ABSTRACT
The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies.
Subject(s)
Cancer-Associated Fibroblasts/metabolism , Colonic Neoplasms/pathology , Mitogen-Activated Protein Kinase 7/genetics , Animals , Cell Line, Tumor , Colonic Neoplasms/blood supply , Colonic Neoplasms/genetics , Disease Progression , Female , Male , Mice , Mice, KnockoutABSTRACT
The number of patients with diabetes continues to increase in Japan, which means that education in disease management is important. However, there have been few investigations into the importance of hospital pharmacists performing outpatient education for diabetes mellitus in Japan. In the diabetes outpatient department of Kitakyushu City Moji Hospital, a pharmacist commenced patient education using check sheets before patients saw the physicians from 2012. We divided the patients into groups with an increase or decrease of hemoglobin A1c (HbA1c) level after 6 months from the start of patient education. To assess the factors related to a decrease of HbA1c level, we compared background factors, and laboratory values between these two groups. In the patients whose HbA1c level decreased, the level was high at the start of patient education and they had less knowledge about their medications. To evaluate the impact of this patient education, we compared HbA1c values before patient education and after 6 months to determine the effect of providing education in the diabetes outpatient department. In the HbA1c≥8% group, the HbA1c level decreased significantly during 6 months of patient education. These results suggest that patient education by hospital pharmacists can be effective if HbA1c level is high at the start of education. This is the first report about the usefulness of patient education by a hospital pharmacist for improvement of HbA1c level in diabetic outpatients in Japan.