JF305 is a highly prolific pancreatic cancer cell line that originated from a Chinese patient. The cell line bears a functional HR double strand DNA repair mechanism but very responsive to PARP treatment a phenomenon ...JF305 is a highly prolific pancreatic cancer cell line that originated from a Chinese patient. The cell line bears a functional HR double strand DNA repair mechanism but very responsive to PARP treatment a phenomenon clearly suggesting presence of an anomaly in the mechanism. Brca1, Brca2 and CHK2 proteins are very important constituents of the HR mechanism whose respective gene coding mutations are strongly associated with several cancers and are widely exploited in anticancer chemotherapy. In this current study, the BRCA1, BRCA2 gene mutation status in JF305 was determined together with the presence of 3 widely reported cancer linked CHK2 founder mutations (1100delC, I157T, IVS2 +IG > A). CHK21100delC genotype was determined using allele specific PCR, while the PCR-RFLP assay was used for I157T, IVS2 +IG > A analysis. PCR and direct sequencing were used for assessing the BRCA1 and BRCA2 gene. Results revealed that JF305 is CHK21100delC heterozygous mutant, CHK2I157T and CHK2IVS2 +IG > A wild type. Furthermore, it was observed that JF305 lacked BRCA1 and BRCA2 gene mutations. The mutation status identification of CHK2 and BRCA1/2 in JF305 provides a major milestone towards elucidating the properties of the cell line which subsequently promises to be an excellent model for evaluating the role of parp inhibitors in pancreatic cancer chemotherapy most especially in the respective cancer cell lines without BRCA1 and BRCA2 gene mutations.展开更多
目的:探讨检测点激酶2(check point kinase2,Chk2)和重构剪切因子1(remodeling and spacing factor1,Rsf1)在卵巢浆液性腺癌(ovarian serous adenocarcinoma,OSA)中表达及其临床意义。方法:采用免疫组化SP法检测58例高级别OSA、14例低级...目的:探讨检测点激酶2(check point kinase2,Chk2)和重构剪切因子1(remodeling and spacing factor1,Rsf1)在卵巢浆液性腺癌(ovarian serous adenocarcinoma,OSA)中表达及其临床意义。方法:采用免疫组化SP法检测58例高级别OSA、14例低级别OSA中Chk2和Rsf1蛋白的表达水平,分析与临床病理参数的关系。并检测27例卵巢交界性浆液性肿瘤(ovarian borderline serous tumor,OBST)中两种蛋白的表达水平,与OSA进行对比分析。结果:Chk2在高级别和低级别OSA中阳性率分别为79.3%(46/58)和50.0%(7/14),差异有统计学意义,χ2=4.99,P=0.026;在OSA和OBST中阳性率分别为77.8%(56/72)和44.4%(12/27),差异有统计学意义,χ2=7.41,P=0.006。Chk2的表达与OSA复发及3年生存期有相关性,P<0.05;而与年龄、肿瘤最大径、淋巴结有无转移、发病部位及pTNM分期无关,P>0.05。Rsf1在高级别和低级别OSA中阳性率分别为86.2%(50/58)和57.1%(8/14),差异有统计学意义,χ2=6.08,P=0.023;在OSA及OBST中阳性率分别为79.2%(57/72)和51.9%(14/27),差异有统计学意义,χ2=8.16,P=0.004。Rsf1的表达与OSA复发及pTNM分期有相关性,P<0.05;而与年龄、肿瘤大小、淋巴结有无转移、发病部位及3年生存期无关,P>0.05。Chk2和Rsf1的表达存在明显相关性,r=0.343,P=0.003。结论:Chk2与Rsf1在OSA的发生发展中起重要作用,可作为临床指导治疗和评价患者预后的重要标志。展开更多
针对目前光滑孪生支持向量回归机(smooth twin support vector regression,STSVR)中采用的Sigmoid光滑函数逼近精度不高,从而导致算法泛化能力不够理想的问题,引入一种具有更强逼近能力的光滑(chen-harker-kanzow-smale,CHKS)函数,采用C...针对目前光滑孪生支持向量回归机(smooth twin support vector regression,STSVR)中采用的Sigmoid光滑函数逼近精度不高,从而导致算法泛化能力不够理想的问题,引入一种具有更强逼近能力的光滑(chen-harker-kanzow-smale,CHKS)函数,采用CHKS函数逼近孪生支持向量回归机的不可微项,并用Newton-Armijo算法求解相应的模型,提出了光滑CHKS孪生支持向量回归机(smooth CHKS twin support vector regression,SCTSVR).不仅从理论上证明了SCTSVR具有严格凸,能满足任意阶光滑和全局收敛的性能,而且在人工数据集和UCI数据集上的实验表明了SCTSVR比STSVR具有更好的回归性能.展开更多
文摘JF305 is a highly prolific pancreatic cancer cell line that originated from a Chinese patient. The cell line bears a functional HR double strand DNA repair mechanism but very responsive to PARP treatment a phenomenon clearly suggesting presence of an anomaly in the mechanism. Brca1, Brca2 and CHK2 proteins are very important constituents of the HR mechanism whose respective gene coding mutations are strongly associated with several cancers and are widely exploited in anticancer chemotherapy. In this current study, the BRCA1, BRCA2 gene mutation status in JF305 was determined together with the presence of 3 widely reported cancer linked CHK2 founder mutations (1100delC, I157T, IVS2 +IG > A). CHK21100delC genotype was determined using allele specific PCR, while the PCR-RFLP assay was used for I157T, IVS2 +IG > A analysis. PCR and direct sequencing were used for assessing the BRCA1 and BRCA2 gene. Results revealed that JF305 is CHK21100delC heterozygous mutant, CHK2I157T and CHK2IVS2 +IG > A wild type. Furthermore, it was observed that JF305 lacked BRCA1 and BRCA2 gene mutations. The mutation status identification of CHK2 and BRCA1/2 in JF305 provides a major milestone towards elucidating the properties of the cell line which subsequently promises to be an excellent model for evaluating the role of parp inhibitors in pancreatic cancer chemotherapy most especially in the respective cancer cell lines without BRCA1 and BRCA2 gene mutations.
文摘针对目前光滑孪生支持向量回归机(smooth twin support vector regression,STSVR)中采用的Sigmoid光滑函数逼近精度不高,从而导致算法泛化能力不够理想的问题,引入一种具有更强逼近能力的光滑(chen-harker-kanzow-smale,CHKS)函数,采用CHKS函数逼近孪生支持向量回归机的不可微项,并用Newton-Armijo算法求解相应的模型,提出了光滑CHKS孪生支持向量回归机(smooth CHKS twin support vector regression,SCTSVR).不仅从理论上证明了SCTSVR具有严格凸,能满足任意阶光滑和全局收敛的性能,而且在人工数据集和UCI数据集上的实验表明了SCTSVR比STSVR具有更好的回归性能.
