Defining best practices for tissue procurement in immuno-oncology clinical trials: consensus statement from the Society for Immunotherapy of Cancer Surgery Committee.

Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells.

Mechanistic Justifications of Systemic Therapeutic Oxygenation of Tumors to Weaken the Hypoxia Inducible Factor 1α-Mediated Immunosuppression.

Long-term studies of anti-pathogen and anti-tumor immunity have provided complementary genetic and pharmacological evidence for the immunosuppressive and immunomodulatory effects of Hypoxia-HIF-1α and adenosine-mediated suppression via the A2A adenosine receptor signaling pathway (Hypoxia-A2A-adenosinergic). This pathway is life saving when it protects inflamed tissues of vital organs from collateral damage by overactive anti-pathogen immune cells or enables the differentiation of cells of adaptive immunity. However, the Hypoxia-A2A-adenosinergic immunosuppression can also prevent tumor rejection by inhibiting the anti-tumor effects of T and NK cells.

Suppression of stress induction of the 78-kilodalton glucose regulated protein (GRP78) in cancer by IT-139, an anti-tumor ruthenium small molecule inhibitor.

In many cancers, combination therapy regimens are successfully improving response and survival rates, but the challenges of toxicity remain. GRP78, the master regulator of the unfolded protein response, is emerging as a target that is upregulated in tumors, specifically following treatment, and one that impacts tumor cell survival and disease recurrence. Here, we show IT-139, an antitumor small molecule inhibitor, suppresses induction of GRP78 from different types of endoplasmic reticulum (ER) stress in a variety of cancer cell lines, including those that have acquired therapeutic resistance, but not in the non-cancer cells being tested.

Imaging the delivery of drug-loaded, iron-stabilized micelles.

Nanoparticle drug carriers hold potential to improve current cancer therapy by delivering payload to the tumor environment and decreasing toxic side effects. Challenges in nanotechnology drug delivery include plasma instability, site-specific delivery, and relevant biomarkers. We have developed a triblock polymer comprising a hydroxamic acid functionalized center block that chelates iron to form a stabilized micelle that physically entraps chemotherapeutic drugs in the hydrophobic core.

PCR-based bioprospecting for homing endonucleases in fungal mitochondrial rRNA genes.

Fungal mitochondrial genomes act as "reservoirs" for homing endonucleases. These enzymes with their DNA site-specific cleavage activities are attractive tools for genome editing and gene therapy applications. Bioprospecting and characterization of naturally occurring homing endonucleases offers an alternative to synthesizing artificial endonucleases.

Evolutionary dynamics of introns and their open reading frames in the U7 region of the mitochondrial rnl gene in species of Ceratocystis.

The mtDNA rnl-U7 region has been examined for the presence of introns in selected species of the genus Ceratocystis. Comparative sequence analysis identified group I and group II introns encoding single and double motif LAGLIDADG open reading frames (ORFs) at the following positions L1671, L1787, and L1923. In addition downstream of the rnl-U7 region group I introns were detected at positions L1971 and L2231, and a group II intron at L2059.

The mtDNA rns gene landscape in the Ophiostomatales and other fungal taxa: twintrons, introns, and intron-encoded proteins.

Comparative sequence analysis of the mitochondrial small subunit ribosomal RNA (rns) gene among species of Ophiostoma, Grosmannia, Ceratocystiopsis and related taxa provides an overview of the types of introns that have invaded this gene within the ophiostomatoid fungi. The rns gene appears to be a reservoir for a number of group I and group II introns along with intron-associated open reading frames such as homing endonucleases and reverse transcriptases. This study uncovered two twintrons, one at position mS917 where a group ID intron encoding a LAGLIDADG ORF invaded another ORF-less group ID intron.

Identification of group I introns within the SSU rDNA gene in species of Ceratocystiopsis and related taxa.

During a recent phylogenetic study, group I introns were noted that interrupt the nuclear small subunit ribosomal RNA (SSU rDNA) gene in species of Ceratocystiopsis. Group I introns were found to be inserted at the following rDNA positions: S943, S989, and S1199. The introns have been characterized and phylogenetic analysis of the host gene and the corresponding intron data suggest that for S943 vertical transfer and frequent loss appear to be the most parsimonious explanation for the distribution of nuclear SSU rDNA introns among species of Ceratocystiopsis.

Molecular evolution of the mtDNA encoded rps3 gene among filamentous ascomycetes fungi with an emphasis on the Ophiostomatoid fungi.

The mitochondrial ribosomal protein S3 (rps3) gene within the fungi is extremely diverse in location and organization, some versions of this gene have been incorporated into a group I intron, others appear to have gained large insertions, microsatellite expansions, or have been invaded by homing endonucleases. Among the ascomycetes fungi the group I intron encoded version of rps3 appears to have a rather complex evolutionary history including first the acquisition of rps3 by a group I intron (mL2449), the loss of the mL2499 intron and the establishment of rps3 as a free-standing gene, and the eventual loss of the intron derived version of rps3.

The sporadic occurrence of a group I intron-like element in the mtDNA rnl gene of Ophiostoma novo-ulmi subsp. americana.

The presence of group I intron-like elements within the U7 region of the mtDNA large ribosomal subunit RNA gene (rnl) was investigated in strains of Ophiostoma novo-ulmi subsp. americana from Canada, Europe and Eurasia, and in selected strains of O. ips, O.