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A Transformative Technology Linking Patient’s mRNA Expression Profile to Anticancer Drug Efficacy 将患者 mRNA 表达谱与抗癌药物疗效联系起来的变革性技术
Pub Date : 2024-07-14 DOI: 10.3390/onco4030012
Chen Yeh, Shu-Ti Lin, Hung-Chih Lai
As precision medicine such as targeted therapy and immunotherapy often have limited accessibility, low response rate, and evolved resistance, it is urgent to develop simple, low-cost, and quick-turnaround personalized diagnostic technologies for drug response prediction with high sensitivity, speed, and accuracy. The major challenges of drug response prediction strategies employing digital database modeling are the scarcity of labeled clinical data, applicability only to a few classes of drugs, and losing the resolution at the individual patient level. Although these challenges have been partially addressed by large-scale cancer cell line datasets and more patient-relevant cell-based systems, the integration of different data types and data translation from pre-clinical to clinical utilities are still far-fetched. To overcome the current limitations of precision medicine with a clinically proven drug response prediction assay, we have developed an innovative and proprietary technology based on in vitro patient testing and in silico data analytics. First, a patient-derived gene expression signature was established via the transcriptomic profiling of cell-free mRNA (cfmRNA) from the patient’s blood. Second, a gene-to-drug data fusion and overlaying mechanism to transfer data were performed. Finally, a semi-supervised method was used for the database searching, matching, annotation, and ranking of drug efficacies from a pool of ~700 approved, investigational, or clinical trial drug candidates. A personalized drug response report can be delivered to inform clinical decisions within a week. The PGA (patient-derived gene expression-informed anticancer drug efficacy) test has significantly improved patient outcomes when compared to the treatment plans without PGA support. The implementation of PGA, which combines patient-unique cfmRNA fingerprints with drug mapping power, has the potential to identify treatment options when patients are no longer responding to therapy and when standard-of-care is exhausted.
由于靶向治疗和免疫疗法等精准医疗往往存在可及性有限、反应率低和耐药性演变等问题,因此迫切需要开发简单、低成本、周转快的个性化诊断技术,以实现高灵敏度、快速和准确的药物反应预测。采用数字数据库建模的药物反应预测策略面临的主要挑战是标注临床数据稀缺、仅适用于少数几类药物,以及失去对患者个体水平的分辨率。虽然大规模癌症细胞系数据集和更多基于患者相关细胞的系统已部分解决了这些难题,但不同数据类型的整合以及从临床前到临床的数据转换仍很遥远。为了通过临床验证的药物反应预测分析克服精准医疗目前存在的局限性,我们开发了一种基于体外患者测试和硅学数据分析的创新专有技术。首先,通过对患者血液中的无细胞 mRNA(cfmRNA)进行转录组分析,建立了源自患者的基因表达特征。其次,进行了基因到药物的数据融合和数据传输的叠加机制。最后,采用半监督方法从约 700 种已批准、在研或临床试验候选药物中进行数据库搜索、匹配、注释和药效排序。可在一周内提供个性化的药物反应报告,为临床决策提供依据。与没有 PGA 支持的治疗方案相比,PGA(患者基因表达信息型抗癌药物疗效)测试显著改善了患者的治疗效果。PGA 将患者独有的 cfmRNA 指纹与药物图谱能力结合在一起,在患者对治疗不再有反应以及用尽标准疗法时,PGA 的实施有可能确定治疗方案。
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引用次数: 0
Revisiting the Role of PD-L1 Overexpression in Prognosis and Clinicopathological Features in Patients with Oral Squamous Cell Carcinoma 重新审视 PD-L1 过表达在口腔鳞状细胞癌患者预后和临床病理特征中的作用
Pub Date : 2024-07-12 DOI: 10.3390/onco4030011
Fernando Leporace-Jiménez, Isabel Portillo-Hernandez, Justino Jiménez-Almonacid, Ignacio Zubillaga Rodriguez, María Mejía-Nieto, Pablo Caballero Pedrero, G. S. Aniceto
Background: PD1 and its ligand PD-L1 are related to prognosis in many solid tumors; however, their role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: A retrospective monocentric study including all patients with OSCC diagnosed and treated between January 2020 and May 2022 was performed. PD-L1 expression was assessed per a combined positive score (CPS), considering a CPS of > or equal to 1 as positive (1–20 indicating “low expression” and ≥20 indicating “high”). A descriptive analysis of the patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recurrence, and survival. Results: In total, 65 patients (65 tumors) were analyzed. A total of 66.15% of the tumors were in advanced stages (III-IV), of which 97.67% expressed PD-L1+, compared with 71.42% in the early stages (I–II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54% in T1 tumors. A total of 50.79% of the tumors showed lymph node involvement (pN+), with 100% of the pN+ showing PD-L1+. The prevalence of pN+ was 59.38% vs. 40.63% for high vs. low PD-L1 expression, respectively. Patients’ follow-ups ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/− (CPS ≥ 1 vs. CPS < 1) or high (CPS ≥ 20) and low (CPS < 20) PD-L1 expression (p < 0.97 and 0.64, respectively). Conclusions: The method used to measure PD-L1 (a laboratory test with Dako 22C3 anti-PD-L1 primary antibodies) was reliable and accurate, with a correlation coefficient between PD-L1 expression in the biopsy and the surgical piece of 0.83 (p < 0.0001). A CPS of ≥1 was observed in large tumors (p < 0.001) and was correlated with that of lymph node metastases (p < 0.004). Further analysis of PD-L1 expression in OSCC and studies to determine its relevance in tumor biology and prognosis is needed.
背景:PD1及其配体PD-L1与许多实体瘤的预后有关,但它们在口腔鳞状细胞癌(OSCC)中的作用仍不清楚。研究方法进行了一项回顾性单中心研究,包括2020年1月至2022年5月期间诊断和治疗的所有OSCC患者。PD-L1表达按综合阳性评分(CPS)进行评估,将CPS大于或等于1视为阳性(1-20表示 "低表达",≥20表示 "高表达")。对患者群和肿瘤进行了描述性分析,包括肿瘤大小、分期、淋巴结受累情况、复发率和生存率。结果共分析了 65 名患者(65 个肿瘤)。共有66.15%的肿瘤处于晚期(III-IV期),其中97.67%的肿瘤表达PD-L1+,而早期(I-II期)为71.42%。T4肿瘤100%表达PD-L1,而T1肿瘤只有54%。共有50.79%的肿瘤显示淋巴结受累(pN+),其中100%的pN+显示PD-L1+。PD-L1高表达与低表达的pN+发生率分别为59.38%和40.63%。患者的随访时间从2个月到34.5个月不等。总生存期(OS)与PD-L1+/-(CPS≥1 vs. CPS <1)或PD-L1高表达(CPS≥20)和低表达(CPS <20)之间无明显差异(P分别<0.97和0.64)。结论用于测量PD-L1的方法(使用Dako 22C3抗PD-L1一抗进行实验室检测)是可靠和准确的,活检和手术切片中PD-L1表达的相关系数为0.83(p < 0.0001)。在大肿瘤中观察到CPS≥1(p < 0.001),并与淋巴结转移相关(p < 0.004)。需要进一步分析PD-L1在OSCC中的表达,并研究其与肿瘤生物学和预后的相关性。
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引用次数: 0
The World of Immunotherapy Needs More Than PD-1/PD-L1—Two of the New Kids on the Block: LAG-3 and TIGIT 免疫疗法世界需要的不仅仅是 PD-1/PD-L1--两种新药:LAG-3和TIGIT
Pub Date : 2024-07-01 DOI: 10.3390/onco4030010
J. Gama, Paulo Teixeira, Rui Caetano Oliveira
Immunotherapy has paved the way for the development of solid tumor new treatments in the last decade. The approval of immune checkpoint inhibitors such as anti PD-1/PD-L1 provided a revolution with optimal results. However, a considerable proportion of patients experience adverse therapeutic effects, and up to 50% may develop secondary resistance in the first three to five years. This has prompted the need for identifying new targets for immunotherapy that have good tolerance and biosafety and, of course, good tumoral response, either alone or in combination. Two of these new targets are the Lymphocyte-activation gene 3 (LAG-3) and the T cell immunoglobulin and ITIM domain (TIGIT). They are responsible for several interactions with the immune system, prompting an immunosuppressive phenotype in the tumor microenvironment. Both LAG-3 and TIGIT can be druggable, alone or in combination with anti-PD-1/PD-L1, with rather safe profiles making them attractive. In this review, we highlight some of the immune mechanisms of TIGIT and LAG-3 and their detection by immunohistochemistry, providing some insight into their use in the clinical setting.
近十年来,免疫疗法为实体瘤新疗法的发展铺平了道路。抗PD-1/PD-L1等免疫检查点抑制剂的批准带来了一场效果最佳的革命。然而,相当一部分患者在治疗过程中会出现不良反应,多达50%的患者可能会在最初的三至五年内产生继发性耐药性。这就促使人们需要为免疫疗法寻找新的靶点,这些靶点要有良好的耐受性和生物安全性,当然还要有良好的肿瘤反应,可以单独使用,也可以联合使用。其中两个新靶点是淋巴细胞活化基因 3 (LAG-3) 和 T 细胞免疫球蛋白和 ITIM 结构域 (TIGIT)。它们负责与免疫系统的多种相互作用,促使肿瘤微环境形成免疫抑制表型。LAG-3和TIGIT都可以单独或与抗PD-1/PD-L1联合使用,具有相当安全的特性,因此很有吸引力。在这篇综述中,我们将重点介绍 TIGIT 和 LAG-3 的一些免疫机制及其免疫组化检测方法,为它们在临床中的应用提供一些启示。
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引用次数: 0
The Prognostic Role of Prognostic Nutritional Index and Controlling Nutritional Status in Predicting Survival in Older Adults with Oncological Disease: A Systematic Review 预后营养指数和控制营养状况在预测老年肿瘤患者生存期中的预后作用:系统综述
Pub Date : 2024-06-02 DOI: 10.3390/onco4020009
Ana Filipa Ferreira, Tatiana Fernandes, Maria do Carmo Carvalho, Helena Soares Loureiro
The increase in new cancer diagnoses in the elderly calls for new, accessible, and easy-to-use prognostic tools that contribute to lowering the burden of the disease. Recognising the importance of inflammation and nutritional status in the progression of the disease, the purpose of this systematic review was to synthesise the evidence on the prognostic role of Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) in predicting survival of older adult cancer patients. A comprehensive search was conducted in PubMed and Web of Science Core Collection databases until 22 February 2024. The articles included in this review (n = 38) examined the relationships of PNI and CONUT with survival outcomes in elderly cancer patients. Despite high heterogeneity between the studies, most concluded that low PNI values are associated with poor overall survival (OS), particularly in gastric cancer patients. Most studies did not find an association between PNI and cancer-specific survival, progression-free survival, disease-free survival, recurrence-free survival, and mortality. Results regarding the prognostic role of CONUT in predicting survival were inconclusive. This study suggests that PNI could be used to predict OS in elderly cancer patients, while more studies are needed to assess the prognostic role of CONUT.
新诊断出的老年癌症患者越来越多,这就需要有新的、方便易用的预后工具来降低疾病负担。认识到炎症和营养状况在疾病进展中的重要性,本系统综述旨在综合预后营养指数(PNI)和控制营养状况(CONUT)在预测老年癌症患者生存率方面的预后作用的证据。截至 2024 年 2 月 22 日,我们在 PubMed 和 Web of Science 核心数据库中进行了全面检索。本综述收录的文章(n = 38)研究了 PNI 和 CONUT 与老年癌症患者生存结果的关系。尽管研究之间存在高度异质性,但大多数研究认为,低 PNI 值与总生存期(OS)差有关,尤其是在胃癌患者中。大多数研究并未发现 PNI 与癌症特异性生存、无进展生存、无疾病生存、无复发生存和死亡率之间存在关联。关于 CONUT 在预测生存率方面的预后作用,研究结果尚无定论。本研究表明,PNI 可用于预测老年癌症患者的 OS,而 CONUT 的预后作用则需要更多的研究来评估。
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引用次数: 0
How Reliable Are Predictions of CD8+ T Cell Epitope Recognition? Lessons for Cancer 对 CD8+ T 细胞表位识别的预测有多可靠?对癌症的启示
Pub Date : 2024-04-17 DOI: 10.3390/onco4020006
A. Lehmann, Paul V Lehmann, Stephen Todryk
Synthetic peptides derived from antigen sequences are essential reagents for the detection of CD8+ cytotoxic T lymphocytes (CTLs), in assays such as ELISPOT/ImmunoSpot®. Indeed, the combination of peptides and ImmunoSpot® has been widely used for immune monitoring in numerous vaccine trials. Target antigens in pathogens or cancers may be large in size and multiple in number, often seemingly necessitating in silico peptide epitope predictions using algorithms and programs for certain HLA alleles to narrow down the numbers of required peptides. In this commentary, we discuss our data in the context of immune responses to viral and cancer antigens, concluding that systematic high-throughput immune monitoring of CD8+ T cells will provide more reliable insights on the host’s response to cancer than the reliance on select CD8+ T cell epitopes, no matter whether these are in silico predicted or even if they had been empirically established. We show the feasibility of large scale, high-throughput systematic CD8+ T cell epitope testing towards this goal.
在 ELISPOT/ImmunoSpot® 等检测方法中,源自抗原序列的合成肽是检测 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 的基本试剂。事实上,多肽与 ImmunoSpot® 的结合已被广泛用于众多疫苗试验中的免疫监测。病原体或癌症中的靶抗原可能体积大、数量多,因此往往需要使用针对某些 HLA 等位基因的算法和程序来进行肽表位预测,以缩小所需肽体的数量。在这篇评论中,我们结合对病毒和癌症抗原的免疫反应讨论了我们的数据,并得出结论:对 CD8+ T 细胞进行系统的高通量免疫监测,比依赖选定的 CD8+ T 细胞表位更能可靠地了解宿主对癌症的反应,无论这些表位是在硅学中预测的,还是根据经验确定的。我们展示了为实现这一目标进行大规模、高通量系统性 CD8+ T 细胞表位测试的可行性。
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引用次数: 0
Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress DNA 损伤修复蛋白的缺乏通过氧化应激促进前列腺癌细胞迁移
Pub Date : 2024-03-28 DOI: 10.3390/onco4020005
Philippa Lantwin, A. Kaczorowski, C. Nientiedt, C. Schwab, Martina Kirchner, V. Schütz, M. Görtz, Markus Hohenfellner, A. Duensing, A. Stenzinger, Stefan Duensing
Introduction: DNA damage repair gene deficiency defines a subgroup of prostate cancer patients with early metastatic progression and unfavorable disease outcome. Whether deficiency in DNA damage repair genes directly promotes metastatic dissemination is not completely understood. Methods: The migratory behavior of prostate cancer cells was analyzed after siRNA-mediated knockdown of DNA damage repair and checkpoint proteins, including BRCA2, ATM, and others, using transwell migration assays, scratch assays and staining for F-actin to ascertain cell circularity. Cells deficient in BRCA2 or ATM were tested for oxidative stress by measuring reactive oxygen species (ROS). The effects of ROS inhibition on cell migration were analyzed using the antioxidant N-acetylcysteine (NAC). The correlation between BRCA2 deficiency and oxidative stress was ascertained via immunohistochemistry for methylglyoxal (MG)-modified proteins in 15 genetically defined primary prostate cancers. Results: Prostate cancer cells showed a significantly increased migratory activity after the knockdown of BRCA2 or ATM. There was a significant increase in ROS production in LNCaP cells after BRCA2 knockdown and in PC-3 cells after BRCA2 or ATM knockdown. Remarkably, the ROS scavenger NAC abolished the enhanced motility of prostate cancer cells after the knockdown of BRCA2 or ATM. Primary prostate cancers harboring genetic alterations in BRCA2 showed a significant increase in MG-modified proteins, indicating enhanced oxidative stress in vivo. Conclusions: Our results indicate that DNA damage repair gene deficiency may contribute to the metastatic dissemination of prostate cancer through enhanced tumor cell migration involving oxidative stress.
导言:DNA 损伤修复基因缺乏症是前列腺癌患者中的一个亚群,该亚群具有早期转移进展和不利的疾病预后。DNA损伤修复基因缺乏是否会直接促进转移扩散,目前尚不完全清楚。研究方法使用经孔迁移试验、划痕试验和 F-肌动蛋白染色来确定细胞的环状性,分析了 siRNA 介导的 DNA 损伤修复和检查点蛋白(包括 BRCA2、ATM 等)敲除后前列腺癌细胞的迁移行为。通过测量活性氧(ROS),对缺乏 BRCA2 或 ATM 的细胞进行氧化应激测试。使用抗氧化剂 N-乙酰半胱氨酸(NAC)分析了抑制 ROS 对细胞迁移的影响。通过免疫组织化学方法检测了 15 例基因定义的原发性前列腺癌中的甲基乙二醛(MG)修饰蛋白,从而确定了 BRCA2 缺乏与氧化应激之间的相关性。结果显示敲除 BRCA2 或 ATM 后,前列腺癌细胞的迁移活动明显增加。BRCA2 基因敲除后,LNCaP 细胞产生的 ROS 明显增加;BRCA2 或 ATM 基因敲除后,PC-3 细胞产生的 ROS 也明显增加。值得注意的是,ROS 清除剂 NAC 可抑制 BRCA2 或 ATM 敲除后前列腺癌细胞运动性的增强。携带 BRCA2 基因改变的原发性前列腺癌的 MG 修饰蛋白显著增加,表明体内氧化应激增强。结论:我们的研究结果表明,DNA损伤修复基因缺陷可能会通过氧化应激增强肿瘤细胞迁移,从而导致前列腺癌的转移扩散。
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引用次数: 0
Dendritic Cell Immunotherapy for Ovarian Cancer: An Overview of Our Achievements 树突状细胞免疫疗法治疗卵巢癌:我们的成就概览
Pub Date : 2024-03-21 DOI: 10.3390/onco4010004
J. Bartůňková
Epithelial ovarian carcinoma (EOC) is the fifth leading cause of cancer-related death in women, largely reflecting the early dissemination of this malignant disease to the peritoneum. Due to its immunological features, EOC has poor response to immune checkpoint inhibitors (ICIs), including a limited tumor mutational burden (TMB), poor infiltration by immune cells, and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of pre-existing immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC), which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of the DCVAC were more pronounced in patients with EOC with lower-than-median TMBs and reduced CD8+ T cell infiltration. Thus, the DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically “cold” EOC. Our findings underscore the need for personalized immunotherapy and the clinical relevance of potential tumor-related biomarkers within the immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of the TMB and immune infiltration at baseline as biomarkers for guiding the clinical management of EOC.
上皮性卵巢癌(EOC)是导致女性癌症相关死亡的第五大原因,这在很大程度上反映了这种恶性疾病向腹膜的早期扩散。由于其免疫学特征,EOC 对免疫检查点抑制剂(ICIs)的反应不佳,包括有限的肿瘤突变负荷(TMB)、免疫细胞浸润差以及活跃的免疫抑制。因此,需要新的策略来克服EOC患者经常缺乏原有免疫力的问题。我们开发并测试了一种基于自体树突状细胞(DC)的疫苗(DCVAC),最近在两项招募EOC患者的独立随机II期临床试验(SOV01,NCT02107937;SOV02,NCT02107950)中,该疫苗被证明是安全的,并能显著改善无进展生存期(PFS)。此外,我们的探索性数据分析表明,在TMB低于中位数、CD8+ T细胞浸润减少的EOC患者中,DCVAC的临床疗效更为显著。因此,基于直流电的疫苗是一种很有前景的临床工具,可以启动免疫 "冷 "EOC患者的抗癌免疫。我们的研究结果强调了个性化免疫疗法的必要性以及免疫疗法领域中潜在的肿瘤相关生物标志物的临床意义。还需要进行更多的临床试验来研究这些策略,以及TMB和基线免疫浸润作为生物标志物在指导EOC临床治疗方面的潜在价值。
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引用次数: 0
When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse 治疗诱导的癌细胞凋亡何时助长肿瘤复发
Pub Date : 2024-02-04 DOI: 10.3390/onco4010003
R. Mirzayans
Most therapeutic strategies for solid tumor malignancies are designed based on the hypothesis that cancer cells evade apoptosis to exhibit therapy resistance. This is somewhat surprising given that clinical studies published since the 1990s have demonstrated that increased apoptosis in solid tumors is associated with cancer aggressiveness and poor clinical outcome. This is consistent with more recent reports demonstrating non-canonical (pro-survival) roles for apoptotic caspases, including caspase 3, as well as the ability of cancer cells to recover from late stages of apoptosis via a process called anastasis. These activities are essential for the normal development and maintenance of a healthy organism, but they also enable malignant cells (including cancer stem cells) to resist anticancer treatment and potentially contribute to clinical dormancy (minimal residual disease). Like apoptosis, therapy-induced cancer cell dormancy (durable proliferation arrest reflecting various manifestations of genome chaos) is also not obligatorily a permanent cell fate. However, as briefly discussed herein, compelling pre-clinical studies suggest that (reversible) dormancy might be the “lesser evil” compared to treacherous apoptosis.
实体瘤恶性肿瘤的大多数治疗策略都是基于癌细胞逃避凋亡以表现出抗药性这一假设而设计的。自 20 世纪 90 年代以来发表的临床研究表明,实体瘤细胞凋亡的增加与癌症的侵袭性和不良的临床预后有关,因此这有点令人惊讶。这与最近的一些报告一致,这些报告表明包括 caspase 3 在内的凋亡 caspase 起着非典型(促生存)的作用,而且癌细胞能够通过一种叫做 "吻合 "的过程从凋亡晚期恢复过来。这些活动对健康生物体的正常发育和维持至关重要,但它们也能使恶性细胞(包括癌症干细胞)抵抗抗癌治疗,并可能导致临床休眠(最小残留病)。与细胞凋亡一样,治疗诱导的癌细胞休眠(反映基因组混乱各种表现的持久增殖停滞)也并非必然是一种永久性的细胞命运。然而,正如本文简要讨论的那样,令人信服的临床前研究表明,与危险的细胞凋亡相比,(可逆的)休眠可能是 "较小的邪恶"。
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引用次数: 0
When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse 治疗诱导的癌细胞凋亡何时助长肿瘤复发
Pub Date : 2024-02-04 DOI: 10.3390/onco4010003
R. Mirzayans
Most therapeutic strategies for solid tumor malignancies are designed based on the hypothesis that cancer cells evade apoptosis to exhibit therapy resistance. This is somewhat surprising given that clinical studies published since the 1990s have demonstrated that increased apoptosis in solid tumors is associated with cancer aggressiveness and poor clinical outcome. This is consistent with more recent reports demonstrating non-canonical (pro-survival) roles for apoptotic caspases, including caspase 3, as well as the ability of cancer cells to recover from late stages of apoptosis via a process called anastasis. These activities are essential for the normal development and maintenance of a healthy organism, but they also enable malignant cells (including cancer stem cells) to resist anticancer treatment and potentially contribute to clinical dormancy (minimal residual disease). Like apoptosis, therapy-induced cancer cell dormancy (durable proliferation arrest reflecting various manifestations of genome chaos) is also not obligatorily a permanent cell fate. However, as briefly discussed herein, compelling pre-clinical studies suggest that (reversible) dormancy might be the “lesser evil” compared to treacherous apoptosis.
实体瘤恶性肿瘤的大多数治疗策略都是基于癌细胞逃避凋亡以表现出抗药性这一假设而设计的。自 20 世纪 90 年代以来发表的临床研究表明,实体瘤细胞凋亡的增加与癌症的侵袭性和不良的临床预后有关,因此这有点令人惊讶。这与最近的一些报告一致,这些报告表明包括 caspase 3 在内的凋亡 caspase 起着非典型(促生存)的作用,而且癌细胞能够通过一种叫做 "吻合 "的过程从凋亡晚期恢复过来。这些活动对健康生物体的正常发育和维持至关重要,但它们也能使恶性细胞(包括癌症干细胞)抵抗抗癌治疗,并可能导致临床休眠(最小残留病)。与细胞凋亡一样,治疗诱导的癌细胞休眠(反映基因组混乱各种表现的持久增殖停滞)也并非必然是一种永久性的细胞命运。然而,正如本文简要讨论的那样,令人信服的临床前研究表明,与危险的细胞凋亡相比,(可逆的)休眠可能是 "较小的邪恶"。
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引用次数: 0
Significance of PET/CT Imaging in Myeloma Assessment: Exploring Novel Applications beyond Osteolytic Lesion Detection and Treatment Response PET/CT 成像在骨髓瘤评估中的意义:探索溶骨病变检测和治疗反应之外的新应用
Pub Date : 2024-01-09 DOI: 10.3390/onco4010002
M. Zirakchian Zadeh
In multiple myeloma (MM), specific cytokines produced by plasma cells disrupt the equilibrium between osteoblasts and osteoclasts. As a result, MM patients experience an increase in osteoclast activity and a decrease in osteoblast activity. This disparity is fundamental to the development of myeloma bone disease. Lytic lesions, which are a feature of MM, can result in pathologic fractures and excruciating pain. For many years, whole-body X-ray radiography has been the standard imaging method for identifying lytic lesions. However, its sensitivity is limited because it can only detect lesions once the bone mass has been reduced by 30% to 50%. Hence, utilizing advanced and sensitive imaging modalities, such as positron emission tomography (PET) fused with computed tomography (CT), is crucial for the early detection of osteolytic lesions. Among radiotracers used in PET imaging, 1⁸F-fluorodeoxyglucose ([18F]FDG) is the most commonly employed in the field of oncology. Currently, most guidelines include [18F]FDG PET/CT in the assessment of myeloma patients, particularly for detecting osteolytic lesions, evaluating treatment response, and assessing extramedullary and residual disease. Nonetheless, in recent years, new applications of PET/CT for evaluating myeloma have been investigated. These include assessing aspects such as bone turnover, dual-time-point imaging (early and delayed scans), the impact of chemotherapy on the brain (commonly known as ‘chemo brain’), innovative PET radiotracers, and the use of artificial intelligence technology. This article aims to provide a comprehensive review of both conventional and innovative uses of PET/CT in evaluating multiple myeloma.
在多发性骨髓瘤(MM)中,浆细胞产生的特定细胞因子会破坏成骨细胞和破骨细胞之间的平衡。因此,MM 患者的破骨细胞活性增加,而成骨细胞活性降低。这种差异是骨髓瘤骨病发展的根本原因。溶解性病变是 MM 的特征之一,可导致病理性骨折和剧烈疼痛。多年来,全身 X 射线照相术一直是识别溶解性病变的标准成像方法。然而,这种方法的灵敏度有限,因为只有当骨质减少 30% 至 50% 时才能发现病变。因此,利用正电子发射断层扫描(PET)与计算机断层扫描(CT)融合等先进而灵敏的成像模式对于早期发现溶骨病变至关重要。在 PET 成像所用的放射性同位素中,1⁸F-氟脱氧葡萄糖([18F]FDG)是肿瘤学领域最常用的一种。目前,大多数指南都将[18F]FDG PET/CT 用于骨髓瘤患者的评估,特别是用于检测溶骨性病变、评估治疗反应以及评估髓外和残留疾病。尽管如此,近年来人们对 PET/CT 评估骨髓瘤的新应用进行了研究。这些应用包括评估骨转换、双时间点成像(早期和延迟扫描)、化疗对大脑的影响(俗称 "化疗脑")、创新的 PET 放射性示踪剂以及人工智能技术的使用等方面。本文旨在全面综述 PET/CT 在评估多发性骨髓瘤方面的传统和创新应用。
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引用次数: 0
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