Search results for "Fluorou"

Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis

2011

Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…

Comparison of a 48-Hour Infusion of 5-Fluorouracil without Folinic Acid with 24-Hour Folinic Acid/5-Fluorouracil in Patients with Metastatic Colorect…

2003

<i>Background:</i> Out of various high-dose 5-fluorouracil (5-FU) regimens given with or without folinic acid (FA), the optimal 5-FU schedule has still to be defined as treatment for metastatic colorectal cancer (CRC). Consequently, we compared toxicity, response and survival following two FA/5-FU regimens in 55 CRC patients refractory to bolus FA/5-FU. <i>Methods:</i> Twenty-eight patients (group A) received 5-FU (60 mg/kg body weight) for 48 h, and 27 (group B) received 2-hour infusions of FA (500 mg/m<sup>2</sup>) and 24-hour infusions of 5-FU (2,600 mg/m<sup>2</sup>) until disease progression. <i>Results:</i> Both groups were a…

Discovery of SI 1/20 and SI 1/22 as Mutual Prodrugs of 5-Fluorouracil and Imidazole-Based Heme Oxygenase 1 Inhibitor with Improved Cytotoxicity in DU…

2023

: In this work, we extend the concept of 5-fluorouracil/heme oxygenase 1 (5-FU/HO-1) inhibitor hybrid as an effective strategy for enhancing 5-FU-based anticancer therapies. For this purpose, we designed and synthesized new mutual prodrugs, named SI 1/20 and SI 1/22, in which the two active parent drugs (i. e., 5-FU and an imidazole-based HO-1 inhibitor) were connected through an easily cleavable succinic linker. Experimental hydrolysis rate, and in silico ADMET predictions were indicative of good drug-likeness and pharmacokinetic properties. Novel hybrids significantly reduced the viability of prostate DU145 cancer cells compared to the parent compounds 5-FU and HO-1 inhibitor administered…

Composite nanoparticles based on hyaluronic acid chemically cross-linked with alpha,beta-polyaspartylhydrazide.

2007

In this paper, new composite nanoparticles based on hyaluronic acid (HA) chemically cross-linked with alpha,beta polyaspartylhydrazide (PAHy) were prepared by the use of a reversed-phase microemulsion technique. HA-PAHy nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence of the chemical cross-linking, dimensional analysis, and transmission electron micrography, showing a sub-micrometer size and spherical shape. Zeta potential measurements demonstrated the presence of HA on the nanoparticle surface. A remarkable affinity of the obtained nanoparticles toward aqueous media that simulate some biological fluids was found. Stability studies showed the absence of chem…

Liposomes as nonspecific nanocarriers for 5-Fluorouracil in the presence of cyclodextrins

2021

Abstract 5-Fluorouracil (5-FU) is one of anticancer drugs with broad activity. Due to its severe side effects, recent studies concentrate on new ways of directed 5-FU delivery and its release in ill tissue. One of selective carriers could be cyclodextrins and liposomes. The combination of novel methods, leading to formation of inclusion complexes (IC) between host molecule of β-cyclodextrin (β-CD) or 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 5-FU guest and its subsequent encapsulation in dipalmitoylphosphatidylcholine (DPPC) liposomes is studied experimentally in the present work. Several methods are applied to proof the encapsulation of the analysed drug and its release over time at 37 …

The actual management of colorectal liver metastases

2020

Colorectal cancer is one of the most frequent cancers in the world and between 50% and 60% of patients will develop colorectal liver metastases (CRLM) during the disease. There have been great improvements in the management of CRLM during the last decades. The combination of modern chemotherapeutic and biological systemic treatments with aggressive surgical resection strategies is currently the base for the treatment of patients considered unresectable until few years ago. Furthermore, several new treatments for the local control of CRLM have been developed and are now part of the arsenal of multidisciplinary teams for the treatment of these complex patients. The aim of this review was to s…

Analisi dei polimorfismi dei geni codificanti per l’enzima UDP-glucuronosiltrasferasi (UGT) e per l’enzima diidropirimidina deidrogenasi (DPD), corre…

2012

Relationship between Thymidylate synthase and p53 and response versus taxane adjuvant chemotherapy for breast carcinoma

2011

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients wit…

Hexyl aminolevulinate, 5‐aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non‐aggressive basal cell carcinomas:…

2020

Background In the photodynamic therapy (PDT) of non‐aggressive basal cell carcinomas (BCCs), 5‐aminolevulinic acid nanoemulsion (BF‐200ALA) has shown non‐inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL‐PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post‐treatment reaction), and cosmetic outcome of MAL, BF‐200 ALA, and low‐concentration HAL in the PDT of non‐aggressive BCCs. Methods Ninety‐eight histologically verified non‐aggressive BCCs met the inclusion criter…

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

2009

AIM: To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors, in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL), on overcoming TRAIL resistance in hepatocellular carcinoma (HCC) and to study the efficacy of agonistic TRAIL antibodies, as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS: Surface expression of TRAIL receptors (TRAIL-R1-4) and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting, respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNA…