AIM： To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarc...AIM： To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma （CCA） and define its correlation with clinical parameters. METHODS： Quantitative real time PCR （qPCR） was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the X^2 test. Cox regression analysis was used for determining patient＇s survival. RESULTS： Amplifications of the TP （22q13.33）, TOB2 （22q13.2-13.31）, D22S283 （22q12.3）, TIMP3 （22q12.3） and NF2 （22q12.2） were found in 35 （53.8%）, 28 （43.1%）, 27 （41.5%）, 24 （36.9%）, and 24 （36.9%）, respectively. Losses at the D22S423 （22q13.1-13.2）and BIK （22q13.31） were detected in 26 （40%） and 23 （35.4%）, respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK （P = 0.025） and D22S283 （P = 0.041）. Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis （P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779） and blood vessel invasion as an independent poor prognostic factor （P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571） in CCA patients. CONCLUSION： This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA, This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.展开更多
Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer...Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.展开更多
O-a-D-Glucopyranosyl-furost-5(6),20(22)-dien-3a,26-diol 1, a new furostanol saponin, was isolated from the water-extract of Dioscorea nipponica Mak., the raw material of a traditional Chinese herbal medicine Wei Ao Xi...O-a-D-Glucopyranosyl-furost-5(6),20(22)-dien-3a,26-diol 1, a new furostanol saponin, was isolated from the water-extract of Dioscorea nipponica Mak., the raw material of a traditional Chinese herbal medicine Wei Ao Xin. The structure of 1 was determined on the basis of its spectral data especially by NMR spectroscopy. The result provides the first example of naturally occurring furostanol saponins with a single saccharide chain at the C-26 position.展开更多
Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functi...The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.展开更多
BACKGROUND The FGFR signaling pathway is activated in multiple tumor types through gene amplifications,single base substitutions,or gene fusions.Novel FGFR gene fusions may represent candidate targets for the developm...BACKGROUND The FGFR signaling pathway is activated in multiple tumor types through gene amplifications,single base substitutions,or gene fusions.Novel FGFR gene fusions may represent candidate targets for the development of tyrosine kinase inhibitors.CASE SUMMARY Herein,we report a patient with colorectal cancer(CRC)harboring a novel FGFR2 fusion gene.A 59-year-old man felt discomfort in his right upper abdomen with loss of appetite for 6 mo.An abdominal computed tomography scan revealed the existence of a space-occupying lesion in the ascending colon.The pathological diagnosis was a poorly differentiated adenocarcinoma.Subsequent biopsy specimen was subjected to next-generation sequencing analysis,and a novel FGFR2-TSC22D1 fusion with complete kinase structure of FGFR2 protein was identified.CONCLUSION We report the first case of CRC harboring FGFR2-TSC22D1,which enriches the FGFR2 fusion spectrum.FGFR2 inhibitors might be effective in the later treatment for this patient.展开更多
基金Supported by The Thailand Research Fund through The Royal Golden Jubilee PhD Program, Grant No. PHD/0037/2544 for Thanasai J and Limpaiboon T
文摘AIM： To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma （CCA） and define its correlation with clinical parameters. METHODS： Quantitative real time PCR （qPCR） was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the X^2 test. Cox regression analysis was used for determining patient＇s survival. RESULTS： Amplifications of the TP （22q13.33）, TOB2 （22q13.2-13.31）, D22S283 （22q12.3）, TIMP3 （22q12.3） and NF2 （22q12.2） were found in 35 （53.8%）, 28 （43.1%）, 27 （41.5%）, 24 （36.9%）, and 24 （36.9%）, respectively. Losses at the D22S423 （22q13.1-13.2）and BIK （22q13.31） were detected in 26 （40%） and 23 （35.4%）, respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK （P = 0.025） and D22S283 （P = 0.041）. Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis （P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779） and blood vessel invasion as an independent poor prognostic factor （P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571） in CCA patients. CONCLUSION： This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA, This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.
文摘Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.
文摘O-a-D-Glucopyranosyl-furost-5(6),20(22)-dien-3a,26-diol 1, a new furostanol saponin, was isolated from the water-extract of Dioscorea nipponica Mak., the raw material of a traditional Chinese herbal medicine Wei Ao Xin. The structure of 1 was determined on the basis of its spectral data especially by NMR spectroscopy. The result provides the first example of naturally occurring furostanol saponins with a single saccharide chain at the C-26 position.
基金Financial support from the National Natural Science foundation of China (No: 29972013) is gratefully acknowledged.
文摘Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
文摘The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.
文摘BACKGROUND The FGFR signaling pathway is activated in multiple tumor types through gene amplifications,single base substitutions,or gene fusions.Novel FGFR gene fusions may represent candidate targets for the development of tyrosine kinase inhibitors.CASE SUMMARY Herein,we report a patient with colorectal cancer(CRC)harboring a novel FGFR2 fusion gene.A 59-year-old man felt discomfort in his right upper abdomen with loss of appetite for 6 mo.An abdominal computed tomography scan revealed the existence of a space-occupying lesion in the ascending colon.The pathological diagnosis was a poorly differentiated adenocarcinoma.Subsequent biopsy specimen was subjected to next-generation sequencing analysis,and a novel FGFR2-TSC22D1 fusion with complete kinase structure of FGFR2 protein was identified.CONCLUSION We report the first case of CRC harboring FGFR2-TSC22D1,which enriches the FGFR2 fusion spectrum.FGFR2 inhibitors might be effective in the later treatment for this patient.
