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Predictive value of testing the sensitivity of anticancer treatment on tumorspheres from patients with metastatic colorectal cancer

ABSTRACT: Primary objectives: The purpose of the present study is to investigate the benefit to patients with metastatic colorectal cancer of post standard anti-cancer therapy based on pretreatment in-vitro testing of drug sensitivity to patient-derived tumorspheres. Primary endpoints: The fraction of patients alive and without progression eight weeks after start of treatment

DISEASE(S): Metastatic Colorectal Cancer

PROVIDER: 2536654 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Choline Kinase Alpha (CHKα) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors

Project description:Choline kinase α (CHKα) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKα in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKα expression, associated with differentiation. CHKα protein expression was directly correlated with sensitivity to MN58b, a CHKα inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKα knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKα inhibition and, in vitro, MN58b had additive or synergistic effects with gemcitabine, 5-fluorouracil, and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKα was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKα did not relate to survival, nuclear CHKα distribution was observed in 43% of samples and was associated with longer survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKα inhibitors, we cultured IMIM-PC-2 cells with increasingly higher concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified upregulation of ABCB1 and ABCB4 multidrug resistance transporters, and functional studies confirmed that their upregulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKα inhibition merits further attention as a therapeutic option in patients with PDAC and that expression levels may predict response.

2018-03-28 | GSE112335 | GEO

Choline kinase alpha (CHKA) as a therapeutic target in pancreatic ductal adenocarcinoma: Expression, predictive value, and sensitivity to inhibitors

Project description:Choline kinase alpha (CHKA) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKA in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKA expression and a good correlation between protein expression and sensitivity to MN58b, a CHKA inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKA knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKA inhibition and, in vitro, MN58b had synergistic effects with gemcitabine, 5-fluorouracil and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKA was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKA did not relate to survival, nuclear CHKA distribution was observed in 43% of samples and was associated with survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKA inhibitors, we cultured IMIM-PC-2 cells with continuous incremental concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified up-regulation of ABCB1 and ABCB4 multidrug resistance transporters and functional studies confirmed that their up-regulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKA inhibition merits further attention as a therapeutic option in patients with PDAC.

2017-08-11 | GSE60321 | GEO

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

Project description: Not available

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The human cumulus cell transcriptome provides poor predictive value for embryo transfer outcome

Project description:Is the transcriptome of cumulus cells a good predictor of the embryo’s developmental competence? The objective of this study was to analyze the transcriptional differences between cumulus cells from oocytes exhibiting different developmental potentials following individual in vitro embryo production and transfer by RNA‐seq. Cumulus cells were allocated into three groups according to the developmental potential of their enclosed oocyte: (1) not able to develop to the blastocyst stage (Bl–), (2) able to develop to the blastocyst stage but failing to establish a pregnancy (P–), or (3) able to develop to the blastocyst stage and to establish a clinical pregnancy (P+).

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Minimizing signal detection time in postmarket sequential analysis: balancing positive predictive value and sensitivity.

Project description: Not available

| S-EPMC7181336 | biostudies-literature

Predictive value of high-sensitivity troponin T in addition to EuroSCORE II in cardiac surgery.

Project description: Not available

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Transcription profiling of human prostatic cancer cell lines and sensitivity to an anticancer tumor agent

Project description:Transcriptional profiling was conducted on RNA from 16 prostatic cancer cell lines to identify genes whose expression level correlate with sensitivity of an anti-tumor agent Experiment Overall Design: Baseline gene expression profiling was performed using 16 prostatic cancer cell lines to identify expression signatures highly correlated with in vitro sensitivity to a particular agent

2008-06-16 | E-GEOD-9633 | biostudies-arrayexpress

Predictive Value of Drug Sensitivity Testing Tumorspheres From Patients With Metastatic Colorectal Cancer

Project description:The purpose of the present study is to investigate the benefit of anti-cancer therapy administered on the basis of drug sensitivity testing. This concerns colorectal cancer patients who have previously received standard treatment.

| 2251938 | ecrin-mdr-crc

Molecular markers of predictive value associated with low birth weight

Project description:Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights. RNA from umbilical cord tissue from full term neonates was extracted and hybridized. Separation into 2 distinct groups, independent of birth weight, but based solely on gene expression levels was analysed by Genespring. After appropriate statistical analysis, one group was keenly associated with a higher birth weight (22 samples) while the other was associated with a lower birth-weight (18 samples). Technical replicates were included for all 40 samples.

2011-10-20 | E-GEOD-24818 | biostudies-arrayexpress

Predictive Value of MicroRNAs in the Progression of Oral Leukoplakias

Project description:Predictive Value of MicroRNAs in the Progression of Oral Leukoplakias Comparison of 10 samples from non-progressive leukoplakias (did not turn into oral squamous cell carcinoma), with 10 samples from progressive leukoplakias (turned into oral squamous cell carcinoma w/in 5 yrs)

2015-02-01 | E-GEOD-62809 | biostudies-arrayexpress

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