Thermal Regulation Performance of Shape-Stabilized-Phase-Change-Material-Based Prefabricated Wall for Green Grain Storage.

In order to meet the great demand for green grain storage and low carbon emissions, paraffin, high-density polyethylene (HDPE), and expanded graphite (EG) were used to produce shape-stabilized phase change material (SSPCM) plates, which were then used to reconstruct building walls for existing granaries. A new type of SSPCM plate was then prefabricated with different thermal conductivities and a high latent heat. This plate could be directly adhered to the existing granary walls.

Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression.

Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified.

Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models.

KRAS is activated by mutation in the vast majority of cases of pancreatic cancer; unfortunately, therapeutic attempts to inhibit KRAS directly have been unsuccessful. Our previous studies showed that inhibition of cyclin-dependent kinase 5 (CDK5) reduces pancreatic cancer growth and progression, through blockage of the centrally important RAL effector pathway, downstream of KRAS. In the current study, the therapeutic effects of combining the CDK inhibitor dinaciclib (SCH727965; MK-7965) with the pan-AKT inhibitor MK-2206 were evaluated using orthotopic and subcutaneous patient-derived human pancreatic cancer xenograft models.

Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth.

To identify potentially important genes dysregulated in pancreatic cancer, we analyzed genome-wide transcriptional analysis of pancreatic cancers and normal pancreatic duct samples and identified the transcriptional coactivator, EYA2 (Drosophila Eyes Absent Homologue-2) as silenced in the majority of pancreatic cancers. We investigated the role of epigenetic mechanisms of EYA2 gene silencing in pancreatic cancers, performed in vitro and in vivo proliferation and migration assays to assess the effect of EYA2 silencing on tumor cell growth and metastasis formation, and expression analysis to identify genes transcriptionally regulated by EYA2. We found loss of tumoral Eya2 expression in 63% of pancreatic cancers (120/189 cases).

Synthesis and cytotoxicity studies of Hedgehog enzyme inhibitors SANT-1 and GANT-61 as anticancer agents.

Cancer-related death is one of the most common causes of mortality in society. Small molecules have the capability to disrupt aberrant signaling pathways in tumors, leading to anticancer activities. Therefore the search for new molecules for cancer treatment continues to draw attention to the scientific research community.

Imaging Axl expression in pancreatic and prostate cancer xenografts.

The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl-Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody.

MicroRNA 223 is upregulated in the multistep progression of Barrett's esophagus and modulates sensitivity to chemotherapy by targeting PARP1.

Purpose: Recent microarray and RNA-sequencing studies have uncovered aberrantly expressed microRNAs (miRNA) in Barrett's esophagus-associated esophageal adenocarcinoma. The functional significance of these miRNAs in esophageal adenocarcinoma initiation and progression is largely unknown.

Experimental Design: Expression levels of miR-199a/b-3p, -199a-5p, -199b-5p, -200b, -200c, -223, and -375 were determined in microdissected tissues from cardiac mucosa, Barrett's esophagus, dysplastic Barrett's esophagus, and esophageal adenocarcinoma using quantitative real-time PCR.

Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma.

MIF is a proinflammatory cytokine and is implicated in cancer. A higher MIF level is found in many human cancer and cancer-prone inflammatory diseases, including chronic pancreatitis and pancreatic cancer. We tested the hypothesis that MIF contributes to pancreatic cancer aggressiveness and predicts disease outcome in resected cases.

Inhibition of OCTN2-mediated transport of carnitine by etoposide.

OCTN2 is a bifunctional transporter that reabsorbs filtered carnitine in a sodium-dependent manner and secretes organic cations into urine as a proton antiport mechanism. We hypothesized that inhibition of OCTN2 by anticancer drugs can influence carnitine resorption. OCTN2-mediated transport inhibition by anticancer drugs was assessed using cells transfected with human OCTN2 (hOCTN2) or mouse Octn2 (mOctn2).

A polymeric nanoparticle encapsulated small-molecule inhibitor of Hedgehog signaling (NanoHHI) bypasses secondary mutational resistance to Smoothened antagonists.

Aberrant activation of the hedgehog (Hh) signaling pathway is one of the most prevalent abnormalities in human cancer. Tumors with cell autonomous Hh activation (e.g.

Polymeric nanoparticle-encapsulated hedgehog pathway inhibitor HPI-1 (NanoHHI) inhibits systemic metastases in an orthotopic model of human hepatocellular carcinoma.

Purpose: To illustrate the prognostic significance of hedgehog (Hh) signaling in patients with hepatocellular carcinoma (HCC) and to evaluate the efficacy of a novel nanoparticle-encapsulated inhibitor of the Hh transcription factor, Gli1 (NanoHHI) using in vitro and in vivo models of human HCCs.

Experimental Design: Patched1 (Ptch1) expression was detected in tumor tissue microarrays of 396 patients with HCC who underwent curative surgical resection during February 2000 to December 2002. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests.

Cisplatin-induced downregulation of OCTN2 affects carnitine wasting.

Purpose: Carnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function.

Experimental Design: Excretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration.

Influence of Oct1/Oct2-deficiency on cisplatin-induced changes in urinary N-acetyl-beta-D-glucosaminidase.

Purpose: This study aimed to test the influence of functional renal organic cation transporters (OCT2 in humans, Oct1 and Oct2 in mice) on biomarkers of cisplatin nephrotoxicity, such as urinary activity of N-acetyl-beta-D-glucosaminidase (NAG).

Experimental Design: Temporal cisplatin-induced nephrotoxicity was assessed by histopathology and biomarkers. Cisplatin-mediated NAG changes and survival were determined in wild-type and Oct1/2(-/-) mice.

Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources.

Apoptosis as a form of programmed cell death is a critical defense mechanism against the formation and progression of cancer and exhibits distinct morphological and biochemical traits. In an in vivo situation, apoptosis functions to eliminate potentially deleterious cells without causing such adverse effects as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents.

Constituents from Clausena excavata.

Three new coumarins containing a C(10) terpenoid side chain, clauslactones R - T (1 - 3), together with 14 known coumarins (4 - 17) and 11 known carbazole alkaloids (18 - 28), were isolated from the leaves and stems of Clausena excavata. Their structures were established by detailed spectroscopic analyses. Furthermore, the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis, which was the first example among coumarins with a C(10) terpenoid side chain.

Interaction of imatinib with human organic ion carriers.

Purpose: The activity of imatinib in leukemia has recently been linked with expression of the organic cation transporter 1 (OCT1) gene SLC22A1. Here, we characterized the contribution of solute carriers to imatinib transport in an effort to further understand mechanisms involved in the intracellular uptake and retention (IUR) of the drug.

Experimental Design: IUR of [3H]imatinib was studied in Xenopus laevis oocytes and HEK293 cells expressing OATP1A2, OATP1B1, OATP1B3, OCT1-3, OCTN1-2, or OAT1-3.

Gambogic acid inhibits the catalytic activity of human topoisomerase IIalpha by binding to its ATPase domain.

This study is intended to characterize the cellular target of gambogic acid (GA), a natural product isolated from the gamboge resin of Garcinia hurburyi tree, which possesses potent in vitro and in vivo antitumor activities. The antiproliferative activity of GA was further confirmed here in a panel of human tumor cells and multidrug-resistant cells. We found that GA significantly inhibited the catalytic activity of topoisomerase (Topo) II and, to a comparatively less extent, of Topo I, without trapping and stabilizing covalent topoisomerase-DNA cleavage complexes.

A novel polypeptide from shark cartilage with potent anti-angiogenic activity.

Using guanidine-HCl extraction, acetone precipitation, ultra-filtration and chromatography, a novel polypeptide with potent anti-angiogenic activity was purified from cartilage of the shark, Prionace glauca. N-terminal amino acid sequence analysis and SDS-PAGE revealed that the substance is a novel polypeptide with MW 15500 (PG155). The anti-angiogenic effects of PG155 were evaluated using zebrafish embryos model in vivo.

Salvicine functions as novel topoisomerase II poison by binding to ATP pocket.

Salvicine, a structurally modified diterpenoid quinone derived from Salvia prionitis, is a nonintercalative topoisomerase II (topo II) poison. The compound possesses potent in vitro and in vivo antitumor activity with a broad spectrum of anti-multidrug resistance activity and is currently in phase II clinical trials. To elucidate the distinct antitumor properties of salvicine and obtain valuable structural information of salvicine-topo II interactions, we characterized the effects of salvicine on human topo IIalpha (htopo IIalpha), including possible binding sites and molecular interactions.