gene expression data of cell lines  (BioSino Inc)

Journal: Cancers

Article Title: Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer

doi: 10.3390/cancers17030446

Figure Lengend Snippet: Assessment of in vitro antiproliferative activity of targeted agents in a panel of SCLC cell lines ( a ); effect of volasertib ( b ) and onvansertib ( c ) on proliferation of SCLC cell lines. Cells were treated for 72 h with indicated agents. Cell proliferation was determined using colorimetric or luminescent assays depending on the degree of clustering of SCLC cell lines in culture. Values represent the mean ± S.D. from a minimum of 3 independent experiments. Blue and orange curves define cell lines with non-disruptive and disruptive p53 mutations, respectively. Basal protein expression in SCLC cell lines ( d ). SCLC subtype based on expression are indicated after each cell line: ASCL1 (A), POU2F3 (P), YAP1 (Y).

Article Snippet: We accessed the gene expression data of human SCLC cell lines previously generated on the Illumina HT-12 platform and deposited in the NCBI Gene Expression Omnibus (GEO accession GSE55830) [ ].

Techniques: In Vitro, Activity Assay, Expressing

Journal: Cancers

Article Title: Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer

doi: 10.3390/cancers17030446

Figure Lengend Snippet: SCLC cell line sensitivity to PLK1 inhibitors measured by IC 50 concentration.

Article Snippet: We accessed the gene expression data of human SCLC cell lines previously generated on the Illumina HT-12 platform and deposited in the NCBI Gene Expression Omnibus (GEO accession GSE55830) [ ].

Techniques: Concentration Assay, Mutagenesis

Journal: Cancers

Article Title: Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer

doi: 10.3390/cancers17030446

Figure Lengend Snippet: Effect of TP53 mutational status on PLK1 inhibitor sensitivity. Comparison of mean IC 50 to TP53 gene mutation status ( a ). TP53 gene status in 166 tumor samples in cbioportal.org ( b ) and 50 SCLC cell lines from publicly available CCLE data ( c ). Activity of PLK1 inhibitor onvansertib in parental and resistant H526 cells (IC 50 concentration in the resistant vs. parent: 447 nM vs. 51 nM) ( d ). Gene expression profiles of matched parental and PLK1 inhibitor resistant H526 cells from 3 separate samples ( e ). Heatmap shows the top differential gene expression ( p -adj < 0.5; logFC > 4 cut-off) with red indicating high and blue indicating low natural log-transformed expression.

Article Snippet: We accessed the gene expression data of human SCLC cell lines previously generated on the Illumina HT-12 platform and deposited in the NCBI Gene Expression Omnibus (GEO accession GSE55830) [ ].

Techniques: Comparison, Mutagenesis, Activity Assay, Concentration Assay, Gene Expression, Transformation Assay, Expressing

Journal: Nucleic Acids Research

Article Title: Passer , a highly active transposon from a fish genome, as a potential new robust genetic manipulation tool

doi: 10.1093/nar/gkad005

Figure Lengend Snippet: Analysis of the PS insertion sites in the human genome. ( A ) Distribution of PS and SB insertions in gene-related regions of the human genome. The y -axis is shown in a square root scale. The asterisks depict the significance ranges of Fisher's exact test. TSS, transcriptional start site; TES, transcriptional end site. ( B ) Distribution of insertion sites within gene bodies. For the analysis, all genes were divided into 10 segments of equal length; 100% stands for the last nucleotide of the genes. ( C ) Insertion site distributions in a 6 kb window centred on the TSSs of genes. ( D ) Integration frequencies in eight gene groups with increasing expression levels in HepG2 cells. ( E ) Insertion site frequencies in functional genomic categories. The categories on the x -axis were established using combined histone modification based on ChIP-Seq, RNA-Seq and DNase-Seq datasets for the HepG2 cell line. The numbers in the boxes are fold change values above the random expected frequencies (arbitrarily set to 1). The dendrogram on the left is based on row means. The red and blue colours stand for over- and under-representation, respectively. The asterisks indicate the significance ranges based on the P -values of Fisher's exact test between the values of PS and SB100X.

Article Snippet: The HepG2 cell line-specific gene expression data were obtained from the Human Protein Atlas ( https://www.proteinatlas.org/about/download ).

Techniques: Expressing, Functional Assay, Modification, ChIP-sequencing, RNA Sequencing

Journal: Cancers

Article Title: Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma

doi: 10.3390/cancers13174476

Figure Lengend Snippet: TP53 mutation status insufficiently predicts the APR-246/PRIMA-1 response. ( a ): PRIMA-1 sensitivity separated according to TP53 mutation status derived from Cancer Cell Line Encyclopedia and CTD 2 portal ( n = 805); ( b ): Expression of p53 is shown in the Western blot of the whole cell lysates of one TP53 nonsense mutated cell line (KNS-42), three TP53 missense mutated cell lines (SJ-GBM2, SF188, SK-N-BE(2)-C) and one TP53 wild type cell line (IMR-32). GAPDH served as loading control. The ratio indicates normalization of p53 to the GAPDH signal; ( c , d ): RT-PCR measurement of TP53 pathway activation. CDKN1A expression is depicted as log2 transformed fold change to solvent control. Treatment was applied for 24 h with doxorubicin or APR-246, alone or in combination, as indicated; ( e , f ): metabolic activity measurement with CellTiter Glo-assay in neuroblastoma cell lines IMR-32 ( e ) and SK-N-BE(2)-C ( f ) after 72 h treatment. IMR-32 ( e ) were treated with 0–100 nM doxorubicin alone (blue) or in combination with a fixed APR-246 concentration of 1 µM (red). SK-N-BE(2)-C ( f ) were treated with 0–1000 nM doxorubicin alone (blue) or in combination with a fixed APR-246 concentration of 20 µM (red). Luminescence was normalized to the solvent control (DMSO). ( g , h ): metabolic activity measurement with CellTiter Glo-assay in pediatric high-grade glioma cell lines SJ-GBM2 ( g ) and SF188 ( h ) upon 72 h treatment. Both were treated with 0–1000 nM doxorubicin alone (blue) or in combination with a fixed APR-246 concentration of 30 µM (red). Luminescence was normalized to the solvent control (DMSO).

Article Snippet: We then looked for differentially expressed genes in the responsive versus less-responsive cohorts using the Cancer Cell Line Encyclopedia (CCLE, Broad Institute, Cambridge, MA, USA) gene expression data set in R2 (R2: microarray and visualization platform: http://r2.amc.nl , accessed on 5 January 2021).

Techniques: Mutagenesis, Derivative Assay, Expressing, Western Blot, Control, Reverse Transcription Polymerase Chain Reaction, Activation Assay, Transformation Assay, Solvent, Activity Assay, Glo Assay, Concentration Assay

Journal: Cancers

Article Title: Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma

doi: 10.3390/cancers13174476

Figure Lengend Snippet: APR-246 response depends on the ROS levels. ( a ): The percentage of ROS positive IMR-32 cells after treatment with 50 µM APR-246 for 5 h compared to solvent control (DMSO) detected after DCFDA staining by FACS; ( b ): Log2 fold change of BODIPY positive IMR-32 cells after treatment with 50 µM APR-246 for 5 h compared to solvent control (DMSO) detected by FACS; ( c ): Basal ROS level in IMR-32, SK-N-BE(2)-C and SJ-GBM2 detected after DCFDA staining by FACS. Data were normalized to IMR-32 signal; ( d ): Log2 fold change of basal ROS level in vincristine resistant SK-N-BE(2)-C compared to control SK-N-BE(2)-C detected after DCFDA staining by FACS; ( e ): Metabolic activity measurement with CellTiter Glo-assay in vincristine resistant SK-N-BE(2)-C (red) and control SK-N-BE(2)-C (blue) after 72 h treatment with APR-246 0–30 µM. Luminescence was normalized to the respective solvent control (DMSO); ( f ): Log2 SLC7A11 expression of PRIMA-1 less responsive cell lines (LowRes, IC50 < 20 µM) compared to responsive cell lines (Res, IC50 > 20 µM) from the Cancer Cell Line Encyclopedia ( n = 744); ( g ): Combination of log2 SLC7A11 expression and PRIMA-1 sensitivity stratified by cancer cell line entities with data obtained from Cancer Cell Line Encyclopedia and CTD 2 portal ( n = 229); ( h ): Plot of the mean log2 SLC7A11 expression of entities ( n = 26) from the CCLE against the mean PRIMA-1 IC50 of the respective entities. Pearson correlation coefficient was calculated using R software; ( i ) Z-scores of SLC7A11 log2 expression from INFORM patient samples stratified by entities and analyzed with R2 ( n = 1643). ACC: adrenocortical carcinoma, ALL: acute lymphoblastic leukemia, AML: acute myeloid leukemia, ATRT: atypical teratoid/rhabdoid tumor, BRA: Brain cancer, EBR: embryonal brain tumor, EPEN: ependymoma, GCT: germ cell tumor, HCC: hepatocellular carcinoma, HBL: hepatoblastoma, HCC: Liver cancer, HGG: high-grade glioma, HNC: Head and Neck Cancer, KID: Kidney Cancer, LYM: Lymphoma, MED: medulloblastoma, MRT: malignant rhabdoid tumor, NB: neuroblastoma, ND: not defined, NHL: non-Hodgkin lymphoma, EWS: Ewing sarcoma, OST: osteosarcoma, RBD: Rhabdoid, RMS: rhabdomyosarcoma, OTHS: other sarcoma, WILMS: nephroblastoma, OTH: other, OTHB: other brain tumor. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: We then looked for differentially expressed genes in the responsive versus less-responsive cohorts using the Cancer Cell Line Encyclopedia (CCLE, Broad Institute, Cambridge, MA, USA) gene expression data set in R2 (R2: microarray and visualization platform: http://r2.amc.nl , accessed on 5 January 2021).

Techniques: Solvent, Control, Staining, Activity Assay, Glo Assay, Expressing, Software

Journal: Cancers

Article Title: Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma

doi: 10.3390/cancers13174476

Figure Lengend Snippet: Identification of a biomarker predicting APR-246 responsiveness ( a ): in silico analysis of log2 SLC7A11 and PRIMA-1 sensitivity (IC50 in µM) with data obtained from Cancer Cell Line Encyclopedia and CTD 2 portal for available neuroblastoma cell lines. The Pearson correlation coefficient (0.145) was calculated using R software ( n = 12); ( b ): volcano plot of differentially expressed genes between less responsive cell lines (PRIMA-1 IC50 app. > 40 µM, n = 303) and responsive cell lines (PRIMA-1 IC50 app. < 10 µM, n = 102) calculated using R2 software. Except for YAP1 and MIR142 (most significantly down and up-regulated gene respectively) all red dots indicate genes that are part of the genetic signature; ( c , d ): boxplot of z-score of in responsive cell lines that were the most significantly downregulated ( c , YAP1 ) and upregulated ( d , MIR142 ) genes plotted with R2; ( e , f ): receiver operating characteristic (ROC) curve calculated with ROCR package in R software for the genetic signature score to discriminate between low-responders (PRIMA-1 IC50 app. > 40 µM, n = 303) and responders (PRIMA-1 IC50 app. < 10 µM, n = 102) ( e ) or to discriminate the IC50s less than or greater than 20 µM ( f ). Responder and low-responder status ( n = 405) ( e ) or the whole CCLE cell lines ( n = 711) with known PRIMA-1 sensitivity data were used as test cohort ( f ); ( g ): in silico analysis of genetic signature score predicting PRIMA-1 responsiveness in neuroblastoma sub-cohort from CCLE ( n = 12). PRIMA-1 sensitivity cut-off 20 µM was chosen. Ten out of twelve cell lines were predicted correctly. SK-N-SH and SK-N-DZ were falsely predicted to be low-responders. LowRes: low-responder ( n = 303), Res: responder ( n = 102).

Article Snippet: We then looked for differentially expressed genes in the responsive versus less-responsive cohorts using the Cancer Cell Line Encyclopedia (CCLE, Broad Institute, Cambridge, MA, USA) gene expression data set in R2 (R2: microarray and visualization platform: http://r2.amc.nl , accessed on 5 January 2021).

Techniques: Biomarker Discovery, In Silico, Software

Journal: Breast Cancer Research : BCR

Article Title: The small G-protein RalA promotes progression and metastasis of triple-negative breast cancer

doi: 10.1186/s13058-021-01438-3

Figure Lengend Snippet: RALA, not RALB, is pro-tumorigenic in preclinical in vivo models of TNBC utilizing CRISPR mediated knockout of RALA/B. a Western blots demonstrating RALA and RALB expression in MDA-MB-231 CRISPR control (Ctrl), RALA CRISPR knockout (RALA-KO), and RALB CRISPR knockout (RALB-KO) cells. b Quantification of RALA and RALB expression in MDA-MB-231 Ctrl, RALA-KO, and RALB-KO cells by ImageJ analysis ( n = 3). c Representative images of RALA and RALB immunofluorescence staining in MDA-MB-231 Ctrl, RALA-KO and RALB-KO cells (red = RALA or RALB, blue = DAPI; scale bars = 20μm). d Quantification of MDA-MB-231 Ctrl ( n = 10), RALA-KO ( n = 8), and RALB-KO ( n = 12) orthotopic mammary tumor growth. e Representative images and H-score quantification of Ki67 immunostaining in MDA-MB-231 CRISPR Ctrl, RALA-KO, and RALB-KO orthotopic mammary tumors (scale bar = 40μm). f Representative images and H-score quantification of cleaved caspase 3 (CC3) immunostaining in MDA-MB-231 Ctrl, RALA-KO, and RALB-KO orthotopic mammary tumors (scale bar = 20μm). Data are presented as mean ± SEM; (*), P < 0.05

Article Snippet: Breast cancer cell line gene expression data was obtained from the Broad Institute Cancer Cell Line Encyclopedia (CCLE, [ ]).

Techniques: In Vivo, CRISPR, Knock-Out, Western Blot, Expressing, Control, Immunofluorescence, Staining, Immunostaining

Journal: Breast Cancer Research : BCR

Article Title: The small G-protein RalA promotes progression and metastasis of triple-negative breast cancer

doi: 10.1186/s13058-021-01438-3

Figure Lengend Snippet: RALA, not RALB, is pro-tumorigenic in preclinical in vivo models of TNBC utilizing short hairpin knockdown of RALA/B. a Western blots demonstrating RALA and RALB expression in MDA-MB-231 shRNA control (shCtrl), shRALA, and shRALB cells. b Comparison of MDA-MB-231 shCtrl ( n = 5) and shRALA ( n = 5) orthotopic mammary tumor growth. c Comparison of MDA-MB-231 shCtrl ( n = 7) and shRALB ( n = 8) orthotopic mammary tumor growth. d Representative Ki67 immunostaining images and H-score quantification of MDA-MB-231 shCtrl ( n = 4) and shRALA ( n = 4) orthotopic mammary tumors. e Representative cleaved caspase 3 (CC3) immunostaining images and H-score quantification of MDA-MB-231 shCtrl ( n = 4) and shRALA ( n = 4) orthotopic mammary tumors. f Quantification of Rala mRNA expression in MVT1 shCtrl and shRALA cells by qRT-PCR (left) and growth of orthotopic mammary tumors (right; n =6 per group). Inset shows western blot confirmation of RALA protein expression in MVT1 shCtrl and shRALA cells. Data are presented as mean ± SEM; (*), P < 0.05; scale bars = 20μm

Article Snippet: Breast cancer cell line gene expression data was obtained from the Broad Institute Cancer Cell Line Encyclopedia (CCLE, [ ]).

Techniques: In Vivo, Knockdown, Western Blot, Expressing, shRNA, Control, Comparison, Immunostaining, Quantitative RT-PCR

Journal: Breast Cancer Research : BCR

Article Title: The small G-protein RalA promotes progression and metastasis of triple-negative breast cancer

doi: 10.1186/s13058-021-01438-3

Figure Lengend Snippet: RALA is elevated in TNBC and is prognostic of overall survival in ER-negative disease. a Western blots demonstrating RALA and RALB expression in a panel of BC cell lines denoted by molecular subtype. b RALA and RALB mRNA expression in a panel of 46 BC cell lines categorized according to molecular subtype. Data from the Broad Institute Cancer Cell Line Encyclopedia (CCLE), (*) P < 0.05. c Box and whisker plots of RALA and RALB expression in normal breast tissue ( n = 61), BC subtypes other than TNBC ( n = 300) , and TNBC ( n = 49). Data from TCGA Research Network. (*) P < 0.05. d Box and whisker plots of RALA and RALB expression in normal breast tissue ( n = 144), BC subtypes other than TNBC ( n = 1725), and TNBC ( n = 250). Data from METABRIC. (*) P < 0.05. e Left: Kaplan-Meier analysis segregates all BC patients by RALA (upper quartile vs lower three-quartiles) and RALB (spilt along the median) expression in METABRIC and TCGA datasets wherein high RALA is prognostic of worse disease specific survival (DSS) in the METABRIC ( P = 0.0079) and overall survival in the TCGA ( P = 0.0003) cohorts and low RALB is prognostic of worse DSS in the METABRIC cohort ( P = 0.0311), but is not prognostic in the TCGA cohort ( P = 0.9477). Right: Within the TNBC population of the METABRIC cohort, RALA (upper tenth percentile vs lower 90th percentail) is prognostic of worse DSS TNBC patients ( P = 0.0544) while RALB (spilt along the median) is not prognostic ( P = 0.9297). Significance determined by log-rank. f Top: Representative high and low RALA immunostaining of BC patient samples. Bottom: Kaplan-Meier analysis segregating all BC patients ( P = 0.0417) and TNBC patients ( P = 0.0440) by RALA H-score (upper tertile vs lower two tertiles) where high RALA is prognostic of worse overall survival (Scale bars = 60μm)

Article Snippet: Breast cancer cell line gene expression data was obtained from the Broad Institute Cancer Cell Line Encyclopedia (CCLE, [ ]).

Techniques: Western Blot, Expressing, Whisker Assay, Immunostaining