Growth-inhibitory effects of combination chemotherapy for human pancreatic cancer cell lines

Matsuno, Seiki; Hisano, Hirotake; Kobari, Masao; Akaishi, Satoshi

doi:10.1002/1097-0142(19901201)66:11<2369::aid-cncr2820661120>3.0.co;2-z

Cited by 12 publications

(4 citation statements)

References 11 publications

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“…Similar concentrations for chemotherapeutic drugs and treatment schedules were used in vitro by other authors, e.g. for 5-FU [51], mitomycin C [52] or oxaliplatin [53]. Interestingly, we found that 5-FU, mitomycin-C and oxaliplatin at the concentrations tested up-regulated distinctly EpCAM and Lewis Y antigen expression.…”

Section: Discussionsupporting

confidence: 84%

Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression

Flieger

Hoff

Sauerbruch

et al. 2001

Clinical and Experimental Immunology

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MoAbs against tumour‐associated antigens (TAA) may be useful for the treatment of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody‐dependent cellular cytotoxicity we examined whether the cytokines IL‐2, IL‐4, IL‐6, IL‐10, IL‐12, interferon‐alpha (IFN‐α), IFN‐γ, granulocyte‐macrophage colony‐stimulating factor, macrophage colony‐stimulating factor and tumour necrosis factor‐alpha can influence EpCAM and LewisY expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN‐α increased significantly whereas IL‐4 decreased both EpCAM and LewisY expression. IFN‐γ significantly increased LewisY expression only. When tumour cells were treated with MoAb, the LewisY‐specific MoAb BR55‐2 down‐regulated LewisY antigen expression, whereas MoAb 17‐1A, which binds to EpCAM, up‐regulated this TAA after 3 days of culture. The cytokines IFN‐α or IFN‐γ combined with MoAb 17‐1A enhanced further slightly the expression of EpCAM. In additional experiments with chemotherapeutic drugs commonly used for the treatment of colorectal cancer, we found that 5‐fluorouracil, mitomycin‐C and oxaliplatin up‐regulated EpCAM and LewisY antigen expression. Raltitrexed enhanced LewisY and down‐regulated EpCAM expression, whereas CPT‐11 had no influence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN‐α, 5‐fluorouracil and MoAb 17‐1A. Our results may be useful for defining combinations of biological and chemotherapeutic drugs for the treatment of colorectal cancer. Further trials should evaluate to what extent these combinations enhance antibody‐dependent cellular cytotoxicity.

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Section: Discussionsupporting

confidence: 84%

Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression

Flieger

Hoff

Sauerbruch

et al. 2001

Clinical and Experimental Immunology

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“…Anderson Cancer Center, Houston, TX, April 2009). Based on previously reported (Matsuno et al 1990) and confirmed inhibitory concentrations, doxorubicin (Bedford Laboratories, Bedford, OH) was diluted to 0.02 μg/mL in complete DMEM and the cells were treated 24 h after plating while control cells were treated with equivolume phosphate-buffered saline instead of doxorubicin.…”

Section: Protocolmentioning

confidence: 85%

A protocol to effectively create single cell suspensions of adherent cells for multiparameter high-throughput flow cytometry

Glazer

Massey

Curley

2009

In Vitro Cell.Dev.Biol.-Animal

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High-throughput flow cytometry of adherent cells is difficult because the creation of single cell suspensions can damage cells and yield artificial results. We describe a protocol to increase the single cell suspension yield of adherent human cells without injury. Doxorubicin, a cytotoxic agent, was administered to adherent human pancreatic carcinoma cell lines (Panc-1 and AsPC-1) to produce alterations in the cell cycle and intracellular protein expression. The cells in 96-well plates were disassociated using a collagenase and trypsin mixture. Fluorescence-activated high-throughput flow cytometry evaluated cellular viability as well as surface and intracellular protein expression. Cell cycle analysis was performed using 7-aminoactinomycin D and intracellular protein characterization was performed using a fluorescein-labeled monoclonal antibody against activated caspase-3. The collagenase-trypsin-based protocol increased single cell events from 31.9 +/- 0.5% using trypsin alone (standard) to a range of 62.1% to 85.5% without adversely affecting viability. High-throughput flow cytometry demonstrated that the addition of collagenase to the disassociation solution not only permitted significantly higher rates of single cell creation, but it did not negatively affect the doxorubicin-induced protein expression. This protocol allows for expedient and effective disassociation of adherent human cells in order to investigate alterations in specific cellular enzymes and pathways.

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“…These included data for cisplatin/paclitaxel (18–21), cisplatin/docetaxel (18), carboplatin/paclitaxel and carboplatin/docetaxel (22). An additional 21 data sets for a variety of drug combinations were collected: 5-fluorouracil/aclarubicin hydrochloride (23); 5-fluorouracil/fleroxacin (24); 5-fluorouracil/mitomycin-C (23); acivicin/asparaginase (25); aclarubicin hydrochloride/mitomycin-C (23); cyclophosphamide and thiotepa (26); erlotinib/rapamycin (27); gemcitabine/TRA-8 (28); imatinib/rapamycin (29); trastuzumab/ZD1839 (30) (31); gemcitabine/OBP-301(32). Cell lines used for these data cells were: A549 (human lung adenocarcinoma); B2-2 (biliary tract); Ba/F-BCR/ABLWT and Ba/F-BCR/ABL T315I (variants of the Ba/F3 murine hematopoietic cell line); BT-474 (human mammary); EMT6 (mouse mammary); MBT-2 (mouse bladder carcinoma); MCF-7 (human mammary); MIA-PaCa-2 (pancreatic); NCI-H23 (lung); PK-1 and PK-8 (human pancreatic); S2-VP10 (subline of a human pancreatic SUIT-2), SK-Br-3 (human mammary); T-24 (human bladder carcinoma); TE-671 (human medulloblastoma); H322 (human lung cancer).…”

Section: Methodsmentioning

confidence: 99%

The additive damage model: A mathematical model for cellular responses to drug combinations

Jones¹,

Secomb²,

Dewhirst³

et al. 2014

Journal of Theoretical Biology

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Mathematical models to describe dose-dependent cellular responses to drug combinations are an essential component of computational simulations for predicting therapeutic responses. Here, a new model, the additive damage model, is introduced and tested in cases where varying concentrations of two drugs are applied with a fixed exposure schedule. In the model, cell survival is determined by whether cellular damage, which depends on the concentrations of the drugs, exceeds a lethal threshold, which varies randomly in the cell population with a prescribed statistical distribution. Cellular damage is assumed to be additive, and is expressed as a sum of separate terms for each drug. Each term has a saturable dependence on drug concentration. The model has appropriate behavior over the entire range of drug concentrations, and is predictive, given single-agent dose-response data for each drug. The proposed model is compared with several other models, by testing their ability to fit 24 data sets for platinum-taxane combinations and 21 data sets for various other combinations. The Akaike Information Criterion is used to assess goodness of fit, taking into account the number of unknown parameters in each model. Overall, the additive damage model provides a better fit to the data sets than any previous model. The proposed model provides a basis for computational simulations of therapeutic responses. It predicts responses to drug combinations based on data for each drug acting as a single agent, and can be used as an improved null reference model for assessing synergy in the action of drug combinations.

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Growth-inhibitory effects of combination chemotherapy for human pancreatic cancer cell lines

Cited by 12 publications

References 11 publications

Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression

Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression

A protocol to effectively create single cell suspensions of adherent cells for multiparameter high-throughput flow cytometry

The additive damage model: A mathematical model for cellular responses to drug combinations

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