br></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br></div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123969&oldid=prevDitmarsf: /* Cancer Immunotherapy */2016-05-17T17:26:37Z<p><span dir="auto"><span class="autocomment">Cancer Immunotherapy</span></span></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 17:26, 17 May 2016</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Cancer Immunotherapy=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Cancer Immunotherapy=</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Cancer immunotherapy <del style="font-weight: bold; text-decoration: none;">in a broad sense </del>is the use of one’s own immune system to treat cancer. These therapies are wide ranging but typically <del style="font-weight: bold; text-decoration: none;">involve </del>T-cell Costimulation. T-cell immune responses of this type are triggered by cancer antigens and enhanced by immune adjuvants. Through introduction of an attenuated or genetically modified <del style="font-weight: bold; text-decoration: none;">virus </del>carrying either the genetic material for cancer antigens or the cancer antigens themselves, <del style="font-weight: bold; text-decoration: none;">thee </del>bodies defense systems can be triggered <del style="font-weight: bold; text-decoration: none;">mounts </del>a <del style="font-weight: bold; text-decoration: none;">defense </del>that targets cells that express these cancer antigens <del style="font-weight: bold; text-decoration: none;">creating a cancer specific immune response</del>.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Cancer immunotherapy is<ins style="font-weight: bold; text-decoration: none;">, broadly, </ins>the use of one’s own immune system to treat cancer. These therapies are wide ranging but <ins style="font-weight: bold; text-decoration: none;">are </ins>typically <ins style="font-weight: bold; text-decoration: none;">centered around </ins>T-cell Costimulation. T-cell <ins style="font-weight: bold; text-decoration: none;">mediated </ins>immune responses of this type are triggered by cancer antigens and enhanced by immune adjuvants. Through introduction of an attenuated or genetically modified <ins style="font-weight: bold; text-decoration: none;">viruses </ins>carrying either the genetic material for cancer antigens or the cancer antigens themselves, <ins style="font-weight: bold; text-decoration: none;">the </ins>bodies defense systems can be triggered <ins style="font-weight: bold; text-decoration: none;">in </ins>a <ins style="font-weight: bold; text-decoration: none;">fashion </ins>that targets cells that express these cancer antigens.</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> </div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Poxvirus==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==Poxvirus==</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Pox.jpg|thumb|300px|right|Cartoon of the structure of a typical poxvirus. [http://www.twiv.tv/virus-structure/ TWIV]]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Pox.jpg|thumb|300px|right|Cartoon of the structure of a typical poxvirus. [http://www.twiv.tv/virus-structure/ TWIV]]]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br>Poxviridae is a class of enveloped viruses with a double stranded DNA genome. Poxviruses enter the cell by attaching to glycoaminoglycans on the surface of the host cells lipid bilayer. Once inside the cell the viral capsid falls apart and viral genes are transcribed in the cytoplasm starting the lytic cycle. Poxviruses were the first class of viruses scientists were able to create vaccines for and are among the best understood viruses on earth. Additionally, Poxviruses, across all classes, contain a number of phenotypes that make them ideal candidates for vaccine-mediated cancer immunotherapy.[23,24]<br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br>Poxviridae is a class of enveloped viruses with a double stranded DNA genome. Poxviruses enter the cell by attaching to glycoaminoglycans on the surface of the host cells lipid bilayer. Once inside the cell the viral capsid falls apart and viral genes are transcribed in the cytoplasm starting the lytic cycle. Poxviruses were the first class of viruses scientists were able to create vaccines for and are among the best understood viruses on earth. Additionally, Poxviruses, across all classes, contain a number of phenotypes that make them ideal candidates for vaccine-mediated cancer immunotherapy.[23,24]<br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The first and one of the most important factors in poxviruses <del style="font-weight: bold; text-decoration: none;">ability to vaccinate against </del>cancer is <del style="font-weight: bold; text-decoration: none;">the fact that </del>transcription and translation <del style="font-weight: bold; text-decoration: none;">of poxvirus genes takes place entirely in </del>the cytoplasm<del style="font-weight: bold; text-decoration: none;">. This phenotype means that </del>there is no risk of genetic integration <del style="font-weight: bold; text-decoration: none;">in the host cells </del>thereby avoiding a constant low level immune response <del style="font-weight: bold; text-decoration: none;">for the rest of an individual’s life </del>which could lead to a number of serious, chronic conditions and even, ironically, cancer. Additionally, cytoplasmic transcription and translation means that translation is independent of many host factors allowing for quick and efficient replication in most patients.[25]<br> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The first and one of the most important factors in poxviruses <ins style="font-weight: bold; text-decoration: none;">utility as a </ins>cancer <ins style="font-weight: bold; text-decoration: none;">vaccine agent </ins>is <ins style="font-weight: bold; text-decoration: none;">its method of </ins>transcription and translation<ins style="font-weight: bold; text-decoration: none;">. Because Poxviruses replicate within </ins>the cytoplasm there is no risk of genetic integration <ins style="font-weight: bold; text-decoration: none;"> </ins>thereby avoiding a constant low level immune response which could lead to a number of serious, chronic conditions and even, ironically, cancer. Additionally, cytoplasmic transcription and translation means that translation is independent of many host factors allowing for quick and efficient replication in most patients.[25]<br> </div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Poxvirus is also among the most diverse viruses in the world and is found in many different species. This <del style="font-weight: bold; text-decoration: none;">ultimately </del>means that there are classes of poxvirus that <del style="font-weight: bold; text-decoration: none;">can get its genome </del>into a human cell but <del style="font-weight: bold; text-decoration: none;">is </del>nonpathogenic. Modified vaccina Ankara (MVA) is a perfect example of this. The original vaccina was originally grown in chicken embryos, however after passing the virus through cell culture 570 times the MVA developed a number of mutations in the pathogenic regions of its genome (INF-a, IFN-b and TNF-a). This means, while it infect mammalian cell lines it cannot cause illness, even in the immune compromised<del style="font-weight: bold; text-decoration: none;">, making it the </del>perfect vector for introducing cancer antigens into the body [26]. Additionally, due to <del style="font-weight: bold; text-decoration: none;">its natural </del>diversity these viruses can be engineered to enter virtually all cell types within the body. Finally, because of its large size poxvirus is able to accommodate large genes that code for large proteins including antigens and other immunomodulation molecules. <del style="font-weight: bold; text-decoration: none;">These antigens and </del>immune <del style="font-weight: bold; text-decoration: none;">adjuvants are expressed within the host cell. The </del>adjuvants in conjunction with the antigens <del style="font-weight: bold; text-decoration: none;">cause a large scale </del>immune response against not only the virus but the host cell as well. Because the antigen that triggered this response was originally from a cancer cell memory T cells are formed and the body develops an adaptive immunity to cancer <del style="font-weight: bold; text-decoration: none;">cells resulting in an immune attack on a person’s cancer cells</del>.<del style="font-weight: bold; text-decoration: none;">[27]<br></del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Poxvirus is also among the most diverse viruses in the world and is found in many different species <ins style="font-weight: bold; text-decoration: none;">of animal</ins>. This means that there are classes of poxvirus that <ins style="font-weight: bold; text-decoration: none;">integrate </ins>into a human cell but <ins style="font-weight: bold; text-decoration: none;">are </ins>nonpathogenic. Modified vaccina Ankara (MVA) is a perfect example of this. The original vaccina was originally grown in chicken embryos, however after passing the virus through cell culture 570 times the MVA developed a number of mutations in the pathogenic regions of its genome (INF-a, IFN-b and TNF-a). This means, while it infect mammalian cell lines it cannot cause illness, even in the immune compromised<ins style="font-weight: bold; text-decoration: none;">. This makes MVA a </ins>perfect vector for introducing cancer antigens into the body [26]. Additionally, <ins style="font-weight: bold; text-decoration: none;">again </ins>due to <ins style="font-weight: bold; text-decoration: none;">the </ins>diversity these viruses<ins style="font-weight: bold; text-decoration: none;">, Poxvirus </ins>can be engineered to enter virtually all cell types within the body. Finally, because of its large size poxvirus is able to accommodate large genes that code for large proteins including antigens and other immunomodulation molecules. <ins style="font-weight: bold; text-decoration: none;">The translation of </ins>immune adjuvants in conjunction with the antigens <ins style="font-weight: bold; text-decoration: none;">causes an </ins>immune response against not only the virus but the host cell as well. Because the antigen that triggered this response was originally from a cancer cell<ins style="font-weight: bold; text-decoration: none;">, </ins>memory T cells are formed and the body develops an adaptive immunity to <ins style="font-weight: bold; text-decoration: none;">that specific type of </ins>cancer.</div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Currently a species of poxvirus containing the tumor-associated antigen PSA, i.e. PSA-TRICOM (PROSTVAC-V/F) is currently in phase III clinical trials in metastatic castration-resistant prostate cancer[28].</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Currently a species of poxvirus containing the tumor-associated antigen PSA, i.e. PSA-TRICOM (PROSTVAC-V/F) is currently in phase III clinical trials in metastatic castration-resistant prostate cancer[28].</div></td></tr>
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</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123968&oldid=prevDitmarsf: /* Herpesvirus */2016-05-17T17:12:33Z<p><span dir="auto"><span class="autocomment">Herpesvirus</span></span></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 17:12, 17 May 2016</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Herpes.diagram.jpg|thumb|300px|right|Herpesvirus virion diagram. From the [http://www.stdgen.lanl.gov/stdgen/bacteria/hhv2/herpes.html Los Alamos National Laboratory Bioscience Division].]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Herpes.diagram.jpg|thumb|300px|right|Herpesvirus virion diagram. From the [http://www.stdgen.lanl.gov/stdgen/bacteria/hhv2/herpes.html Los Alamos National Laboratory Bioscience Division].]]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><br>Herpesviridae is a class of enveloped viruses with double stranded DNA that <del style="font-weight: bold; text-decoration: none;">cause </del>latent infections that when triggered can become lytic. Herpesvirus enters the cell using viral <del style="font-weight: bold; text-decoration: none;">Glycoproteins </del>attached to the outside of its lipid bilayer that attach to the host cells cell membrane<del style="font-weight: bold; text-decoration: none;">, causing </del>the cell to internalize the herpes virion. Once the viron enters the cell it rapidly decays and viral DNA migrates to the nucleus where transcription and replication of viral genes begins to take place.[16] <br></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><br>Herpesviridae is a class of enveloped viruses with <ins style="font-weight: bold; text-decoration: none;">a </ins>double stranded DNA <ins style="font-weight: bold; text-decoration: none;">genome </ins>that <ins style="font-weight: bold; text-decoration: none;">causes </ins>latent infections that<ins style="font-weight: bold; text-decoration: none;">, </ins>when triggered<ins style="font-weight: bold; text-decoration: none;">, </ins>can become lytic. Herpesvirus enters the cell using viral <ins style="font-weight: bold; text-decoration: none;">glycoproteins </ins>attached to the outside of its lipid bilayer that attach to the host cells cell membrane<ins style="font-weight: bold; text-decoration: none;">. When attached these glycoproteins cause </ins>the cell to internalize the herpes virion. Once the viron enters the cell it rapidly decays and <ins style="font-weight: bold; text-decoration: none;">its </ins>viral DNA migrates to the nucleus where transcription and replication of viral genes begins to take place.[16] <br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Herpesvirus was one of the first classes of viruses that was successfully turned oncogenic with the HSV1716 strain, a mutant form of the herpes simplex virus 1. HSV1716 takes advantage of innate somatic cell defense systems targeting cancer cells in a mechanism relatively similar to many other oncolytic viruses like H101. HSV1716 contains a full deletion of the gene ICP34.5 which allows for neurovirulence (viral replication within nerve cells)[17,18]. The ICP34.5 gene functions by counteracting PKR mediated blocks on viral replication and apoptosis. PKR is typically activated by double-stranded RNA, PACT or heparin. Once activated PKR deactivates cellular transcription, halting viral replication. Under extreme viral stress PKR is able to induce apoptosis through the activation of inferon cytokines [19]. PKR <del style="font-weight: bold; text-decoration: none;">is </del>also <del style="font-weight: bold; text-decoration: none;">known to interact </del>with p53 which is also <del style="font-weight: bold; text-decoration: none;">known to be </del>inactivated in cancer cells[20]. A knockout of this gene <del style="font-weight: bold; text-decoration: none;">would cause the </del>virus to <del style="font-weight: bold; text-decoration: none;">target tumor </del>cells due to <del style="font-weight: bold; text-decoration: none;">most cancer cells </del>inactivation of PKR (PKR is known to activate PP2A, a tumor suppression protein).<br></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Herpesvirus was one of the first classes of viruses that was successfully turned oncogenic with the HSV1716 strain, a mutant form of the herpes simplex virus 1. HSV1716 takes advantage of innate somatic cell defense systems targeting cancer cells in a mechanism relatively similar to many other oncolytic viruses like H101. HSV1716 contains a full deletion of the gene ICP34.5 which allows for neurovirulence (viral replication within nerve cells)[17,18]. The ICP34.5 gene functions by counteracting PKR mediated blocks on viral replication and apoptosis. PKR is typically activated by double-stranded RNA, PACT or heparin. Once activated PKR deactivates cellular transcription, halting viral replication. Under extreme viral stress PKR is able to induce apoptosis through the activation of inferon cytokines [19]. PKR also <ins style="font-weight: bold; text-decoration: none;">interacts </ins>with p53 <ins style="font-weight: bold; text-decoration: none;">which is </ins>which is also <ins style="font-weight: bold; text-decoration: none;">typically </ins>inactivated in cancer cells[20].</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>HSV1716 is currently undergoing a number of clinical trials to determine its usefulness in humans and recently finished phase III trials.[21] <del style="font-weight: bold; text-decoration: none;">Additionally it was </del>reported <del style="font-weight: bold; text-decoration: none;">by Liu </del>that by upregulating US11, GM-CSF and downregulating ICP47 <del style="font-weight: bold; text-decoration: none;">can increase </del>rates of tumor destruction, tumor reduction and antigen presentation as well as enhancing anti-tumor immune response. [22]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>A knockout of this gene <ins style="font-weight: bold; text-decoration: none;">results in a </ins>virus <ins style="font-weight: bold; text-decoration: none;">that while unable </ins>to <ins style="font-weight: bold; text-decoration: none;">infect somatic cells maintains virulence in most cancerous </ins>cells due to <ins style="font-weight: bold; text-decoration: none;">the </ins>inactivation of PKR (PKR is known to activate PP2A, a tumor suppression protein).<br></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>HSV1716 is currently undergoing a number of clinical trials to determine its usefulness in humans and recently finished phase III trials.[21] <ins style="font-weight: bold; text-decoration: none;">Recently some have </ins>reported that by upregulating US11, GM-CSF and downregulating ICP47 rates of tumor destruction, tumor reduction and antigen presentation <ins style="font-weight: bold; text-decoration: none;">can be increased </ins>as well as enhancing <ins style="font-weight: bold; text-decoration: none;">an </ins>anti-tumor immune response. [22]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Cancer Immunotherapy=</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=Cancer Immunotherapy=</div></td></tr>
</table>Ditmarsfhttps://microbewiki.kenyon.edu/index.php?title=Viral_Oncology&diff=123967&oldid=prevDitmarsf: /* Why Viruses? */2016-05-17T15:45:46Z<p><span dir="auto"><span class="autocomment">Why Viruses?</span></span></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 15:45, 17 May 2016</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br> While the medical community has been aware of the correlation between remission and viral infection since the mid-1800s, medical professionals were unsure as to why this correlation existed, until we began to understand the molecular and genetic mechanisms behind cancer and cancer replication. Cancer cells are the product of small scale evolution, which is to say that the accumulation of point mutations and chromosomal shifts, along with chromosomal instability, have resulted in a phenotype drastically different from its ancestor. Typically, in cancer cells, we see a selection for growth advantages over somatic cells. These increased growth factors include immunity to density and anchorage dependence as well as up and down regulation of certain genes such as telomerase or p53.[6]<br> </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br> While the medical community has been aware of the correlation between remission and viral infection since the mid-1800s, medical professionals were unsure as to why this correlation existed, until we began to understand the molecular and genetic mechanisms behind cancer and cancer replication. Cancer cells are the product of small scale evolution, which is to say that the accumulation of point mutations and chromosomal shifts, along with chromosomal instability, have resulted in a phenotype drastically different from its ancestor. Typically, in cancer cells, we see a selection for growth advantages over somatic cells. These increased growth factors include immunity to density and anchorage dependence as well as up and down regulation of certain genes such as telomerase or p53.[6]<br> </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>While these genetic and molecular changes result in a massive increase in fitness when compared to somatic cells, often times certain defensive mechanisms are sacrificed. For example in many cancer cells a number of genetic repair enzymes are shut off as well as proteins that defend against mutations in the genome and foreign DNA.<br></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>While these genetic and molecular changes result in a massive increase in fitness when compared to somatic cells, often times certain defensive mechanisms are sacrificed. For example in many cancer cells a number of genetic repair enzymes are shut off as well as proteins that defend against mutations in the genome and foreign DNA.<br></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Without the ability to defend against foreign DNA many cancer cells are left vulnerable to viral attacks. By exploiting the innate viral sensitivity of most cancer cells scientists have been able to engineer viruses that can not only selectively kill cancer cells but generate an cancer specific immune response within the patients body. [7]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Without the ability to defend against foreign DNA many cancer cells are left vulnerable to viral attacks. By exploiting the innate viral sensitivity of most cancer cells scientists have been able to engineer viruses that can not only selectively kill cancer cells but <ins style="font-weight: bold; text-decoration: none;">also </ins>generate an cancer specific immune response within the patients body. [7]</div></td></tr>
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</table>Ditmarsf