Background The FOXP3 mRNA expression and the other regulatory T cell-related molecules were investigated and compared with clinicopathological parameters in human primary breast cancer. Method This study included 136 breast cancer patients operated in our department from 2003 to 2006. Total RNA was extracted from frozen normal breast and breast cancer tissues, and the expression of FOXP3, IL-10, TGF 1 and CCL22 mRNA was evaluated using quantitative real-time RT-PCR. Result FOXP3, IL-10, TGF 1 and CCL22 mRNA expressions were signiWcantly higher in cancer tissue than in normal tissue, not only at pT1, 2, and 3 stages but also at the DCIS stage. There were positive correlations between FOXP3 and IL-10, FOXP3 and TGF 1, as well as FOXP3 and CCL22 mRNA expressions, respectively. FOXP3 and IL-10 mRNA expressions were signiWcantly upregulated in PgR-negative or HER2-positive tumors. ConclusionThese results suggest that regulatory T cells are involved in tumor onset and progression in human primary breast cancer, possibly contributing to poor prognosis of patients with breast cancer.

The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.

BackgroundMetastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a new method to directly transplant biopsy specimens to the liver of immunocompromised mice.ResultsBy using two metastatic uveal melanoma cell lines, we demonstrated that the liver provides a more suitable microenvironment for tumor growth compared to subcutaneous sites and that surgical orthotopic implantation (SOI) of tumor pieces allows the creation of a liver tumor in immunocompromised mice. Subsequently, 10 of 12 hepatic metastasis specimens from patients were successfully xenografted into the immunocompromised mice (83.3% success rate) using SOI, including 8 of 10 needle biopsy specimens (80%). Additionally, four cryopreserved PDX tumors were re-implanted to new mice and re-establishment of PDX tumors was confirmed in all four mice. The serially passaged xenograft tumors as well as the re-implanted tumors after cryopreservation were similar to the original patient tumors in histologic, genomic, and proteomic expression profiles. CT imaging was effective for detecting and monitoring PDX tumors in the liver of living mice. The expression of Ki67 in original patient tumors was a predictive factor for implanted tumor growth and the success of serial passages in PDX mice.ConclusionsSurgical orthotopic implantation of hepatic metastasis from uveal melanoma is highly successful in the establishment of orthotopic PDX models, enhancing their practical utility for research applications. By using CT scan, tumor growth can be monitored, which is beneficial to evaluate treatment effects in interventional studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1247-z) contains supplementary material, which is available to authorized users.