Identification of Peptides That Inhibit the DNA Binding, trans-Activator, and DNA Replication Functions of the Human Papillomavirus Type 11 E2 Protein

Peptide antagonists of the human papillomavirus type 11 (HPV-11) E2-DNA association were identified using a filamentous bacteriophage random peptide library. Synthetic peptides antagonized the E2-DNA interaction, effectively blocked E2-mediated transcriptional activation of a reporter gene in cell culture, and inhibited E1-E2-mediated HPV-11 DNA replication in vitro. These peptides may prove to be useful tools for characterizing E2 function and for exploring the effectiveness of E2-inhibitor-based treatments for HPV-associated diseases

Initial Treatment Patterns Over Time for Anaplastic Oligodendroglial Tumors

Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 19812007. Prior to 1990, most patients received radiotherapy (RT) alone as initial postoperative treatment. After 1990, approximately 50 of patients received both RT and chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone became significantly less common (67 in 19801984 vs 5 in 20052007, P \u3c .0001). CT alone was more frequently administered in later years (0 in 19801984 vs 38 in 20052007; P \u3c .0001), especially in patients with 1p19q codeleted tumors (57 of codeleted vs 4 with no deletion in 20052007; P \u3c .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RT (87 vs 2 in 20052007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RT with temozolomide was a significantly more common treatment strategy than either CT or RT alone in cases with no deletion (P \u3c .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P \u3c .0001), 1p19q codeletion (P \u3c .0001), pure anaplastic oligodendroglioma histology (P \u3c .01), and frontal lobe predominance (P \u3c .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy

International Retrospective Study of Over 1000 Adults With Anaplastic Oligodendroglial Tumors

Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed from 1981-2007 treated initially with RT alone (n 5 200), CT 1 RT (n 5 528), CT alone (n 5 201), or other strategies (n 5 84). Median overall survival (OS) was 6.3 years and time to progression (TTP) was 3.1 years. 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion. In codeleted cases, median TTP was longer following CT 1 RT (7.2 y) than following CT (3.9 y, P 5.003) or RT (2.5 y, P \u3c.001) alone but without improved OS; median TTP was longer following treatment with PCV alone than temozolomide alone (7.6 vs. 3.3 y, P 5.019). In cases with no deletion, median TTP was longer following CT 1 RT (3.1 y) than CT (0.9 y, P 5.0124) or RT (1.1 y, P \u3c.0001) alone; OS also favored CT 1 RT (median 5.0 y) over CT (2.2 y, P 5.02) or RT (1.9 y, P \u3c.0001) alone. In codeleted cases, CT alone did not appear to shorten OS in comparison with CT 1 RT, and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage. Combined CT 1 RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion. Ongoing trials will address these issues prospectively