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Thymus,a main organ for T cell development,plays a pivotal role in adaptive immune response and dealing with the threaten from pathogens and tumors.With the deep understanding of the thymus,people have been realizing that the thymus is extremely sensitive to acute and chronic injuries as well as involution with age.Thymus regeneration can recover its function to a certain level.Up to now,these methods including adoptive thymic epithelial progenitor cells immunotherapy,injection of IL-2 and angiogenesis factor and regulation of c-Met signal are able to promote thymus recovery and T cell regeneration.
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Osteosarcoma( OS) is one common type of bone malignancy. Conventional treatments improved survival dramatically. However, conventional therapies have a few effects on patients with metastatic disease. Targeting os-teosarcoma-associated antigen, chimeric antigen receptor-modified T cell( CAR-T) therapy may promote efficacy of treatment. Specific CAR-T treatments of osteosarcoma including targeting HER-2, IL-11Rα, ROR1 and GD2 have shown a certain therapeutic effect on osteosarcoma in some basic and clinical studies.
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<p><b>OBJECTIVE</b>To investigate the correlation between methylation status and gene expression of APC (adenomatous polyposis coli) gene in HeLa, CaSki and SiHa cell lines of cervical carcinoma, and explore the effect of hydralazine on the transcription regulation of the 5'CpG island demethylation of APC gene and the proliferation and apoptosis of the cell lines.</p><p><b>METHODS</b>Methylation status and the expression of APC gene were analyzed using methylated specific PCR, RT-PCR and FQ-PCR methods. The expression of beta-catenin protein which correlates closely with APC was detected by SP method after treatment with Hydralazine. MTT and FCM assays were used to observe the changes of proliferation activity and apoptosis of the cells after Hydralazine treatment.</p><p><b>RESULTS</b>(1) APC gene was methylated or hemimethylated respectively in HeLa and CaSki cell lines, at the same time, APC gene was not methylated in SiHa cell. (2) After having been treated by 40 micromol/L Hydralazine for 72 hours, growth inhibitory ratios of HeLa, CaSki and SiHa cell lines were (52.12 +/- 3.78)%, (44.31 +/- 2.59)% and (47.73 +/- 4.73)% respectively, on the contrary, normal cell HECV's growth inhibitory ratio was only (27.18 +/- 0.79)%. APC gene in HeLa and CaSki cell lines which were treated by 40 micromol/L Hydralazine for 72 hours was demethylated and expressed positively, the expression of APC mRNA in HeLa, CaSki and SiHa cell lines increased to 10.35, 11.40 and 0.73 times respectively. (3) Hydralazine, when used at the concentration of 40 micromol/L for 72 hours, induced S phase and G2/M phase arrest and apoptosis in HeLa and CaSki cells. beta-catenin protein can be expressed in cell membrane after treatment with Hydralazine.</p><p><b>CONCLUSION</b>APC gene methylation plays an important role in the carcinogenesis of cervical cells and can re-express after the treatment with Hydralazine which also could inhibit the growth of the cervical cancer cells.</p>