Search results for "adenocarcinoma"
showing 10 items of 589 documents
Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma
2016
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrin…
Ellagitannin-rich cloudberry inhibits hepatocyte growth factorinduced cell migration and phosphatidylinositol 3-kinase/AKT activation in colon carcin…
2016
// Anne-Maria Pajari 1, 2 , Essi Paivarinta 1 , Lassi Paavolainen 3 , Elina Vaara 1 , Tuuli Koivumaki 4 , Ritu Garg 5 , Anu Heiman-Lindh 1 , Marja Mutanen 1 , Varpu Marjomaki 3 , Anne J. Ridley 2, 5 1 Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, Helsinki, Finland 2 University College London, Ludwig Institute for Cancer Research, London, UK 3 Department of Biological and Environmental Science / Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland 4 Department of Food and Environmental Sciences, Division of Food Chemistry, University of Helsinki, Helsinki, Finland 5 Randall Division of Cell & Molecular Biophysics, King’s College Lond…
Multidisciplinary management of stage II-III gastric and gastro-oesophageal junction cancer.
2019
The aim of this manuscript is to discuss the viewpoint of the European Organisation for Research and Treatment of Cancer (EORTC) Gastric Cancer Taskforce and Japan Clinical Oncology Group (JCOG) Gastric Cancer Study Group on the current challenges in the multidisciplinary management of stage II-III gastric and gastro-oesophageal junction (GEJ) cancer. We seek to outline how these challenges are addressed in current trials of both groups. Key elements of future trials of EORTC and JCOG in this indication are described, and a joint vision on how multidisciplinary research of gastric and GEJ cancer patients should be organised is outlined. ispartof: EUROPEAN JOURNAL OF CANCER vol:124 pages:67-…
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
2018
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003–2011. Paired-end exome sequencing was…
JC Virus and Lung Adenocarcinoma: Fact or Myth?
2017
Background/aim An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis. Materials and methods Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR. Results Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. N…
Cross-Talk between Myeloid-Derived Suppressor Cells and Mast Cells Mediates Tumor-Specific Immunosuppression in Prostate Cancer.
2018
Abstract Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell–deficient KitWsh mice. TRAMP mice are tolerant to the SV40 Large T antigen, which is o…
Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro…
2018
BACKGROUND: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. PATIENTS AND METHODS: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, …
Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma
2021
A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…
PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability
2020
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 express…
Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium
2017
AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infe…