塞来昔布治疗裸鼠前列腺癌骨转移研究

目的建立裸鼠前列腺癌骨转移模型,探讨塞来昔布作为血管抑制剂对前列腺癌骨转移的形成及生长的影响。方法将30只前列腺癌骨转移裸鼠随机分成二组,第一组隔日予以生理盐水,腹腔注射;第二组隔日予以塞来昔布30 mg/kg,腹腔注射;30 d后处死。检测血清碱性磷酸酶,采用免疫组化和图象分析系统测定血管内皮生长因子(VEGF)和肿瘤微血管密度(MVD),光镜下观察各组肿瘤组织,流式细胞仪检测肿瘤细胞的凋亡。结果治疗组肿瘤的生长明显受到抑制(P<0.01),塞来昔布组肿瘤组织中的VEGF和MVD与对照组比较无统计学意义(P<0.01),抑瘤率为54.47%,凋亡指数由(4.68±1.83)%上升到(24.93±6.14)%,血清碱性磷酸酶由(26.5±4.93)U/L下降到(17.17±3.13)U/L。结论塞来昔布能显著抑制裸鼠前列腺癌骨转移瘤的生长和新生血管形成。     

比卡鲁胺治疗前列腺癌的临床应用

比卡鲁胺是一种新型的非甾体抗雄激素药物,内分泌治疗是前列腺癌治疗的主要手段。本文就比卡鲁胺单药治疗前列腺癌、联合化疗治疗前列腺癌及联合放疗或去势手术治疗前列腺癌的临床疗效作一综述。     

塞来昔布致急性胰腺炎

1例43岁女性患者因肩周炎服用塞来昔布胶囊0．2g,2次／d,共服用2周。末次服药后2h上腹出现持续性钝痛,伴腹胀、恶心、呕吐。实验室检查示血清淀粉酶1822U／L,胰淀粉酶1529U／L,脂肪酶1410U／L,白细胞计数12．7×10^9／L,中性粒细胞0．74,淋巴细胞0．16。腹部超声检查和磁共振胰胆管造影示胰腺弥漫性增大、胰腺周围有液性渗出,诊断为急性胰腺炎。停用塞来昔布,禁食,给予营养支持和抑酶、抑酸、抗感染治疗13d,患者腹痛、腹胀消失,实验室检查示淀粉酶86U／L,胰淀粉酶48U／L,脂肪酶55U／L,白细胞计数7．2×10^9／L,中性粒细胞0．65,淋巴细胞0．32。胰腺CT示胰头、胰体和胰尾位于同一层面,形态及大小基本正常。     

索拉非尼联合塞来昔布在体外对肝癌HepG2细胞的影响

目的研究索拉非尼联合塞来昔布在体外对肝癌Hep G2细胞增殖的影响。方法以不同浓度索拉非尼和塞来昔布分别组成单药组和联合用药组作用于Hep G2细胞,MTT法检测增殖抑制率,流式细胞仪检测细胞周期。Western blot检测Cyclin D1、Cyclin D3、CDK4蛋白的表达。结果索拉非尼、塞来昔布单药与联用均能抑制Hep G2细胞增殖,呈时间-剂量依赖效应,两药联用有协同效应(P<0.05)。药物组与空白组相比,G0/G1期细胞比例增高,联合用药组最高。联合用药组与单药及空白对照组相比,Hep G2细胞中Cyclin D1、Cyclin D3蛋白的表达显著降低。结论索拉非尼联合塞来昔布可能通过下调Cyclin D1、Cyclin D3表达,增强G0/G1期阻滞,发挥协同抑制Hep G2细胞增殖的作用。     

塞来昔布对大鼠骨组织的影响

目的探讨塞来昔布对大鼠骨组织的影响。方法 16只3月龄雌性SD大鼠随机分为两组:正常对照组和塞来昔布给药组,每组8只。塞来昔布组大鼠每天灌胃给予塞来昔布50 mg·kg-1,正常对照组给予等量生理盐水。给药时间为8周,每周记录大鼠体重。实验结束时取大鼠左侧股骨用双能X线骨密度仪(DXA)测定骨密度,用三点弯曲法测定股骨生物力学特性,然后再用离子发射光谱仪测定股骨中的Ca、P、Mg的含量。另取大鼠胫骨中段皮质骨做不脱钙骨磨片测定骨形态计量学参数。结果塞来昔布50 mg·kg-1用药8周与对照组相比,明显降低大鼠股骨骨密度,但是对皮质骨骨量、骨形成率、矿化沉积率、股骨最大载荷和断裂载荷等均未产生显著性损害,也并未降低股骨中Ca、P、Mg的含量。结论塞来昔布用药8周明显降低股骨骨密度,但并未进一步损害皮质骨骨量、骨形成、骨矿无机质含量和骨生物力学特性。     

比卡鲁胺治疗中晚期前列腺癌的疗效及安全性分析

目的：评价并探讨比卡鲁胺（Bicalutamide capsules）治疗中晚期前列腺癌的临床疗效及治疗的安全性。方法：2005年6月1日～2008年5月31日,我院收治前列腺癌患者42例,年龄58～86岁,平均72岁。均经前列腺穿刺活检证实为腺癌。血清PSA值2.6～168.2ng·mL^-1,Gleason评分2～4分6例,5～7分28例,8～10分8例。采用手术去势加雄激素阻断[比卡鲁胺（岩列舒）50mg]的30例,药物去势[戈舍瑞林3.6mg·（28d）^-1]加雄激素阻断（比卡鲁胺50mg·d^-1）12例,连续治疗12个月,之后根据PSA水平采用间歇治疗。随访症状改善情况、肿瘤消退情况、肝肾功能、血PSA值及生存时间。结果：42例治疗后,开始PSA均有下降,随访第1年时,37例血PSA降至正常,第2年,33例病情稳定,6例下降不满意或出现反跳,改用其他治疗方式。到目前为止,36例存活,其余3例死于前列腺癌进展,3例死于其他疾病。结论：内分泌治疗是中晚期前列腺癌的主要治疗方法,可明显改善症状,控制疾病进展,延长生存时间,且不良反应轻微。     

比卡鲁胺与氟他胺治疗晚期去势抵抗性前列腺癌的临床比较

目的探讨比卡鲁胺与氟他胺治疗晚期去势抵抗性前列腺癌的疗效比较。方法分别以比卡鲁胺、氟他胺联合雄激素阻断治疗晚期前列腺癌,观察治疗前后的临床症状、血清PSA和血清睾酮不同时期的水平。结果比卡鲁胺组与氟他胺组服药后PSA值24、32、42月组间差异比较有统计学差异,临床表现改善比卡鲁胺组优于氟他胺组(P<0.05),两组间血清睾酮水平无显著差异。结论比卡鲁胺治疗晚期前列腺癌能明显控制前列腺癌疾病进展,改善尿路梗阻与骨痛等症状,与氟他胺相比,可减少去势抵抗性前列腺癌的发生。     

戈舍瑞林联合比卡鲁胺间歇性治疗晚期前列腺癌28例

目的 比较戈舍瑞林联合比卡鲁胺间歇性与持续性治疗晚期前列腺癌临床疗效. 方法晚期前列腺癌患者56例随机分为间歇组和持续组,每组28例. 两组患者均口服比卡鲁胺50 mg,qd,皮下注射戈舍瑞林3.6 mg,每4周1次,每个月复查血清前列腺特异性抗原(prostate specific antigen,PSA)值. 间歇组当血清PSA值降到<0.2 ng&#8226;mL-1停用2种药物, PSA>4 ng&#8226;mL^-1开始新一轮治疗,如此循环,持续组血清PSA值无论是否正常,均连续使用药物12个月. 比较两组治疗前及治疗后3,6,9,12个月时血清PSA值、临床症状改善情况及骨转移灶的变化. 结果 两组患者3,6,9,12个月血清PSA值均显著下降,与治疗前差异有统计学意义(P<0.01),组间差异无统计学意义(P>0.05). 所有患者治疗后直肠指诊或影像学检查前列腺体积明显缩小. 两组患者治疗前后临床症状改善情况及骨转移灶的变化差异有统计学意义(P<0.05),治疗前后组间差异无统计学意义(P>0.05). 结论 戈舍瑞林联合比卡鲁胺间歇性与持续性治疗晚期前列腺癌均能明显控制前列腺癌疾病进展,改善尿路梗阻与骨痛等症状.     

比卡鲁胺联合戈舍瑞林治疗晚期前列腺癌疗效观察

目的观察比卡鲁胺与戈舍瑞林联用间歇性与持续性治疗治疗晚期前列腺癌的临床疗效。方法选取2009年10到2011年10月期间我院收治的晚期前列腺癌患者共72例,患者被随机间歇治疗组(A组)和持续治疗组(B组)。A组:36例,同时给予比卡鲁胺和戈舍瑞林治疗,当患者血清前列腺特异性抗原值小于0.4ng·mL-1时,暂停服用药物比卡鲁胺;当患者血清前列腺特异性抗原值大于4ng·mL-1时,重新开始服用药物比卡鲁胺。B组:36例,同时给予比卡鲁胺和戈舍瑞林治疗,不间断治疗。经治疗4、8、12个月后,观察比较两组患者血清前列腺特异性抗原值和疼痛缓解结果。结果在患者血清PSA值恢复效果、疼痛缓解效果、排尿梗阻症状治疗效果上,间歇治疗组(A组)和持续治疗组(B组)差异不明显,无统计学意义(P>0.05)。结论间歇治疗和持续治疗对晚期前列腺癌治疗效果无明显差异,都能在一定程度上缓解患者的病情和提高患者的生活质量,但间歇性治疗能有效降低患者治疗的经济负担,值得临床推广。     

塞来昔布联合多柔比星对乳腺癌细胞增殖及凋亡的影响

目的研究COX-2选择性抑制剂塞来昔布与多柔比星(doxorubicin,ADM)联合应用对乳腺癌MCF-7细胞和Sk-Br-3细胞的抗肿瘤作用,探讨塞来昔布是否对多柔比星具有减毒增效作用。方法实验分为对照组,塞来昔布组,多柔比星组和联合用药组。用MTT法检测药物对MCF-7细胞和Sk-Br-3细胞的生长抑制效应;Western blot测定MCF-7细胞和Sk-Br-3细胞bcl-2的表达;PI染色检测细胞凋亡;克隆形成法测定药物对MCF-7细胞和Sk-Br-3细胞系的细胞毒作用。结果 MTT结果显示,30μmol·L-1塞来昔布与0.625mg·L-1多柔比星联合作用于MCF-7细胞的72 h存活率为68.53%,作用于Sk-Br-3细胞的72 h存活率为32.66%,较多柔比星单用能明显降低乳腺癌细胞的存活率,且具有时间和剂量依赖性。流式细胞仪PI染色结果显示,联合用药诱导的细胞凋亡率分别为MCF-7细胞59.7%,Sk-Br-3细胞65.8%,较单用多柔比星诱导的凋亡率(MCF-7细胞25.9%,Sk-Br-3细胞28.7%)明显提高。Western blot结果显示单用多柔比星可以使蛋白bcl-2表达下调,合用后较单用下调更加明显。两者联合处理乳腺癌细胞后,caspases-3的活性明显增强。结论塞来昔布和多柔比星对乳腺癌MCF-7细胞和Sk-Br-3细胞有增殖抑制及促凋亡作用,两药联合表现为协同或相加作用。     

Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells

Glycyrrhetinic acid (GA) is the active metabolite of glycyrrhizic acid, one of the components of liquorice extract. It has been shown to possess anti-inflammatory activity and to inhibit hepatic tumour growth. In this preliminary study, we have shown that GA could significantly reduce the rate of proliferation of LNCaP androgen dependent prostate cancer cells, whereas it had no effect on proliferation of PC3 and DU145 androgen-independent prostate cancer cells. Additionally, GA could significantly reduce the production of prostate-specific antigen by LNCaP cells maintained in-vitro. This study provides a sound platform for further investigation.     

Verapamil inhibits proliferation of LNCaP human prostate cancer cells influencing K+ channel gating

The mechanisms of verapamil and tetraethylammonium (TEA) inhibition of voltage-gated K+ channels in LNCaP human prostate cancer cells were studied in whole-cell and outside/inside-out patch-clamp configurations. Rapidly activating outward K+ currents (I(K)) exhibited neither C-type, nor rapid (human ether á go-go-related gene-type) inactivation. With 2 mM [Mg(2+)](o), I(K) activation kinetics was independent of holding potential, suggesting the absence of ether á go-go-type K+ channels. Extracellular applications of TEA and verapamil (IC(50) = 11 microM) rapidly (12 s) inhibited I(K) in LNCaP cells. Blocking was also rapidly reversible. Intracellular TEA (1 mM), verapamil (1 mM), and membrane-impermeable N-methyl-verapamil (25 microM) did not influence whole-cell I(K), although both phenylalkylamines inhibited single-channel currents in inside-out patches. Extracellular application of N-methyl-verapamil (25 microM) had no influence on I(K). Our results are compatible with the hypothesis that, in LNCaP cells expressing C-type inactivation-deficient voltage-activated K+ channels, phenylalkylamines interact with an intracellular binding site, and probably an additional hydrophobic binding site that does not bind charged phenylalkylamines. The inhibiting effects of verapamil and TEA on I(K) were additive, suggesting independent K+-channel blocking mechanisms. Indeed, TEA (1 mM) reduced a single-channel conductance (from 7.3 +/- 0.5 to 3.2 +/- 0.4 pA at a membrane potential of +50 mV, n = 6), whereas verapamil (10 microM) reduced an open-channel probability (from 0.45 +/- 0.1 in control to 0.1 +/- 0.09 in verapamil-treated cells, n = 9). The inhibiting effects of verapamil and TEA on LNCaP cell proliferation were not multiplicative, suggesting that both share a common antiproliferative mechanism initiated through a K+ channel block.     

近距离放疗联合比卡鲁胺150mg在前列腺癌治疗中的应用

目的 探讨近距离放疗联合比卡鲁胺150 mg单药治疗前列腺癌的可行性.方法 将符合入选标准的71例前列腺癌患者按随机数字表分为单药组(34例)和联合药物组(37例).接受近距离放疗后,单药组采用比卡鲁胺150 mg单药内分泌治疗;联合药物组接受戈舍瑞林3.6 mg+比卡鲁胺50 mg内分泌治疗.分别观察治疗前后的前列腺特异抗原(PSA)变化情况,第一阶段用药时间,严密记录治疗过程中的不良事件,并进行安全性评价.结果 单药组有2例、联合药物组有1例在治疗1年后血清PSA不能下降到术前的50％予以剔除.2组患者在接受近距离放疗联合药物治疗1个月后,PSA值均出现了“断崖式”的下降.在随后的治疗中,联合药物组和单药组不良反应发生率差异无统计学意义[(41.7％(15/36)比31.3％(10/32),P=0.37].PSA抑制率二者差异有统计学意义[(96±24)％比(98±24)％,P＜0.01),但对于低危患者,二者差异无统计学意义[(98±24)％比(100±25)％,P＞0.05).联合药物组用药时间短于单药组[(8.1±2.0)个月比(9.5±2.5)个月,P＜0.01],但对于低危患者,二者之间差异无统计学意义(P＞0.05).结论 前列腺癌的近距离放疗联合戈舍瑞林3.6 mg+比卡鲁胺50 mg双药内分泌治疗效果较好,而对于低危患者,采用比卡鲁胺150 mg单药联合近距离放疗的方案,亦能达到同样效果.     

miR-34a通过调控雄激素受体基因抑制前列腺癌细胞系LNCaP增殖

目的:探究miR-34a对雄激素受体(AR)基因的调控作用及对前列腺癌(PCa)LNCaP细胞增殖、凋亡的影响。方法:收集2016年10月至2019年9月本院泌尿外科行前列腺穿刺活检确诊为PCa患者组织标本36例,另取同期行手术治疗切除的良性前列腺增生(BPH)组织标本41例。体外培养LNCaP细胞,分别转染miR-34a mimics(mimics组),miR-34a mimic NC(NC组),设正常生长细胞为空白对照组(BC组),另在mimics组基础上转染AR过表达(AR过表达组)载体及其对照(AR对照组),采用CCK-8试剂盒检测细胞活性,Annexin V-FITC/PI双染色流式细胞凋亡检测试剂盒检测细胞凋亡率,实时定量PCR(RT-qPCR)检测miR-34a及AR mRNA表达水平,免疫印迹法检测AR蛋白、细胞周期蛋白D1(cyclinD1)及原癌基因产物(c-Mcy)、细胞凋亡相关蛋白(Bcl-2、Bax、capase-3)的表达水平。结果:与BPH组织比较,PCa组织中miR-34a表达水平显著降低(P<0.05),AR mRNA及蛋白表达水平均显著增加(P<0.05);与BC、NC组比较,mimics组LNCap细胞miR-34a表达水平、细胞凋亡率、Bax蛋白表达水平显著增加(P<0.05),AR、Cyclin D1、Bcl-2、Bax蛋白表达水平显著降低(P<0.05),同一时间LNCap细胞活力均显著降低(P<0.05);双荧光素酶实验结果显示,miR-34a与AR可能存在一定的调控关系,过表达AR基因可逆转miR-34a mimics对LNCaP细胞增殖抑制,促进凋亡作用。结论:miR-34a可能通过调控AR抑制前列腺癌LNCaP细胞增殖,促进其凋亡。     

An update on bicalutamide in the treatment of prostate cancer

In this update, bicalutamide (Casodex, Zeneca Pharmaceuticals) has been confirmed as an effective, well-tolerated and convenient non-steroidal anti-androgen for advanced prostate cancer. Preclinical and clinical studies have indicated its potential as monotherapy, with quality of life advantages compared with castration. A head-to-head comparison with flutamide, where both anti-androgens were used as part of combined androgen blockade, has suggested that the choice of components in this regimen can influence outcome, and has demonstrated that bicalutamide is better tolerated than flutamide. There is also preliminary evidence to support the potential use of bicalutamide in treatment of early-stage disease and tumours that are refractory to other non-steroidal anti-androgens.     

Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells.

The in vitro anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on human prostate cancer LNCaP cells was investigated. The uptake of the PLGA-mPEG nanoparticles by the LNCaP cells was also studied. Blank PLGA-mPEG nanoparticles exhibited low cytotoxicity, which increased with increasing PLGA/PEG ratio in the PLGA-mPEG copolymer used to prepare the nanoparticles, possibly due to the increased cell uptake observed with increasing PLGA/PEG ratio. PLGA-mPEG nanoparticles loaded with cisplatin exerted in vitro anticancer activity against LNCaP cells that was comparable to the activity of free (non-entrapped in nanoparticles) cisplatin. Little differences in the in vitro anticancer activity of the different nanoparticle compositions were found, which may result from the differences observed between the different nanoparticles compositions in the uptake by the LNCaP cells and in the leakage of cisplatin from the nanoparticles during incubation with the cells. Visual evidence of nanoparticles' uptake by the LNCaP cells was obtained with nanoparticles labeled with PLGA(4165)-PyrBu(274) or dextran-rhodamine B isothiocyanate using fluorescence microscopy. Moreover, in some cases fluorescence around or inside cell nuclei was observed, which, if verified by further studies, would indicate that PLGA-PEG nanoparticles might prove to be useful in site-specific delivery of drugs whose site of pharmacological activity is cell nucleus.     

比卡鲁胺胶囊对前列腺癌术后患者恢复效果的影响

目的观察比卡鲁胺胶囊对前列腺癌术后患者恢复效果的影响。方法选取2016年4月-2019年12月新疆生产建设兵团第十三师红星医院收治的前列腺癌患者80例,根据随机数字表法分为观察组和对照组,各40例。对照组患者接受前列腺癌手术去势治疗,观察组在对照组治疗基础上加用比卡鲁胺胶囊治疗。比较2组患者近期疗效,治疗前后前列腺特异性抗原(PSA)与血管内皮生长因子(VEGF)水平变化,生活质量改善情况及不良反应(性功能降低、骨骼疼痛、尿路梗阻、乳房发育、脊髓压迫)发生情况。结果治疗6个月后,观察组总有效率为97.50%,高于对照组的85.00%(χ²=3.914,P=0.048);治疗后2组患者PSA和VEGF水平均较治疗前明显降低,且观察组PSA和VEGF水平低于对照组(P均<0.01);观察组生活质量总改善率为97.50%,高于对照组的82.50%(χ²=5.000,P=0.025);观察组不良反应总发生率为20.00%,低于对照组的55.00%(χ²=10.453,P=0.001)。结论比卡鲁胺胶囊用于前列腺癌患者术后恢复效果显著,可快速改善患者临床症状,提高患者术后生活质量,降低了患者不良反应发生风险,值得临床推广应用。     

甲磺酸伊马替尼联合塞来昔布对胃肠间质瘤细胞增殖及凋亡的影响

目的观察甲磺酸伊马替尼和塞来昔布联合对胃肠间质瘤细胞增殖及凋亡的影响。方法甲磺酸伊马替尼及塞来昔布单独或联合处理胃肠间质瘤细胞株GIST-T1,MTT法检测药物对胃肠间质瘤细胞株的生长抑制,Western blot检测Bax及Bcl-2蛋白表达。结果甲磺酸伊马替尼与塞来昔布联合应用显著增强甲磺酸伊马替尼对胃肠间质瘤细胞增殖;和甲磺酸伊马替尼及塞来昔布单用相比,二者联用后胃肠间质瘤细胞Bax表达增高及Bcl-2表达降低。结论甲磺酸伊马替尼和塞来昔布联合应用显著抑制胃肠间质瘤细胞增殖,可能和促肿瘤细胞凋亡有关,其机制可能与Bax表达上调及Bcl-2表达下调有关。