ABSTRACT
Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.
Subject(s)
Breast Neoplasms , Pioglitazone , Thiazolidinediones , Animals , Breast Neoplasms/drug therapy , Cell Proliferation , Cell Survival , Female , Humans , Janus Kinase 2/drug effects , Mice , Mice, Nude , PPAR gamma/genetics , PPAR gamma/metabolism , Pioglitazone/pharmacology , STAT3 Transcription Factor/drug effects , Thiazolidinediones/pharmacologyABSTRACT
STUDY DESIGN: A retrospective epidemiological study. OBJECTIVES: To provide recent epidemiological characteristics of traumatic spinal cord injuries (TSCIs) in adults living in Tianjin. SETTING: Tianjin, China. METHODS: This study included all TSCI patients aged 15 years or older who were admitted to tertiary hospitals in Tianjin from 2004 to 2008. Epidemiological characteristics, such as age, sex, date of admission, causes of injury, level of injury, America Spinal Injury Association impairment scale and date of discharge were included. RESULTS: A total of 869 patients were included, with an estimated annual incidence was 23.7 per million populations. The male/female ratio was 5.63:1. Mean age of TSCI was 46.0±14.2 years (men 45.8±14.2 years, women 47.5±14.5 years), with a range of 16-90 years. Falls were regarded as the leading causes of injury, followed by motor vehicle collisions. The lesion level was cervical in 71.5%, thoracic in 13.3% and lumbar/sacral in 15.1%. The frequency of tetraplegia (71.5%) was higher than paraplegia (28.5%), and roughly four-fifth of tetraplegia cases were incomplete injury. CONCLUSION: To our knowledge, national or local epidemiological study of spinal cord injury (SCI) has not been carried out previously in China. The number of SCI patients in this country is large and would increase gradually. Similar to other developing countries, falls were the main causes of TSCI. Low falls were more common in those over 60 years old. As the ageing society coming, the number of low falls-induced TSCI would increase gradually, which poses a challenge to the society health system.
