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Evolving insights in blood-based liquid biopsies for prostate cancer interrogation. 基于血液的液体活检在前列腺癌审讯中的发展见解。
Pub Date : 2023-11-30 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.592
R Daniel Bonfil, Ghaith Al-Eyd

During the last decade, blood sampling of cancer patients aimed at analyzing the presence of cells, membrane-bound vesicles, or molecules released by primary tumors or metastatic growths emerged as an alternative to traditional tissue biopsies. The advent of this minimally invasive approach, known as blood-based liquid biopsy, began to play a pivotal role in the management of diverse cancers, establishing itself as a vital component of precision medicine. Here, we discuss three blood-based liquid biopsies, namely circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and tumor-derived exosomes, as they relate to prostate cancer (PCa) management. The advances achieved in the molecular characterization of these types of liquid biopsies and their potential to predict recurrence, improve responses to certain treatments, and evaluate prognosis, in PCa patients, are highlighted herein. While there is currently full clinical validation for only one CTC-based and one ctDNA-based liquid biopsy for patients with metastatic castration-resistant PCa, the adoption of additional methods is anticipated as they undergo standardization and achieve analytical and clinical validation. Advantages and disadvantages of different blood-based liquid biopsy approaches in the context of PCa are outlined herein, while also considering potential synergies through combinatory strategies.

在过去的十年中,癌症患者的血液采样旨在分析原发肿瘤或转移性肿瘤释放的细胞,膜结合囊泡或分子的存在,作为传统组织活检的替代方法。这种被称为基于血液的液体活检的微创方法的出现,开始在各种癌症的治疗中发挥关键作用,使其成为精准医学的重要组成部分。在这里,我们讨论了三种基于血液的液体活检,即循环肿瘤细胞(CTCs),循环肿瘤DNA (ctDNA)和肿瘤来源的外泌体,因为它们与前列腺癌(PCa)的管理有关。本文强调了在前列腺癌患者中,这些类型的液体活检的分子特征及其预测复发、改善对某些治疗的反应和评估预后的潜力所取得的进展。虽然目前只有一种基于ctc和一种基于ctdna的液体活检对转移性去雄耐药PCa患者进行了全面的临床验证,但随着它们经过标准化并获得分析和临床验证,预计将采用其他方法。本文概述了前列腺癌背景下不同血液液体活检方法的优缺点,同时也考虑了通过组合策略的潜在协同作用。
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引用次数: 0
Be mindful of potential pitfalls when using the Cre-LoxP system in cancer research 在癌症研究中使用Cre-LoxP系统时,要注意潜在的陷阱
Pub Date : 2023-11-14 DOI: 10.18632/oncoscience.591
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引用次数: 0
An immunoinformatics assessment of the cancer testis antigen, DDX53, as a potential early esophageal cancer antigen. 睾丸癌抗原DDX53作为潜在的早期食管癌抗原的免疫信息学评估。
Pub Date : 2023-11-10 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.590
Peter Cheng, Konrad J Cios, Mallika Varkhedi, Vayda R Barker, Michelle Yeagley, Andrea Chobrutskiy, Boris I Chobrutskiy, George Blanck

T-lymphocytes have been implicated in facilitating a pro-inflammatory, pro-tumorigenic microenvironment that worsens prognosis for esophageal carcinoma (ESCA). In this study, we identified tumor resident, T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences and employed an algorithm particularly suited to the big data setting to evaluate TCR CDR3-cancer testis antigen (CTA) chemical complementarities. Chemical complementarity of the ESCA TCR CDR3s and the cancer testis antigen DDX53 represented a disease-free survival (DFS) distinction, whereby the upper fiftieth percentile complementarity group correlated with worse DFS. The high TCR CDR3-DDX53 complementarity group also represented a greater proportion of tumor samples lacking DDX53 expression. These data and analyses raise the question of whether the TCR CDR3-DDX53 chemical complementarity assessment detected an ESCA immune response that selected for DDX53-negative cells?

t淋巴细胞参与促进促炎、促肿瘤微环境,从而恶化食管癌(ESCA)的预后。在本研究中,我们鉴定了肿瘤驻留t细胞受体(TCR)互补决定区3 (CDR3)氨基酸序列,并采用特别适合大数据设置的算法来评估TCR CDR3-癌睾丸抗原(CTA)化学互补。ESCA TCR CDR3s和睾丸癌抗原DDX53的化学互补性代表了无病生存(DFS)的区别,其中,50百分位互补性较高的组与较差的DFS相关。高TCR CDR3-DDX53互补组也代表了更大比例的缺乏DDX53表达的肿瘤样本。这些数据和分析提出了一个问题,即TCR CDR3-DDX53化学互补性评估是否检测到选择ddx53阴性细胞的ESCA免疫反应?
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引用次数: 0
Diagnosis and management of postoperative wound infections in the head and neck region. 头颈部术后伤口感染的诊断和处理。
Pub Date : 2023-10-04 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.589
Filip Barbarewicz, Kai-Olaf Henkel, Florian Dudde
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引用次数: 0
The mutational signatures of cancer: can passengers set a direction for prognosis? 癌症的突变特征:乘客能为预后设定方向吗?
Pub Date : 2023-10-02 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.588
Peeter Karihtala
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引用次数: 0
Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma. 帕唑帕尼在EWSR1-NFATC2易位相关骨肉瘤中的活性。
Pub Date : 2023-09-20 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.587
Mohamed A Gouda, Maria A Zarzour, Ara A Vaporciyan, Kalevi Kairemo, Hubert H Chuang, Vivek Subbiah

Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma. In this case report, we discuss the case of a patient with a EWSR1-NFATC2 fusion positive bone sarcoma who had exceptional tumor control through using pazopanib and surgery for an overall duration exceeding 5 years. We also review the literature on EWSR1-NFATC2 translocation-associated sarcomas and use of pazopanib in bone sarcomas.

帕唑帕尼是一种多激酶抑制剂,目前已被批准用于治疗晚期肾细胞癌和化疗难治性软组织肉瘤。在本病例报告中,我们讨论了一名EWSR1-NFATC2融合阳性骨肉瘤患者的病例,该患者通过使用帕唑帕尼和手术获得了特殊的肿瘤控制,总持续时间超过5年。我们还回顾了EWSR1-NFATC2易位相关肉瘤的文献以及帕唑帕尼在骨肉瘤中的应用。
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引用次数: 0
Multi-disciplinary management of recurrent gastrointestinal stromal tumor harboring KIT exon 11 mutation with the switch-control kinase inhibitor ripretinib and surgery. 应用开关控制激酶抑制剂瑞普替尼对携带KIT外显子11突变的复发性胃肠道间质瘤进行多学科治疗和手术。
Pub Date : 2023-09-20 eCollection Date: 2023-01-01 DOI: 10.18632/oncoscience.586
Mohamed A Gouda, Filip Janku, Neeta Somaiah, Kelly K Hunt, Sireesha Yedururi, Vivek Subbiah

Ripretinib is a tyrosine kinase inhibitor that was approved by the United States FDA in 2020 for treatment of advanced gastrointestinal stromal tumor (GIST) in patients who received prior treatment with three or more tyrosine kinase inhibitors. In this case report, we show the durable clinical benefit achieved in a patient with GIST by using ripretinib and repeated timely surgical resection of limited disease progression. The total time on ripretinib was 43 months which is longer than the current reported data from ripretinib clinical trials. Such approach for using multi-disciplinary disease management can improve the durability of response to tyrosine kinase inhibitors, including ripretinib, and associated clinical outcomes.

瑞普替尼是一种酪氨酸激酶抑制剂,于2020年被美国食品药品监督管理局批准用于治疗既往接受三种或多种酪氨酸激酶抑制剂治疗的晚期胃肠道间质瘤(GIST)患者。在本病例报告中,我们展示了通过使用瑞普替尼和对有限疾病进展进行反复及时手术切除,在GIST患者中获得的持久临床益处。使用瑞普替尼的总时间为43个月,比目前报道的瑞普替尼临床试验数据更长。这种使用多学科疾病管理的方法可以提高对酪氨酸激酶抑制剂(包括瑞普替尼)的反应的持久性和相关的临床结果。
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引用次数: 0
A CRISPR-p53 interactome with potential implications for clinical CRISPR/Cas9 use CRISPR-p53相互作用组对临床CRISPR/Cas9应用的潜在影响
Pub Date : 2022-05-09 DOI: 10.18632/oncoscience.557
Long Jiang, F. Wermeling
CRISPR/Cas9-based tools are anticipated to transform the gene therapy field by facilitating the correction of disease-causing mutations. However, CRISPR/Cas9 generates DNA damage, which triggers a DNA damage response centered around the tumor-suppressor p53. In this research perspective, we discuss implications of this and describe a CRISPR-p53 interactome with cancer-related genes that, if mutated, can give cells a selective advantage following exposure to CRISPR/Cas9. We propose that the genes in the CRISPR-p53 interactome should be monitored in the clinical setting and describe that transient p53 inhibition could be used to limit the enrichment of cells with such mutations.
基于CRISPR/ cas9的工具有望通过促进致病突变的纠正来改变基因治疗领域。然而,CRISPR/Cas9会产生DNA损伤,从而引发以肿瘤抑制因子p53为中心的DNA损伤反应。从这个研究的角度来看,我们讨论了这一点的含义,并描述了CRISPR-p53与癌症相关基因的相互作用组,如果发生突变,可以使细胞在暴露于CRISPR/Cas9后具有选择性优势。我们建议在临床环境中对CRISPR-p53相互作用组中的基因进行监测,并描述了短暂的p53抑制可用于限制具有此类突变的细胞的富集。
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引用次数: 0
HSP90 as an emerging barrier to immune checkpoint blockade therapy HSP90作为免疫检查点阻断治疗的新屏障
Pub Date : 2022-04-22 DOI: 10.18632/oncoscience.554
D. Tang, Rui Kang
Immunotherapy, especially the use of immune checkpoint inhibitors, has improved overall survival in cancer patients. However, a large proportion of patients initially do not respond to treatment or relapse after a period of response. Heat shock protein 90 (HSP90) is a conserved molecular chaperone that promotes the maturation and folding of substrate proteins involved in many different cellular pathways. Our recent drug screen and functional assay identified HSP90 as a universal control of the protein stability of nuclear transcription factor STAT1 in a variety of different cancer cells, thereby promoting subsequent gene expression of immune checkpoint molecules (IDO1 and PD-L1). In vivo, we used different mouse models of pancreatic cancer and demonstrated that targeting HSP90 enhanced the efficacy of PD-1 blockade therapy. These findings establish HSP90 as a targetable vulnerability in immune therapy.
免疫疗法,特别是免疫检查点抑制剂的使用,提高了癌症患者的总生存率。然而,很大一部分患者最初对治疗没有反应或在一段时间后复发。热休克蛋白90 (HSP90)是一种保守的分子伴侣,它促进底物蛋白的成熟和折叠,参与许多不同的细胞途径。我们最近的药物筛选和功能分析发现,HSP90是多种不同癌细胞中核转录因子STAT1蛋白稳定性的普遍控制因子,从而促进免疫检查点分子(IDO1和PD-L1)的后续基因表达。在体内,我们使用不同的胰腺癌小鼠模型,证明靶向HSP90可增强PD-1阻断治疗的疗效。这些发现证实了HSP90在免疫治疗中是一个可靶向的易感性。
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引用次数: 1
Crosstalk between KIF15 and AR in castrate-resistant prostate cancers 去势抵抗性前列腺癌中KIF15和AR之间的串扰
Pub Date : 2022-04-22 DOI: 10.18632/oncoscience.556
Han Yang, Xuesen Dong
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引用次数: 0
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