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									                                                   sees may be more important in deter-          amic acid decreased tumor growth and
                                                   mining whether they receive androgen          weight, liver metastasis, and Sp1, Sp3,
     IN THIS ISSUE                                 deprivation therapy than tumor or patient
                                                                                                 Sp4, and VEGF levels in tumors. The
                                                                                                 authors conclude that tolfenamic acid may
                                                      In an editorial, Schellhammer (p. 802)     be a good lead drug to develop more potent
                                                   writes that, because combined androgen        NSAIDs for pancreatic cancer treatment.
  A New Tumor Suppressor In                        deprivation and radiation therapy worked
  Non–Small-Cell Lung Cancer                       well in advanced disease, an unproven         Cadmium and Breast
      HLJ1 is a heat shock protein associ-         extrapolation followed that this therapy      Cancer Risk
  ated with tumor invasion. To determine           could be beneficial for less advanced dis-         Cadmium, a toxic heavy metal that
  its role in non–small-cell lung cancer, Tsai     ease. He also notes that lack of PSA data     accumulates in the body and persists in
  et al. (p. 825) measured its anti-tumori-        and the grade assumptions made in their       the environment, has been designated a
  genic effects in vitro and in a mouse            analysis of the SEER data could place both    probable human carcinogen. Cigarette
  model of lung adenocarcinoma, as well            high-risk and low-risk patients in the same   smoke is the main source of cadmium
  as its prognostic value in human tumors.         category, which could be problematic.         exposure in smokers and food the main
  HLJ1 expression reduced lung cancer cell                                                       source for nonsmokers. Laboratory data
  proliferation, tumorigenesis, and inva-          Silibinin and Lung Tumor                      have indicated that cadmium may increase
  sion in vitro through a p53-independent          Growth and Progression                        the risk of breast cancer. McElroy et al.
  pathway. HLJ1 expression was lower in               The milk thistle derivative silibinin      (p. 869) report on a population-based
  human tumors than in adjacent normal             inhibits tumor growth in several rodent       case–control study that confirms this as-
  tissues, and loss of heterozygosity at the       models. Singh et al. (p. 846) examined        sociation. Women in the top quartile of
  HLJ1 gene locus was observed in the              dietary silibinin’s effects in a mouse        creatinine-adjusted cadmium levels had
  majority of tumors. Non–small-cell lung          model of urethane-induced lung tumors.        twice the breast cancer risk of those in
  cancer patients with high HLJ1 expres-           Urethane-injected mice fed silibinin had      the lowest quartile. Moreover, the risk
  sion had reduced recurrence and longer           fewer lung tumors than urethane-injected      increased with increasing level of cad-
  overall survival than those with low             control mice fed a diet lacking silibinin.    mium. The authors caution that it remains
  expression. Validation in an independent         Mice that received urethane and 1%            to be determined whether cadmium is a
  cohort confirmed the association between          dietary silibinin for 18 weeks had 93%        causal factor for breast cancer, noting that
  HLJ1 expression and outcome. The au-             fewer lung tumors than control mice. Their    if the association is real it could possibly
  thors conclude that HLJ1 is a novel tumor        lung tumors also had fewer proliferating      reflect release of cadmium from tissue
  suppressor in non–small-cell lung cancer.        tumor cells. Tumor microvessel density        stores in response to disease or treatment.
      In an editorial, Albini and Pfeffer          was reduced by up to 89% with silibinin
  (p. 800) note that the findings of Tsai           treatment. Silibinin decreased lung tumor     Klatskin Tumors and Bile
  et al. will be clinically relevant and dis-      expression of vascular endothelial growth     Duct Cancer Incidence
  cuss potential mechanisms by which               factor (VEGF) and inducible nitric oxide         Cholangiocarcinomas (cancers of the
  HLJ1 may act to inhibit metastasis               synthase and cyclooxygenase-2, two en-        bile duct) are anatomically categorized
  through anti-angiogenic pathways.                zymes that promote lung tumor growth          as intrahepatic or extrahepatic according
                                                   and progression by inducing VEGF ex-          to their location within the bile tract.
  Urologist’s Role in Androgen                     pression. The authors conclude that silib-    Although hilar cholangiocarcinomas
  Deprivation Therapy Use                          inin inhibits lung tumor angiogenesis in      (Klatskin tumors) are extrahepatic, the
      Androgen deprivation therapy use for         this model and that it merits investigation   second edition of the International
  prostate cancer has been increasing, even        as a chemopreventive agent for suppress-      Classification of Diseases for Oncology,
  though there is little evidence of its effi-      ing lung cancer progression.                  which was used from 1992 to 2000, as-
  cacy in some clinical situations. Shahinian                                                    signed them to a histology code that was
  et al. (p. 839) assessed the importance of
                                                   Tolfenamic Acid and                           cross-referenced to intrahepatic cholan-
  physician, patient, and tumor character-         Pancreatic Cancer                             giocarcinoma. To investigate the impact
  istics in the use of this therapy by analyz-        Transcription factors Sp1, Sp3, and        of this misclassification on site-specific
  ing the Surveillance, Epidemiology and           Sp4 regulate cell proliferation and VEGF      cholangiocarcinoma incidence rates in
  End-Results (SEER)–Medicare linked               expression, and Sp proteins are over-         the United States, Welzel et al. (p. 873)
  database. The percentage of total vari-          expressed in many cancer cell lines.          used data from the SEER program from
  ance in use of androgen deprivation ther-        Abdelrahim et al. (p. 855) screened vari-     1973 through 2002. During 1992–2000,
  apy use attributable to the urologist was        ous nonsteroidal antiinflammatory drugs        the misclassification of Klatskin tumors
  consistently higher than that attributable       (NSAIDs), including tolfenamic acid, to       resulted in an overestimation of intrahe-
  to tumor or patient characteristics. Its use     determine whether they can decrease lev-      patic cholangiocarcinoma incidence by
  was most pronounced among patients               els of Sp1, Sp3, and Sp4 proteins, as well    13% and underestimation of extrahepatic
  diagnosed after the 1997 publication of          as mouse pancreatic tumor growth and          cholangiocarcinoma incidence by 15%.
  clinical trial results showing a benefit          metastasis. Tolfenamic acid induced deg-      However, even after excluding Klatskin
  associated with androgen deprivation             radation of Sp1, Sp3, and Sp4 and inhib-      tumors, the annual incidence of intra-
  therapy with radiation therapy for locally       ited VEGF mRNA and protein expression         hepatic cholangiocarcinoma increased
  advanced prostate cancer. The authors            in pancreatic cancer cells. In mice with      approximately 4% from 1992 through
  conclude that which physician a patient          pancreatic tumors, treatment with tolfen-     2000.

Journal of the National Cancer Institute, Vol. 98, No. 12, June 21, 2006                                                 IN THIS ISSUE     799

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