Search results for "HEP"
showing 10 items of 12243 documents
Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - The SHELTER study
2016
Background & Aims No established therapies for patients with hepatocellular carcinoma (HCC) and progression on first-line sorafenib treatment currently exist. This phase I/II trial investigated safety, pharmacokinetics and potential biomarkers of the histone deacetylase inhibitor resminostat and a combination therapy with resminostat and sorafenib. Methods Patients with HCC and radiologically confirmed progression on sorafenib were treated in an exploratory, multi-center, open-label, uncontrolled, non-randomized, parallel group phase I/II study. In the combination group (n=38) four dose levels ranged from daily 200 to 600mg resminostat plus 400 to 800mg sorafenib. The monotherapy group (n=1…
International consensus guidelines for scoring the histopathological growth patterns of liver metastasis
2017
BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver var…
Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis.
2016
Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metast…
Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence.
2018
Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the sixth leading cause of cancer and the third leading cause of cancer-related mortality. Patient stratification and treatment allocation are based on tumor stage, liver function, and performance status. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate stage HCC, including those with large or multinodular HCC, well-preserved liver function, and no cancer-related symptoms or evidence of vascular invasion or extrahepatic spread. Two TACE techniques have been used since 2004, convent…
SENP1 activity sustains cancer stem cell in hypoxic HCC
2017
Hepatocellular carcinoma (HCC) represents the fifth most common cancer and the third leading cause of cancer mortality worldwide, with a minority of patients surviving at 5 years from diagnosis, despite treatment.1 HCC usually develops in conditions of chronic liver disease (CLD), mostly on the background of a cirrhotic liver, with liver transplantation at present being the only treatment strategy to cure both HCC and the specific CLD. All the other therapeutic strategies, because of the underlying liver cirrhosis, have to take into account, and may be limited in their feasibility, by the residual liver function of the individual patient, a critical parameter affecting the patient's prognos…
Innovative Therapeutic Strategies Targeting Colorectal Cancer Stem Cells
2017
Colorectal cancer is the fourth most common cause of cancer-related death. Although many advances in the treatment of this disease have been made, a large number of patients develop metastasis and resistance to current therapies. The current evidence indicates that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) have crucial roles in colorectal carcinogenesis and metastasis. It is also very important to understand the mechanisms that allow the survival of CSCs, such as metabolic reprogramming, which permits them to obtain specific properties or the activation of alternative signaling pathways in response to first-line therapies. In this review, we discuss the failure…
Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer
2015
Abstract Aim A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer. Methods By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to …
Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve patients’ selection
2018
The identification of reliable predictive biomarkers of efficacy or resistance to immune-oncology (I–O) agents is a major issue for translational research and clinical practice. However, along with PDL1 and molecular features other clinical, radiological and laboratory factors can be considered for the selection of those patients who would not be the best candidate for immune-checkpoint inhibitors (ICPIs). We examined these factors, emerging from the results of currently available studies in non-small cell lung cancer (NSCLC), aiming to provide a useful and manageable tool which can help Oncologists in their everyday clinical practice. A thorough patient evaluation and close clinical monito…
Contribution of the Cancer Stem Cell Phenotype to Hepatocellular Carcinoma Resistance
2017
The cancer stem cell (CSC) hypothesis is an increasingly accepted concept in cancer research that provides a plausible explanation for the considerable phenotypic and molecular heterogeneities observed in hepatocellular carcinoma (HCC) which hampers therapeutic progress. The hypothesis infers that CSCs share functional properties similar to adult stem cells, such as self-renewal and differentiation capacity, and are exclusively responsible for tumor evolution. By definition, CSCs are held responsible not only for tumor initiation and progression but also acquisition of chemoresistance and the fueling of relapse after therapy. Therefore, the CSC model has significant implications both for tr…
Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins
2017
MF6p/FhHDM-1 is a small cationic heme-binding protein which is recognized by the monoclonal antibody (mAb) MF6, and abundantly present in parenchymal cells and secreted antigens of Fasciola hepatica. Orthologs of this protein (MF6p/HDMs) also exist in other causal agents of important foodborne trematodiasis, such as Clonorchis sinensis, Opisthorchis viverrini and Paragonimus westermani. Considering that MF6p/FhHDM-1 is relevant for heme homeostasis in Fasciola and was reported to have immunomodulatory properties, this protein is expected to be a useful target for vaccination. Thus, in this study we mapped the epitope recognized by mAb MF6 and evaluated its antigenicity in sheep. The sequenc…