Total protein concentration and stability of Amb a 1 in glycerinated ragweed sublingual immunotherapy stored at room temperature and refrigerated cold temperature.

Background: Few studies have investigated optimal storage conditions or expiration dates for sublingual immunotherapy (SLIT) formulations prepared from glycerinated allergen extracts.

Hypothesis/objectives: The objective of this study was to compare concentrations of short ragweed major allergen (Amb a 1) and total protein in SLIT formulations stored at two different temperatures. It was hypothesised that protein concentrations would show greater decline over time in a formulation stored at room temperature (RT) than in one stored under refrigeration.

Regiodivergent (3 + 2) annulation reactions of oxyallyl cations.

We report a new method for the regiodivergent dearomative (3 + 2) reaction between 3-substituted indoles and oxyallyl cations. Access to both regioisomeric products is possible and is contingent on the presence or absence of a bromine atom on the substituted oxyallyl cation. In this way, we are able to prepare molecules that contain highly-hindered, stereodefined, vicinal, quaternary centers.

Mechanistic Investigation of Site-specific DNA Methylating Agents Targeting Breast Cancer Cells.

We previously described the development of a DNA-alkylating compound that showed selective toxicity in breast cancer cells. This compound contained an estrogen receptor α (ERα)-binding ligand and a DNA-binding/methylating component that could selectively methylate the N3-position of adenines at adenine-thymine rich regions of DNA. Herein, we describe mechanistic investigations that demonstrate that this class of compounds facilitate the translocation of the ERα-compound complex to the nucleus and induce the expression of ERα target genes.

Diversification of Nucleophile-Intercepted Beckmann Fragmentation Products and Related Density Functional Theory Studies.

The nucleophile-intercepted Beckmann fragmentation (NuBFr) has the potential to be broadly applicable to the synthesis of indoline alkaloid-based natural products. However, the reaction has not been widely adopted, in part, because of limitations associated with the availability of appropriate promoter- reagents. We have devised a stereospecific Ag(I)-promoted reaction for functionalizing NuBFr products to give novel compositions of matter that may be useful in synthesis and medicinal chemistry.

Impact of Sequencing Radiation Therapy and Immune Checkpoint Inhibitors in the Treatment of Melanoma Brain Metastases.

Purpose: Melanoma brain metastases (MBM) occur in ∼50% of melanoma patients. Although both radiation therapy (RT) and immune checkpoint inhibitor (ICI) are used alone or in combination for MBM treatment, the role of this combination and how these treatments could best be sequenced remains unclear.

Methods And Materials: We conducted a retrospective analysis of patients with resected MBM who underwent treatment with RT, ICI, or a combination of RT and ICI.