Abstract 1285:In vitrocharacterization of sotorasib and other RAS ‘His95-groove' binders and investigation of resistance mechanisms

2021 ◽  
Author(s):  
Anne Y. Saiki ◽  
Deanna Mohn ◽  
Yu Li ◽  
Tao Osgood ◽  
Karen Rex ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Groove Binders

Resistance mechanisms ofPrunusrootstocks to root-knot nematode,Meloidogyne incognita

Fruits ◽  
2009 ◽  
Vol 64 (5) ◽  
pp. 295-303 ◽  
Author(s):  
Hang Ye ◽  
Wen-jun Wang ◽  
Guo-jie Liu ◽  
Li-xin Zhu ◽  
Ke-gong Jia
Keyword(s):  
Meloidogyne Incognita ◽  
Resistance Mechanisms ◽  
Root Knot Nematode

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 48-49
Author(s):  
Javaid Ahmad Bhat ◽  
Shariq Rashid Masoodi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Tertiary Care ◽  
Resistance Mechanisms ◽  
North India ◽  
Global Public Health ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Effective Prevention ◽  
Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

2019 ◽  
Author(s):  
Daniel Sun ◽  
Soumya Poddar ◽  
Roy D. Pan ◽  
Juno Van Valkenburgh ◽  
Ethan Rosser ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Small Cell Lung Carcinoma ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Tumor Models ◽  
Cell Lung Carcinoma ◽  
Adaptive Resistance ◽  
Cancer Models ◽  
Nanomolar Range

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone <b>HCT-13</b>, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC<sub>90</sub> values in the low-to-mid nanomolar range.<b> </b>We show that the cytotoxicity of <b>HCT-13</b> is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following <b>HCT-13 </b>treatment. Taken together, <b>HCT-13 </b>is potent against solid tumor models and warrants <i>in vivo</i> evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

2019 ◽  
Author(s):  
Bram Frohock ◽  
Jessica M. Gilbertie ◽  
Jennifer C. Daiker ◽  
Lauren V. Schnabel ◽  
Joshua Pierce
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Matrix Model ◽  
Bacterial Load ◽  
Collagen Matrix ◽  
Resistance Mechanisms ◽  
Novel Therapeutics ◽  
Innovative Treatment ◽  
Antibiotic Action ◽  
Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

MICROORGANISMS ANTIBIOTIC RESISTANCE MECHANISMS – PRESENT VIEW

2019 ◽  
Vol 21 (10) ◽  
pp. 125-130
Author(s):  
Пушилина А.Д. ◽  
◽  
Коменкова Т.С. ◽  
Зайцева Е.А. ◽  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mechanisms ◽  
Present View

Persistent Apical Periodontitis: Bacterial Taxonomic Analysis and Treatment Through Intentional Replantation

2020 ◽  
Author(s):  
Fernando Eduardo Coria-Valdiosera
Keyword(s):  
Antibiotic Therapy ◽  
Root Canal ◽  
Resistance Mechanisms ◽  
Apical Periodontitis ◽  
Infectious Process ◽  
Identification Of Bacteria ◽  
The Right ◽  
Apical Lesions ◽  
Endodontic Retreatment

Introduction: The microorganisms own different resistance mechanisms that allow them to resist the chemo-mechanical cleanliness of root canal and antibiotic therapies causing the persistence of apical lesions. Methods: This clinical case describes a male patient diagnosed with pulp necrosis in the right lower central incisor due to trauma, which developed apical periodontitis manifesting itself extra orally. Root canal treatment along with antibiotic therapy was performed, but because the infectious process persisted, endodontic retreatment and a new antibiotic therapy were carried out, however, the clinical evolution was not favorable. For this reason, the intentional replantation was chosen as the outright treatment, performing apicectomy and curettage of the periapical lesion, from which the isolation and taxonomic study of microorganisms were carried out, with the respective antibiogram. Results: In the 10-day clinical follow-up, the extraoral infectious process disappeared almost completely and 6 months later, a complete repair of the bone tissue was observed on the tomography. Conclusion: A better understanding of the persistence of apical periodontitis was achieved by taxonomic identification of bacteria and the intentional replantation allowed to remove the apical biofilm gaining an excellent wound healing.

Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems

2018 ◽  
Vol 25 (28) ◽  
pp. 3319-3332 ◽  
Author(s):  
Chuanmin Zhang ◽  
Shubiao Zhang ◽  
Defu Zhi ◽  
Jingnan Cui
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Resistance Mechanisms ◽  
Delivery Systems ◽  
Cell Cycle Checkpoints ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
Cancer Models ◽  
Anti Cancer

There are several mechanisms by which cancer cells develop resistance to treatments, including increasing anti-apoptosis, increasing drug efflux, inducing angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs are hard to reach curative effects due to these resistance mechanisms. It has been suggested that liposomes based co-delivery systems, which can deliver drugs and genes to the same tumor cells and exhibit synergistic anti-cancer effects, could be used to overcome the resistance of cancer cells. As the co-delivery systems could simultaneously block two or more pathways, this might promote the death of cancer cells by sensitizing cells to death stimuli. This article provides a brief review on the liposomes based co-delivery systems to overcome cancer resistance by the synergistic effects of drugs and genes. Particularly, the synergistic effects of combinatorial anticancer drugs and genes in various cancer models employing multifunctional liposomes based co-delivery systems have been discussed. This review also gives new insights into the challenges of liposomes based co-delivery systems in the field of cancer therapy, by which we hope to provide some suggestions on the development of liposomes based co-delivery systems.

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Biology ◽  
Soft Tissues ◽  
Three Dimensional ◽  
3D Culture ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Tumour Spheroids ◽  
Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

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