Transcriptomic profiling of pancreatic stellate cells and pancreatic cancer cells in a gemcitabine-driven tumor-stroma supernatant transfer model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE324779 | GEO | 2026/03/18
REPOSITORIES: GEO
Similar Datasets
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis. Immortalized human pancreatic CAFs were grown for 30 days in either control media or media containing 100nM gemcitabine. RNA was then isolated and hybidized on U133 Plus 2.0 Affymetrix arrays.
2016-03-09 | E-GEOD-78982 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis.
2016-03-09 | GSE78982 | GEO
Project description:Zhu2015 - Combined gemcitabine and birinapant
in pancreatic cancer cells - basic PD model
Mathematical model to illustrate the
effectiveness of combination chemotherapy involving gemcitabine and
birinapant against pancreatic cancer.
This model is described in the article:
Mechanism-based mathematical
modeling of combined gemcitabine and birinapant in pancreatic
cancer cells.
Zhu X, Straubinger RM, Jusko
WJ.
J Pharmacokinet Pharmacodyn 2015 Oct;
42(5): 477-496
Abstract:
Combination chemotherapy is standard treatment for
pancreatic cancer. However, current drugs lack efficacy for
most patients, and selection and evaluation of new combination
regimens is empirical and time-consuming. The efficacy of
gemcitabine, a standard-of-care agent, combined with
birinapant, a pro-apoptotic antagonist of Inhibitor of
Apoptosis Proteins (IAPs), was investigated in pancreatic
cancer cells. PANC-1 cells were treated with vehicle,
gemcitabine (6, 10, 20 nM), birinapant (50, 200, 500 nM), and
combinations of the two drugs. Temporal changes in cell
numbers, cell cycle distribution, and apoptosis were measured.
A basic pharmacodynamic (PD) model based on cell numbers, and a
mechanism-based PD model integrating all measurements, were
developed. The basic PD model indicated that synergistic
effects occurred in both cell proliferation and death
processes. The mechanism-based model captured key features of
drug action: temporary cell cycle arrest in S phase induced by
gemcitabine alone, apoptosis induced by birinapant alone, and
prolonged cell cycle arrest and enhanced apoptosis induced by
the combination. A drug interaction term Ψ was employed in
the models to signify interactions of the combination when data
were limited. When more experimental information was utilized,
Ψ values approaching 1 indicated that specific mechanisms
of interactions were captured better. PD modeling identified
the potential benefit of combining gemcitabine and birinapant,
and characterized the key interaction pathways. An optimal
treatment schedule of pretreatment with gemcitabine for 24-48 h
was suggested based on model predictions and was verified
experimentally. This approach provides a generalizable modeling
platform for exploring combinations of cytostatic and cytotoxic
agents in cancer cell culture studies.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000668.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000668 | BioModels
Project description:Zhu2015 - combined gemcitabine and birinapant
in pancreatic cancer cells - mechanistic PD model
Mechanistic mathematical model to
illustrate the effectiveness of combination chemotherapy involving
gemcitabine and birinapant against pancreatic cancer.
This model is described in the article:
Mechanism-based mathematical
modeling of combined gemcitabine and birinapant in pancreatic
cancer cells.
Zhu X, Straubinger RM, Jusko
WJ.
J Pharmacokinet Pharmacodyn 2015 Oct;
42(5): 477-496
Abstract:
Combination chemotherapy is standard treatment for
pancreatic cancer. However, current drugs lack efficacy for
most patients, and selection and evaluation of new combination
regimens is empirical and time-consuming. The efficacy of
gemcitabine, a standard-of-care agent, combined with
birinapant, a pro-apoptotic antagonist of Inhibitor of
Apoptosis Proteins (IAPs), was investigated in pancreatic
cancer cells. PANC-1 cells were treated with vehicle,
gemcitabine (6, 10, 20 nM), birinapant (50, 200, 500 nM), and
combinations of the two drugs. Temporal changes in cell
numbers, cell cycle distribution, and apoptosis were measured.
A basic pharmacodynamic (PD) model based on cell numbers, and a
mechanism-based PD model integrating all measurements, were
developed. The basic PD model indicated that synergistic
effects occurred in both cell proliferation and death
processes. The mechanism-based model captured key features of
drug action: temporary cell cycle arrest in S phase induced by
gemcitabine alone, apoptosis induced by birinapant alone, and
prolonged cell cycle arrest and enhanced apoptosis induced by
the combination. A drug interaction term Ψ was employed in
the models to signify interactions of the combination when data
were limited. When more experimental information was utilized,
Ψ values approaching 1 indicated that specific mechanisms
of interactions were captured better. PD modeling identified
the potential benefit of combining gemcitabine and birinapant,
and characterized the key interaction pathways. An optimal
treatment schedule of pretreatment with gemcitabine for 24-48 h
was suggested based on model predictions and was verified
experimentally. This approach provides a generalizable modeling
platform for exploring combinations of cytostatic and cytotoxic
agents in cancer cell culture studies.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000669.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000669 | BioModels
Project description:Pancreatic cancer exhibits a characteristic tumor microenvironment (TME) due to enhanced fibrosis and hypoxia and is particularly resistant to conventional chemotherapy. However, the molecular mechanisms underlying TME-associated treatment resistance in pancreatic cancer are not fully understood. Here, we developed an in vitro TME mimic system comprising pancreatic cancer cells, fibroblasts and immune cells, and a stress condition, including hypoxia and gemcitabine. Cells with high viability under stress showed evidence of increased direct cell-to-cell transfer of biomolecules. The resulting derivative cells (CD44high/SLC16A1high) were similar to cancer stem cell-like-cells (CSCs) with enhanced anchorage-independent growth or invasiveness and acquired metabolic reprogramming. Furthermore, CD24 was a determinant for transition between the tumorsphere formation or invasive properties. Pancreatic cancer patients with CD44low/SLC16A1low expression exhibited better prognoses compared to other groups. Our results suggest that crosstalk via direct cell-to-cell transfer of cellular components foster chemotherapy-induced tumor evolution and that targeting of CD44 and MCT1(encoded by SLC16A1) may be useful strategy to prevent recurrence of gemcitabine-exposed pancreatic cancers.
2023-03-11 | PXD037275 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, and the five-year survival rate is still less than 5%. However, Gemcitabine, a first-line chemotherapy drug of PDAC, has serious side effects and chemotherapy resistance. It is imperative to find new therapies to treat patients with advanced pancreatic cancer. With the computational screening, we found the gene sginature of ovarian serous carcinoma is anti-correlated with that of PDAC. Then we established an animal model of pancreatic cancer xenografts and injected ovarian cancer cell SKOV3 into xenografts to observe whether the SKOV3 could inhibit the growth of pancreatic cancer. We used RNA-sequencing to compare the tumor treated with SKOV3 to that with normal saline.
2022-08-30 | GSE212173 | GEO
Project description:We evaluated the TGFβ blocking antibody NIS793 in combination with either gemcitabine/n(ab)-paclitaxel or FOLFIRINOX chemotherapy in orthotopic pancreatic cancer. Blockade of TGFβ with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. TGFβ blockade decreased total aSMA+ fibroblasts but had minimal effect on fibroblast heterogeneity.
2023-04-23 | GSE224688 | GEO
Project description:No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma. MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern. Gemcitabine-resistant variants of two mutant p53 human pancreatic adenocarcinoma cell lines were established. MicroRNA screening was investigated by microarray. Gemcitabine-resistant PANC-1 (PANC-1-GR) and MIA-PaCa-2 (MIA-PaCa-2-GR) cell clones were produced by exposing the parental cells to repeated pulsatile gemcitabine treatment over 3 days with constant sublethal concentrations followed by recovery-periods with agent-free medium until the cells recovered exponentially. Parental PANC-1 cells were treated with 0.4µM gemcitabine cycles for approximately 9 months. Parental MIA-PaCa-2 cells were exposed to 0.06µM gemcitabine cycles for approximately 12 months. Affymetrix GeneChip miRNA microarrays (Affymetrix UK Ltd., High Wycombe, UK) were performed in parental and chemoresistant PANC-1 and MIA-PaCa-2 cells after 29 chemotherapy cycles using the manufacturers´ protocols. The samples were prepared from 1µg of total-RNA in accordance with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit. The targets were hybridized overnight to Affymetrix GeneChip miRNA arrays. Following hybridization, the arrays were washed and stained using the Affymetrix GeneChip Fluidics Station 450 and scanned using the Affymetrix GeneChip Scanner 3000 7G. Microarray data quality was checked as recommended by the manufacturer and by the quality metrics in the Partek Genomics Suite software (Partek Inc., St. Louis, MO).
2015-11-03 | E-GEOD-74565 | biostudies-arrayexpress
Project description:No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma. MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern. Gemcitabine-resistant variants of PANC-1, a mutant p53 human pancreatic adenocarcinoma cell line, were established. MicroRNA screening was investigated by microarray. Gemcitabine-resistant PANC-1 (PANC-1-GR) cell clones were produced by exposing the parental cells to repeated pulsatile gemcitabine treatment over 3 days with constant sublethal concentrations followed by recovery-periods with agent-free medium until the cells recovered exponentially. Parental PANC-1 cells were treated with 0.4µM gemcitabine cycles for approximately 9 months. Affymetrix GeneChip miRNA microarrays (Affymetrix UK Ltd., High Wycombe, UK) were performed in parental and chemoresistant PANC-1 cells after 17 chemotherapy cycles using the manufacturers´ protocols. The samples were prepared from 1µg of total-RNA in accordance with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit. The targets were hybridized overnight to Affymetrix GeneChip miRNA arrays. Following hybridization, the arrays were washed and stained using the Affymetrix GeneChip Fluidics Station 450 and scanned using the Affymetrix GeneChip Scanner 3000 7G. Microarray data quality was checked as recommended by the manufacturer and by the quality metrics in the Partek Genomics Suite software (Partek Inc., St. Louis, MO).
2015-11-03 | E-GEOD-74562 | biostudies-arrayexpress
Project description:Pancreatic cancer is a highly malignant tumor that is well known for its poor prognosis. It has been reported that aspirin can reduce the risk of various cancers, but the potential role of aspirin and gemcitabine in pancreatic cancer pathogenesis and chemotherapy has not been studied.
2023-09-08 | E-MTAB-11517 | biostudies-arrayexpress