4D Tumorigenesis Model for Quantitating Coalescence, Directed Cell Motility and Chemotaxis, Identifying Unique Cell Behaviors, and Testing Anticancer Drugs

2016 ◽  
pp. 229-250 ◽  
Author(s):  
Spencer Kuhl ◽  
Edward Voss ◽  
Amanda Scherer ◽  
Daniel F. Lusche ◽  
Deborah Wessels ◽  
...  
Keyword(s):  
Cell Motility ◽  
Anticancer Drugs ◽  
Cell Behaviors ◽  
Unique Cell

Notochord morphogenesis in Xenopus laevis: simulation of cell behavior underlying tissue convergence and extension

Development ◽  
1991 ◽  
Vol 113 (4) ◽  
pp. 1231-1244 ◽  
Author(s):  
M. Weliky ◽  
S. Minsuk ◽  
R. Keller ◽  
G. Oster
Keyword(s):  
Xenopus Laevis ◽  
Cell Motility ◽  
Cell Polarization ◽  
Contact Inhibition ◽  
Cell Behavior ◽  
Directional Bias ◽  
Cell Movements ◽  
Cell Behaviors ◽  
Geometric Conditions

Cell intercalation and cell shape changes drive notochord morphogenesis in the African frog, Xenopus laevis. Experimental observations show that cells elongate mediolaterally and intercalate between one another, causing the notochord to lengthen and narrow. Descriptive observations provide few clues as to the mechanisms that coordinate and drive these cell movements. It is possible that a few rules governing cell behavior could orchestrate the shaping of the entire tissue. We test this hypothesis by constructing a computer model of the tissue to investigate how rules governing cell motility and cell-cell interactions can account for the major features of notochord morphogenesis. These rules are drawn from the literature on in vitro cell studies and experimental observations of notochord cell behavior. The following types of motility rules are investigated: (1) refractory tissue boundaries that inhibit cell motility, (2) statistical persistence of motion, (3) contact inhibition of protrusion between cells, and (4) polarized and nonpolarized protrusive activity. We show that only the combination of refractory boundaries, contact inhibition and polarized protrusive activity reproduces normal notochord development. Guided by these rules, cells spontaneously align into a parallel array of elongating cells. Self alignment optimizes the geometric conditions for polarized protrusive activity by progressively minimizing contact inhibition between cells. Cell polarization, initiated at refractory tissue boundaries, spreads along successive cell rows into the tissue interior as cells restrict and constrain their neighbors' directional bias. The model demonstrates that several experimentally observed intrinsic cell behaviors, operating simultaneously, may underlie the generation of coordinated cell movements within the developing notochord.

scholarly journals COX5B-Mediated Bioenergetic Alterations Modulate Cell Growth and Anticancer Drug Susceptibility by Orchestrating Claudin-2 Expression in Colorectal Cancers

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Yu-De Chu ◽  
Siew-Na Lim ◽  
Chau-Ting Yeh ◽  
Wey-Ran Lin
Keyword(s):  
Cell Growth ◽  
Anticancer Drugs ◽  
Disease Free Survival ◽  
Postoperative Outcome ◽  
Drug Susceptibility ◽  
Colorectal Cancers ◽  
Expression Ratio ◽  
Cell Behaviors ◽  
Potential Biomarker ◽  
Junction Protein

Oxidative phosphorylation (OXPHOS) consists of four enzyme complexes and ATP synthase, and is crucial for maintaining physiological tissue and cell growth by supporting the main bioenergy pool. Cytochrome c oxidase (COX) has been implicated as a primary regulatory site of OXPHOS. Recently, COX subunit 5B (COX5B) emerged as a potential biomarker associated with unfavorable prognosis by modulating cell behaviors in specific cancer types. However, its molecular mechanism remains unclear, particularly in colorectal cancers (CRCs). To understand the role of COX5B in CRCs, the expression and postoperative outcome associations using independent in-house patient cohorts were evaluated. A higher COX5B tumor/nontumor expression ratio was associated with unfavorable clinical outcomes (p = 0.001 and 0.011 for overall and disease-free survival, respectively. In cell-based experiments, the silencing of COX5B repressed cell growth and enhanced the susceptibility of CRCs cells to anticancer drugs. Finally, downstream effectors identified by RNA sequencing followed by RT-qPCR and functional compensation experiments revealed that the tight junction protein Claudin-2 (CLDN2) acts downstream of COX5B-mediated bioenergetic alterations in controlling cell growth and the sensitivity to anticancer drugs in CRCs cells. In conclusion, it was found that COX5B promoted cell growth and attenuated anticancer drugs susceptibility in CRCs cells by orchestrating CLDN2 expression, which may contribute to unfavorable postoperative outcomes of patients with CRCs.

Toxicity testing in the development of anticancer drugs

2002 ◽  
Vol 3 (7) ◽  
pp. 440-441
Author(s):  
N Barnard
Keyword(s):  
Anticancer Drugs ◽  
Toxicity Testing

Toxicity testing in the development of anticancer drugs

2002 ◽  
Vol 3 (7) ◽  
pp. 439-440
Author(s):  
N Barrass
Keyword(s):  
Anticancer Drugs ◽  
Toxicity Testing

Erythrocytes and the transfer of anticancer drugs and metabolites: A possible relationship with therapeutic outcome

2001 ◽  
Vol 28 (2F) ◽  
pp. 24-28 ◽  
Author(s):  
Herlinde Dumez ◽  
Martin Highley ◽  
Gunther Guetens ◽  
Gert De Boeck ◽  
Axel Hanauske ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Therapeutic Outcome ◽  
Drugs And Metabolites

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

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