Biomarker Analyses Investigating Disease Biology and Associations with Outcomes in the JAVELIN Merkel 200 Trial of Avelumab in Metastatic Merkel Cell Carcinoma.

Purpose: Avelumab (anti-PD-L1) became the first approved treatment for metastatic Merkel cell carcinoma (mMCC) based on results from the phase II JAVELIN Merkel 200 trial. In this study, we report exploratory biomarker analyses from the trial.

Patients And Methods: Patients with mMCC (n = 88) with or without prior first-line chemotherapy received avelumab 10 mg/kg every 2 weeks.

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study.

Background: Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.

Methods: Patients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks.

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.

Discovering metabolic disease gene interactions by correlated effects on cellular morphology.

Objective: Impaired expansion of peripheral fat contributes to the pathogenesis of insulin resistance and Type 2 Diabetes (T2D). We aimed to identify novel disease-gene interactions during adipocyte differentiation.

Methods: Genes in disease-associated loci for T2D, adiposity and insulin resistance were ranked according to expression in human adipocytes.

Total CAD/CAM Supported Method for Manufacturing Removable Complete Dentures.

The incorporation of computer-aided design/computer-aided manufacturing (CAD/CAM) technology into complete denture fabrication brings about several advantages to the fabrication process, providing better predictability of the desired outcomes and high accuracy of denture fit, mainly because the milling of prepolymerized acrylic resin eliminates the shrinkage of the acrylic base. Also, there is a decrease in the porosity when compared to a conventionally processed denture, and consequently there is a decrease in the retention of on the denture base. The presented workflow for complete denture fabrication presents a totally wax-free manufacturing process, combining rapid prototyping (RP) and rapid milling.

Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215.

Cell cycle arrest in response to DNA damage is an important antitumorigenic mechanism. MicroRNAs (miRNAs) were recently shown to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G(1) arrest by down-regulating multiple cell cycle-related transcripts.

Essential role for Dicer during skeletal muscle development.

microRNAs (miRNAs) regulate gene expression post-transcriptionally by targeting mRNAs for degradation or by inhibiting translation. Dicer is an RNase III endonuclease which processes miRNA precursors into functional 21-23 nucleotide RNAs that are subsequently incorporated into the RNA-induced silencing complex. miRNA-mediated gene regulation is important for organogenesis of a variety of tissues including limb, lung and skin.

An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals.

Expansion of the polymorphic CGG repeats within the 5'-UTR of the FMR1 gene is associated with variable transcriptional regulation of FMR1. Here we report a novel gene, ASFMR1, overlapping the CGG repeat region of FMR1 and transcribed in the antisense orientation. The ASFMR1 transcript is spliced, polyadenylated and exported to the cytoplasm.

MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.

Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes.

Strength, reliability, and mode of fracture of bilayered porcelain/core ceramics.

Purpose: The aim of this investigation was to compare the biaxial flexural strength, its reliability, and the mode of fracture of bilayered disks made of two core materials (In-Ceram Alumina and In-Ceram Zirconia), both veneered with conventional feldspathic porcelain (Vita Alpha).

Materials And Methods: One hundred forty specimens (monolithic and bilayered) of In-Ceram Alumina, In-Ceram Zirconia, and Vita Alpha were made and tested with the biaxial flexural test. Finite element analysis was used to estimate the maximum tensile stress at fracture.

Tax recruitment of CBP/p300, via the KIX domain, reveals a potent requirement for acetyltransferase activity that is chromatin dependent and histone tail independent.

Robust transcription of human T-cell leukemia virus type 1 (HTLV-1) genome requires the viral transactivator Tax. Although Tax has been previously shown to interact with the KIX domain of CBP/p300 in vitro, the precise functional relevance of this interaction remains unclear. Using two distinct approaches to interrupt the physical interaction between Tax and KIX, we find that Tax transactivation from chromatin templates is strongly dependent on CBP/p300 recruitment via the KIX domain.

p300-mediated tax transactivation from recombinant chromatin: histone tail deletion mimics coactivator function.

Efficient transcription of the human T-cell leukemia virus type 1 (HTLV-1) genome requires Tax, a virally encoded oncogenic transcription factor, in complex with the cellular transcription factor CREB and the coactivators p300/CBP. To examine Tax transactivation in vitro, we used a chromatin assembly system that included recombinant core histones. The addition of Tax, CREB, and p300 to the HTLV-1 promoter assembled into chromatin activated transcription several hundredfold.