Journal: Cancer Cell International

Article Title: Characterization of G2/M checkpoint classifier for personalized treatment in uterine corpus endometrial carcinoma

doi: 10.1186/s12935-025-03667-4

Figure Lengend Snippet: Validation of real-world cohort based on the classifier. A The expression levels of CDC7, ASPM, CENPE, KIF23 and DEPDC1B on qRT-PCR results. B By inputting the mRNA levels of the 5 model genes into the classifier, the real-world UCEC cohort was identified as two G2MC subtypes. Representative immunohistochemistry images of CDC7, ASPM, CENPE, KIF23, and DEPDC1B in the two G2MC subtypes, magnification 40x. C K-M survival analysis of two G2MC subtypes based on optimal cutoff value grouping. The ending events are PFS. D The proportion of progression after treatment in the two groups of G2MC subtypes. E Comparing the proportion of patients with pathological grades G1 to G3 in the two G2MC subtypes in the real-world cohort. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Article Snippet: Subsequently, the sections were first incubated with primary antibodies CDC7 (1:200, CUSABIO, China), ASPM (1:200, CUSABIO, China), CENPE (1:500, Sanying, China), KIF23 (1:200, CUSABIO, China), and DEPDC1B (1:200, CUSABIO, China) at 4 °C overnight, and then incubated with multimerized anti-rabbit IgG-HRP secondary antibodies at room temperature for 90 min.

Techniques: Biomarker Discovery, Expressing, Quantitative RT-PCR, Immunohistochemistry

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: Box–whisker plots showing the expression of CDC7 in subgroups of esophageal carcinoma. Notes: ( A ) Boxplot showing relative expression of CDC7 in normal and esophageal carcinoma tissues. ( B and D ) Boxplot showing relative expression of CDC7 in all histology types ( B ), all stages ( C ), and all tumor grades ( D ) of esophageal carcinoma vs normal tissues from TCGA dataset. * P <0.05; ** P <0.01; *** P <0.001. Abbreviations: EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; TCGA, The Cancer Genome Atlas.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Whisker Assay, Expressing

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: CDC7 is highly expressed in ESCC tissues. Notes: ( A ) Representative IHC images of CDC7 expression in ESCC and matched adjacent normal tissues, top-left panel, negative staining in adjacent normal tissues; top-right panel, weak staining in ESCC; bottom-left panel, and moderate staining in ESCC; bottom-right panel, strong staining in ESCC. Magnification: 100×. ( B ) The IHC score of CDC7 was determined in ESCC and matched adjacent normal tissues; *** P <0.001. Abbreviations: ESCC, esophageal squamous cell carcinoma; IHC, immunohistochemistry.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Expressing, Negative Staining, Staining, Immunohistochemistry

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: Effect of CDC7 on proliferation of ESCC cells. Notes: ( A ) Protein levels of CDC7 in ESCC cells were analyzed by Western blotting. ( B and C ) KYSE150 cells were transfected with siCDC7 for 48 hours and KYSE30 cells were transfected with pcDNA3.1-CDC7 for 48 hours. RT-qPCR and Western blotting were performed to examine CDC7 mRNA and protein levels, respectively. KYSE150 cells were transfected with siCDC7 or treated with PHA-767491 (2.5 µM), and KYSE30 cells were transfected with pcDNA3.1-CDC7. ( D and E ) MTS assays were performed. ( F and G ) Colony formation assays were performed. Data are presented as the mean ± SD (n=3); * P <0.05; ** P <0.01. Abbreviations: ESCC, esophageal squamous cell carcinoma.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Western Blot, Transfection, Quantitative RT-PCR

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: Effect of CDC7 on cell cycle transition and apoptosis of ESCC cells. Notes: KYSE150 cells were transfected with siCDC7 or treated with PHA-767491 for 48 hours, and KYSE30 cells were transfected with pcDNA3.1-CDC7 for 48 hours. ( A and B ) Flow cytometry assays were performed to assess the effect of cell cycle transition. ( C and D ) Annexin V-FITC apoptosis assays were performed to assess the effect of apoptosis. Data are presented as the mean ± SD (n=3); * P <0.05; ** P <0.01; *** P <0.001. Abbreviations: ESCC, esophageal squamous cell carcinoma; FITC, fluorescein isothiocyanate.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Transfection, Flow Cytometry

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: Effect of CDC7 on migration and invasion of ESCC cells. Notes: KYSE150 cells were transfected with siCDC7 or treated with PHA-767491 for 48 hours, and KYSE30 cells were transfected with pcDNA3.1-CDC7 for 48 hours. ( A and B ) Effect of CDC7 on the migration was measured by wound-healing assays. The relative distances were calculated and compared in the bar graphs below. ( C and D ) Effect of CDC7 on the invasion was measured by transwell assays. The number of invaded cells were counted and compared in the bar graphs below. Magnification ×100. Data are presented as the mean ± SD (n=3) ( * P <0.05; ** P <0.01). Abbreviations: ESCC, esophageal squamous cell carcinoma.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Migration, Transfection

Journal: OncoTargets and therapy

Article Title: Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma

doi: 10.2147/OTT.S183629

Figure Lengend Snippet: Effect of CDC7 on sensitivity of ESCC cells to chemotherapy. Notes: KYSE150 cells were transfected with siCDC7 (scrambled RNA served as a control), and KYSE30 cells were transfected with pcDNA3.1-CDC7 (pcDNA3.1 plasmid served as a control). After 48 hours, KYSE150 cells were treated with Cis (10 µM) or 5-FU (2 µM) for 24 hours, and KYSE30 cells were treated with Cis (7 µM) or 5-FU (18 µg/mL) for 24 hours. Cell survival was evaluated by MTS assay ( A and B ) and the apoptosis was analyzed by flow cytometry ( C and D ). Data are presented as the mean ± SD (n=3); * P <0.05; ** P <0.01; *** P <0.001. Abbreviations: Con, control; Cis, cisplatin; ESCC, esophageal squamous cell carcinoma; 5-FU, fluorouracil.

Article Snippet: Antibodies used for Western blotting assay were as follows: CDC7 (sc-56275, Santa Cruz Biotechnology Inc., Dallas, TX, USA); E-Cadherin (CST-14472, Cell Signaling Technology, Danvers, MA, USA); Snail (CST-3879, Cell Signaling Technology); Nrf2 (CST-12721, Cell Signaling Technology); Lamin B1 (CST-13435, Cell Signaling Technology); and α-tubulin (PM054; MBL, Nagoya, Japan).

Techniques: Transfection, Control, Plasmid Preparation, MTS Assay, Flow Cytometry

Journal: Cell Death Discovery

Article Title: Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening

doi: 10.1038/s41420-023-01315-2

Figure Lengend Snippet: A Schematic of the screening process using resistant SCLC cells H69-AR with GeCKOv2 library. B Volcano plot of differentially enriched sgRNAs between negative treatment and chemo-treatment. C Workflow of potential synergistic targets identification. D Expression of CDC7 in SCLC and normal tissues from GSE43346. Independent sample t-test were used to examine statistical significance. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: Antibodies used in this study are as follow: CDC7, MCM2, PARP, Caspase3, cleaved-Caspase3, Bcl-2, Bax, Cyclin E1, Cyclin D1, and GAPDH were purchased from Proteintech Group, UK.

Techniques: Expressing

Journal: Cell Death Discovery

Article Title: Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening

doi: 10.1038/s41420-023-01315-2

Figure Lengend Snippet: A qRT-PCR analyses of CDC7 expression in H69-AR(left) and H446-DDP(right) 48 h after transfected with CDC7 siRNA. B Western blot analyses of CDC7 and MCM2 in H69-AR(left) and H446-DDP(right) 48 h after transfected with CDC7 siRNA. IC 50 and the statistics of IC 50 of DDP in H69-AR ( C , D ) and H446-DDP ( E , F ) transfected with scramble or si- CDC7 . Cell viability of H69-AR ( G ) and H446-DDP ( H ) transfected with si- CDC7 using CCK-8 assay. All data are representative of three independent experiments (mean ± SEM).

Article Snippet: Antibodies used in this study are as follow: CDC7, MCM2, PARP, Caspase3, cleaved-Caspase3, Bcl-2, Bax, Cyclin E1, Cyclin D1, and GAPDH were purchased from Proteintech Group, UK.

Techniques: Quantitative RT-PCR, Expressing, Transfection, Western Blot, CCK-8 Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: CDC7 is upregulated during NE transformation in lung and prostate tumors. a Schematic of the generation of a PDX-derived, short-term cultured cell line generation, derived from the T-SCLC PDX Lx_151, and handling for the performance of CRISPR-Cas9 KO screen to identify therapeutic vulnerabilities of T-SCLC. Created with BioRender.com. b Plot showing genes for which sgRNAs were depleted in the CRISPR-Cas9 KO screen, ranked by p-value. Red dots are indicative of genes passing the p-value threshold. CDC7 mRNA expression c and protein abundance ( d ) in lung cancer clinical specimens, categorized as control never transformed adenocarcinomas (LUAD, RNA n = 11, protein n = 46), transforming adenocarcinomas (T-LUAD, RNA n = 11, protein n = 10) and small cell carcinomas (T-SCLC, RNA n = 11, protein n = 20) and control de novo small cell carcinomas (SCLC, RNA n = 16, protein n = 50). For ( d ), H-score medians and standard deviations (right) and representative immunohistochemistry (IHC) images (left) are shown. ( e ) CDC7 mRNA expression in prostate adenocarcinoma (PRAD) tumors with ( n = 22) or without ( n = 210) NE features (data from. ( f ) CDC7 protein expression in PRAD ( n = 30) and NEPC ( n = 7) PDX, as assessed by IHC. H-score medians and standard deviation (right) and representative images (left) are shown. p-value legend: *<0.05, **<0.01, ***<0.001

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Transformation Assay, Derivative Assay, Cell Culture, CRISPR, Expressing, Quantitative Proteomics, Control, Immunohistochemistry, Standard Deviation

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: TP53 and RB1 inactivation drive CDC7 upregulation in lung and prostate adenocarcinoma. a CDC7 mRNA expression in adenocarcinoma clinical specimens, categorized by TP53/RB1 mutational status. Data obtained from LUAD TCGA (PanCancer, n = 237 wild type (wt), 33 mutated), LUAD OncoSG ( n = 109 wt, 6 mutated) and PRAD SU2C/PCF Dream Team ( n = 107 wt, 19 mutated) ( b ) Western blot images showing CDC7 protein expression in isogenic H1563 (LUAD) and 22PC (PRAD) cell lines with or without induced loss of function of TP53 and/or RB1 by shRNA against RB1 and dominant negative TP53 gene overexpression (H1563) or CRISPR/Cas9 knock out (22PC). Representative western blot image is shown (top) with quantification shown, as volume of the CDC7 band normalized by the volume of actin, and again normalized to control expression, which takes the value of 1. c Binding score for TP53 and E2F1 in the transcription start site of the CDC7 gene in different experimental settings including specimens from prostate and other tissues. Data obtained from The Signaling Pathways Project (ChIP-seq Atlas). d Barplot exhibiting data from CDC7 gene promoter reporter assays in isogenic H1563 (LUAD) and 22PC (PRAD) cell lines with or without induced inactivation of TP53 and/or and RB1, or with E2F1 overexpression. Normalized luciferase activity of a representative biological replicate is shown. e Barplot showing a representative biological replicate of an experiment assessing viability of control and TP53/RB1-inactivated H1563 (LUAD), 22PC and LnCap/AR (PRAD) cells treated with 0.5 µM simurosertib. Each condition shown was normalized to their matched untreated condition and represented as a normalized percentage for viability. For d and e , p -values were calculated using the Student’s t test (unpaired, heterogeneous variances, two-tailed). p -value legend: *<0.05, **<0.01, ***<0.001, ns, not significant

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Expressing, Western Blot, shRNA, Dominant Negative Mutation, Over Expression, CRISPR, Knock-Out, Control, Binding Assay, Protein-Protein interactions, ChIP-sequencing, Luciferase, Activity Assay, Two Tailed Test

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: CDC7 inhibition suppresses NE transformation. a In vivo treatment of cell line xenografts for TP53/RB1-inactivated (DKO) LnCap/AR and 22PC cells with vehicle ( N = 8 for LnCap/AR and N = 4 for 22PC) enzalutamide ( N = 10, N = 6), simurosertib ( N = 9, N = 4) or their combination ( N = 10, N = 7). b Barplot showing the average ± standard deviation of the intratumoral percentages of adenocarcinoma and NE histology in tumors collected at endpoint for each treatment arm, including vehicle ( N = 5), enzalutamide ( N = 7), simurosertib ( N = 6) and their combination ( N = 4). Barplot showing the average ± standard deviation of H-score quantification ( c ) and representative images ( d ) for immunohistochemical assessment of the expression of androgen receptor (AR), synaptophysin (SYP) and chromogranin A (CHGA) staining in LnCap/AR tumors collected at endpoint for each experimental arm. e Trajectory analyses on single-cell transcriptomic data for the control and enzalutamide-treated DKO LnCap/AR tumors, illustrating changes in expression of gene of interest and in enrichment for gene signatures of interest. The lower panel consists of a heatmap of gene trends of select genes of relevance in NE transformation ordered by the putative transition from adenocarcinoma to NEPC in control and enzalutamide-treated cells from the in vivo treatment experiment in Fig. 3a. The top panel shows a spline fit of the average Z -score for GSEA pathways of interest. f H&E and IHC staining for markers of interest for the EGFR -mutant combined NSCLC/SCLC PDX tumor MSK_Lx151. g In vivo treatment of the MSK_Lx151 PDX with vehicle ( N = 5), Osimertinib ( N = 6), simurosertib ( N = 5) or their combination ( N = 7). For a – c and j , p -values were calculated using the Student’s t test (unpaired, heterogeneous variances, two-tailed). p -value legend: *<0.05, **<0.01, ***<0.001, ****<0.0001, ns not significant

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Inhibition, Transformation Assay, In Vivo, Standard Deviation, Immunohistochemical staining, Expressing, Staining, Control, Immunohistochemistry, Mutagenesis, Two Tailed Test

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: In combination with targeted therapy, CDC7 inhibition induces downregulation of genes involved in pathways associated to NE transformation. a Dotplots showing results for the pathway enrichment analysis on DEGs from combo- versus enzalutamide-treated tumor conditions in the transcriptomic data from TP53/RB1-inactivated 22PC and LnCap/AR xenografts treated in vivo and collected at an intermediate timepoint (day 17). Categorized pathways of interest, previously implicated in NE transformation, , are shown. b Force-directed layouts (FDLs) for single-cell transcriptomic data in tumors collected during a time course experiment from a GEMM prostate NE transformation model (PtRP) described in ref. showing increased NE transformation phenotype over time. FDLs are separated by time point, and cells undergoing NE transformation are labeled according to their trancriptomic profile resembling PRAD or NEPC. c FDLs separated by time point, with cells for each time point colored by CDC7 expression levels. d Dotplot showing the magnitude of CDC7 expression and percentage of CDC7-expressing cells at the different time points of the time course GEMM experiment. e Heatmap of gene trends of select genes of relevance in NE transformation ordered by the putative transition from adenocarcinoma to NEPC, with gene labels colored in the same way the aforementioned groups (scale gene trends of imputed expression, −0.5 to 2.0). The top panel shows a spline fit of the average Z -score for GSEA pathways of interest

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Inhibition, Transformation Assay, In Vivo, Labeling, Expressing

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: CDC7 inhibition-induced MYC degradation prevents NE transformation. a Western blots of tumors collected from our in vivo experiments in NE transformation models of prostate and lung (Fig. ) at an intermediate time point (day 17), assessing the expression of the transcription factor MYC. a Barplots showing CDC7 mRNA expression determined by RNAseq in transcripts per million (TPM) units in the tumors collected from our in vivo experiments in NE transformation models of prostate (Fig. ). c Barplots showing proteasome 20 s activity in TP53/RB1-inactivated LUAD (H1563) and prostate (22PC) cell lines with pharmacological (simurosertib) or genetic (CRISPR-Cas9 KO) CDC7 inhibition. Proteasome activity is shown as normalized by the control condition. d Western blots for isogenic cell lines of TP53/RB1-inactivated 22PC and LnCap/AR prostate models of NE transformation, with or without MYC T58A exogenous overexpression. Cells were treated with enzalutamide, simurosertib or their combination in vitro for 7 days, and cells were collected for protein extraction, to assess NE marker (NCAM1, SYP) and MYC expression. e Schematic model of CDC7 inhibition in NE transformation. Briefly, TP53/RB1 inactivation leads to increased expression of and dependency on CDC7 in lung and prostate adenocarcinomas. Targeted therapy can promote NE transformation, involving MYC induction in the process, and leading to poor prognosis. However, CDC7 inhibition in combination with targeted therapy activates proteosomal degradation of MYC. Without the action of MYC, NE transformation and adaptation to therapy is constrained, leading to extended response to treatment. Tumors may eventually acquire resistance to therapy via alternative mechanisms of resistance. Created with BioRender.com. For b and c , p -values were calculated using the Student’s t test (unpaired, heterogeneous variances, two-tailed). p -value legend: *<0.05, **<0.01, ***<0.001, ns not significant

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Inhibition, Transformation Assay, Western Blot, In Vivo, Expressing, Activity Assay, CRISPR, Control, Over Expression, In Vitro, Protein Extraction, Marker, Two Tailed Test

Journal: Signal Transduction and Targeted Therapy

Article Title: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

doi: 10.1038/s41392-024-01908-y

Figure Lengend Snippet: CDC7 inhibition dramatically sensitizes de novo SCLC PDX to first and second line chemotherapy. In vitro synergy assays in H82 (SCLC-N, left) and H146 (SCLC-A, right) cell lines of the combination of simurosertib and cisplatin or irinotecan ( a ), or in Lx1042 (T-SCLC) and H660 (NEPC) with the combination of simurosertib and cisplatin ( b ), with average synergy score displayed, as assessed by Highest Single Agent (HSA) method, and calculated using SynergyFinder. Representative plots are shown. In vivo treatments of high (Lx1231, SCLC-A), intermediate (Lx33, SCLC-N) and low (Lx276, SCLC-A) CDC7-expressing PDX derived from treatment-naïve tumors ( c ), of high (Lx761c, SCLC-N), intermediate (Lx674c, SCLC-A) and low (Lx95, SCLC-A) CDC7-expressing PDX derived from tumors progressed on chemotherapy ( d ), and of NE-transformed PDX (Lx1042 and H660)( e ), to compare the efficacy of the combination of simurosertib with cisplatin versus that of cisplatin and etoposide (chemotherapy-naïve PDX, including NE-transformed PDX) or of simurosertib with irinotecan versus irinotecan alone (progressed on treatment PDX). p -values for ( a ), ( d ), and ( e ) were calculated using the Student’s t-test (unpaired, heterogeneous variances, two-tailed). p -value legend: *<0.05, **<0.01, ***<0.001

Article Snippet: A Promoter reporter clone for the human CDC7 gene (HPRM35138-LvPG04, Genecopoeia) was used in combination with a GAPDH positive control clone (GAPDH-LvPG04, Genecopoeia) and a negative control clone (NEG-LvPG04, Genecopoeia).

Techniques: Inhibition, In Vitro, In Vivo, Expressing, Derivative Assay, Transformation Assay, Two Tailed Test