Immunomodulators

免疫调节剂
  • 文章类型: Journal Article
    转移是一个复杂而强大的病理生理过程,包括癌细胞从原发肿瘤体扩散到远处器官。它是一种深刻而毁灭性的现象,是癌症相关死亡率的主要驱动因素。尽管癌症研究和治疗取得了长足的进步,量身定制的抗转移疗法要么缺乏,要么成功有限,需要对驱动癌症侵袭的内在因素有更深入的了解。这篇全面的综述提出了对癌症转移领域内关键方面的当代阐明,从归巢和入侵的复杂过程开始。血管生成的过程,支持肿瘤生长和转移,已被解决,连同转移前的生态位,其中所述原发肿瘤在远处为随后的转移性定植准备了有利的微环境。转移相关遗传和表观遗传机制的景观,转移基因和转移抑制基因的参与,和microRNAs(miRNA)也被讨论。此外,讨论了免疫调节剂对转移的影响及其作为治疗靶标的潜力。癌细胞和免疫系统之间的相互作用,包括转移细胞使用的免疫逃避机制,被讨论,强调靶向免疫调节在阻止转移进展中的重要性。最后,这篇综述从对转移机制的见解中提出了有希望的治疗机会。确定新的治疗靶标并开发创新策略以破坏转移性级联反应对于改善患者预后并最终降低癌症相关死亡率具有极好的潜力。
    Metastasis is an intricate and formidable pathophysiological process encompassing the dissemination of cancer cells from the primary tumour body to distant organs. It stands as a profound and devastating phenomenon that constitutes the primary driver of cancer-related mortality. Despite great strides of advancements in cancer research and treatment, tailored anti-metastasis therapies are either lacking or have shown limited success, necessitating a deeper understanding of the intrinsic elements driving cancer invasiveness. This comprehensive review presents a contemporary elucidation of pivotal facets within the realm of cancer metastasis, commencing with the intricate processes of homing and invasion. The process of angiogenesis, which supports tumour growth and metastasis, is addressed, along with the pre-metastatic niche, wherein the primary tumour prepares for a favorable microenvironment at distant sites for subsequent metastatic colonization. The landscape of metastasis-related genetic and epigenetic mechanisms, involvement of metastasis genes and metastasis suppressor genes, and microRNAs (miRNA) are also discussed. Furthermore, immune modulators\' impact on metastasis and their potential as therapeutic targets are addressed. The interplay between cancer cells and the immune system, including immune evasion mechanisms employed by metastatic cells, is discussed, highlighting the importance of targeting immune modulation in arresting metastatic progression. Finally, this review presents promising treatment opportunities derived from the insights gained into the mechanisms of metastasis. Identifying novel therapeutic targets and developing innovative strategies to disrupt the metastatic cascade holds excellent potential for improving patient outcomes and ultimately reducing cancer-related mortality.
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  • 文章类型: Case Reports
    大疱性类天疱疮(BP)是一种常见的免疫介导的水疱性疾病,主要累及皮肤,偶尔有口腔表现。口腔粘膜的囊泡性病变具有相似的临床特征,因此,有价值的主席调查有助于进行临床诊断,脱落细胞学。在本例中进行的细胞学检查排除了天疱疮,因为涂片中没有Tzanck细胞。活检和直接免疫荧光进一步证实了BP的诊断。从全身性类固醇和免疫调节剂开始治疗,口服局部应用曲安奈德可在2个月内完全缓解.此病例报告强调了细胞学在同时出现皮肤和口腔病变的BP患者的膀胱囊性病变和治疗方案的诊断中的作用。
    Bullous pemphigoid (BP) is a common immune-mediated blistering disorder with predominant skin involvement and occasionally oral manifestations. Vesiculobullous lesions of the oral mucosa present with similar clinical features, and hence arriving at a clinical diagnosis is aided by a valuable chairside investigation, exfoliative cytology. Cytology done in the present case ruled out pemphigus because of the absence of Tzanck cells in the smear. Biopsy and direct immunofluorescence further confirmed the diagnosis of BP. Treatment initiated with systemic steroids and immunomodulators, along with oral topical application of triamcinolone acetonide resulted in complete remission in 2 months. This case report highlights the role of cytology in the diagnosis of vesiculobullous lesions and management protocol for BP patients presenting with simultaneous skin and oral lesions.
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  • 文章类型: Journal Article
    免疫疗法彻底改变了癌症管理,基于抗体的治疗由于其优越的药效学而领先,包括增强的有效性和特异性。然而,这些疗法受到诸如延长半衰期等限制的阻碍,组织和肿瘤渗透不良,和最小的口服生物利用度。此外,它们的免疫原性会引起不良影响。因此,焦点转向基于小分子的免疫疗法,它有可能克服这些缺点。作为一个有希望的替代方案,小分子提供治疗抗体和免疫调节剂的好处,组合时通常会产生协同效应。小分子癌症免疫疗法的最新进展值得注意,以抑制剂为特征,激动剂,和降解物作为免疫调节剂。本文深入探讨了小分子免疫治疗在癌症治疗中的现状,突出了靶向关键途径如Toll样受体(TLR)的新型药物,PD-1/PD-L1,趋化因子受体,和干扰素基因(STING)的刺激物。这篇综述强调了新发现的分子实体及其在肿瘤发生中的调节作用。其中许多已经进入临床试验,旨在提供癌症治疗前沿发展的全面快照,由小分子免疫调节剂驱动。
    Immunotherapy has revolutionized cancer management, with antibody-based treatments leading the charge due to their superior pharmacodynamics, including enhanced effectiveness and specificity. However, these therapies are hampered by limitations such as prolonged half-lives, poor tissue and tumor penetration, and minimal oral bioavailability. Additionally, their immunogenic nature can cause adverse effects. Consequently, the focus is shifting towards small-molecule-based immunotherapies, which potentially overcome these drawbacks. Emerging as a promising alternative, small molecules offer the benefits of therapeutic antibodies and immunomodulators, often yielding synergistic effects when combined. Recent advancements in small-molecule cancer immunotherapy are notable, featuring inhibitors, agonists, and degraders that act as immunomodulators. This article delves into the current landscape of small-molecule immunotherapy in cancer treatment, highlighting novel agents targeting key pathways such as Toll-like receptors (TLR), PD-1/PD-L1, chemokine receptors, and stimulators of interferon genes (STING). The review emphasizes newly discovered molecular entities and their modulatory roles in tumorigenesis, many of which have progressed to clinical trials, that aims to provide a comprehensive snapshot of the evolving frontier in cancer treatment, driven by small-molecule immunomodulators.
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  • 文章类型: Journal Article
    CAR-T细胞疗法是一种很有前途的免疫疗法,为对标准和传统治疗方法无反应的癌症患者提供成功的结果。然而,有一些限制因素会在治疗中产生障碍,使其发挥最佳作用。CAR-T细胞耗尽,产生积极的抗肿瘤反应,甚至可能产生毒性反应。具体来说,在实体瘤的情况下,嵌合抗原受体T(CAR-T)细胞无法产生所需的结果。然后,需要使用补充剂,如免疫系统修饰免疫调节剂开始发挥作用。研究了一系列文献来评估免疫调节剂的作用,包括植物化学物质,美国食品和药物管理局(FDA)批准的靶向药物,和IL支持他们在提高CAR-T细胞治疗效率方面的成就。本文报道了其中一些最有前途的。预计通过使用正确的免疫疗法组合,免疫调节剂,和传统的癌症治疗方法,最好的癌症抵抗结果可能会在未来产生。
    CAR T-cell therapy is a promising immunotherapy, providing successful results for cancer patients who are unresponsive to standard and traditional therapeutic approaches. However, there are limiting factors which create a hurdle in the therapy performing its role optimally. CAR T cells get exhausted, produce active antitumor responses, and might even produce toxic reactions. Specifically, in the case of solid tumors, chimeric antigen receptor T (CAR-T) cells fail to produce the desired outcomes. Then, the need to use supplementary agents such as immune system modifying immunomodulatory agents comes into play. A series of the literature was studied to evaluate the role of immunomodulators including a phytochemical, Food and Drug Administration (FDA)-approved targeted drugs, and ILs in support of their achievements in boosting the efficiency of CAR-T cell therapy. Some of the most promising out of them are reported in this article. It is expected that by using the right combinations of immunotherapy, immunomodulators, and traditional cancer treatments, the best possible cancer defying results may be produced in the future.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    克罗恩病的并发症远远超出了手术后的渗漏,感染,和肠外瘘.营养不良,肠衰竭,和复发性疾病都需要持续关注。这些患者的治疗可能因需要慢性免疫抑制而进一步复杂化。基本原则继续包括优化营养状况,并在可能的情况下保留肠道长度。然而,该疾病的医学和外科治疗最近取得了一些进展。了解肠系膜对炎症的贡献,Kono-S吻合术和扩大肠系膜切除术等新的手术技术正在减少重复切除的需要。
    Complications of Crohn\'s disease reach far beyond postsurgical leak, infection, and enterocutaneous fistula. Malnutrition, intestinal failure, and recurrent disease all will require ongoing attentions. The management of these patients may further be complicated by the need for chronic immunosuppression. The underlying principles continue to include optimization of nutritional status, and preservation of bowel length when possible. However, there have been several recent advances in both the medical and surgical management of the disease. Understanding the contribution of the mesentery to inflammation, new surgical techniques such as the Kono-S anastomosis and extended mesenteric resection is decreasing the need for repeated resections.
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  • 文章类型: Journal Article
    本研究调查了底栖芽孢杆菌(Cb)益生菌酵母和雪草(Ce)水果的饮食效果,单一(0.5%)或组合(Cb:Ce,0.25:0.25%),关于增长绩效,血清和皮肤粘液的体液免疫,以及14天和28天后尼罗罗非鱼(Oreochromisniloticus)的肠道形态。Cb组比生长率最高(P<0.05),体重增加,和绝对增长率相对于对照组。免疫测定表明,Cb,Ce和Cb:Ce组血清一氧化氮浓度较对照组升高(P<0.05)。Cb和Cb:Ce组在第14天和第28天血清髓过氧化物酶活性最高(P<0.05);Cb:Ce组皮肤粘液中髓过氧化物酶活性最高(P<0.05)。超氧化物歧化酶活性不受影响。第28天Cb,Ce,Cb:Ce组血清和皮肤粘液中过氧化氢酶活性较高和较低(P<0.05),分别,与对照组相比。与对照组相比,仅Cb组具有更高的(P<0.05)血清(第14天)和皮肤粘液(第14天和第28天)总蛋白浓度。与对照组相比,Cb组的血清(第28天)和皮肤粘液(第14天)中的溶菌酶活性更高(P<0.05)。只有Ce组的皮肤粘液对达克气单胞菌具有杀菌活性(P<0.05)。组织学研究表明,Cb和Cb:Ce组增加了微绒毛高度,Cb,Ce和Cb:与对照组相比,Ce在第14天增加了杯状细胞面积(P<0.05)。在第28天,与对照组相比,所有组的微绒毛高度均较高,Cb和Ce组的上皮内白细胞数量增加(P<0.05)。离体实验显示,白细胞中的达克氏杆菌降低了细胞活力,与对照组相似(P<0.05)。主成分分析(PCA)证实了结果。总之,日粮中底栖杆菌是提高尼罗罗非鱼生长和免疫力的最佳补品。
    This study investigates Cystobasidium benthicum (Cb) probiotic yeast and Cyrtocarpa edulis (Ce) fruit dietary effects, single (0.5 %) or combined (Cb:Ce, 0.25:0.25 %), on growth performance, humoral immunity in serum and skin mucus, and intestinal morphology of Nile tilapia (Oreochromis niloticus) after 14 and 28 days. The Cb group presented the highest (P < 0.05) specific growth rate, weight gain, and absolute growth rate with respect to the control group. Immunological assays indicated that Cb, Ce and Cb:Ce groups increased serum nitric oxide concentration compared to the control group (P < 0.05). Cb and Cb:Ce groups showed the highest serum myeloperoxidase enzyme activity at day 14 and 28, respectively (P < 0.05); whereas, Cb:Ce group had the highest (P < 0.05) myeloperoxidase activity in skin mucus. The superoxide dismutase enzyme activity was unaffected. On day 28, Cb, Ce, and Cb:Ce groups showed higher and lower (P < 0.05) catalase enzyme activity in serum and skin mucus, respectively, compared with the control group. Only the Cb group had higher (P < 0.05) total protein concentration in serum (day 14) and skin mucus (day 14 and 28) with respect to the control group. The lysozyme activity in serum (day 28) and skin mucus (day 14) was higher (P < 0.05) in the Cb group compared to the control group. Only the skin mucus of Ce group showed bactericidal activity against Aeromonas dhakensis (P < 0.05). Histological studies indicated that Cb and Cb:Ce groups increased microvilli height, and Cb, Ce and Cb:Ce augmented goblet cell area at day 14 compared to the control group (P < 0.05). At day 28, microvilli height was higher in all groups and the number of intraepithelial leukocytes increased in Cb and Ce groups with respect to the control group (P < 0.05). The ex vivo assay revealed that A. dhakensis in leukocytes decreased cell viability similar to the control group (P < 0.05). A principal component analysis (PCA) confirmed the results. In conclusion, C. benthicum in the diet was the best supplement to improve the growth and immunity of Nile tilapia.
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    文章类型: Journal Article
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  • 文章类型: Journal Article
    炎症性肠病(IBD)正在进入联合疗法的潜在新时代。Triantafillidis等人对联合治疗的现状进行了有见地的回顾,重点是使用组合的生物和免疫调节剂,以及关于双重生物治疗(DBT)未来潜力的新数据。虽然目前关于DBT的证据有限,令人鼓舞的安全性和正在进行的试验表明,这种方法的前景更加光明.在建立新的治疗范式时应强调对照试验的重要性。正在进行的DBT前瞻性随机试验以及未来生物制剂和小分子疗法的组合有望指导下一代IBD护理。
    Inflammatory bowel disease (IBD) is entering a potentially new era of combined therapeutics. Triantafillidis et al provide an insightful review of the current state of combination therapy, with a focus on the use of a combined biologic and immunomodulator, as well as emerging data on the future potential of dual-biologic therapy (DBT). While current evidence for DBT is limited, encouraging safety profiles and ongoing trials suggest a brighter future for this approach. The importance of controlled trials should be stressed in establishing new treatment paradigms. Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
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  • 文章类型: Editorial
    这篇社论评论了《世界胃肠病学杂志》上一篇题为“使用酪氨酸激酶抑制剂的肿瘤患者乙型肝炎病毒再激活的风险:病例报告和文献分析”的文章。在这篇社论中,我们专注于提供更全面的探索与酪氨酸激酶抑制剂(TKIs)使用相关的乙型肝炎病毒再激活(HBVr)。它包括对潜在的HBV再激活机制的见解,TKIs与HBV再激活的时间关系,和预防措施。目的是了解需要核苷(t)ide类似物(NAT)和系列血液测试的早期识别的再激活和急性肝损伤,以及管理策略。TKI被认为是HBVr的中间体(1%-10%)。目前的指南规定,患者接受治疗与高或中度风险的再激活或最近的癌症诊断必须有至少测试乙肝表面抗原,抗乙型肝炎核心抗原(HBc),和抗乙型肝炎表面抗体。在高流行地区进行抗HBc筛查意味着测试阴性的人应该接种HBV疫苗。核苷或核苷酸类似物(NAs)如恩替卡韦(ETV),富马酸替诺福韦酯(TDF),替诺福韦艾拉酚胺(TAF)是免疫抑制期间HBV再激活预防和治疗的基础。相反,拉米夫定,替比夫定,和阿德福韦通常是不鼓励,因为它们的抗病毒功效降低和培养耐药病毒株的风险较高。然而,在ETV,TDF,和TAF不是可行的治疗选择。
    This editorial commented on an article in the World Journal of Gastroenterology titled \"Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors: Case Report and Literature Analysis\" by Colapietro et al. In this editorial, we focused on providing a more comprehensive exploration of hepatitis B virus reactivation (HBVr) associated with the usage of tyrosine kinase inhibitors (TKIs). It includes insights into the mechanisms underlying HBV reactivation, the temporal relationship between TKIs and HBV reactivation, and preventive measures. The aim is to understand the need for nucleos(t)ide analogs (NAT) and serial blood tests for early recognition of reactivation and acute liver injury, along with management strategies. TKIs are considered to be an intermediate (1%-10%) of HBVr. Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen, anti-hepatitis B core antigen (HBc), and anti-hepatitis B surface antibody. Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV. Nucleoside or nucleotide analogs (NAs) like entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) form the basis of HBV reactivation prophylaxis and treatment during immunosuppression. Conversely, lamivudine, telbivudine, and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains. However, these less effective NAs may still be utilized in cases where ETV, TDF, and TAF are not feasible treatment options.
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