First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.

Purpose: The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors.

PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.

Programmed death 1 ligand 1 (PD-L1) is an immune regulatory molecule that limits antitumor immune activity. Targeting of PD-L1 and other immune checkpoint proteins has shown therapeutic activity in various tumor types. The expression of PD-L1 and its correlation with response to neoadjuvant chemotherapy in breast cancer has not been studied extensively.

Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion.

Purpose: To deepen our understanding of mutant ROS1 expression, localization, and frequency in non-small cell lung cancer (NSCLC), we developed a highly specific and sensitive immunohistochemistry (IHC)-based assay that is useful for the detection of wild-type and mutant ROS1.

Experimental Design: We analyzed 556 tumors with the ROS1 D4D6 rabbit monoclonal antibody IHC assay to assess ROS1 expression levels and localization. A subset of tumors was analyzed by FISH to determine the percentage of these tumors harboring ROS1 translocations.

A neural model of sequential movement planning and control of eye movements: Item-Order-Rank working memory and saccade selection by the supplementary eye fields.

How does working memory store multiple spatial positions to control sequences of eye movements, particularly when the same items repeat at multiple list positions, or ranks, during the sequence? An Item-Order-Rank model of working memory shows how rank-selective representations enable storage and recall of items that repeat at arbitrary list positions. Rank-related activity has been observed in many areas including the posterior parietal cortices (PPC), prefrontal cortices (PFC) and supplementary eye fields (SEF). The model shows how rank information, originating in PPC, may support rank-sensitive PFC working memory representations and how SEF may select saccades stored in working memory.

IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation.

Objective: Mast cell and basophil activation contributes to inflammation, bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-independent stimulation.

Methods: Because the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied the effects of IL-33 on these pathways.

Reward-related neuronal activity in the rat superior colliculus.

The activity of single units in the intermediate and deep layers of the superior colliculus was recorded while rats performed an operant conditioning task. On all trials, each animal pressed a bar and then inserted his snout into a food cup; on half of the trials, food reinforcement was available. To test for tactile sensitivity, on half of the trials the rats received a puff of air to the face when the snout entered the food cup.

Cloning and characterization of a functional type II gonadotropin-releasing hormone receptor with a lengthy carboxy-terminal tail from an ancestral vertebrate, the sea lamprey.

A full-length transcript encoding a functional type II GnRH receptor was cloned from the pituitary of the sea lamprey, Petromyzon marinus. The current study is the first to identify a pituitary GnRH receptor transcript in an agnathan, which is the oldest vertebrate lineage. The cloned receptor retains the conserved structural features and amino acid motifs of other known GnRH receptors and notably includes a C-terminal intracellular tail of approximately 120 amino acids, the longest C-terminal tail of any vertebrate GnRH receptor identified to date.

Cloning and analysis of the lamprey GnRH-III cDNA from eight species of lamprey representing the three families of Petromyzoniformes.

The lamprey, which are divided into three families, including the Petromyzonidae, Geotriidae, and Mordaciidae, have been shown to regulate the reproductive axis through a functional hypothalamic-pituitary-gonadal axis. To date, two forms of gonadotropin-releasing hormone (GnRH) have been identified in the sea lamprey (Petromyzon marinus), lamprey GnRH-I (decapeptide and cDNA) and lamprey GnRH-III (decapeptide), both of which have been shown to be expressed in the preoptic-anterior hypothalamic region and both forms have been demonstrated to regulate reproductive function (i.e.