Murine monoclonal antibody (MoAb) BB4.3, raised against the human gastric cancer cell line BGC823, was puriffied with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. It was then conjugated w...Murine monoclonal antibody (MoAb) BB4.3, raised against the human gastric cancer cell line BGC823, was puriffied with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. It was then conjugated with a hematoporphyrin derivative (HPD) by using carbodiimide. The qualitative analysis of this conjugate showed that the amount of free HPD was negligible and there were no IgG aggregates among the conjugates. The conjugate retained both the antibody and photochemical activity of HPD.In vitro, the phototoxic effect of this HPD-BB4.3 conjugate on target cells was about 15 times higher than that of free HPD. The quality of selective photocytotoxicity was proven by the greater cytotoxi-city this conjugate showed than that of corresponding normal mouse IgG (NIgG) conjugated with HPD. It showed less cytotoxicity to colon cancer cell line B-80 (negative reaction to MoAb BB4.3) than to BGC825. Moreover, its cytotoxicity to BGC823 cells could be blocked specifically by excess BB4.3 antibody, but not by another MoAb 3G9, which combines with BGC823 at different binding sites from MoAb BB4.3.Nude mice inoculated with 2 × 10- BGC823 cells were given HPD-BB4.3, HPD, HPD-NIgG, HPD plus BB4.3 and PBS, respectively then exposed to light. Four out of six animals treated with the HPD-BB4.3 conjugate remained tumor-free for a long period. Although two developed tumors, there was a significant difference between the HPD-BB4.3-treated group and all the control groups in tumor induction time, tumor growth rate, and survival time (p<0.001). The HPD-BB4.3 conjugate inhibited the growth of established tumors by more than 40% in comparison with control groups (p<0.05).展开更多
Human sperm membrane antigens extracted by deoxycholate (DOC) were used to immunizeBALB/c mice.Hybrid cell lines secreting sperm-specific monoclonal antibodies were generatedby cell fusion in a semi-solid medium and s...Human sperm membrane antigens extracted by deoxycholate (DOC) were used to immunizeBALB/c mice.Hybrid cell lines secreting sperm-specific monoclonal antibodies were generatedby cell fusion in a semi-solid medium and screened by indirect immunofluorescent assay usinglive and methanol-fixed sperm.Out of 850 hybrid clones from cell fusion,28 were shownto secrete sperm-specific antibodies which reacted with the acrosome,equatorial segment,whole surface plasma membrane or tail of spermatozoa.Finally,seven hybrid cell lineswere established and shown to secrete monoclonal antibodies which had no cross-reactivitywith arty human tissues other than testis and sperm.The majority were also shown toinhibit fertilization of mouse oocytes in vitro and human sperm penetration of zona-freehamster ova.Western blot analysis revealed that some of these antibodies reacted withsperm membrane antigens of distinct molecular size.展开更多
Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of c...Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers.Immunotherapeutic agents have gained immense popularity due to their tumorspecific action.Immunotherapy is slowly transforming into a separate therapeutic entity,and the fifth pillar of management for cancers alongside surgery,radiotherapy,chemotherapy,and targeted therapy.However,like any therapeutic entity it has its own adverse effects.With the increasing use of immunotherapeutic agents,it is vital for physicians to acquaint themselves with these adverse effects.The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents.We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems,as well as an extensive discussion of the current recommendations for treatment and clinical trial data.As we continue to see increasing usage of these agents in clinical practice,it is vital for physicians to familiarize themselves with these effects.展开更多
Background Monoclonal antibodies such as rituximab(RTX),eculizumab,inebilizumab,satralizumab,and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease(NMOSD)in several clinica...Background Monoclonal antibodies such as rituximab(RTX),eculizumab,inebilizumab,satralizumab,and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease(NMOSD)in several clinical randomized controlled trials.Objective The purpose of this meta-analysis of randomized controlled trials was to assess the efficacy and safety of monoclonal antibodies in the treatment of NMOSD.Methods We searched the following databases for relevant English language literature from the establishment of the database to June 2021:PubMed,Embase,Cohorane Library,the Central Register of Controlled Trials(CENTRAL),and Web of Science.Randomized controlled trials of monoclonal antibodies were the targets of the review.Results We included seven trials containing 775 patients(485 in the monoclonal antibody group and 290 in the control group).Patients in the monoclonal group(HR 0.24,95%CI:0.14 to 0.40,P<0.00001),as well as patients with seropositive AQP4-IgG(HR 0.18,95%CI:0.11 to 0.29,P<0.00001),both had a higher free recurrence rate than that in the control group.In the first year(HR 0.25,95%CI:0.09 to 0.71,P=0.009)and the second year(HR 0.32,95%CI:0.13 to 0.81,P=0.02),no relapses were documented.The average changes of the expanded disability status scale(EDSS)score decreased by 0.29(95%CI:−0.09 to 0.51,P=0.005).Upper respiratory tract infection(OR 1.52,95%CI:0.76 to 3.04,P=0.24),urinary tract infection(OR 0.79,95%CI:0.51 to 1.21,P=0.27),and headache(OR 1.30,95%CI:0.78 to 2.17,P=0.31)were three most frequent adverse reactions.Conclusions Monoclonal antibodies are particularly effective treatments in avoiding recurrence for NMOSD patients,according to this meta-analysis.The associated adverse responses are not significantly different from those seen with traditional immunosuppressants.展开更多
Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commo...Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commonly associated with monoclonal antibodies when administered to patients with mCRC. Methods: This study extracted data for patients newly diagnosed with mCRC from a large US claims database from January 2005 to June 2008. The first distant metastasis diagnosis date was defined as the index date. Main outcomes were length of hospital stay (days) and hospitalisation costs (2010 US$) for AEs (identified by primary discharge diagnoses). All analyses are presented descriptively. Results: The study population (aged ≥18 years;n = 12,648) was balanced according to gender and was mainly aged 50 years or older (90.1%). Most patients had colon cancer (70.1%) as opposed to rectal cancer. Gastrointestinal (GI) perforation incurred the longest median length of stay (11.5 days) for hospitalisations, followed by wound-healing complications (7 days), arterial and venous thromboembolism (5.5 and 4 days, respectively), and congestive heart failure (4 days). The highest inpatient cost per event was for GI perforations (mean $66,224 and median $ 34,027), followed by arterial thromboembolism ($40,992 and $18,587), wound-healing complications ($36,440 and $21,163), interstitial lung disease ($26,705 and $19,111) and acute myocardial infarction ($22,395 and $15,223). Skin toxicity (mean $6475 and median $6110) and hypertension ($14,108 and $6047) were associated with relatively low costs. Conclusions: Hospital costs for monoclonal antibody treatment-related AEs in patients with mCRC vary greatly. This study provides source data for economic evaluations of head-to-head comparisons of monoclonal antibody treatments.展开更多
An antigastric cancer monoclonal antibody, 3H11, and its Fab fragment, were labeled using p-(211At)-astatobenzoic acid (pAtBA) intermediate, in the yields of more than 30%. The results of in vitro experiments show tha...An antigastric cancer monoclonal antibody, 3H11, and its Fab fragment, were labeled using p-(211At)-astatobenzoic acid (pAtBA) intermediate, in the yields of more than 30%. The results of in vitro experiments show that 211At-3H11 and 211At-3H11Fab are stable, and have specific immunoreactivities and cytotoxic effects to human gastric cancer cell M85. The cytotoxic effects are dependent on the concentration of 211At-3H11 or 211At-3H11 Fab and obviously stronger than that of Na211At.展开更多
目的分析阿替利珠单抗发生不良反应(adverse reactions,ADRs)的临床特点与规律,为临床安全用药提供参考。方法搜索中国知网、维普、万方、Web of Science、PubMed数据库,收集关于阿替利珠单抗所致不良反应的报道文献并进行分析,研究时间...目的分析阿替利珠单抗发生不良反应(adverse reactions,ADRs)的临床特点与规律,为临床安全用药提供参考。方法搜索中国知网、维普、万方、Web of Science、PubMed数据库,收集关于阿替利珠单抗所致不良反应的报道文献并进行分析,研究时间为2022年4—8月。结果阿替利珠致不良反应报道共94例;其中男性56例(59.57%),女性38例(40.43%),男性占比较高;年龄(62.8±12.0)岁,中老年人居多;多数发生在用药后的90 d内(71例,71.0%);阿替利珠单抗致ADRs累及多个系统/器官,其中以神经系统损害(22例,22.0%)占比最多;3~4级严重ADRs占比最多(64例,64.0%);94例经治疗和(或)停药后,好转或治愈80例,死亡5例。结论阿替利珠单抗所致ADRs涉及不同性别与年龄段病人,累及多个系统/器官,临床使用应随时监测,警惕ADRs的发生,做到及时识别与治疗。展开更多
BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-C...BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.展开更多
OBJECTIVE: To observe the localization of adrenomedullin (AM) in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells (MsC). METHODS: A monoclonal antibody against AM developed by ...OBJECTIVE: To observe the localization of adrenomedullin (AM) in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells (MsC). METHODS: A monoclonal antibody against AM developed by our laboratory was used to detect the localization of AM protein in rat kidney tissue by avidin-biotin complex immunohistochemistry. The expressions of AM and its receptor CRLR mRNA on cultured glomerular epithelial cells (GEC) and MsC were investigated by Northern blot assay, and the possible effect of AM secreted by GEC on MsC proliferation was observed using [3H]thymidine incorporation as an index. RESULTS: A specific monoclonal antibody against AM was succesfully developed. AM was immunohistochemically localized mainly in glomeruli (GEC and endothelial cells), some cortical proximal tubules, medullary collecting duct cells, interstitial cells, vascular smooth muscle cells and endothelial cells. Northern blot assay showed that AM mRNA was expressed only on cultured GEC, but not on MsC, however, AM receptor CRLR mRNA was only expressed on MsC. GEC conditioned medium containing AM can inhibit MsC growth and AM receptor blocker CGRP8-37 may partially decreased this inhibitory effect. CONCLUSION: AM produced by GEC inhibits the proliferation of MsC, which suggests that AM as an important regulator is involved in glomerular normal physiological functions and pathologic processes.展开更多
目的分析结直肠癌靶向和单抗类药物基因组学与不良反应相关研究的现状,探索其发展趋势,为后期相关研究提供参考。方法以Web of Science核心合集为数据来源,结合CiteSpace软件的可视化功能,采用文献计量学方法对2012-2022年抗结直肠癌靶...目的分析结直肠癌靶向和单抗类药物基因组学与不良反应相关研究的现状,探索其发展趋势,为后期相关研究提供参考。方法以Web of Science核心合集为数据来源,结合CiteSpace软件的可视化功能,采用文献计量学方法对2012-2022年抗结直肠癌靶向及单抗类药物基因组学及不良反应方面相关研究文献的作者、研究机构、发文国家、引用文献、发表期刊及关键词进行分析。结果经过筛选纳入近10年来5893篇相关文献。涉及基因组学的相关文献4509篇,美国、日本、意大利、中国是该领域研究的核心国家,掌握绝大多数核心研究;涉及不良反应的相关文献1384篇,作者平均发文数量较低,且相对独立,形成少数高产作者引领的作者群。关键词整体指向结直肠癌靶向药物、药物治疗靶点、不良反应、预后的生物标记、分子亚型、抗肿瘤联合化疗、药物基因组学生物标志物等。通过对靶向治疗药物的生物标志物的突显,可以对结直肠癌的晚期治疗或者转移性治疗方案进行预后评估。同时可以寻找与靶向治疗药物代谢相关的特殊诊断靶点,发现其生物标志的标记,将会成为今后的研究热点。结论为研究者准确把握抗结直肠癌靶向及单抗类药物的研究现状和发展态势提供参考。展开更多
目的系统评价外用维生素K预防和治疗靶向表皮生长因子受体(EGFR)单抗相关性皮疹的有效性和安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网、维普和万方数据库,检索时限为各数据库自建库起至2022年4...目的系统评价外用维生素K预防和治疗靶向表皮生长因子受体(EGFR)单抗相关性皮疹的有效性和安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网、维普和万方数据库,检索时限为各数据库自建库起至2022年4月。筛选文献、提取数据,评价文献质量,对结果数据进行描述性分析或采用RevMan 5.3软件进行Meta分析。结果纳入12项研究。涉及的EGFR单抗主要为西妥昔单抗,外用维生素K的剂型主要是乳膏,给药方法多为浓度0.05%~0.1%的维生素K每天外用1次或2次,大部分研究所用维生素K亚型为K1。3项对照试验的Meta分析结果显示,相比对照组,试验组≥2级皮疹的发生率未显著降低[RR=1.18,95%CI(0.96,1.45),P=0.12],同时凝血功能异常及其他皮肤不良事件发生率也无显著差异;除3项对照试验外,纳入的病例系列结论虽均认为外用维生素K可降低≥2级皮疹的发生率,并缩短皮疹持续时间,但以上研究未设置对照组,不能排除外用制剂中保湿剂等辅料的保护作用。结论当前证据表明,浓度0.05%~0.1%的维生素K每天外用1次或2次预防和治疗靶向EGFR单抗相关性皮疹有效性不明确,也未见额外的安全性问题。未来需在维生素K给药剂量、频次、人群分层等方面进一步探索。展开更多
文摘Murine monoclonal antibody (MoAb) BB4.3, raised against the human gastric cancer cell line BGC823, was puriffied with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. It was then conjugated with a hematoporphyrin derivative (HPD) by using carbodiimide. The qualitative analysis of this conjugate showed that the amount of free HPD was negligible and there were no IgG aggregates among the conjugates. The conjugate retained both the antibody and photochemical activity of HPD.In vitro, the phototoxic effect of this HPD-BB4.3 conjugate on target cells was about 15 times higher than that of free HPD. The quality of selective photocytotoxicity was proven by the greater cytotoxi-city this conjugate showed than that of corresponding normal mouse IgG (NIgG) conjugated with HPD. It showed less cytotoxicity to colon cancer cell line B-80 (negative reaction to MoAb BB4.3) than to BGC825. Moreover, its cytotoxicity to BGC823 cells could be blocked specifically by excess BB4.3 antibody, but not by another MoAb 3G9, which combines with BGC823 at different binding sites from MoAb BB4.3.Nude mice inoculated with 2 × 10- BGC823 cells were given HPD-BB4.3, HPD, HPD-NIgG, HPD plus BB4.3 and PBS, respectively then exposed to light. Four out of six animals treated with the HPD-BB4.3 conjugate remained tumor-free for a long period. Although two developed tumors, there was a significant difference between the HPD-BB4.3-treated group and all the control groups in tumor induction time, tumor growth rate, and survival time (p<0.001). The HPD-BB4.3 conjugate inhibited the growth of established tumors by more than 40% in comparison with control groups (p<0.05).
基金This study was partly supported by a Biotechnology Career Fellowship awarded to Yang Yuzhou by the Rockefeller Foundation
文摘Human sperm membrane antigens extracted by deoxycholate (DOC) were used to immunizeBALB/c mice.Hybrid cell lines secreting sperm-specific monoclonal antibodies were generatedby cell fusion in a semi-solid medium and screened by indirect immunofluorescent assay usinglive and methanol-fixed sperm.Out of 850 hybrid clones from cell fusion,28 were shownto secrete sperm-specific antibodies which reacted with the acrosome,equatorial segment,whole surface plasma membrane or tail of spermatozoa.Finally,seven hybrid cell lineswere established and shown to secrete monoclonal antibodies which had no cross-reactivitywith arty human tissues other than testis and sperm.The majority were also shown toinhibit fertilization of mouse oocytes in vitro and human sperm penetration of zona-freehamster ova.Western blot analysis revealed that some of these antibodies reacted withsperm membrane antigens of distinct molecular size.
文摘Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers.Immunotherapeutic agents have gained immense popularity due to their tumorspecific action.Immunotherapy is slowly transforming into a separate therapeutic entity,and the fifth pillar of management for cancers alongside surgery,radiotherapy,chemotherapy,and targeted therapy.However,like any therapeutic entity it has its own adverse effects.With the increasing use of immunotherapeutic agents,it is vital for physicians to acquaint themselves with these adverse effects.The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents.We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems,as well as an extensive discussion of the current recommendations for treatment and clinical trial data.As we continue to see increasing usage of these agents in clinical practice,it is vital for physicians to familiarize themselves with these effects.
基金supported by the Ministry of Science and Technology of the People's Republic of China Core Project(2018YFE0113900).
文摘Background Monoclonal antibodies such as rituximab(RTX),eculizumab,inebilizumab,satralizumab,and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease(NMOSD)in several clinical randomized controlled trials.Objective The purpose of this meta-analysis of randomized controlled trials was to assess the efficacy and safety of monoclonal antibodies in the treatment of NMOSD.Methods We searched the following databases for relevant English language literature from the establishment of the database to June 2021:PubMed,Embase,Cohorane Library,the Central Register of Controlled Trials(CENTRAL),and Web of Science.Randomized controlled trials of monoclonal antibodies were the targets of the review.Results We included seven trials containing 775 patients(485 in the monoclonal antibody group and 290 in the control group).Patients in the monoclonal group(HR 0.24,95%CI:0.14 to 0.40,P<0.00001),as well as patients with seropositive AQP4-IgG(HR 0.18,95%CI:0.11 to 0.29,P<0.00001),both had a higher free recurrence rate than that in the control group.In the first year(HR 0.25,95%CI:0.09 to 0.71,P=0.009)and the second year(HR 0.32,95%CI:0.13 to 0.81,P=0.02),no relapses were documented.The average changes of the expanded disability status scale(EDSS)score decreased by 0.29(95%CI:−0.09 to 0.51,P=0.005).Upper respiratory tract infection(OR 1.52,95%CI:0.76 to 3.04,P=0.24),urinary tract infection(OR 0.79,95%CI:0.51 to 1.21,P=0.27),and headache(OR 1.30,95%CI:0.78 to 2.17,P=0.31)were three most frequent adverse reactions.Conclusions Monoclonal antibodies are particularly effective treatments in avoiding recurrence for NMOSD patients,according to this meta-analysis.The associated adverse responses are not significantly different from those seen with traditional immunosuppressants.
文摘Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commonly associated with monoclonal antibodies when administered to patients with mCRC. Methods: This study extracted data for patients newly diagnosed with mCRC from a large US claims database from January 2005 to June 2008. The first distant metastasis diagnosis date was defined as the index date. Main outcomes were length of hospital stay (days) and hospitalisation costs (2010 US$) for AEs (identified by primary discharge diagnoses). All analyses are presented descriptively. Results: The study population (aged ≥18 years;n = 12,648) was balanced according to gender and was mainly aged 50 years or older (90.1%). Most patients had colon cancer (70.1%) as opposed to rectal cancer. Gastrointestinal (GI) perforation incurred the longest median length of stay (11.5 days) for hospitalisations, followed by wound-healing complications (7 days), arterial and venous thromboembolism (5.5 and 4 days, respectively), and congestive heart failure (4 days). The highest inpatient cost per event was for GI perforations (mean $66,224 and median $ 34,027), followed by arterial thromboembolism ($40,992 and $18,587), wound-healing complications ($36,440 and $21,163), interstitial lung disease ($26,705 and $19,111) and acute myocardial infarction ($22,395 and $15,223). Skin toxicity (mean $6475 and median $6110) and hypertension ($14,108 and $6047) were associated with relatively low costs. Conclusions: Hospital costs for monoclonal antibody treatment-related AEs in patients with mCRC vary greatly. This study provides source data for economic evaluations of head-to-head comparisons of monoclonal antibody treatments.
文摘An antigastric cancer monoclonal antibody, 3H11, and its Fab fragment, were labeled using p-(211At)-astatobenzoic acid (pAtBA) intermediate, in the yields of more than 30%. The results of in vitro experiments show that 211At-3H11 and 211At-3H11Fab are stable, and have specific immunoreactivities and cytotoxic effects to human gastric cancer cell M85. The cytotoxic effects are dependent on the concentration of 211At-3H11 or 211At-3H11 Fab and obviously stronger than that of Na211At.
文摘目的分析阿替利珠单抗发生不良反应(adverse reactions,ADRs)的临床特点与规律,为临床安全用药提供参考。方法搜索中国知网、维普、万方、Web of Science、PubMed数据库,收集关于阿替利珠单抗所致不良反应的报道文献并进行分析,研究时间为2022年4—8月。结果阿替利珠致不良反应报道共94例;其中男性56例(59.57%),女性38例(40.43%),男性占比较高;年龄(62.8±12.0)岁,中老年人居多;多数发生在用药后的90 d内(71例,71.0%);阿替利珠单抗致ADRs累及多个系统/器官,其中以神经系统损害(22例,22.0%)占比最多;3~4级严重ADRs占比最多(64例,64.0%);94例经治疗和(或)停药后,好转或治愈80例,死亡5例。结论阿替利珠单抗所致ADRs涉及不同性别与年龄段病人,累及多个系统/器官,临床使用应随时监测,警惕ADRs的发生,做到及时识别与治疗。
文摘BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.
文摘OBJECTIVE: To observe the localization of adrenomedullin (AM) in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells (MsC). METHODS: A monoclonal antibody against AM developed by our laboratory was used to detect the localization of AM protein in rat kidney tissue by avidin-biotin complex immunohistochemistry. The expressions of AM and its receptor CRLR mRNA on cultured glomerular epithelial cells (GEC) and MsC were investigated by Northern blot assay, and the possible effect of AM secreted by GEC on MsC proliferation was observed using [3H]thymidine incorporation as an index. RESULTS: A specific monoclonal antibody against AM was succesfully developed. AM was immunohistochemically localized mainly in glomeruli (GEC and endothelial cells), some cortical proximal tubules, medullary collecting duct cells, interstitial cells, vascular smooth muscle cells and endothelial cells. Northern blot assay showed that AM mRNA was expressed only on cultured GEC, but not on MsC, however, AM receptor CRLR mRNA was only expressed on MsC. GEC conditioned medium containing AM can inhibit MsC growth and AM receptor blocker CGRP8-37 may partially decreased this inhibitory effect. CONCLUSION: AM produced by GEC inhibits the proliferation of MsC, which suggests that AM as an important regulator is involved in glomerular normal physiological functions and pathologic processes.
文摘目的分析结直肠癌靶向和单抗类药物基因组学与不良反应相关研究的现状,探索其发展趋势,为后期相关研究提供参考。方法以Web of Science核心合集为数据来源,结合CiteSpace软件的可视化功能,采用文献计量学方法对2012-2022年抗结直肠癌靶向及单抗类药物基因组学及不良反应方面相关研究文献的作者、研究机构、发文国家、引用文献、发表期刊及关键词进行分析。结果经过筛选纳入近10年来5893篇相关文献。涉及基因组学的相关文献4509篇,美国、日本、意大利、中国是该领域研究的核心国家,掌握绝大多数核心研究;涉及不良反应的相关文献1384篇,作者平均发文数量较低,且相对独立,形成少数高产作者引领的作者群。关键词整体指向结直肠癌靶向药物、药物治疗靶点、不良反应、预后的生物标记、分子亚型、抗肿瘤联合化疗、药物基因组学生物标志物等。通过对靶向治疗药物的生物标志物的突显,可以对结直肠癌的晚期治疗或者转移性治疗方案进行预后评估。同时可以寻找与靶向治疗药物代谢相关的特殊诊断靶点,发现其生物标志的标记,将会成为今后的研究热点。结论为研究者准确把握抗结直肠癌靶向及单抗类药物的研究现状和发展态势提供参考。
