Nanosphere pharmacodynamics improves safety of immunostimulatory cytokine therapy.

Systemic administration of interleukin (IL)-12 induces potent anti-tumor immune responses in preclinical cancer models through the systemic activation of effector immune cells and release of proinflammatory cytokines. IL-12-loaded PLGA nanospheres (IL12ns) are hypothesized to improve therapeutic efficacy and thwart unwanted side effects observed in previous human clinical trials. Through the investigation of peripheral blood and local tissue immune responses in healthy BALB/c mice, the immune-protective pharmacodynamics of IL12ns were suggested.

Immunostaining for hepatitis B viral antigens in liver: Association with clinical, biochemical, and virologic features of disease.

Background And Aim: Staining for hepatitis B viral antigens is often done in liver biopsies from patients with chronic hepatitis B, but its correlates with clinical phenotypes are not well described.

Methods: Biopsies were collected from a large cohort of adults and children with chronic hepatitis B viral infection through the Hepatitis B Research Network. Immunohistochemical staining of sections was done for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and then centrally read by the pathology committee.

A Locus on Chromosome 15 Contributes to Acute Ozone-induced Lung Injury in Collaborative Cross Mice.

Ozone (O)-induced respiratory toxicity varies considerably within the human population and across inbred mouse strains, indicative of gene-environment interactions (GxE). Though previous studies have identified several quantitative trait loci (QTL) and candidate genes underlying responses to O exposure, precise mechanisms of susceptibility remain incompletely described. We sought to update our understanding of the genetic architecture of O responsiveness using the Collaborative Cross (CC) recombinant inbred mouse panel.

A Prospective Cohort Study of Novel Markers of Hepatitis B Virus Replication in Human Immunodeficiency Virus Coinfection.

Background & Aims: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining.

Methods: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study.

Transcriptome and Exome Analyses of Hepatocellular Carcinoma Reveal Patterns to Predict Cancer Recurrence in Liver Transplant Patients.

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. Liver transplantation has been an effective approach to treat liver cancer. However, significant numbers of patients with HCC experience cancer recurrence, and the selection of suitable candidates for liver transplant remains a challenge.

Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha-Methylacyl-Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen-Activated Protein Kinase.

Chromosome rearrangement is one of the hallmarks of human malignancies. Gene fusion is one of the consequences of chromosome rearrangements. In this report, we show that gene fusion between solute carrier family 45 member 2 (SLC45A2) and alpha-methylacyl-coenzyme A racemase (AMACR) occurs in eight different types of human malignancies, with frequencies ranging from 45% to 97%.

Delivery of Cinnamic Aldehyde Antioxidant Response Activating nanoParticles (ARAPas) for Vascular Applications.

Selective delivery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators to the injured vasculature at the time of vascular surgical intervention has the potential to attenuate oxidative stress and decrease vascular smooth muscle cell (VSMC) hyperproliferation and migration towards the inner vessel wall. To this end, we developed a nanoformulation of cinnamic aldehyde (CA), termed Antioxidant Response Activating nanoParticles (ARAPas), that can be readily loaded into macrophages ex vivo. The CA-ARAPas-macrophage system was used to study the effects of CA on VSMC in culture.

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

Objective: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm).

Co-exposure to inorganic arsenic and fluoride prominently disrupts gut microbiota equilibrium and induces adverse cardiovascular effects in offspring rats.

Co-exposure to inorganic arsenic (iAs) and fluoride (F) and their collective actions on cardiovascular systems have been recognized as a global public health concern. Emerging studies suggest an association between the perturbation of gut bacterial microbiota and adverse cardiovascular effects (CVEs), both of which are the consequence of iAs and F exposure in human and experimental animals. The aim of this study was to fill the gap of understanding the relationship among co-exposure to iAs and F, gut microbiota perturbation, and adverse CVEs.

Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings.

Inactivation of Pten gene through deletions and mutations leading to excessive pro-growth signaling pathway activations frequently occurs in cancers. Here, we report a Pten derived pro-cancer growth gene fusion Pten-NOLC1 originated from a chr10 genome rearrangement and identified through a transcriptome sequencing analysis of human cancers. Pten-NOLC1 fusion is present in primary human cancer samples and cancer cell lines from different organs.

Donor derived hepatitis B virus infection: Analysis of the Organ Procurement & Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee.

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009-2017. Proven, probable or possible transmission of HBV occurred in 25 (23.

Ten years of donor-derived disease: A report of the disease transmission advisory committee.

Despite clinical and laboratory screening of potential donors for transmissible disease, unexpected transmission of disease from donor to recipient remains an inherent risk of organ transplantation. The Disease Transmission Advisory Committee (DTAC) was created to review and classify reports of potential disease transmission and use this information to inform national policy and improve patient safety. From January 1, 2008 to December 31, 2017, the DTAC received 2185 reports; 335 (15%) were classified as a proven/probable donor transmission event.

Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome.

Background: Hepatic angiomyolipoma (HAML) may easily be misdiagnosed as a malignancy. The study aim was to assess diagnostic dilemmas, clinical management and outcome of this rare tumor.

Methods: This retrospective international multicenter study included all patients with pathologically proven HAML diagnosed between 1997 and 2017.

Renal cell carcinoma suspected at time of organ donation 2008-2016: A report of the OPTN ad hoc Disease Transmission Advisory Committee Registry.

All 179 reports to the OPTN of potential renal cell carcinoma (RCC) transmission from 1/1/2008 through 12/31/2016 were reviewed. Cases were divided into those with donor tumor known or suspected at time of transplant (N = 147 donors), and those in which tumor was initially found after transplant (N = 32). We sought to understand the risk of transplanting either the affected kidney, the contralateral kidney or non-renal organs from donors with a suspected/confirmed unilateral RCC.

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

Objective: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens.

Design: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures.

Identification of recurrent fusion genes across multiple cancer types.

Chromosome changes are one of the hallmarks of human malignancies. Chromosomal rearrangement is frequent in human cancers. One of the consequences of chromosomal rearrangement is gene fusions in the cancer genome.

Hepatic Angiosarcoma: A Multi-institutional, International Experience with 44 Cases.

Background: Hepatic angiosarcoma is a rare primary liver tumor. The aim of this current study was to evaluate the presentation and treatment outcomes in a modern cohort.

Methods: This was a retrospective, multi-institutional, observational study of patients with histopathologic diagnoses of primary hepatic angiosarcoma from four institutions.

Circular DNA tumor viruses make circular RNAs.

Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) cause ∼2% of all human cancers. RNase R-resistant RNA sequencing revealed that both gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV abundantly expressed both exon-only and exon-intron circRNAs from the BamHI A rightward transcript (BART) locus (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA region.

MAN2A1-FER Fusion Gene Is Expressed by Human Liver and Other Tumor Types and Has Oncogenic Activity in Mice.

Background & Aims: Human tumors and liver cancer cell lines express the product of a fusion between the first 13 exons in the mannosidase α class 2A member 1 gene (MAN2A1) and the last 6 exons in the FER tyrosine kinase gene (FER), called MAN2A1-FER. We investigated whether MAN2A1-FER is expressed by human liver tumors and its role in liver carcinogenesis.

Methods: We performed reverse transcription polymerase chain reaction analyses of 102 non-small cell lung tumors, 61 ovarian tumors, 70 liver tumors, 156 glioblastoma multiform samples, 27 esophageal adenocarcinomas, and 269 prostate cancer samples, as well as 10 nontumor liver tissues and 20 nontumor prostate tissues, collected at the University of Pittsburgh.