© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 9, 739,
May 5, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Arsenic trioxide can induce clinical remission in patients with acute promyelocytic leukemia. This anticancer effect is brought about by the induction of cellular differentiation and apoptosis (programmed cell death). Zhu et al. (p. 772) have investigated whether clinically achievable concentrations of arsenic trioxide could also cause growth inhibition, differentiation, and apoptosis in malignant lymphocytes. They found that therapeutic concentrations (1-2 µM) of arsenic trioxide could substantially inhibit cell growth and induce apoptosis in most of the malignant lymphocytic cell types studied. According to the authors, these results suggest that arsenic trioxide may prove useful in the treatment of lympho-proliferative disorders.
In an editorial, Kroemer and de Thé (p. 743) discuss the probable modes of action of arsenic trioxide and posit that, in view of a large number of potential cellular targets, issues such as dose become critical. At relatively low doses, they say, arsenic trioxide may exert anticancer effects on tumor cells but not acute toxic effects on normal cells. They look upon arsenic trioxide as a welcome addition to the clinician's armamentarium for the chemotherapy for leukemia.
Exposure to Dioxin and Cancer
Steenland et al. (p. 779) report a mortality analysis involving a cohort of 5132 workers at 12 chemical plants in the United States who were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Their analysis suggests that high exposure to TCDD results in an excess of all types of cancer, without any marked specificity. However, this excess of cancer was limited to workers who had the highest exposure levels, i.e., workers with exposures perhaps 100-1000 times higher than that experienced by the general population.
In an editorial, Hoover (p. 745) comments on the dilemmas encountered in dealing with the data on dioxins, and he discusses how the results of Steenland et al. add to our knowledge of the risks associated with TCDD exposure. The editorialist states that he believes, based on all available evidence, that TCDD should be considered a human carcinogen but that many questions remain to be answered.
Gastric Cardia Cancer Misclassification
Reports of dramatic increases in the incidence of gastric cardia cancer led Ekström et al. (p. 786) to investigate the possibility of cancer misclassification. The authors took advantage of a comprehensive organization in Sweden for the rapid ascertainment of patients newly diagnosed with gastric cancer. Their search resulted in the identification of more than 1300 individuals who were uniformly characterized with regard to gastric cancer site. This group of patients formed a gold standard that was used to evaluate the classification of gastric cardia cancer in the Swedish Cancer Registry. The authors report that overall completeness of gastric cancer registration in the Swedish Cancer Registry was excellent but that accuracy in registering gastric cardia tumors was surprisingly low. The margin of error could accommodate the observed increase in gastric cardia cancer in Sweden. The authors conclude that secular trends in gastric cardia cancer incidence should be interpreted cautiously.
In an editorial, Devesa and Fraumeni (p. 747) state that the study by Ekström et al. illustrates the need to evaluate the specificity and the accuracy of diagnoses in interpreting reported increases in gastric cardia cancer, which corresponds in other populations to marked increases in esophageal adenocarcinoma. With improvements in the quality of data collected by cancer surveillance systems worldwide, the editorial writers say it should be possible to limit the potential sources of bias and error and thus identify temporal and other patterns of cancer that give rise to etiologic hypotheses.
A Molecular Key to Uterine Leiomyosarcomas?
Leiomyosarcomas, smooth muscle tumors of the uterus, have been found to have reduced expression of calponin h1, a basic actin-binding protein that is a normal constituent of smooth muscle cells. To explore the possibility that reduced expression of this protein plays a role in the development of leiomyosarcoma, Horiuchi et al. (p. 790) used a plasmid to introduce and express human calponin h1 complementary DNA into two human leiomyosarcoma cell lines, SKN and SK-LMS-1. They found that calponin h1-transfected tumor cells exhibited an approximately 30% reduction in proliferation compared with control cells. Calponin h1-transfected cells also had a statistically significant reduction in anchorage-independent growth and tumorigenicity in immunodeficient nude mice. The authors conclude from these findings that calponin h1 may function as a tumor suppressor in leiomyosarcoma.
Gene Therapy for Lung Cancer
Restoring expression of wild-type p53 protein in cancer cells holds promise in stopping the growth of tumors. In this issue, Swisher et al. (p. 763) report results from a phase I clinical trial in which the tumors of 28 patients with non-small-cell lung cancer were injected with an adenovirus vector containing a complementary DNA encoding p53 protein. In this trial, patients with inoperable lung cancer received injections of the vector ranging from 106 to 1011 plaque-forming units. The researchers report no serious toxic effects related to the adenovirus vector or its administration, and they observed a partial response in two patients.
Detecting Nasopharyngeal Cancer
In countries of the Pacific Rim and near the Mediterranean Sea, nasopharyngeal carcinoma (NPC) is an important tumor. This tumor is generally diagnosed late in its development, has a low 10-year survival, and is almost always associated with Epstein-Barr virus (EBV) infection. Tune et al. (p. 796) tested whether a nasopharyngeal brush biopsy done in an ambulatory setting could provide sufficient tumor-cell DNA for the detection of EBV and whether the detection of EBV in this locale reflected the presence of tumor cells or that the patient was a virus carrier. After collecting specimens from 21 patients with NPC and 157 subjects with other otolaryngologic complaints, the authors concluded that the technique detects NPC with a sensitivity of at least 90% and a specificity of approximately 99%, thus meriting further investigation as a possible screening test in high-risk populations.
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