| 1. |
- Chen, Min-Wei, et al.
(författare)
-
H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM
- 2010
-
Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:20, s. 7830-7840
-
Tidskriftsartikel (refereegranskat)abstract
- G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression.
|
|
| 2. |
- Hua, Kuo-Tai, et al.
(författare)
-
N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
-
Ingår i: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
-
Tidskriftsartikel (refereegranskat)abstract
- N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
|
|
| 3. |
- Huang, Ya-Yao, et al.
(författare)
-
A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes
- 2016
-
Ingår i: Annals of Nuclear Medicine. - : Springer. - 0914-7187 .- 1864-6433. ; 30:8, s. 563-571
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The GE FASTlab radiosynthesis module is routinely used for the production of [18F]FDG, utilizing the commercially available phosphate cassettes. Because of the observation of a white precipitate in the product vial before the product expiry time, we re-examined the quality of the produced [18F]FDG solution.Methods: Phosphate buffered [18F]FDG solution was synthesized on the FASTlab and analyzed at both National Taiwan University Hospital (NTUH) of Taiwan and Royal Brisbane and Women’s Hospital (RBWH) of Australia. In addition to the standard product quality control (QC), the concentration of aluminum (Al3+) as probable cause of the precipitations in the [18F]FDG solution was analyzed by inductively coupled plasma mass spectrometry (ICP-MS at RBWH) and inductively coupled plasma optical emission spectrometry (ICP-OES at NTUH), and using three semi-quantitative methods at NTUH, Advantec® Alumi Check Test Strip, Quantofix® Aluminum Test Strip and MColortest™ Aluminum Test kit.Results: The precipitates were observed in the [18F]FDG solution within 24 (NTUH) and 6 (RBWH) hours after the end of synthesis in 38–100 % of the batches, dependent on the batch of the FASTlab cassettes. Addition of metal-free HCl(aq) to aliquots of [18F]FDG containing precipitate, followed by ICP-MS analysis revealed Al3+ concentrations of 70–80 ppm. Al3+ concentrations of 10–12 ppm were detected in [18F]FDG batches that did not show any precipitation. In contrast, less than 5 ppm of the residual Al3+ was detected by semi-quantitative methods in all batches.Conclusion: The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [18F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [18F]FDG production. Although testing for Al3+ is not listed in the [18F]FDG monographs of the USP, BP and EP, residual Al3+ levels should be considered in the interests of patient safety.
|
|
