© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 9, 671,
May 3, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
A previous randomized trial conducted by the Gynecologic Oncology Group in the United States showed a better outcome for patients with advanced ovarian cancer on a paclitaxel–cisplatin regimen compared with those on a standard cyclophosphamide–cisplatin regimen. Before considering the paclitaxel–cisplatin regimen as a new "standard," Piccart et al. (p. 699) planned a confirmatory phase III trial. This new trial observed a higher overall clinical response rate (58.4% versus 44.7%) and a higher complete clinical remission rate (40.7% versus 27.3%) in the paclitaxel group compared with the cyclophosphamide group. At a median follow-up of 38.5 months, longer progression-free survival and longer overall survival were observed with the paclitaxel regimen. The investigators recommend paclitaxel–cisplatin as the new standard regimen for the treatment of patients with advanced ovarian cancer.
In an editorial, McGuire (p. 674) echoes the conclusions of Piccart et al. He points out that the design and accrual of this multinational trial allowed for efficient use of patient resources and provided generalizable results. He suggests that this strategy be adopted in future trial designs.
Human Papillomaviruses and Head and Neck Cancers
High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital cancers and have been detected in some head and neck squamous cell carcinomas (HNSCCs). Gillison et al. (p. 709) investigated whether HPVs play an etiologic role in HNSCC. They tested tumor tissue from 253 patients for the presence and type of HPV and evaluated the association between HPV and lifestyle factors, tumor characteristics, and patient survival. HPV was detected in 25% of the specimens, and 90% of those showed presence of high-risk, tumorigenic HPV16; the virus was localized within the cancer cell nuclei and was detected in preinvasive, invasive, and lymph node disease. The HPV presence was independently associated with poor tumor grade and oropharyngeal site. As compared with HPV-negative cancers, HPV-positive cancers were less frequent among moderate to heavy drinkers and smokers, had a characteristic morphology, and had an improved disease-specific survival. These data suggest a likely causal association between HPV infection and HPV-positive oropharyngeal cancers.
In an accompanying editorial, Wong and Münger (p. 675) point out that standard reagents or methodology may not always be adequate to detect all new virus variants that are active in oral keratinocytes, so they suggest more thorough evaluation of HPVs associated with oral cancers.
Kaposi’s Sarcoma: Transgenic Mouse Model
The human immunodeficiency virus type 1 transactivator (Tat) protein, which is encoded by two exons, has been linked to the development of Kaposi’s sarcoma (KS) associated with acquired immunodeficiency disease syndrome. To evaluate the growth-promoting effects of Tat in an animal model, Prakash et al. (p. 721) developed transgenic mice expressing the one-exon-encoded Tat72 protein and the two-exon-encoded Tat86 protein. They injected human KS SLK cells subcutaneously into CD4+ T-cell-depleted male mice. Tat86 mice produced much larger tumors compared with Tat72 mice or nontransgenic control mice. Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. Tat86 mice, compared with the other two groups, showed in their tumors increased expression of a leukocyte-associated metallo-proteinase and several growth-promoting cytokines. The authors suggest from their data that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.
HHV8 Sequences in Kaposi’s Sarcoma and Other Diseases
Human herpesvirus 8 (HHV8) infection is associated with Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and some forms of multicentric Castleman’s disease (MCD). However, the pathogenic role of HHV8 in these tumors has remained unclear, as has the question of whether KS is monoclonal (i.e., one cell among many derived from HHV8-infected cells replicates to form tumors) or polyclonal (i.e., tumors form from multiple HHV8-infected cells). Judde et al. (p. 729) examined tumors for the number of terminal repeat (TR) sequences in the fused TR region of HHV8 and found that all PEL tumors and some KS tumors contained monoclonal or oligoclonal fused TR fragments. However, the MCD tumors and some KS tumors contained polyclonal fragments. The authors conclude that some KS lesions are clonal expansions of a single HHV8-infected cell, supporting an etiologic role of latent HHV8. They also suggest that, because different KS lesions display different patterns of clonality, KS begins as a polyclonal disease and subsequently evolves into a monoclonal process.
In an accompanying editorial, Weiss and Boshoff (p. 677) propose new experiments in light of observations made by Prakash et al. and Judde et al. and review some of the current issues facing researchers in the field of KS.
"The size heterogeneity of HHV8-fused TRs provides a unique molecular tool to study the clonality of HHV8-infected tumors."
—Judde et al.
Lung Cancer Risk, Growth Factors, and Genetic Instability
In a case–control study, Wu et al. (p. 737) examined whether an individual’s intrinsic sensitivity to carcinogens (as indicated by mutagen sensitivity) and cell proliferation potential (as indicated by levels of insulin-like growth factors [IGFs]) are associated with an increased risk of lung cancer. The authors report that a particularly high risk of lung cancer was associated with higher levels of IGF-I and with greater sensitivity to carcinogens. Furthermore, they note that patients with advanced lung cancer tended to have higher levels of IGF-I and a higher molar ratio of IGF-I to IGF-binding protein-3. The authors conclude that individuals who are more sensitive to mutagens and have a higher proliferation potential appear to be at greater risk of lung cancer.
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