Chemosensitivity Prediction of Tumours Based on Expression, miRNA, and Proteomics Data

The chemosensitivity of tumours to specific drugs can be predicted based on molecular quantities, such as gene expressions, miRNA expressions, and protein concentrations. This finding is important for improving drug efficacy and personalizing drug use. In this paper, the authors present an analysis strategy that, compared to prior work, retains more information in the data for analysis and may lead to improved chemosensitivity prediction. The authors apply improved methods for estimating the GI50 value of a drug (an indicator of the response to the drug), regression methods for constructing predictive models of the GI50 value, advanced variable selection techniques, such as MMPC, and a multi-task variable selection technique for identifying a small-size signature that is simultaneously predictive for several drugs and cell lines. The methods are applied on gene expression, miRNA expression, and proteomics data from 53 tumour cell lines after treatment with 120 drugs, obtained from the National Cancer Institute databases. A biological interpretation and discussion of the results is presented for the most clinically important subset of 14 drugs.

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Screening of Venezuelan medicinal plant extracts for cytostatic and cytotoxic activity against tumour cell lines

Planta Medica ◽

10.1055/s-0032-1320482 ◽

2012 ◽

Vol 78 (11) ◽

Author(s):

P Taylor ◽

M Arsenak ◽

MJ Abad ◽

Á Fernández ◽

R Gonto ◽

...

Keyword(s):

Medicinal Plant ◽

Cytotoxic Activity ◽

Cell Lines ◽

Plant Extracts ◽

Tumour Cell ◽

Medicinal Plant Extracts ◽

Tumour Cell Lines

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Cytotoxic activity against tumour cell lines and anti-inflammatory effects of compounds isolated from Xylopia aromatica

Planta Medica ◽

10.1055/s-0033-1352067 ◽

2013 ◽

Vol 79 (13) ◽

Author(s):

O Estrada ◽

L González ◽

M Mijares ◽

Á Fernández ◽

M Ruiz ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Tumour Cell ◽

Tumour Cell Lines ◽

Anti Inflammatory

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Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines

Endocrine Abstracts ◽

10.1530/endoabs.31.p149 ◽

2013 ◽

pp. 1-1

Author(s):

E Kate Lines ◽

U Katherine Gaynor ◽

Mark Stevenson ◽

J Paul Newey ◽

E Sian Piret ◽

...

Keyword(s):

Cell Lines ◽

Tumour Cell ◽

Neuroendocrine Tumour ◽

Epigenetic Modifiers ◽

Tumour Cell Lines

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How to improve infectious disease prediction by integrating environmental data: an application of a novel ensemble analysis strategy to predict HFMD

Epidemiology and Infection ◽

10.1017/s0950268821000091 ◽

2021 ◽

Vol 149 ◽

Author(s):

Junwen Tao ◽

Yue Ma ◽

Xuefei Zhuang ◽

Qiang Lv ◽

Yaqiong Liu ◽

...

Keyword(s):

Variable Selection ◽

Mean Squared Error ◽

Moving Average ◽

Dynamic Bayesian Networks ◽

Environmental Data ◽

Control Measures ◽

Coefficient Of Determination ◽

Percentage Error ◽

Analysis Strategy ◽

Ensemble Analysis

Abstract This study proposed a novel ensemble analysis strategy to improve hand, foot and mouth disease (HFMD) prediction by integrating environmental data. The approach began by establishing a vector autoregressive model (VAR). Then, a dynamic Bayesian networks (DBN) model was used for variable selection of environmental factors. Finally, a VAR model with constraints (CVAR) was established for predicting the incidence of HFMD in Chengdu city from 2011 to 2017. DBN showed that temperature was related to HFMD at lags 1 and 2. Humidity, wind speed, sunshine, PM10, SO2 and NO2 were related to HFMD at lag 2. Compared with the autoregressive integrated moving average model with external variables (ARIMAX), the CVAR model had a higher coefficient of determination (R2, average difference: + 2.11%; t = 6.2051, P = 0.0003 < 0.05), a lower root mean-squared error (−24.88%; t = −5.2898, P = 0.0007 < 0.05) and a lower mean absolute percentage error (−16.69%; t = −4.3647, P = 0.0024 < 0.05). The accuracy of predicting the time-series shape was 88.16% for the CVAR model and 86.41% for ARIMAX. The CVAR model performed better in terms of variable selection, model interpretation and prediction. Therefore, it could be used by health authorities to identify potential HFMD outbreaks and develop disease control measures.

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Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

BMC Veterinary Research ◽

10.1186/s12917-020-02709-5 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Michela Levi ◽

Roberta Salaroli ◽

Federico Parenti ◽

Raffaella De Maria ◽

Augusta Zannoni ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Lines ◽

Tumour Cell ◽

S Phase ◽

Mammary Tumour ◽

Cancer Resistance ◽

Neoplastic Cells ◽

Canine Mammary Tumour ◽

Tumour Cell Lines

Abstract Background Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC). Results Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis. Conclusions DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.

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Oxonium Ion Guided Analysis of Quantitative Proteomics Data Reveals Site-Specific O-Glycosylation of Anterior Gradient Protein 2 (AGR2)

International Journal of Molecular Sciences ◽

10.3390/ijms22105369 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5369

Author(s):

Martina Pirro ◽

Yassene Mohammed ◽

Arnoud H. de Ru ◽

George M. C. Janssen ◽

Rayman T. N. Tjokrodirijo ◽

...

Keyword(s):

Cell Lines ◽

Quantitative Proteomics ◽

Glycosylation Site ◽

Total Cell ◽

Tandem Mass ◽

Proteomics Data ◽

Site Specific ◽

Oxonium Ions ◽

Tandem Mass Tag ◽

Colorectal Cancer Cell Lines

Developments in mass spectrometry (MS)-based analyses of glycoproteins have been important to study changes in glycosylation related to disease. Recently, the characteristic pattern of oxonium ions in glycopeptide fragmentation spectra had been used to assign different sets of glycopeptides. In particular, this was helpful to discriminate between O-GalNAc and O-GlcNAc. Here, we thought to investigate how such information can be used to examine quantitative proteomics data. For this purpose, we used tandem mass tag (TMT)-labeled samples from total cell lysates and secreted proteins from three different colorectal cancer cell lines. Following automated glycopeptide assignment (Byonic) and evaluation of the presence and relative intensity of oxonium ions, we observed that, in particular, the ratio of the ions at m/z 144.066 and 138.055, respectively, could be used to discriminate between O-GlcNAcylated and O-GalNAcylated peptides, with concomitant relative quantification between the different cell lines. Among the O-GalNAcylated proteins, we also observed anterior gradient protein 2 (AGR2), a protein which glycosylation site and status was hitherto not well documented. Using a combination of multiple fragmentation methods, we then not only assigned the site of modification, but also showed different glycosylation between intracellular (ER-resident) and secreted AGR2. Overall, our study shows the potential of broad application of the use of the relative intensities of oxonium ions for the confident assignment of glycopeptides, even in complex proteomics datasets.

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