scholarly journals In Vitro Anticancer Drug Sensitivity Sensing through Single-Cell Raman Spectroscopy

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 286
Author(s):  
Jingkai Wang ◽  
Kaicheng Lin ◽  
Huijie Hu ◽  
Xingwang Qie ◽  
Wei E. Huang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Line ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Metabolic Activity ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Sensitivity Testing

Traditional in vitro anticancer drug sensitivity testing at the population level suffers from lengthy procedures and high false positive rates. To overcome these defects, we built a confocal Raman microscopy sensing system and proposed a single-cell approach via Raman-deuterium isotope probing (Raman-DIP) as a rapid and reliable in vitro drug efficacy evaluation method. Raman-DIP detected the incorporation of deuterium into the cell, which correlated with the metabolic activity of the cell. The human non-small cell lung cancer cell line HCC827 and human breast cancer cell line MCF-7 were tested against eight different anticancer drugs. The metabolic activity of cancer cells could be detected as early as 12 h, independent of cell growth. Incubation of cells in 30% heavy water (D2O) did not show any negative effect on cell viability. Compared with traditional methods, Raman-DIP could accurately determine the drug effect, meanwhile, it could reduce the testing period from 72–144 h to 48 h. Moreover, the heterogeneity of cells responding to anticancer drugs was observed at the single-cell level. This proof-of-concept study demonstrated the potential of Raman-DIP to be a reliable tool for cancer drug discovery and drug susceptibility testing.

scholarly journals Matching anticancer compounds and tumor cell lines by neural networks with ranking loss

2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Paul Prasse ◽  
Pascal Iversen ◽  
Matthias Lienhard ◽  
Kristina Thedinga ◽  
Chris Bauer ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Cancer Cell ◽  
Drug Sensitivity ◽  
Inhibitory Concentration ◽  
Cancer Cell Line ◽  
Tumor Cell Line ◽  
Ranking Problem ◽  
Ranking Loss

ABSTRACT Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug’s inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model’s capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.

22 The Cancer Cell Line Encyclopedia - Using Preclinical Models to Predict Anticancer Drug Sensitivity

2012 ◽  
Vol 48 ◽  
pp. S5-S6 ◽  
Author(s):  
J. Barretina ◽  
G. Caponigro ◽  
N. Stransky ◽  
K. Venkatesan ◽  
A.A. Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Preclinical Models ◽  
Cancer Cell Line Encyclopedia

scholarly journals Cflar Splicing SNP As Predictor of Chemo-Sensitivity to Anticancer Drugs

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2056-2056
Author(s):  
Lata Chauhan ◽  
Emilie J Bergsma ◽  
Jatinder K Lamba
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Extrinsic Pathway ◽  
Wide Range

Abstract Background: Anticancer therapeutics leverages activation of apoptosis signal transduction pathways (extrinsic and intrinsic apoptotic pathways) in cancer cells. Apoptosis induced by the extrinsic pathway complements that induced by the intrinsic pathway, so targeting extrinsic pathway is considered a useful new therapeutic approach. Preclinical data suggests TNF related apoptosis inducing ligand (TRAIL) as a promising approach as apoptosis of tumor cells is achievable in vivo without lethal toxicities. CASP8 and FADD-like apoptosis regulator (CFLAR) is an inhibitor of death receptor signaling that inhibits TRAIL-mediated caspase 8 auto-activation and subsequent apoptosis. We recently identified a splicing single nucleotide polymorphism (SNP) rs10190751 G>A in CFLAR, where presence of the variant allele (A) was associated with alternate splicing as well as with chemo-sensitivity to chemotherapeutic agent triptolide. However role of CFLAR and the splicing SNP on chemo-sensitivity to wide array of anticancer drugs is not known. Objective: Given the central role of CFLAR in apoptotic pathway, the goal of this study was to investigate impact of CFLAR and its splicing SNP on cytotoxicity of wide range of chemotherapeutic drugs including the ones extensively used in hematological malignancies. Methods: We selected chemotherapeutic agents with wide range of mechanisms of action as blocking DNA biosynthesis, interfering with structure or function of DNA or protein synthesis, interfering with DNA transcription or replication as well as drugs that are cell cycle specific or not. We selected nine Epstein-Barr-virus transformed lymphoblastoid cell lines (LCLs) that are part of International HapMap project representing different genotype for rs10190751 (CFLAR splicing polymorphism; 3 in each genotype category) with twelve different chemotherapeutic agents. Further validation of CFLAR's role in in vitro chemosensitivity was evaluated using CFLAR knockdown and overexpression studies in pancreatic and leukemic cell lines such as Panc-1 and THP1. Results: CFLAR splicing SNP rs10190751, was associated with in vitro cytotoxicity of several chemotherapeutic agents (Bortezomib, SAHA, doxorubicin, sorafenib). The results of screening of 122 FDA approved drugs and their relation with CFLAR as well as its splicing SNP will be presented at the annual meeting. As an example we show below that knock down of CFLAR isoforms have a significant impact on in vitro chemosensitivity to bortezomib and SAHA (Figure 1) Conclusion: Our results suggest critical role of CFLAR in anticancer drug mediated cell death. Additionally splicing SNP in CFLAR seems to play an important role in drug sensitivity/resistance. Therapeutic strategies to directly or indirectly inhibit the expression and/or function of CFLAR might be an attractive option to overcome resistance to wide range of chemotherapeutic agents. Figure 1. Impact of siRNA mediated knockdown or of CFLAR on Bortezomib and SAHA sensitivity in THP1 and Panc-1 cancer cell line. Figure 1. Impact of siRNA mediated knockdown or of CFLAR on Bortezomib and SAHA sensitivity in THP1 and Panc-1 cancer cell line. Disclosures No relevant conflicts of interest to declare.

scholarly journals Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

Nature ◽  
2018 ◽  
Vol 565 (7738) ◽  
pp. E5-E6 ◽  
Author(s):  
Jordi Barretina ◽  
Giordano Caponigro ◽  
Nicolas Stransky ◽  
Kavitha Venkatesan ◽  
Adam A. Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Predictive Modelling ◽  
Cancer Cell Line Encyclopedia

scholarly journals The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

Nature ◽  
2012 ◽  
Vol 483 (7391) ◽  
pp. 603-607 ◽  
Author(s):  
Jordi Barretina ◽  
Giordano Caponigro ◽  
Nicolas Stransky ◽  
Kavitha Venkatesan ◽  
Adam A. Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Predictive Modelling ◽  
Cancer Cell Line Encyclopedia

Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

Nature ◽  
2012 ◽  
Vol 492 (7428) ◽  
pp. 290-290 ◽  
Author(s):  
Jordi Barretina ◽  
Giordano Caponigro ◽  
Nicolas Stransky ◽  
Kavitha Venkatesan ◽  
Adam A. Margolin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Cancer Cell Line ◽  
Predictive Modelling ◽  
Cancer Cell Line Encyclopedia

New Platinum (II) Ternary Complexes of Formamidine and Pyrophosphate: Synthesis, Characterization and DFT Calculations and In vitro Cytotoxicity

2020 ◽  
Vol 23 (7) ◽  
pp. 611-623
Author(s):  
Ahmed A. Soliman ◽  
Fawzy A. Attaby ◽  
Othman I. Alajrawy ◽  
Azza A.A. Abou-hussein ◽  
Wolfgang Linert
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Theoretical Calculations ◽  
Thermal Analyses ◽  
Cancer Cell Line ◽  
Cellular Growth ◽  
Planar Geometry ◽  
Square Planar ◽  
Vis Spectroscopy

Aim and Objective: Platinum (II) and platinum (IV) of pyrophosphate complexes have been prepared and characterized to discover their potential as antitumor drugs. This study was conducted to prepare and characterize new ternary platinum (II) complexes with formamidine and pyrophosphate as an antitumor candidate. Materials and Methods: The complexes have been characterized by mass, infrared, UV-Vis. spectroscopy, elemental analysis, magnetic susceptibility, thermal analyses, and theoretical calculations. They have been tested for their cytotoxicity, which was carried out using the fastcolorimetric assay for cellular growth and survival against MCF-7 (breast cancer cell line), HCT- 116 (colon carcinoma cell line), and HepG-2 (hepatocellular cancer cell line). Results: All complexes are diamagnetic, and the electronic spectral data displayed the bands due to square planar Pt(II) complexes. The optimized complexes structures (1-4) indicated a distorted square planar geometry where O-Pt-O and N-Pt-N bond angles were 82.04°-96.44°, respectively. Conclusion: The complexes showed noticeable cytotoxicity and are considered as promising antitumor candidates for further applications.

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