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	<title>DNALC Blogs &#187; biology</title>
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	<link>http://blogs.dnalc.org</link>
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		<title>Tumor Treatment: Whether to Shrink or Not to Shrink</title>
		<link>http://blogs.dnalc.org/2012/02/06/tumor-treatment-whether-to-shrink-or-not-to-shrink/</link>
		<comments>http://blogs.dnalc.org/2012/02/06/tumor-treatment-whether-to-shrink-or-not-to-shrink/#comments</comments>
		<pubDate>Mon, 06 Feb 2012 22:03:22 +0000</pubDate>
		<dc:creator><![CDATA[Bruce Nash]]></dc:creator>
				<category><![CDATA[Inside Cancer]]></category>
		<category><![CDATA[angiogenesis]]></category>
		<category><![CDATA[biology]]></category>
		<category><![CDATA[blood vessels]]></category>
		<category><![CDATA[breast]]></category>
		<category><![CDATA[Cancer]]></category>
		<category><![CDATA[drugs]]></category>

		<guid isPermaLink="false">http://blogs.dnalc.org/?p=4513</guid>
		<description><![CDATA[Just like normal tissue, tumors need blood vessels to grow. Because of this, drugs that stop angiogenesis, or the formation of new blood vessels, are one important approach to treating cancers. These angiogenesis inhibitors stop tumor growth by starving them of oxygen and nutrients, usually by interfering with signals from the tumor cells that promote&#8230;]]></description>
				<content:encoded><![CDATA[<p>Just like normal tissue, tumors need blood vessels to grow. Because of this, drugs that stop angiogenesis, or the formation of new blood vessels, are one important approach to treating cancers. These angiogenesis inhibitors stop tumor growth by starving them of oxygen and nutrients, usually by interfering with signals from the tumor cells that promote blood vessel formation in the surrounding tissue.<br />
Angiog<a href="http://blogs.dnalc.org/wp-content/uploads/2012/02/angio.jpg"><img class="size-full wp-image-4516 alignleft" src="http://blogs.dnalc.org/wp-content/uploads/2012/02/angio.jpg" alt="" width="72" height="72" /></a>enesis inhibitors have been shown to be effective in the treatment of several cancer types, but the results aren’t always as expected. Several recent studies show how complicated this can be. For instance, FDA approval of the drug Avastin to treat metastatic breast cancer was revoked in November, 2011. Although Avastin works to stop tumor growth, and can even shrink these tumors, the effects are temporary. More importantly, Avastin does not seem to help prolong patient survival for this kind of breast cancer.<br />
At first, it does not seem to make sense that a drug that shrinks tumors could have no effect on survival. However, a recent study might provide an explanation: breast cancer cells fight back when starved of oxygen.  By growing breast cancer cells in mice, Max Wicha and his colleagues have shown that the number of cancer stem cells in tumors increases after treatment with anti-angiogenesis drugs. They could also increase the number of cancer stem cells when growing breast cancer cells in a low-oxygen environment, suggesting that the drugs were affecting stem cell populations because they induce hypoxia, or low oxygen levels . Cancer stem cells are cells that are capable of producing new cancer cells, and can also form new tumors, which may explain why tumors could shrink but end up being just as deadly.<br />
This doesn’t necessarily mean that these drugs should never be used to treat breast cancer. For one, it may be possible to shrink the tumors and simultaneously block the formation of cancer stem cells, and this may prove to be very effective. Also, early results from studies where Avastin is used before breast cancer surgery for patients with earlier stage cancer suggest that shrinking the tumor before surgery can help eliminate these cancers and reduce the amount of normal tissue that needs to be removed.  So, as seems to be the case more often than not, the biology of cancer and cancer treatment are more complicated than we might initially think, and whether to “shrink” a tumor or not will depend on the specific tumor type.<br />
Reference: <a title="PNAS" href="http://www.pnas.org/content/early/2012/01/18/1018866109.abstract">Proceedings of the National Academy of Sciences Early Edition, DOI: 10.1073/pnas.1018866109</a>.</p>
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		<title>Cockroach Brains as Medicine</title>
		<link>http://blogs.dnalc.org/2010/09/22/cockroach-brains-as-medicine/</link>
		<comments>http://blogs.dnalc.org/2010/09/22/cockroach-brains-as-medicine/#comments</comments>
		<pubDate>Wed, 22 Sep 2010 16:05:01 +0000</pubDate>
		<dc:creator><![CDATA[Erin McKechnie]]></dc:creator>
				<category><![CDATA[DNA From The Beginning]]></category>
		<category><![CDATA[bacteria]]></category>
		<category><![CDATA[biology]]></category>
		<category><![CDATA[cockroach]]></category>
		<category><![CDATA[medicine]]></category>
		<category><![CDATA[microbes]]></category>

		<guid isPermaLink="false">http://5.277</guid>
		<description><![CDATA[Each day your body works to defend you against invaders.  Harmful bacteria, viruses, and fungi can enter your system and cause diseases.  In addition to relying on your immune system, it is helpful to avoid contact with germs by thoroughly washing your hands and keeping your environment clean. How is it possible that some organisms&#8230;]]></description>
				<content:encoded><![CDATA[<p><a href="http://blogs.dnalc.org/wp-content/uploads/2010/09/cockroach-150x150.jpg"><img class="alignleft size-full wp-image-3424" title="cockroach-150x150" src="http://blogs.dnalc.org/wp-content/uploads/2010/09/cockroach-150x150.jpg" alt="" width="150" height="150" /></a>Each day your body works to defend you against invaders.  Harmful bacteria, viruses, and fungi can enter your system and cause diseases.  In addition to relying on your immune system, it is helpful to avoid contact with germs by thoroughly washing your hands and keeping your environment clean.</p>
<p>How is it possible that some organisms have the ability to survive in some of the dirtiest places on earth?  What survival mechanisms do they have that differ from ours?</p>
<p>Scientists ground up the brains and other nerve tissues from two species of insects, the American cockroach and the desert locust.  Material extracted from the samples was shown to kill more than 90 percent of a harmful type of <em>E.coli</em> bacteria.  In addition, the tissue extracts killed a type of staph bacteria.  There seem to be nine molecules within the tissue that are involved in defense against microbes.</p>
<p>Although the nine molecules have not been identified, scientists may be able to utilize the molecules in the future as a form of disease prevention in humans.</p>
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		<title>Psychosis &#8211; New Study Links Gene Variant to Brain Structures</title>
		<link>http://blogs.dnalc.org/2009/05/12/psychosis-new-study-links-gene-variant-to-brain-structures/</link>
		<comments>http://blogs.dnalc.org/2009/05/12/psychosis-new-study-links-gene-variant-to-brain-structures/#comments</comments>
		<pubDate>Tue, 12 May 2009 14:47:54 +0000</pubDate>
		<dc:creator><![CDATA[connolly]]></dc:creator>
				<category><![CDATA[G2C Online]]></category>
		<category><![CDATA[biology]]></category>
		<category><![CDATA[genetics]]></category>
		<category><![CDATA[genomics]]></category>
		<category><![CDATA[imaging]]></category>
		<category><![CDATA[neuroimaging]]></category>
		<category><![CDATA[psychology]]></category>
		<category><![CDATA[psychosis]]></category>
		<category><![CDATA[schizophrenia]]></category>

		<guid isPermaLink="false">http://4.45</guid>
		<description><![CDATA[A study published in last week&#8217;s Science magazine shows how genomic science and neuroimaging can be combined to deliver insights into cognitive disorders. As well as providing an intriguing look into the neurobiology of psychosis, the study reflects a growing trend toward inter-disciplinary research in the neurosciences, What did the study show? Psychosis is a&#8230;]]></description>
				<content:encoded><![CDATA[<p><a href="http://blogs.dnalc.org/wp-content/uploads/2009/05/g2cblog_psychosis_thumb.jpg"><img class="alignleft size-thumbnail wp-image-3115" title="g2cblog_psychosis_thumb" src="http://blogs.dnalc.org/wp-content/uploads/2009/05/g2cblog_psychosis_thumb-150x150.jpg" alt="" width="150" height="150" /></a>A <a title="Esslinger, Walter et al. Psychosis" href="http://www.sciencemag.org/cgi/content/abstract/324/5927/605" target="_blank">study published in last week&#8217;s <em>Science </em>magazine</a> shows how genomic science and neuroimaging can be combined to deliver insights into cognitive disorders. As well as providing an intriguing look into the neurobiology of psychosis, the study reflects a growing trend toward inter-disciplinary research in the neurosciences,</p>
<p><strong>What did the study show? </strong></p>
<p>Psychosis is a disordered cognitive state that can include disorganized thoughts, delusions, or hallucinations. It is a common symptom of schizophrenia and has been linked to a number of brain areas, including the the dorsolateral <a title="G2C Online - Prefronal Cortex" href="http://www.g2conline.org/1251" target="_blank">prefrontal cortex</a> (DLPFC) and the <a title="G2C Online - Hippocampus" href="http://www.g2conline.org/1164" target="_self">hippocampus</a>. Schizophrenia is also strongly associated with a<a title="G2C Online - Schizophrneia Genes" href="http://www.g2conline.org/1243" target="_blank"> number of genes</a>, and a<a title="Pubmed - genome-wide association study" href="http://www.ncbi.nlm.nih.gov/pubmed/18677311?ordinalpos=3&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank"> recent genome-wide association study </a>identified a single nucleotide polymorphism in ZNF804A  as particularly important. Now, for the first time, a<a title="Pubmed - Psychosis, Genes, Brain" href="http://www.ncbi.nlm.nih.gov/sites/entrez" target="_blank"> German research team has confirmed a link between ZNF804A </a>and these brain structures. The group compared 115 participants who were either risk-allele carriers or non-risk-allele carriers and found differences in how their brains connect. For risk-allele carriers, connections were reduced within the DLPFC and also between left and right DLPFC . Conversely, risk-allele carriers showed increased connectivity between the DLPFC and hippocampal areas.</p>
<p>The study, primarily based at the University of Heidelberg, Germany, focused on a single nucleotide polymorphism (SNP) in<em> ZNF804A</em> (rs1344706)</p>
<p>Schizophrenia is a devastating, highly heritable brain disorder<sup> </sup>of unknown etiology. Recently, the first common genetic variant<sup> </sup>associated on a genome-wide level with schizophrenia and possibly<sup> </sup>bipolar disorder was discovered in <em>ZNF804A</em> (rs1344706). We show,<sup> </sup>by using an imaging genetics approach, that healthy carriers<sup> </sup>of rs1344706 risk genotypes exhibit no changes in regional activity<sup> </sup>but pronounced gene dosage–dependent alterations in functional<sup> </sup>coupling (correlated activity) of dorsolateral prefrontal cortex<sup> </sup>(DLPFC) across hemispheres and with hippocampus, mirroring findings<sup> </sup>in patients, and abnormal coupling of amygdala. , show that<sup> </sup>rs1344706 or variation in linkage disequilibrium is functional<sup> </sup>in human brain, and validate the intermediate phenotype strategy<sup> </sup>in psychiatry.</p>
<p>The study is important for a number of reasons. Firstly, it highlights the importance of connectivity (or dysconnectivity) as a neurobiological marker of schizophrenia. Secondly, it establishes <em>ZNF804A</em> as functional in the human brain. Thirdly, it is an example of how genome-wide association studies can align with anatomical data &#8211; to quote the authors, it affirms that &#8220;the pathophysiology of overt disease&#8221; can &#8220;mirror candidate gene effects&#8221;.</p>
<p><strong>Functional Genomics and Big Picture Science</strong></p>
<p>This third point is important to how we view science as a whole. Scientific research has traditionally relied upon reductionism as the primary means of discovery. To understand the world, reductionism tells us, we must strip it down to its barest elements. The sequencing of the human genome represents the ultimate triumph of this principle — the dis-assembly of an enormously complex living thing into its three billion molecular constituents. While unraveling the genomic structure ushered in a new era for biology and medicine, it laid bare a new problem—that of genomic function. Now that we have disassembled the machine, we have to figure out how to put it back together again.</p>
<p>Scientists have, in many ways, been forced to abandon reductionism and to look instead at the bigger picture &#8211; to see how things fits together. Increasingly we see large multi-disciplinary groups, each of which holds a different piece of the picture. In the current example, we have neuroimaging experts, who look at the gross structure of the brain, collaborating with geneticists, who look at m0lecules, and psychiatrists who look at behavior. These collaborations are exciting, because they integrate a number of different perspectives. Ultimately, this represents a triumph for &#8220;big picture&#8221; science.</p>
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		<title>Can We Diagnose PTSD with Brain Scans?</title>
		<link>http://blogs.dnalc.org/2009/04/18/can-we-diagnose-ptsd-with-brain-scans/</link>
		<comments>http://blogs.dnalc.org/2009/04/18/can-we-diagnose-ptsd-with-brain-scans/#comments</comments>
		<pubDate>Sat, 18 Apr 2009 20:51:32 +0000</pubDate>
		<dc:creator><![CDATA[connolly]]></dc:creator>
				<category><![CDATA[G2C Online]]></category>
		<category><![CDATA[biology]]></category>
		<category><![CDATA[brain]]></category>
		<category><![CDATA[fmri]]></category>
		<category><![CDATA[functional magnetic resonance imaging]]></category>
		<category><![CDATA[neuroimaging]]></category>
		<category><![CDATA[posttraumatic stress disorder]]></category>
		<category><![CDATA[psychology]]></category>
		<category><![CDATA[ptsd]]></category>

		<guid isPermaLink="false">http://4.32</guid>
		<description><![CDATA[Duke University&#8217;s Rajendra Morey was in the news this week following a presentation at the World Psychiatric Association Congress in Italy. Dr Morey&#8217;s group recently published a paper equating symptoms of post posttraumatic stress disorder (PTSD) with &#8220;markedly different neural activity&#8221;. Dr. Morey raised the possibility of using brain scans to diagnose PTSD, thereby catapulting&#8230;]]></description>
				<content:encoded><![CDATA[<p><a href="http://blogs.dnalc.org/wp-content/uploads/2009/04/g2cblog_ptsd_thumb.jpg"><img class="alignleft size-thumbnail wp-image-3113" title="g2cblog_ptsd_thumb" src="http://blogs.dnalc.org/wp-content/uploads/2009/04/g2cblog_ptsd_thumb-150x150.jpg" alt="" width="150" height="150" /></a>Duke University&#8217;s Rajendra Morey was in the news this week following a presentation at the World Psychiatric Association Congress in Italy. Dr Morey&#8217;s group recently <a title="Morey et al. 2008" href="http://www.ncbi.nlm.nih.gov/pubmed/19091328?log$=activity" target="_blank">published a paper</a> equating symptoms of post posttraumatic stress disorder (PTSD) with &#8220;markedly different neural activity&#8221;. Dr. Morey raised the possibility of using brain scans to diagnose PTSD, thereby catapulting herself into the science pages of <a title="Forbes PTSD" href="http://www.forbes.com/feeds/hscout/2009/04/03/hscout625693.html" target="_blank">Forbes</a>, <a title="Reuters PTSD" href="http://uk.reuters.com/article/healthNewsMolt/idUKTRE53200T20090403" target="_blank">Reuters</a> <em>et al</em>. She joins a lengthy list of researchers that have whetted our appetite with tantalizing suggestions about the predictive power of neuroimaging. Sadly, the list of those who have followed through on this promise is not quite so long.</p>
<p><strong>What are PTSD and fMRI? </strong></p>
<p>PTSD is an anxiety disorder commonly seen in individuals who have survived extremely stressful situations such as war, assault, or other events that lead to severe psychological trauma. There is some evidence of a genetic association &#8211; an intriguing paper by <a title="Binder et al. PTSD and FKBP5" href="http://www.ncbi.nlm.nih.gov/pubmed/18349090?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank">Binder <em>et al. </em>(2008)</a> links PTSD with genetic polymorphisms at the stress-related gene <em>FKBP5</em>. A number of recent studies (e.g. <a title="Bryant et al. 2005 - neural correlates of PTSD" href="http://www.ncbi.nlm.nih.gov/pubmed/16038681?ordinalpos=2&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank">Bryant <em>et al.</em>, 2005)</a> have used functional magnetic resonance imaging (fMRI) to link PTSD with specific brain networks including the <a title="G2C Online - Cingulate" href="http://www.g2conline.org/2106" target="_blank">anterior cingulate</a> and <a title="G2C Online - Amygdala" href="http://www.g2conline.org/2104" target="_self">amygdala</a>. Dr. Morey&#8217;s group essentially replicates these findings, with PTSD patients showing greater activity in emotion-processing areas (the cingulate and amygdala are often associated with fear-processing) and reduced activity in the prefrontal cortex (often associated with vigilance and monitoring).</p>
<p><a title="G2C Online - fMRI" href="http://www.g2conline.info/2276" target="_blank">FMRI</a>, the neuroimaging technique used by Morey&#8217;s group, uses a large magnet to monitor blood flow, which is very precisely related to activity in the brain.  When a region becomes active, there is an increase in blood flow to neurons, which leads to a very slight change in the magnetic signal. Although very slight, this change can be detected by extremely powerful magnets. By tracking magnetic changes in the brain, researchers can infer increased or reduced neural activity.</p>
<p><strong>What is the evidence? </strong></p>
<p>Every week, at least 3 or 4 neuroimaging papers report a neurological correlate to a particular emotion, behavior, or even <a title="Bad Science - Your Brain on Politics" href="http://www.badscience.net/2007/11/this-is-your-brain-this-is-your-brain-on-politics-any-questions/" target="_blank">voting preference</a>. I recently<a title="G2C Online - Thomas Insel interview" href="http://www.g2conline.org/2276" target="_blank"> interviewed Thomas Insel</a>, Director of the National Institute of Mental Health (NIMH) and he made the point that despite over 19,000 neuroimaging publications in the last two decades, he could not point to a single neuroimaging study that affected practice, that changed the way we diagnose or treat any cognitive disorder. This, I think, is a very important point. There is no doubt that neuroimaging has potential, but, to date, its promise remains unfulfilled.</p>
<p>There is no grounds, therefore, for claiming that fMRI or any other neuroimaging technique can be used to diagnose PTSD. Accepted, the groups&#8217; claims relate to future uses of fMRI, presumably an off-hand to an ill-informed news source. Nevertheless, this is an irresponsible comment given that there is currently no consensus among researchers about what the neural correlates of PTSD actually are. Sure, your study may have pointed to differences in prefrontal cortex and amygdala, but these areas are 1) associated with a host of executive and emotional processes, and 2) in the case of the prefronal cortex (or even the dorsolateral prefrontal cortex), extremely large and therefore unspecific.</p>
<p>Alzheimer&#8217;s disease is realistically the only cognitive disorder, where researchers have come close to developing a <a title="Alzheimer's and Neuroimaging - G2C Online Interview with Donna Wilcock" href="http://www.g2conline.org/2187" target="_blank">neuroimaging diagnosis</a>. This is because Alzheimer&#8217;s has a very specific neuropathology that is clearly visible with autopsy. PTSD is absolutely different, any speculation linking PTSD to a neuroimaging diagnosis is distracting and misleading. When there are so many interesting science studies published each week, it is extremely disappointing to see stories such as this grab the limelight.</p>
<p><strong>To conclude&#8230; </strong></p>
<p>The short answer to my title question is a firm no. Maybe in the future it will be possible to make diagnoses of this kind, but we are currently not even close to this scenario. Any comments to the contrary are misguided, sensationalist, or downright untrue.</p>
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