MM, multiple myeloma

MM,多发性骨髓瘤
  • 文章类型: Journal Article
    蛋白酶体抑制剂(PIs)是多发性骨髓瘤和AL淀粉样变性患者联合治疗的骨干,同时也出现在Waldenström巨球蛋白血症和其他恶性肿瘤中。PIs作用于蛋白酶体肽酶,由于积累聚集而导致蛋白质组不稳定,展开,和/或受损的多肽;持续的蛋白质组不稳定性然后诱导细胞周期停滞和/或细胞凋亡。卡菲佐米,静脉内不可逆PI,与口服给药的Ixazomib或静脉内可逆性PI如硼替佐米相比,表现出更严重的心血管毒性特征。心血管毒性包括心力衰竭,高血压,心律失常,和急性冠脉综合征。因为PI是血液系统恶性肿瘤和淀粉样变性治疗的关键组成部分,管理他们的心血管毒性包括识别有风险的患者,在临床前水平早期诊断毒性,并在需要时提供心脏保护。未来的研究需要阐明潜在的机制,改善风险分层,定义最优管理策略,并开发具有安全心血管特征的新PI。
    Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström\'s macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.
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  • 文章类型: Journal Article
    免疫球蛋白轻链(AL)淀粉样变性是一种无法治愈的浆细胞疾病,其特征是错误折叠的免疫球蛋白游离轻链(FLC)的原纤维在靶器官中沉积,导致失败。心脏受累在AL淀粉样变性中很常见,并且是最不利的预后特征。具有快速组织诊断和组合开始的高临床怀疑指数,高效的细胞减灭剂治疗对于阻止淀粉样蛋白沉积过程和保持器官功能至关重要。分子靶向药物的临床使用,如蛋白酶体抑制剂和免疫调节剂,单克隆抗体,如daratumumab,对符合条件的患者进行风险调整后的自体干细胞移植,从根本上改变了AL淀粉样变性的自然史。这里,我们回顾了AL淀粉样变性最先进的治疗方案,着眼于未来的治疗场所,以影响这一毁灭性疾病的结局.
    Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as proteasome inhibitors and immunomodulatory agents, monoclonal antibodies such as daratumumab, and risk-adjusted autologous stem cell transplant in eligible patients, has radically changed the natural history of AL amyloidosis. Here, we review the state-of-the-art treatment landscape in AL amyloidosis with an eye toward future therapeutic venues to impact the outcome of this devastating illness.
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  • 文章类型: Journal Article
    静脉血栓栓塞症(VTE),包括深静脉血栓形成和肺栓塞,是癌症患者发病和死亡的主要原因。动脉血栓栓塞,包括心肌梗塞和中风,也很普遍。亚组的风险不同,在包括胰腺在内的特定癌症中观察到更高的发病率,胃,和多发性骨髓瘤.建议对大多数因内科疾病住院和进行大型癌症手术后的活动性癌症患者进行血栓预防。门诊血栓预防不是常规建议,但新出现的数据表明,可以使用经过验证的风险工具来识别受益于药物血栓预防的高危人群.直接口服抗凝药正在成为治疗癌症相关VTE的首选新选择。尽管低分子量肝素仍然是高出血风险患者的标准药物.超过前6个月的VTE管理和具有挑战性的临床情况,包括颅内转移和血小板减少症,需要谨慎管理,以平衡抗凝的益处和风险,并且仍然存在主要的证据知识空白。
    Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Arterial thromboembolism, including myocardial infarction and stroke, is also prevalent. Risk differs in subgroups, with higher rates observed in specific cancers including pancreas, stomach, and multiple myeloma. Thromboprophylaxis is recommended for most patients with active cancer hospitalized for medical illnesses and after major cancer surgery. Outpatient thromboprophylaxis is not routinely recommended, but emerging data suggest that a high-risk population that benefits from pharmacological thromboprophylaxis can be identified using a validated risk tool. Direct oral anticoagulants are emerging as the preferred new option for the treatment of cancer-associated VTE, although low-molecular-weight heparin remains a standard for patients at high bleeding risk. Management of VTE beyond the first 6 months and challenging clinical situations including intracranial metastases and thrombocytopenia require careful management in balancing the benefits and risks of anticoagulation and remain major knowledge gaps in evidence.
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  • 文章类型: Journal Article
    环状RNA(circularRNAs,circRNAs)是一类非常令人感兴趣的保守单链RNA分子,其通过前体mRNA反向剪接衍生自外显子或内含子序列。与典型的线性RNA不同,circRNAs形成共价闭合,连续的稳定环,没有5'端盖和3'末端聚(A)尾部,因此对外切核酸酶消化有抗性。大多数circRNAs是高度丰富的,并在不同物种中保守,具有组织或发育阶段特异性表达。circRNAs已被证明作为microRNA海绵发挥重要作用,基因剪接和转录的调节因子,RNA结合蛋白海绵和蛋白/肽翻译。新的证据表明,circRNAs在各种人类疾病中起作用,特别是癌症,并可能作为癌症治疗更好的预测生物标志物和治疗靶点。考虑到它们潜在的临床相关性,circRNAs已成为肿瘤病理领域新的研究热点。在本研究中,目前对生物发生的理解,特点,数据库,研究方法,生物学功能亚细胞分布,表观遗传调控,讨论了circRNAs的细胞外运输和降解。特别是,首先总结了circRNA研究中涉及的多个数据库和方法,以及确定circRNAs在肿瘤生长中潜在作用的最新进展,移民和入侵,这使得circRNAs更好的预测生物标志物,被描述。此外,提出了circRNAs在癌症患者管理中的临床应用的未来观点,这可以为将来的circRNAs提供新的见解。
    Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5\'end cap and 3\'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.
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  • 文章类型: Case Reports
    胃肠道的髓外浆细胞瘤(EMP)极为罕见。EMPs的临床表现多种多样,取决于肿瘤的位置和进展。在这里,我们报告了一个80岁的EMP累及直肠的病例,排便习惯改变的男性患者.计算机断层扫描证实了一个界限,等衰减质量具有明显的异质增强。患者接受腹腔镜手术切除,浆细胞瘤最终经病理证实。此外,我们对胃肠道EMP进行了文献综述,以获得进一步的研究。最后,我们发现影像学检查没有特异性。EMP的诊断仍取决于组织病理学。
    Extramedullary plasmacytoma (EMP) of the gastrointestinal tract is an extreme rarity. Clinical manifestations of EMPs are varied, depending on the position and progress of tumor. Here we report a case of an EMP involving rectum in an 80-year-old, male patient with a change of bowel habit. Computed tomography scanning confirmed a circumscribed, iso-attenuating mass with the obvious heterogeneous enhancement. Patient received the surgical resection by laparoscope and the plasmacytoma was finally confirmed by the pathology. Furthermore, we made a literature review about the EMP of gastrointestinal tract to get the further study. Finally, we found out there is no specificity in imaging examination. Diagnosis of EMP still depends on the histopathology.
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