The Utilization of the Accelerated Approval Pathway in Oncology: A Case Study of Pembrolizumab.

The accelerated approval (AA) pathway was established by the United States Food and Drug Administration (FDA) to provide earlier access to therapies for patients with serious medical conditions and unmet medical needs. Since its inception, the AA pathway has been used for novel treatments across different therapeutic areas, but most prominently in oncology, including the immune checkpoint inhibitor class. This review article describes the history of regulatory approvals for pembrolizumab, an immunotherapy agent targeting programmed death receptor-1 (PD-1), and use of the AA pathway and the corresponding regulatory decisions made by the FDA.

Relative frequency of dentigerous cyst in Iranian population: A 20-year retrospective study.

Purpose: Dentigerous cyst (DC) is the most common type of developmental odontogenic cysts which apparently develops via accumulation of fluid between the reduced enamel epithelium and crown of the tooth. The aim of this study is to analyze the frequency of DC in Iranian population.

Materials And Methods: The files of oral pathology, Shahid Beheshti University of Medical Sciences, served as the source of the materials from 1992 to 2012 for this study.

Comparison of insulin lispro with regular human insulin for the treatment of type 1 diabetes in adolescents.

Background: Although insulin lispro (insulin LP) has been shown to improve postprandial blood glucose (BG) control and reduce hypoglycemic episodes in adult patients with type I diabetes, there appear to have been few clinical studies focusing on its use in adolescents.

Objective: This study compared the effects of insulin LP with those of regular human insulin (insulin R) on postprandial BG control and hypoglycemia in adolescents with type diabetes.

Methods: In this crossover, open-label study, adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were randomized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals, in addition to daily intermediate-acting insulin.

Insulin lispro lowers postprandial glucose in prepubertal children with diabetes.

Objective: This study compared the glucose-lowering effect of insulin lispro, given before or after meals, with regular human insulin given before meals in prepubertal children with diabetes.

Research Design And Methods: A 3-way crossover, open-label study involving 61 prepubertal children (ages 2.9-11.

Safety of insulin lispro: pooled data from clinical trials.

The safety of insulin lispro was compared with that of regular human insulin of recombinant DNA origin (Humulin R, Lilly), with special emphasis on the development and progression of the chronic complications of diabetes mellitus in relation to insulin therapy. Ten clinical trials of 3634 patients with type 1 and type 2 diabetes mellitus were analyzed. The primary focus was treatment-emergent adverse events, and the secondary focus was the development and progression of the chronic complications of diabetes.

Health-related quality-of-life results from multinational clinical trials of insulin lispro. Assessing benefits of a new diabetes therapy.

Objective: To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R).

Research Design And Methods: We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores.

The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter.

Disruption of Epstein-Barr virus latency is induced by expression of either the BZLF1 (in B cells and epithelial cells) or BRLF1 (in epithelial cells only) immediate-early protein. Regulation of BZLF1 and BRLF1 transcription may therefore modulate the stringency of viral latency. The cellular transcription factor YY1 negatively regulates BZLF1 transcription.

Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism.

Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, is a human herpesvirus associated with epithelial cell malignancies (nasopharyngeal carcinoma) as well as B-cell malignancies. Understanding how viral latency is disrupted is a central issue in herpesvirus biology. Epithelial cells are the major site of lytic EBV replication within the human host, and viral reactivation occurs in EBV-associated nasopharyngeal carcinomas.

Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication.

The Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1 are both essential for lytic EBV replication. BZLF1 is a transcriptional activator which binds directly to the lytic origin of replication (oriLyt) and plays a critical role in the disruption of viral latency. The BMRF1 protein is required for viral polymerase processivity.

The Zif268 cellular transcription factor activates expression of the Epstein-Barr virus immediate-early BRLF1 promoter.

The Epstein-Barr virus immediate-early protein BZLF1 mediates the switch from latent to lytic infection. BZLF1 transcription can be derived from either the BZLF1 promoter or the BRLF1 promoter (Rp). Productive viral infection of EBV-infected B cells can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, as well as cross-linking of surface immunoglobulin with antiimmunoglobulin antibody.

The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor.

Disruption of viral latency in Epstein-Barr virus-infected cells is mediated through the activation of the BZLF1 (Z) immediate-early gene product. The Z protein can be derived from either of two promoters: the BZLF1 promoter, which directs transcription of a 1.0-kb mRNA encoding the Z gene product alone, or the upstream BRLF1 promoter, which directs transcription of a 2.

Ascorbic acid concentration of human fetal tissues in relation to fetal size and gestational age.

1. Studies were carried out on the distribution of ascorbic acid in human fetal tissues with the progress of gestation. 2.

Ascorbic acid and reduced glutathione concentration of human fetal tissues in relation to gestational age, fetal size and maternal nutritional status.

Studies were carried out on ascorbic acid and glutathione concentration in human fetal tissues with the progress of gestation. The glutathione concentration in human fetal liver and adrenal showed a decline during late gestation, the decline in the brain being earlier. This is consistent with the fall in ascorbic acid concentration in all tissues during late gestation.