© Oxford University Press 2006.
IN THIS ISSUE
A New Tumor Suppressor In Non–Small-Cell Lung CancerHLJ1 is a heat shock protein associated with tumor invasion. To determine its role in non–small-cell lung cancer, Tsai et al. (p. 825) measured its anti-tumorigenic effects in vitro and in a mouse model of lung adenocarcinoma, as well as its prognostic value in human tumors. HLJ1 expression reduced lung cancer cell proliferation, tumorigenesis, and invasion in vitro through a p53-independent pathway. HLJ1 expression was lower in human tumors than in adjacent normal tissues, and loss of heterozygosity at the HLJ1 gene locus was observed in the majority of tumors. Non–small-cell lung cancer patients with high HLJ1 expression had reduced recurrence and longer overall survival than those with low expression. Validation in an independent cohort confirmed the association between HLJ1 expression and outcome. The authors conclude that HLJ1 is a novel tumor suppressor in non–small-cell lung cancer.
In an editorial, Albini and Pfeffer (p. 800) note that the findings of Tsai et al. will be clinically relevant and discuss potential mechanisms by which HLJ1 may act to inhibit metastasis through anti-angiogenic pathways.
Urologist's Role in Androgen Deprivation Therapy Use
Androgen deprivation therapy use for prostate cancer has been increasing, even though there is little evidence of its efficacy in some clinical situations. Shahinian et al. (p. 839) assessed the importance of physician, patient, and tumor characteristics in the use of this therapy by analyzing the Surveillance, Epidemiology and End-Results (SEER)–Medicare linked database. The percentage of total variance in use of androgen deprivation therapy use attributable to the urologist was consistently higher than that attributable to tumor or patient characteristics. Its use was most pronounced among patients diagnosed after the 1997 publication of clinical trial results showing a benefit associated with androgen deprivation therapy with radiation therapy for locally advanced prostate cancer. The authors conclude that which physician a patient sees may be more important in determining whether they receive androgen deprivation therapy than tumor or patient characteristics.
In an editorial, Schellhammer (p. 802) writes that, because combined androgen deprivation and radiation therapy worked well in advanced disease, an unproven extrapolation followed that this therapy could be beneficial for less advanced disease. He also notes that lack of PSA data and the grade assumptions made in their analysis of the SEER data could place both high-risk and low-risk patients in the same category, which could be problematic.
Silibinin and Lung Tumor Growth and Progression
The milk thistle derivative silibinin inhibits tumor growth in several rodent models. Singh et al. (p. 846) examined dietary silibinin's effects in a mouse model of urethane-induced lung tumors. Urethane-injected mice fed silibinin had fewer lung tumors than urethane-injected control mice fed a diet lacking silibinin. Mice that received urethane and 1% dietary silibinin for 18 weeks had 93% fewer lung tumors than control mice. Their lung tumors also had fewer proliferating tumor cells. Tumor microvessel density was reduced by up to 89% with silibinin treatment. Silibinin decreased lung tumor expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase and cyclooxygenase-2, two enzymes that promote lung tumor growth and progression by inducing VEGF expression. The authors conclude that silibinin inhibits lung tumor angiogenesis in this model and that it merits investigation as a chemopreventive agent for suppressing lung cancer progression.
Tolfenamic Acid and Pancreatic Cancer
Transcription factors Sp1, Sp3, and Sp4 regulate cell proliferation and VEGF expression, and Sp proteins are overexpressed in many cancer cell lines. Abdelrahim et al. (p. 855) screened various nonsteroidal antiinflammatory drugs (NSAIDs), including tolfenamic acid, to determine whether they can decrease levels of Sp1, Sp3, and Sp4 proteins, as well as mouse pancreatic tumor growth and metastasis. Tolfenamic acid induced degradation of Sp1, Sp3, and Sp4 and inhibited VEGF mRNA and protein expression in pancreatic cancer cells. In mice with pancreatic tumors, treatment with tolfenamic acid decreased tumor growth and weight, liver metastasis, and Sp1, Sp3, Sp4, and VEGF levels in tumors. The authors conclude that tolfenamic acid may be a good lead drug to develop more potent NSAIDs for pancreatic cancer treatment.
Cadmium and Breast Cancer Risk
Cadmium, a toxic heavy metal that accumulates in the body and persists in the environment, has been designated a probable human carcinogen. Cigarette smoke is the main source of cadmium exposure in smokers and food the main source for nonsmokers. Laboratory data have indicated that cadmium may increase the risk of breast cancer. McElroy et al. (p. 869) report on a population-based case–control study that confirms this association. Women in the top quartile of creatinine-adjusted cadmium levels had twice the breast cancer risk of those in the lowest quartile. Moreover, the risk increased with increasing level of cadmium. The authors caution that it remains to be determined whether cadmium is a causal factor for breast cancer, noting that if the association is real it could possibly reflect release of cadmium from tissue stores in response to disease or treatment.
Klatskin Tumors and Bile Duct Cancer Incidence
Cholangiocarcinomas (cancers of the bile duct) are anatomically categorized as intrahepatic or extrahepatic according to their location within the bile tract. Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic, the second edition of the International Classification of Diseases for Oncology, which was used from 1992 to 2000, assigned them to a histology code that was cross-referenced to intrahepatic cholangiocarcinoma. To investigate the impact of this misclassification on site-specific cholangiocarcinoma incidence rates in the United States, Welzel et al. (p. 873) used data from the SEER program from 1973 through 2002. During 1992–2000, the misclassification of Klatskin tumors resulted in an overestimation of intrahepatic cholangiocarcinoma incidence by 13% and underestimation of extrahepatic cholangiocarcinoma incidence by 15%. However, even after excluding Klatskin tumors, the annual incidence of intrahepatic cholangiocarcinoma increased approximately 4% from 1992 through 2000.
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