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    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265773505620"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&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 authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_234"
                     title="ASCO GI: Test May Spot Pancreatic Cancer Early"
                     score="-0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18090?impressionId=1265773505620"
                     
      &lt;p&gt;ORLANDO -- A blood test for pancreatic cancer identified a majority of stage I tumors in a preliminary evaluation involving tumor specimens.&lt;/p&gt;
&lt;p&gt;Based on detection of an antigen specific to pancreatic cancer, the assay had an overall sensitivity of 81%, ranging from 62% for stage I cancers to 91% for stage III/IV cancers.&lt;/p&gt;
&lt;p&gt;The monoclonal antibody to the PAM4 antigen yielded false-positive results in just 5% of nonpancreatic cancer specimens, resulting in a specificity of 95%, as reported at a press briefing prior to the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;PAM4 blood test is very specific for pancreatic cancer,&quot; said David Gold, PhD, of the Garden State Cancer Center in Belleville, N.J. &quot;If the assay is positive, there is a high positive diagnostic likelihood that the patient has pancreatic cancer.&quot;&lt;/p&gt;
&lt;p&gt;In a separate presentation, the investigators showed that the monoclonal antibody, known as clivatuzumab, might have therapeutic potential as a delivery vehicle for anticancer agents.&lt;/p&gt;
&lt;p&gt;Treatment with a radiolabeled version of the antibody led to partial responses in a fourth of patients with pancreatic cancer and to stable disease in another 45%.&lt;/p&gt;
&lt;p&gt;The PAM4 mucin glycoprotein is expressed by 90% of pancreatic cancers, but not by normal tissue, other types of cancer, or in patients who have pancreatitis. As a result, PAM4 constitutes a unique biomarker useful for early diagnosis of pancreatic cancer.&lt;/p&gt;
&lt;p&gt;&quot;Pancreatic cancer has a poor prognosis with an overall five-year survival of 2% to 3%,&quot; said Gold. &quot;However, early detection can substantially improve the prognosis, as five-year survival for stage I disease is 20%.&quot;&lt;/p&gt;
&lt;p&gt;To evaluate the diagnostic potential of the PAM4 enzyme immunoassay, investigators studied surgically resected tumor specimens from 68 patients with pancreatic cancer and normal tissue from 19 healthy volunteers.&lt;/p&gt;
&lt;p&gt;The monoclonal antibody correctly identified 13 of 21 (62%) stage I cancers, 12 of 14 (86%) stage II cancers, and 30 of 33 (91%) stage III/IV cancers. The test incorrectly identified one of 19 normal-tissue specimens as cancer.&lt;/p&gt;
&lt;p&gt;The study also showed a correlation between the serum level of PAM4 and the extent of pancreatic cancer, suggesting the test may inform on tumor stage in addition to its diagnostic capability, said Gold.&lt;/p&gt;
&lt;p&gt;Overall, the tumor specimens were associated with a median serum PAM4 level of 9.85 U/mL. Median values increased from 4.53 U/mL for stage I disease to 10.39 U/mL for stage II disease to 13.37 U/mL for stage III/IV cancer.&lt;/p&gt;
&lt;p&gt;In contrast, normal tissue specimens had a median serum value of 1.18 U/mL.&lt;/p&gt;
&lt;p&gt;Interest in therapeutic applications of clivatuzumab arose from the observation that a single dose of 90Y-labeled antibody showed transient antitumor activity in advanced pancreatic cancer.&lt;/p&gt;
&lt;p&gt;The finding led to a clinical trial wherein about two dozen patients with untreated, inoperable locally advanced or metastatic pancreatic cancer received four weekly doses of gemcitabine (Gemzar) plus 90Y-labeled clivatuzumab on weeks two through four.&lt;/p&gt;
&lt;p&gt;The therapy led to partial responses in 23% of patients and stable disease in 45% for a total clinical benefit of 68%. The treatment was well tolerated, including few nonhematologic adverse events.&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;One of the co-authors is employed in a leadership position at and has stock ownership in Immunomedics.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1693"
                     title="ASCO: Vaccine Trains Killer Cells to Battle Melanoma"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCO/tb/14457?impressionId=1265773505620"
                     
      ORLANDO, May 31 -- A vaccine approach that trains immune cells and sends them marching into battle has shown promise in advanced melanoma, a researcher said here.
              &lt;p&gt; 
              &lt;p&gt;The vaccine, used along with a powerful stimulant of the immune system, shrank melanoma metastases and prolonged the time before the disease resumed progression, according to Patrick Hwu, M.D., of M.D. Anderson Cancer Center in Houston.
              &lt;p&gt; 
              &lt;p&gt;In the phase III controlled trial, there was also a trend to longer overall survival that did not reach statistical significance, Dr. Hwu said at the annual meeting of the American Society of Clinical Oncology.
              &lt;p&gt; 
              &lt;p&gt;The vaccine consists of part of a molecule -- dubbed gp100 -- that is on the surface of melanoma cells. It&apos;s delivered along with interleukin-2, a powerful immune system stimulant.
              &lt;p&gt; 
              &lt;p&gt;The vaccine, Dr. Hwu said, &quot;takes T cells to boot camp&quot; and trains them to attack the tumor. The interleukin-2 multiplies the killer cells into a &quot;large army that can then attack the tumors to kill them.&quot;
              &lt;p&gt; 
              &lt;p&gt;The approach is not new -- a 1998 early stage trial in 31 patients showed good response -- but this is the first phase III trial to show positive results, Dr. Hwu said.
              &lt;p&gt; 
              &lt;p&gt;The researchers randomized 185 patients with metastatic melanoma in 21 centers to get either interleukin-2 alone or interleukin-2 with the gp100 vaccine. 
              &lt;p&gt; 
              &lt;p&gt;The primary endpoint was clinical response, but the researchers also measured time to relapse.
              &lt;p&gt; 
              &lt;p&gt;The overall response rate was 22.1% in the vaccine arm, compared with 9.7% in the patients who got interleukin-2 alone, Dr. Hwu said.
              &lt;p&gt; 
              &lt;p&gt;Progression-free survival also favored the vaccine, at 2.9 months compared with 1.6 months for interleukin-2 alone -- a difference that was significant at &lt;em&gt;P&lt;/em&gt;=0.0101.
              &lt;p&gt; 
              &lt;p&gt;The median overall survival favored the vaccine -- at 17.6 months compared with 12.8 -- but the difference did not reach statistical significance, Dr. Hwu said.
              &lt;p&gt; 
              &lt;p&gt;The finding is very preliminary, according to Len Lichtenfeld, M.D., of the American Cancer Society, who was not part of the study.
              &lt;p&gt; 
              &lt;p&gt;&quot;There&apos;s a long way to go before it can be generally applied,&quot; he said.
              &lt;p&gt; 
              &lt;p&gt;But he said much of the progress in cancer care has been composed of small steps and this study is part of the pattern.
              &lt;p&gt; 
              &lt;p&gt;&quot;A lot of our advances in cancer treatment take years if not decades,&quot; he said, &quot;and those years and decades are made up of small changes over a very long time.&quot;
              &lt;p&gt; 
              &lt;p&gt;The findings are &quot;definitely very promising for a very poor-prognosis group of patients,&quot; said Sonali Smith, M.D., of the University of Chicago Medical Center, who moderated a press conference at which the research was presented.
              &lt;p&gt; 
              &lt;p&gt;She said the approach might act as a &quot;platform&quot; for more refined and potent vaccines.
              &lt;p&gt; 
              &lt;p&gt;Indeed, Dr. Hwu noted, the results mean that about 80% of patients did not respond. &quot;We have to do better and I think we can&quot; by employing different immune stimulants, he said.
              &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 study was sponsored by the NIH. Some of the researchers reported financial links with Novartis.
              &lt;p&gt; 
              &lt;p&gt;Dr. Lichtenfeld is an employee of the American Cancer Society.
              &lt;p&gt; 
              &lt;p&gt;Dr. Smith said she had no disclosures to report.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
       
    </recommendedItem>
    <recommendedItem id="20090101_19_1727"
                     title="ASCO: Vaccines Create Buzz but HER-2 in Stomach Cancer May Change Practice"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCO/tb/14461?impressionId=1265773505620"
                     
      ORLANDO, June 2 -- A pair of investigational therapeutic cancer vaccines -- one for lymphoma and the other for melanoma -- highlight this &lt;em&gt;MedPage Today&lt;/em&gt; InFocus discussion.
              &lt;p&gt; 
              &lt;p&gt;The history of cancer vaccines is littered with studies that reported early promising results but failed to deliver significant benefit when the full data were analyzed. Sonali Smith, M.D., associate professor of medicine at the University of Chicago Medical Center, says it&apos;s too early to make the call on the latest chapter in the cancer vaccine story.
              &lt;p&gt; 
              &lt;p&gt;But Dr. Smith told Peggy Peck, &lt;em&gt;MedPage Today&lt;/em&gt; executive editor, that the finding that the breast cancer oncogene HER-2 is present in a percentage of stomach cancer is a finding that has legs and could change clinical practice.  
        
    </recommendedItem>
    <recommendedItem id="20090101_1_146"
                     title="Invasive Melanoma Rising Among California Hispanics"
                     score="-0.006"
                     href="