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Detection of Muscularis propria Invasion in Urothelial Carcinoma Using Artificial Intelligence. 利用人工智能检测尿路上皮癌的固有肌层侵犯
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241257479
Ibrahim Fahoum, Rabab Naamneh, Keren Silberberg, Rami Hagege, Dov Hershkovitz

Background & Objective: Assessment of muscularis propria invasion is a crucial step in the management of urothelial carcinoma since it necessitates aggressive treatment. The diagnosis of muscle invasion is a challenging process for pathologists. Artificial intelligence is developing rapidly and being implemented in various fields of pathology. The purpose of this study was to develop an algorithm for the detection of muscularis propria invasion in urothelial carcinoma. Methods: The Training cohort consisted of 925 images from 50 specimens of urothelial carcinoma. Ninety-seven images from 10 new specimens were used as a validation cohort. Clinical validation used 127 whole specimens with a total of 617 slides. The algorithm determined areas where tumor and muscularis propria events were in nearest proximity, and presented these areas to the pathologist. Results: Analytical evaluation showed a sensitivity of 72% for muscularis propria and 65% for tumor, and a specificity of 46% and 77% for muscularis propria and tumor detection, respectively. The incorporation of the spatial proximity factor between muscularis propria and tumor in the clinical validation significantly improved the detection of muscularis propria invasion, as the algorithm managed to identify all except for one case with muscle invasive bladder cancer in the clinical validation cohort. The case missed by the algorithm was nested urothelial carcinoma, a rare subtype with unusual morphologic features. The pathologist managed to identify muscle invasion based on the images provided by the algorithm in a short time, with an average of approximately 5 s. Conclusion: The algorithm we developed may greatly aid in accurate identification of muscularis propria invasion by imitating the thought process of the pathologist.

背景与目的:由于尿路上皮癌需要积极治疗,因此评估固有肌层侵犯是治疗尿路上皮癌的关键步骤。对病理学家来说,肌肉侵犯的诊断是一个具有挑战性的过程。人工智能正在迅速发展,并被应用于病理学的各个领域。本研究的目的是开发一种用于检测尿路腺癌固有肌层侵犯的算法。研究方法训练队列包括来自 50 个尿路癌标本的 925 张图像。来自 10 个新标本的 97 张图像被用作验证队列。临床验证使用了 127 个完整标本,共计 617 张切片。该算法确定肿瘤和固有肌事件最接近的区域,并将这些区域呈现给病理学家。结果显示分析评估显示,固有肌和肿瘤的灵敏度分别为 72% 和 65%,而固有肌和肿瘤检测的特异性分别为 46% 和 77%。在临床验证中加入肌固有膜和肿瘤之间的空间邻近性因素,大大提高了肌固有膜侵犯的检测率,因为在临床验证队列中,除了一例肌浸润性膀胱癌病例外,该算法成功识别了所有病例。该算法漏诊的病例是巢状尿路上皮癌,这是一种罕见的亚型,具有不寻常的形态特征。病理学家根据算法提供的图像在很短的时间(平均约 5 秒)内成功识别出肌肉浸润:我们开发的算法可以模仿病理学家的思维过程,从而大大有助于准确识别固有肌层受侵。
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引用次数: 0
Advances in Molecular Pathology, Diagnosis and Treatment of Spinal Cord Astrocytomas. 脊髓星形细胞瘤的分子病理学、诊断和治疗进展。
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241262483
Zijun Zhao, Zihan Song, Zairan Wang, Fan Zhang, Ze Ding, Tao Fan

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.

脊髓星形细胞瘤(SCA)是星形细胞瘤的一种罕见亚型,给诊断和治疗带来了挑战。低级别星形细胞瘤仅通过手术就能获得长期生存,而高级别星形细胞瘤即使经过综合治疗,预后也令人失望。颅内星形细胞瘤的诊断标准和标准治疗对 SCA 有明显的局限性。对SCA分子机制的研究远远落后于对颅内星形细胞瘤的研究。近年来,星形细胞瘤的分子病理学研究取得了巨大突破,并出现了 DNA 甲基化分析和放射组学等新技术。这些进展使得对星形细胞瘤进行精确诊断并制定相应的治疗策略成为可能。我们的目的是回顾SCA的诊断和治疗现状,总结最新的研究进展,包括肿瘤亚型、分子特征、诊断技术和潜在的治疗策略,从而加深我们对这种不常见肿瘤类型的认识,为准确诊断和治疗提供指导。
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引用次数: 0
Large Foundation Model for Cancer Segmentation. 用于癌症分类的大型基础模型
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241266205
Zeyu Ren, Yudong Zhang, Shuihua Wang

Recently, large language models such as ChatGPT have made huge strides in understanding and generating human-like text and have demonstrated considerable success in natural language processing. These foundation models also perform well in computer vision. However, there is a growing need to use these technologies for specific medical tasks, especially for identifying cancer in images. This paper looks at how these foundation models, such as the segment anything model, could be used for cancer segmentation, discussing the potential benefits and challenges of applying large foundation models to help with cancer diagnoses.

最近,大型语言模型(如 ChatGPT)在理解和生成类人文本方面取得了巨大进步,并在自然语言处理方面取得了相当大的成功。这些基础模型在计算机视觉方面也表现出色。然而,越来越多的人需要将这些技术用于特定的医疗任务,特别是用于识别图像中的癌症。本文探讨了如何将这些基础模型(如segment anything 模型)用于癌症分割,讨论了应用大型基础模型帮助癌症诊断的潜在优势和挑战。
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引用次数: 0
Predicting Calcein Release from Ultrasound-Targeted Liposomes: A Comparative Analysis of Random Forest and Support Vector Machine. 预测超声靶向脂质体的钙黄绿素释放:随机森林与支持向量机的比较分析。
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241296725
Ibrahim Shomope, Kelly M Percival, Nabil M Abdel Jabbar, Ghaleb A Husseini

Objective: This study presents a comparative analysis of RF and SVM for predicting calcein release from ultrasound-triggered, targeted liposomes under varied low-frequency ultrasound (LFUS) power densities (6.2, 9, and 10 mW/cm2).

Methods: Liposomes loaded with calcein and targeted with seven different moieties (cRGD, estrone, folate, Herceptin, hyaluronic acid, lactobionic acid, and transferrin) were synthesized using the thin-film hydration method. The liposomes were characterized using Dynamic Light Scattering and Bicinchoninic Acid assays. Extensive data collection and preprocessing were performed. RF and SVM models were trained and evaluated using mean absolute error (MAE), mean squared error (MSE), coefficient of determination (R²), and the a20 index as performance metrics.

Results: RF consistently outperformed SVM, achieving R2 scores above 0.96 across all power densities, particularly excelling at higher power densities and indicating a strong correlation with the actual data.

Conclusion: RF outperforms SVM in drug release prediction, though both show strengths and apply based on specific prediction needs.

研究目的本研究比较分析了 RF 和 SVM 在不同低频超声(LFUS)功率密度(6.2、9 和 10 mW/cm2)条件下预测超声触发靶向脂质体释放钙黄绿素的方法:采用薄膜水合法合成了负载钙黄绿素的脂质体,并以七种不同的分子(cRGD、雌酮、叶酸、赫赛汀、透明质酸、乳糖酸和转铁蛋白)为靶标。利用动态光散射和双喹啉酸测定法对脂质体进行了表征。进行了广泛的数据收集和预处理。使用平均绝对误差(MAE)、平均平方误差(MSE)、决定系数(R²)和 a20 指数作为性能指标,对 RF 和 SVM 模型进行了训练和评估:结果:RF 的性能始终优于 SVM,在所有功率密度下的 R2 得分都超过了 0.96,尤其是在较高的功率密度下表现尤为突出,并且与实际数据具有很强的相关性:结论:在药物释放预测方面,RF 的表现优于 SVM,但两者都有各自的优势,并可根据具体预测需求进行应用。
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引用次数: 0
High Expression of SRSF10 Promotes Colorectal Cancer Progression by Aberrant Alternative Splicing of RFC5. SRSF10的高表达通过RFC5的异常替代剪接促进结直肠癌的进展
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241271906
Shuai Xu, Fangmin Zhong, Junyao Jiang, Fangyi Yao, Meiyong Li, Mengxin Tang, Ying Cheng, Yulin Yang, Wen Wen, Xueru Zhang, Bo Huang, Xiaozhong Wang

Background: Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer.

Methods: Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis.

Result: The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5.

Conclusion: In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC.

背景:结肠直肠癌(CRC)的发病率和死亡率居高不下,仍然是全球关注的健康问题。然而,人们对 CRC 的具体发病机制仍然知之甚少。本研究旨在探讨富丝氨酸和精氨酸剪接因子 10(SRSF10)在结直肠癌中的作用和发病机制:方法:采用生物信息学分析预测 SRSF10 基因在 CRC 患者中的表达。使用 CCK8、transwell、划痕试验和流式细胞术进行了 SRSF10 基因敲除和过表达的功能实验。此外,还利用 PRIdictor 网站预测了 SRSF10 与 RFC5 的相互作用位点。通过琼脂糖凝胶电泳鉴定了SRSF10作用于RFC5前mRNA的不同转录本:结果:SRSF10的敲除抑制了CRC细胞的增殖和迁移能力,同时促进了CRC细胞的凋亡和DNA复制的改变。相反,当 SRSF10 高表达时,它能增强 CRC 细胞的增殖和迁移能力,并引起结直肠癌细胞周期的变化。这项研究揭示了 SRSF10 敲除后大肠癌细胞中复制因子 C 亚基 5(RFC5)基因的变化。此外,研究还证实SRSF10增加了RFC5外显子2-AS1(S)的转录变异,从而通过AS1对RFC5外显子2的排斥促进了结直肠癌的发生:总之,本研究表明,SRSF10 通过在 RFC5 第 2 外显子内产生异常剪接的 AS1 排斥异构体,促进了结直肠癌的发展。这些发现表明,SRSF10 可作为临床诊断和治疗 CRC 的关键靶点。
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引用次数: 0
Alternative Splicing Landscape of Head and Neck Squamous Cell Carcinoma. 头颈部鳞状细胞癌的替代剪接图谱
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241272051
Kehan Wu, Qianhui Sun, Dongxu Liu, Jiayi Lu, Deyu Wen, Xiyan Zang, Li Gao

Head and neck malignancies are a significant global health concern, with head and neck squamous cell carcinoma (HNSCC) being the sixth most common cancer worldwide accounting for > 90% of cases. In recent years, there has been growing recognition of the potential role of alternative splicing (AS) in the etiology of cancer. Increasing evidence suggests that AS is associated with various aspects of cancer progression, including tumor occurrence, invasion, metastasis, and drug resistance. Additionally, AS is involved in shaping the tumor microenvironment, which plays a crucial role in tumor development and response to therapy. AS can influence the expression of factors involved in angiogenesis, immune response, and extracellular matrix remodeling, all of which contribute to the formation of a supportive microenvironment for tumor growth. Exploring the mechanism of AS events in HNSCC could provide insights into the development and progression of this cancer, as well as its interaction with the tumor microenvironment. Understanding how AS contributes to the molecular changes in HNSCC cells and influences the tumor microenvironment could lead to the identification of new therapeutic targets. Targeted chemotherapy and immunotherapy strategies tailored to the specific AS patterns in HNSCC could potentially improve treatment outcomes and reduce side effects. This review explores the concept, types, processes, and technological advancements of AS, focusing on its role in the initiation, progression, treatment, and prognosis of HNSCC.

头颈部恶性肿瘤是全球关注的重大健康问题,其中头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症,占90%以上的病例。近年来,人们越来越认识到替代剪接(AS)在癌症病因学中的潜在作用。越来越多的证据表明,AS 与癌症进展的各个方面有关,包括肿瘤发生、侵袭、转移和耐药性。此外,AS 还参与了肿瘤微环境的形成,而肿瘤微环境在肿瘤的发展和治疗反应中起着至关重要的作用。AS可影响参与血管生成、免疫反应和细胞外基质重塑的因子的表达,所有这些都有助于形成有利于肿瘤生长的微环境。探索 AS 在 HNSCC 中的作用机制有助于深入了解这种癌症的发展和恶化过程,以及它与肿瘤微环境之间的相互作用。了解AS如何促进HNSCC细胞的分子变化并影响肿瘤微环境,有助于确定新的治疗靶点。针对 HNSCC 中特定 AS 模式的靶向化疗和免疫治疗策略有可能改善治疗效果并减少副作用。本综述探讨了AS的概念、类型、过程和技术进展,重点关注其在HNSCC的发生、发展、治疗和预后中的作用。
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引用次数: 0
Predictive Role of Elevated Neutrophil-Lymphocyte Ratio for Bone Metastasis in Esophageal Cancer. 中性粒细胞-淋巴细胞比率升高对食管癌骨转移的预测作用
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241272043
Xuan Wang, Ying Gao, Junyang Wang, Ling Chen, Xin Zhang, Min Chen, Ning Lan, Wenyang Li, Fang Wu, Juan Ren

Purpose: Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC.

Methods: Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients' coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers.

Results: ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P < 0.001), significantly enhancing the predictability of bone metastasis in EC.

Conclusion: NLR, as a convenient, non-invasive, and cost-effective inflammatory indicator, could predict bone metastasis in EC. Combining NLR with tumor markers can significantly improve the diagnostic accuracy of bone metastasis in EC.

研究目的有关食管癌骨转移的研究相对有限。患者一旦发生骨转移,预后较差,严重影响患者的生活质量。目前,缺乏方便的肿瘤标志物用于早期识别食管癌骨转移。我们的研究旨在探讨中性粒细胞-淋巴细胞比值(NLR)能否预测EC患者的骨转移:方法:对604例EC患者的临床指标进行回顾性分析。方法:对604例EC患者的临床指标进行回顾性分析,以是否发生骨转移为标准进行分组,并收集患者的凝血相关检查、血常规、肿瘤标志物等指标。采用接收者操作特征曲线(ROC)确定NLR等参数对EC骨转移的预测能力,并进行单变量和多变量Logistic回归分析,以确定各指标对骨转移的影响。利用二元逻辑回归得出NLR结合肿瘤标志物的预测概率:ROC曲线分析表明,NLR的曲线下面积(AUC)为0.681,敏感性为79.2%,特异性为52.6%,可作为EC骨转移的预测因素。多变量逻辑回归分析表明,高 NLR(几率比[OR]:2.608,95% 置信区间[CI]:1.395-4.874)可作为骨转移的预测因素:1.395-4.874,P = 0.003)可作为EC患者骨转移的独立危险因素。此外,高PT、高APTT、高FDP、高CEA、高CA724、低血红蛋白和低血小板水平也可预测EC患者的骨转移。当 NLR 与肿瘤标志物相结合时,曲线下面积为 0.760(95% CI:0.713-0.807,P 结论:NLR 与肿瘤标志物的结合可预测骨转移:NLR作为一种方便、无创、经济的炎症指标,可以预测EC的骨转移。将NLR与肿瘤标志物相结合可显著提高EC骨转移的诊断准确性。
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引用次数: 0
A Pyroptosis-Related Gene Signature Predicts Prognosis and Tumor Immune Microenvironment in Colorectal Cancer. 预测结直肠癌预后和肿瘤免疫微环境的热蛋白沉积相关基因信号
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241277584
Linjing Li, Yuyi Li, Junyi Lin, Wenjing Pang

Pyroptosis is a programmed cell death, which garners increasing attention by relating to immune and therapy response. However, the role of pyroptosis in colorectal cancer (CRC) remains unclear. Our study mainly to explore the role of pyroptosis in CRC. The mRNA expression data and corresponding clinical information of CRC patients were achieved from The Cancer Genome Atlas (TCGA). Pyroptosis-related genes (PRGs) were identified using DESeq2 R package and biological function was analyzed using cluster Profiler R package. A PRGs-based prognosis model was constructed by a univariate Cox and LASSO regression analyses. Then, the affecting of risk signature to clinicopathological characteristics, immune status and infiltrated immune cells, immune checkpoint and chemotherapy sensitivity was analyzed. qRT-PCR and IHC were performed for the expression level of PRGs. Moreover, a nomogram predict model was constructed. Total 57 PRGs were identified between 500 CRC samples and 44 normal samples. Those PRGs mainly enriched in immune-related and pyroptosis-related pathways. GABRD, NADK, TMEM240, RER1, AGRN, UBE2J2, CALML6, PLCH2, TMEM88B have been identified as gene signature and a prognostic model was constructed and validated. CRC patients with high-risk score showed poor survival, high TMB score, high proportion of CD4 + memory T cells, common lymphoid progenitors, cancer associated fibroblasts, mast cells, and neutrophils. The immune checkpoint related genes, CD160, CD200R1, CD244, CD28, CD40LG, CD44, CD48, CD80, CD86, HHLA2, ICOS, IDO1, TIGIT, TNFRSF25, TNFRSF4, TNFRSF9, TNFSF15, TNFSF18 also increased in high-risk score group. CRC patients with high-risk score more sensitive to docetaxel and rapamycin but resistance to gemcitabine and mitomycin. Moreover, a predictive nomogram for 1-, 3-, 5-year for CRC patients was established and validated. In the study, a PRGs-based prognostic model and a predictive model were constructed. These models are effective and robust in prediction the 1-, 3-, and 5-year survival of CRC patients.

嗜热细胞增多症是一种程序性细胞死亡,因与免疫和治疗反应有关而日益受到关注。然而,热噬在结直肠癌(CRC)中的作用仍不清楚。我们的研究主要是探讨热噬在 CRC 中的作用。我们从癌症基因组图谱(TCGA)中获取了 CRC 患者的 mRNA 表达数据和相应的临床信息。使用DESeq2 R软件包鉴定了热蛋白沉积相关基因(PRGs),并使用cluster Profiler R软件包分析了这些基因的生物学功能。通过单变量 Cox 和 LASSO 回归分析,构建了基于 PRGs 的预后模型。然后,分析了风险特征对临床病理特征、免疫状态和浸润免疫细胞、免疫检查点和化疗敏感性的影响。此外,还构建了一个提名图预测模型。在 500 份 CRC 样本和 44 份正常样本中,共鉴定出 57 个 PRGs。这些PRGs主要富集于免疫相关通路和化脓相关通路。GABRD、NADK、TMEM240、RER1、AGRN、UBE2J2、CALML6、PLCH2、TMEM88B被鉴定为基因特征,并构建和验证了预后模型。高风险评分的 CRC 患者生存率低,TMB 评分高,CD4 + 记忆 T 细胞、常见淋巴祖细胞、癌相关成纤维细胞、肥大细胞和中性粒细胞比例高。免疫检查点相关基因 CD160、CD200R1、CD244、CD28、CD40LG、CD44、CD48、CD80、CD86、HHLA2、ICOS、IDO1、TIGIT、TNFRSF25、TNFRSF4、TNFRSF9、TNFSF15、TNFSF18 在高风险评分组中也有所增加。高风险评分的 CRC 患者对多西他赛和雷帕霉素更敏感,但对吉西他滨和丝裂霉素耐药。此外,还建立并验证了 CRC 患者 1 年、3 年和 5 年的预测提名图。该研究构建了基于 PRGs 的预后模型和预测模型。这些模型在预测 CRC 患者的 1 年、3 年和 5 年生存率方面既有效又稳健。
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引用次数: 0
FXR, MRP-1 and SLC7A5: New Targets for the Treatment of Hepatocellular Carcinoma. FXR、MRP-1 和 SLC7A5:治疗肝细胞癌的新靶点。
IF 2.7 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338241276889
Xi-Yue Zhang, Ming Luo, Shu Qin, Wen-Guang Fu, Meng-Yu Zhang

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

检测法尼类固醇 X 受体(FXR)、多重耐药相关蛋白-1(MRP-1)和溶质运载家族 7 成员 5(SLC7A5)在大鼠肝细胞癌(HCC)模型中的表达,从而为 HCC 的基因治疗提供新的治疗靶点。将 60 只雄性 Wistar 大鼠随机分为三组。实验组给大鼠灌胃0.2%的二乙基亚硝胺(DEN),剂量为10毫克/千克,每周3次,12周后停药。对照组大鼠灌胃生理盐水,假手术组大鼠不灌胃任何东西。10 周时,实验组的一只大鼠被安乐死,并记录肝脏的变化。12 周后重复上述过程。12 周后,只有实验组出现了肝癌。通过病理检查确认肿瘤形成后,取三组的肝组织和肿瘤组织。检测肝组织和肿瘤组织中 FXR、MRP-1 和 SLC7A5 的表达。7 周后,实验组大鼠进食减少,体重明显下降。三个月后,实验组的 15 只大鼠被检测出患有 HCC。三组大鼠的 FXR/GAPDH mRNA、MRP-1/GAPDH mRNA、SLC7A5/GAPDH mRNA 的比值有明显差异。光镜下,FXR 蛋白、MRP-1 蛋白和 SLC7A5 蛋白与各自的抗体反应,呈颗粒状表达。每组的病理切片中都有不同数量的阳性细胞。FXR在大鼠HCC中的表达明显低于正常肝组织,但MRP-1和SLC7A5在HCC中的表达明显高于正常肝组织,这表明靶向FXR、MRP-1和SLC7A5的药物可能是治疗HCC的新策略。
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引用次数: 0
Multileaf Collimator Modeling and Commissioning for Complex Radiation Treatment Plans Using 2-Dimensional (2D) Diode Array MapCHECK2. 使用二维 (2D) 二极管阵列 MapCHECK2 为复杂的放射治疗计划进行多叶准直器建模和调试。
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.1177/15330338231225864
Jian Guo, Meng Zhu, Weijin Zeng, He Wang, Songbing Qin, Zhibin Li, Yu Tang, Binbin Ying, Jiugao Sang, Ming Ji, Kuo Meng, Zhouguang Hui, Jianyang Wang, Juying Zhou, Yin Zhou, Jian Huan

Purpose: This study aims to develop a data-collecting package ExpressMLC and investigate the applicability of MapCHECK2 for multileaf collimator (MLC) modeling and commissioning for complex radiation treatment plans. Materials and methods: The MLC model incorporates realistic parameters to account for sophisticated MLC features. A set of 8 single-beam plans, denoted by ExpressMLC, is created for the determination of parameters. For the commissioning of the MLC model, 4 intensity modulated radiation therapy (IMRT) plans specified by the AAPM TG 119 report were transferred to a computed tomography study of MapCHECK2, recalculated, and compared to measurements on a Varian accelerator. Both per-beam and composite-beam dose verification were conducted. Results: Through sufficient characterization of the MLC model, under 3%/2 mm and 2%/2 mm criteria, MapCHECK2 can be used to accurately verify per beam dose with gamma passing rate better than 90.9% and 89.3%, respectively, while the Gafchromic EBT3 films can achieve gamma passing rate better than 89.3% and 85.7%, respectively. Under the same criteria, MapCHECK2 can achieve composite beam dose verification with a gamma passing rate better than 95.9% and 90.3%, while the Gafchromic EBT3 films can achieve a gamma passing rate better than 96.1% and 91.8%; the p-value from the Mann Whitney test between gamma passing rates of the per beam dose verification using full MapCHECK2 package calibrated MLC model and film calibrated MLC model is .44 and .47, respectively; the p-value between those of the true composite beam dose verification is .62 and .36, respectively. Conclusion: It is confirmed that the 2-dimensional (2D) diode array MapCHECK2 can be used for data collection for MLC modeling with the combination of the ExpressMLC package of plans, whose doses are sufficient for the determination of MLC parameters. It could be a fitting alternative to films to boost the efficiency of MLC modeling and commissioning without sacrificing accuracy.

目的:本研究旨在开发一个数据收集软件包 ExpressMLC,并研究 MapCHECK2 在多叶准直仪(MLC)建模和复杂放射治疗计划调试中的适用性。材料和方法:多叶准直仪模型包含现实参数,以考虑复杂的多叶准直仪特征。为确定参数,创建了一组 8 个单光束计划(以 ExpressMLC 表示)。为了调试 MLC 模型,将 AAPM TG 119 报告中指定的 4 个调强放射治疗(IMRT)计划转移到 MapCHECK2 的计算机断层扫描研究中,重新计算,并与瓦里安加速器上的测量结果进行比较。对每个光束和复合光束的剂量都进行了验证。结果:通过对 MLC 模型的充分表征,在 3%/2 mm 和 2%/2 mm 标准下,MapCHECK2 可用于精确验证每束剂量,伽马通过率分别优于 90.9% 和 89.3%,而 Gafchromic EBT3 薄膜的伽马通过率分别优于 89.3% 和 85.7%。在相同标准下,MapCHECK2 可实现伽马通过率优于 95.9% 和 90.3% 的复合射束剂量验证,而 Gafchromic EBT3 薄膜可实现伽马通过率优于 96.1% 和 91.8%;使用全 MapCHECK2 软件包校准的 MLC 模型和薄膜校准的 MLC 模型进行每束剂量验证的伽马通过率之间的曼-惠特尼检验的 p 值分别为 0.44 和 0.47;真实复合束剂量验证的 p 值分别为 0.62 和 0.36。结论二维(2D)二极管阵列 MapCHECK2 可用于 MLC 建模的数据收集,并与 ExpressMLC 计划包相结合,其剂量足以确定 MLC 参数。它可以替代薄膜,在不影响精度的情况下提高 MLC 建模和调试的效率。
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Technology in Cancer Research & Treatment
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