Sensitivity of breast cell lines to gemcitabine in relationship with Bcl-2 expression.

<p>(A) IC₅₀ of gemcitabine to breast cancer cell lines. Mean IC₅₀±Standard Error (SE) of at least two independent experiments were performed in triplicates. Cells were treated with gemcitabine for 72 hr and cell proliferation was assessed using the MTS assay. (B) Immunoblot of Bcl-2 baseline expression in breast cancer cell lines.</p

Mechanism of reversal of gemcitabine resistance by gossypol in high Bcl-2 cell lines.

<p>Immunoblots of apoptotic protein expressions in gemcitabine resistant cell lines (GEM-R) when treated with combination of gossypol and gemcitabine for 48 hours. The results shown are representative of two independent experiments.</p

IC₅₀ of gossypol in different types of cancer cell lines.

<p>Nasopharyngeal (n = 4), breast (n = 3) and gastric (n = 3) cancer cell lines were tested for their sensitivity to gossypol. Mean IC₅₀ of ±Standard Error (SE) of at least two independent experiments were performed in triplicates. Cells were treated with gossypol for 72 hr and cell proliferation was assessed using the MTS assay.</p

Sensitivity of nasopharyngeal cancer cell lines to gemcitabine in relationship with Bcl-2 expression.

<p>(A) IC₅₀ of gemcitabine to nasopharyngeal cancer cell lines. Mean IC₅₀±Standard Error (SE) of at least two independent experiments were performed in triplicates. Cells were treated with gemcitabine for 72 hr and cell proliferation was assessed using the MTS assay. (B) Immunoblot of Bcl-2 baseline expression in nasopharyngeal cancer cell lines.</p

Sensitivity of gastric cell lines to gemcitabine in relationship with Bcl-2 expression.

<p>(A) IC₅₀ of gemcitabine to gastric cancer cell lines. Mean IC₅₀ of ±Standard Error (SE) of at least two independent experiments were performed in triplicates. Cells were treated with gemcitabine for 72 hr and cell proliferation was assessed using the MTS assay. (B) Immunoblot of Bcl-2 baseline expression in gastric cancer cell lines.</p

Gene expression analysis in response to gemcitabine and combined treatment.

<p>Heatmap of 2702 significant differentially expressed genes in gemcitabine resistant, GEM-R and gemcitabine sensitive, GEM-S treated with gemcitabine alone (Gem) or in combination with gossypol (Gem+GOS) relative to untreated matched control cell lines. The expression levels of each gene are higher and lower than control is depicted in red and green, respectively.</p

Comparison of IC₅₀ between gossypol and AT101 in 3 gastric cancer cell lines.

<p>Cells were treated with gossypol for 72 hr and cell proliferation was assessed using the MTS assay. Mean IC₅₀ of ±Standard Error (SE) of at least two independent experiments were performed in triplicates. P-value is calculated by unpaired t test with Welch’s correction.</p

Anti- and pro-apoptotic gene expressions in GEM-R and GEM-S cell lines after combined treatment.

<p>The relative log₂ fold change for anti-apoptotic gene cluster (A–B) and pro-apoptotic gene cluster (C–D), treated with gemcitabine alone (Gem) and in combination with gossypol (Gem+GOS). Only genes that were significantly differentially expressed from control untreated group are represented in the graph. All values on the y-axis were compared to the untreated controls of respective cell lines. Values above zero indicated genes that were up-regulated in its expression. Values below zero indicated genes that were down-regulated in its expression and values at zero indicated no change to gene expression. The log₂ levels of associated genes were normalized to the untreated sample.</p

Synergistic drug interaction between gossypol and gemcitabine.

<p>Combination treatment of masitinib and gemcitabine was tested on nasopharyngeal (n = 4), breast (n = 3) and gastric (n = 3) cancer cell lines. Combination index (CI) were generated by Calcusyn software for combination of gossypol and gemcitabine. CI <1 is indicated as synergistic of the combination treatment.</p>*<p>indicates gemcitabine resistance cell lines. High/low Bcl-2 expression is defined by the presence or absence of Bcl-2 expression based on immunoblot of the gene.</p

Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time

Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs