Search results for " multidrug resistance"
showing 10 items of 29 documents
Tumor Microenvironment And Epithelial Mesenchymal Transition As Targets To Overcome Tumor Multidrug Resistance
2020
It is well established that multifactorial drug resistance hinders successful cancer treatment. Tumor cell interactions with the tumor microenvironment (TME) are crucial in epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). TME-induced factors secreted by cancer cells and cancer-associated fibroblasts (CAFs) create an inflammatory microenvironment by recruiting immune cells. CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) and inflammatory tumor associated macrophages (TAMs) are main immune cell types which further enhance chronic inflammation. Chronic inflammation nurtures tumor-initiating/cancer stem-like cells (CSCs), induces both EMT and MDR leading to tumor re…
Molecular bases of the poor response of liver cancer to chemotherapy
2018
Summary A characteristic shared by most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in adults, and in a lesser extent hepatoblastoma (HB) mainly in children, is their high refractoriness to chemotherapy. This is the result of synergic interactions among complex and diverse mechanisms of chemoresistance (MOC) in which more than 100 genes are involved. Pharmacological treatment, although it can be initially effective, frequently stimulates the expression of MOC genes, which results in the relapse of the tumor, usually with a more aggressive and less chemosensitive phenotype. Identification of the MOC genetic signature accounting fo…
Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline…
2017
Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Aci…
Italian young doctors’ knowledge, attitudes and practices on antibiotic use and resistance: A national cross-sectional survey
2020
Abstract Objectives Antimicrobial resistance (AMR) is one of the major health issues worldwide. Clinicians should play a central role to fight AMR, and medical training is a pivotal issue to combat it; therefore, assessing levels of knowledge, attitudes and practices among young doctors is essential for future antimicrobial stewardship (AMS) programmes. Methods A nationwide, cross-sectional, multicentre survey was conducted in Italy. A descriptive analysis of knowledge and attitudes was performed, along with a univariate and multivariate analysis of their determinants. Results Overall, 1179 young doctors accessed the survey and 1055 (89.5%) completed all sections. Regarding the knowledge se…
Efficiency of Target Larvicides Is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii
2018
Anisakiasis is among the most significant emerging foodborne parasitoses contracted through consumption of thermally unprocessed seafood harboring infective Anisakis species larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol and the conventional anthelminthics abamectin and levamisole in the presence/absence of MK-571 and Valspodar, which inhibit the ABC transporter proteins multidrug resistance protein (MRP-like) and P-glycoprotein (P-gp),…
Pharmacogenomics of Scopoletin in Tumor Cells
2016
Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS onc…
Chemoresistance and chemosensitization in cholangiocarcinoma
2017
One of the main difficulties in the management of patients with advanced cholangiocarcinoma (CCA) is their poor response to available chemotherapy. This is the result of powerful mechanisms of chemoresistance (MOC) of quite diverse nature that usually act synergistically. The problem is often worsened by altered MOC gene expression in response to pharmacological treatment. Since CCA includes a heterogeneous group of cancers their genetic signature coding for MOC genes is also diverse; however, several shared traits have been defined. Some of these characteristics are shared with other types of liver cancer, namely hepatocellular carcinoma and hepatoblastoma. An important goal in modern onco…
Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo
2021
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells v…
Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effe…
2004
<i>Background:</i> The effects of the A<sub>3</sub> adenosine receptor (A<sub>3</sub>AR) agonist IB-MECA were examined in HL-60 leukemia and in its multidrug-resistant variant HL-60R cells. <i>Methods:</i> Cytotoxicity was evaluated by MTS assays and apoptosis by flow cytometry analyses of DNA fragmentation and phosphatidylserine exposure. The mRNAs of A<sub>3</sub>AR and inhibitor of apoptosis proteins (IAPs) were determined by RT-PCR. <i>Results:</i> A<sub>3</sub>AR expression was similar in HL-60 and HL-60R cells. At ≧100 µ<i>M</i>, IB-MECA exhibited strong cytotoxic and apoptotic effects in H…
Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer
2009
We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system…