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Assessing Sarcopenia in Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Case Series 评估接受新辅助化疗的晚期卵巢癌患者的肌肉疏松症:病例系列。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2155
Christelle Schofield, Dennis R. Taaffe, Robert U. Newton, Daniel A. Galvão, Paul A. Cohen, Jin-Soo Kim, Tarek Meniawy, Carolyn Peddle-McIntyre

Objectives

In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer-related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy.

Methods

We assessed sarcopenia risk with the SARC-F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point <16 kg) and five times sit-to-stand test (cut point >15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point <38.5 cm2/m2), and physical performance with a 4-m gait speed test (cut point ≤0.8 m/s).

Results

Of six participants, none were identified as “at risk” for sarcopenia based on SARC-F scores. Two participants were severely sarcopenic based on EWGSOP2 criteria (had low muscle strength, mass, and physical performance), and five participants were sarcopenic based on muscle mass only.

Discussion

Ovarian cancer patients with low muscle mass during neoadjuvant chemotherapy may not be identified as sarcopenic based on the EWGSOP2 diagnostic algorithm. While lacking a universally accepted definition for cancer-related sarcopenia and cancer-specific recommendations for the screening, diagnosis, and treatment of sarcopenia, ovarian cancer clinicians should focus on the diagnosis and treatment of low muscle mass and density.

目的:在卵巢癌和其他癌症中,低肌肉质量和密度与较差的临床预后有关。然而,与癌症相关的肌肉疏松症(通常定义为肌肉质量低)筛查并未常规开展。欧洲老年人肌肉疏松症工作组(EWGSOP)推荐了一种在临床环境中进行肌肉疏松症筛查和诊断的算法,根据肌肉力量和质量以及体能表现来判断肌肉疏松症的严重程度。我们探讨了 EWGSOP2 算法在六名接受新辅助化疗的卵巢癌患者肌少症评估中的应用:我们使用 SARC-F 筛选问卷评估了肌肉疏松症的风险(风险≥4 分),使用手握力测试评估了肌肉力量(切点为 15 秒),使用骨骼肌指数评估了肌肉质量(根据单张计算机断层扫描 [CT] 图像计算的骨骼肌指数,单位为 cm2/m2;切点为 2/m2),使用 4 米步速测试评估了身体表现(切点为≤0.8 米/秒):根据 SARC-F 评分,六名参与者中没有人被确定为 "高危 "肌肉疏松症患者。根据 EWGSOP2 标准(肌肉力量、质量和体能低下),两名参与者属于严重肌少症,五名参与者仅根据肌肉质量属于肌少症:讨论:根据 EWGSOP2 诊断算法,在新辅助化疗期间肌肉质量较低的卵巢癌患者可能不会被认定为肌无力患者。卵巢癌临床医生在筛查、诊断和治疗与癌症相关的肌少症方面缺乏公认的定义和针对特定癌症的建议,因此应重点关注低肌肉质量和密度的诊断和治疗。
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引用次数: 0
Survival Outcomes in Older Adult Acute Lymphoblastic Leukemia Patients Analyzed by Facility Volume and Type: A National Cancer Database Analysis 按医疗机构数量和类型分析老年急性淋巴细胞白血病患者的生存结果:全国癌症数据库分析》。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2162
Kaitlyn C. Dykes, Jiling Chou, Allison O. Taylor, Albert C. Shu, Sarah E. Mudra, Xiaoyang Ma, Jaeil Ahn, Catherine E. Lai

Bakground

It is important to understand the outcomes of adult acute lymphoblastic leukemia (ALL) patients at different facilities as treatment paradigms change.

Aims

Our primary objective was to determine adult ALL overall survival (OS) by facility volume and type. Secondary objectives included identifying sociodemographic factors that may have impacted outcomes and analyzing treatment patterns by facility volume and type.

Methods

This was a retrospective analysis of the National Cancer Database (NCDB) that included patients ≥40 years diagnosed with ALL between 2004 and 2016.

Results

A total of 14 593 patients were included in this study. Univariate OS was greatest at low volume (LV) and community programs (CPs) and the least at high volume (HV) and academic programs (AP). This difference was lost after multivariable Cox proportional hazards model analysis, which found no difference in survival by facility volume or type, however, survival was significantly influenced by age, race, Hispanic ethnicity, insurance, and residence location (p < 0.05). Patients treated at HV and APs compared to LV and CP received more anti-neoplastic directed therapy.

Conclusion

Our results suggest treatment facility volume and type do not impact older adult ALL patient (≥40 years) survival, however confounding sociodemographic differences do impact survival outcomes, despite more aggressive and novel treatment approaches provided at HV and APs.

背景:随着治疗模式的改变,了解成人急性淋巴细胞白血病(ALL)患者在不同医疗机构的治疗效果非常重要。目的:我们的首要目标是根据医疗机构的规模和类型确定成人ALL的总生存率(OS)。次要目标包括确定可能影响疗效的社会人口学因素,并根据医疗机构的规模和类型分析治疗模式:这是一项对国家癌症数据库(NCDB)的回顾性分析,其中包括2004年至2016年间确诊为ALL的年龄≥40岁的患者:本研究共纳入14 593名患者。单变量OS在低容量(LV)和社区项目(CPs)中最大,在高容量(HV)和学术项目(AP)中最小。多变量考克斯比例危险模型分析发现,设施数量或类型对存活率没有影响,但年龄、种族、西班牙裔、保险和居住地对存活率有显著影响(P 结论:我们的研究结果表明,治疗设施数量和类型对存活率没有影响:我们的研究结果表明,治疗机构的数量和类型不会影响老年 ALL 患者(≥40 岁)的存活率,但是,尽管 HV 和 AP 提供了更积极、更新颖的治疗方法,社会人口统计学差异仍会影响存活率。
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引用次数: 0
RNF135 Promotes Human Osteosarcoma Cell Growth and Inhibits Apoptosis by Upregulating the PI3K/AKT Pathway RNF135 通过上调 PI3K/AKT 通路促进人骨肉瘤细胞生长并抑制其凋亡
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2159
Bingyao Chen, Yinglong Zhang, Guangze Song, Xing Wei

Background

Ring finger protein 135 (RNF135) is an E3 ubiquitin ligase that has been implicated in the tumorigenesis of multiple human malignancies. However, whether RNF135 plays a role in the development of human osteosarcoma (OS) remains unknown.

Methods

RNF135 expression in 20 human OS and 20 human osteochondroma specimens were evaluated by means of immunohistochemistry staining. The effects of shRNA-mediated RNF135 knockdown on human OS cell growth and apoptosis were evaluated through a panel of in vitro studies on cell proliferation, colony formation, exposure of phosphatidylserine on the cell surface, and caspase 3/7 activation. The protein levels of PI3K, AKT, and p-AKT were determined by western blot analysis.

Results

We detected significantly higher RNF135 levels in human OS tissues than human osteochondroma tissues. In in vitro studies, shRNA-mediated RNF135 knockdown in human OS cells inhibited proliferation and induced apoptosis. In addition, RNF135 knockdown reduced PI3K and p-AKT protein levels and activated caspase 3 and 7.

Conclusions

These results supported that RNF135 contributes to human OS development through PI3K/AKT-dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.

背景:环指蛋白135(RNF135)是一种E3泛素连接酶,与多种人类恶性肿瘤的肿瘤发生有关。然而,RNF135是否在人类骨肉瘤(OS)的发病过程中发挥作用仍是未知数:方法:通过免疫组化染色评估了20例人类OS和20例人类骨软骨瘤标本中RNF135的表达。通过对细胞增殖、集落形成、细胞表面磷脂酰丝氨酸暴露和 caspase 3/7 激活等一系列体外研究,评估了 shRNA 介导的 RNF135 基因敲除对人类 OS 细胞生长和凋亡的影响。PI3K、AKT和p-AKT的蛋白水平通过Western印迹分析进行测定:结果:我们在人类OS组织中检测到的RNF135水平明显高于人类骨软骨瘤组织。在体外研究中,shRNA介导的人OS细胞RNF135敲除抑制增殖并诱导凋亡。此外,RNF135敲除可降低PI3K和p-AKT蛋白水平,激活caspase 3和7:这些结果支持RNF135通过PI3K/AKT依赖性机制促进人类OS的发展。以RNF135为靶点可能为治疗这种人类恶性肿瘤提供一种新的治疗方法。
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引用次数: 0
Evaluation of different methods of transoral minimally invasive surgery for supraglottic laryngeal carcinoma 经口微创手术治疗声门上型喉癌的不同方法评估。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2077
Lingwa Wang, Qi Zhong, Fan Yang, Lizhen Hou, Hongzhi Ma, Ling Feng, Shizhi He, Yifan Yang, Jugao Fang, Ru Wang

Background and objectives

To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors.

Methods

Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence-free survival (RFS), and postoperative functions were analyzed.

Results

Sixty-two patients were early-stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty-eight patients were scored Grade-1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan–Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki-67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS.

Conclusions

The positive margin, Ki-67 index ≥40% and P53(+)&Ki-67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.

背景与目的分析经口微创手术(TMIS)治疗声门上型喉癌(SGLC)的肿瘤学和功能效果,并研究独立的预后因素:方法:纳入70例接受TMIS治疗的声门上型喉癌患者。方法:纳入70例接受TMIS治疗的SGLC患者,分析其总生存期(OS)、无复发生存期(RFS)和术后功能:62例患者为早期(Tis、T1和T2),8例患者为T3。11名患者接受了术前诱导化疗(IC)。60名患者接受了经口激光显微手术(TLM),10名患者接受了经口机器人手术(TORS)。58名患者通过水吞咽测试被评为1级,49名患者通过等级、粗糙度、呼吸困难、气喘、劳累被评为0级。所有患者的 1、3 和 5 年 OS 分别为 95.450%、84.877% 和 78.026%,RFS 分别为 89.167%、78.052% 和 75.451%。Kaplan-Meier生存分析显示,N分期和临床分期与OS相关,吸烟、临床分期、手术切缘和Ki-67指数与RFS相关。术前IC或直接手术、TLM或TORS无明显差异。Cox分析显示,吸烟和手术切缘是RFS的独立预后因素:结论:阳性边缘、Ki-67指数≥40%和P53(+)&Ki-67指数≥40%是影响SGLC患者复发的较差因素。吸烟和手术切缘都是影响复发的独立预后因素。
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引用次数: 0
IBSP Promotes Breast Cancer Bone Metastasis and Proliferation via BMP-SMAD Signaling Pathway IBSP 通过 BMP-SMAD 信号通路促进乳腺癌骨转移和增殖
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2153
Wei Ding, Di Lv, Mengshen Wang, Dongsheng Pei

Background

Integrin-Binding Sialoprotein (IBSP) has been implicated in tumor progression across various cancers. However, the specific role of IBSP in breast cancer remains underexplored. There is a need to investigate the mechanisms by which IBSP influences breast cancer progression and its potential as a therapeutic target.

Aims

This study aims to elucidate the role of IBSP in breast cancer, particularly its impact on tumor progression and its relationship with prognosis. We also seek to understand the underlying mechanisms, including the involvement of the BMP-SMAD signaling pathway, and to explore the potential of targeting IBSP for therapeutic interventions.

Methods and Results

Overexpression of IBSP in breast cancer cells led to increased migration and invasion, whereas IBSP interference reduced these behaviors, indicating its role in enhancing tumor progression. Differentially expressed genes were significantly enriched in the BMP-SMAD signaling pathway, a critical pathway for osteogenic differentiation. Transcription Factor Binding: Dual luciferase reporter assays demonstrated that SMAD4 specifically binds to the IBSP promoter, establishing a regulatory link between SMAD4 and IBSP expression. Silencing IBSP (si-IBSP) mitigated the effects of SMAD4-induced tumor proliferation, confirming that IBSP acts as a downstream target of SMAD4 in the BMP signaling pathway.

Conclusion

Our study reveals that IBSP plays a significant role in breast cancer progression through the BMP-SMAD4 signaling pathway. Targeting IBSP could be a promising therapeutic strategy for breast cancer treatment. Further research into IBSP inhibitors may offer new avenues for improving treatment outcomes and managing breast cancer more effectively.

背景:Integrin-Binding Sialoprotein (IBSP) 与各种癌症的肿瘤进展有关。然而,IBSP 在乳腺癌中的具体作用仍未得到充分探索。目的:本研究旨在阐明 IBSP 在乳腺癌中的作用,尤其是对肿瘤进展的影响及其与预后的关系。我们还试图了解其潜在的机制,包括 BMP-SMAD 信号通路的参与,并探索以 IBSP 为靶点进行治疗干预的潜力:乳腺癌细胞过表达IBSP会导致迁移和侵袭增加,而干扰IBSP则会减少这些行为,这表明IBSP在促进肿瘤进展中的作用。差异表达的基因明显富集于BMP-SMAD信号通路,这是成骨分化的关键通路。转录因子结合:双荧光素酶报告实验表明,SMAD4 与 IBSP 启动子特异性结合,建立了 SMAD4 与 IBSP 表达之间的调控联系。沉默 IBSP(si-IBSP)可减轻 SMAD4 诱导的肿瘤增殖的影响,证实了 IBSP 是 SMAD4 在 BMP 信号通路中的下游靶点:结论:我们的研究揭示了IBSP通过BMP-SMAD4信号通路在乳腺癌进展过程中发挥着重要作用。以 IBSP 为靶点可能是一种很有前景的乳腺癌治疗策略。对 IBSP 抑制剂的进一步研究可能会为改善治疗效果和更有效地控制乳腺癌提供新的途径。
{"title":"IBSP Promotes Breast Cancer Bone Metastasis and Proliferation via BMP-SMAD Signaling Pathway","authors":"Wei Ding,&nbsp;Di Lv,&nbsp;Mengshen Wang,&nbsp;Dongsheng Pei","doi":"10.1002/cnr2.2153","DOIUrl":"10.1002/cnr2.2153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Integrin-Binding Sialoprotein (IBSP) has been implicated in tumor progression across various cancers. However, the specific role of IBSP in breast cancer remains underexplored. There is a need to investigate the mechanisms by which IBSP influences breast cancer progression and its potential as a therapeutic target.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to elucidate the role of IBSP in breast cancer, particularly its impact on tumor progression and its relationship with prognosis. We also seek to understand the underlying mechanisms, including the involvement of the BMP-SMAD signaling pathway, and to explore the potential of targeting IBSP for therapeutic interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Overexpression of IBSP in breast cancer cells led to increased migration and invasion, whereas IBSP interference reduced these behaviors, indicating its role in enhancing tumor progression. Differentially expressed genes were significantly enriched in the BMP-SMAD signaling pathway, a critical pathway for osteogenic differentiation. Transcription Factor Binding: Dual luciferase reporter assays demonstrated that SMAD4 specifically binds to the IBSP promoter, establishing a regulatory link between SMAD4 and IBSP expression. Silencing IBSP (si-IBSP) mitigated the effects of SMAD4-induced tumor proliferation, confirming that IBSP acts as a downstream target of SMAD4 in the BMP signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study reveals that IBSP plays a significant role in breast cancer progression through the BMP-SMAD4 signaling pathway. Targeting IBSP could be a promising therapeutic strategy for breast cancer treatment. Further research into IBSP inhibitors may offer new avenues for improving treatment outcomes and managing breast cancer more effectively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 8","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia 鉴定家族性急性髓性白血病的新型潜在致病变异基因
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2141
Chiara Ronchini, Federica Gigli, Martina Fontanini, Raffaella Furgi, Viviana Amato, Fabio Giglio, Giuliana Gregato, Francesco Bertolini, Michela Rondoni, Francesco Lanza, Atto Billio, Enrico Derenzini, Corrado Tarella, Pier Giuseppe Pelicci, Myriam Alcalay, Elisabetta Todisco

Background

Myeloid neoplasms, including acute myeloid leukemia, have been traditionally among the less investigated cancer types concerning germline predisposition. Indeed, myeloid neoplasms with germline predisposition are challenging to identify because often display similar clinical and morphological characteristics of sporadic cases and have similar age at diagnosis. However, a misidentifications of familiarity in myeloid neoplasms have a critical impact on clinical management both for the carriers and their relatives.

Aims

We conducted a family segregation study, in order to identify novel cancer predisposing genes in myeloid neoplasms and classify novel identified variants.

Methods and Results

We performed a thorough genomic analysis using a large custom gene panel (256 genes), the Myelo-Panel, targeted on cancer predisposing genes. In particular, we assessed both germline and somatic variants in four families, each with two siblings, who developed hematological neoplasms: seven acute myeloid leukemia and one Philadelphia-positive chronic myeloid leukemia. In each family, we identified at least one novel potentially predisposing variant, affecting also genes not included in the current European LeukemiaNet guidelines for AML management. Moreover, we suggest reclassification of two germline variants as pathogenic: likely pathogenic p.S21Tfs*139 in CEPBA and VUS p.K392Afs*66 in DDX41.

Conclusion

We believe that predisposition to hematological neoplasms is still underestimated and particularly difficult to diagnosed. Considering that misidentification of familiarity in myeloid neoplasms have a critical impact on the clinical management both for the carriers and their relatives, our study highlights the importance of revision, in this clinical context, of clinical practices that should include thorough reconstruction of family history and in-depth genetic testing.

背景:髓系肿瘤(包括急性髓系白血病)历来是对种系倾向性研究较少的癌症类型之一。事实上,具有种系倾向的髓系肿瘤很难鉴别,因为其临床和形态特征往往与散发性病例相似,而且确诊时的年龄也相似。目的:我们进行了一项家系分离研究,以鉴定髓样肿瘤中的新型癌症易感基因,并对鉴定出的新型变异进行分类:我们使用一个大型定制基因面板(256 个基因)--髓系面板(Myelo-Panel),针对癌症易感基因进行了全面的基因组分析。特别是,我们评估了四个家族的种系变异和体细胞变异,每个家族都有两个罹患血液肿瘤的兄弟姐妹:七个急性髓性白血病家族和一个费城阳性慢性髓性白血病家族。在每个家族中,我们都发现了至少一种新的潜在易感变体,这些变体影响的基因也未被纳入当前欧洲白血病网络(European LeukemiaNet)急性髓细胞白血病管理指南中。此外,我们建议将两个种系变异重新归类为致病变异:CEPBA 中的 p.S21Tfs*139 可能致病,DDX41 中的 p.K392Afs*66 VUS:我们认为,血液肿瘤的易感性仍被低估,尤其难以诊断。考虑到对髓细胞肿瘤熟悉性的误诊会对携带者及其亲属的临床治疗产生至关重要的影响,我们的研究强调了在这种临床背景下修订临床实践的重要性,其中应包括彻底重建家族史和深入的基因检测。
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引用次数: 0
Deciphering the Molecular Complexity of Hepatocellular Carcinoma: Unveiling Novel Biomarkers and Therapeutic Targets Through Advanced Bioinformatics Analysis 解密肝细胞癌的分子复杂性:通过先进的生物信息学分析揭示新型生物标记物和治疗靶点。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-08-08 DOI: 10.1002/cnr2.2152
Ata Moghimi, Nasrin Bani Hosseinian, Mahdi Mahdipour, Ehsan Ahmadpour, Alberto Miranda-Bedate, Saeid Ghorbian
<div> <section> <h3> Background</h3> <p>Hepatocellular carcinoma (HCC) represents a primary liver tumor characterized by a bleak prognosis and elevated mortality rates, yet its precise molecular mechanisms have not been fully elucidated. This study uses advanced bioinformatics techniques to discern differentially expressed genes (DEGs) implicated in the pathogenesis of HCC. The primary objective is to discover novel biomarkers and potential therapeutic targets that can contribute to the advancement of HCC research.</p> </section> <section> <h3> Methods</h3> <p>The bioinformatics analysis in this study primarily utilized the Gene Expression Omnibus (GEO) database as data source. Initially, the Transcriptome analysis console (TAC) screened for DEGs. Subsequently, we constructed a protein–protein interaction (PPI) network of the proteins associated to the identified DEGs with the STRING database. We obtained our hub genes using Cytoscape and confirmed the results through the GEPIA database. Furthermore, we assessed the prognostic significance of the identified hub genes using the GEPIA database. To explore the regulatory interactions, a miRNA-gene interaction network was also constructed, incorporating information from the miRDB database. For predicting the impact of gene overexpression on drug effects, we utilized CANCER DP.</p> </section> <section> <h3> Results</h3> <p>A comprehensive analysis of HCC gene expression profiles revealed a total of 4716 DEGs, consisting of 2430 upregulated genes and 2313 downregulated genes in HCC sample compared to healthy control group. These DEGs exhibited significant enrichment in key pathways such as the PI3K-Akt signaling pathway, nuclear receptors meta-pathway, and various metabolism-related pathways. Further exploration of the PPI network unveiled the P53 signaling pathway and pyrimidine metabolism as the most prominent pathways. We identified 10 hub genes (<i>ASPM</i>, <i>RRM2</i>, <i>CCNB1</i>, <i>KIF14</i>, <i>MKI67</i>, <i>SHCBP1</i>, <i>CENPF</i>, <i>ANLN</i>, <i>HMMR</i>, and <i>EZH2</i>) that exhibited significant upregulation in HCC samples compared to healthy control group. Survival analysis indicated that elevated expression levels of these genes were strongly associated with changes in overall survival in HCC patients. Lastly, we identified specific miRNAs that were found to influence the expression of these genes, providing valuable insights into potential regulatory mechanisms underlying HCC progression.</p> </section> <section> <h3> Conclusion</h3> <p>The findings of this study have successfully id
背景:肝细胞癌(HCC)是一种原发性肝脏肿瘤,其特点是预后不良、死亡率高,但其确切的分子机制尚未完全阐明。本研究利用先进的生物信息学技术来识别与 HCC 发病机制有关的差异表达基因 (DEG)。其主要目的是发现新的生物标志物和潜在的治疗靶点,从而推动 HCC 研究的发展:本研究的生物信息学分析主要利用基因表达总库(GEO)数据库作为数据源。首先,转录组分析控制台(TAC)筛选出 DEGs。随后,我们利用 STRING 数据库构建了一个蛋白质-蛋白质相互作用(PPI)网络,其中包含了与已识别 DEGs 相关的蛋白质。我们利用 Cytoscape 获得了中心基因,并通过 GEPIA 数据库确认了结果。此外,我们还利用 GEPIA 数据库评估了所发现的中心基因的预后意义。为了探索调控相互作用,我们还结合 miRDB 数据库的信息构建了 miRNA 基因相互作用网络。为了预测基因过表达对药物效果的影响,我们使用了CANCER DP:对HCC基因表达谱的全面分析显示,与健康对照组相比,HCC样本中共有4716个DEGs,其中包括2430个上调基因和2313个下调基因。这些DEGs在PI3K-Akt信号通路、核受体元通路和各种代谢相关通路等关键通路中表现出明显的富集。对 PPI 网络的进一步探索发现,P53 信号通路和嘧啶代谢是最重要的通路。与健康对照组相比,我们发现有10个枢纽基因(ASPM、RRM2、CCNB1、KIF14、MKI67、SHCBP1、CENPF、ANLN、HMMR和EZH2)在HCC样本中表现出显著上调。生存期分析表明,这些基因表达水平的升高与 HCC 患者总生存期的变化密切相关。最后,我们确定了影响这些基因表达的特定 miRNA,为了解 HCC 进展的潜在调控机制提供了有价值的见解:本研究的结果成功鉴定了与 HCC 发病机制有关的关键基因和通路。这些新发现有可能在分子水平上大大提高我们对 HCC 的认识,为开发靶向疗法和改善预后评估开辟新的途径。
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引用次数: 0
Successful Application of Tocilizumab in a Patient With Neoadjuvant Immunochemotherapy-Induced Cytokine Release Syndrome 新辅助免疫化疗诱发细胞因子释放综合征患者成功应用托昔单抗
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-07-25 DOI: 10.1002/cnr2.2145
Soichiro Minami, Yosuke Kawashima, Yasuhiko Munakata, Masahiro Matsuno, Shuichiro Hara, Yusuke Yamazaki, Tsuyoshi Doman, Shin Saito, Tetsuo Odaka, Takahiro Ogasawara, Hisashi Shimizu, Jun Sugisaka, Tomoiki Aiba, Yukihiro Toi, Shinsuke Yamanda, Yuichiro Kimura, Shunichi Sugawara

Background

The expansion of preoperative immunochemotherapy has led to an increase in the number of patients with lung cancer receiving immune checkpoint inhibitors (ICIs). Therefore, oncologists should manage a variety of immune-related adverse events (irAEs). One of the rare, life-threatening, and recently proposed irAEs is cytokine release syndrome (CRS). Although the standard treatment of irAE is systemic administration of steroids, it has been suggested that tocilizumab may be an effective treatment option for CRS.

Case

This case describes a 69-year-old man with stage IIIA lung adenocarcinoma who received chemotherapy and nivolumab, which is an ICI, as neoadjuvant immunochemotherapy. After the first administration, the patient developed severe skin rash, fever, and arthralgia. We suspected irAEs and administered systemic steroids. However, fever and arthralgia did not improve, although the skin rash disappeared. These were also significant challenges for surgery. Noting the elevated levels of inflammatory cytokines, we consulted a rheumatologist. Finally, we decided to terminate neoadjuvant therapy after one cycle and administer tocilizumab. Tocilizumab dramatically improved the patient's symptoms and allowed him to undergo radical surgery. Pathological findings revealed that the patient achieved a major pathological response.

Conclusion

This indicates the potential effectiveness of early tocilizumab administration for ICI-induced CRS, even in mild cases.

背景:随着术前免疫化疗的推广,接受免疫检查点抑制剂(ICIs)治疗的肺癌患者人数不断增加。因此,肿瘤学家应处理各种免疫相关不良事件(irAEs)。细胞因子释放综合征(CRS)是一种罕见的、危及生命的、最近才被提出的irAEs。虽然irAE的标准治疗方法是全身应用类固醇,但有人认为托珠单抗可能是治疗CRS的一种有效方法。病例:本病例描述的是一名患有IIIA期肺腺癌的69岁男性患者,他接受了化疗和作为新辅助免疫化疗的ICI药物nivolumab。首次用药后,患者出现严重皮疹、发热和关节痛。我们怀疑是虹膜异位症,于是给予全身类固醇治疗。然而,虽然皮疹消失了,但发烧和关节痛并未改善。这些也是手术面临的重大挑战。考虑到炎症细胞因子水平升高,我们咨询了风湿病专家。最后,我们决定在一个周期后终止新辅助治疗,并使用妥昔单抗。妥昔单抗显著改善了患者的症状,使他得以接受根治手术。病理结果显示,患者获得了重大病理反应:结论:这表明早期使用托西珠单抗对 ICI 引起的 CRS 有潜在疗效,即使是轻度病例也是如此。
{"title":"Successful Application of Tocilizumab in a Patient With Neoadjuvant Immunochemotherapy-Induced Cytokine Release Syndrome","authors":"Soichiro Minami,&nbsp;Yosuke Kawashima,&nbsp;Yasuhiko Munakata,&nbsp;Masahiro Matsuno,&nbsp;Shuichiro Hara,&nbsp;Yusuke Yamazaki,&nbsp;Tsuyoshi Doman,&nbsp;Shin Saito,&nbsp;Tetsuo Odaka,&nbsp;Takahiro Ogasawara,&nbsp;Hisashi Shimizu,&nbsp;Jun Sugisaka,&nbsp;Tomoiki Aiba,&nbsp;Yukihiro Toi,&nbsp;Shinsuke Yamanda,&nbsp;Yuichiro Kimura,&nbsp;Shunichi Sugawara","doi":"10.1002/cnr2.2145","DOIUrl":"10.1002/cnr2.2145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The expansion of preoperative immunochemotherapy has led to an increase in the number of patients with lung cancer receiving immune checkpoint inhibitors (ICIs). Therefore, oncologists should manage a variety of immune-related adverse events (irAEs). One of the rare, life-threatening, and recently proposed irAEs is cytokine release syndrome (CRS). Although the standard treatment of irAE is systemic administration of steroids, it has been suggested that tocilizumab may be an effective treatment option for CRS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>This case describes a 69-year-old man with stage IIIA lung adenocarcinoma who received chemotherapy and nivolumab, which is an ICI, as neoadjuvant immunochemotherapy. After the first administration, the patient developed severe skin rash, fever, and arthralgia. We suspected irAEs and administered systemic steroids. However, fever and arthralgia did not improve, although the skin rash disappeared. These were also significant challenges for surgery. Noting the elevated levels of inflammatory cytokines, we consulted a rheumatologist. Finally, we decided to terminate neoadjuvant therapy after one cycle and administer tocilizumab. Tocilizumab dramatically improved the patient's symptoms and allowed him to undergo radical surgery. Pathological findings revealed that the patient achieved a major pathological response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This indicates the potential effectiveness of early tocilizumab administration for ICI-induced CRS, even in mild cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 7","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A case of biopsy-proven acute interstitial nephritis following atezolizumab-bevacizumab treatment of advanced unresectable hepatocellular carcinoma 一例阿特珠单抗-贝伐单抗治疗晚期不可切除肝癌后经活检证实的急性间质性肾炎病例。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-07-25 DOI: 10.1002/cnr2.2110
Reema Patel, Omar Elghawy, Amanda Gibbs, Srishti Gupta, Varinder Kaur

Background

The advent of immune checkpoint inhibitors (ICIs) represented a significant breakthrough in cancer therapy. Recently, the combined use of atezolizumab and bevacizumab was approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Exposure to a novel and diverse spectrum of immune-related adverse events (irAEs) has increased with the growing utilization of ICIs, however, a comprehensive understanding surrounding newer agents is still lacking. The incidence of kidney toxicities is rare but rising, often underreported due to the lack of confirmatory biopsies. Here, we present a rare case of biopsy-proven acute interstitial nephritis (AIN) following atezolizumab-bevacizumab treatment of advanced unresectable HCC.

Case

An 84-year-old male with T4N0M0 hepatocellular carcinoma was admitted after cycle 5 of atezolizumab due to decreased urine output and dysuria with a serum creatine of 4.7 mg/dL compared to a baseline of 1.3 mg/dL. To confirm the diagnosis of possible intrinsic renal injury, an ultrasound-guided non-focal biopsy of the left kidney was performed, revealing AIN. Potential exacerbatory medications, such as proton-pump inhibitors, were discontinued. The patient was discharged on oral steroids with improvement in serum creatinine. Before completing the steroid taper, the patient developed pneumocystis pneumonia and eventually transitioned to hospice care.

Conclusion

This case highlights the valuable role renal biopsy can play in accurately capturing irAEs and guiding appropriate management in the setting of ICI-induced AKI. It also exemplifies important considerations for steroid treatment of irAEs in the setting of comorbidities, such as diabetes.

背景:免疫检查点抑制剂(ICIs)的出现是癌症治疗领域的重大突破。最近,阿特珠单抗和贝伐珠单抗的联合使用被批准作为不可切除肝细胞癌(HCC)的一线治疗药物。随着 ICIs 使用率的不断提高,免疫相关不良事件(irAEs)的新颖性和多样性也随之增加,然而,人们对新型药物仍缺乏全面的了解。肾脏毒性的发生率虽然罕见,但却在不断上升,由于缺乏确诊活检,其发生率往往被低估。在此,我们介绍一例罕见的阿特珠单抗-贝伐珠单抗治疗晚期不可切除 HCC 后经活检证实的急性间质性肾炎(AIN)病例:一名 84 岁男性患者患有 T4N0M0 型肝细胞癌,在阿特珠单抗治疗第 5 个周期后因尿量减少和排尿困难入院,血清肌酸为 4.7 mg/dL,而基线值为 1.3 mg/dL。为确诊可能存在内在肾损伤,患者接受了超声引导下的左肾非灶性活检,结果显示为AIN。患者停用了质子泵抑制剂等可能加重病情的药物。患者出院时口服类固醇,血清肌酐有所改善。在完成类固醇减量之前,患者出现了肺孢子菌肺炎,最终转入临终关怀:本病例强调了肾活检在准确捕捉虹膜急性缺氧反应和指导 ICI 引起的 AKI 的适当治疗方面所能发挥的重要作用。本病例还体现了在糖尿病等合并症的情况下,类固醇治疗虹膜AEs的重要注意事项。
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引用次数: 0
Study of the stress in adults diagnosed with meningioma: Insights from a tertiary neurosurgical hospital 研究被诊断患有脑膜瘤的成年人的压力:一家三级神经外科医院的启示。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-07-25 DOI: 10.1002/cnr2.2105
Karashash Menlibayeva, Chingiz Nurimanov, Saken Nuradilov, Serik Akshulakov

Background

Meningiomas are the most common type of primary brain tumor, originating from the meninges – the protective membranes that surround the brain and spinal cord. Several well-studied risk factors for meningiomas include gender, age, radiation exposure, genetic factors, and hormonal factors. Moreover, the influence of a person's psycho-emotional stateon their overall health and mental well-being, specifically stress, iscurrently a significant and relevant topic of discussion.

Aims

This case–control study aimed to study the association between perceived stress, chronic stress, and meningioma in adult patients.

Methods and results

The study included cases, which comprised adult patients with histologically confirmed meningioma, and controls, consisting of adult patients with no history of brain cancer. Data collection involved the use of three types of questionnaires. The first questionnaire focused on patients' personal information, geographic factors, and lifestyle habits. Two additional questionnaires “The Perceived Stress Scale” and “The Chronic Stress Scale” were employed to assess perceived stress and chronic stress. The questioning was conducted by a neurologist. Microsoft Excel and Stata 14 were used for the data analysis. Overall, 148 questionnaires were completed and included in the analyses. The average age of participants was 45.60 ± 13.90 years. Females outnumbered males in both groups. Patients with meningioma diagnosis had a higher level of perceived high stress compared to those without meningioma (p = .045). Respondents without a diagnosis of meningioma have reported having more chronic stress in general and ambient problems (p = .004), financial issues (p = .006), work (p < .001), non-employment (p = .008), love and marriage (p < .001), isolation (p < .001), and residence (p < .001). Patients with meningioma, however, had less chronic stress compared to meningioma-free patients.

Conclusion

This study revealed no discernible connection between stress and meningioma within our study sample. Further research with matched case–control methodology with a larger sample size is warranted to thoroughly evaluate the potential role of stress in patients with meningioma.

背景:脑膜瘤是原发性脑肿瘤中最常见的一种,起源于脑膜--环绕大脑和脊髓的保护膜。脑膜瘤的风险因素包括性别、年龄、辐射暴露、遗传因素和荷尔蒙因素。此外,一个人的心理情绪状态对其整体健康和精神状态的影响,特别是压力,也是当前一个重要的相关讨论话题。目的:本病例对照研究旨在探讨感知到的压力、慢性压力与成年脑膜瘤之间的关系:研究对象包括病例和对照组,病例包括经组织学证实患有脑膜瘤的成年患者,对照组包括无脑癌病史的成年患者。数据收集包括使用三种类型的问卷。第一种问卷主要涉及患者的个人信息、地理因素和生活习惯。另外还使用了 "感知压力量表 "和 "慢性压力量表 "两种问卷来评估感知压力和慢性压力。问卷调查由一名神经科医生进行。数据分析使用 Microsoft Excel 和 Stata 14。共完成 148 份问卷并纳入分析。参与者的平均年龄为 45.60 ± 13.90 岁。两组中女性均多于男性。与未患脑膜瘤的患者相比,确诊脑膜瘤的患者感受到的高度压力更高(p = .045)。未确诊脑膜瘤的受访者在一般情况和环境问题(p = .004)、财务问题(p = .006)、工作(p 结论)方面的长期压力更大:本研究表明,在我们的研究样本中,压力与脑膜瘤之间没有明显的联系。为了彻底评估压力在脑膜瘤患者中的潜在作用,有必要使用匹配病例对照方法和更大的样本量进行进一步研究。
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引用次数: 0
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