scholarly journals Inter Molecular Level Interaction Studies of Combination Drug Crizotinib And Temozolomide in Glioblastoma Multiforme Targets: An In-silico Approach

Author(s):  
Saleena younus ◽  
Vinod Chandra S.S ◽  
Sheeba K ◽  
Achuth Sankar S. Nair

Abstract Combination drug treatments are frequently used in many diseases, including cancers and AIDS. The main aims of these treatments are to reduce toxicity, decrease or delay drug resistance, and improve drug efficacy by inhibiting the activity of a specific target or groups of targets in a cell. The net effect of combination drug efficacy is mainly quantified and interpreted by various terminologies like synergy, additive, agonism, and antagonism based on drugs dose ratio. In single or combination drug treatment, drug action occurs on cells due to the intermolecular level interaction of drugs with protein/DNA/RNA/Enzyme. This type of inter molecular level interaction can be detected with the help of docking software. The current study aims to identify the inter-molecular level interaction of combination drug Crizotinib and Temozolomide with C-MET, C-ROS1, and ALK targets in Glioblastoma Multiforme(GBM). To identify this, we performed forward and reverse docking of drugs with these proteins, and the results were evaluated by drug properties and the complex energy. From the analysis study, we recognized that first, Crizotinib and then, after Temozolomide bounded docked complexes showed the least complex energy in all the docked complex structures, and the better complexes were identified from the result by MD simulation.

2016 ◽  
Vol 16 (9) ◽  
pp. 1190-1197 ◽  
Author(s):  
Dziugas Meskelevicius ◽  
Kastytis Sidlauskas ◽  
Ruta Bagdonaviciute ◽  
Julius Liobikas ◽  
Daiva Majiene

1984 ◽  
Vol 4 (10) ◽  
pp. 2098-2102
Author(s):  
E Flatau ◽  
F A Gonzales ◽  
L A Michalowsky ◽  
P A Jones

A cell line (T17) was derived from C3H 10T1/2 C18 cells after 17 treatments with increasing concentrations of 5-aza-2'-deoxycytidine. The T17 cell line was very resistant to the cytotoxic effects of 5-aza-2'-deoxycytidine, and the 50% lethal dose for 5-aza-2'-deoxycytidine was ca. 3 microM, which was 30-fold greater than that of the parental C3H 10T1/2 C18 cells. Increased drug resistance was not due to a failure of the T17 cell line to incorporate 5-aza-2'-deoxycytidine into DNA. The cells were also slightly cross-resistant to 5-azacytidine. The percentage of cytosines modified to 5-methylcytosine in T17 cells was 0.7%, a 78% decrease from the level of 3.22% in C3H 10T1/2 C18 cells. The DNA cytosine methylation levels in several clones isolated from the treated lines were on the order of 0.7%, and clones with methylation levels lower than 0.45% were not obtained even after further drug treatments. These highly decreased methylation levels appeared to be unstable, and DNA modification increased as the cells divided in the absence of further drug treatment. The results suggest that it may not be possible to derive mouse cells with vanishingly low levels of 5-methylcytosine and that considerable de novo methylation can occur in cultured lines.


2021 ◽  
Vol 15 (12) ◽  
pp. 3264-3267
Author(s):  
Safia Khatoon ◽  
Muhammad Ilyas Shaikh ◽  
Arslan Mahmood ◽  
Priya Rani Harjani ◽  
Sarang Suresh ◽  
...  

Background: Evaluate the efficacy of using combination drug treatment to relieve post extraction pain of impacted mandibular third molar by using Naproxen plus Gabapentin versus Naproxen alone. Aim: To evaluate the efficacy of using combination drug treatment to relieve post extraction pain of impacted mandibular third molar by using Naproxen plus Gabapentin versus Naproxen alone. Methods: Randomized control study, outcome was evaluated by measuring Pre – Operative and 24-Hour Post – Operative Pain status on Visual Analogue Scale and Wong Baker’s Face Pain Rating Scale. Results: Combination therapy (Naproxen and Gabapentin) was effective in significant pain reduction at 12 Hour and 24-Hour Post Extraction period. With 26 patients out 31 presented with Pain Scale of 0 on combination therapy while only 3 out of 31 for naproxen alone after 24 hours. Conclusion: Enhanced effect of combination therapy of naproxen with gabapentin in reducing post extraction pain of impacted mandibular third molar with respect to naproxen alone. Keywords: Naproxen, Gabapentin, Combination Therapy, Post Extraction Pain, Post Extraction Analgesia, Efficacy.


2018 ◽  
Vol 114 (3) ◽  
pp. 222a
Author(s):  
Alessa Ringel ◽  
Turgay Kilic ◽  
Jessica Devant ◽  
Kerstin Ruoff ◽  
Anna Koromyslova ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 703 ◽  
Author(s):  
Robin Demuynck ◽  
Iuliia Efimova ◽  
Abraham Lin ◽  
Heidi Declercq ◽  
Dmitri V. Krysko

The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is largely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug screening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged to be a better model of the in vivo environment, but detailed cell death assays for 3D cultures (including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis method, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types including ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses Sytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in spheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton X-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from all cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that 2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death induction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death type in 3D cultures, including spheroids.


2016 ◽  
Vol 31 (3) ◽  
pp. 270-275 ◽  
Author(s):  
Hong-qi Hu ◽  
Lai-guang Sun ◽  
Wu-jun Guo

Objective The primary purpose of this paper is to investigate the relationship between the microRNA 146a (miR-146a) and the proliferation of cells occurring in glioblastoma multiforme. The secondary purpose of the paper is to investigate abnormalities of expression in miR-146a. Methods A real-time PCR assay was used to investigate the abnormal expression of miR-146a in glioma and adjacent tissue. Lipofection was used to transfect a mimic of miR-146a and induce the upregulation of miR-146a. Real-time PCR was used to observe the expression level of miR-146a. A cell viability analysis was conducted using MTT. A luciferase report vector was used to identify potential targets for miR-146a. Results The miR-146a component was found to be downregulated in glioma tissue compared with adjacent nontumor tissue (p<0.05). The upregulation of miR-146a in glioma cells through miR-146a mimic transfection led to reduction of cell viability and to an increase in the percentage of apoptosis. Notch1 was the name of the potential targeted gene for miR-146a in glioma. Conclusions The study found that the presence of miR-146a potentially affected the proliferation of glioma cells by regulating the rate of Notch1 expression.


1986 ◽  
Vol 26 (5) ◽  
pp. 231-236 ◽  
Author(s):  
Eugene Uzogara ◽  
David V. Sheehan ◽  
Theo C. Manschreck ◽  
Kenneth J. Jones

2006 ◽  
Vol 48 (1) ◽  
Author(s):  
Änne Glass ◽  
Thomas Karopka ◽  
Olaf Wolkenhauer

SummaryOver the last decade, the areas of bioinformatics and genomics have identified, catalogued and characterised, at the molecular level, the components that make up the complex system of a cell. The next step is to describe how the many components interact to create the complex behaviour that underlies development and disease. The following article is to describe some of the research areas and challenges involved.


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