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Antibody-drug Conjugates in Cancer Treatment: An Overview 癌症治疗中的抗体药物共轭物:概述
Pub Date : 2024-07-25 DOI: 10.9734/jcti/2024/v14i3259
Nikita Gupta, L. S. Geethika, Payavula Sneha
The development of antibody-drug conjugates (ADCs) has significantly impacted cancer therapy, progressing from foundational discoveries in the late 19th century to contemporary clinical applications. With the approval of the first ADC in 2000 and subsequent advancements, including over 30 ADCs in advanced clinical development, the therapeutic landscape for cancer patients has undergone a notable transformation. From initial cleavable linker technologies to the latest third-generation ADCs, continuous innovation in ADC design has been evident. Novel conjugation and linker technologies, alongside the identification of specific target antigens in solid cancers, have reinvigorated prospects for treating challenging malignancies. However, challenges such as off-target toxicity and heterogeneous antigen expression persist. The prevailing empirical approach to systemic cancer therapy administration presents challenges, including potential under-treatment of aggressive disease and over-treatment of indolent conditions, along with frequent adverse effects. Robust prognostic markers are essential to differentiate disease aggressiveness levels, guide treatment decisions, and anticipate adverse effects. Companion diagnostics for targeted therapies, such as HER-2 status for trastuzumab in breast cancer and BCR–ABL mutations for imatinib resistance in CML, enable personalized treatment strategies. Similarly, BRCA mutations predict response to PARP inhibitors in breast and ovarian cancers, while BRAF mutations guide treatment with BRAF inhibitors in melanoma. Patient selection strategies for clinical trials involving ADCs rely on prospective selection or retrospective analysis, each with its merits and challenges.
抗体药物结合体(ADC)的发展对癌症治疗产生了重大影响,从 19 世纪末的基础发现发展到当代的临床应用。随着第一种 ADC 于 2000 年获得批准以及随后取得的进展(包括 30 多种处于后期临床开发阶段的 ADC),癌症患者的治疗格局发生了显著变化。从最初的可裂解连接体技术到最新的第三代 ADC,ADC 设计的不断创新有目共睹。新型共轭和连接体技术以及实体瘤特异性靶抗原的确定,为治疗具有挑战性的恶性肿瘤带来了新的希望。然而,脱靶毒性和抗原表达异质性等挑战依然存在。目前对全身性癌症治疗采用的经验性方法也带来了挑战,包括可能对侵袭性疾病治疗不足,对轻度疾病治疗过度,以及频繁出现的不良反应。可靠的预后标志物对于区分疾病的侵袭程度、指导治疗决策和预测不良反应至关重要。靶向治疗的辅助诊断,如乳腺癌曲妥珠单抗的 HER-2 状态和慢性骨髓性白血病伊马替尼耐药的 BCR-ABL 基因突变,可实现个性化治疗策略。同样,BRCA 基因突变可预测乳腺癌和卵巢癌患者对 PARP 抑制剂的反应,而 BRAF 基因突变则可指导黑色素瘤患者使用 BRAF 抑制剂进行治疗。ADC 临床试验的患者选择策略取决于前瞻性选择或回顾性分析,每种策略都有其优点和挑战。
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引用次数: 0
The Role of Magnetic Resonance Imaging in Early Detection of Cancer: Present and Prospective Challenges for Future Research 磁共振成像在癌症早期检测中的作用:未来研究的现状与前瞻性挑战
Pub Date : 2024-04-19 DOI: 10.9734/jcti/2024/v14i1249
Yvanne Komenan
Aim: Records have been reported on the inflicting attributes of cancer in society and how early detection is necessary for preventive measure and as a proactive step. The use of Magnetic Resonance Imaging (MRI) has been proved as an effective and proficient diagnostic method for the early detection of cancer. This paper is an eye-opener for future researchers willing to investigate the use of magnetic resonance imaging in early detection of cancer. It critically discusses the present and prospective challenges in this area.Objectives: In this paper, historical records of cancer and the application of MRI in the early detection of cancer are presented. The mechanism of MRI operation together with comprehensive concepts behind its application for early cancer detection are also presented. Recent challenges regarding the subject matter are presented for the benefits of future researchers.Methodology: Literature review on recent studies conducted between 2009 and 2024 on using MRI for early cancer detection was discussed revealing the objectives, methodologies, results and conclusions from various studies.Conclusions: Several limitations and constraints from previous studies and those perceived are presented in this paper for future consideration of research studies in this area. In conclusion, twenty research limitations are stated therein which are gaps that should be bridged by future researchers.
目的:有关癌症在社会中的危害性以及早期发现对于预防措施和积极措施的必要性的记录已有报道。磁共振成像(MRI)已被证明是一种有效、熟练的早期癌症检测诊断方法。本文为未来愿意研究磁共振成像在癌症早期检测中的应用的研究人员提供了一个大开眼界的机会。它批判性地讨论了这一领域目前和未来的挑战:本文介绍了癌症的历史记录以及磁共振成像在癌症早期检测中的应用。本文还介绍了核磁共振成像的运行机制及其应用于早期癌症检测背后的综合概念。此外,还介绍了有关该主题的最新挑战,供未来研究人员参考:方法:讨论了 2009 年至 2024 年期间关于使用核磁共振成像进行早期癌症检测的最新研究文献综述,揭示了各项研究的目标、方法、结果和结论:本文介绍了以往研究中的若干限制和制约因素,以及所认识到的限制和制约因素,供今后在这一领域开展研究时参考。最后,本文提出了 20 项研究局限性,这些局限性是未来研究人员应弥补的差距。
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引用次数: 0
Optimization of PD-1 / PD-L1 Blockade to Increase NK Cells Cytotoxicity in Killing Cancer Cells: Article Review” 优化 PD-1 / PD-L1 阻断疗法,提高 NK 细胞杀死癌细胞的细胞毒性:文章综述"
Pub Date : 2024-04-08 DOI: 10.9734/jcti/2024/v14i1248
Joko Wibowo Sentoso, Agung Putra, I. Alif
Anti-PD-1 and anti-PD-L1 are therapies that have shown success in cancer treatment. However, while treating cancer with PD-1/PD-L1 blockade is similar, the clinical response rate is still low in certain cancers at around 40%. Therefore, therapeutic strategies are needed to increase PD-L1 expression and optimize PD-1/PD-L1 blockade therapy, so as to improve satisfactory therapeutic results. In tumors, IFNγ induces the expression of PD-L1 which is a cytokine secreted by Natural Killer cells. A study showed that PM21-NK cells induced large amounts of IFNγ and transfected PM21-NK cells adaptively induced PD-L1 expression. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, in vivo a significant increase in the antitumor effect of Natural Killer cells was found when combined with anti-PD-L1. PD-L1 blockade also resulted in increased persistence of Natural Killer cells in vivo and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with Natural Killer cell therapy regardless of baseline tumor PD-L1 status and suggest that Natural Killer cell therapy will likely increase the applicability of anti-PD-L1 treatment. In this review article, the author will discuss the method of optimizing PD-L1 blockade combined with Natural Killer cell therapy to increase the efficacy of treatment on cancer stem cells in the dormant phase.
抗-PD-1 和抗-PD-L1 是在癌症治疗中取得成功的疗法。然而,虽然 PD-1/PD-L1 阻断疗法治疗癌症的效果相似,但在某些癌症中,临床反应率仍然很低,约为 40%。因此,需要增加 PD-L1 表达和优化 PD-1/PD-L1 阻断疗法的治疗策略,以提高满意的治疗效果。在肿瘤中,IFNγ会诱导PD-L1的表达,而PD-L1是一种由自然杀伤细胞分泌的细胞因子。一项研究表明,PM21-NK 细胞能诱导大量 IFNγ,转染的 PM21-NK 细胞能适应性地诱导 PD-L1 的表达。在体外实验中,抗 PD-L1 处理对 PD-1 阴性 PM21-NK 细胞对 PD-L1+ 靶点的细胞毒性或细胞因子分泌没有直接影响。然而,在体内,当与抗-PD-L1联合使用时,自然杀伤细胞的抗肿瘤效果明显增强。PD-L1 阻断还能增加自然杀伤细胞在体内的持续性,并保留其细胞毒性表型。这些结果支持将抗PD-L1与自然杀伤细胞疗法结合使用,而不论肿瘤的基线PD-L1状态如何,并表明自然杀伤细胞疗法很可能会提高抗PD-L1疗法的适用性。在这篇综述文章中,作者将讨论优化PD-L1阻断与自然杀伤细胞疗法相结合的方法,以提高对休眠期癌症干细胞的疗效。
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引用次数: 0
Targeting Unique Features of Quiescent Cancer Stem Cells to Overcome Resistance and Recurrence in Cancer Therapy: A Review 针对静止癌症干细胞的独特特征克服癌症治疗中的抗药性和复发:综述
Pub Date : 2024-04-05 DOI: 10.9734/jcti/2024/v14i1247
Joko Wibowo Sentoso, Agung Putra, I. Alif
Quiescent cancer stem cells (QCSC) are non-proliferating cells that survive in the G0 phase and have low ki-67 expression and high p27 expression. QCSCs have the ability to evade most chemotherapy, and some subsequent treatments may result in a higher proportion of quiescent cancer stem cells in the tumor. QCSCs are also associated with cancer recurrence rates because they can re-enter the cell cycle to proliferate when tumor environmental conditions are favorable. QCSCs cause high rates of drug resistance and tumor recurrence, therefore it is necessary to understand the properties of QCSCs. QCSCs have a mechanism that regulates the transition between the proliferative phase and the stationary phase in cancer cells, therefore it is necessary to find new treatments to eliminate QCSCs in tumors. In this review, the authors discuss the mechanisms of QCSCs in inducing drug resistance and tumor recurrence as well as therapies to target QCSCs so that the rate of drug resistance and tumor recurrence can be reduced, including in this review: (i) identifying reactive quiescent cancer cells and eliminating them through anticancer reagents. cell cycle dependent; (ii) modulating the transition from the quiescent to the proliferative phase; and (iii) eliminate QCSC by targeting its unique features. Targeting cancer cells that are in proliferating and stationary phase may ultimately be used as a more effective therapeutic strategy for cancer treatment.
静止癌症干细胞(QCSC)是存活于G0期的非增殖细胞,具有低ki-67表达和高p27表达。静止癌干细胞有能力逃避大多数化疗,一些后续治疗可能会导致肿瘤中静止癌干细胞的比例升高。QCSCs还与癌症复发率有关,因为当肿瘤环境条件有利时,它们可以重新进入细胞周期进行增殖。QCSCs导致高耐药率和肿瘤复发率,因此有必要了解QCSCs的特性。QCSCs具有调控癌细胞增殖期和静止期过渡的机制,因此有必要寻找新的治疗方法来消除肿瘤中的QCSCs。在这篇综述中,作者讨论了QCSCs诱导耐药和肿瘤复发的机制以及针对QCSCs的疗法,从而降低耐药率和肿瘤复发率,其中包括以下内容:(细胞周期依赖性;(ii) 调节从静止期向增殖期的过渡;(iii) 针对 QCSC 的独特特征消灭它们。以处于增殖期和静止期的癌细胞为靶标,最终可能成为一种更有效的癌症治疗策略。
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引用次数: 0
Present State and Recent Developments of Artificial Intelligence and Machine Learning in Gastric Cancer Diagnosis and Prognosis: A Systematic Review 人工智能和机器学习在胃癌诊断和预后中的应用现状和最新发展:系统综述
Pub Date : 2024-02-24 DOI: 10.9734/jcti/2024/v14i1241
Rushin Patel, Mrunal Patel, Zalak Patel, Himanshu Kavani, Afoma Onyechi, Jessica Ohemeng-Dapaah, Dhruvkumar Gadhiya, Darshil Patel, Chieh Yang
Objective: The objective of this study is to thoroughly investigate the use of artificial intelligence (AI) and machine learning (ML) techniques for diagnosing and predicting prognosis in gastric cancer, utilizing the latest available data.Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)guidelines, a systematic review investigated AI and ML applications in gastric cancer diagnosis and prognostic prediction. PubMed and Google Scholar were searched from February 2019 to January 2024 using specific syntax. Eligible trials were selected based on inclusion criteria including recent publication, focus on AI and ML in gastric cancer, and reporting diagnostic or prognostic outcomes. Data were extracted and quality assessed independently, with discrepancies resolved through discussion. Due to design heterogeneity, detailed analysis was omitted, and descriptive summaries of included articles were provided.Results: This review included a total of 8 articles. AI and ML techniques, including  convolutional neural networks (CNN) and deep learning models, have played pivotal roles in accurately diagnosing chronic atrophic gastritis, predicting postoperative gastric cancer prognosis, and identifying peritoneal metastasis in gastric cancer patients. These technologies offer potential advantages such as streamlining diagnostic procedures, guiding treatment decisions,  and enhancing patient outcomes in gastric cancer management.Conclusion: In the near future, AI applications may have a significant role in the diagnosis and prognosis prediction of gastric cancer.
研究目的本研究旨在利用现有的最新数据,深入研究人工智能(AI)和机器学习(ML)技术在胃癌诊断和预后预测中的应用:按照系统综述和荟萃分析首选报告项目(PRISMA)指南,对人工智能和机器学习技术在胃癌诊断和预后预测中的应用进行了系统综述。使用特定语法检索了2019年2月至2024年1月期间的PubMed和Google Scholar。根据纳入标准筛选出符合条件的试验,包括近期发表、关注胃癌中的人工智能和ML、报告诊断或预后结果。数据提取和质量评估均由双方独立完成,不一致之处通过讨论解决。由于设计存在异质性,因此省略了详细分析,只提供了纳入文章的描述性摘要:本综述共纳入 8 篇文章。包括卷积神经网络(CNN)和深度学习模型在内的人工智能和 ML 技术在准确诊断慢性萎缩性胃炎、预测胃癌术后预后和识别胃癌患者腹膜转移方面发挥了关键作用。这些技术具有潜在的优势,如简化诊断程序、指导治疗决策、提高胃癌患者的治疗效果等:在不久的将来,人工智能应用可能会在胃癌诊断和预后预测方面发挥重要作用。
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引用次数: 0
Predictivity of Human Telomerase Reverse Transcriptase (h-TERT) in Oral Squamous Cell Carcinoma: Immunohistochemical Study 口腔鳞状细胞癌中人类端粒酶逆转录酶(h-TERT)的预测性:免疫组化研究
Pub Date : 2023-12-23 DOI: 10.9734/jcti/2023/v13i3237
Eman Mosaad, H. Elhendawy, Mina Mahfouz Elias Shenouda, N. El-sissy
Aims: Determine the potential role of h-TERT as a prognostic marker for oral squamous cell carcinoma by evaluating its immunohistochemical expression in different OSCC histologic grades in comparison with normal oral mucosa. Study Design: A retrospective study. Place and Duration: Oncology Center, Mansoura University, and Oral Pathology Department, Faculty of Dentistry, Mansoura University. The worked sample selected from the years (2015-2019). Methodology: Our study was accomplished on 30 OSCC cases and a control group of normal oral mucosa. Histopathologic grading of OSCCs was made using the WHO grade and Anneroth`s grading systems. Immunohistochemical expression of h-TERT was assessed in relation to different clinicopathological parameters. The data was analyzed using Pearson`s chi-square test to compare the differences between groups. Spearman's correlation co-efficiency test was used to test the association between different variables. A P value ≤ 0.05 was considered to be statistically significant. Results: A significant increased h-TERT expression was recorded from normal to OSCC groups (P=0.000). Additionally, elevated h-TERT expression was significantly correlated with the higher carcinoma histologic grade (P =0.025). There were high statistically significant differences in h-TERT expression concerning the parameters; Anneroth pattern of invasion (P= 0.049), depth of invasion (DOI, P=0.024), and lymphoplasmacytic infiltration (LPI, P=0.009). There were no statistically significant differences in h-TERT immunoexpression considering the clinical parameters; patient age, gender, anatomical sites, clinical shape of lesion, T, N, M, and TNM stages (Chi-square test, P values were > 0.05). Conclusions: Increased h-TERT immunoexpression from normal to OSCC groups suggests its involvement in malignant transformation. Additionally, the significant differential expression of h-TERT among different OSCC histologic grades signaling its valuable use as a biomarker for assessing the cellular malignant progression of oral carcinomas, but unreliable as a clinical tumor progression marker. Moreover, the significant correlation of h-TERT expression with LPI, DOI and pattern of invasion indicating its possible reliable role in tumor host relation during multistage carcinogenesis.
目的:通过评估 h-TERT 在不同 OSCC 组织学分级中的免疫组化表达,并与正常口腔黏膜进行比较,确定 h-TERT 作为口腔鳞状细胞癌预后标志物的潜在作用。 研究设计:回顾性研究。 地点和时间:曼苏尔大学肿瘤中心和曼苏尔大学牙科学院口腔病理学系。工作样本选自(2015-2019 年)。 研究方法:我们的研究对象是 30 例 OSCC 病例和正常口腔黏膜对照组。OSCC 的组织病理学分级采用 WHO 分级和 Anneroth's 分级系统。评估了 h-TERT 的免疫组化表达与不同临床病理参数的关系。数据采用皮尔逊卡方检验进行分析,以比较组间差异。斯皮尔曼相关系数检验用于检验不同变量之间的关联。P值≤0.05为具有统计学意义。 结果从正常组到 OSCC 组,h-TERT 表达均有明显增加(P=0.000)。此外,h-TERT表达的升高与癌组织学分级的升高明显相关(P=0.025)。h-TERT 表达与以下参数有高度统计学差异:Anneroth 侵袭模式(P= 0.049)、侵袭深度(DOI,P=0.024)和淋巴浆细胞浸润(LPI,P=0.009)。考虑到临床参数(患者年龄、性别、解剖部位、病变临床形态、T、N、M 和 TNM 分期),h-TERT 免疫表达差异无统计学意义(卡方检验,P 值均大于 0.05)。 结论从正常组到 OSCC 组,h-TERT 免疫表达的增加表明它参与了恶性转化。此外,h-TERT在不同OSCC组织学分级中的表达存在显著差异,这表明它可作为评估口腔癌细胞恶性进展的生物标记物,但作为临床肿瘤进展标记物并不可靠。此外,h-TERT的表达与LPI、DOI和侵袭模式有明显的相关性,表明它在多期癌变过程中可能在肿瘤与宿主的关系中发挥可靠的作用。
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引用次数: 0
Anterior Thigh Myxofibrosarcoma with Management of Wide Excision and Modified Anterior Thigh Compartment Resection: A Case Report 大腿前侧肌纤维肉瘤,采用大范围切除和改良的大腿前室切除术治疗:病例报告
Pub Date : 2023-12-23 DOI: 10.9734/jcti/2023/v13i3238
Joko Wibowo Sentoso, K. Yarsa
Introduction: Myxofibrosarcoma (MFS) is a type of malignancy from the group of malignant fibrous histiocytoma. Myfxofibrosarcoma is a type of soft tissue neoplasm that is aggressive. The clinical symptoms are not pathognomonic and the histological picture is very heterogeneous, often receiving delayed treatment and causing misdiagnosis. Complementary histochemical and immunohistochemical staining is mandatory to confirm the diagnosis of MFS. Extensive surgical treatment and followed by radiotherapy is the first choice of myxofibrosarcoma treatment. Case Presentation: A 54-years old woman complained of a lump on her left thigh that had been getting bigger for the past 2 years. The lump initially looked the size of a marble, then grew to the size of a tennis ball in the last 7 months. On physical examination, a mass was found in the left thigh area, a hard, fixed mass, the size of a tennis ball. Fine needle aspiration examination showed suspicious results for myxofibrosarcoma. The patient underwent a Magnetic Resonance Imaging examination in the left lower extremity area and underwent wide excision and anterior thigh compartment resection surgery. Discussion: Wide resection is the standard treatment for MFS [4]. The choice of procedure for each patient is different and should be based on tumor size, location, stage, surrounding neurovascular and bony elements, as well as functional and cosmetic considerations [4]. The minimum resection margin in MFS is at least 1 cm which aims to minimize the risk of local recurrence [4]. The recommended resection margin is at least 2 cm for MFS resection [4]. We had plan a 2 cm margin of the entire preoperative MRI enhancement area. It should be noted that the local recurrence rate for MFS in margin-negative resections is relatively high compared with other STS subtypes. Conclusion: We recommend Wide Excison and Modified Anterior Thigh compartment Resection is recommended procedure for anterior thigh myxofibrosarcoma. This procedure involves preserving uncontaminated thigh neurovascular, and only resecting one of the sarcoma-infiltrated muscle heads and preserving the other quadriceps muscle head of the thigh to maintain knee extension function. This paper is the first report on the successful treatment of anterior thigh myxofibrosarcoma without weakness of knee extension complication.
简介肌纤维肉瘤(MFS)是恶性纤维组织细胞瘤中的一种恶性肿瘤。肌纤维肉瘤是一种侵袭性软组织肿瘤。其临床症状并不具有致病性,组织学表现也很不一致,往往会延误治疗并造成误诊。组织化学和免疫组化染色是确诊 MFS 的必备条件。广泛手术治疗和随后的放射治疗是治疗肌纤维肉瘤的首选方法。 病例介绍:一名 54 岁的女性主诉其左大腿上有一个肿块,且在过去两年中不断增大。肿块最初看起来像弹珠大小,然后在过去 7 个月中增大到网球大小。体格检查时,在左大腿部位发现了一个肿块,肿块坚硬、固定,有网球大小。细针穿刺检查结果显示疑似肌纤维肉瘤。患者接受了左下肢区域的磁共振成像检查,并接受了大腿前隔间切除手术。 讨论:广泛切除是 MFS 的标准治疗方法[4]。每位患者选择的手术方式不同,应根据肿瘤大小、位置、分期、周围神经血管和骨质以及功能和外观等因素综合考虑[4]。MFS 的最小切除边缘至少为 1 厘米,目的是将局部复发的风险降至最低[4]。建议 MFS 的切除边缘至少为 2 厘米[4]。我们在整个术前磁共振成像增强区规划了2厘米的切缘。值得注意的是,与其他 STS 亚型相比,边缘阴性切除的 MFS 局部复发率相对较高。 结论:对于大腿前侧肌纤维肉瘤,我们推荐采用宽切除和改良大腿前室切除术。该手术保留未受污染的大腿神经血管,仅切除肉瘤浸润的一个肌头,保留大腿另一个股四头肌肌头,以维持膝关节伸展功能。本文首次报道了成功治疗大腿前侧肌纤维肉瘤而无膝关节伸展无力并发症的病例。
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引用次数: 0
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Journal of Cancer and Tumor International
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