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《Mayo Clinic proceedings. Mayo Clinic》2019,94(7):1321-1329
Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase. 相似文献
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Kensuke Kudou Hiroshi Saeki Yuichiro Nakashima Shun Sasaki Tomoko Jogo Kosuke Hirose Qingjiang Hu Yasuo Tsuda Koichi Kimura Ryota Nakanishi Nobuhide Kubo Koji Ando Eiji Oki Tetsuo Ikeda Yoshihiko Maehara 《American journal of surgery》2019,217(4):757-763
Background
There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).Methods
Patients with AEG and UGC who were judged as non-sarcopenic before surgery were reassessed the presence of postoperative development of sarcopenia 6 months after surgery. Patients were divided into the development group or non-development group, and clinicopathological factors and prognosis between these two groups were analyzed.Results
The 5-year overall survival rates were significantly poorer in the development group than non-development group (68.0% vs. 92.6%, P?=?0.0118). Multivariate analyses showed that postoperative development of sarcopenia was an independent prognostic factor for poor overall survival (P?=?0.0237).Conclusions
Postoperative development of sarcopenia was associated with a poor prognosis in patients with AEG and UGC. 相似文献5.
目的 探讨中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定,并依此分NLR<2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素,最佳临界值为2.64。NLR<2.64组术后中位DFS为39.10月,中位OS为52.30月;NLR≥2.64组术后中位DFS为27.35月,中位OS为37.35月。2组术后DFS和OS比较,差异具有统计学意义(P<0.05)。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素,具有重复性强、非侵袭性、方便实用等特性,可用于预测三阴性乳腺癌临床预后。 相似文献
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《中国现代医生》2020,58(14):5-8
目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月~2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。 相似文献
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《Vaccine》2020,38(10):2315-2325
In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM197 and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design. 相似文献
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目的 检测亚硒酸钠是否能够削弱或解除顺铂对植物血球凝激素(PHA)刺激的人体外周血淋巴细胞的增殖抑制。方法 用顺铂和亚硒酸钠单独或联合处理PHA刺激的人体外周血淋巴细胞,顺铂(0.05,0.20,0.50mg/L)在细胞培养24h时加入,亚硒酸钠(0.05mg/L)在不同处理中分别在细胞培养开始时加入或与顺铂同时加入;培养72h后检测转化淋巴细胞的有丝分裂指数。结果0.05mg/L亚硒酸钠在培养开始时加入,PHA刺激转化的淋巴细胞有丝分裂指数较对照增长42.8%(P<0.05),与顺铂同时加入,有丝分裂指数增长13.7%(P>0.05)。0.05与0.20mg/L顺铂处理细胞,有丝分裂指数未发生显性改变,当顺铂剂量为0.50mg/L时,细胞有丝分裂指数较对照降低54.5%(P<0.001)。亚硒酸钠预处理细胞可以解除0.50mg/L顺铂所致的细胞增殖抑制,使有丝分裂指数恢复正常,但亚硒酸钠与顺铂同时加入时,被顺铂抑制的有丝分裂指数只能部分提高。结论0.05mg/L亚硒酸钠单独作用于淋巴细胞可直接促进细胞增殖,与顺铂联合处理细胞时,可降低顺铂毒性,拮抗顺铂的抗增殖作用。亚硒酸钠在细胞培养开始时加入培养体系效果更佳。 相似文献
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The B cell functional response following ligation of surface(s) lgM is dependent upon the differentiation stage of the populationstudied: cross-linking slgM promotes proliferation of restingtonsillar follicular mantle (FM) B lymphocytes but induces apoptosisin the susceptible Epstein- Barr virus genome-negative Burkittlymphoma (BL) cell line Ramos (Ramos-BL). This study investigateswhether phosphatidylinositol-3-kinase (Pl3-kinase), which hasbeen reported to be intimately involved in the regulation ofcellular growth, plays a role in the regulation of these sig-promoted B cell responses, and uses the selective and irreversibleinhibitor of Pl3-kinase activity, wortmannin (Wm). In Ramos-BLB cells, at 8 h post-treatment, Wm triggers a transient increasein apoptosis of 16 ± 6.9% with a concomitant cellularloss of 16 ± 6.1% from the G1 phase of cell cycle; [3H]thymidineincorporation also decreases by 33 ± 5.0%, from 37,274c.p.m. ± 10% to 25,127 c.p.m. ± 4.0%. Moreover,at 72 h culture, Wm inhibits anti-lgM-induced FM B lymphocytelevels of [3H]thymidine incorporation typically by 47% and triggers80% apoptosis from the G0G1 phase of cell cycle. Ramos-BL Bcells exhibit high basal levels of Pl3-kinase activity, as determinedby immunoprecipitation with antibody to the p85 regulatory subunitof Pl3-kinase and 32P incorporation into phosphatidylinositol,which is not significantly affected by anti-lgM stimulation;by contrast, anti-lgM stimulates significant Pl3-kinase activityover negligible basal levels in FM B lymphocytes. Pre-treatmentwith Wm inhibits Pl3-kinase activity in both cell types. Takentogether these data indicate that in Ramos-BL B cells slgM-triggeredgrowth arrest and apoptosis is Pl3- kinase independent, whereasPl3-kinase activity is critical for slgM-triggered mitogenesisof FM B lymphocytes. Thus Pl3-kinase plays a pivotal role inthe regulation of both normal and neoplastic B lymphocyte progressionthrough the cell cycle, such that if this Pl3-kinase-dependentpathway is inhibited these cells default to apoptosis. 相似文献