Search results for "Phenylurea Compounds"
showing 10 items of 93 documents
Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer
2020
Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 rece…
Kinase Inhibitors in Multitargeted Cancer Therapy
2017
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…
NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance
2016
AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…
Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational …
2019
Abstract Background Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. Methods The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adve…
Efficacy and Safety of the Oral Multikinase Regorafenib in Metastatic Colorectal Cancer.
2017
<b><i>Background/Aim:</i></b> A clinical trial demonstrated that treatment with oral multikinase regorafenib improved overall survival (OS), progression-free survival (PFS), and disease control [García-Alfonso et al.: J Clin Transl Oncol 2016;18:1072-1081; Bertocchi et al.: J Chemother 2017;29:102-105]. In this study, we aimed to evaluate its effectiveness in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) progressing after chemotherapy with docetaxel plus prednisone. <b><i>Materials and Methods:</i></b> 60 patients were enrolled. OS has been assessed as the primary endpoint while PFS, quality o…
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…
Nanoparticles of a polyaspartamide-based brush copolymer for modified release of sorafenib: In vitro and in vivo evaluation.
2017
Abstract In this paper, we describe the preparation of polymeric nanoparticles (NPs) loaded with sorafenib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer, named PHEA-BIB-ButMA (PBB), was synthesized by Atom Trasnfer Radical Polymerization (ATRP) starting from the α-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA) and poly butyl methacrylate (ButMA). Empty and sorafenib loaded PBB NPs were, then, produced by using a dialysis method and showed spherical morphology, colloidal size, negative ζ potential and the ability to allow a sustained sorafenib release in physiological environment. Sorafenib loaded PBB NPs were tested in vitro on HCC cells in order to e…
Preparation and Promotion of Fruit Growth in Kiwifruit of Fluorinated N-Phenyl-N‘-1,2,3-thiadiazol-5-yl Ureas
2004
Seventeen phenyl-fluorinated analogues of thidiazuron [N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea, TDZ] have been prepared and characterized. The effects of each fluorinated urea on growth and quality of kiwifruits (Actinidia deliciosa) were evaluated by comparison with untreated (control) and TDZ-treated fruits. The results obtained showed a clear dependence of the growth-promoting activity of these fluorinated ureas on the pattern and degree of fluorine substitution in the phenyl ring. The most effective for promoting fruit growth was N-(2,3,5,6-tetrafluorophenyl)-N'-(1',2',3'-thiadiazol-5'-yl)urea at 25 ppm (at harvest, treated fruits were 58% heavier than untreated ones) followed by N-(3,5…
Safety and Efficacy of Sorafenib in Patients With Advanced Hepatocellular Carcinoma in Consideration of Concomitant Stage of Liver Cirrhosis
2009
GOALS AND BACKGROUND: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. METHODS: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Fifteen patients…
A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
2021
Aim: To determine a recommended Phase II dose of the oral fluoropyrimidine trifluridine/tipiracil (FTD/TPI) combined with the multi-kinase inhibitor regorafenib (REG) in refractory metastatic colorectal cancer patients. Materials & methods: A conventional 3 + 3 dose finding design was used. FTD/TPI was administered on days 1–5 and 8–12 of a 28-day cycle, REG on days 2–22. Two dose levels were used: FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m2 b.i.d. + REG 120 mg/d. Results: In total, 12 patients were treated at two dose levels. Three dose-limiting toxicities were observed; all were grade 3 hypertension causally attributed to REG. Recommended Phase II dose …