Computational modeling of schedule-specific chemotherapy outcomes in mouse tumor model

Despite the rapid development of new innovative strategies in cancer treatment like immunotherapy, chemotherapy still remains a common choice in many cases. Standard protocols of chemotherapeutic administration rely on a maximal tolerated dose paradigm, however there is growing evidence that this approach is not always optimal. Alternative scheduling, like metronomic - low dose continuous drug administration - were recently proved their efficacy. The space of available variants of drug administration protocols is prohibitively large to be explored empirically, and there is an urgent need of predictive mathematical models for rational chemotherapeutic scheduling design. In this work we tested the ability of the minimal pharmacokinetic-pharmacodynamics model to describe schedule-specific tumor volume time evolution in different mouse tumor models.

Nuclear FOXP3 inhibits tumor growth and induced apoptosis in hepatocellular carcinoma by targeting c-Myc

The status of FOXP3 and its isoforms in hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the expression and function of FOXP3 and its isoforms in HCC. The study was performed on 84 HCC patients, HCC cell lines and a mouse tumor model. The levels of FOXP3 and its isoforms were determined by nested PCR, quantitative real-time PCR and immunohistochemistry (IHC) staining. The correlation between their levels and clinicopathologic characteristics was analyzed. The full length of FOXP3 (FOXP3) and exon 3-deleted FOXP3 (FOXP3Δ3) were found to be the major isoforms in HCC. The levels of FOXP3Δ3 mRNA and protein in HCC tumor samples were not significantly different from their adjacent normal tissues. The high expression of FOXP3 protein in HCC patients showed a good overall survival. The overexpression of FOXP3 significantly reduced tumor cell proliferation, migration and invasion. The immunofluorescence result indicated that FOXP3 needed to be translocated into the nucleus to exert its inhibitory function. The luciferase assay demonstrated that FOXP3 could be synergistic with Smad2/3/4 to inhibit the oncogene c-Myc. The co-immunoprecipitation results further revealed that FOXP3 could interact with Smad2/3/4. The chromatin immunoprecipitation (ChIP) assay showed that both FOXP3 and Smad2/3/4 bound the promoter of the c-Myc to inhibit it. The in vivo mouse tumor model study confirmed the inhibitory effect of FOXP3. Collectively, the expression of tumor FOXP3 can inhibit the growth of HCC via suppressing c-Myc directly or indirectly via interacting with Smad2/3/4. Therefore, FOXP3 is a tumor suppressor in HCC.

FOXP3 inhibits tumor growth and induced apoptosis in hepatocellular carcinoma by targeting c-Myc

Background The status of FOXP3 and its isoforms in hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the expression and function of FOXP3 and its isoforms in HCC. Methods The study was performed on 84 HCC patients, HCC cell lines and a mouse tumor model. The levels of FOXP3 and its isoforms were determined by nested PCR, quantitative real-time PCR and immunohistochemistry (IHC) staining. The correlation between their levels and clinicopathologic characteristics was analyzed. Results The full length of FOXP3 (FOXP3) and exon 3-deleted FOXP3 (FOXP3Δ3) were found to be the major isoforms in HCC. The levels of FOXP3Δ3 mRNA and protein in HCC tumor samples were not significantly different from their adjacent normal tissues. The high expression of FOXP3 protein in HCC patients showed a good overall survival. The overexpression of FOXP3 significantly reduced tumor cell proliferation, migration and invasion. The immunofluorescence result indicated that FOXP3 needed to be translocated into the nucleus to exert its inhibitory function. The luciferase assay demonstrated that FOXP3 could be synergistic with Smad2/3/4 to inhibit the oncogene c-Myc. The co-immunoprecipitation results further revealed that FOXP3 could interact with Smad2/3/4. The chromatin immunoprecipitation (ChIP) assay showed that both FOXP3 and Smad2/3/4 bound the promoter of the c-Myc to inhibit it. The in vivo mouse tumor model study confirmed the inhibitory effect of FOXP3. Conclusion Collectively, the expression of tumor FOXP3 can inhibit the growth of HCC via suppressing c-Myc directly or indirectly via interacting with Smad2/3/4. Therefore, FOXP3 is a tumor suppressor in HCC.