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Circulating serum exosomes i-tRF-AspGTC and tRF-1-SerCGA as diagnostic indicators for non-small cell lung cancer 作为非小细胞肺癌诊断指标的循环血清外泌体 i-tRF-AspGTC 和 tRF-1-SerCGA
Pub Date : 2024-03-19 DOI: 10.1007/s12094-024-03423-6
Jiefei Peng, Yue Zhang, Guangfei Zhou, Luolin Shao, Lin Li, Zhijun Zhang

Background

tRF-RNA—a representative of non-coding RNA (ncRNA)—is a precursor or fragment of mature tRNA and plays a crucial regulatory role in the occurrence and development of cancer. There is currently little research on tRF-RNA as a diagnostic marker in cancer, especially for NSCLC from serum exosomes.

Method

Serum exosomes were successfully extracted from serum; their physical morphology was captured by transmission electron microscopy (TEM); appropriate particle size detection was performed using qNano; surface labeling was verified through western blotting. Serum exosomes i-tRF-AspGTC and tRF-1-SerCGA were selected through gene microarray, and qPCR was used to validate their significance in 242 patients and 201 healthy individuals. The area under the curve (AUC) was used to evaluate the diagnostic indicators of non-small cell lung cancer (NSCLC).

Result

Compared with 201 healthy individuals, i-tRF-AspGTC and tRF-1-SerCGA were significantly downregulated in 242 NSCLC patients and 95 early-stage patients. For tRF-AspGTC and tRF-1-SerCGA, the predictive diagnostic efficiency rates of AUC were 0.690 and 0.680, respectively, whereas the early diagnostic efficiency rates were 0.656 and 0.688, respectively. The result of combined diagnosis with CEA and CYFRA21-1 was 0.928, and the early diagnostic efficiency was 0.843, which is a very high biological predictive factor for NSCLC.

Conclusion

The expression of serum exosomes i-tRF-AspGTC and tRF-1-SerCGA was significantly downregulated in NSCLC patients. These exosomes could be used as predictive indicators for diagnosis or early diagnosis of NSCLC.

背景tRF-RNA是非编码RNA(ncRNA)的代表,是成熟tRNA的前体或片段,在癌症的发生和发展中起着重要的调控作用。方法成功地从血清中提取了血清外泌体;用透射电子显微镜(TEM)捕捉了它们的物理形态;用qNano进行了适当的粒度检测;通过Western印迹验证了表面标记。通过基因芯片筛选出血清外泌体i-tRF-AspGTC和tRF-1-SerCGA,并在242名患者和201名健康人中使用qPCR验证其意义。结果与201名健康人相比,242名NSCLC患者和95名早期患者的i-tRF-AspGTC和tRF-1-SerCGA显著下调。tRF-AspGTC和tRF-1-SerCGA的预测诊断有效率AUC分别为0.690和0.680,早期诊断有效率分别为0.656和0.688。结论 在 NSCLC 患者中,血清外泌体 i-tRF-AspGTC 和 tRF-1-SerCGA 的表达显著下调。这些外泌体可作为诊断或早期诊断 NSCLC 的预测指标。
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引用次数: 0
Doxorubicin-induced chemoresistance in Duke’s type B colon adenocarcinoma cell line is aggravated in the presence of TGF-β2 through non-apoptotic cell death 多柔比星诱导的杜克 B 型结肠腺癌细胞系化疗耐药性在 TGF-β2 的存在下通过非凋亡性细胞死亡而加剧
Pub Date : 2024-02-03 DOI: 10.1007/s12094-023-03380-6
Sruthi Sritharan, Nageswaran Sivalingam

Background

The current challenge in clinical cancer treatment is chemoresistance. Colon cells have inherently higher xenobiotic transporters expression and hence can attain resistance rapidly. Increased levels of TGF-β2 expression in patients have been attributed to cancer progression, aggressiveness, and resistance. To investigate resistance progression, we treated doxorubicin (dox) to HT-29 colon adenocarcinoma cells in the presence or absence of TGF-β2 ligand.

Methods

After 1, 3-, and 7-day treatment, we investigated cell proliferation, viability, and cytotoxicity by MTT, trypan blue staining, and lactate dehydrogenase enzyme release. The mechanism of cell death was elucidated by hoechst33342 and propidium iodide dual staining and apoptosis assay. The development of resistance was detected by rhodamine123 efflux and P-glycoprotein (P-gp)/MDR1 antibody staining through fluorimetry and flow cytometry. The colony formation ability of the cells was also elucidated.

Results

Inhibition of cell proliferation was noted after day 1, while a significant reduction in viability and a significant increase in lactate dehydrogenase release was detected after day 3. Reduction of intracellular rhodamine123 levels was detected after day 3 and was significantly lower in dox with TGF-β2 treatment compared to dox alone. Increased surface P-gp levels after days 3 and 7 were observed in the treated groups. Hoechst33342/propidium iodide staining and apoptosis assay indicated non-apoptotic cell death. The cells treated with TGF-β2 had higher colony formation ability.

Conclusions

TGF-β2 expression might play a significant role in the development of chemoresistance to doxorubicin in Duke’s type B colon adenocarcinoma cell line, HT-29.

背景 目前临床癌症治疗面临的挑战是化疗耐药性。结肠细胞本身具有较高的异种生物转运体表达,因此可迅速产生耐药性。患者体内 TGF-β2 表达水平的升高被认为与癌症进展、侵袭性和耐药性有关。为了研究耐药性的进展,我们在有或没有 TGF-β2 配体的情况下对 HT-29 结肠腺癌细胞进行了多柔比星(dox)处理。方法在 1 天、3 天和 7 天的处理后,我们通过 MTT、胰蓝染色和乳酸脱氢酶释放来研究细胞的增殖、活力和细胞毒性。通过 hoechst33342 和碘化丙啶双重染色和细胞凋亡检测阐明了细胞死亡的机制。通过荧光测定法和流式细胞术,利用罗丹明123外流和P-糖蛋白(P-gp)/MDR1抗体染色检测耐药性的发展。结果第 1 天后发现细胞增殖受到抑制,第 3 天后发现细胞活力显著降低,乳酸脱氢酶释放量显著增加。第 3 天后检测到细胞内罗丹明 123 水平降低,与单独使用多克隆相比,多克隆与 TGF-β2 处理的罗丹明 123 水平明显降低。治疗组在第 3 天和第 7 天后观察到表面 P-gp 水平升高。Hoechst33342/propidium iodide 染色和细胞凋亡检测表明细胞未凋亡。结论TGF-β2 的表达可能在杜克 B 型结肠腺癌细胞株 HT-29 对多柔比星产生化疗耐药性的过程中起着重要作用。
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引用次数: 0
CAR-T cell therapy: a game-changer in cancer treatment and beyond CAR-T 细胞疗法:改变癌症治疗及其他领域的游戏规则
Pub Date : 2024-01-20 DOI: 10.1007/s12094-023-03368-2
Kumar Utkarsh, Namita Srivastava, Sachin Kumar, Azhar Khan, Gunjan Dagar, Mukesh Kumar, Mayank Singh, Shabirul Haque

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.

近年来,癌症已成为导致死亡的主要原因之一,全球每年约有 1 000 万人死于癌症。最先进的嵌合抗原受体(CAR)T 细胞免疫疗法已成为治疗癌症的有效方法。CAR-T 细胞疗法包括对从患者血液中提取的 T 细胞进行基因改造,然后输回患者体内。CAR-T 细胞免疫疗法大大提高了血液肿瘤的缓解率。目前,CAR-T 细胞疗法仅限于血液癌症,但人们正在努力开发更多的 CAR 构建,如双特异性 CAR、串联 CAR、抑制性 CAR、联合抗原、CRISPR 基因编辑和纳米颗粒递送。随着这些技术的进步,CAR-T 细胞疗法有望改善化疗和放疗等传统癌症治疗方法,同时减少相关毒性。本综述将介绍 CAR-T 细胞免疫疗法的最新进展和优势。
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引用次数: 0
Changes in the fecal microbiota of breast cancer patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis 基于 16S rRNA 基因测序的乳腺癌患者粪便微生物群变化:系统综述和荟萃分析
Pub Date : 2024-01-13 DOI: 10.1007/s12094-023-03373-5
Biqing Luan, Fei Ge, Xingjia Lu, Zhiqiang Li, Hong Zhang, Jingxuan Wu, Qizhi Yang, Liang Chen, Wenzhu Zhang, Wenlin Chen

Purpose

Breast cancer (BC) is a devastating disease for women. Microbial influences may be involved in the development and progression of breast cancer. This study aimed to investigate the difference in intestinal flora abundance between breast cancer patients and healthy controls (HC) based on previous 16S ribosomal RNA (rRNA) gene sequencing results, which have been scattered and inconsistent in previous studies.

Materials and methods

In agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched for pertinent literature in Pubmed, Embase, Cochrane Library, and Web of Science databases from build until February 1, 2023. Relative abundance, diversity of intestinal microflora by level, microbial composition, community structure, diversity index, and other related data were extracted. We used a fixed or random effects model for data analysis. We also conducted funnel plot analysis, sensitivity analysis, Egger's, and Begg’s tests to assess the bias risk.

Results

A total of ten studies involving 734 BC patients were enrolled. It was pointed out that there were significant differences in the Chao index between BC and HC in these studies [SMD = − 175.44 (95% CI − 246.50 to − 104.39)]. The relative abundance of Prevotellaceae [SMD = − 0.27 (95% CI − 0.39 to − 0.15)] and Bacteroides [SMD = 0.36 (95% CI 0.23–0.49)] was significantly different. In the included articles, the relative abundance of Prevotellaceae, Ruminococcus, Roseburia inulinivorans, and Faecalibacterium prausnitzii decreased in BC. Accordingly, the relative richness of Erysipelotrichaceae was high in BC.

Conclusions

This observational meta-analysis revealed that the changes in gut microbiota were correlated with BC, and the changes in some primary fecal microbiota might affect the beginning of breast cancer.

目的乳腺癌(BC)对女性来说是一种毁灭性疾病。微生物的影响可能与乳腺癌的发生和发展有关。本研究旨在根据以往研究中分散且不一致的 16S 核糖体 RNA(rRNA)基因测序结果,调查乳腺癌患者与健康对照组(HC)之间肠道菌群丰度的差异。材料与方法根据系统综述和荟萃分析首选报告项目(PRISMA),我们在 Pubmed、Embase、Cochrane Library 和 Web of Science 数据库中检索了从建立到 2023 年 2 月 1 日的相关文献。提取了相对丰度、各级肠道微生物菌群的多样性、微生物组成、群落结构、多样性指数和其他相关数据。我们采用固定效应或随机效应模型进行数据分析。我们还进行了漏斗图分析、敏感性分析、Egger's 检验和 Begg's 检验,以评估偏倚风险。研究指出,在这些研究中,BC和HC的Chao指数存在显著差异[SMD = - 175.44 (95% CI - 246.50 to - 104.39)]。前鞭毛菌科(Prevotellaceae)[SMD = - 0.27 (95% CI - 0.39 to - 0.15)]和乳杆菌(Bacteroides)[SMD = 0.36 (95% CI 0.23-0.49)]的相对丰度存在显著差异。在所收录的文章中,前鞭毛菌科(Prevotellaceae)、反刍球菌(Ruminococcus)、Roseburia inulinivorans 和普氏粪杆菌(Faecalibacterium prausnitzii)的相对丰度在 BC 中有所下降。结论这项观察性荟萃分析表明,肠道微生物群的变化与乳腺癌相关,一些原发性粪便微生物群的变化可能会影响乳腺癌的发病。
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引用次数: 0
MicroRNA-128 acts as a suppressor in the progression of gastrointestinal stromal tumor by targeting B-lymphoma Mo-MLV insertion region 1 MicroRNA-128通过靶向B淋巴瘤Mo-MLV插入区1抑制胃肠道间质瘤的进展
Pub Date : 2023-12-16 DOI: 10.1007/s12094-023-03354-8
Jinbao Wu, Changjuan Wang, Xia Cui, Lin Liu, Lu Wang, Jing Wang, Xiaohui Xue, Tong Dang

Introduction

The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism.

Methods

Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed.

Results

We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells.

Conclusion

Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.

简介:microRNA-128(miR-128)在胃肠道相关疾病中的关键作用已被证实。本研究试图阐明 miR-128 在胃肠道间质瘤(GIST)中的特殊作用及其内在机制。然后,对临床组织样本和细胞系中 miR-128 和 B 淋巴瘤 Mo-MLV 插入区 1(BMI-1)的表达模式进行了表征,并验证了它们之间的相关性。结果我们在 78 名患者的 GIST 组织和 4 个 GIST 细胞系中发现了 miR-128 的低表达和 BMI-1 的高表达。异位表达 miR-128 或沉默 BMI-1 可抑制 GIST-T1 细胞的恶性潜能。作为 miR-128 的靶点,BMI-1 的再次表达可以部分抵消 miR-128 对 GIST-T1 细胞恶性程度的抑制作用。
{"title":"MicroRNA-128 acts as a suppressor in the progression of gastrointestinal stromal tumor by targeting B-lymphoma Mo-MLV insertion region 1","authors":"Jinbao Wu, Changjuan Wang, Xia Cui, Lin Liu, Lu Wang, Jing Wang, Xiaohui Xue, Tong Dang","doi":"10.1007/s12094-023-03354-8","DOIUrl":"https://doi.org/10.1007/s12094-023-03354-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiovascular comorbidities and their prognostic value in small cell lung cancer patients with chemoradiotherapy 小细胞肺癌化疗患者的心血管合并症及其预后价值
Pub Date : 2023-12-16 DOI: 10.1007/s12094-023-03359-3
Hanyang Liang, Tianjie Wang, Dong Liu, Hao Wang, Zhengqing Ba, Ying Xiao, Yilu Liu, Jiansong Yuan, Weixian Yang

Background

Small cell lung cancer (SCLC) is an extremely malignant subtype of lung cancer because of its high potential for metastases. Cardiac invasion of SCLC is a serious concern that may lead to systemic embolism or tract obstruction. It has aroused much concern that cardiovascular comorbidities may significantly affect the survival of SCLC patients and their treatment decisions.

Methods

We consecutively recruited 772 small cell lung cancer (SCLC) patients between January 2011 and December 2018 from 4 cancer specialty hospitals in China. Only newly diagnosed primary cancer inpatients were included. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratios (HRs) for mortality and corresponding 95% confidence intervals (95% CIs) were calculated.

Results

The prevalence of cardiovascular diseases (CVDs) was 34.6% in all SCLC patients. Log-rank analysis presented statistically significant differences in median survival time (MST) between patients with CVD and without CVD in all SCLC patients (9.0 months vs. 15.0 months, P = 0.005) and patients with chemotherapy only (12.0 months vs. 18.0 months, P = 0.048). Pericardial effusion (HR 1.671, 95% CI 1.082–2.580, P = 0.021) and heart failure (HR 1.752, 95% CI 1.290–2.379, P < 0.001) were independent risk factors associated with mortality in all SCLC patients. VTE is related to poorer prognosis in patients with chemotherapy only (HR 5.558, 95% CI 1.335–23.135, P = 0.018) and chemoradiotherapy (HR 3.057, 95% CI 1.270–7.539, P = 0.013).

Conclusions

Comprehensive management of CVD comorbidities is of vital importance for the long-term prognosis of SCLC patients.

背景小细胞肺癌(SCLC)是肺癌中恶性程度极高的一种亚型,因为它极有可能发生转移。小细胞肺癌的心脏侵犯是一个严重问题,可能导致全身性栓塞或呼吸道梗阻。心血管合并症可能会严重影响SCLC患者的生存及其治疗决策,这引起了人们的广泛关注。方法我们在2011年1月至2018年12月期间从中国的4家肿瘤专科医院连续招募了772名小细胞肺癌(SCLC)患者。仅纳入新诊断的原发性癌症住院患者。采用单变量和多变量调整 Cox 比例危险模型评估与死亡率相关的风险因素。结果所有SCLC患者的心血管疾病(CVDs)患病率为34.6%。对数秩分析显示,在所有SCLC患者(9.0个月 vs. 15.0个月,P = 0.005)和仅接受化疗的患者(12.0个月 vs. 18.0个月,P = 0.048)中,有CVD和无CVD患者的中位生存时间(MST)差异有统计学意义。心包积液(HR 1.671,95% CI 1.082-2.580,P = 0.021)和心力衰竭(HR 1.752,95% CI 1.290-2.379,P <0.001)是与所有SCLC患者死亡率相关的独立危险因素。VTE与仅接受化疗(HR 5.558,95% CI 1.335-23.135,P = 0.018)和化放疗(HR 3.057,95% CI 1.270-7.539,P = 0.013)的患者预后较差有关。
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引用次数: 0
Exploratory analyses of treatment subgroup interaction by PD-L1 status and according to PD-L1 expression in the JAVELIN Bladder 100 trial JAVELIN Bladder 100试验中按PD-L1状态和PD-L1表达对治疗亚组相互作用的探索性分析
Pub Date : 2023-12-15 DOI: 10.1007/s12094-023-03358-4
Miguel Ángel Climent, Carlos Álvarez, Rafael Morales, Pablo Maroto, Alejo Rodríguez-Vida, María José Méndez-Vidal, Xavier García del Muro, Javier Puente, Nuria Láinez, Sergio Vázquez, Daniel Castellano, Carmen Gómez Lang, Jing Wang, Alessandra di Pietro, Craig Davis, Belén Sanz-Castillo, M. Victoria Bolós, Begoña P. Valderrama

Purpose

Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC).Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Everything is correct

Methods

JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay).

Results

No significant interaction between treatment and PD-L1 status was observed for OS. Clinically meaningful and robust survival data were observed in favor of avelumab using the different ≥ 1% TC/IC PD-L1 expression cutoff.

Conclusions

These results demonstrate the benefit of avelumab maintenance in la/mUC regardless of PD-L1 expression, consistent with approved labels.

目的对阿维列单抗维持治疗局部晚期/转移性尿路上皮癌(la/mUC)的JAVELIN Bladder 100试验进行事后分析,以确定程序性死亡配体1(PD-L1)状态对总生存期(OS)的交互作用,并根据肿瘤细胞或免疫细胞(TC/IC)中≥1%的不同PD-L1表达截断值对生存期进行额外分析。请检查并确认作者及其各自的所属单位是否已被正确识别,如有必要请进行修改。方法JAVELIN Bladder 100数据被用于分析PD-L1状态(按试验中使用的截断值)对OS的交互作用,以及按不同的≥1% TC/IC PD-L1表达截断值(Ventana SP263检测)进行的OS和无进展生存期(PFS)分析。使用不同的≥1% TC/IC PD-L1 表达截止值,观察到的有临床意义的、稳健的生存数据有利于阿维单抗。结论这些结果表明,无论 PD-L1 表达如何,阿维单抗在 la/mUC 中的维持治疗均有获益,这与批准的标签一致。
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引用次数: 0
High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China 头颈部腺样囊性癌高级别转化显示出独特的临床病理特征和不良预后:中国最大系列的匹配病例对照研究
Pub Date : 2023-12-14 DOI: 10.1007/s12094-023-03357-5
Ting-yao Ma, Jun Wu, Shi-zhi He, Xue-lian Wang, Guo-liang Yang, Shu-jing Zhang, Jin Zhou, Yi-ming Ding, Li-feng Li, Hong-fei Liu, Lan-lan Xuan, Xiao-hong Chen

Purpose

Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications.

Methods

A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes.

Results

The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group.

Conclusion

This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

目的 在腺样囊性癌(ACC)罕见的高级别转化(HGT)中,本研究对其侵袭性和临床影响提供了前所未有的见解。方法 从412例ACC病例中提取23例HGT患者与非HGT患者进行1:1匹配比较,重点剖析独特的临床病理特征和预后结果。值得注意的是,实性亚型是 HGT 中最常见的类型,占 69.6%。与非HGT相比,HGT队列的淋巴结转移率(39.1% vs. 8.7%; P <0.05)、神经周围浸润率(60.9% vs. 26.1%; P <0.05)和Ki-67增殖指数(35.0% vs. 10.0%; P <0.05)明显更高。此外,HGT区域通常显示出p63表达减少或缺失,以及高级别病理形态。HGT与复发(55.0%)和远处转移(78.3%)增加有关,导致平均生存期为35.9个月,3年死亡率为35.0%。结论这项研究是我们所知的规模最大的单中心 HGT 病例群,强调了其在鼻窦和泪腺的频繁发生以及与较差预后的关联。研究结果支持将 ACC 中的 HGT 分为 4 级,以反映其严重程度。
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引用次数: 0
Transforming growth factors β and their signaling pathway in renal cell carcinoma and peritumoral space—transcriptome analysis 肾细胞癌及其瘤周空间中的转化生长因子 β 及其信号通路--转录组分析
Pub Date : 2023-12-12 DOI: 10.1007/s12094-023-03350-y
Dariusz Kajdaniuk, Dorota Hudy, Joanna Katarzyna Strzelczyk, Krystyna Młynarek, Szymon Słomian, Andrzej Potyka, Ewa Szymonik, Janusz Strzelczyk, Wanda Foltyn, Beata Kos-Kudła, Bogdan Marek

Purpose

The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?.

Methods

Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR.

Results

The study showed that the expression of the genes of TGFβ/Smads pathway is dysregulated in both RCC and the TME: TGFβ1, TGFβ3 expression is increased in the TME in comparison to the NK tissues; TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFβRI, TGFβRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues.

Conclusion

On the one hand, the underexpression of the TGFβ signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFβ/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.

目的 该研究旨在验证以下假设:转化生长因子TGFβ1-3、其受体TGFβI-III和细胞内信使蛋白Smad1-7是否与肾癌的发病机制有关?TGFβ/Smads通路基因在肾细胞癌(RCC)组织、瘤周组织(TME;肿瘤微环境)和正常肾脏(NK)组织中的表达情况如何? 方法20例接受全肾切除术的RCC患者被纳入分子分析。通过 RT-qPCR 对这些基因的 mRNA 表达进行定量分析。结果研究表明,TGFβ/Smads通路基因在RCC和TME中均表达失调:与 NK 组织相比,TME 中 TGFβ1、TGFβ3 表达增加;与 TME 组织相比,RCC 中 TGFβ2、TGFβ3、TGFβRI、TGFβRIII、Smad1、Smad2、Smad3 和 Smad6 表达不足;与 NK 组织相比,RCC 中 TGFβRI、TGFβRIII 和 Smad2 表达不足。结论 一方面,TGFβ信号通路基因在恶性肿瘤中表达不足可能导致该细胞因子失去抗增殖和促凋亡活性。另一方面,TME 中的 TGFβ/Smads 信号通路基因表达量高于肿瘤或 NK 组织,很可能会对肿瘤周围空间产生免疫抑制作用,并可能对 TME 中的非肿瘤细胞产生抗增殖和促凋亡作用。该区域的功能和形态一致性可能决定肿瘤的侵袭性和肿瘤扩散的时间。
{"title":"Transforming growth factors β and their signaling pathway in renal cell carcinoma and peritumoral space—transcriptome analysis","authors":"Dariusz Kajdaniuk, Dorota Hudy, Joanna Katarzyna Strzelczyk, Krystyna Młynarek, Szymon Słomian, Andrzej Potyka, Ewa Szymonik, Janusz Strzelczyk, Wanda Foltyn, Beata Kos-Kudła, Bogdan Marek","doi":"10.1007/s12094-023-03350-y","DOIUrl":"https://doi.org/10.1007/s12094-023-03350-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The study showed that the expression of the genes of TGFβ/Smads pathway is dysregulated in both RCC and the TME: TGFβ1, TGFβ3 expression is increased in the TME in comparison to the NK tissues; TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFβRI, TGFβRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>On the one hand, the underexpression of the TGFβ signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFβ/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138577273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparing the survival rates of patients with stage IIIC endometrial cancer undergoing sandwich therapy to those undergoing sequential chemotherapy and radiotherapy: a meta-analysis 比较接受三明治疗法和连续化疗及放疗的 IIIC 期子宫内膜癌患者的生存率:一项荟萃分析
Pub Date : 2023-12-11 DOI: 10.1007/s12094-023-03355-7
Meng-Meng Zhang, Yu-Kun Chen, Li Shi, Jing Ma, Jing-De Jia, Xi-Wa Zhao

Background

The use of additional treatment after surgery for stage IIIC endometrial cancer (EC) according to the Federation of Gynecology and Obstetrics (FIGO) is still a topic of discussion. This meta-analysis examined the effects of sandwich treatment and sequential treatment on the survival of individuals diagnosed with stage IIIC EC.

Methods

We examined the literature from various databases regarding the overall survival (OS) and adverse effects of the two additional therapies following surgery in individuals diagnosed with stage IIIC EC. Revman 5.4.1 was utilized to combine hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) for OS and toxicities.

Results

The findings comprised of five retrospective investigations involving a combined total of 800 individuals. The patients who underwent sandwich treatment did not demonstrate a notable improvement in survival rates over a period of 3 years. Upon eliminating the impact of extensive samples, it was discovered that sandwich therapy exhibited a superior 5-year overall survival compared to patients receiving sequential therapy. The effectiveness of sandwich therapy was superior to sequential therapy in terms of a 3-year OS for non-endometrioid histology, although the outcome did not reach statistical significance. The toxicities of both treatments were similar.

Conclusions

In terms of long-term survival, sandwich therapy was found to be more advantageous than sequential therapy for patients with stage IIIC EC, with no significant disparity observed in the 3-year OS and toxicities between the two treatments. Sandwich therapy exhibited a tendency towards improved effectiveness in patients with histology other than endometrioid.

背景根据妇产科联盟(FIGO)的规定,IIIC期子宫内膜癌(EC)手术后使用额外治疗仍是一个讨论话题。这项荟萃分析研究了夹心治疗和序贯治疗对确诊为IIIC期EC患者生存期的影响。方法我们研究了各种数据库中关于确诊为IIIC期EC患者术后两种额外疗法的总生存期(OS)和不良反应的文献。结果研究结果包括五项回顾性调查,共涉及 800 名患者。接受三明治治疗的患者在3年内的生存率没有明显改善。在剔除大量样本的影响后,发现三明治疗法的 5 年总生存率优于接受连续疗法的患者。就非子宫内膜样组织学而言,三明治疗法的3年生存率优于序贯疗法,但结果未达到统计学意义。结论 对于IIIC期EC患者,就长期生存率而言,三明治疗法比序贯疗法更有优势,两种疗法的3年生存率和毒性均无明显差异。夹心疗法对子宫内膜异位症以外组织学的患者有改善疗效的趋势。
{"title":"Comparing the survival rates of patients with stage IIIC endometrial cancer undergoing sandwich therapy to those undergoing sequential chemotherapy and radiotherapy: a meta-analysis","authors":"Meng-Meng Zhang, Yu-Kun Chen, Li Shi, Jing Ma, Jing-De Jia, Xi-Wa Zhao","doi":"10.1007/s12094-023-03355-7","DOIUrl":"https://doi.org/10.1007/s12094-023-03355-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The use of additional treatment after surgery for stage IIIC endometrial cancer (EC) according to the Federation of Gynecology and Obstetrics (FIGO) is still a topic of discussion. This meta-analysis examined the effects of sandwich treatment and sequential treatment on the survival of individuals diagnosed with stage IIIC EC.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We examined the literature from various databases regarding the overall survival (OS) and adverse effects of the two additional therapies following surgery in individuals diagnosed with stage IIIC EC. Revman 5.4.1 was utilized to combine hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) for OS and toxicities.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The findings comprised of five retrospective investigations involving a combined total of 800 individuals. The patients who underwent sandwich treatment did not demonstrate a notable improvement in survival rates over a period of 3 years. Upon eliminating the impact of extensive samples, it was discovered that sandwich therapy exhibited a superior 5-year overall survival compared to patients receiving sequential therapy. The effectiveness of sandwich therapy was superior to sequential therapy in terms of a 3-year OS for non-endometrioid histology, although the outcome did not reach statistical significance. The toxicities of both treatments were similar.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>In terms of long-term survival, sandwich therapy was found to be more advantageous than sequential therapy for patients with stage IIIC EC, with no significant disparity observed in the 3-year OS and toxicities between the two treatments. Sandwich therapy exhibited a tendency towards improved effectiveness in patients with histology other than endometrioid.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138568002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Clinical and Translational Oncology
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