scholarly journals In vitro model for resistance in oncogene-dependent tumors at the limit of radiological detectability

2019 ◽  
Author(s):  
Nina Müller ◽  
Johannes Brägelmann ◽  
Carina Lorenz ◽  
Ulrich P. Michel ◽  
Dennis Plenker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Vitro Model ◽  
Large Population ◽  
Cancer Cell Line ◽  
Resistance Mechanisms ◽  
Lung Cancer Cell Line ◽  
Resistance Mutations ◽  
Activating Egfr Mutation ◽  
Vitro Model

In solid tumors, the response to targeted therapy is typically short-lived, as therapy-resistant mutants can quickly expand during therapy. Here we analyze the spectrum of such resistance mutations coexisting in a large population of cancer cells. We use an iterative scheme of artificial evolution to amplify and isolate different resistance mechanisms. As a proof of concept, we apply our scheme to PC-9 cells, a human non-small cell lung cancer cell line with an activating EGFR mutation. The mechanisms we find comprise the well-known gatekeeper-mutation T790M in EGFR, a mutation in NRAS, the amplification of MET-ligand HGF, as well as induction of AKT-mTOR signaling. In this model, a combination of four drugs targeting these mechanisms prevents not only the expansion of resistant cells, but also inhibits the growth of drug-tolerant cells, which can otherwise act as a reservoir for further resistance mutations. These data suggest that a finite number of drugs specifically acting on individual resistant clones may be able to control resistance in oncogenically driven lung cancer.

scholarly journals In VitroModel for Studying Malignancy Associated Changes

2003 ◽  
Vol 25 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Xiao Rong Sun ◽  
Yonghong Zheng ◽  
Calum MacAulay ◽  
Stephen Lam ◽  
Alexei Doudkine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Function Analysis ◽  
Cancer Cell Line ◽  
Bronchial Epithelium ◽  
Lung Cancer Cell Line ◽  
Human Respiratory Tract ◽  
Normal Cells ◽  
Nuclear Features

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non‐small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tractin vivoto see if the MAC‐like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co‐cultured with cells derived from a lung cancer cell line NCI‐H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed onhttp://www.esacp.org/acp/2003/25‐2/sun.htm.

Synthesis and in vitro Evaluation of Dihydrobenzimidazole Thiopyranooxazinone Derivatives as a Potent Biological Agents

2020 ◽  
Vol 5 (2) ◽  
pp. 164-170
Author(s):  
Deepak P. Kardile ◽  
Mrunal K. Shirsat
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Cancer Cell Line ◽  
Docking Studies ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Anticancer Activities ◽  
In Silico Molecular Docking

In the present study, dihydrobenzimidazole thiopyranooxazinone derivatives were efficiently synthesized, which were further characterized and authenticated by means of TLC and different spectral analysis such as IR and 1H NMR. The synthesized compounds DPK2d2 to DPK2d8 were screened for their in vitro antimicrobial, antitubercular and anticancer activities. The results showed that the titled compounds DPK3d1, DPK3d2 and DPK3d4 exhibited potent antimicrobial activity, shows a broadspectrum activity against Bacillus subtilis, Escherichia coli (antibacterial) and Aspergillus niger (antifungal) as compared to ciprofloxacin and fluconazole, respectively. Compounds DPK3d1, DPK3d3 and DPK3d5 exhibited potent antitubercular activities against Mycobacterium tuberculosis as compared to pyrazinamide, ciprofloxacin and streptomycin. Compounds DPK3d3, DPK3d4 and DPK3d5 showed highly potent cytotoxic activity against human lung cancer cell line (A549) as compared to adriamycin. In silico molecular docking studies shown that all the ligands highest binding affinity range -6.7 to -8.7 for selected 1CB4 PDB of superoxide dismutase, which recognized that ligands having antioxidant activity.

scholarly journals Identification of Secreted Proteins that Mediate Cell-Cell Interactions in an In vitro Model of the Lung Cancer Microenvironment

2008 ◽  
Vol 68 (17) ◽  
pp. 7237-7245 ◽  
Author(s):  
Li Zhong ◽  
Jonathon Roybal ◽  
Raghothama Chaerkady ◽  
Wan Zhang ◽  
Kuicheon Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Vitro Model ◽  
Cell Interactions ◽  
Secreted Proteins ◽  
Cancer Microenvironment ◽  
Mediate Cell ◽  
Vitro Model ◽  
Cell Cell

scholarly journals RETRACTED ARTICLE: Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line

2012 ◽  
Vol 10 (1) ◽  
Author(s):  
Abolfazl Akbarzadeh ◽  
Mohammad Samiei ◽  
Sang Woo Joo ◽  
Maryam Anzaby ◽  
Younes Hanifehpour ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Magnetic Nanoparticles ◽  
Cancer Cell Line ◽  
Covalent Bonding ◽  
Lung Cancer Cell Line ◽  
Magnetic Nanocomposites ◽  
Lung Cancer Cell ◽  
A549 Lung Cancer Cell ◽  
A549 Lung

Abstract Background The aim of present study was to develop the novel methods for chemical and physical modification of superparamagnetic iron oxide nanoparticles (SPIONs) with polymers via covalent bonding entrapment. These modified SPIONs were used for encapsulation of anticancer drug doxorubicin. Method At first approach silane–grafted magnetic nanoparticles was prepared and used as a template for polymerization of the N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) via radical polymerization. This temperature/pH-sensitive copolymer was used for preparation of DOX–loaded magnetic nanocomposites. At second approach Vinyltriethoxysilane-grafted magnetic nanoparticles were used as a template to polymerize PNIPAAm-MAA in 1, 4 dioxan and methylene-bis-acrylamide (BIS) was used as a cross-linking agent. Chemical composition and magnetic properties of Dox–loaded magnetic hydrogel nanocomposites were analyzed by FT-IR, XRD, and VSM. Results The results demonstrate the feasibility of drug encapsulation of the magnetic nanoparticles with NIPAAm–MAA copolymer via covalent bonding. The key factors for the successful prepardtion of magnetic nanocomposites were the structure of copolymer (linear or cross-linked), concentration of copolymer and concentration of drug. The influence of pH and temperature on the release profile of doxorubicin was examined. The in vitro cytotoxicity test (MTT assay) of both magnetic DOx–loaded nanoparticles was examined. The in vitro tests showed that these systems are no toxicity and are biocompatible. Conclusion IC50 of DOx–loaded Fe3O4 nanoparticles on A549 lung cancer cell line showed that systems could be useful in treatment of lung cancer.

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