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    <recommendedItem id="20100101_19_174"
                     title="AACR-IASLC: MicroRNA Linked to SCLC Response (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/AACR-IASLC/tb/18008?impressionId=1265751921265"
                     
      &lt;p&gt;CORONADO, Calif.  --  Tiny genetic segments may give a big tip-off to platinum chemoresistance in patients with small cell lung cancer, researchers said.&lt;/p&gt;
&lt;p&gt;Three microRNAs were linked to de novo chemoresistance in a small study led by Glen J. Weiss, MD, of Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), both in Scottsdale, Ariz.&lt;/p&gt;
&lt;p&gt;He presented the results here at the Joint Conference on Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.&lt;/p&gt;
&lt;p&gt;Further validation would be needed before denying any patient chemotherapy based on the findings, cautioned Tyler Jacks, PhD, of the Massachusetts Institute of Technology and president of the AACR.&lt;/p&gt;
&lt;p&gt;However, &quot;biomarkers of this sort will be useful in diagnosing patients and applying relevant therapies  --  in this instance perhaps applying novel therapies, given the belief that the conventional therapies will be of no value to these individuals,&quot; he said as discussant on the study at a press conference.&lt;/p&gt;
&lt;p&gt;Weiss agreed.&lt;/p&gt;
&lt;p&gt;&quot;This is early stage,&quot; he said in an interview. &quot;But hopefully down the road it will have implications for treating patients with small cell [lung cancer].&quot;&lt;/p&gt;
&lt;p&gt;Non-small cell lung cancer has been a success story for personalized treatment.&lt;/p&gt;
&lt;p&gt;It was revolutionized by discovery of epidermal growth factor receptor (EGFR) mutations as both a prognostic factor and treatment target for the EGFR tyrosine kinase inhibitors.&lt;/p&gt;
&lt;p&gt;But for small cell lung cancer, the standard treatment is platinum-based chemotherapy with only two real options in first-line treatment, the researchers said.&lt;/p&gt;
&lt;p&gt;Worse, 15% to 30% of small cell tumors are intrinsically resistant to platinum chemotherapy and never respond.&lt;/p&gt;
&lt;p&gt;&quot;[Small cell] lung cancer patients haven&apos;t had a real advance in 15 years or more for chemotherapy,&quot; Weiss told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;What we&apos;re trying to do is identify the group that doesn&apos;t respond to standard therapy so that we can identify new treatments for them up front instead of treating everyone the same.&quot;&lt;/p&gt;
&lt;p&gt;Among the genetic possibilities for these efforts, microRNA  --  RNA molecules of around 20 nucleotides in length  --  are a good option, Weiss explained.&lt;/p&gt;
&lt;p&gt;They regulate gene expression like messenger RNA but are smaller and more stable across a variety of fluid and tissue types, he said.&lt;/p&gt;
&lt;p&gt;In the study, the researchers analyzed diagnostic tumor samples from 34 patients with small cell lung cancer.&lt;/p&gt;
&lt;p&gt;Among them, 19% had de novo chemoresistance marked by progressive disease. Most had had a partial or complete response to chemotherapy (61.9% and 9.5%, respectively).&lt;/p&gt;
&lt;p&gt;After extraction of total RNA, microRNA profiling revealed 16 top candidates for association with progressive disease.&lt;/p&gt;
&lt;p&gt;The 28 samples with sufficient RNA for further testing showed three microRNAs linked to chemoresistance that were validated by quantitative real-time PCR: &lt;ul&gt; &lt;li&gt;miR-92a-2* with a &lt;em&gt;P&lt;/em&gt;-value of 0.010&lt;/li&gt; &lt;li&gt;miR-147 with a &lt;em&gt;P&lt;/em&gt;-value of 0.018&lt;/li&gt; &lt;li&gt;miR-574-5p with a &lt;em&gt;P&lt;/em&gt;-value of 0.039&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Many of the patients had comorbidities at baseline, including 47.1% with hypertension and 32% with emphysema or chronic obstructive pulmonary disease. But these did not predict chemotherapy response.&lt;/p&gt;
&lt;p&gt;The next step is to validate the biomarkers in an independent cohort of small cell lung cancer patients, the researchers concluded.&lt;/p&gt;
&lt;p&gt;Then studies will need to determine what does work in these chemoresistant patients, Weiss said.&lt;/p&gt;
&lt;p&gt;&quot;We&apos;ve learned that if we&apos;re going to make the next hurdle and if we&apos;re going to better treat this disease, we need more personalized care,&quot; agreed Roy Herbst, MD, PhD, of M.D. Anderson Cancer Center in Houston.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the American Cancer Society-Sylvia Chase Pilot Grant, IBIS Foundation of Arizona, and the TGen Foundation.&lt;/p&gt;&lt;p&gt;Weiss reported recieving lab support from TGen Foundation and Scottsdale Healthcare Foundation as well as being party to provisional patents related to microRNAs in lung cancer.&lt;/p&gt;&lt;p&gt;Jacks provided no information on conflicts of interest.&lt;/p&gt;&lt;p&gt;Herbst has reported financial relationships with Genentech, Lilly, Amgen, and AstraZeneca. &lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1549"
                     title="ATS: New Drug Delivery Methods in Spotlight"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ATS/tb/14265?impressionId=1265751921265"
                     
      SAN DIEGO, May 19 -- Early-phase treatment modalities -- ranging from a stem cell attack on metastatic cancer to what may be a true silver bullet against pulmonary infection -- were highlighted at the annual meeting of the American Thoracic Society.
              &lt;br&gt; 
              &lt;br&gt;The studies are all in the preclinical stages but could represent &quot;exciting&quot; new approaches to a range of illnesses, according to Beth Laube, Ph.D., of Johns Hopkins University School of Medicine, who moderated a press conference at which the studies were discussed.
              &lt;br&gt; 
              &lt;br&gt;The stem cell study combines two separate areas of research, according to Michael Loebinger, M.D., of University College London.
              &lt;p&gt; 
              &lt;p&gt;On one hand, he said, it has been known for some time that mesenchymal stem cells in bone marrow have the ability to home in on and bind to tumor cells.
              &lt;p&gt; 
              &lt;p&gt;On the other, he said, researchers have known that the molecule dubbed TNF-related apoptosis-inducing ligand -- or TRAIL -- kills cancer cells but not normal cells.
              &lt;p&gt; 
              &lt;p&gt;Combining the two using genetic engineering, Dr. Loebinger told reporters, the new cells induced programmed cell death in vitro in a variety of cancer cells, including lung, squamous cell, breast, and cervical cancer cells, while leaving normal cells intact.
              &lt;p&gt; 
              &lt;p&gt;In mice, Dr, Loebinger said, injections of the cells reduced tumor growth significantly (at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 compared with sham injections) when the researchers grafted tumor cells into the animals.
              &lt;p&gt; 
              &lt;p&gt;And in animals prone to develop lung tumors (similar to human lung metastases), intravenous injections of the engineered cells meant that 38% of the animals did not develop tumors at all, and the rest had significantly reduced (at &lt;em&gt;P&lt;/em&gt;=0.03) growth and number of tumors.
              &lt;p&gt; 
              &lt;p&gt;&quot;The two different aspects of this therapy have been used in humans,&quot; he said, but not together. TRAIL, for instance, has been used in phase I and II trials and appears to be safe.
              &lt;p&gt; 
              &lt;p&gt;The combination,&quot; he said, &quot;is quite promising&quot; and would be applicable to a wide range of cancers.
              &lt;p&gt; 
              &lt;p&gt;Dr. Laube said the experiments are &quot;very, very exciting,&quot; not least because of the ability of the cells to seek out and destroy tumor cells wherever they are in the body.
              &lt;p&gt; 
              &lt;p&gt;&quot;That&apos;s got to be helpful to patients,&quot; she said.
              &lt;p&gt; 
              &lt;p&gt;Another new treatment modality targeted cystic fibrosis. In CF, the ion channel defects reduce airway surface liquid, which results in reduced mucociliary clearance and recurrent infections, said Andrew Hirsh, Ph.D., of Parion Sciences in Durham, N.C.
              &lt;p&gt; 
              &lt;p&gt;One treatment that is sometimes used is the sodium channel blocker amiloride (Midamor), but it has several disadvantages, Dr. Hirsh said, including a relatively short effective span that requires frequent use.
              &lt;p&gt; 
              &lt;p&gt;Dr. Hirsh was reporting preclinical data on a new sodium channel blocker, dubbed GS-9411, that he said was 100 times more potent than amiloride (in terms of the 50% inhibition concentration).
              &lt;p&gt; 
              &lt;p&gt;The drug also was able to maintain 85% of sodium channel blockage after multiple washes, compared with less than 10% for amiloride, which should translate to longer effective time in the body, he said.
              &lt;p&gt; 
              &lt;p&gt;The drug, delivered as an aerosol, is now in phase I clinical trials with healthy volunteers, Dr. Hirsh said.
              &lt;p&gt; 
              &lt;p&gt;Meanwhile, researchers led by Carolyn Cannon, M.D., Ph.D., of Washington University School of Medicine in St. Louis, are studying how to deliver tiny nanoparticles containing silver compounds to lung infections.
              &lt;p&gt; 
              &lt;p&gt;So-called silver carbene complexes have been shown to have antibiotic activity and one developed by Dr. Cannon and colleagues -- SCC1 -- is now the subject of an investigational new drug application, she said.
              &lt;p&gt; 
              &lt;p&gt;For technical reasons, that compound can&apos;t be put in nanoparticles, which she and colleagues thought would allow them to reduce the dose and number of doses needed to achieve a clinical effect.
              &lt;p&gt; 
              &lt;p&gt;So they synthesized another molecule -- dubbed SCC22 -- which could be loaded into nanoparticles of L-tyrosine polyphosphate and delivered using a nebulizer.
              &lt;p&gt; 
              &lt;p&gt;In mice infected with &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt;, Dr. Cannon said, 100% survived if they were treated intranasally with the SCC-loaded particles, while all of the untreated mice died.
              &lt;p&gt; 
              &lt;p&gt;The survival advantage left the researchers &quot;surprised and thrilled,&quot; Dr. Cannon said.
              &lt;p&gt; 
              &lt;p&gt;With the nano approach, she said, the mice could be given a smaller dose of the compound and be treated only once a day, compared with twice a day for the drug alone.
              &lt;p&gt; 
              &lt;p&gt;Although the drug was tested in vivo against &lt;em&gt;P. aeruginosa&lt;/em&gt;, Dr. Cannon said, it has been shown in vitro to be &quot;effective against every bacterial species tested to date.&quot;
              &lt;p&gt; 
              &lt;p&gt;It has not escaped her notice, she said, that -- if the animal studies are replicated in humans -- the compounds will be a true silver bullet against bacteria.
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The stem cell study was supported by the Medical Research Council of the U.K. Dr. Loebinger said he had no conflicts.
              &lt;p&gt; 
              &lt;p&gt;The sodium channel blocker study was supported by Parion Sciences. Dr. Hirsh is an employee of the company and holds stock options.
              &lt;p&gt; 
              &lt;p&gt;The silver study was supported by the NIH and an internal grant from Washington University. Dr. Cannon said she had no conflicts.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
            
    </recommendedItem>
    <recommendedItem id="20090101_1_280"
                     title="The Year in Cancer"
                     score="-0.006"
                     href="