Fibroblast activation protein-α (FAP) is a type II integral serine protease that is specifically expressed by activated fibroblasts. Cancer-associated fibroblasts (CAFs) in the tumor stroma have an abundant and stable expression of FAP, which plays an important role in promoting tumor growth, invasion, metastasis, and immunosuppression. For example, in females with a high incidence of breast cancer, CAFs account for 50–70% of the cells in the tumor’s microenvironment. CAF overexpression of FAP promotes tumor development and metastasis by influencing extracellular matrix remodeling, intracellular signaling, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. This review discusses the basic biological characteristics of FAP and its applications in the diagnosis and treatment of various cancers. We review the emerging basic and clinical research data regarding the use of nanomaterials that target FAP.
Highlights Established a new in vitro tumor model called novel conditionally reprogrammed (termed i-CR). Accomplished personalized drug tests within 2–3 weeks. Achieved 100% sensitivity, 85.7% specificity, 91.7% positive predictive value, and 100% negative predictive value. i-CR guided a inoperable patient with metastases converted to radical surgery.
Salt stress is a major abiotic stress factor affecting crop production, and understanding of the response mechanisms of seed germination to salt stress can help to improve crop tolerance and yield. The differences in regulatory pathways during germination in different salt-tolerant barley seeds are not clear. Therefore, this study investigated the responses of different salt-tolerant barley seeds during germination to salt stress at the proteomic and metabolic levels. To do so, the proteomics and metabolomics of two barley seeds with different salt tolerances were comprehensively examined. Through comparative proteomic analysis, 778 differentially expressed proteins were identified, of which 335 were upregulated and 443 were downregulated. These proteins, were mainly involved in signal transduction, propanoate metabolism, phenylpropanoid biosynthesis, plant hormones and cell wall stress. In addition, a total of 187 salt-regulated metabolites were identified in this research, which were mainly related to ABC transporters, amino acid metabolism, carbohydrate metabolism and lipid metabolism; 72 were increased and 112 were decreased. Compared with salt-sensitive materials, salt-tolerant materials responded more positively to salt stress at the protein and metabolic levels. Taken together, these results suggest that salt-tolerant germplasm may enhance resilience by repairing intracellular structures, promoting lipid metabolism and increasing osmotic metabolites. These data not only provide new ideas for how seeds respond to salt stress but also provide new directions for studying the molecular mechanisms and the metabolic homeostasis of seeds in the early stages of germination under abiotic stresses.
Hepatocellular Carcinoma (HCC) is a major health problem, as the fifth most common cancer and the third most common cause of cancer death worldwide. Many pharmaceutical companies lead the effort to design new medicines on this cancer type. The overwhelming need to improve preclinical models of HCC requires robust models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Here we successfully validated subcutaneous and orthotopic xenograft models derived from HepG2, SK-HEP-1, Hep3B, PLC/PRF/5, HUH-1, HUH-7 and MHCC97H cell lines and also directly from HCC patient tumors (HuPrime®). Four HCC serum markers (AFP, α-fetoprotein; AFP-L3; DCP, Des-gamma-Carboxyprothrombin; GP73, Golgi Protein-73) have been used or will be potentially used clinically in detection of this disease. AFP is the most widely used biomarker in HCC, somehow it is not always correlated well with the liver cancer progress, even it gives false result, and some liver lesion or liver cirrhosis can also produce high level of AFP; while GP73 is reported a promising alternative as HCC serum marker. AFP and GP73 were tested at both mRNA level and protein level. They were also compared in the sensitivity and correlation with the tumor burden using the blood samples from the orthotopic xenograft models. Our results demonstrated that biomarkers released by the tumor models could well monitor the tumor take rate, growth and response to treatments. Furthermore, Sorafenib, one popular anti- HCC medicine, was tested, and the serum biomarkers could be utilized for confidence in evaluating the efficacy of Sorafenib. In conclusion, the use of HCC xenograft models combined with the biomarker strategies is helpful in maximizing the value of in vivo research and designing clinical trials Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1611. doi:10.1158/1538-7445.AM2011-1611
Gene expression analysis has led to the identification of 5 subtypes of breast cancer (basal-like, HER2-like, luminal A and B, and normal-like) that have distinct biological features, clinical outcomes, and responses to conventional chemotherapy and targeted therapy. Animal models possessing genetic and other biomarker abnormalities similar to each subtype of the human counterpart are thus of crucial importance in the development of new therapeutic strategies. Human breast cancer xenograft model is one of the more difficult models with transplantation of either established cell lines or primary tumors. We have successfully established 6 xenograft models derived from established cell lines and 2 xenograft models by transplanting primary human tumor fragments. The immunohistochemical results classified the 9 models into 4 major groups: ER negative and HER2 negative (MX-1, MDA-MB-231, MCF-7-CB1, and SKBR3-CB1), ER negative and HER2 positive (BT-474-CB1), ER positive and HER2 negative (MCF-7), and ER positive and HER2 positive (BT-474), which well resembled basal-like/normal-like, HER2-like, luminal A, and luminal B breast cancer types in human. The mutation status of TP53, BRCA1, BRCA2 and EGFR was investigated, and compared with the in vivo efficacy results by using various test drugs including cytotoxic agents, paclitaxel and doxorubicin; ER antagonist, tamoxifen; anti-HER2 monoclonal antibody, trastuzumab; HER2 inhibitor, HKI-272 and EGFR inhibitor, erlotinib. These data closely mimicked the heterogeneity in clinical outcomes of the human disease. Therefore, these models provide valuable platform for the development of personalized therapy for breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 647.
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