The E7 early viral protein of the oncogenic human papillomavirus type 16 (HPV-16) has been strongly implicated in the maintenance of the malignant phenotype in cervical cancers and cancer-derived cell lines. HPV-16 E7 is a nuclear phosphoprotein that can cooperate with ras to transform baby rat kidney cells, transactivates the adenovirus E2 promoter, and binds to the retinoblastoma (RB) protein. The E7 phosphoprotein of the nononcogenic HPV-6b, which is generally associated with benign genital warts, is similar to the HPV-16 E7 in amino acid sequence but differs dramatically in migration in sodium dodecyl sulfatepolyacrylamide gels, sedimentation in nondenaturing glycerol gradients, and the ability to bind the RB protein. Our results indicate that the RB protein preferentially binds the phosphorylated form of HPV-6b E7, which comprises a minor fraction of the total E7 expressed in transiently transfected COS-7 cells. These characteristics may help to explain the difference in the oncogenic potential of the oncogenic and nononcogenic types of genital papillomaviruses. * Corresponding author. viral proteins ElA, LgT, and E7 of HPV-16 can bind to the RB protein has led to the hypothesis that these interactions may functionally eliminate RB protein from the cell and allow uncontrolled proliferation (21). The experiments described here demonstrate some of the differences and similarities in the E7 proteins of the oncogenic HPV-16 and the nononcogenic HPV-6b. We now report that the two E7 proteins differ in migration in sodium dodecyl sulfate (SDS)-acrylamide gels, sedimentation in glycerol gradients, and ability to bind the RB protein. MATERIALS AND METHODS Antisera. The HPV-6b E7-TrpE fusion protein plasmid was constructed by cloning the 1.1-kilobase-pair NsiI fragment between nucleotides 534 and 1644 of HPV-6b into the PstI site of the bacterial TrpE fusion protein vector, pATH 11 (generously provided by T. J. Korner and A. Tzagoloff).
Objective:To assess long-term safety and efficacy of anti–calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).Methods:Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data.Results:Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28–822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo.Conclusions:One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM.Clinicaltrials.gov identifier:NCT01952574.Classification of evidence:This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.