The Treatment Landscape of Advanced Hepatocellular Carcinoma.

The systemic treatment of advanced hepatocellular carcinoma (HCC) has significantly evolved. Immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy and more favorable toxicity profiles compared to multikinase inhibitors. Combination therapy with ICIs may provide greater anti-tumor activity compared to ICI monotherapy.

Untangling the Multidisciplinary Care Web: Streamlining Care Through an Immune-Related Adverse Events (IRAE) Tumor Board.

Immune-related adverse events (IRAEs) are becoming increasingly common as the use of immune checkpoint inhibitors expands into more tumor types and treatment settings. Although the majority of IRAEs are mild and can be managed in the outpatient setting by the medical oncologist, severe IRAEs can be life threatening and often require complex care coordination among multiple providers. These providers include a variety of non-oncology specialists who have interest and expertise in managing IRAEs.

Investigating the Impact of Geographic Location on Colorectal Cancer Stage at Diagnosis: A National Study of the SEER Cancer Registry.

Background: Early detection of colorectal cancer (CRC) is associated with decreased mortality and potential avoidance of chemotherapy. CRC screening rates are lower in rural communities and patient outcomes are poorer. This study examines the extent to which United States' rural residents present at a more advanced stage of CRC compared to nonrural residents.

Biomarker-Driven and Molecular Targeted Therapies for Hepatobiliary Cancers.

The recent accumulation of molecular profiling data for primary hepatobiliary malignancies, including hepatocellular carcinoma and biliary tract cancers, has led to a proliferation of promising therapeutic investigations in recent years. Treatment with pathway-specific targeted inhibitors and immunotherapeutic agents have demonstrated promising early clinical results. Key molecular alterations in common hepatobiliary cancers and ongoing interventional clinical trials of molecularly targeted systemic agents focusing on hepatocellular carcinoma and biliary tract cancer are reviewed.

Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Purpose: MINT1526A is a monoclonal antibody that blocks the interaction of integrin alpha 5 beta 1 (α5β1) with its extracellular matrix ligands. This phase I study evaluated the safety and pharmacokinetics of MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Methods: MINT1526A was administered every 3 weeks (Q3W) as monotherapy (arm 1) or in combination with bevacizumab 15 mg/kg, Q3W (arm 2).

Targeting the Tumor Stroma: the Biology and Clinical Development of Pegylated Recombinant Human Hyaluronidase (PEGPH20).

The tumor stroma is increasingly recognized as a key player in tumorigenesis through its effects on cell signaling, immune responses, and access of therapeutic agents. A major component of the extracellular matrix is hyaluronic acid (HA), which raises the interstitial gel fluid pressure within tumors and reduces drug delivery to malignant cells, and has been most extensively studied in pancreatic ductal adenocarcinoma (PDA). Pegylated recombinant human hyaluronidase (PEGPH20) is a novel agent that degrades HA and normalizes IFP to enhance the delivery of cytotoxic agents.

Targeting the protein ubiquitination machinery in melanoma by the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924).

Background The neddylation pathway conjugates NEDD8 to cullin-RING ligases and controls the proteasomal degradation of specific proteins involved in essential cell processes. Pevonedistat (MLN4924) is a selective small molecule targeting the NEDD8-activating enzyme (NAE) and inhibits an early step in neddylation, resulting in DNA re-replication, cell cycle arrest and death. We investigated the anti-tumor potential of pevonedistat in preclinical models of melanoma.

A Cost-Effectiveness Analysis of Using the JBR.10-Based 15-Gene Expression Signature to Guide Adjuvant Chemotherapy in Early Stage Non-Small-Cell Lung Cancer.

Background: Adjuvant chemotherapy (ACT) improved survival in the NCIC Clinical Trials Group JBR.10 trial of resected stage IB/II non-small-cell lung cancer. A prognostic 15-gene expression signature was developed, which may also predict for benefit from ACT.

Validation of a robust PCR-based assay for quantifying fragile X CGG repeats.

Background: Sizing of FMR1 trinucleotide repeats in the clinical laboratory requires the use of capillary sequencer by PCR, or by a labor intensive measurement using Southern blot method. Our aim was to validate an accurate and robust PCR assay for quantification of CGG repeats.

Methods: We performed an analytical and clinical validation of a new PCR-based method that utilizes a low-cost capillary electrophoresis instrument and the FragilEase™ reagent kit.

The changing landscape of phase I trials in oncology.

Advances in our knowledge of the molecular pathogenesis of cancer have led to increased interest in molecularly targeted agents (MTAs), which target specific oncogenic drivers and are now a major focus of cancer drug development. MTAs differ from traditional cytotoxic agents in various aspects, including their toxicity profiles and the potential availability of predictive biomarkers of response. The landscape of phase I oncology trials is evolving to adapt to these novel therapies and to improve the efficiency of drug development.

A comparison of parecoxib and thoracic epidural analgesia for postoperative analgesia following Nuss procedure.

Background: The purpose of this study was to compare the results of thoracic epidural analgesia (TEA) and parecoxib in controlling postoperative pain after the Nuss procedure.

Methods: Between August 2005 and July 2014, 120 adolescents and adults underwent Nuss procedures and received either TEA or parecoxib for postoperative pain control. Demographic data, preoperative preparation times, visual analog scale (VAS) pain scores from postoperative day 1 to day 5, medical costs of pain control, days to Foley catheter removal, days to being able to sit up, days to being able to walk, days of hospital stay, nausea/vomiting scores, and complications related to pain control were compared.

Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers.

Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.

Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly.

Incidence and risk factors for early hepatotoxicity and its impact on survival in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) is commonly associated with hepatic complications. Patients with myelofibrosis (MF) often develop liver dysfunction in the early posttransplantation period; however, this has not yet been studied in a systematic fashion. We retrospectively evaluated 53 patients with MF who underwent HCT to assess the prevalence of acute liver toxicity and risk factors and the impact on survival.

Unraveling the genetics of cancer: genome sequencing and beyond.

Advances in next-generation sequencing technology are enabling the systematic analyses of whole cancer genomes, providing insights into the landscape of somatic mutations and the great genetic heterogeneity that defines the unique signature of an individual tumor. Moreover, integrated studies of the genome, epigenome, and transcriptome reveal mechanisms of tumorigenesis at multiple levels. Progress in sequencing technologies and bioinformatics will improve the costs, sensitivity, and accuracy of detecting somatic mutations, while large-scale projects are underway to coordinate cancer genome sequencing at the global level to facilitate the generation and dissemination of high-quality uniform genetic data.

The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection.

Background & Aims: This report describes the use of a novel sensitive and specific ELISA for the measurement of human fibrinogen-like protein 2 (FGL2/fibroleukin), a novel effector of natural regulatory T (Treg) cells, to predict the course of chronic hepatitis C viral infection (HCV).

Methods: Plasma levels of FGL2 were measured in HCV patients and compared to healthy controls and to patients with alcoholic liver disease.

Results: FGL2 levels were significantly higher in HCV patients (84.

The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis.

Unlabelled: Fulminant viral hepatitis (FH) remains an important clinical problem in which the underlying pathogenesis is not well understood. Here, we present insight into the immunological mechanisms involved in FH caused by murine hepatitis virus strain 3 (MHV-3), indicating a critical role for CD4(+)CD25(+) regulatory T cells (Tregs) and production of the novel Treg effector molecule FGL2. Before infection with MHV-3, susceptible BALB/cJ mice had increased numbers of Tregs and expression of fgl2 messenger RNA (mRNA) and FGL2 protein compared with resistant A/J mice.

Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis.

Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild-type recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, Th 1 polarization, and increased numbers of Ab-producing B cells following immunization with T-independent Ags.

Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive.

Intubation conditions with low dose rocuronium under sevoflurane induction for children.

Background: During short surgical procedures and when there is a need to avoid the use of anticholinesterase at the end of surgery, the use of a smaller intubation dose of neuromuscular blocking drug is preferred. The aim of this study was to evaluate tracheal intubation conditions using smaller doses of rocuronium for children under sevoflurane induction.

Methods: Eighty American Society of Anesthesiologists classification physical status I or II children were enrolled.

Caudal epidural block for minor gynecologic procedures in outpatient surgery.

Background: Caudal epidural block (CEB) has become increasingly important for pediatric analgesia in recent years. However, data regarding CEB in adult ambulatory surgery are scarce. The aim of this study was to verify whether CEB could be applied as a simple, safe and economic method of anesthesia for adult patients undergoing minor gynecologic procedures (MGP).

Aspiration of a dislodged endotracheal tube: a rare cause of acute total airway obstruction.

We report an unusual cause of acute total airway obstruction after aspiration of a dislodged tube that was separated from its metallic connector. A 5-year-old boy had an emergence agitation and bucking to the endotracheal tube with a vigorous bite before extubation of the trachea. The whole uncuffed endotracheal tube was aspirated deep into the lower trachea causing laryngotracheal obstruction.