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Added value of molecular karyotype in childhood acute lymphoblastic leukemia 儿童急性淋巴细胞白血病分子核型的附加值
Pub Date : 2023-06-01 DOI: 10.1002/cai2.67
Margaux Camuset, Baptiste Le Calvez, Olivier Theisen, Catherine Godon, Audrey Grain, Caroline Thomas, Marie-Laure Couec, Marie C. Béné, Fanny Rialland, Marion Eveillard

Background

Thanks to an improved therapeutic regimen in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 5 year-overall survival now exceeds 90%. Unfortunately, the 25% of children who relapse have an initial poor prognosis, potentially driven by pre-existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping.

Methods

Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP-ALL and in a prospective cohort of 38 newly diagnosed childhood cases.

Results

In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B-cell development, cell proliferation, transcription and molecular pathways.

Conclusion

SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.

背景 由于儿童 B 细胞前体急性淋巴细胞白血病(BCP-ALL)治疗方案的改进,目前 5 年总生存率已超过 90%。不幸的是,25%的复发患儿最初预后较差,这可能是由已经存在或新出现的分子异常引起的。后者最初基本上是通过细胞遗传学确定的。然而,有些微妙的改变在核型检查中并不明显。 方法 单核苷酸多态性(SNP)阵列是染色体分析的另一种方法,可以更深入地评估染色体的改变,如评估拷贝数改变(CNA)和杂合性缺失(LOH)。本文将这种方法应用于 7 名 BCP-ALL 儿童的回顾性诊断/复发配对样本和 38 例新诊断儿童病例的前瞻性队列。 结果 在配对研究中,与初始核型相比,SNP 阵列分析将两名患者重新归类为预后不良病例。4 例 CNA 和 0.9 例 LOH 在复发过程中发生了改变。在前瞻性研究中,SNP 将 10 例中等核型患者重新分类为 7 例预后良好和 3 例预后不良。最终,与传统核型相比,SNP 阵列可在所有受测儿童中发现更多异常,完善其预后价值,并发现一些可用于精准医疗的药物异常。总体而言,检测到的异常可分为四组,分别涉及 B 细胞发育、细胞增殖、转录和分子通路。 结论 因此,SNP 似乎是 BCP ALL 综合诊断的首选方法,尤其是对于最初被归类为中等预后的患者。这种细胞遗传学和高通量测序的互补方法可以获得更多的分类信息,并在这些技术失效时发挥作用。
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引用次数: 0
PD-1/L1 inhibitors can improve but not replace chemotherapy for advanced urothelial carcinoma: A systematic review and network meta-analysis PD-1/L1抑制剂可以改善但不能取代晚期尿路上皮癌的化疗:一项系统综述和网络荟萃分析
Pub Date : 2023-05-19 DOI: 10.1002/cai2.75
Longkun Mao, Meihua Yang, Xinxiang Fan, Wenjie Li, Xiaodong Huang, Wang He, Tianxin Lin, Jian Huang

Background

Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma. Therefore, a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary.

Methods

We comprehensively searched PubMed, Web of Science, Embase, and Cochrane Library databases and performed a meta-analysis of randomized controlled trials up to July 2021. We considered overall survival as the primary outcome, and progression-free survival, objective response rate, and treatment-related adverse events as secondary outcomes.

Results

Overall, 3584 patients from five studies were evaluated. Compared with first-line chemotherapy, programmed cell death-1/ligand 1 inhibitors were significantly associated with worse progression-free survival (p < 0.001) and adverse objective response rates (p < 0.001). However, the treatments were not significantly different in terms of overall survival (p = 0.33). Compared with second-line chemotherapy, programmed cell death-1/ligand 1 inhibitors significantly improved overall survival (p < 0.001), and there was no statistically significant difference in progression-free survival (p = 0.89) or objective response rate (p = 0.34). Compared with chemotherapy, programmed cell death-1/ligand 1 inhibitors were well tolerated (first-line chemotherapy: p < 0.001; second-line chemotherapy: p < 0.001).

Conclusions

The efficacy of programmed cell death-1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first-line platinum-based chemotherapy but is better than second-line chemotherapy; however, programmed cell death-1/ligand 1 inhibitors are safer than first- and second-line chemotherapy and have a broader prospect for use in combination therapy.

背景程序性细胞死亡-1/配体1抑制剂是晚期尿路上皮癌的一种新的治疗策略。因此,与化疗相比,有必要对其疗效和毒性进行比较评估。方法我们全面搜索PubMed、Web of Science、Embase和Cochrane Library数据库,并对截至2021年7月的随机对照试验进行荟萃分析。我们认为总生存率是主要结果,无进展生存率、客观缓解率和治疗相关不良事件是次要结果。结果总共对来自5项研究的3584名患者进行了评估。与一线化疗相比,程序性细胞死亡-1/配体1抑制剂与较差的无进展生存率显著相关(p <; 0.001)和不良客观反应率(p <; 0.001)。然而,就总生存率而言,两种治疗没有显著差异(p = 0.33)。与二线化疗相比,程序性细胞死亡-1/配体1抑制剂显著提高了总生存率(p <; 0.001),并且在无进展生存率方面没有统计学上的显著差异(p = 0.89)或客观应答率(p = 0.34)。与化疗相比,程序性细胞死亡-1/配体1抑制剂耐受性良好(一线化疗:p <; 0.001;二线化疗:p <; 0.001)。结论程序性细胞死亡-1/配体1抑制剂治疗晚期尿路上皮癌的疗效并不优于一线铂类化疗,但优于二线化疗;然而,程序性细胞死亡-1/配体1抑制剂比一线和二线化疗更安全,在联合治疗中有更广阔的应用前景。
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引用次数: 0
Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022 2000-2002年肿瘤标志物在癌症诊断中应用的文献计量和可视化分析
Pub Date : 2023-05-19 DOI: 10.1002/cai2.74
Shi-Peng Ke, Si-Mei Chen, Yi Jiang, Heng-Xin Gong, Jia-Li Yu, Xu Li, Yin-Yi Chen, Xiao-Hang Li, Qun-Xia Wang, Yan-Zhao Liu

Background

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity.

Methods

Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection.

Results

A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. “Carcinoembryonic antigen (CEA) as tumor marker in lung cancer” was the top reference with the most citations, Lung Cancer was the core journal, and “serum tumor marker” experienced a citation burst over the past 5 years.

Conclusion

This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

背景癌症(LC)是全球癌症相关死亡的主要原因。肿瘤标志物(TM)检测可以指示肿瘤的存在和生长,因此被广泛用于诊断LC。在这里,我们进行了文献计量分析,以检查用于LC诊断的TM相关出版物,以说明该领域的现状和未来趋势,以及以高灵敏度识别另外的有前景的TM。方法从Web of Science Core Collection下载有关TM在LC诊断中的出版物。CiteSpace被应用于对与该领域相关的期刊、论文作者、关键词和参考文献进行文献计量分析。VOSviewer用于生成关于国家、机构、作者和关键词的简明图表。通过引文突发检测分析TM研究前沿的变化。结果共分析990项研究。合作网络分析显示,中华人民共和国、延世大学和莫利纳大学分别是生产力最高的国家、机构和学者。此外,莫利纳R是被引用次数最多的作者。国家自然科学基金是最大的资金来源。“癌胚抗原(CEA)作为癌症肿瘤标志物”是引用次数最多的参考文献,《癌症》是核心期刊,《血清肿瘤标志物》在过去5年中经历了引用暴增。结论本文献计量学分析TM在LC诊断中的应用,揭示了该领域的发展趋势和前沿。我们总结了该领域的研究现状和提高传统血清TM诊断疗效的方法,并为提高LC临床检出率提供了新的方向和思路。应优先考虑将计算机辅助诊断技术转化为临床应用。此外,循环肿瘤细胞、外泌体和微小RNA是目前最前沿的TM。
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引用次数: 0
The antiferroptotic role of TRIM7: Molecular mechanism and synergistic effect with temozolomide TRIM7的反铁作用:分子机制及与替莫唑胺的协同作用
Pub Date : 2023-05-15 DOI: 10.1002/cai2.77
Luyao Wang, Rongyang Xu, Chengying Huang, Shanqiang Qu

Nuclear receptor coactivator 4 (NCOA4) protein is a selective cargo receptor that plays a crucial role in ferritinophagy by targeting and delivering the ferritin iron storage protein to lysosomes for degradation and releasing iron. TRIM7 overexpression inhibits ferroptosis in glioblastoma cells by ubiquitinating NCOA4 protein.

核受体共激活因子4(NCOA4)蛋白是一种选择性货物受体,通过靶向铁蛋白-铁储存蛋白并将其递送至溶酶体进行降解和释放铁,在铁蛋白吞噬中发挥关键作用。TRIM7过表达通过泛素化NCOA4蛋白抑制胶质母细胞瘤细胞中的脱铁性贫血。
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引用次数: 0
A case report of multimodal ultrasound imaging in the diagnosis of giant retroperitoneal ganglioneuroma 多模式超声显像诊断腹膜后巨大神经节细胞神经瘤1例报告
Pub Date : 2023-05-10 DOI: 10.1002/cai2.73
Li Feng, Yong Wang

Retroperitoneal ganglioneuroma is a rare benign tumor that is challenging in terms of clinical diagnosis. Computed tomography and magnetic resonance imaging are usually performed for diagnosis rather than convenient and inexpensive ultrasonography. Here, we present the case of a 21-year-old female patient who was diagnosed by multimodal ultrasound imaging and whose diagnosis was confirmed by ultrasound-guided core needle biopsy before surgery. We hope that this rare case will help clinicians and radiologists realize the advantages of multimodal ultrasound imaging in the diagnosis of retropeitoneal solid tumors, and reduce misdiagnosis.

腹膜后神经节细胞神经瘤是一种罕见的良性肿瘤,在临床诊断方面具有挑战性。计算机断层扫描和磁共振成像通常用于诊断,而不是方便和廉价的超声检查。在这里,我们介绍了一例21岁的女性患者,她通过多模式超声成像诊断,并在手术前通过超声引导下的核心针活检证实了诊断。我们希望这一罕见病例能帮助临床医生和放射科医生认识到多模式超声成像在腹膜后实体瘤诊断中的优势,减少误诊。
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引用次数: 0
A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer 免疫检查点抑制剂在晚期癌症三阴性中的现实研究
Pub Date : 2023-04-23 DOI: 10.1002/cai2.70
Zheng Zhang, Yadi Zhang, Chuanling Liu, Jiakang Shao, Yimeng Chen, Yimin Zhu, Li Zhang, Boyu Qin, Ziqing Kong, Xixi Wang, Yutong Wang, Deqin Huang, Liqun Liu, Yuxin Zhou, Ran Tao, Zengjie Yang, Mei Liu, Weihong Zhao

Background

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.

Methods

The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed.

Results

Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable.

Conclusions

ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

背景癌症三阴性(TNBC)是癌症最具侵袭性的类型。免疫检查点抑制剂(ICIs)已被广泛用于治疗各种肿瘤,并改变了肿瘤管理的格局,但用于TNBC治疗的ICIs的真实世界研究数据仍然有限。本研究的目的是在现实世界中评估ICIs治疗晚期TNBC患者的疗效,并探索可能的相关性。方法收集在中国人民解放军总医院接受ICI治疗的晚期TNBC患者的临床资料。评估治疗反应、结果和不良事件(AE)。结果81例患者被纳入研究。确诊客观有效率(ORR)为32.1%,疾病控制率(DCR)为64.2%。中位无进展生存期(PFS)为4.2个月,中位总生存期(OS)为11.0个月。从ICIs中获得临床益处的患者的PFS和OS更长,而接受后期ICIs和较高炎症水平的患者的FS和OS更短;特别是TIL较高的患者PFS较长。总体AE尚可。结论ICIs治疗晚期TNBC疗效确切,不良反应可耐受。鉴定了一组生物标志物,包括LDH、ALP和bNLR,以预测ICIs在TNBC治疗中的疗效。
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引用次数: 0
Particle implantation combined with chemotherapy for rhabdomyosarcoma of the head and neck: A 8-year long-term follow-up case report 粒子植入联合化疗治疗头颈部横纹肌肉瘤8年长期随访报告
Pub Date : 2023-04-20 DOI: 10.1002/cai2.71
Sidou He, Shuhang Tian, Na Xu, Jianguo Zhang, Chao Duan, Xiaoli Ma

Rhabdomyosarcomas (RMSs) are highly malignant soft-tissue sarcomas. Head and neck RMSs often pose unique challenges to treatment because of their closeness to important structures. We here report a rare case of a 1-year-old boy with a 1-month history of right eye swelling and an eye mass. Biopsy of deep tumors in the maxillofacial region supports embryonal RMS. Postoperative positron emission computed tomography showed a 5.0 cm × 4.8 cm × 4.2 cm malignant tumor in the right maxillary region. In accordance with the international RMS study group guideline, the child was diagnosed with IIIa and TNM stage T2bN1M1 embryonal RMS. The child was treated with a combination of chemotherapy and 125I seed implantation radiotherapy and eventually achieved partial remission. This case report shows that 125I seed implantation is a safe and effective means of delivering radiotherapy to young children with head and neck RMSs. It may be an option for children with RMSs for whom surgery or external radiotherapy is unsuitable.

横纹肌肉瘤是一种高度恶性的软组织肉瘤。头部和颈部RMS通常对治疗提出独特的挑战,因为它们靠近重要结构。我们在此报告一个1岁男孩的罕见病例,他有1个月的右眼肿胀和眼部肿块病史。颌面部深层肿瘤的活检支持胚胎RMS。术后正电子发射计算机断层扫描显示5.0 厘米 × 4.8 厘米 × 4.2 cm恶性肿瘤。根据国际RMS研究小组指南,该儿童被诊断为IIIa和TNM期T2bN1M1胚胎性RMS。该儿童接受了化疗和125I种子植入放疗的联合治疗,最终获得部分缓解。该病例报告表明,125I粒子植入是一种安全有效的头颈部RMS患儿放射治疗方法。对于不适合手术或外部放射治疗的RMS儿童来说,这可能是一种选择。
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引用次数: 0
Severe graft-versus-host disease post allogeneic hematopoietic stem cell transplantation due to loss of HLA heterozygosity in recipient lymphocytes after full graft rejection 同种异体造血干细胞移植术后完全排斥反应后受体淋巴细胞HLA杂合性缺失引起的严重移植物抗宿主病
Pub Date : 2023-04-18 DOI: 10.1002/cai2.72
Song Xue, Lili Miao, Zimu Gong, Wenqiu Huang, Yongping Zhang, Fuhong Liu, Jingbo Wang

Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially effective therapy, but graft-versus-host disease (GVHD) is a life-threatening complication. We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD-like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.

生殖细胞肿瘤并发血液系统恶性肿瘤是一种罕见的临床现象。异基因造血干细胞移植是一种潜在的有效治疗方法,但移植物抗宿主病是一种危及生命的并发症。我们报告了一例13岁的女性患者,被诊断为生殖细胞肿瘤,随后并发急性淋巴细胞白血病。化疗后,她接受了异基因造血干细胞移植,6个月后她的嵌合率迅速降至接近零,没有HM复发的证据。然而,她出现了严重的多器官移植物抗宿主病样表现。DNA分析显示,移植物抗宿主病的发病机制是受体造血细胞HLA杂合性的丧失。
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引用次数: 0
High BRCA1 expression is an independent prognostic biomarker in LUAD and correlates with immune infiltration BRCA1高表达是LUAD的独立预后生物标志物,与免疫浸润相关
Pub Date : 2023-04-13 DOI: 10.1002/cai2.65
Fengzhu Guo, Cong Li, Shuning Liu, Zhijun Li, Jingtong Zhai, Zhiwu Wang, Binghe Xu

Lung adenocarcinoma (LUAD) patients with elevated breast cancer susceptibility gene 1 (BRCA1) expression had markedly worse overall survival and progression-free survival compared to those with reduced BRCA1 levels. In contrast, BRCA1 expression did not correlate with survival outcomes in squamous cell carcinoma patients. The overexpression of BRCA1 was an independent risk factor for LUAD and was indicative of an immune-suppressive tumor microenvironment.

与BRCA1水平降低的患者相比,乳腺癌症易感性基因1(BRCA1)表达升高的肺腺癌(LUAD)患者的总生存率和无进展生存率明显较差。相反,BRCA1的表达与鳞状细胞癌患者的生存结果无关。BRCA1的过度表达是LUAD的一个独立风险因素,表明肿瘤微环境具有免疫抑制作用。
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引用次数: 0
Correction to “Pooled analyses of randomized controlled trials on pyrotinib plus capecitabine and a rethink of the first-line options for HER2-positive relapsed or metastatic breast cancer” 更正“焦替尼加卡培他滨随机对照试验的汇总分析和对HER2阳性复发或转移性癌症一线选择的反思”
Pub Date : 2023-04-11 DOI: 10.1002/cai2.69

Guan X, Ma F, Xu B. Pooled analyses of randomized controlled trials on pyrotinib plus capecitabine and a rethink of the first-line options for HER2-positive relapsed or metastatic breast cancer. Cancer Innovation.2022;1-5.

In the funding information, the Grant/Award Number of National Nature Science Foundation of China was incorrect. The Grant/Award Number should be “82103634”.

We apologize for this error.

Guan X,Ma F,Xu B.对焦替尼加卡培他滨随机对照试验的汇总分析,以及对HER2阳性复发或转移性癌症一线选择的反思。癌症创新2022;1-5.在资助信息中,国家自然科学基金资助/奖励编号不正确。授予/奖励编号应为“82103634”。我们对此错误深表歉意。
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引用次数: 0
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Cancer Innovation
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