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Journal articles on the topic 'Multiple resistance mechanisms'

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Published: 10 December 2022
Last updated: 28 January 2023

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1

EADY, E. ANNE, JEREMY I. ROSS, and JONATHAN H. COVE. "Multiple mechanisms of erythromycin resistance." Journal of Antimicrobial Chemotherapy 26, no. 4 (1990): 461–65. http://dx.doi.org/10.1093/jac/26.4.461.

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2

Barrio Garcia, Santiago, Umair Munawar, Thorsten Stuehmer, Hermann Einsele, and K. Martin Kortüm. "Molecular Resistance Mechanisms in Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 471. http://dx.doi.org/10.1182/blood-2018-99-118700.

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Abstract Mechanisms of drug resistance in Multiple Myeloma (MM) are poorly understood. Mutations and/or changes in the protein expression of the CRBN pathway and proteasome subunits have been identified to induce resistance to IMiDs and PIs. However, only few patients are affected by these alterations. To determine the specific genomic fingerprint of MM relapse we selected 57 MM patients from the CoMMpass trial (version IA11) that have genomic data of paired samples available (diagnosis/relapse). 35 of them have also sequential FISH-seq data. We focused on acquired mutations in first relapse and filtered all mutations and genetic alterations already present at diagnosis. Doing so, we found 1.274 mutations, representing an average of 23 new mutations/patient (range; 2-76). Of interest, 66% of the acquired mutations were present in a sub-clonal level (Variant read frequency (VRF) < 25%). Most common mutations include known hotspots of the RAS pathway (NRAS 12%, KRAS 7% and BRAF 4%). Notably, all 7 NRAS mutations in relapse were located at Q61K, suggesting a functional role of disease progression for this specific and known hotspot location. In total 5 of 35 cases (14%) with FISH-seq data developed a 17p13 deletion in relapse. Of these, three patients acquired a bi-allelic alteration in addition to a preexisting TP53 mutation and one developed a biallelic inactivation of TP53 (VRF = 100%), through parallel acquisition of del17p and TP53 mutation. Gain of 1q21 was observed in relapse in 5 of 35 (14%) cases, and one 1q gain was lost from diagnosis to relapse. Two cases (4%) presented mutations in IMiD treatment related genes, with two mutations in the CRBN pathway. One harbored a missense mutation in the Lenalidomide (LEN) degron sequence of IKZF3 (G159A) (VRF = 36%), known to be essential for the IMiD action in vitro, 45 months after continuous exposition to LEN . The other case presented two subclonal frameshift mutations in CUL4B (VRF = 5% and 32%), detected after more than three years of LEN containing therapy. We functionally validated in vitro LEN resistance through CRISPR/Cas9 knockout of CUL4B, suggesting a resistance inducing effect of the acquired CUL4B mutations. Six cases (11%) harbored acquired mutations in proteasome subunit genes (PSMC2, PSMC6, PSMD8, PSME4, PSMB9 (two mutations)), all of them had undergone prior proteasome inhibitor (PI) containing therapy. We validated earlier the 19S protein subunits PSMC6 and PSMC2 (KO and/or point mutations) as inducers of PI resistance in vitro, thus we hypothesize contribution to resistance induction / disease progression through these 19s mutations. Remarkably ubiquitin (E3, E2 and SUBs) and histone related genes (histones and histone methylases and deacetylases) were found mutated in 51% and 19% of the relapsed patients. Genes for drug transporters (ATP-binding cassette (ABC) and Solute Carrier (SLC) transporters) were hit in 32% of cases and genes for mucins (previously related with genotoxic agents and immunotherapy resistance) in 19%. Notably, RRBP1 presented 10 mutations in 6 patients (11%) with the mutations clustering within 30 amino-acids (aa) of exons 9 and 10 and 3 hotspots (2 patients each) in aa Q426P, K430R and Q436P. RRBP1 is involved in the binding of the ribosome to the endoplasmic reticulum (ER) and is related with the unfolded protein response and ER stress via GRP78. All the patients with RRBP1 mutations were pretreated with PI inhibitors and exhibited worst survival outcome affecting PFS (Pval<0.001) and OS (Pval=0.0016) in this limited dataset. The mutations were detected on average 433 days (range: 258-568) after diagnosis. Five of the 6 patients died on average 180 days after RRBP1 mutation detection (range: 18-446) further suggesting high risk features of such acquired mutations. In summary, we observe clonal selection of known high-risk related alterations like TP53 mutations, 17p deletions or 1q13 in early relapse data of the CoMMpass trial. Furthermore we identify RRBP1 mutations as a new acquired high-risk biomarker of MM. Alterations are specifically related to subclonal selection by therapy, thus we suggest that the definition of high-risk disease in MM needs to be revisited and should also include clonal selection processes under anti-tumor therapy. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
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3

Baguley, Bruce C. "Multiple Drug Resistance Mechanisms in Cancer." Molecular Biotechnology 46, no. 3 (August 18, 2010): 308–16. http://dx.doi.org/10.1007/s12033-010-9321-2.

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4

Deng, Wei, Zhiwen Duan, Yang Li, Cheng Peng, and Shuzhong Yuan. "Multiple Resistance Mechanisms Involved in Glyphosate Resistance in Eleusine indica." Plants 11, no. 23 (November 23, 2022): 3199. http://dx.doi.org/10.3390/plants11233199.

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Glyphosate is a non-selective herbicide and is widely used for weed control in non-cultivated land in China. One susceptible (S) and five putative glyphosate-resistant (R1, R2, R3, R4, and R5) Eleusine indica biotypes were selected to investigate their resistance levels and the potential resistance mechanisms. Based on the dose–response assays, the R3 and R5 biotypes showed a low-level (2.4 to 3.5-fold) glyphosate resistance, and the R1, R2, and R4 biotypes exhibited a moderate- to high-level (8.6 to 19.2-fold) resistance, compared with the S biotype. The analysis of the target-site resistance (TSR) mechanism revealed that the P106A mutation and the heterozygous double T102I + P106S mutation were found in the R3 and R4 biotypes, respectively. In addition, the similar EPSPS gene overexpression was observed in the R1, R2, and R5 biotypes, suggesting that additional non-target-site resistance (NTSR) mechanisms may contribute to glyphosate resistance in R1 and R2 biotypes. Subsequently, an RNA-Seq analysis was performed to identify candidate genes involved in NTSR. In total, ten differentially expressed contigs between untreated S and R1 or R2 plants, and between glyphosate-treated S and R1 or R2 plants, were identified and further verified with RT-qPCR. One ATP-binding cassette (ABC) transporter gene, one aldo-keto reductases (AKRs) gene and one cytochrome P450 monooxygenase (CytP450) gene were up-regulated in R1 or R2 plants. These results indicated that EPSPS overexpression, single or double mutation was a common TSR mechanisms in E. indica. Additional NTSR mechanisms could play an essential role in glyphosate resistance. Three genes, ABCC4, AKR4C10, and CYP88, could serve as important candidate genes and deserve further functional studies.
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5

Higgins, Christopher F. "Multiple molecular mechanisms for multidrug resistance transporters." Nature 446, no. 7137 (April 2007): 749–57. http://dx.doi.org/10.1038/nature05630.

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6

Nikesitch, Nicholas, and Silvia C. W. Ling. "Molecular mechanisms in multiple myeloma drug resistance." Journal of Clinical Pathology 69, no. 2 (November 23, 2015): 97–101. http://dx.doi.org/10.1136/jclinpath-2015-203414.

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7

Dimaano, Niña Gracel, Tohru Tominaga, and Satoshi Iwakami. "Thiobencarb resistance mechanism is distinct from CYP81A-based cross-resistance in late watergrass (Echinochloa phyllopogon)." Weed Science 70, no. 2 (January 20, 2022): 160–66. http://dx.doi.org/10.1017/wsc.2022.4.

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AbstractThe genetic and molecular basis of resistance evolution in weeds to multiple herbicides remains unclear despite being a great threat to agriculture. A population of late watergrass [Echinochloa phyllopogon (Stapf.) Koso-Pol.] was reported to exhibit resistance to ≥15 herbicides from six sites of action, including thiobencarb (TB). While previous studies disclosed that the resistance to a majority of herbicides such as acetolactate synthase (ALS) and acetyl-CoA carboxylase inhibitors is caused by the overexpression of herbicide-metabolizing cytochrome P450s (CYP81A12 and CYP81A21), the resistance mechanisms to some herbicides remain unknown. Here, we analyzed the resistance segregation in the progenies between resistant and sensitive populations and performed a transgenic plant sensitivity assay to resolve whether TB resistance is endowed by the same CYP81A12/21-based cross-resistance mechanism or other unknown multiple-resistance mechanisms. In the F6 progenies, resistance to the ALS inhibitor bensulfuron-methyl cosegregated with the resistances to many other herbicides under the CYP81A12/21-based cross-resistance mechanism; however, TB resistance segregated independently. Furthermore, CYP81A12/21 failed to confer TB resistance in transgenic Arabidopsis thaliana L. Heynh, thus confirming that TB resistance in resistant E. phyllopogon is not endowed by the two P450s that are responsible for the metabolism-based cross-resistance. This study provides evidence that resistance in E. phyllopogon to herbicides with multiple sites of action is endowed by both P450-based and other uncharacterized non–target site based mechanisms. Our findings add another layer in the understanding of resistance evolution to multiple herbicides in E. phyllopogon. Identification of the key genes endowing TB resistance will be the future direction of this research.
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8

Jiménez-Alcázar, Miguel, Álvaro Curiel-García, Paula Nogales, Javier Perales-Patón, Alberto J. Schuhmacher, Marcos Galán-Ganga, Lucía Zhu, Scott W. Lowe, Fátima Al-Shahrour, and Massimo Squatrito. "Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma." Molecular Cancer Therapeutics 20, no. 6 (April 12, 2021): 1029–38. http://dx.doi.org/10.1158/1535-7163.mct-20-0319.

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9

Vazquez, V. Figueroa, S. S. Mughal, B. Brors, and M. S. Raab. "Characterization of dabrafenib resistance mechanisms in multiple myeloma." European Journal of Cancer 61 (July 2016): S116. http://dx.doi.org/10.1016/s0959-8049(16)61411-9.

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10

Waldschmidt, Johannes M., Jake Kloeber, Tushara Vijaykumar, Antonis Kokkalis, Praveen Anand, Sayalee Potdar, Julia Frede, et al. "Determining resistance mechanisms in BRAF-mutated multiple myeloma." Clinical Lymphoma Myeloma and Leukemia 19, no. 10 (October 2019): e22. http://dx.doi.org/10.1016/j.clml.2019.09.032.

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11

Waldschmidt, Johannes M., Jake A. Kloeber, Tushara Vijaykumar, Antonis Kokkalis, Praveen Anand, Sayalee Potdar, Julia Frede, et al. "Determining Resistance Mechanisms in BRAF-mutated Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 316. http://dx.doi.org/10.1182/blood-2019-130313.

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Introduction: Constant clonal evolution and outgrowth of clones that harbor resistance mutations are likely explanations for the emergence of drug-resistant disease in multiple myeloma (MM). Activating mutations in BRAF, KRAS and NRAS have been suggested as potential therapeutic targets. In this study, we investigate resistance to BRAF inhibition in the context of BRAF-mutated MM which accounts for about 5-12% of all patients with relapsed/ refractory MM. Methods: Resistance to dabrafenib was modeled in vitro in the BRAF-mutated MM cell lines (MMCL) U266 (K601Nmut) and DP6 (BRAFV600Emut). Low-pass whole genome sequencing (LPWGS), RNA sequencing, ChIP sequencing and immunoblotting were performed for genomic, transcriptomic, epigenomic and molecular characterization. Functional validation was performed by genome editing using CRISPR/Cas9 technology. Results: Modeling of dabrafenib resistance in vitro revealed an initial decline of cell numbers, followed by a plateau phase and a gradual outgrowth of resistant cells after ~80 days of treatment. As expected, exposure of BRAFmut MMCL to dabrafenib led to initial downregulation of pERK and pMEK. At later timepoints, upregulation of pERK and pMEK was observed, suggesting that re-activation of the ERK/MEK pathway ultimately overcomes BRAF inhibition. This outgrowth was associated with highly distinct copy number profiles in each resistant clone, implying clonal selection with outgrowth of genetically resistant clones as one mechanism of drug resistance in MM. Additionally, we found that BRAF inhibition of BRAFmut MMCL promotes changes of the transcriptional circuitry that appears independent of clonal outgrowth of genetically resistant clones. These transcriptional changes were highly homogenous, occurred as early as 7-14 days after starting treatment and were associated with de-differentiation of MMCL into a more immature B lymphocytic phenotype. This phenotype was associated with greater mRNA expression of CD19 and CD81, as well as upregulation of the B-lymphocyte activation antigen B7-2 (CD86) and PI3K pathway genes. We next investigated if targeting the PI3K pathway and B7.2 can be exploited for effective killing of dabrafenib-resistant BRAFmut MM cells. Studies for the PI3Kδ inhibitor idelalisib in dabrafenib-persistent MMCL revealed higher sensitivity as compared to dabrafenib-naïve controls. Genome editing suggests a survival advantage for CD86WT as compared to CD86KO MMCL. Conclusions: Our data suggest that resistance to BRAF inhibition in vitro is mediated by two distinct mechanisms: 1) clonal outgrowth of genetically distinct resistant clones, and 2) transcriptional rewiring that leads to activation of alternative signaling pathways. The latter is characterized by changes in cellular differentiation and upregulation of PI3K and CD28/CD86 signaling. These concepts may provide a framework for revealing therapeutic vulnerabilities and to overcome drug resistance mediated by genetic heterogeneity in MM. Disclosures Munshi: Oncopep: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Oncopep: Consultancy; Abbvie: Consultancy; Adaptive: Consultancy; Amgen: Consultancy. Anderson:Sanofi-Aventis: Other: Advisory Board; Bristol-Myers Squibb: Other: Scientific Founder; Oncopep: Other: Scientific Founder; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Yee:Karyopharm: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Adaptive: Consultancy. Raje:Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Lohr:Celgene: Research Funding; T2 Biosystems: Honoraria. OffLabel Disclosure: Dabrafenib is a potent inhibitor of BRAF mutated at codon 600 (BRAFV600). Here we explored the efficacy of dabrafenib a preclinical model of multiple myeloma cell lines with BRAFV600E and BRAFK601N mutations.
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12

Murray, Megan Y., Martin J. Auger, and Kristian M. Bowles. "Overcoming bortezomib resistance in multiple myeloma." Biochemical Society Transactions 42, no. 4 (August 1, 2014): 804–8. http://dx.doi.org/10.1042/bst20140126.

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The introduction of the proteasome inhibitor bortezomib in 2003 significantly improved treatment of the B-cell malignancy MM (multiple myeloma). Relapse following bortezomib therapy is inevitable, however, and MM remains an incurable disease. In the present mini-review, we explore the mechanisms by which bortezomib resistance occurs in MM, including inherent and acquired mutation, and inducible pro-survival signalling. We also outline the importance of MM cell interaction with the BMSC (bone marrow stromal cell) microenvironment as a pro-survival mechanism, and examine some potential druggable targets within this milieu, such as IGFs (insulin-like growth factors) and Btk (Bruton's tyrosine kinase). Although our understanding of bortezomib resistance is far from complete, there are a number of scientific developments that can help inform clinical decisions in relapsed MM.
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13

Knievel, Judith, Wolfgang Schulz, Annemarie Greife, Christiane Hader, Tobias Lübke, Ingo Schmitz, Peter Albers, and Günter Niegisch. "Multiple Mechanisms Mediate Resistance to Sorafenib in Urothelial Cancer." International Journal of Molecular Sciences 15, no. 11 (November 7, 2014): 20500–20517. http://dx.doi.org/10.3390/ijms151120500.

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14

Thomson, Joshua J., Sarah C. Plecha, and Eric S. Krukonis. "Ail provides multiple mechanisms of serum resistance toYersinia pestis." Molecular Microbiology 111, no. 1 (October 26, 2018): 82–95. http://dx.doi.org/10.1111/mmi.14140.

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15

Huang, Ning, Juan Mao, Yan Zhao, Mingzhong Hu, and Xiaoyu Wang. "Multiple Transcriptional Mechanisms Collectively Mediate Copper Resistance inCupriavidus gilardiiCR3." Environmental Science & Technology 53, no. 8 (March 28, 2019): 4609–18. http://dx.doi.org/10.1021/acs.est.8b06787.

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16

Gaines, Todd A., Stephen O. Duke, Sarah Morran, Carlos A. G. Rigon, Patrick J. Tranel, Anita Küpper, and Franck E. Dayan. "Mechanisms of evolved herbicide resistance." Journal of Biological Chemistry 295, no. 30 (May 19, 2020): 10307–30. http://dx.doi.org/10.1074/jbc.rev120.013572.

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The widely successful use of synthetic herbicides over the past 70 years has imposed strong and widespread selection pressure, leading to the evolution of herbicide resistance in hundreds of weed species. Both target-site resistance (TSR) and nontarget-site resistance (NTSR) mechanisms have evolved to most herbicide classes. TSR often involves mutations in genes encoding the protein targets of herbicides, affecting the binding of the herbicide either at or near catalytic domains or in regions affecting access to them. Most of these mutations are nonsynonymous SNPs, but polymorphisms in more than one codon or entire codon deletions have also evolved. Some herbicides bind multiple proteins, making the evolution of TSR mechanisms more difficult. Increased amounts of protein target, by increased gene expression or by gene duplication, are an important, albeit less common, TSR mechanism. NTSR mechanisms include reduced absorption or translocation and increased sequestration or metabolic degradation. The mechanisms that can contribute to NTSR are complex and often involve genes that are members of large gene families. For example, enzymes involved in herbicide metabolism–based resistances include cytochromes P450, GSH S-transferases, glucosyl and other transferases, aryl acylamidase, and others. Both TSR and NTSR mechanisms can combine at the individual level to produce higher resistance levels. The vast array of herbicide-resistance mechanisms for generalist (NTSR) and specialist (TSR and some NTSR) adaptations that have evolved over a few decades illustrate the evolutionary resilience of weed populations to extreme selection pressures. These evolutionary processes drive herbicide and herbicide-resistant crop development and resistance management strategies.
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17

Maloney, Sara M., Camden A. Hoover, Lorena V. Morejon-Lasso, and Jenifer R. Prosperi. "Mechanisms of Taxane Resistance." Cancers 12, no. 11 (November 10, 2020): 3323. http://dx.doi.org/10.3390/cancers12113323.

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The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.
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18

Vivekanandhan, Sneha, and Keith L. Knutson. "Resistance to Trastuzumab." Cancers 14, no. 20 (October 19, 2022): 5115. http://dx.doi.org/10.3390/cancers14205115.

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One of the most impactful biologics for the treatment of breast cancer is the humanized monoclonal antibody, trastuzumab, which specifically recognizes the HER2/neu (HER2) protein encoded by the ERBB2 gene. Useful for both advanced and early breast cancers, trastuzumab has multiple mechanisms of action. Classical mechanisms attributed to trastuzumab action include cell cycle arrest, induction of apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). Recent studies have identified the role of the adaptive immune system in the clinical actions of trastuzumab. Despite the multiple mechanisms of action, many patients demonstrate resistance, primary or adaptive. Newly identified molecular and cellular mechanisms of trastuzumab resistance include induction of immune suppression, vascular mimicry, generation of breast cancer stem cells, deregulation of long non-coding RNAs, and metabolic escape. These newly identified mechanisms of resistance are discussed in detail in this review, particularly considering how they may lead to the development of well-rationalized, patient-tailored combinations that improve patient survival.
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19

Kim, Young-Joon, Si-Woo Lee, Jum-Rae Cho, Hyung-Man Park, and Young-Joon Ahn. "Multiple Resistance and Biochemical Mechanisms of Dicofol Resistance in Tetranychus urticae (Acari: Tetranychidae)." Journal of Asia-Pacific Entomology 10, no. 2 (June 2007): 165–70. http://dx.doi.org/10.1016/s1226-8615(08)60348-9.

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20

Nascimento, Adriana M., Gustavo H. Goldman, Steven Park, Salvatore A. E. Marras, Guillaume Delmas, Uma Oza, Karen Lolans, Michael N. Dudley, Paul A. Mann, and David S. Perlin. "Multiple Resistance Mechanisms among Aspergillus fumigatus Mutants with High-Level Resistance to Itraconazole." Antimicrobial Agents and Chemotherapy 47, no. 5 (May 2003): 1719–26. http://dx.doi.org/10.1128/aac.47.5.1719-1726.2003.

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ABSTRACT A collection of Aspergillus fumigatus mutants highly resistant to itraconazole (RIT) at 100 μg ml−1 were selected in vitro (following UV irradiation as a preliminary step) to investigate mechanisms of drug resistance in this clinically important pathogen. Eight of the RIT mutants were found to have a mutation at Gly54 (G54E, -K, or -R) in the azole target gene CYP51A. Primers designed for highly conserved regions of multidrug resistance (MDR) pumps were used in reverse transcriptase PCR amplification reactions to identify novel genes encoding potential MDR efflux pumps in A. fumigatus. Two genes, AfuMDR3 and AfuMDR4, showed prominent changes in expression levels in many RIT mutants and were characterized in more detail. Analysis of the deduced amino acid sequence encoded by AfuMDR3 revealed high similarity to major facilitator superfamily transporters, while AfuMDR4 was a typical member of the ATP-binding cassette superfamily. Real-time quantitative PCR with molecular beacon probes was used to assess expression levels of AfuMDR3 and AfuMDR4. Most RIT mutants showed either constitutive high-level expression of both genes or induction of expression upon exposure to itraconazole. Our results suggest that overexpression of one or both of these newly identified drug efflux pump genes of A. fumigatus and/or selection of drug target site mutations are linked to high-level itraconazole resistance and are mechanistic considerations for the emergence of clinical resistance to itraconazole.
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21

Kim, Young-Joon, Hyung-Man Park, Jum-rae Cho, and Young-joon Ahn. "Multiple Resistance and Biochemical Mechanisms of Pyridaben Resistance in Tetranychus urticae (Acari: Tetranychidae)." Journal of Economic Entomology 99, no. 3 (June 1, 2006): 954–58. http://dx.doi.org/10.1093/jee/99.3.954.

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22

Jones, Alfred. "BREEDING SWEETPOTATO FOR RESISTANCE TO MULTIPLE INSECT PESTS." HortScience 25, no. 9 (September 1990): 1177G—1178. http://dx.doi.org/10.21273/hortsci.25.9.1177.

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Sweetpotato [Ipomoea batatas (L.) Lam.] cultivars with high levels of resistance to root damaging insects have been developed through the collaborative efforts of a multidisciplinary research team. These resistances were combined with other traits necessary for a successful cultivar such as: disease resistances; high yield; long storage life; prolific sprout production; marketable root size, shape and skin at tributes; and culinary excellence. Adpotion of quantitative genetic principles, development of a wide gene base, sequential selection schemes, use of effective selection criteria and appropriate susceptible standards contributed to the program's success. These achievements were made with, little prior knowledge about inheritance patterns, gene action, mechanisms of resistance or a complete knowledge of the insects concerned. The value of insect resistant cultivars has become better appreciated with the recent decrease in chemical alternatives.
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Jones, Alfred. "BREEDING SWEETPOTATO FOR RESISTANCE TO MULTIPLE INSECT PESTS." HortScience 25, no. 9 (September 1990): 1177g—1178. http://dx.doi.org/10.21273/hortsci.25.9.1177g.

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Sweetpotato [Ipomoea batatas (L.) Lam.] cultivars with high levels of resistance to root damaging insects have been developed through the collaborative efforts of a multidisciplinary research team. These resistances were combined with other traits necessary for a successful cultivar such as: disease resistances; high yield; long storage life; prolific sprout production; marketable root size, shape and skin at tributes; and culinary excellence. Adpotion of quantitative genetic principles, development of a wide gene base, sequential selection schemes, use of effective selection criteria and appropriate susceptible standards contributed to the program's success. These achievements were made with, little prior knowledge about inheritance patterns, gene action, mechanisms of resistance or a complete knowledge of the insects concerned. The value of insect resistant cultivars has become better appreciated with the recent decrease in chemical alternatives.
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24

Zhu, Guangtao, Hao Wang, Haitao Gao, Ying Liu, Jun Li, Zhike Feng, and Liyao Dong. "Multiple Resistance to Three Modes of Action of Herbicides in a Single Italian Ryegrass (Lolium multiflorum L.) Population in China." Agronomy 13, no. 1 (January 10, 2023): 216. http://dx.doi.org/10.3390/agronomy13010216.

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Italian ryegrass (Lolium multiflorum L.), a cross-pollinated grass, is gradually becoming a predominant weed in wheat fields in China and is evolving resistance to many groups of herbicides. The aim of this study is to determine the resistance levels of a single L. multiflorum population from a wheat field in Henan Province China, to three modes of action (MoAs) of herbicides and to further characterize the potential resistance mechanisms. This L. multiflorum population evolved multiple herbicide resistances to pyroxsulam [acetolactate synthase (ALS)], pinoxaden [acetyl-CoA carboxylase (ACCase)] and isoproturon [photosystem II (PSII)]. Target-site resistance (TSR) mutations (Pro-197-Gln, Pro-197-Thr, and Trp-574-Leu) and non-target-site resistance (NTSR) mediated by cytochrome P450 monooxygenase (CYP450) genes were associated with pyroxsulam resistance. Pinoxaden resistance was conferred by two TSR mutations, which referred to a rare Ile-2041-Val mutation and a common Ile-1781-Leu mutation but with two different nucleotide substitutions (CTA/TTA). CYP450- and glutathione-S-transferase (GST)-mediated resistances were the main resistance mechanisms for this multiple herbicide-resistant (MHR) population to the PSII inhibitor isoproturon. This is the first case of a single L. multiflorum population evolving multiple resistance to three herbicide MoAs (ALS, ACCase and PSII) in China. Diverse resistance mechanisms including TSR and NTSR mean L. multiflorum exhibits a high degree of resistance plasticity.
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25

Saha, Mousumi, and Agniswar Sarkar. "Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century." Journal of Xenobiotics 11, no. 4 (December 13, 2021): 197–214. http://dx.doi.org/10.3390/jox11040013.

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With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.
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Hall, L. M., F. J. Tardif, and S. B. Powles. "Mechanisms of cross and multiple herbicide resistance in Alopecurus myosuroides and Lolium rigidum." Comptes rendus 75, no. 4 (April 12, 2005): 17–23. http://dx.doi.org/10.7202/706068ar.

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Alopecurus myosuroides and Lolium rigidum have developed resistance to herbicides with several modes of action in many herbicide classes. A. myosuroides biotype Peldon A1 from England exhibits non-target site cross resistance to substituted urea and aryloxyphenoxypropionate herbicides (APP) due to enhanced metabolism. L. rigidum biotype SLR 31 from Australia has multiple resistance mechanisms, including both non-target site cross resistance and target site cross resistance. The majority of the SLR 31 population has enhanced metabolism of chlorsulfuron and diclofop-methyl and a mechanism correlated with altered plasma membrane response, which correlates with resistance to some APP and cyclohexanedione (CHD) herbicides. A small proportion of the population also has target site cross resistance to APP and CHD herbicides. While A myosuroides and L. rigidum share common biological elements, they are not unique. Non-target site cross resistance and multiple herbicide resistance is predicted to develop in other weed species. The repercussions of cross and multiple resistance warrant proactive measures to prevent or delay onset.
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Saltarella, Ilaria, Vanessa Desantis, Assunta Melaccio, Antonio Giovanni Solimando, Aurelia Lamanuzzi, Roberto Ria, Clelia Tiziana Storlazzi, Maria Addolorata Mariggiò, Angelo Vacca, and Maria Antonia Frassanito. "Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma." Cells 9, no. 1 (January 9, 2020): 167. http://dx.doi.org/10.3390/cells9010167.

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Daratumumab (Dara) is the first-in-class human-specific anti-CD38 mAb approved for the treatment of multiple myeloma (MM). Although recent data have demonstrated very promising results in clinical practice and trials, some patients do not achieve a partial response, and ultimately all patients undergo progression. Dara exerts anti-MM activity via antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and immunomodulatory effects. Deregulation of these pleiotropic mechanisms may cause development of Dara resistance. Knowledge of this resistance may improve the therapeutic management of MM patients.
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Zhu, Yuan Xiao, Laura Ann Bruins, Joseph Ahmann, Cecilia Bonolo De Campos, Esteban Braggio, Xianfeng Chen, Mariano Arribas, Susie Darvish, Gregory J. Ahmann, and Rafael Fonseca. "Identifying Mechanisms Associated with Venetoclax Resistance in Multiple Myeloma (MM)." Blood 138, Supplement 1 (November 5, 2021): 2668. http://dx.doi.org/10.1182/blood-2021-153747.

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Abstract Venetoclax (VTX) is a selective small-molecule inhibitor of BCL-2 that exhibits antitumoral activity against MM cells presenting lymphoid features and those with translocation t(11;14). Despite its impressive clinical activity, VTX therapy for a prolonged duration can lead to drug resistance. Therefore, it is important to understand the underlying mechanisms of resistance in order to develop strategies to prevent or overcome resistance. In the present study, we established four VTX resistant human myeloma cell lines (HMCLs) from four sensitive HMCLs, including three with t(11;14), in culture with a stepwise increase in treatment dose with VTX. To identify the molecular basis of acquired VTX resistance, whole exon sequencing (WES), mRNA-sequencing (mRNAseq), and protein expression assays were performed in the four isogenic VTX-sensitive/resistant HMCLs and three MM patients with samples collected before VTX administration and after clinical resistance to the drug. Compared with sensitive cell lines and patient samples collected before VTX administration, mRNAseq analysis identified downregulation of BIM and upregulation of BCLXL in both resistant cell lines and MM cells from relapse patients. Other transcriptional changes detected included upregulation of AURKA, BIRC3, BIRC5, and IL32. Enrichment analysis of differentially expressed genes suggested involvement of PI3K and MAPK signaling, likely associated with cytokines, growth factors (EGF, FGF and IGF family members), and receptor tyrosine kinase (EGF and FGF). Western blot analysis was performed to compare BCL2 family expression in resistant cell lines versus sensitive cell lines and it showed upregulation of BCL2 survival members (such as MCL-1 and BCLXL), and downregulation of pro-apoptotic BH3 members (such as BIM and PUMA). BIM expression was completely lost in one resistant cell line, and introduction of exogenous BIM into this cell line enhanced VTX sensitivity. Interestingly, BCL2 was upregulated in some resistant cell lines generated after a long-term treatment with VTX, suggesting BCL2 expression level may not be suitable as a marker of VTX sensitivity for acquired resistance. Unlike in CLL, BCL2 mutations were not identified through WES in any resistant cell lines or primary patient sample harvested after relapse. While 8 genes were mutated in two resistant samples , no clear mutational pattern emerged . Based on the above, we further tested some specific inhibitors in in vitro or ex vivo cell models to help understanding resistant mechanism and identify strategies to overcome VTX resistance. We found that inhibition of MCL-1, with the compound S68345, substantially enhanced VTX sensitivity in three resistant HMCLs and in primary cells from one relapsed MM patient. A BCLXL inhibitor (A155463) only significantly enhanced VTX sensitivity in one resistant cell line after co-treatment with VTX. Co-treatment of the other three resistant cell lines with VTX, S68345 and A155463 resulted in the most synergistic anti-myeloma activity, suggesting those cell lines are co-dependent on MCL-1, BCLXL, and BCL2 for survival, although they are more dependent on MCL-1. We also found that inhibition of PI3K signaling, IGF1, RTK (EGF and FGF) and AURKA significantly increased VTX sensitivity, partially through downregulation of MCL-1, and BCLXL, and upregulation of BIM. Conventional anti-MM drugs such as dexamethasone, bortezomib and lenalidomide, were shown to have little activity on augmenting VTX sensitivity in most resistant cell lines. In summary, we find that acquired resistance to VTX in MM is largely associated with BCL2 family regulation, including upregulation of survival members such as MCL-1, BCLXL, BCL2, and downregulation of pro-apoptotic members, especially BIM. Our study also indicates that upstream signaling involved in BCL2 family regulation during acquired resistance is likely related to cytokine, growth factor, and/or RTK-induced cell signaling such as PI3K. Co-inhibition of MCL-1, or BCLXL, as well as the upstream PI3K, RTK (FGF and EGF), IGF-1 mediated signaling were effective in overcoming VTX resistance. Disclosures Fonseca: Mayo Clinic in Arizona: Current Employment; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; AbbVie: Consultancy; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees.
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29

Franssen, Laurens E., Claudia A. M. Stege, Sonja Zweegman, Niels W. C. J. van de Donk, and Inger S. Nijhof. "Resistance Mechanisms towards CD38−Directed Antibody Therapy in Multiple Myeloma." Journal of Clinical Medicine 9, no. 4 (April 22, 2020): 1195. http://dx.doi.org/10.3390/jcm9041195.

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Antibodies targeting CD38 are rapidly changing the treatment landscape of multiple myeloma (MM). CD38−directed antibodies have several mechanisms of action. Fc−dependent immune effector mechanisms include complement-dependent cytotoxicity (CDC), antibody−dependent cell−mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis. In addition, direct effects and immunomodulatory effects contribute to the efficacy of CD38−directed antibodies. Daratumumab, the first−in−class anti−CD38 monoclonal antibody, is now part of standard treatment regimens of both newly diagnosed as well as relapsed/refractory MM patients. The FDA has recently approved isatuximab in combination with pomalidomide and dexamethasone for relapsed/refractory MM patients after at least two prior therapies. Further, the other CD38−targeting antibodies (i.e., MOR202 and TAK-079) are increasingly used in clinical trials. The shift to front-line treatment of daratumumab will lead to an increase in patients refractory to CD38 antibody therapy already after first−line treatment. Therefore, it is important to gain insight into the mechanisms of resistance to CD38−targeting antibodies in MM, and to develop strategies to overcome this resistance. In the current review, we will briefly describe the most important clinical data and mechanisms of action and will focus in depth on the current knowledge on mechanisms of resistance to CD38-targeting antibodies and potential strategies to overcome this.
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Volm, M., and J. Mattern. "Detection of Multiple Resistance Mechanisms in Untreated Human Lung Cancer." Oncology Research and Treatment 16, no. 3 (1993): 189–94. http://dx.doi.org/10.1159/000218256.

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31

Sanglard, Dominique, Françoise Ischer, David Calabrese, Michelle de Micheli, and Jacques Bille. "Multiple resistance mechanisms to azole antifungals in yeast clinical isolates." Drug Resistance Updates 1, no. 4 (January 1998): 255–65. http://dx.doi.org/10.1016/s1368-7646(98)80006-x.

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32

Guerra, Beatriz, Burkhard Malorny, Andreas Schroeter, and Reiner Helmuth. "Multiple Resistance Mechanisms in Fluoroquinolone-Resistant Salmonella Isolates from Germany." Antimicrobial Agents and Chemotherapy 47, no. 6 (June 2003): 2059. http://dx.doi.org/10.1128/aac.47.6.2059.2003.

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33

Kaneti, Galoz, Hadar Sarig, Ibrahim Marjieh, Zaknoon Fadia, and Amram Mor. "Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus." FASEB Journal 27, no. 12 (August 22, 2013): 4834–43. http://dx.doi.org/10.1096/fj.13-237610.

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34

Albertson, G. D., M. Niimi, R. D. Cannon, and H. F. Jenkinson. "Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance." Antimicrobial Agents and Chemotherapy 40, no. 12 (December 1996): 2835–41. http://dx.doi.org/10.1128/aac.40.12.2835.

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Fluconazole-susceptible Candida albicans strains accumulated [3H]fluconazole at a rate of approximately 2 pmol/min per 10(9) cells. Fluconazole accumulation was not affected by the pretreatment of cells with sodium azide or with 2-deoxyglucose. The rate of fluconazole accumulation became saturated at high fluconazole concentrations and was not affected by the addition of ketoconazole, and there was no fluconazole accumulation in cells incubated at 4 degrees C. A fluconazole-resistant mutant of C. albicans SGY-243 was isolated following growth enrichment in fluconazole-containing medium. Cells of the mutant strain, designated FR2, showed a reduced rate of fluconazole accumulation compared with SGY-243 and were not resistant to other azole antifungal agents. The rates of fluconazole accumulation by C. albicans FR2 and the other azole-resistant strains, B59630, AD, and KB, were increased in the presence of sodium azide, suggesting that fluconazole resistance in these strains may be associated with an energy-dependent drug efflux. Fluconazole-resistant C. albicans strains all contained elevated amounts (2- to 17-fold) of mRNA encoding Cdr1, and an ATP-binding cassette-type transporter. In addition, C. albicans FR2 also contained increased amounts of mRNA encoding Benr, a major facilitator superfamily transporter. These results suggest that fluconazole enters C. albicans cells by facilitated diffusion and that fluconazole resistance may involve energy-dependent drug efflux associated with increased expression of Benr and/or Cdr1.
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Yang, Wen-Chi, and Sheng-Fung Lin. "Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma." BioMed Research International 2015 (2015): 1–17. http://dx.doi.org/10.1155/2015/341430.

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Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM.
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Sen, B., and S. G. Joshi. "Studies on Acinetobacter baumannii involving multiple mechanisms of carbapenem resistance." Journal of Applied Microbiology 120, no. 3 (February 23, 2016): 619–29. http://dx.doi.org/10.1111/jam.13037.

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37

Ozben, Tomris. "Mechanisms and strategies to overcome multiple drug resistance in cancer." FEBS Letters 580, no. 12 (February 17, 2006): 2903–9. http://dx.doi.org/10.1016/j.febslet.2006.02.020.

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38

Friedberg, Jonathan W. "Unique Toxicities and Resistance Mechanisms Associated with Monoclonal Antibody Therapy." Hematology 2005, no. 1 (January 1, 2005): 329–34. http://dx.doi.org/10.1182/asheducation-2005.1.329.

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Abstract Anti-CD20 therapy has had a truly dramatic impact on treatment and outcome of patients with follicular lymphoma. Unfortunately, the majority of responses to single-agent rituximab are incomplete, and all patients with follicular lymphoma will experience disease progression at some point following rituximab therapy. Rituximab has multiple mechanisms of inducing in vivo cytotoxicity, including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, direct apoptotic signaling, and possible vaccinal effects. The cellular microenvironment within follicular lymphoma has a profound impact on which mechanism is dominant, and confers resistance in many situations. Both tumor-associated and host-associated factors also contribute to rituximab resistance. There are multiple potential approaches to overcoming rituximab resistance, including rational biologic combination immunotherapy, engineered antibodies, and radioimmunoconjugates. Improved ability to overcome resistance will require further elucidation of critical signaling pathways involved in rituximab induced cytotoxicity and a comprehensive understanding of interactions between its multiple mechanisms of action.
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39

Wójcicki, Michał, Olga Świder, Kamila J. Daniluk, Paulina Średnicka, Monika Akimowicz, Marek Ł. Roszko, Barbara Sokołowska, and Edyta Juszczuk-Kubiak. "Transcriptional Regulation of the Multiple Resistance Mechanisms in Salmonella—A Review." Pathogens 10, no. 7 (June 24, 2021): 801. http://dx.doi.org/10.3390/pathogens10070801.

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The widespread use of antibiotics, especially those with a broad spectrum of activity, has resulted in the development of multidrug resistance in many strains of bacteria, including Salmonella. Salmonella is among the most prevalent causes of intoxication due to the consumption of contaminated food and water. Salmonellosis caused by this pathogen is pharmacologically treated using antibiotics such as fluoroquinolones, ceftriaxone, and azithromycin. This foodborne pathogen developed several molecular mechanisms of resistance both on the level of global and local transcription modulators. The increasing rate of antibiotic resistance in Salmonella poses a significant global concern, and an improved understanding of the multidrug resistance mechanisms in Salmonella is essential for choosing the suitable antibiotic for the treatment of infections. In this review, we summarized the current knowledge of molecular mechanisms that control gene expression related to antibiotic resistance of Salmonella strains. We characterized regulators acting as transcription activators and repressors, as well as two-component signal transduction systems. We also discuss the background of the molecular mechanisms of the resistance to metals, regulators of multidrug resistance to antibiotics, global regulators of the LysR family, as well as regulators of histone-like proteins.
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40

da Silva Ferreira, Márcia Eliana, José Luiz Capellaro, Everaldo dos Reis Marques, Iran Malavazi, David Perlin, Steven Park, James B. Anderson, et al. "In Vitro Evolution of Itraconazole Resistance in Aspergillus fumigatus Involves Multiple Mechanisms of Resistance." Antimicrobial Agents and Chemotherapy 48, no. 11 (November 2004): 4405–13. http://dx.doi.org/10.1128/aac.48.11.4405-4413.2004.

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ABSTRACT We investigated the evolution of resistance to the antifungal drug itraconazole in replicate populations of Aspergillus fumigatus that were founded from a strain with a genotype of sensitivity to a single drug and then propagated under uniform conditions. For each population, conidia were serially transferred 10 times to agar medium either with or without itraconazole. After 10 transfers in medium supplemented with itraconazole, 10 itraconazole-resistant mutant strains were isolated from two populations. These mutant strains had different growth rates and different levels of itraconazole resistance. Analysis of the ergosterol contents of these mutants showed that they accumulate ergosterol when they are grown in the presence of itraconazole. The replacement of the CYP51A gene of the wild-type strain changed the susceptibility pattern of this strain to one of itraconazole resistance only when CYP51A genes with N22D and M220I mutations were used as selectable marker genes. Real-time quantitative reverse transcription-PCR was used to assess the levels of expression of the Afumdr1, Afumdr2, Afumdr3, Afumdr4, AtrF transporter, CYP51A, and CYP51B genes in these mutant strains. Most mutants showed either constitutive high-level expression or induction upon exposure of Afumdr3, Afumdr4, and AtrF to itraconazole. Our results suggest that overexpression of drug efflux pumps and/or selection of drug target site mutations are at least partially responsible for itraconazole resistance and could be considered mechanisms for the emergence of clinical resistance to this drug.
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Palma-Bautista, Candelario, José G. Vázquez-García, José Alfredo Domínguez-Valenzuela, Kassio Ferreira Mendes, Ricardo Alcántara de la Cruz, Joel Torra, and Rafael De Prado. "Non-Target-Site Resistance Mechanisms Endow Multiple Herbicide Resistance to Five Mechanisms of Action in Conyza bonariensis." Journal of Agricultural and Food Chemistry 69, no. 49 (December 2, 2021): 14792–801. http://dx.doi.org/10.1021/acs.jafc.1c04279.

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42

Uyuklu, Tolga, A. Ugur Ural, Meral Sarper, Ferit Avcu, Yusuf Baran, Pinar Elci, and Nejat Akar. "A Study of Multiple Drug Resistance Mechanisms Improved Against Bortezomib on Multiple Myeloma Cell Lines In Vitro." Blood 110, no. 11 (November 16, 2007): 4183. http://dx.doi.org/10.1182/blood.v110.11.4183.4183.

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Abstract The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM cases. In this study, bortezomib resistant human MM cell lines; RPMI-8226, secreting lambda light chain, and ARH-77, secreting IgG, were developed and responsible resistance mechanisms were investigated. For this purpose, by exposing to the cells to sequentially gradual doses of Bor in vitro conditions, resistant cell lines were acquired throughout one year. The IC50 values for Bor were determined after 48 hour incubation by MTT cytotoxicity assay (IC50:1,16nM for RPMI-8226 and IC80:0,6nM for ARH-77) against wild type cells. Throughout one year some cell lines resistant to 1,3nM Bor were acquired by performing Bor to both cell lines in gradual doses. In resistant cell lines IC50:18,07 for RPMI-8226 and IC50:97,56 nM for ARH-77 were determined by MTT assay. In parallel of the gradual increase in drug concentration; the expression changes of the genes of ATP binding cassette protein; MDR1 (Multi Drug Resistance Protein), MRP1 (Multi Drug Resistance Associated Protein), BCRP (Breast Cancer Resistance Protein); and LRP (Lung Resistant Protein) which is responsible for accumulation of the drug in cytoplasm with the aid of nuclear membrane were determined with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and densitometric analysis. In resistant cells, high expression of MDR1, MRP1, BRCP and LRP genes showed that; pumping the drug out of the cell membrane and decrease in accumulation of the drug in the cytoplasm had effects on the resistant mechanisms against Bor. Furthermore, expression changes of an important sing of apoptosis ‘caspase-3’, pro-apoptotic ‘bax’ and an anti-apoptotic ‘bcl-2’ genes were examined by RT-PCR and we could come to a point that when compared the sensitive cells to resistant cells, expression of caspase-3 gene and pro-apoptotic bax protein decreased but bcl-2 gene expression increased in resistant cell lines. Finally, we concluded that resistant cell lines acquired resistance against apoptosis by means of mitochondria. By means of this project, the genes which are responsible for secondary drug resistance in ARH-77 and RPMI-8226 MM cell lines in vitro conditions against Bor were determined. Also resistance mechanisms against apoptosis were demonstrated. Cross resistance to different chemotherapeutic agents mechanisms are still continuing.
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Zhang, Wenluan, Dehui Wang, Zhengnan Sun, Jianing Song, and Xu Deng. "Robust superhydrophobicity: mechanisms and strategies." Chemical Society Reviews 50, no. 6 (2021): 4031–61. http://dx.doi.org/10.1039/d0cs00751j.

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44

Albrecht, Alfredo Junior Paiola, Vinicius Gabriel Caneppele Pereira, Cristian Natalino Zanfrilli de Souza, Luiz Henrique Saes Zobiole, Leandro Paiola Albrecht, and Fernando Storniolo Adegas. "Multiple resistance of Conyza sumatrensis to three mechanisms of action of herbicides." Acta Scientiarum. Agronomy 42 (April 3, 2020): e42485. http://dx.doi.org/10.4025/actasciagron.v42i1.42485.

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Fleabane (Conyza spp.) is an important weed in grain production systems and is currently one of the most problematic weeds in Brazil. An important factor related to weeds such as fleabane is the characteristic of herbicide-resistant biotypes developed under selection pressure, with multiple resistance previously detected for Conyza spp. Thus, the aim of this study was to demonstrate the multiple resistance of Conyza sumatrensis to the herbicides paraquat, glyphosate, and chlorimuron. From the F2 seeds of biotypes with suspected resistance to paraquat, glyphosate, and chlorimuron, dose-response greenhouse experiments were conducted for the three herbicides. Herbicides were applied when the plants had 6-8 leaves that were at a height of 8 cm. At the end of the evaluations, 28 days after application, multiple resistance to paraquat, glyphosate, and chlorimuron was observed, with resistance factors (RF50) for the control of 7.43, 3.58, and 14.35 and for the reduction of dry mass of 2.65, 2.79, and 11.31, respectively. All the established criteria for demonstrating new cases of weed resistance were met; thus, the first case worldwide of a Conyza species with resistance to herbicides with three different mechanisms of action was confirmed.
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Patra, Sandip, Mayur Raney, Aditi Pareek, and Rupinder Kaur. "Epigenetic Regulation of Antifungal Drug Resistance." Journal of Fungi 8, no. 8 (August 19, 2022): 875. http://dx.doi.org/10.3390/jof8080875.

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In medical mycology, epigenetic mechanisms are emerging as key regulators of multiple aspects of fungal biology ranging from development, phenotypic and morphological plasticity to antifungal drug resistance. Emerging resistance to the limited therapeutic options for the treatment of invasive fungal infections is a growing concern. Human fungal pathogens develop drug resistance via multiple mechanisms, with recent studies highlighting the role of epigenetic changes involving the acetylation and methylation of histones, remodeling of chromatin and heterochromatin-based gene silencing, in the acquisition of antifungal resistance. A comprehensive understanding of how pathogens acquire drug resistance will aid the development of new antifungal therapies as well as increase the efficacy of current antifungals by blocking common drug-resistance mechanisms. In this article, we describe the epigenetic mechanisms that affect resistance towards widely used systemic antifungal drugs: azoles, echinocandins and polyenes. Additionally, we review the literature on the possible links between DNA mismatch repair, gene silencing and drug-resistance mechanisms.
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46

Schultz, John L., Laura A. Chatham, Chance W. Riggins, Patrick J. Tranel, and Kevin W. Bradley. "Distribution of Herbicide Resistances and Molecular Mechanisms Conferring Resistance in Missouri Waterhemp (Amaranthus rudisSauer) Populations." Weed Science 63, no. 1 (March 2015): 336–45. http://dx.doi.org/10.1614/ws-d-14-00102.1.

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A survey of soybean fields containing waterhemp was conducted just prior to harvest in 2012 to determine the scope and extent of herbicide resistance and multiple herbicide resistances among a sample of Missouri waterhemp populations. Resistance was confirmed to glyphosate and to acetolactate synthase (ALS), protoporphyrinogen oxidase (PPO), photosystem II (PSII), and 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors, but not to 2,4-D. Of the 187 populations tested, 186 exhibited resistance to chlorimuron. The proportions of populations with atrazine or glyphosate resistance were similar, with 30 and 29% of the populations surviving the 3× rates. Lactofen resistance was observed in 5% of the populations, whereas mesotrione resistance was only found in 1.6% of the populations. All populations tested were susceptible to 2,4-D at the 3× rate. At least 52% of the waterhemp populations tested exhibited resistance to herbicides from two mechanism of action. Resistance to atrazine plus chlorimuron as well as glyphosate plus chlorimuron was present in 29% of the populations. Three-way resistance, primarily comprised of resistance to atrazine plus chlorimuron plus glyphosate, was present in 11% of the populations. Resistance to herbicides from four mechanisms of action was found in 2% of the populations, and one population exhibited resistance to herbicides from five mechanisms of action. DNA analysis of a subsample of plants revealed that previously documented mechanisms of resistance in waterhemp, including the ΔG210 deletion conferring PPO-inhibitor resistance, the Trp574Leu amino acid substitution conferring ALS-inhibitor resistance, and elevated 5-enolypyruvyl-shikimate-3-phosphate synthase copy number and the Pro106Ser amino acid substitution resulting in glyphosate resistance, explained survival in many, but not all, instances. Atrazine resistance was not explained by the Ser264Gly D1 protein substitution. Overall, results from these experiments indicate that Missouri soybean fields contain waterhemp populations with resistance to glyphosate, ALS-, PPO-, PSII-, and HPPD-inhibiting herbicides, which are some of the most common mechanisms of action currently utilized for the control of this species in corn and soybean production systems. Additionally, these results indicate that slightly more than half of the populations tested exhibit resistance to more than one herbicide mechanisms of action. Managing the current resistance levels in existing populations is of utmost importance. The use of multiple, effective herbicide modes of action, both preemergence and postemergence, and the integration of optimum cultural and mechanical control practices will be vital in the management of Missouri waterhemp populations in the future.
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Ahamed, SK Tousif, and Nabanita Giri. "Shigellosis and Development of Multiple Antimicrobial Resistance Mechanisms of Shigella spp." Biosciences Biotechnology Research Asia 18, no. 4 (December 30, 2021): 703–18. http://dx.doi.org/10.13005/bbra/2953.

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Shigellosis is a serious public health issue. Millions of people suffer from this deadly food and water borne disease each year. The main manifestations of affected persons are bloody diarrhea with excessive dehydration. The causative agent of this disease is the bacteria Shigella spp. which has four serogroups. Though Shigella flexneri and Shigella dysenteriae are the dominant serogroups in developing countries, reports of other serogroups, namely Shigella boydii and Shigella sonnei, in the food contaminations are available. There are seasonal variations of Shigella infection throughout the world. In Asian subcontinent, monsoon and post monsoon times are the ideal for infection. The transmission of the bacteria in human is usually caused by feco-oral route or by contaminated food and water. There are several groups of antibiotics like foscomycin, macrolide, amiglycoside, tetracycline etc. which were used before. But they are now become useless as Shigella spp. is getting resistant against those drugs. The quinolone groups of antibiotics like ciprofloxacin, ofloxacin, norflxacin, ceftriaxone etc. are the important drugs for the cure of the disease shigellosis but prevalence of drug resistant strains of Shigella spp. against those drugs are a great concern nowadays. The occurrence of plasmid mediated quinolone resistance genes (PMQR), efflux pump proteins and effective mutations at drug binding region of gyrA etc. are the major mechanisms for the development of drug resistance.
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Arienti, Chiara, Michele Zanoni, Sara Pignatta, Alberto Del Rio, Silvia Carloni, Michela Tebaldi, Gianluca Tedaldi, and Anna Tesei. "Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer." Oncotarget 7, no. 14 (February 22, 2016): 18424–39. http://dx.doi.org/10.18632/oncotarget.7575.

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49

Zeng, Leli, Jia Li, Chen Zhang, Yun-Kai Zhang, Wei Zhang, Juanjuan Huang, Charles R. Ashby, Zhe-Sheng Chen, and Hui Chao. "An organoruthenium complex overcomes ABCG2-mediated multidrug resistance via multiple mechanisms." Chemical Communications 55, no. 26 (2019): 3833–36. http://dx.doi.org/10.1039/c9cc00882a.

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50

Shammas, Masood A., Hemant Koley, Cheng Li, Kenneth C. Anderson, Robert J. S. Reis, and Nikhil C. Munshi. "Molecular Mechanisms Underlying the Development of Drug Resistance in Multiple Myeloma." Blood 104, no. 11 (November 16, 2004): 3409. http://dx.doi.org/10.1182/blood.v104.11.3409.3409.

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Abstract:
Abstract A prominent feature of most cancers including multiple myeloma (MM) is a striking genetic instability, leading to ongoing accrual of mutational changes some of which underlie tumor progression, including development of drug resistance and metastasis. The molecular basis for the generation of genetic diversity in cancer cells has thus emerged as an important focus of investigation and a target for successful eradication. We have previously observed that homologous recombination (HR) is upregulated in MM. Utilizing a genomewide LOH assay based on SNP genotyping (Affymetrix) as a tool to estimate the rate of mutation and genomic instability, we have observed that over time elevated HR leads to progressive accumulation of genetic variation in MM cell lines and patient cells; and inhibition of HR activity in MM cells by altering components of the HR pathway concordantly affects the acquisition of new genetic changes. As HR activity is dependent on concerted action of number of genes, instead of over expressing single HR related gene, we utilized nickel chloride, a known recombinogen to evaluate effects of increased HR activity on the development of genomic diversity. We cultured ARP cells in the presence or absence of nickel chloride, over a period of 90 days. Genome-wide LOH was evaluated by comparing genotypes before and after the 90-day interval. In three independent experiments treatment of cells with nickel chloride increased the number of new LOH sites by more than 12-fold. We next evaluated the effect of induction of HR and the consequent increase in genetic aberrations, on development of drug resistance in MM. Myeloma cells were cultured with nickel chloride as a potent inducer of HR and dexamethasone (10−8M); control cells were exposed to dexamethasone alone. The cell viability was measured weekly. No live cells were detected in cultures exposed to dexamethasone alone; while &gt;95% cells exposed to both nickel chloride and dexamethasone were alive following 2 weeks culture. These findings were confirmed by 3 independent experiments. The development of drug resistance was further confirmed by demonstrating no significant effects of dexamethasone on these cells at 10−6M concentrations for &gt;1 week. Dexamethasone at this concentration kills all control cells by day 3. Evaluation of development of resistance to other agents is underway. We propose that continued accumulation of new genetic changes mediated by HR, as demonstrated here, provides the molecular events required to develop drug resistance; and its inhibition may allow us to successfully treat MM cells without the currently observed development of resistance. HR may be a potential therapeutic target to maintain chemo sensitivity of the tumors.
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