Search results for "Fen"
showing 10 items of 3710 documents
Development of an RNA-based kit for easy generation of TCR-engineered lymphocytes to control T-cell assay performance.
2018
Cell-based assays to monitor antigen-specific T-cell responses are characterized by their high complexity and should be conducted under controlled conditions to lower multiple possible sources of assay variation. However, the lack of standard reagents makes it difficult to directly compare results generated in one lab over time and across institutions. Therefore TCR-engineered reference samples (TERS) that contain a defined number of antigen-specific T cells and continuously deliver stable results are urgently needed. We successfully established a simple and robust TERS technology that constitutes a useful tool to overcome this issue for commonly used T-cell immuno-assays. To enable users t…
Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublis…
2018
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing…
Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placeb…
2018
Summary Background Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. Methods We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotec…
A phase 2 study of galunisertib (TGF-Β R1 inhibitor) and sorafenib in patients with advanced hepatocellular carcinoma (HCC).
2017
4097 Background: TGFβ signaling is associated with HCC progression. Inhibition of TGFβ R1 potentiates activity of sorafenib in in-vitro and in-vivo models. Here we report the clinical activity of galunisertib (G) plus sorafenib (S) in pts with incurable HCC and no prior systemic therapy. Methods: Eligibility criteria included incurable HCC with measurable disease per RECIST 1.1, no prior systemic therapy, Child Pugh A, ECOG PS ≤1.G was administered as 80 mg PO BID (lead-in Cohort 1) or 150 mg PO BID (lead-in Cohort 2 and expansion cohort), as intermittent dosing of 14 days on/off (28 days = 1 cycle). S was administered continuously as a 400 mg PO BID. Primary objective was to characterize …
Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells
2017
BACKGROUND: Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. METHODS: 24 hour fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cyto…
Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines
2017
Background Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. Methods Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated. Radiosensitizing effects were functionally assessed by annexin-V apoptosis and clonogenic assays and confirmed by Western blot. Additionally, we surveyed human HNSCC tissue …
Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a rando…
2019
PMC6682346; Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naive hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion fol…
The role of molecular enrichment on future therapies in hepatocellular carcinoma
2017
Summary Hepatocellular carcinomas (HCCs) are characterised by considerable phenotypic and molecular heterogeneity. Treating HCC and designing clinical trials are particularly challenging because co-existing liver disease, present in most patients, limits aggressive therapeutic options. Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities. However, failure of several large randomised controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of tran…
Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference
2020
Proper trial design is critical for the success of clinical investigations. Hepatocellular carcinoma (HCC) is a complex disease that has several unique properties. In 2008, after the approval of sorafenib, a panel of experts proposed guidelines for trial design and endpoints in HCC that have been instrumental during the last decade and provided a framework to allow an homogeneous analysis of reported investigations. Since then, several phase III studies have been reported and novel challenges have emerged. A panel of experts conveyed by AASLD organized a Special Topic Conference on trial design and endpoints to address those emerging challenges. This review summarizes the analysis and concl…
Role of the antioxidant defence system and telomerase in arsenic-induced genomic instability
2016
Arsenic (AS) is a reactive oxygen species (ROS)-inducer carcinogen, whose mode of action is still unclear. To defend against ROS, cells use enzymatic and non-enzymatic antioxidants, such as superoxide dismutase (SOD) and catalase. Failure of antioxidant systems (AXS) can result in dicentric chromosomes formation as well as telomere associations for the reduced activity of telomerase. In order to clarify the long-term effects of a past AS exposure, we evaluated the efficiency of the AXS and the telomerase activity in the progeny of arsenite-treated cells named ASO (arsenic shake-off) cells, previously obtained from arsenite-treated V79 cells and selected by shake-off. Despite SOD1 expression…