Genetic Variant of PP2A Subunit Gene Confers an Increased Risk of Primary Liver Cancer in Chinese.

Background: Protein phosphatase 2A (PP2A, a serine/threonine phosphatase) is frequently inactivated in many types of cancer, including primary liver cancer (PLC). Genetic variations in PP2A subunits have been reported to be associated with the risk of many types of cancer but rarely in PLC. This study aims to assess the association between functional polymorphisms of PP2A subunit genes and the risk of PLC in Chinese.

Feasibility of using digital confocal microscopy for cytopathological examination in clinical practice.

Optical imaging modalities are emerging as digital microscopy tools for tissue examination. The investigation of these techniques for potential applications in anatomic pathology practice has focused primarily on surgical pathology and has not included cytopathological specimens. We evaluated the feasibility of using digital confocal microscopy (CM) to examine cytopathological specimens.

Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study.

Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen.

Comparison of Real-Time Fluorescence Confocal Digital Microscopy With Hematoxylin-Eosin-Stained Sections of Core-Needle Biopsy Specimens.

Importance: Strategies to procure high-quality core-needle biopsy (CNB) specimens are critical for making basic tissue diagnoses and for ancillary testing.

Objectives: To investigate acquisition of fluorescence confocal microscopy (FCM) images of interventional radiology (IR)-guided CNB in real time in the radiology suite and to compare the accuracy of FCM diagnoses with those of hematoxylin-eosin (H&E)-stained CNB sections.

Design, Setting, And Participants: In this diagnostic study, FCM imaging of IR-guided CNBs was performed in the radiology suite at a major cancer center for patients with an imaging abnormality from August 1, 2016, to April 30, 2019.

Confocal Fluorescence Microscopy Platform Suitable for Rapid Evaluation of Small Fragments of Tissue in Surgical Pathology Practice.

Context.—: Rapid advances in the fields of biophotonics, computer science, and instrumentation have allowed for high-resolution imaging of biologic tissues.

Objective.

RET Signaling in Prostate Cancer.

Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its coreceptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Because both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer.

Intraluminal tranexamic acid inhibits intestinal sheddases and mitigates gut and lung injury and inflammation in a rodent model of hemorrhagic shock.

Background: Intravenous tranexamic acid (TXA) is an effective adjunct after hemorrhagic shock (HS) because of its antifibrinolytic properties. TXA is also a serine protease inhibitor, and recent laboratory data demonstrated that intraluminal TXA into the small bowel inhibited digestive proteases and protected the gut. A Disintegrin And Metalloproteinase 17 (ADAM-17) and tumor necrosis factor α (TNF-α) are effective sheddases of intestinal syndecan-1, which when shed, exposes the underlying intestinal epithelium to digestive proteases and subsequent systemic insult.

Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice.

We have shown in a rodent model of hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces lung inflammation and injury that are correlated with restitution of syndecan-1. As the gut is believed to contribute to distant organ injury and inflammation after shock, the current study sought to determine if the protective effects of plasma would extend to the gut and to elucidate the contribution of syndecan-1 to this protective effect. We also examined the potential role of TNFα, and a disintegrin and metalloproteinase (ADAM)-17, both intestinal sheddases of syndecan-1.

Inhibition of ERK1/2 worsens intestinal ischemia/reperfusion injury.

Background: The role of extracellular signal-regulated protein kinase (ERK) in intestinal ischemia/reperfusion (I/R) injury has not been well investigated. The aim of the current study was to examine the effect of inhibition of the ERK pathway in an in vitro and in vivo model of intestinal I/R injury.

Methods: ERK1/2 activity was inhibited using the specific inhibitor, U0126, in intestinal epithelial cells under hypoxia/reoxygenation conditions and in mice subjected to 1 hour of intestinal ischemia followed by 6 hours reperfusion.

Protective role of p70S6K in intestinal ischemia/reperfusion injury in mice.

The mTOR signaling pathway plays a crucial role in the regulation of cell growth, proliferation, survival and in directing immune responses. As the intestinal epithelium displays rapid cell growth and differentiation and is an important immune regulatory organ, we hypothesized that mTOR may play an important role in the protection against intestinal ischemia reperfusion (I/R)-induced injury. To better understand the molecular mechanisms by which the mTOR pathway is altered by intestinal I/R, p70S6K, the major effector of the mTOR pathway, was investigated along with the effects of rapamycin, a specific inhibitor of mTOR and an immunosuppressant agent used clinically in transplant patients.

Syndecan 1 plays a novel role in enteral glutamine's gut-protective effects of the postischemic gut.

Syndecan 1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells and, like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan 1 would abrogate the gut-protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia-reperfusion (IR) was utilized.

Inhibition of the NADPH oxidase regulates heme oxygenase 1 expression in chronic myeloid leukemia.

Background: Patients with chronic myelogenous leukemia (CML) in blast crisis have a poor response to tyrosine kinase inhibitors designed to inhibit the breakpoint cluster region-v-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) oncogene. Recent work has demonstrated that heme oxygenase 1 (HO-1) expression is increased in BCR-ABL1-expressing cells and that the inhibition of HO-1 in CML leads to reduced cellular growth, suggesting that HO-1 may be a plausible target for therapy. The objective of the current study was to clarify the mechanism of HO-1 overexpression and the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a contributor to this mechanism in CML.

Arginine decreases peroxisome proliferator-activated receptor-γ activity via c-Jun.

We have previously shown in the post ischemic gut that enteral arginine enhanced injury and inflammation via c-Jun/AP-1 and abrogated peroxisome proliferator-activated receptor (PPAR) γ activity. In the current study, we investigated the mechanism by which arginine inhibited PPARγ in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPARγ transcriptional activity in a time and dose-dependent fashion.

Glutamine activates peroxisome proliferator-activated receptor-γ in intestinal epithelial cells via 15-S-HETE and 13-OXO-ODE: a novel mechanism.

Glutamine possesses gut-protective effects both clinically and in the laboratory. We have shown in a rodent model of mesenteric ischemia-reperfusion that enteral glutamine increased peroxisome proliferator-activated receptor-γ (PPAR-γ) and was associated with a reduction in mucosal injury and inflammation. The mechanism by which glutamine activates PPAR-γ is unknown, and we hypothesized that it was via a ligand-dependent mechanism.

Mammalian target of rapamycin regulates expression of β-catenin in hepatocellular carcinoma.

Although evidence has shown that both the mammalian target of rapamycin and β-catenin are involved in hepatocellular carcinoma, little is known about their relationship in pathogenesis of hepatocellular carcinoma. To investigate the expression of phosphorylated mammalian target of rapamycin and β-catenin and their prognostic impacts, as well as their relationship in hepatocellular carcinoma, we analyzed 63 human hepatocellular carcinoma samples by immunohistochemistry. Phosphorylated mammalian target of rapamycin cytoplasmic and β-catenin cytoplasmic/nuclear-positive immunoreactivities were observed in 63.

Enteral arginine modulates inhibition of AP-1/c-Jun by SP600125 in the postischemic gut.

We previously demonstrated that enteral arginine increased c-Jun/activator protein-1 (AP-1) DNA-binding activity and iNOS expression in a rodent model of mesenteric ischemia/reperfusion (I/R). The objective of this study was to specifically investigate the role of AP-1 in arginine's deleterious effect on the postischemic gut. We hypothesized that AP-1 inhibition would mitigate the effects of arginine.

Glutamine protects against apoptosis via downregulation of Sp3 in intestinal epithelial cells.

Glutamine plays a key role in intestinal growth and maintenance of gut function, and as we have shown protects the postischemic gut (Kozar RA, Scultz SG, Bick RJ, Poindexter BJ, Desoigne R, Weisbrodt NW, Haber MM, Moore FA. Shock 21: 433-437, 2004). However, the precise mechanisms of the gut protective effects of glutamine have not been well elucidated.

Identifying serological biomarkers of hepatocellular carcinoma using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy.

Lack of sensitive and specific biomarkers is a major reason for the high rate of hepatocellular carcinoma (HCC) related mortality. The aim of this study was to use surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS) technology to identify potential protein patterns specific for HCC. Eighty-one patients with hepatitis B-related HCC and 80 healthy controls were randomly divided into a training set (48 HCC, 47 controls) and a testing set (33 HCC, 33 controls).

Oxidative stress promotes transcriptional up-regulation of Fyn in BCR-ABL1-expressing cells.

Signaling initiated by the BCR-ABL1 kinase causes chronic myelogenous leukemia (CML). Recently, we reported that expression of Fyn, a Src kinase, is heightened in CML cells and patient specimens and confers in vitro and in vivo proliferative advantages. Fyn is regulated by redox, and because BCR-ABL1 raises intracellular oxidant levels, which have been implicated in CML progression, we explored the molecular regulation of Fyn.

Enteral glutamine: a novel mediator of PPARgamma in the postischemic gut.

Early enteral nutrition supplemented with glutamine, arginine, omega-3 fatty acids, and nucleotides has been shown to decrease infection complications in critically injured patients. Concern has been raised, however, that under conditions of hyperinflammation, these diets may be injurious through the induction of inducible NO synthase by enteral arginine. In a rodent model of gut ischemia/reperfusion, inflammation and injury are intensified by enteral arginine and abrogated by glutamine.

BCR-ABL1 mediates up-regulation of Fyn in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) invariably progresses to blast crisis, which represents the most proliferative phase of the disease. The BCR-ABL1 oncogene stimulates growth and survival pathways by phosphorylating numerous substrates, including various Src family members. Here we describe up-regulation, in contrast to activation, of the ubiquitously expressed Src kinase, Fyn, by BCR-ABL1.

[Expression and exon 3 mutation of beta-catenin in human hepatocellular carcinoma].

Background & Objective: South Guangxi is an area with high incidence of hepatocellular carcinoma (HCC), and with severe contamination of dietary aflatoxin B1 (AFB1). The activation of beta-Catenin is involved in many cancers. AFB1 may play a key role in hepatocarcinogenesis.

NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells.

The proteasome has been successfully targeted for the treatment of multiple myeloma and mantle cell lymphoma; however, in other hematologic malignancies, bortezomib has been less effective as a single agent. Here, we describe effects of NPI-0052, a novel proteasome inhibitor, in leukemia model systems. In cell lines, NPI-0052 inhibits all 3 proteolytic activities associated with the proteasome: chymotrypsin-, trypsin-, and caspase-like.