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1.
程序性细胞死亡蛋白1(programmed death-1,PD-1)及其配体(PD-L1)抑制剂是免疫哨点单抗药物,是近年来肿瘤免疫疗法研究的热点。已上市的尼伏单抗(nivolumab)和潘利珠单抗(pembrolizumab)属于PD-1抑制剂,主要用于黑素瘤和非小细胞肺癌的治疗,对肾细胞癌、膀胱癌、霍奇金淋巴瘤等的疗效还在大规模临床试验中。PD-L1抑制剂阿替珠单抗(atezolizumab)、度伐单抗(durvalumab)和阿维单抗(avelumab)已被批准用于治疗尿道上皮癌,还有其他几种药物尚处于早期临床试验阶段。本文对上述PD-1/PD-L1抑制剂的研究进展做一综述。  相似文献   

2.
目的回顾性分析阿帕替尼(Apatinib)联合雷替曲塞(Retitrexed)治疗常规治疗失败的结直肠癌肝转移(m CRC)中的临床疗效。方法 2012年8月至2018年8月6年间54例常规治疗失败的结直肠癌肝转移患者分为对照组和实验组,均病理证实为结直肠癌肝转移,常规方案治疗后病情进展判定为常规治疗失败.对照组(贝伐单抗+替吉奥) 26例:贝伐单抗5 mg/kg,替吉奥40~60 mg/m2D1~14,3周1疗程;实验组(阿帕替尼+雷替曲塞) 28例:阿帕替尼500 mg/d直至病情进展或无法耐受,雷替曲塞3 mg/m2,3周1疗程.比较2组临床疗效、T细胞亚群及不良反应情况。结果对照组和实验组2组客观有效率(ORR)分别为65.4%和82.1%,疾病控制率(DCR)分别为34.6%和53.6%,2组无疾病进展生存期(PFS)分别为(15.2±7.1)个月和(22.2±6.8)个月,总生存时间(OS)分别为(17.2±7.1)个月和(24.2±6.9)个月;2组ORR、DCR、PFS、OS比较有显著性差异(P <0.05);实验组CD3、CD4、CD8及CD4/CD8水平均高于... 更多  相似文献   

3.
  目的  探索XELOX方案联合贝伐珠单抗一线诱导治疗晚期结直肠癌序贯卡培他滨联合贝伐珠单抗或卡培他滨单药维持治疗的疗效与安全性。  方法  100例晚期结直肠癌患者,一线予以XELOX方案(奥沙利铂和卡培他滨)联合贝伐珠单抗诱导治疗6周期,疗效评价为完全缓解、部分缓解或疾病稳定,按1∶1分成卡培他滨联合贝伐珠单抗组(n = 50例)和卡培他滨单药组(n = 50例)维持治疗至首次疾病进展或毒副反应不可耐受。主要研究终点为维持治疗至疾病进展时间(PFS1),次要研究终点为诱导治疗开始至疾病进展时间(PFS2)、总生存时间(OS)和毒副反应。  结果   100例晚期结直肠癌患者进行维持治疗,2组基线临床病理学特征均衡,卡培他滨联合贝伐珠单抗维持治疗的中位PFS1、中位PFS2及中位OS均较卡培他滨单药组显著延长,分别为9.0(95%CI:8.52~9.47)比7.2(6.16~8.24,P < 0.0001)个月、13.5(12.55~14.45)比12.3(11.21~13.38,P < 0.0001)个月和27.0(25.31~28.69)比26.2(24.09~28.31,P = 0.011)个月。亚组分析显示,联合维持治疗显著延长同时性转移、RAS/BRAF突变亚组的PFS1及男性、肝转移亚组的OS。2组化疗相关毒副反应相似,最常见为中性粒细胞下降、粘膜炎、手足综合征和腹泻。联合组高血压(20% 比4%)及蛋白尿(14% 比 2%)的发生率明显高于单药组。  结论   卡培他滨联合贝伐珠单抗及卡培他滨单药均可作为安全有效的晚期结直肠癌一线经XELOX方案联合贝伐珠单抗诱导治疗获得疾病控制后维持治疗的选择。卡培他滨联合贝伐珠单抗维持治疗有更好的生存获益。  相似文献   

4.
《中国现代医生》2021,59(5):158-160+164
在本报道中,2例晚期口腔腺癌患者化疗后进展,改用安罗替尼治疗,肿瘤有缩小(疗效评价为SD)。病例1于安罗替尼治疗后2.8个月出现耐药,肿瘤进展,给予PD-1抑制剂(特瑞普利单抗)治疗1个周期,后再次使用安罗替尼治疗,肿瘤再次缩小(疗效评价为SD),目前仍然在维持治疗中。安罗替尼治疗的第1次无进展生存时间(PFS1)为2.8个月,第2次无进展生存时间(PFS2)为12.8+个月。病例2于安罗替尼治疗后15.5个月出现耐药,肿瘤进展,给予PD-1抑制剂(卡瑞利珠单抗)治疗4个周期,后再次使用安罗替尼治疗,肿瘤再次缩小(疗效评价为SD),目前仍然在维持治疗中。安罗替尼治疗的第1次无进展生存时间(PFS1)为15.5个月,第2次无进展生存时间(PFS2)为6.0+个月。这些病例显示,PD-1抑制剂可能逆转安罗替尼的获得性耐药,值得进一步研究。  相似文献   

5.
目的 探讨卡瑞利珠单抗联合阿帕替尼在不同微卫星状态的晚期结直肠癌(CRC)中的疗效.方法 回顾性分析2019年5月至2020年12月郑州大学第一附属医院肿瘤科收治的36例晚期CRC患者的临床资料.根据患者微卫星状态分为微卫星高度不稳定(MSI-H)组(17例)和微卫星稳定(MSS)组(19例).给予所有患者卡瑞利珠单抗...  相似文献   

6.
目的:评估帕博西尼(Palbociclib)单独或联合表皮生长因子缀体抑制剂厄洛替尼(Erlotinib)治疗结直肠癌(colorectal cancer,CRC)的有效性。方法:采用Alamar blue法和克隆形成实验检测帕博西尼单独或联合厄洛替尼对CRC细胞系增殖的影响;采用DNA含量定量法检测细胞周期分布变化;分别通过β?半乳糖苷酶和DCFH?DA染色检测细胞衰老和活性氧积累的情况;通过Western blot分析相关蛋白表达水平;在CRC患者来源异种移植模型中检测联合治疗的效果。结果:帕博西尼单独治疗有效抑制CRC细胞增殖,诱导细胞G1期阻滞、细胞衰老和胞内活性氧积累。帕博西尼和厄洛替尼联合治疗CRC具有协同作用,厄洛替尼进一步增强帕博西尼对CRC的多种抑制效应和多信号通路抑制,在CRC患者来源的异种移植模型中显示出了良好的协同抑制作用。结论:帕博西尼联合厄洛替尼在体外和体内能够协同抑制结直肠癌的生长。  相似文献   

7.
目的 复制表皮生长因子受体抑制剂相关皮疹动物模型并进行进一步优化和探索。方法 应用西妥昔单抗注射液,按照20、40、80 mg/kg对雌性SCID小鼠进行腹腔注射,给药频次为每周一、三、五,共干预28 d。实验过程中持续关注小鼠皮肤形态学变化,在实验结束后对小鼠皮肤进行切片,观察HE染色表现。应用吉非替尼、厄洛替尼、卵清蛋白分别按照按照37.5 mg/kg、23.5 mg/kg、1 mg/只进行灌胃口服,1次/d,共给药45 d。实验过程中持续观察大鼠皮肤形态学变化,实验结束后对大鼠皮肤进行切片,观察HE染色表现。并应用ELISA法对大鼠血清中TNF-α、IL-6、IgE等因子进行测定。结果 西妥昔单抗腹腔注射后,SCID小鼠未出现典型的皮疹、结痂表现;皮肤病理未显示出明显的炎症表现。吉非替尼组大鼠皮肤可见明显的皮疹、结痂、渗出等表现,且皮肤HE染色可见大量的炎症细胞浸润、角化不全、棘层松解、表皮增厚等表现;空白组、卵清蛋白组、厄洛替尼组大鼠皮肤形态学观察及病理切片未见明显的炎症表现。在IgE、TNF-α浓度方面,各组间均未见明显差异(P=0.061,P=0.057);而 在 IL-6 方面,吉非替尼组较空白组明显升高,差异具有统计学意义(P=0.016),而厄洛替尼组较空白组未见明显差异(P= 0.910)。结论 应用西妥昔单抗不能在SCID小鼠中建立表皮生长因子受体抑制剂相关皮疹模型。应用吉非替尼可以在BN大鼠中建立表皮生长因子受体抑制剂相关皮疹模型;应用厄洛替尼不能在BN大鼠中诱发皮疹。  相似文献   

8.
目的 探讨替雷利珠单抗所致Stevens-Johnson综合征的防治方法,保障患者用药安全。方法 回顾性分析替雷利珠单抗所致Stevens-Johnson综合征病例1例,结合文献对替雷利珠单抗所致Stevens-Johnson综合征的诊断标准、临床表现、防治方法等进行分析。结果 患者因肺癌脑转移给予替雷利珠单抗200 mg静脉滴注,用药8 d后患者全身出现红斑,胸背部出现水疱,部分破溃糜烂,尼氏征阳性,伴瘙痒,考虑程序性死亡受体抑制剂1替雷利珠单抗所致Stevens-Johnson综合征。立即收住入院,加强皮肤护理,予以糖皮质激素、抗组胺药及局部外用药物等治疗。14 d后患者全身红斑消退,新生表皮形成,无瘙痒等不适,予以出院。门诊随访患者2月,无新发皮疹,病情控制稳定。结论 替雷利珠单抗所致Stevens-Johnson综合征为4级严重皮肤不良反应,一旦发生应永久停药,收住入院治疗,保障患者用药安全。  相似文献   

9.
背景 以细胞程序性死亡受体1(PD-1)和细胞程序性死亡配体1(PD-L1)抑制剂类为代表的免疫靶向治疗在多种肿瘤治疗中显示较高的有效率,我国已获批上市的PD-1/PD-L1抑制剂类抗肿瘤药物应用时间相对较短。 目的 探讨国产PD-1抑制剂卡瑞利珠单抗联合阿帕替尼一线治疗中晚期原发性肝癌的疗效和安全性。 方法 纳入池州市4家医院(池州市人民医院、池州市第二人民医院、东至县人民医院、石台县人民医院)肿瘤科2018年6月至2021年1月收治的中晚期原发性肝癌患者86例,其均初始服用甲磺酸阿帕替尼片同时联用卡瑞利珠单抗静脉滴注。评估患者治疗1、3个月时的临床疗效,并对患者进行随访,随访终点为患者疾病出现进展、全因死亡或2021-08-31。统计患者治疗期间毒副作用发生情况。 结果 86例患者中无因严重毒副作用退出研究者。患者治疗1、3个月总缓解率(ORR)分别为58.14%(50/86)和65.12%(56/86),疾病控制率(DCR)分别为76.74%(66/86)和82.56%(68/86)。截至2021-08-31,86例患者的随访时间为4~26个月,平均随访时间为(12±6)个月,共35例患者死亡,所有患者中位无进展生存期(PFS)为8〔95%CI(5.18,11.89)〕个月,中位总生存期(OS)为12〔95%CI(8.97,15.97)〕个月。86例患者治疗期间出现的主要毒副作用为胃肠道反应〔52例(60.47%)〕、继发性高血压〔31例(36.05%)〕、手足综合征〔18例(20.93%)〕和蛋白尿〔12例(13.95%)〕,其中胃肠道反应〔6例(6.98%)〕、继发性高血压〔2例(2.33%)〕和手足综合征〔1例(1.16%)〕出现3~5级毒副作用。 结论 国产PD-1抑制剂卡瑞利珠单抗联合阿帕替尼一线治疗中晚期原发性肝癌的疗效良好,毒副作用相对可控。  相似文献   

10.
背景 以程序性死亡蛋白-1(PD-1)抑制剂为代表的免疫治疗近年来逐步成为晚期非小细胞肺癌(NSCLC)的标准治疗方案,改变了该病的治疗格局。大部分PD-1抑制剂相关研究排除了70或75岁以上的老年晚期NSCLC患者,使得老年患者使用PD-1抑制剂治疗的疗效及安全性数据相对较少。目的 本研究旨在探讨PD-1抑制剂在老年晚期NSCLC患者中的疗效及安全性。方法 选取2018年10月至2021年11月在甘肃中医药大学第四附属医院胸外科和肿瘤科接受PD-1抑制剂单药治疗的65岁及以上的晚期NSCLC患者,最终纳入符合标准的患者63例。本研究中PD-1抑制剂均为已经在中国获批上市的PD-1抑制剂单抗,包括卡瑞利珠单抗、信迪利单抗和帕博利珠单抗。通过医院电子病历系统整理患者接受治疗后的疗效及安全性数据,并对患者进行定期随访获取长期生存数据,随访至2022-03-15,收集患者PD-1抑制剂的疗效资料、老年晚期NSCLC患者的预后情况和接受PD-1抑制剂治疗的毒副作用情况,采用Cox比例风险模型探讨老年晚期NSCLC患者预后的影响因素。结果 63例老年晚期NSCLC患者的中位年龄为71(65,89...  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

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