HPMC在盐酸二苯美仑片中的应用

ＨＰＭＣ在盐酸二苯美仑片中的应用谢安云，邓君芳（湖南医药工业研究所，长沙４１００１４）ＡＰＰＬＩＣＡＴＩＯＮＯＦＨＰＭＣＩＮＢＩＦＥＭＥＬＡＮＥＨＹＤＲＯＣＨＬＯＲＩＤＥＴＡＢＬＥＴＳ￥ＸＩＥＡｎ－Ｙｕｎ；ＤＥＮＧＪｕｎ－Ｆａｎｇ（ＨｕｎａｎＩｎｓｔ...     

地昔帕明对脑胶质瘤C6细胞的增殖抑制和凋亡诱导作用

目的研究地昔帕明（ＤＭＩ）对大鼠脑胶质瘤Ｃ６的增殖抑制和凋亡诱导作用,为三环类抗抑郁药作为肿瘤辅助治疗提供新的理论和实验依据。方法用ＭＴＴ比色法测定Ｃ６细胞活力,用透射电镜、流式细胞术（ＦＣＭ）检测细胞凋亡,用免疫组化法分析ｂｃｌ－２蛋白的表达。结果ＤＭＩ对Ｃ６细胞的增殖具有明显的浓度依赖性抑制作用, ＩＣ５０（ ９５ ％置信区间）为２０．７（１７．３～２４．２）μｍｏｌ·Ｌ－１,细胞阻滞于Ｇ０～Ｇ１期。ＤＭＩ（４０μｍｏｌ·Ｌ－１）使细胞发生典型的凋亡形态改变,ＤＮＡ含量分析显示 Ｇ０峰左侧出现亚二倍体细胞凋亡峰,呈浓度依赖性,蛋白合成抑制剂ＣＨＸ可显著抑制ＤＭＩ诱导的细胞凋亡。同时,ＤＭＩ（１０ μｍｏｌ·Ｌ－１）可下调细胞 ｂｃｌ－２蛋白的表达。结论ＤＭＩ体外对Ｃ６细胞的增殖具浓度依赖性抑制作用,并诱导细胞凋亡。     

盐酸环丙沙星片的溶出度测定

盐酸环丙沙星片的溶出度测定ＩＮＶＥＳＴＩＧＡＴＩＯＮＯＮＤＩＳＳＯＬＵＴＩＯＮＯＦＣＩＰＲＯＦＬＯＸＡＣＩＮＨＹＤＲＯＣＬＯＲＩＤＥＴＡＢＬＥＴＳ童荣生＊陈素华张研林（四川省人民医院药剂科，成都６１００７２）ＴＯＮＧＲｏｎｇ－Ｓｈｅｎｇ＊，ＣＨＥＮＳ...     

多药耐药基因与体外药敏检测在急性白血病中的临床意义

目的：研究急性白血病（ＡＬ）多药耐药－１（ＭＤＲ１）基因表达与临床疗效的关系，提高对肿瘤细胞耐药情况预测的准确性。方法：采用逆转录敏－多聚酶链反应（ＲＴ－ＰＣＲ）检测了３０例ＡＬ患者骨髓中ＭＤＲ１基因的表达，同时对每例均进行体外化疗药物敏感性（ＴＭＭ）检测。结果：３０例ＡＬ ＭＤＲ１基因过度表达占４０％，ＭＴＴ检出耐药为３０％（１０／３０），即有ＭＤＲ１基因过量表达又显示耐药者２７％（８／３０）；     

西咪替丁A晶型和混晶型的质量探讨

西咪替丁Ａ晶型和混晶型的质量探讨钱树德，刘有龙（苏州市药品检验所，江苏２１５００６）ＱＵＡＬＩＴＡＴＩＶＥＳＴＵＤＹＯＮＣＲＹＳＴＡＬＦＯＲＭＡＡＮＤＭＩＸＥＤＣＲＹＳＴＡＬＦＯＲＭＳＯＦＣＩＭＥＴＩＤＩＮＥ￥ＱＩＡＮＳｈｕ－Ｄｅ；ＬＩＵＹｏｕ－Ｌｏ...     

粉防己碱逆转肿瘤多药抗药性细胞的凋亡抗性作用

目的探讨粉防己碱逆转ＭＤＲ细胞凋亡抗性的作用及其机制。方法ＭＤＲ细胞株ＭＣＦ－７／Ａｄｒ与其相应的敏感株ＭＣＦ－７进行对比研究。比较粉防己碱对阿霉素（Ｄｏｘ）诱导ＭＤＲ细胞及其相应的敏感株的凋亡作用。并比较粉防己碱对ＭＤＲ细胞及其相应的敏感株的细胞ｂｃｌ－２蛋白的表达的影响。细胞凋亡及ｂｃｌ－２蛋白表达的测定以流式细胞仪法。结果加入Ｄｏｘ共同培养２４ｈ可诱导７４．６％ＭＣＦ－７细胞凋亡，而只引起１４．３％的ＭＣＦ－７／Ａｄｒ细胞凋亡。只加入粉防己碱共同培养２４ｈ，未见明显增加ＭＤＲ细胞及其相应敏感细胞的凋亡百分比。Ｄｏｘ＋粉防己碱能显著地使ＭＤＲ细胞的凋亡增至４７．０％，与单独用Ｄｏｘ组相比较，差异有显著性（Ｐ＜０．０１），而敏感细胞株为７７．８％，与单独用Ｄｏｘ组相比较，差异无显著性（Ｐ＞０．０５）。ＭＤＲ细胞株与其相应的敏感株ｂｃｌ－２蛋白表达水平均较低且差异无显著性。加入粉防己碱对ＭＤＲ细胞株与其相应的敏感株ｂｃｌ－２蛋白表达水平均未见明显影响。结论粉防己碱能逆转ＭＤＲ细胞对Ｄｏｘ的凋亡抗性。其逆转机制可能与ｂｃｌ－２蛋白表达无关。粉防己碱逆转ＭＤＲ细胞ＭＣＲ－７／ＡＤＲ对Ｄｏｘ的凋亡抗性的机制有待进?     

盐酸异丙嗪－β－环糊精包合物的制备及其稳定性的初步研究

盐酸异丙嗪－β－环糊精包合物的制备及其稳定性的初步研究孙伟张，刘明蓉，曹仁杰，景利（成都军区总医院四川６１００８３）ＰＲＥＰＡＲＡＴＩＯＮＯＦβ－ＣＹＣＬＯＤＥＸＴＲＩＮＩＮＣＬＵＳＩＯＮＣＯＭＰＯＵＮＤＯＦＰＲＯＭＥＴＨＡＺＩＮＥＨＹＤＲＯＣＨＬＯ...     

新研制的查耳酮类似物的人癌细胞体外评价

类黄酮化合物中查耳酮具有化学预防和抗肿瘤活性。新合成 1 0个查耳酮类似物 ,用 2个人乳腺癌细胞系和 1个人Ｔ细胞白血病细胞系进行研究 ,皮苷用作对照化合物。人乳腺癌ＭＤＡ ＭＢ2 31细胞系培养在最少必需物介质中 ;ＭＣＦ 7ＡＤＲｒ为多柔比星选择性耐药细胞系 ,生长于ＲＰＭＩ 1 640介质及添加 1 0 %胎牛血清和2 0 0ｋＵ·Ｌ- 1 青霉素中。人Ｔ细胞白血病Ｊｕｒｋａｔ细胞系培养介质与ＭＣＦ 7ＡＤＲｒ细胞系相同。抗增殖活性以用药 72ｈ后细胞计数评价。ＤＮＡ分析和氧化还原活性用流量细胞计数评价。凋亡形态学分析用ＹＯＹＯ 1为…     

盐酸去氯羟嗪片的酸性染料比色测定

盐酸去氯羟嗪片的酸性染料比色测定ＡＣＩＤＩＣＤＹＥＣＯＬＯＲＩＭＥＴＲＹＯＦＤＥＣＬＯＸＩＺＩＮＥＨＹＤＲＯＣＨＬＯＲＩＤＥＴＡＢＬＥＴＳ戴斌＊周丽ａ（上海衡山药业有限公司，上海２０１１００；ａ山东省曹县药品检验所，山东２７４４００）ＤＡＩＢｉｎ＊，...     

THE CHEMISTRY AND DISTRIBUTION OF TAXANE DITERPENOIDS AND ALK

ＴＨＥＣＨＥＭＩＳＴＲＹＡＮＤＤＩＳＴＲＩＢＵＴＩＯＮＯＦＴＡＸＡＮＥＤＩＴＥＲＰＥＮＯＩＤＳＡＮＤＡＬＫＡＬＯＩＤＳＦＲＯＭＧＥＮＵＳＴＡＸＵＳＪＺＺｈａｎｇ（ＩｎｓｔｉｔｕｔｅｏｆＭａｔｅｒｉａＭｅｄｉｃａ，ＣｈｉｅｓｅＡｃａｄｅｍｙｏｆＭｅｄｉ...     

通关藤提取物体外对Jurkat、Raji、RPMI8226细胞的抑制作用研究

目的探讨通关藤提取物对Jurkat、Raji、RPMI8226细胞的抑制作用及可能机制。方法以不同浓度通关藤提取物处理Jurkat、Raji、RPMI8226细胞,MTT法检测其对3种细胞的抑制作用,Annexin V/PI双染法观察细胞形态并检测细胞的凋亡率,JC-1染色法检测细胞线粒体跨膜电位(ΔΨm)水平。结果通关藤提取物对Jurkat细胞的抑制作用最强,对RPMI8226细胞最不敏感。25,50μL/mL的通关藤提取物能降低Jurkat、Raji细胞内ΔΨm,并促进其凋亡。100μL/mL的通关藤提取物也可降低RPMI8226细胞ΔΨm而诱导其凋亡。结论通关藤提取物体外对部分淋巴细胞白血病细胞株和骨髓瘤细胞株有不同程度的诱导凋亡作用,可能是通过降低ΔΨm途径触发这些细胞凋亡。     

Cooperation between Apo2L/TRAIL and bortezomib in multiple myeloma apoptosis

The proteasome inhibitor bortezomib is currently an important drug for treatment of relapsed and refractory multiple myeloma (MM) and for elderly patients. However, cells from some patients show resistance to bortezomib. We have evaluated the possibility of improving bortezomib therapy with Apo2L/TRAIL, a death ligand that induces apoptosis in MM but not in normal cells. Results indicate that cotreatment with low doses of bortezomib significantly increased apoptosis of MM cells showing partial sensitivity to Apo2L/TRAIL. Bortezomib treatment did not significantly alter plasma membrane amount of DR4 and DR5 but increased Apo2L/TRAIL-induced caspase-8 and caspase-3 activation. Apo2L/TRAIL reverted bortezomib-induced up-regulation of β-catenin, Mcl-1 and FLIP, associated with the enhanced cytotoxicity of combined treatment. More important, some cell lines displaying resistance to bortezomib were sensitive to Apo2L/TRAIL-induced apoptosis. A cell line made resistant by continuous culture of RPMI 8226 cells in the presence of bortezomib (8226/7B) was highly sensitive to Apo2L/TRAIL-induced apoptosis. Moreover, RPMI 8226 cells overexpressing Mcl-1 (8226/Mcl-1) or Bcl-x_L (8226/Bcl-x_L) also showed enhanced resistance to bortezomib, but co-treatment with Apo2L/TRAIL reverted this resistance. These results indicate that Apo2L/TRAIL can cooperate with bortezomib to induce apoptosis in myeloma cells and can be an useful adjunct for MM therapy.     

苦参碱诱导RPMI8226细胞凋亡及其对Bcl-2、增殖细胞核抗原蛋白表达的影响

目的：研究苦参碱是否具有诱导RPMI8226细胞凋亡的生物学活性,探讨苦参碱对RPMI8226细胞Bcl-2及增殖细胞核抗原（PCNA）表达水平的影响及其作用的分子机制。方法：CCK-8法检测一定浓度的苦参碱对RPMI8226细胞的体外增殖抑制作用;AnnexinV/PI双染色法检测细胞凋亡;PI单染色法检测细胞周期改变;同时应用流式细胞术检测Bcl-2及PCNA蛋白表达的变化。结果：苦参碱对RPMI8226细胞生长具有明显的抑制作用,呈量效和时效关系;苦参碱能诱导RPMI8226细胞凋亡,呈量效关系;细胞周期分析,G0/G1期细胞相对增多、S期相对减少、G2/M期无明显变化。苦参碱处理组RPMI8226细胞中Bcl-2及PCNA蛋白的表达跟未加药组相比阳性表达率均降低。结论：苦参碱对RPMI8226细胞生长具有明显抑制作用,其作用主要通过诱导RPMI8226细胞产生细胞周期阻滞和凋亡,降低PCNA的表达。苦参碱诱导RPMI8226细胞凋亡过程中,Bcl-2蛋白表达下调对调控细胞凋亡有重要作用。     

尿多酸肽抑制多发性骨髓瘤细胞株RPIMI 8226增殖及其机制研究

目的 探讨尿多酸肽（CDA-2）抑制多发性骨髓瘤细胞株RPMI8226增殖作用及其机制。方法 采用四甲基偶氮唑（MTT）比色法检测CDA-2对RPMI8226抑制作用并筛选研究浓度;通过Hoechst33258、Annexin-V/PI、细胞周期分析、DNA琼脂糖凝胶电泳等方法检测CDA-2诱导RPMI8226凋亡作用;使用Western Blot法检测caspase-8、caspase-3及其激活物的表达改变;半定量RT-PCR法检测TNF、FADD、TRAF3mRNA表达。结果 CDA-2能够抑制RPMI8226细胞株增殖,并呈浓度依赖性,IC50为1.64mg·mL1;经CDA-2作用后,Hoechst33258荧光染色提示细胞核浓集及出现凋亡小体,Annexin-V/PI分析示早期凋亡细胞比例呈时间依赖增加,细胞周期分析提示呈浓度依赖上调凋亡峰及下调G1期比例,DNA凝胶电泳可见断裂成180~200bp及其倍数的片断梯形条带,故CDA-2可诱导RPMI8226细胞株凋亡;WesternBlot检测发现随药物作用时间延长caspase-8、caspase-3表达明显下降,而active-caspase8、active-caspase3表达上升;半定量RT-PCR证实凋亡相关基因TNF、FADD、TRAF3mRNA表达上调。结论 CDA-2可抑制RPMI8226增殖,且可通过死亡受体途径诱导细胞凋亡。     

Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity

AIM: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x(L), XIAP and Bax protein were detected using Western blotting analysis. RESULTS: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x(L) and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64+/-8 micromol/L, 93+/-11 micromol/L, and 153+/-11 micromol/L, respectively.Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. CONCLUSION: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.     

雷公藤红素对多发性骨髓瘤细胞株RPMI 8226的体外抑制作用研究

目的研究雷公藤红素（Celastrol）对多发性骨髓瘤细胞株RPMI 8226的抑制作用;方法使用CCK-8试剂研究生长抑制作用,使用An-nexin-V/PI双染色法,研究诱导凋亡作用;使用流式细胞仪进行sub-G1峰及细胞周期分析;结果雷公藤红素能够抑制RPMI 8226细胞生长,呈现剂量依赖性,IC50值为1.87μmol.L-1;通过Annexin-V/PI双染色法以及sub-G1峰分析,证实雷公藤红素可以诱导肿瘤细胞凋亡;并使肿瘤细胞的S期细胞减少;结论雷公藤红素可以抑制骨髓瘤细胞株RPMI 8226生长,诱导细胞凋亡,并使S期细胞减少。     

异硫氰酸苯己酯对骨髓瘤细胞增殖抑制机制的体外研究

目的观察异硫氰酸苯己酯(PHI)体外抑制骨髓瘤细胞增殖的机制。方法 MTT检测PHI对骨髓瘤细胞株RPMI8226增殖的影响;流式细胞术检测药物处理后细胞周期的变化;实时荧光定量PCR检测PHI对Jag2、发状相关增强子基因(Hes1)及人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)表达的影响。结果 PHI可抑制RPMI8226细胞增殖,使细胞滞留于G0/G1期。剂量较大的2个实验组较对照组,Jag2表达量的减少与PTEN表达量的增加具有统计学意义(P<0.05);各实验组较对照组Hes1表达量减少均具统计学意义(P<0.05)。结论 PHI可通过靶向抑制Notch信号,上调抑癌基因PTEN,抑制骨髓瘤细胞株的体外增殖。     

Anti-CD19 mAb modified mesoporous titanium dioxide as exclusively targeting vector for efficient B-lymphoblastic leukemia therapy

B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy. In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle. The CD19-PEG-MTN/DOX nanoparticle could recognize CD19⁺ B-LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2, MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19^?cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.     

Synthesis and Evaluation of 2‐Alkylthio‐4‐(N‐substituted sulfonamide)pyrimidine Hydroxamic Acids as Anti‐myeloma Agents

A series of pyrimidine hydroxamic acids with a sulfide substituent at the second position and a sulfonamide substituent at the fourth position have been synthesized and evaluated for their activity against human myeloma cell line RPMI 8226. Several compounds exhibited significant anti‐cancer potency. It was found that representative compound 6a selectively killed cancerous but not normal cells. Moreover, compound 6a was effective in causing apoptosis in RPMI 8226 cells and exhibited promising HDAC‐inhibitory activities.