Preface: Acquired Resistance and Natural Insensitivity to Chemotherapeutic Drugs

2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fred E. Hahn
Keyword(s):  
Acquired Resistance ◽  
Chemotherapeutic Drugs

Molecular basis of bortezomib resistance: proteasome subunit β5 (PSMB5) gene mutation and overexpression of PSMB5 protein

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2489-2499 ◽  
Author(s):  
Ruud Oerlemans ◽  
Niels E. Franke ◽  
Yehuda G. Assaraf ◽  
Jacqueline Cloos ◽  
Ina van Zantwijk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Drug Resistance ◽  
Molecular Basis ◽  
Proteasome Inhibitor ◽  
Acquired Resistance ◽  
Binding Pocket ◽  
Cross Resistance ◽  
Chemotherapeutic Drugs ◽  
Proteasome Subunits

AbstractThe proteasome inhibitor bortezomib is a novel anticancer drug that has shown promise in the treatment of refractory multiple myeloma. However, its clinical efficacy has been hampered by the emergence of drug-resistance phenomena, the molecular basis of which remains elusive. Toward this end, we here developed high levels (45- to 129-fold) of acquired resistance to bortezomib in human myelomonocytic THP1 cells by exposure to stepwise increasing (2.5-200 nM) concentrations of bortezomib. Study of the molecular mechanism of bortezomib resistance in these cells revealed (1) an Ala49Thr mutation residing in a highly conserved bortezomib-binding pocket in the proteasome β5-subunit (PSMB5) protein, (2) a dramatic overexpression (up to 60-fold) of PSMB5 protein but not of other proteasome subunits including PSMB6, PSMB7, and PSMA7, (3) high levels of cross-resistance to β5 subunit-targeted cytotoxic peptides 4A6, MG132, MG262, and ALLN, but not to a broad spectrum of chemotherapeutic drugs, (4) no marked changes in chymotrypsin-like proteasome activity, and (5) restoration of bortezomib sensitivity in bortezomib-resistant cells by siRNA-mediated silencing of PSMB5 gene expression. Collectively, these findings establish a novel mechanism of bortezomib resistance associated with the selective overexpression of a mutant PSMB5 protein.

Probenazole induces systemic acquired resistance in Arabidopsis with a novel type of action

2001 ◽  
Vol 25 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Keiko Yoshioka ◽  
Hideo Nakashita ◽  
Daniel F. Klessig ◽  
Isamu Yamaguchi
Keyword(s):  
Systemic Acquired Resistance ◽  
Acquired Resistance

Parallel Acquired Resistance Heterogeneity: Novel Patient Derived Synchronous Cell Pair with Distinct Mutations in an ALK-Translocated Lung Adenocarcinoma

2019 ◽  
Author(s):  
Balazs Hegedüs ◽  
Paul Stockhammer ◽  
Till Plönes ◽  
Luca Hegedüs ◽  
Agnes Bankfalvi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Acquired Resistance ◽  
Cell Pair ◽  
Synchronous Cell

Antistaphylococcal activity of carbonic acid extract of hops

2018 ◽  
Vol 22 (2) ◽  
pp. 297-300
Author(s):  
V.V. Nevmerzhitsky ◽  
V.Yu. Ivannik ◽  
V.V. Kazmirchuk ◽  
T.N. Moiseenko ◽  
T.A. Volkov ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antimicrobial Agents ◽  
Carbonic Acid ◽  
Inflammatory Diseases ◽  
Acquired Resistance ◽  
Biologically Active ◽  
Antibacterial Drugs ◽  
Antistaphylococcal Activity ◽  
Prevention And Treatment ◽  
Main Disadvantage

The fight against staphylococcal infection, increasing the effectiveness of methods of prevention and treatment of diseases of staphylococcal etiology is of interest to scientists and practitioners, both in Ukraine and around the world. The urgency of this problem is growing rapidly, as there is a tendency to increase the resistance of not only staphylococci, but also other gram-positive bacteria. The spread of methicillin-resistant staphylococci restricts the choice of antibiotics for the treatment of diseases of staphylococcal etiology. Staphylococcus aureus is the most common and dangerous type, which is one of the main factors of purulent-inflammatory lesions of the skin and mucous membranes. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. One of the unique and promising medicinal plants, which contains a rich complex of biologically active substances (BAS), is common hops (Humulus lupulus L.). The complex of BAS (flavonoids, hormones, vitamins, bitter, phenolic compounds, essential oils) causes anti-inflammatory, bactericidal, hyposensitizing and analgesic action of hops. The purpose of this work is to determine the antistaphylococcal activity of the carbon dioxide extract of hops and to justify the development on its basis of new antimicrobial agents for the prevention and treatment of infectious and purulent-inflammatory diseases. The following methods were used: microbiological (method of diffusion into agar (well method)) and mathematical and statistical. The high antimicrobial activity of the carbon dioxide extract of hops has been established for museum test strains of the genus Staphylococcus. The results of the studies testify to the prospects of further study of the bactericidal properties of the extract of hops carbon dioxide with the aim of creating effective antimicrobial agents on its basis for the prevention and treatment of infectious and purulent-inflammatory diseases of staphylococcal etiology.

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