scholarly journals Anti-Cancer Drug Sensitivity Assay with Quantitative Heterogeneity Testing Using Single-Cell Raman Spectroscopy

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2903 ◽  
Author(s):  
Yong Zhang ◽  
Jingjing Xu ◽  
Yuezhou Yu ◽  
Wenhao Shang ◽  
Anpei Ye
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Drug Sensitivity ◽  
Principal Component ◽  
Coefficient Of Determination ◽  
Cancer Drug ◽  
Sensitivity Testing ◽  
Anti Cancer ◽  
Cytotoxic Compounds

A novel anti-cancer drug sensitivity testing (DST) approach was developed based on in vitro single-cell Raman spectrum intensity (RSI). Generally, the intensity of Raman spectra (RS) for a single living cell treated with drugs positively relates to the sensitivity of the cells to the drugs. In this study, five cancer cell lines (BGC 823, SGC 7901, MGC 803, AGS, and NCI-N87) were exposed to three cytotoxic compounds or to combinations of these compounds, and then they were evaluated for their responses with RSI. The results of RSI were consistent with conventional DST methods. The parametric correlation coefficient for the RSI and Methylthiazolyl tetrazolium assay (MTT) was 0.8558 ± 0.0850, and the coefficient of determination was calculated as R2 = 0.9529 ± 0.0355 for fitting the dose–response curve. Moreover, RSI data for NCI-N87 cells treated by trastuzumab, everolimus (cytostatic), and these drugs in combination demonstrated that the RSI method was suitable for testing the sensitivity of cytostatic drugs. Furthermore, a heterogeneity coefficient H was introduced for quantitative characterization of the heterogeneity of cancer cells treated by drugs. The largest possible variance between RSs of cancer cells were quantitatively obtained using eigenvalues of principal component analysis (PCA). The ratio of H between resistant cells and sensitive cells was greater than 1.5, which suggested the H-value was effective to describe the heterogeneity of cancer cells. Briefly, the RSI method might be a powerful tool for simple and rapid detection of the sensitivity of tumor cells to anti-cancer drugs and the heterogeneity of their responses to these drugs.

scholarly journals Effects of light-activated diazido-Pt IV complexes on cancer cells in vitro

2013 ◽  
Vol 371 (1995) ◽  
pp. 20120118 ◽  
Author(s):  
Patrick J. Bednarski ◽  
Katharina Korpis ◽  
Aron F. Westendorf ◽  
Steffi Perfahl ◽  
Renate Grünert
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Calf Thymus Dna ◽  
Cross Resistance ◽  
Cancer Drug ◽  
Cancer Cell Growth ◽  
Calf Thymus ◽  
Anti Cancer ◽  
Cellular Dna

Various Pt IV diazides have been investigated over the years as light-activatable prodrugs that interfere with cell proliferation, accumulate in cancer cells and cause cell death. The potencies of the complexes vary depending on the substituted amines (pyridine=piperidine>ammine) as well as the coordination geometry ( trans diazide> cis ). Light-activated Pt IV diazides tend to be less specific than cisplatin at inhibiting cancer cell growth, but cells resistant to cisplatin show little cross-resistance to Pt IV diazides. Platinum is accumulated in the cancer cells to a similar level as cisplatin, but only when activated by light, indicating that reactive Pt species form photolytically. Studies show that Pt also becomes attached to cellular DNA upon the light activation of various Pt IV diazides. Structures of some of the photolysis products were elucidated by LC–MS/MS; monoaqua- and diaqua-Pt II complexes form that are reactive towards biomolecules such as calf thymus DNA. Platination of calf thymus DNA can be blocked by the addition of nucleophiles such as glutathione and chloride, further evidence that aqua-Pt II species form upon irradiation. Evidence is presented that reactive oxygen species may be generated in the first hours following photoactivation. Cell death does not take the usual apoptotic pathways seen with cisplatin, but appears to involve autophagy. Thus, photoactivated diazido-Pt IV complexes represent an interesting class of potential anti-cancer agents that can be selectively activated by light and kill cells by a mechanism different to the anti-cancer drug cisplatin.

scholarly journals Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells

2017 ◽  
Vol 5 (3) ◽  
pp. 532-550 ◽  
Author(s):  
Muhammad Gulfam ◽  
Teresa Matini ◽  
Patrícia F. Monteiro ◽  
Raphaël Riva ◽  
Hilary Collins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Vitro Activity ◽  
Cancer Drug ◽  
In Vitro Activity ◽  
Anti Cancer ◽  
Poly Caprolactone ◽  
Core Polymer

PEG-poly(caprolactone) co-polymers with disulfide-linked cores are highly efficient for delivery of the anti-cancer drug methotrexate in vitro.

scholarly journals Abstract 2168: Anti-cancer drug sensitivity assay using in vitro primary culture cells

2018 ◽  
Author(s):  
Shiki Fujino ◽  
Norikatsu Miyoshi ◽  
Masayuki Ohue ◽  
Kazuhiro Saso ◽  
Tsunekazu Mizushima ◽  
...  
Keyword(s):  
Primary Culture ◽  
Drug Sensitivity ◽  
Cancer Drug ◽  
Culture Cells ◽  
Anti Cancer ◽  
Drug Sensitivity Assay

RRM1 expression is verified as a biomarker predicting the drug sensitivity for GEM with in vitro 3D drug sensitivity test in non-small cell lung cancer tumor.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20054-e20054
Author(s):  
Nariyasu Nakashima ◽  
Dage Liu ◽  
Takayuki Nakano ◽  
Yusuke Kita ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Predictive Value ◽  
Drug Sensitivity ◽  
Collagen Gel ◽  
Small Cell ◽  
Cancer Drug ◽  
Small Cell Lung ◽  
Drug Sensitivity Test ◽  
Anti Cancer

e20054 Background: Ribonucleotide reductase M1 (RRM1) is involved in regulation of cell proliferation and synthesis of deoxyribonucleotides for DNA. It is also a cellular target for gemcitabine (GEM) and overexpression of RRM1 was reported to be associated with the resistance to GEM. Though RRM1 expression has been reported as the biomarkers in predicting the response to chemotherapy clinically, the value of GEM remains inconsistent and controversial. Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is a newly developed in vitro chemosensitivity test that could directly inspect the anti-cancer drug sensitivity with fresh tumor tissue. With use of CD-DST test, we have verified the predictive value of RRM1 expression to the anti-cancer agent sensitivity for GEM in non-small cell lung cancer (NSCLC) tumor. Here, the predictive value of biomarker RRM1 to GEM was further verified with CD-DST. Methods: Twenty-five patients with primary NSCLC were used in this study. Expression of RRM1 was assessed by immunohistochemistry. For CD-DST test, viable cells were collected from fresh surgical specimen and embed into the collagen gel droplets in 3D condition. Tumor cells were exposed to GEM for 1 hour and further incubated with serum-free culture medium for 7 days. The in vitro sensitivity was expressed as the percentage T/C ratio, where T was the total volume of the treated group and C was the total volume of the control group. Results: 1)Anti-cancer drug sensitivity: The sensitivity for GEM (T/C%) was 76.2 ± 30.5. 2)Expression of biomarkers: RRM1 expression was 39.2 ± 28.2 %. 3) Correlation: The expression of RRM1 significantly correlated with drug sensitivity for GEM (r = 0.446, p = 0.0256). Higher expression of RRM1 indicated worse anti-cancer drug sensitivity for GEM. Conclusions: The significant correlation between the RRM1 expression and sensitivity to GEM was proved with CD-DST in NSCLC tumors. The expression of RRM1 may become a useful biomarker in predicting the drug sensitivity for GEM in NSCLC.

scholarly journals Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy

2021 ◽  
Vol 22 (5) ◽  
pp. 2408
Author(s):  
Bin Zhang ◽  
Jiamei Zou ◽  
Qiting Zhang ◽  
Ze Wang ◽  
Ning Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Elongation Factor ◽  
Cancer Drug ◽  
Discovery Research ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Drug Discovery Research ◽  
Anti Cancer

Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure–activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo, with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.

scholarly journals Anti-cancer drug sensitivity testing in transplantable human osteosarcoma from mandible in nude mouse.

1990 ◽  
Vol 36 (3) ◽  
pp. 459-464 ◽  
Author(s):  
Jouji NOMURA ◽  
Toshirou TAGAWA ◽  
Jun MATSUMOTO ◽  
Madoka INUI ◽  
Hiroyuki KIHIRA
Keyword(s):  
Nude Mouse ◽  
Drug Sensitivity ◽  
Cancer Drug ◽  
Sensitivity Testing ◽  
Drug Sensitivity Testing ◽  
Human Osteosarcoma ◽  
Anti Cancer

scholarly journals Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

Theranostics ◽  
2018 ◽  
Vol 8 (19) ◽  
pp. 5259-5275 ◽  
Author(s):  
Yeonho Jo ◽  
Nakwon Choi ◽  
Kyobum Kim ◽  
Hyung-Jun Koo ◽  
Jonghoon Choi ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Drug Development ◽  
Cancer Cells ◽  
In Vitro Models ◽  
Cancer Drug ◽  
Anti Cancer

scholarly journals In vitro biophysical, microspectroscopic and cytotoxic evaluation of metastatic and non-metastatic cancer cells in responses to anti-cancer drug

2015 ◽  
Vol 7 (24) ◽  
pp. 10162-10169 ◽  
Author(s):  
Qifei Li ◽  
Lifu Xiao ◽  
Sitaram Harihar ◽  
Danny R. Welch ◽  
Elizabeth Vargis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Cancer ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Metastatic Cancer Cells

Breast cancer cells with or without BRMS1 in response to doxorubicin (DOX).

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