Proteomics of Temozolomide for Glioblastoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Brain
SUBMITTER: 
linyong shi
LAB HEAD: linyong shi
PROVIDER: PXD042080 | Pride | 2023-05-17
REPOSITORIES: Pride
Dataset's files
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|---|---|---|---|---|
| Z8357TQ_1.raw | Raw | |||
| Z8357TQ_10.raw | Raw | |||
| Z8357TQ_11.raw | Raw | |||
| Z8357TQ_12.raw | Raw | |||
| Z8357TQ_13.raw | Raw |
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Project description:Primary human hepatocytes (PHH) are a main instrument in drug metabolism research and in the prediction of drug-induced phase I/II enzyme induction in humans. The HepG2 liver-derived cell line is commonly used as a surrogate for human hepatocytes, but their use in ADME and toxicity studies can be limited because of lowered basal levels of metabolizing enzymes. Despite their widespread use, the transcriptome of HepG2 cells compared to PHH is not well characterized. In this study, microarray analysis was conducted to ascertain the differences and similarities in mRNA expression between HepG2 cells and human hepatocytes before and after exposure to a panel of fluoroquinolone compounds. Comparison of the naïve HepG2 cell and PHH transcriptomes revealed a substantial number of basal gene expression differences. When HepG2 cells were dosed with a series of fluoroquinolones, trovafloxacin, which has been associated with human idiosyncratic hepatotoxicity, induced substantially more gene expression changes than the other quinolones, similar to previous observations with PHH. While TVX-treatment resulted in many gene expression differences between HepG2 cells and PHH, there were also a number of TVX-induced commonalities, including genes involved in RNA processing and mitochondrial function. Taken together, these results provide insight for interpretation of results from drug metabolism and toxicity studies conducted with HepG2 cells in lieu of PHH, and could provide further insight into the mechanistic evaluation of TVX-induced hepatotoxicity. Experiment Overall Design: HepG2 cells were obtained from the American Type Culture Collection (Rockville, MD). The cells were cultured in Minimum Essential Medium (Invitrogen Life Technologies, Carlsbad,CA) with 10% Fetal Bovine Serum under a humidified 5% CO2 atmosphere using T-162 plastic culture flasks. The cells were split when they reached approximately 70-85% confluence after washing with sterile phosphate buffered saline and detachment of the cells with trypsin (Invitrogen Life Technologies, Carlsbad, CA). The HepG2 cells were cultured in 6-well plastic plates upon exposure to quinolone compounds. Primary human hepatocytes, obtained from In Vitro Technologies (IVT, Baltimore, MD) in 6-well type I collagen coated plates, were cultured with 2 mL of Hepatocyte Incubation Media (IVT) at 37°C with 5% CO2 for 24 hours after receipt. Experiment Overall Design: For the genomic experiments, quinolone compounds, dissolved in 0.1 N KOH (Sigma Chemical Co., St. Louis, MO), were added to the wells with fresh media at levels of 100 µM (HepG2) or 400 µM (primary human hepatocytes) for 24 hours using at least two technical replicates. Trovafloxacin was dosed using two separate preparations of HepG2 cells and two separate donors of human hepatocytes. Vehicle control cells were dosed with an equivalent volume of 0.1N KOH as the experimental samples. For intracellular comparison (HepG2 cells vs PHH), naïve cells were harvested using TRIzol� reagent (Invitrogen Life Technologies, Carlsbad, CA). Experiment Overall Design: Total RNA was isolated from the TRIzol� extracts using the standard procedure from the manufacturer. O.D. at 260 nm determined RNA concentrations. RNA quality was accessed using an Agilent Technologies bioanalyzer before proceeding to microarray sample preparation. Microarray analysis was performed using the standard protocol provided by Affymetrix Inc. (Santa Clara, CA) and as previously described, starting with 5 µg of total RNA (Richert et al., 2006). Experiment Overall Design: Fragmented, labeled cRNA was hybridized to an Affymetrix human genome U133A array, which contains sequences corresponding to roughly 22,200 transcripts at 45°C overnight. The arrays were washed, developed, and scanned.
2008-06-16 | E-GEOD-9166 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgG levels for the training set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42019 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgM levels for the training set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42020 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). Total immunoglobin (IgM + IgG + IgA) levels for the training set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42145 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). Total immunoglobin (IgM + IgG + IgA) levels for the training set measured at serum dilution of 1:200 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42150 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgG levels for the validation set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42163 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). Total immunoglobin (IgM + IgG + IgA) levels for the validation set measured at serum dilution of 1:200 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42179 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgM levels for the validation set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42175 | biostudies-arrayexpress
Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). Total immunoglobin levels (IgM + IgG + IgA) for the validation set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.
2013-04-01 | E-GEOD-42176 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-04-01 | E-GEOD-42184 | biostudies-arrayexpress