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151.
Background Under the circumstance of the New Medical Reform in Mainland of China,lowering drug prices has become an approach to relieving increase of medical expenses,and lowering brand-name medication price is a key strategy.This study,by comparing and analyzing brand-name medication prices between Mainland of China and Taiwan,explores how to adjust brand-name medication prices in Mainland of China in the consideration of the drug administrative strategies in Taiwan.Methods By selecting brand-name drug with generic name and dose types matched in Mainland and Taiwan,calculate the average unit price and standard deviation and test it with the paired t-test.In the mean time,drug administrative strategies between Mainland and Taiwan are also compared systematically.Results Among the 70 brand-name medications with generic names and matched dose types,54 are at higher prices in Mainland of China than Taiwan,which is statistically significant in t-test.Also,among the 47 medications with all of matched generic names,dose types,and manufacturing enterprises,38 are at higher prices in Mainland than Taiwan,and the gap is also statistically significant in t-test.In Mainland of China,brand-name medication took cost-plus pricing and price-based price adjustment,while in Taiwan,brand-name medication took internal and external reference pricing and market-based price adjustment.Conclusions Brand-name drug prices were higher in Mainland of China than in Taiwan.The adjustment strategies of drug orices are scientific in Taiwan and are worth reference by Mainland of China. 相似文献
152.
153.
Karin Beelen Mark Opdam Tesa M Severson Rutger HT Koornstra Andrew D Vincent Jelle Wesseling Jettie J Muris Els MJJ Berns Jan B Vermorken Paul J van Diest Sabine C Linn 《Breast cancer research : BCR》2014,16(1):R13
Introduction
Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway can overcome endocrine resistance in estrogen receptor (ER) α-positive breast cancer, but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking. PIK3CA mutations frequently occur in ERα-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro. Nevertheless, the prognostic and treatment-predictive value of these mutations in ERα-positive breast cancer is contradictive. We tested the clinical validity of PIK3CA mutations and other canonic pathway drivers to predict intrinsic resistance to adjuvant tamoxifen. In addition, we tested the association between these drivers and downstream activated proteins.Methods
Primary tumors from 563 ERα-positive postmenopausal patients, randomized between adjuvant tamoxifen (1 to 3 years) versus observation were recollected. PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry. Immunohistochemistry was performed for human epidermal growth factor receptor 2 (HER2), phosphatase and tensin homolog (PTEN), and insulin-like growth factor 1 receptor (IGF-1R). We tested the association between these molecular alterations and downstream activated proteins (like phospho-protein kinase B (p-AKT), phospho-mammalian target of rapamycin (p-mTOR), p-ERK1/2, and p-p70S6K). Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonic pathway drivers, by using Cox proportional hazard models, including a test for interaction.Results
PIK3CA mutations (both exon 9 and exon 20) were associated with low tumor grade. An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors. PIK3CA exon 20 mutations were not associated with downstream-activated proteins. No significant interaction between PIK3CA mutations or any of the other canonic pathway drivers and tamoxifen-treatment benefit was found.Conclusion
PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERα- positive, postmenopausal, early breast cancer patients. 相似文献154.
Karin Beelen Mark Opdam Tesa M Severson Rutger HT Koornstra Andrew D Vincent Jelle Wesseling Jettie J Muris Els MJJ Berns Jan B Vermorken Paul J van Diest Sabine C Linn 《Breast cancer research : BCR》2014,16(1):R6
Introduction
Activation of the phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen resistance in vitro, but a biomarker with clinical validity to predict intrinsic resistance has not been identified. In metastatic breast cancer patients with previous exposure to endocrine therapy, the addition of a mammalian target of rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear. A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting. We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients.Methods
We recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen (1–3 years) versus observation. After constructing a tissue micro-array, cores from 563 estrogen receptor α positive were immunostained for p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy.Results
Interactions were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p-ERK1/2. Applying a conservative level of significance, p-p70S6K remained significantly associated with tamoxifen resistance. Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001), while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K was associated with a decreased risk for recurrence.Conclusions
Patients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway activation, have a favorable prognosis, but do not benefit from adjuvant tamoxifen. A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored. 相似文献155.
156.
BACKGROUND: Toluidine blue is a useful stain for detecting basal cell carcinoma during Mohs' micrographic surgery. OBJECTIVE: To demonstrate the efficacy of alkalinization on the toluidine blue stain. METHODS: A 1% aqueous toluidine blue-1% aqueous sodium borate solution was used to stain microscope slides for basal cell carcinoma during Mohs' micrographic surgery. RESULTS: Total toluidine blue staining time was reduced to less than 2.5 minutes, without compromising the quality of the stain. CONCLUSIONS: The rapid toluidine blue stain reduces staining time while maintaining staining quality, including the advantages specific to the toluidine blue stain. 相似文献
157.
Mitochondrial tRNALeu isoforms in lung carcinoma cybrid cells containing the np 3243 mtDNA mutation 总被引:1,自引:0,他引:1
We have investigated the representation of structural isoforms of the two
mitochondrial leucyl tRNAs in lung carcinoma cybrid cell lines containing
the np 3243 (MELAS) mtDNA mutation, alone or in combination with the np
12300 suppressor mutation. The mutant tRNALeu(UUR) is aminoacylated very
poorly or not at all, whereas the suppressor tRNALeu(CUN) is efficiently
aminoacylated. Deacylated mitochondrial tRNALeu(CUN) is present, in all
human cells tested, in two structural isoforms that are separable on
denaturing gels, indicating a difference in primary structure. The ratio of
the two isoforms differs between cell types and is strongly biased towards
one isoform in lung carcinoma cybrids containing high levels of the np 3243
mutation, compared with control cybrids. We propose that structural
modification of tRNALeu(CUN) could be a natural suppression mechanism for
the np 3243 and other mitochondrial tRNALeu(UUR) mutations and could
underlie some of the phenotypic variability of np 3243 disease.
相似文献
158.
159.
Comparison of Mohs Micrographic Surgery and Wide Excision for Extramammary Paget''s Disease 总被引:5,自引:0,他引:5
William J. O''Connor MD Katherine K. Lim MD Mark J. Zalla MD Maureen. Gagnot HT Clark C. Otley MD Tri H. Nguyen MD Randall K. Roenigk MD 《Dermatologic surgery》2003,29(7):723-727
BACKGROUND: Extramammary Paget's disease is a rare cutaneous adenocarcinoma that occurs in an apocrine gland distribution mainly in the anogenital region. OBJECTIVE: To formulate treatment recommendations for this rare disease, we examined clinical and follow-up data of patients with it. METHODS: A retrospective review is given about the treatment and outcome for 95 patients at Mayo Clinic, Rochester, Minnesota, and Scottsdale, Arizona, between 1976 and 2001. The literature regarding diagnosis and treatment of this disease is also reviewed. RESULTS: Of the 95 patients, 86 had primary disease and 9 had recurrent disease. At mean follow-up (wide excision, 65 months; Mohs surgery, 24 months), disease had recurred in 18 of 83 (22%) who underwent standard wide excision, compared with recurrence in 1 of 12 (8%) who had the Mohs micrographic excision. CONCLUSION: Mohs micrographic surgery compares favorably with wide excision. Intraoperative immunostaining with cytokeratin 7 is helpful in delineating disease, as are preoperative scouting biopsies and photodynamic diagnosis. 相似文献
160.
目的:观察低氧促进大鼠骨骼肌成肌细胞增殖的作用,并分析CoCl2对成肌细胞增殖的影响。方法:实验于2005-05/2006-07在解放军军事医学科学院基础医学研究所神经肌肉发育研究室完成。①低氧CO2温箱(Forma Scientific,美国);CoCl2(北京化工厂)。②选取4~5周龄Wistar雄性大鼠5只,脱颈处死无菌切取后腿肌群,剪除脂肪和筋膜,制备单细胞悬液。以连续贴壁法筛选大鼠骨骼肌成肌细胞,接种于96孔板进行单克隆培养。采用成肌细胞特异性标志抗原desmin免疫化学染色,鉴定成肌细胞标志蛋白——结蛋白的表达,弃去desmin阴性的细胞克隆,继续培养desmin阳性的细胞克隆,隔天换液1次,7d进行酶消化传代,获得大量扩增的细胞,并可冻存复苏,用于实验。③以1×107L-1接种于20个35mm培养皿中,接种细胞3h后,将培养皿随机数字表法分为5组:常氧对照组、轻度低氧组、中度低氧组、CoCl2组、轻度低氧 CoCl2组,4皿/组。常氧对照组置于体积分数为0.2的O2常规氧气环境中;轻、中度低氧组分别于低氧温箱中维持体积分数为0.1与0.03的O2低氧环境中;CoCl2组向培养皿中加入终浓度为15μmol/L的CoCl2;轻度低氧 CoCl2组向细胞培养皿中加入终浓度为15μmol/L的CoCl2后,放入体积分数为0.1的O2低氧温箱。低氧培养24,48,72h时,各组取出培养皿进行细胞消化离心,倒置相差显微镜下观察细胞生长情况,血球计数板计数法进行细胞计数。④以1×108L-1接种于8个60mm培养皿中,接种细胞3h后,将培养皿随机数字表法分为2组:常氧对照组、轻度低氧组,4皿/组。两组干预措施同细胞计数过程。低氧培养48h时,两组取出培养皿进行细胞消化离心,流式细胞仪检测细胞周期。结果:①骨骼肌成肌细胞的单克隆培养结果:成肌细胞可在体外存活6个月,增殖旺盛期约为3个月,可传代15次以上。单克隆培养2周后,可以由单个细胞长满96孔板中的1个孔,并不断扩增,最终可以得到细胞类型专一单克隆化的成肌细胞。②成肌细胞特异性标志抗原desmin鉴定结果:镜下不同视野desmin阳性率达100%,即培养的成肌细胞单克隆纯度达100%。③细胞计数结果:与常氧对照组比较,低氧培养24,48,72h时轻、中度低氧组均可明显促进大鼠骨骼肌成肌细胞体外增殖,且轻度低氧组作用尤为明显(t=4.98,P<0.001);CoCl2组无明显变化,但轻度低氧 CoCl2组细胞数量显著增加(t=4.62,P<0.001)。④细胞周期分布:与常氧对照组比较,低氧48h时轻度低氧组处于S期的细胞明显增多[(26.67±0.89)%,(65.43±0.23)%,t=2.36,P<0.01],且增殖指数亦显著上升(33.4%,67.1%,t=2.15,P<0.01)。结论:①轻中度低氧可以促进大鼠骨骼肌成肌细胞的增殖,为体外大量扩增细胞提供了新思路。②CoCl2对骨骼肌成肌细胞没有促增殖作用。 相似文献