scholarly journals Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance

2004 ◽  
Vol 112 (6) ◽  
pp. 974-985 ◽  
Author(s):  
Anamaria Brozovic ◽  
Gerhard Fritz ◽  
Markus Christmann ◽  
Jochen Zisowsky ◽  
Ulrich Jaehde ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Carcinoma Cells ◽  
P38 Kinase ◽  
Human Carcinoma ◽  
Acquired Drug Resistance ◽  
Fas L

scholarly journals Rapid induction of morphological changes in human carcinoma cells A-431 by epidermal growth factors.

1979 ◽  
Vol 83 (1) ◽  
pp. 260-265 ◽  
Author(s):  
M Chinkers ◽  
J A McKanna ◽  
S Cohen
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Growth Factors ◽  
Morphological Changes ◽  
Carcinoma Cells ◽  
Human Carcinoma ◽  
Rapid Induction ◽  
Epidermal Growth ◽  
Scanning Electron

The morphological effects of epidermal growth factor (EGF) on human carcinoma cells A-431 have been examined by scanning electron microscopy. These flat polygonal cells normally exhibit only small membrane folds, but show extensive ruffling and extension of filopodia within 5 min of exposure to EGF at 37 degrees C. This ruffling activity is transient, subsiding within another 5--15 min, but several other changes in surface morphology follow. Within the first hour of exposure to the hormone, the cell surface becomes exceedingly smooth and the nuclei seem to protrude above the plane of the otherwise thin monolayer, giving the cells a "fried egg" appearance. Cells at the edges of colonies gradually retract from the substrate, leading to reorganization, by 12 h, of the monolayer into multilayered colonies. EGF thus induces both rapid and long-term alterations in the morphology of these epidermoid cells.

scholarly journals The Long-Term DEHP Exposure Confers Multidrug Resistance of Triple-Negative Breast Cancer Cells through ABC Transporters and Intracellular ROS

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 949
Author(s):  
Mahendra Jadhao ◽  
Eing-Mei Tsai ◽  
Ho-Chun Yang ◽  
Yih-Fung Chen ◽  
Shih-Shin Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Abc Transporters ◽  
Breast Cancer Cells ◽  
Acquired Drug Resistance ◽  
Intracellular Ros ◽  
Dehp Exposure

The characteristics of phthalates had been thought to be similar to endocrine disruptors, which increases cancer risk. The role of phthalates in acquired drug resistance remains unclear. In this study, we investigated the effect of di-(2-ethylhexyl) phthalate (DEHP) on acquired drug resistance in breast cancer. MCF7 and MDA-MB-231 breast cancer cells were exposed to long-term physiological concentration of DEHP for more than three months. Long-exposure DEHP permanently attenuated the anti-proliferative effect of doxorubicin with estrogen receptor-independent activity even after withdrawal of DEHP. Long term DEHP exposure significantly reduced ROS (O2−) level in MDA-MB-231 cells while increased in MCF7 cells. ATP-binding cassette (ABC) transporters possess a widely recognized mechanism of drug resistance and are considered a target for drug therapy. Upregulation of ABC family proteins, ABCB-1 and ABCC-1 observed in DEHP-exposed clones compared to doxorubicin-resistant (DoxR) and parental MDA-MB-231 cells. A viability assay showed enhanced multidrug resistance in DEHP-exposed clones against Dox, topotecan, and irinotecan. Inhibition of ABC transporters with tariquidar, enhanced drug cytotoxicity through increased drug accumulation reversing acquired multidrug resistance in MDA-MB-231 breast cancer cells. Tariquidar enhanced Dox cytotoxicity by increasing intracellular ROS production leading to caspase-3 mediated apoptosis. Activation of PI3K/Akt signaling enhanced proliferation and growth of DEHP-exposed MDA-MB-231 cells. Overall, long-term DEHP exposure resulted in acquired multidrug resistance by upregulating ABCB-1 and ABCC1; apart from proliferation PI3K/Akt may be responsible for acquired drug resistance through ABC transporter upregulation. Targeting ABCB1 and ABCC1 with tariquidar may be a promising strategy for reversing the acquired multidrug resistance of triple-negative breast cancer cells.

scholarly journals Long-term non-invasive drug treatments for adult zebrafish

2021 ◽  
Author(s):  
Yuting Lu ◽  
E. Elizabeth Patton
Keyword(s):  
Drug Resistance ◽  
Drug Efficacy ◽  
Drug Formulation ◽  
Tumour Regression ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Invasive Approach ◽  
Acquired Drug Resistance ◽  
Non Invasive

Zebrafish embryos are widely used for drug-discovery however administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we develop a drug formulation and administration method for adult zebrafish by producing food-based drug pellets which are consumed voluntarily. We apply this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Short-term, precise, and daily dosing with drug-pellets made with the BRAFV600E inhibitor, vemurafenib, led to tumour regression. On-target drug efficacy was determined by phospho-ERK staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies, and can be widely applied to any adult zebrafish model.

scholarly journals Angiogenesis and chemotherapy resistance: optimizing chemotherapy scheduling using mathematical modeling

2021 ◽  
Author(s):  
Mariusz Bodzioch ◽  
Piotr Bajger ◽  
Urszula Foryś
Keyword(s):  
Mathematical Modeling ◽  
Drug Resistance ◽  
Chemotherapy Resistance ◽  
Maximum Tolerated Dose ◽  
Attractive Alternative ◽  
Acquired Drug Resistance ◽  
Control Techniques ◽  
Drug Doses ◽  
Metronomic Therapy

AbstractChemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active discussion among researchers. One of the proposed solutions is to shift the therapeutic paradigm from complete eradication of cancer to maintenance, i.e., to treat it as a chronic disease. A concept of metronomic therapy (low chemotherapy doses applied continuously) emerged in early 2000s and was henceforth shown to offer a number of benefits, including targeting endothelial cells and reducing acquired drug resistance. Using mathematical modeling and optimal control techniques, we investigate the hypothesis that lower doses of chemotherapy are beneficial for patients. Our analysis of a mathematical model of tumor growth under angiogenic signaling proposed by Hahnfeldt et al. adapted to heterogeneous tumors treated by combined anti-angiogenic agent and chemotherapy offers insights into the effects of metronomic therapy. Firstly, assuming constant long-term drug delivery, the model suggests that the longest survival time is achieved for intermediate drug doses. Secondly, by formalizing the notion of the therapeutic target being maintenance rather than eradication, we show that in the short term, optimal chemotherapy scheduling consists mainly of a drug applied at a low dose. In conclusion, we suggest that metronomic therapy is an attractive alternative to maximum tolerated dose therapies to be investigated in experimental settings and clinical trials.

scholarly journals Expression of Drug Resistance Genes in VP-16 and mAMSA-selected Human Carcinoma Cells

2001 ◽  
Vol 92 (7) ◽  
pp. 778-784 ◽  
Author(s):  
Yoshihito Matsumoto ◽  
Hiroshi Takano ◽  
Katsuzo Kunishio ◽  
Seigo Nagao ◽  
Tito Fojo
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Carcinoma Cells ◽  
Human Carcinoma

scholarly journals The Inhibition of CDK8/19 Mediator Kinases Prevents the Development of Resistance to EGFR-Targeting Drugs

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 144
Author(s):  
Amanda C. Sharko ◽  
Chang-Uk Lim ◽  
Martina S. J. McDermott ◽  
Chuck Hennes ◽  
Kingsavanh P. Philavong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Growth Factor Receptor ◽  
Tumor Resistance ◽  
Acquired Drug Resistance ◽  
Transcriptional Reprogramming ◽  
Development Of Resistance ◽  
Transcriptional Changes ◽  
Epidermal Growth

Drug resistance is the main obstacle to achieving cures with both conventional and targeted anticancer drugs. The emergence of acquired drug resistance is initially mediated by non-genetic transcriptional changes, which occur at a much higher frequency than mutations and may involve population-scale transcriptomic adaptation. CDK8/19 kinases, through association with transcriptional Mediator complex, regulate transcriptional reprogramming by co-operating with different signal-responsive transcription factors. Here we tested if CDK8/19 inhibition could prevent adaptation to drugs acting on epidermal growth factor receptor (EGFR/ERBB1/HER1). The development of resistance was analyzed following long-term exposure of BT474 and SKBR3 breast cancer cells to EGFR-targeting small molecules (gefitinib, erlotinib) and of SW48 colon cancer cells to an anti-EGFR monoclonal antibody cetuximab. In all cases, treatment of small cell populations (~105 cells) with a single dose of the drug initially led to growth inhibition that was followed by the resumption of proliferation and development of drug resistance in the adapted populations. However, this adaptation was always prevented by the addition of selective CDK8/19 inhibitors, even though such inhibitors alone had only moderate or no effect on cell growth. These results indicate that combining EGFR-targeting drugs with CDK8/19 inhibitors may delay or prevent the development of tumor resistance to therapy.

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