scholarly journals Dynamic Proteomics Reveals High Plasticity of Cellular Proteome: Growth-Related and Drug-Induced Changes in Cancer Cells are Comparable

PROTEOMICS ◽  
2018 ◽  
Vol 18 (24) ◽  
pp. 1800118 ◽  
Author(s):  
Pierre Sabatier ◽  
Amir Ata Saei ◽  
Shiyu Wang ◽  
Roman A. Zubarev
Keyword(s):  
Cancer Cells ◽  
High Plasticity ◽  
Drug Induced ◽  
Induced Changes

scholarly journals Single cell tracing reveals heterogeneous drug-, dose-, and time-dependent effects on cancer cell fates

2020 ◽  
Author(s):  
Sean M. Gross ◽  
Crystal Sanchez-Aguila ◽  
Paulina J. Zhan ◽  
Laura M. Heiser
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Cancer Cells ◽  
Cell Fate ◽  
Drug Dose ◽  
Time Dependent ◽  
Cell Fates ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Induced Changes

ABSTRACTUnderstanding the molecular basis for drug-induced changes in cellular responses is critical for the identification of effective cancer treatments. Measurement of endpoint viability across a range of drug doses is the standard approach to quantify drug efficacy. While informative, this read-out does not account for the multiple cell fate decisions individual cancer cells undergo in response to drug treatment. As a consequence, the basis for drug-induced changes in cell numbers remains poorly defined. To evaluate the impact of cancer drugs on individual cells, we engineered AU565 breast cancer cells to express a fluorescent cell cycle reporter and then assessed dynamic responses to a panel of drugs. Detailed population and single cell analyses revealed heterogeneous drug-, dose-, and time-dependent effects on cell cycle durations and cell fates. Lapatinib induced dose-dependent extension of G1 duration and limited apoptosis. In contrast, cell fate responses varied with gemcitabine dose: low gemcitabine doses induced extension of S-G2 durations, whereas high doses induced apoptosis after prolonged exposure. Lastly, paclitaxel induced apoptosis and caused only modest cell cycle effects. Overall, our analyses revealed that each drug induced distinct impacts on cell fate that were dependent on the dose and duration of treatment. Understanding these differences has implications for the mechanisms of therapeutic resistance and the identification of effective drug combinations and treatment schedules.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

scholarly journals Albendazole Exhibits Anti-Neoplastic Actions against Gastric Cancer Cells by Affecting STAT3 and STAT5 Activation by Pleiotropic Mechanism(s)

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 362
Author(s):  
Min Hee Yang ◽  
In Jin Ha ◽  
Jae-Young Um ◽  
Kwang Seok Ahn
Keyword(s):  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Small Interfering Rna ◽  
Oxygen Species ◽  
Gastric Cancer Cells ◽  
Drug Induced ◽  
Cellular Apoptosis ◽  
Interfering Rna

Albendazole (ABZ) has been reported to display anti-tumoral actions against various maliganncies, but possible impact of ABZ on gastric cancer has not been deciphered. As aberrant phosphorylation of STAT3 and STAT5 proteins can regulate the growth and progression of gastric cancer, we postulated that ABZ may interrupt the activation of these oncogenic transcription factors. We found that ABZ exposure abrogated STAT3/5 activation, inhibited phosphorylation of Janus-activated kinases 1/2 and Src and enhanced the levels of SHP-1 protein. Silencing of SHP-1 gene by small interfering RNA (siRNA) reversed the ABZ-promoted attenuation of STAT3 as well as STAT5 activation and cellular apoptosis. In addition, these effects were noted to be driven by an augmented levels of reactive oxygen species caused by drug-induced GSH/GSSG imbalance. Thus, the data indicates that ABZ can modulate the activation of STAT3 and STAT5 by pleiotropic mechanisms in gastric cancer cells.

scholarly journals A Novel Nanobody Precisely Visualizes Phosphorylated Histone H2AX in Living Cancer Cells under Drug-Induced Replication Stress

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3317
Author(s):  
Eric Moeglin ◽  
Dominique Desplancq ◽  
Audrey Stoessel ◽  
Christian Massute ◽  
Jeremy Ranniger ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mammalian Cells ◽  
Chromatin Modification ◽  
Replication Stress ◽  
Living Cells ◽  
Single Step ◽  
Dna Double Strand Breaks ◽  
Drug Induced ◽  
Histone H2ax ◽  
C Terminus

Histone H2AX phosphorylated at serine 139 (γ-H2AX) is a hallmark of DNA damage, signaling the presence of DNA double-strand breaks and global replication stress in mammalian cells. While γ-H2AX can be visualized with antibodies in fixed cells, its detection in living cells was so far not possible. Here, we used immune libraries and phage display to isolate nanobodies that specifically bind to γ-H2AX. We solved the crystal structure of the most soluble nanobody in complex with the phosphopeptide corresponding to the C-terminus of γ-H2AX and show the atomic constituents behind its specificity. We engineered a bivalent version of this nanobody and show that bivalency is essential to quantitatively visualize γ-H2AX in fixed drug-treated cells. After labelling with a chemical fluorophore, we were able to detect γ-H2AX in a single-step assay with the same sensitivity as with validated antibodies. Moreover, we produced fluorescent nanobody-dTomato fusion proteins and applied a transduction strategy to visualize with precision γ-H2AX foci present in intact living cells following drug treatment. Together, this novel tool allows performing fast screenings of genotoxic drugs and enables to study the dynamics of this particular chromatin modification in individual cancer cells under a variety of conditions.

Drug induced changes in free, labile and stable acetylcholine of guinea-pig brain

1969 ◽  
Vol 18 (6) ◽  
pp. 1315-1324 ◽  
Author(s):  
L. Beani ◽  
C. Bianchi ◽  
P. Megazzini ◽  
L. Ballotti ◽  
G. Bernardi
Keyword(s):  
Guinea Pig ◽  
Drug Induced ◽  
Pig Brain ◽  
Induced Changes ◽  
Guinea Pig Brain
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