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Enhanced Diagnosis of Lung and Colon Cancer Severity Through Deep Feature Analysis Using DenseNet201 and SVM With Histopathological Images: A Super-Resolution Approach 基于组织病理图像的DenseNet201和SVM深度特征分析增强肺癌和结肠癌严重程度诊断:一种超分辨率方法。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-23 DOI: 10.1002/cnr2.70439
Pragati Patharia, B. Surya Prasad Rao, Prabira Kumar Sethy, Ashoka Kumar Ratha, Aziz Nanthaamornphong

Background and Aim

The worldwide healthcare system faces significant challenges due to the increasing prevalence of lung and colon cancer, highlighting the need for timely and accurate detection to improve patient prognosis. The precision of cancer diagnosis is highly dependent on the expertise of histopathologists, making it a complex and demanding endeavor. A shortage of sufficiently skilled experts can lead to the ineffective allocation of healthcare resources, potential misdiagnoses, and unwarranted interventions, ultimately threatening patient well-being. However, technological advancements have introduced deep learning as a powerful tool in clinical applications, particularly in the field of medical imaging. This study aims to develop a novel diagnostic method leveraging deep learning techniques to enhance the accuracy of lung and colon cancer detection.

Methods

The study utilized the LC25000 dataset, which comprises 25 000 histopathological images of lung and colon tissue. A novel approach was implemented using a Fast Super-Resolution Convolutional Neural Network (FSRCNN) for image enhancement and a Support Vector Machine (SVM) model based on DenseNet201 for classification. The FSRCNN was employed to improve the clarity and detail of images by increasing their resolution, which is crucial for accurate cancer detection.

Results

The proposed model demonstrated superior performance compared to existing Convolutional Neural Network (CNN) models. It achieved an overall accuracy of 98.00%, precision of 98.10%, sensitivity of 98%, F1 score of 0.98, and specificity of 99.50%. These metrics indicate a significant enhancement in diagnostic accuracy and reliability, underscoring the effectiveness of the FSRCNN and SVM-based DenseNet201 model.

Conclusion

The implementation of the FSRCNN and SVM-based DenseNet201 model provided substantial improvements in the detection of lung and colon cancer, as evidenced by high accuracy and specificity metrics. While the LC25000 dataset offered a solid foundation for this analysis, future research should aim to validate the model's effectiveness using a broader array of diverse and extensive datasets. Additionally, integrating supplementary diagnostic techniques, such as genetic data and electronic health records, could further enhance the model's diagnostic precision and practical application in cancer diagnosis.

背景与目的:由于肺癌和结肠癌患病率的增加,全球医疗保健系统面临着重大挑战,突出了及时准确检测以改善患者预后的必要性。癌症诊断的准确性高度依赖于组织病理学家的专业知识,使其成为一项复杂而艰巨的工作。缺乏足够熟练的专家可能导致医疗资源的无效分配、潜在的误诊和无根据的干预,最终威胁到患者的健康。然而,技术进步使深度学习成为临床应用的有力工具,特别是在医学成像领域。本研究旨在开发一种新的诊断方法,利用深度学习技术来提高肺癌和结肠癌检测的准确性。方法:本研究利用LC25000数据集,该数据集包含25000张肺和结肠组织病理图像。采用快速超分辨率卷积神经网络(FSRCNN)进行图像增强,采用基于DenseNet201的支持向量机(SVM)模型进行分类。FSRCNN通过提高图像的分辨率来提高图像的清晰度和细节,这对于准确检测癌症至关重要。结果:与现有的卷积神经网络(CNN)模型相比,所提出的模型表现出更好的性能。总体准确度为98.00%,精密度为98.10%,灵敏度为98%,F1评分为0.98,特异性为99.50%。这些指标表明诊断准确性和可靠性显著提高,强调了FSRCNN和基于svm的DenseNet201模型的有效性。结论:FSRCNN和基于svm的DenseNet201模型的实施在肺癌和结肠癌的检测方面提供了实质性的改进,具有较高的准确性和特异性指标。虽然LC25000数据集为这一分析提供了坚实的基础,但未来的研究应该旨在使用更广泛的多样化和广泛的数据集来验证模型的有效性。此外,整合辅助诊断技术,如遗传数据和电子健康记录,可以进一步提高模型的诊断精度和在癌症诊断中的实际应用。
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引用次数: 0
Incidence and Clinical Outcomes of Vitamin D Status and Myeloma Bone Disease Among Patients With Newly Diagnosed Multiple Myeloma (MM) in a Tropical Country—Retrospective Cohort Study 在一项热带国家回顾性队列研究中,新诊断的多发性骨髓瘤(MM)患者中维生素D状态和骨髓瘤骨病的发病率和临床结果
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-23 DOI: 10.1002/cnr2.70431
Chi Ching Lim, Wai San Wilson Tam, Widanalage Sanjay Prasad De Mel, Siew Ping Lang, Wee Joo Chng, Cinnie Yentia Soekojo, Fang Fang Song, Melissa Gaik Ming Ooi

Objective

The retrospective data analysis on 80 patients from 2018 to 2022 aimed to determine the incidence and clinical outcomes of vitamin D status and myeloma bone disease among newly diagnosed multiple myeloma (MM) patients in Singapore.

Method

Patients' demographics, bone health data and bone disease management were collected. Chi-square test was conducted to compare variables between patients who survived versus those who demised. Survival differences were compared using log-rank analysis and plotted using Kaplan–Meier estimates. Multivariable survival analysis was conducted using Cox Regression.

Results

Fifty-nine (73.8%) patients had myeloma bone disease at diagnosis, and 42 (71.2%) of these patients had skeletal-related adverse events at diagnosis. The compliance to bone health management needs to be optimized, as only 70 patients had their vitamin D level tested at diagnosis, of which 48 (68.7%) patients were vitamin D insufficient or deficient. Bone disease data did not correlate with mortality. Higher mortality was initially observed among patients with non-Chinese (p = 0.03), R-ISS 3 (p = 0.001), and renal involvement at diagnosis (p = 0.035). R-ISS staging remained the only statistically significant variable after adjusting for race (adjusted HR 3.99; 95% CI 1.58–10.07).

Conclusion

The study found no correlation between myeloma bone health data and survival outcomes in our centre.

目的:回顾性分析2018 - 2022年新加坡80例患者的数据,旨在确定新加坡新诊断的多发性骨髓瘤(MM)患者维生素D状况与骨髓瘤骨病的发病率和临床结局。方法:收集患者人口统计资料、骨健康资料和骨病管理资料。采用卡方检验比较存活患者和死亡患者之间的变量。生存差异采用对数秩分析进行比较,并采用Kaplan-Meier估计绘制。采用Cox回归进行多变量生存分析。结果:骨髓瘤骨病59例(73.8%),其中42例(71.2%)有骨骼相关不良事件。仅70例患者在诊断时进行了维生素D水平检测,其中48例(68.7%)患者维生素D不足或缺乏,需要优化骨骼健康管理依从性。骨病数据与死亡率无关。在非华裔(p = 0.03)、R-ISS 3 (p = 0.001)和诊断时肾脏受累(p = 0.035)的患者中,最初观察到较高的死亡率。在种族因素调整后,R-ISS分期仍然是唯一具有统计学意义的变量(调整后HR为3.99;95% CI为1.58-10.07)。结论:研究发现骨髓瘤骨骼健康数据与我们中心的生存结果没有相关性。
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引用次数: 0
Risk Factors for Infectious Adverse Events in Newly Diagnosed Acute Myeloid Leukemia Patients Treated With Venetoclax Combinations: A Retrospective Single-Centre Real-World Experience 新诊断急性髓系白血病患者联合Venetoclax治疗感染性不良事件的危险因素:一项回顾性单中心真实世界经验。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-22 DOI: 10.1002/cnr2.70432
Olgu Erkin Çınar, Azade Kanat, Kerim Erer, Rasim Şahin, Esma Eryılmaz Eren, Esra Yıldızhan

Background

Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern.

Aims

This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting.

Methods and Results

We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥ 2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5–35). A total of 34 (23.8%) grade ≥ 2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR = 1.037, p = 0.005) and interacting concomitant medications (OR = 9.99, p < 0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs.

Conclusion

IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.

背景:venetoclax为基础的(ven)联合治疗已成为急性髓性白血病(AML)患者不适合强化化疗的标准治疗方案。然而,相关的感染性不良事件(iae)风险仍然是一个重要的临床问题。目的:本研究旨在评估在现实环境中接受venetoclax联合治疗的新诊断AML患者iae的发生率、特征和危险因素。方法和结果:我们对联合低甲基化药物或低剂量阿糖胞苷(LDAC)治疗的AML患者进行了回顾性队列研究,并以治疗周期为基础进行了分析。收集临床和实验室数据,包括IAE特征、中性粒细胞减少持续时间和伴随用药,并根据CTCAE v5.0标准纳入≥2级IAE。该队列包括143个治疗周期的43名患者,中位中性粒细胞减少持续时间为13天(5-35天)。共发生34例(23.8%)≥2级iae,发生率为每121患者天1例。多因素分析确定了中性粒细胞减少延长(天,OR = 1.037, p = 0.005)和联合用药(OR = 9.99, p)。结论:在venetoclax治疗的AML患者中,iae仍然存在很大的风险,特别是在中性粒细胞减少延长和同时存在药物相互作用的情况下。优化venetoclax方案和仔细管理相互作用的药物可以减轻这些风险。
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引用次数: 0
Successful Combination Therapy With Lenvatinib Plus Pembrolizumab for Rare Case of Advanced Renal Cell Carcinoma With Ocular Adnexal Metastasis Lenvatinib联合Pembrolizumab成功治疗罕见的晚期肾癌伴眼附件转移病例。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-21 DOI: 10.1002/cnr2.70437
Yozo Mitsui, Masato Uetani, Fumito Yamabe, Hideyuki Kobayashi, Aki Mitsuda, Naobumi Tochigi, Koichi Nakajima

Background

Ocular adnexal (OA) metastasis from renal cell carcinoma (RCC) is a very rare end-stage entity with a poor prognosis. Reported here is a case of metastatic RCC for which combination therapy with lenvatinib plus pembrolizumab was given for OA metastasis and achieved an excellent response.

Case

A 54-year-old man was referred to our hospital complaining of right eye pain, with a right intraocular tumor showing a maximum diameter of 3 cm subsequently revealed by computed tomography (CT) imaging. Additionally, masses in the right kidney, both lungs, and right iliac bone were noted, while a subsequent percutaneous renal needle biopsy indicated RCC with multiple metastases (cT3aN0M1). Administration of lenvatinib plus pembrolizumab combination therapy was given as first-line treatment, with rapid improvement of the elevated inflammatory response and anemia noted. Findings obtained 17 months following initiation of therapy showed significant shrinkage of the primary and iliac bone lesions, while the OA and lung metastatic lesions had completely disappeared.

Conclusion

These results highlight the potential of lenvatinib plus pembrolizumab combination therapy for the treatment of RCC with OA metastasis, which is generally considered to be an end stage for cancer cases.

背景:眼附件(OA)转移肾细胞癌(RCC)是一个非常罕见的终末期实体,预后差。本文报告一例转移性RCC,给予lenvatinib + pembrolizumab联合治疗OA转移,并取得了极好的疗效。病例:一名54岁男性,因右眼疼痛就诊,经CT检查发现右眼内肿瘤,最大直径3cm。此外,右肾、双肺和右髂骨均可见肿块,随后经皮肾穿刺活检显示肾细胞癌伴多发转移灶(cT3aN0M1)。给予lenvatinib + pembrolizumab联合治疗作为一线治疗,炎症反应升高和贫血得到快速改善。开始治疗后17个月的结果显示原发性和髂骨病变明显缩小,而OA和肺转移性病变完全消失。结论:这些结果突出了lenvatinib + pembrolizumab联合治疗RCC合并OA转移的潜力,OA转移通常被认为是癌症病例的终末期。
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引用次数: 0
Fuelling Neuroblastoma: Genomic Analysis of Ketolytic and Glycolytic Gene Expression in Relation to MYCN Oncogene Amplification, Stage and Prognosis 促进神经母细胞瘤:与MYCN癌基因扩增、分期和预后相关的酮解和糖酵解基因表达的基因组分析。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-19 DOI: 10.1002/cnr2.70429
Joseph W. Molloy, Karl Keogh, Mary-Kate McLoughlin, Lauren Devitt, David Lee, Eric Downer, David Robert Grimes, Denis Barry

Background

Neuroblastoma (NB) is a childhood cancer of the sympathetic nervous system, and its prognosis is poor. NB cells undergo transcriptional changes to utilise aerobic glycolysis as their primary metabolic pathway, which provides an immediate source of ATP to meet high biosynthetic demands. Alternative metabolic fuel inputs, including ketone bodies which require oxidative phosphorylation, may impact the proliferative capacity of NB.

Aims

In this exploratory study, the expression of glycolytic and ketolytic genes in the context of MYCN oncogene amplification, tumour staging 1–4 and Kaplan–Meier survivability was investigated using the R2: Genomics analysis and visualisation platform (http://r2.amc.nl), database.

Methods and Results

Three NB genomics datasets were assessed in the R2 platform and further analysed in GraphPad Prism to investigate the relationships between glycolytic and ketolytic gene expression and prognosis. Glycolytic gene expression is increased in MYCN amplified, metastatic tumours and is associated with worse event free survival. Ketolytic gene expression is lower in metastatic tumours and is associated with better event free survivability. The glycolytic gene expression profile of NB suggests that elevated levels correlate with a low probability of survival. Ketolytic gene expression patterns suggest a decreased reliance for ketolytic energy, which may be exploited to slow tumourigenic growth.

Conclusions

This study validates glycolytic and ketolytic gene expression profiles in metastatic and MYCN amplified NB tumours and through conditional analysis suggests the potential use of these genes in prognosis prediction. Furthermore, the study highlights the reliability and utility of genomic databases as oncogenomic tools for NB research.

背景:神经母细胞瘤(Neuroblastoma, NB)是一种儿童期交感神经系统肿瘤,预后较差。NB细胞通过转录变化利用有氧糖酵解作为其主要代谢途径,这提供了ATP的直接来源,以满足高生物合成需求。替代代谢燃料输入,包括需要氧化磷酸化的酮体,可能会影响NB的增殖能力。目的:在这项探索性研究中,使用R2:基因组学分析和可视化平台(http://r2.amc)研究糖酵解和酮解基因在MYCN癌基因扩增、肿瘤分期1-4和Kaplan-Meier生存能力背景下的表达。问),数据库。方法与结果:在R2平台上评估3个NB基因组数据集,并在GraphPad Prism中进一步分析糖酵解和酮解基因表达与预后的关系。糖酵解基因表达在MYCN扩增的转移性肿瘤中增加,并与较差的无事件生存相关。在转移性肿瘤中,酮解基因表达较低,与更好的无事件生存率相关。NB的糖酵解基因表达谱表明,高水平的糖酵解与低存活率相关。酮解基因表达模式表明对酮解能量的依赖性降低,这可能被用来减缓肿瘤的生长。结论:本研究验证了糖酵解和酮解基因在转移性和MYCN扩增的NB肿瘤中的表达谱,并通过条件分析提示这些基因在预后预测中的潜在应用。此外,该研究强调了基因组数据库作为NB研究的肿瘤基因组工具的可靠性和实用性。
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引用次数: 0
Assessing Second-Line Treatment Strategies and Outcomes in Epidermal Growth Factor Receptor (EGFR) Oncogene-Driven Stage IV Non-Small Cell Lung Cancer, Following a First-Line EGFR-TKI Therapy 评估表皮生长因子受体(EGFR)癌基因驱动的IV期非小细胞肺癌在一线EGFR- tki治疗后的二线治疗策略和结果
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-17 DOI: 10.1002/cnr2.70428
Meghana Maddula, Annelise Decaria, Bea Brown, John Simes, Michael Boyer, Venessa Chin
<div> <section> <h3> Background</h3> <p>Oncogene-driven metastatic non-small cell lung cancer (mNSCLC) is associated with poor survival outcomes, despite advancements in first-line tyrosine kinase inhibitor (TKI) therapies.</p> </section> <section> <h3> Aims</h3> <p>This study aimed to characterise second-line treatment strategies for epidermal growth factor receptor (EGFR)-driven mNSCLC, and to evaluate associated clinical outcomes using real-world data.</p> </section> <section> <h3> Materials</h3> <p>The EnRICH study prospectively collected clinical data on patients diagnosed with lung cancer from NSW, Australia. Patients with EGFR-driven mNSCLC who received second-line therapy following progression on first-line EGFR-TKI were included in this analysis. Outcomes assessed included progression-free survival (PFS2) and overall survival (OS), measured from second-line treatment.</p> </section> <section> <h3> Results</h3> <p>Of 2000 patients with newly diagnosed lung cancer, between 2016 and 2021, 1720 had NSCLC and 679 had metastatic disease. Among these, 647 underwent molecular testing, with 133 harboring an EGFR mutation. Of these 133, 80 patients received first-line TKI therapy. From this group, 68 who subsequently received second-line treatment following disease progression on first-line TKI were included in this analysis. Of these 68 patients, 77% (<i>n</i> = 52/68) were treated with a first- or second-generation TKI (Erlotinib: <i>n</i> = 39, Gefitinib: <i>n</i> = 7, Afatinib: <i>n</i> = 6) in the first-line setting. The remaining 16 patients received the third-generation TKI Osimertinib. Of the total 68 patients in this cohort, in the second-line setting, 45 patients underwent a change in their systemic therapy, and the remaining 23 patients received radiotherapy either with cessation of first-line TKI (<i>n</i> = 11) or in addition to continuation of first-line TKI (<i>n</i> = 12). Of the 45 patients who underwent a change in their systemic therapy, 32 received systemic therapy alone in the second-line setting and 13 received radiotherapy in addition to a change in systemic therapy. Of these 45 patients, 33 received a TKI, with the majority receiving Osimertinib (<i>n</i> = 28). Median PFS2 was 3.0 months (95% CI: 1.32–5.49), with no significant difference between patients treated with second-line TKI and those receiving other therapies (<i>p</i> = 0.24). Median OS was 15.0 months (95% CI: 13.24–23.66) and similarly did not differ significantly between second-line TKI and alternative treatment strategies (<i>p</i> = 0.17).</p>
背景:尽管一线酪氨酸激酶抑制剂(TKI)治疗取得了进展,但癌基因驱动的转移性非小细胞肺癌(mNSCLC)与较差的生存结果相关。目的:本研究旨在描述表皮生长因子受体(EGFR)驱动的小细胞肺癌的二线治疗策略,并使用现实世界数据评估相关的临床结果。资料:EnRICH研究前瞻性地收集了澳大利亚新南威尔士州诊断为肺癌的患者的临床数据。在一线EGFR-TKI治疗进展后接受二线治疗的egfr驱动的小细胞肺癌患者被纳入该分析。评估的结果包括无进展生存期(PFS2)和总生存期(OS),从二线治疗开始测量。结果:在2016年至2021年期间,2000例新诊断的肺癌患者中,1720例为非小细胞肺癌,679例为转移性疾病。其中,647人接受了分子检测,133人携带EGFR突变。在这133名患者中,80名患者接受了一线TKI治疗。从这一组中,68名在一线TKI治疗后疾病进展后接受了二线治疗的患者被纳入本分析。在这68名患者中,77% (n = 52/68)在一线接受了第一代或第二代TKI治疗(厄洛替尼:n = 39,吉非替尼:n = 7,阿法替尼:n = 6)。其余16例患者接受第三代TKI奥西替尼治疗。在该队列的68名患者中,在二线治疗中,45名患者改变了全身治疗,其余23名患者在停止一线TKI治疗(n = 11)或在继续一线TKI治疗的同时接受放疗(n = 12)。在45例改变全身治疗的患者中,32例在二线环境中单独接受全身治疗,13例在改变全身治疗的同时接受放疗。在这45例患者中,33例接受了TKI,其中大多数接受了奥西替尼(n = 28)。中位PFS2为3.0个月(95% CI: 1.32-5.49),接受二线TKI治疗的患者与接受其他治疗的患者之间无显著差异(p = 0.24)。中位OS为15.0个月(95% CI: 13.24-23.66),二线TKI和替代治疗策略之间同样无显著差异(p = 0.17)。结论:使用来自EnRICH的真实世界数据,这是澳大利亚该队列中最大的回顾性分析,并且在很大程度上早于一线奥西替尼的使用。研究结果显示二线使用奥西替尼的趋势,即使在一线TKI后,生存率也没有显着差异。然而,在方法上仍然存在显著的异质性。然而,缺乏可靠的二线数据强调了研究新的治疗方法的必要性。
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引用次数: 0
Toward Precision Medicine: Gene Therapy Applications in the Management of Uveal Melanoma 迈向精准医学:基因治疗在葡萄膜黑色素瘤治疗中的应用。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-14 DOI: 10.1002/cnr2.70425
Alireza Azani, Vahid Ghassemifar, Zahra Mehrdad, Maryam Saberivand, Anahid Bagheripour, Safa Tahmasebi, Hossein Gharedaghi, Malihe Sharafi, Hassan Foroozand, Mohammad Saeed Soleimani Meigoli, Saba Pourali, Arash Salmaninejad, Faeze Ahmadi Beni, Qumars Behfar

Background

Uveal melanoma (UM) is the prevailing malignant tumor that develops within the eye in adults, and it has a bleak outlook because of the few treatment choices available and the high likelihood of returning after treatment. Currently, surgical intervention, radiation therapy, and a combination of both modalities are available therapeutic modalities for controlling UM. However, these techniques are associated with notable adverse effects and have limited efficacy. Therefore, there is a lack of sufficient and reliable therapies for UM, especially for advanced and metastatic UM forms. This review aims to summarize the clinical features and current therapies of UM and highlight recent progress in gene therapy approaches.

Recent Findings

Significant developments in gene therapy have introduced multiple strategies for targeting UM. Gene silencing using siRNA and shRNA has shown efficacy in downregulating oncogenic pathways. CRISPR/Cas9-based editing has enabled selective disruption of tumor-promoting genes, sensitizing tumor cells to targeted inhibitors. Restoration of tumor-suppressive miRNAs has reduced proliferation, migration, and invasion of UM cells in preclinical models. Suicide gene therapy has demonstrated potent cytotoxicity in xenografts. Moreover, oncolytic viruses and stem-cell–associated delivery systems provide novel mechanisms for tumor-selective gene expression and immune activation. Although challenges persist—such as delivery efficiency, immune responses, and genetic heterogeneity—ongoing innovations in vector design, non-viral nanoformulations, and mutation-guided therapies continue to enhance clinical feasibility.

Conclusion

Gene therapy provides improved safety profiles and the possibility of tailored treatment strategies by integrating information on gene expression patterns and DNA alterations. In the future, gene therapy has the potential to improve the treatment of UM by targeting specific genetic mutations driving tumor growth and may offer new hope for patients with advanced stages of UM.

背景:葡萄膜黑色素瘤(Uveal melanoma, UM)是发生在成人眼内的常见恶性肿瘤,由于可用的治疗选择很少,且治疗后复发的可能性很高,因此前景黯淡。目前,外科手术、放射治疗和两者结合是控制UM的有效治疗方式。然而,这些技术有明显的副作用,疗效有限。因此,对于UM,特别是晚期和转移性UM,缺乏足够和可靠的治疗方法。本文综述了UM的临床特点和目前的治疗方法,并重点介绍了基因治疗方法的最新进展。最近的发现:基因治疗的重大发展已经引入了多种针对UM的策略。使用siRNA和shRNA进行基因沉默已显示出下调致癌途径的有效性。基于CRISPR/ cas9的编辑能够选择性地破坏肿瘤促进基因,使肿瘤细胞对靶向抑制剂敏感。在临床前模型中,肿瘤抑制mirna的恢复减少了UM细胞的增殖、迁移和侵袭。自杀基因疗法在异种移植物中显示出强大的细胞毒性。此外,溶瘤病毒和干细胞相关的传递系统为肿瘤选择性基因表达和免疫激活提供了新的机制。尽管挑战依然存在,例如递送效率、免疫反应和遗传异质性,但在载体设计、非病毒纳米制剂和突变引导疗法方面正在进行的创新继续提高临床可行性。结论:通过整合基因表达模式和DNA改变的信息,基因治疗提供了更好的安全性和定制治疗策略的可能性。在未来,基因治疗有可能通过靶向驱动肿瘤生长的特定基因突变来改善UM的治疗,并可能为晚期UM患者带来新的希望。
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引用次数: 0
Exploitation of Biocomputational Approaches for siRNA-Mediated Gene Silencing of HPV: A Novel Therapeutic Strategy for Cervical Cancer 利用sirna介导的HPV基因沉默的生物计算方法:一种新的宫颈癌治疗策略。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-14 DOI: 10.1002/cnr2.70434
Md. Habib Ullah Masum, Rehana Parvin, Homaira Pervin Heema, Aklima Akter, Jannatul Ferdous

Background

With recurrent high-risk human papillomavirus (HPV) infections, especially HPV16 and HPV18, cervical cancer is the fourth most common disease among women. The functional alterations of the E6 and E7 proteins are essential to the oncogenic process of high-risk HPVs and cervical cancer development.

Aims

The objective of this research is to design highly targeted and efficient small interfering RNAs (siRNAs) that target both HPV16 and HPV18, employing cutting-edge computational approaches to enhance therapeutic potential through a systematic bioinformatics-driven approach.

Methods and Results

This study utilized the i-Score Designer to identify and evaluate four potential small interfering RNAs (siRNAs) (E6_69, E6_451, E7_66, and E7_193) based on various algorithm criteria, including Ui-Tei, Amarzguioui, i-Score, and Reynolds scores. Consequently, a docking analysis was conducted to elucidate the intermolecular interactions between the RNA-induced silencing complex (RISC) proteins and the designed siRNAs. All siRNAs passed the recommended cutoff values, indicating a strong potential for gene silencing. Thermodynamic and structural analyses revealed that the designed siRNAs had favrable melting temperatures and free energies, suggesting adequate stability for effective gene silencing. Further, docking analysis demonstrated significant binding affinities and interaction profiles with the major RISC proteins (Dicer, Ago2, TRBP). The E6_69 and E7_193 significantly showed strong binding and intermolecular interactions, especially with Ago2, highlighting the potential for HPV gene silencing.

Conclusion

The study revealed the potential of the designed siRNAs in silencing the E6 and E7 genes and their therapeutic applications against HPV. Future research should focus on validating these findings across various experiments, both in vivo and in vitro, and exploring alternative delivery approaches to enhance therapeutic efficacy.

背景:随着复发性高危人乳头瘤病毒(HPV)感染,特别是HPV16和HPV18,宫颈癌是女性中第四大常见疾病。E6和E7蛋白的功能改变对高危hpv和宫颈癌的发生至关重要。目的:本研究的目的是设计靶向HPV16和HPV18的高靶向和高效的小干扰rna (sirna),采用尖端的计算方法,通过系统的生物信息学驱动方法增强治疗潜力。方法与结果:本研究利用i-Score Designer基于Ui-Tei、Amarzguioui、i-Score和Reynolds评分等多种算法标准,对4种潜在的小干扰rna (sirna) (E6_69、E6_451、E7_66和E7_193)进行鉴定和评价。因此,进行对接分析以阐明rna诱导沉默复合体(RISC)蛋白与设计的sirna之间的分子间相互作用。所有sirna都通过了推荐的截止值,表明基因沉默的可能性很大。热力学和结构分析表明,所设计的sirna具有良好的熔化温度和自由能,表明其具有足够的稳定性,可以实现有效的基因沉默。此外,对接分析显示了与主要RISC蛋白(Dicer, Ago2, TRBP)的显著结合亲和力和相互作用谱。E6_69和E7_193表现出强烈的结合和分子间相互作用,特别是与Ago2,突出了HPV基因沉默的潜力。结论:该研究揭示了所设计的sirna在沉默E6和E7基因及其治疗HPV方面的潜力。未来的研究应侧重于在体内和体外的各种实验中验证这些发现,并探索替代的给药方法以提高治疗效果。
{"title":"Exploitation of Biocomputational Approaches for siRNA-Mediated Gene Silencing of HPV: A Novel Therapeutic Strategy for Cervical Cancer","authors":"Md. Habib Ullah Masum,&nbsp;Rehana Parvin,&nbsp;Homaira Pervin Heema,&nbsp;Aklima Akter,&nbsp;Jannatul Ferdous","doi":"10.1002/cnr2.70434","DOIUrl":"10.1002/cnr2.70434","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With recurrent high-risk human papillomavirus (HPV) infections, especially HPV16 and HPV18, cervical cancer is the fourth most common disease among women. The functional alterations of the E6 and E7 proteins are essential to the oncogenic process of high-risk HPVs and cervical cancer development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The objective of this research is to design highly targeted and efficient small interfering RNAs (siRNAs) that target both HPV16 and HPV18, employing cutting-edge computational approaches to enhance therapeutic potential through a systematic bioinformatics-driven approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This study utilized the i-Score Designer to identify and evaluate four potential small interfering RNAs (siRNAs) (E6_69, E6_451, E7_66, and E7_193) based on various algorithm criteria, including Ui-Tei, Amarzguioui, i-Score, and Reynolds scores. Consequently, a docking analysis was conducted to elucidate the intermolecular interactions between the RNA-induced silencing complex (RISC) proteins and the designed siRNAs. All siRNAs passed the recommended cutoff values, indicating a strong potential for gene silencing. Thermodynamic and structural analyses revealed that the designed siRNAs had favrable melting temperatures and free energies, suggesting adequate stability for effective gene silencing. Further, docking analysis demonstrated significant binding affinities and interaction profiles with the major RISC proteins (Dicer, Ago2, TRBP). The E6_69 and E7_193 significantly showed strong binding and intermolecular interactions, especially with Ago2, highlighting the potential for HPV gene silencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study revealed the potential of the designed siRNAs in silencing the E6 and E7 genes and their therapeutic applications against HPV. Future research should focus on validating these findings across various experiments, both in vivo and in vitro, and exploring alternative delivery approaches to enhance therapeutic efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755447","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 New Radiotranscriptomic Approach to Analyze Combined Sets of T3b Stage-Specific Genes and Radiomic Features in Prostate Cancer 一种新的放射转录组学方法分析前列腺癌T3b分期特异性基因组合和放射组学特征。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-12 DOI: 10.1002/cnr2.70391
Qian Yang, Peng Tang, Jiao Mo, Qiuyang Li, Jiahui Huang, Xiaoyu Han, Hao Xu, Xi Liu, Jie Tang

Background

Current clinical staging of prostate cancer (PCa) using the tumor-node-metastasis (TNM) system and serum biomarkers remains limited in distinguishing locally advanced (T3b) PCa from organ-confined (T2c) disease.

Aims

Building on our previous biomarker discovery in differentiating PCa from that of benign prostatic hyperplasia, this study pioneers a radiotranscriptomic model to distinguish T3b stage PCa from T2c stage PCa by integrating contrast-enhanced ultrasound (CEUS) radiomics with stage-specific transcriptomic signatures, addressing a critical knowledge gap in precision staging.

Methods and Results

This prospective study was approved by the review board of Chinese PLA General Hospital (S2021-565-01), and all participants provided written informed consent. Transrectal B-mode ultrasound images and contrast-enhanced ultrasound images on two imaging planes were prospectively analyzed in 48 patients with biopsy-confirmed PCa (35 patients with stage T2c and 13 with stage T3b). Textural features were evaluated using microvascular ultrasonography and contrast-enhanced ultrasound. Radiomic data were then retrieved from all modes. An across-the-board investigation of mRNA and miRNA expressions was also performed in the two PCa stages. Six biomarkers (frizzled 4, ribosomal protein S7, ribosomal protein L29, miR-374c, miR-9, and miR-6510) were identified to differentiate T3b stage from T2c stage. The area under the curve (AUC) values of the combined set (AUC = 0.887, 0.956, and 0.996 for random forest, naïve Bayes, and support vector machine, respectively) and radiomic features alone (AUC = 0.921, 0.957, and 0.998, respectively) were found to be more accurate than those of the transcriptomic data alone (AUC = 0.583, 0.716, and 0.898, respectively) or clinical features alone (AUC = 0.585, 0.675, and 0.953, respectively). The PCa gene regulatory network comprised of four miRNAs (miR-148, miR-141, miR-342, and miR-210) may contribute to accelerating tumor progression.

Conclusion

We established the new radiotranscriptomic signatures specifically optimized for differentiating T3b stage from T2c stage by decoding stage-specific imaging-genomic crosstalk. This new approach may overcome TNM staging limitations.

背景:目前使用肿瘤-淋巴结-转移(TNM)系统和血清生物标志物对前列腺癌(PCa)的临床分期在区分局部晚期(T3b)前列腺癌和器官局限性(T2c)前列腺癌方面仍然有限。目的:在我们之前发现的鉴别前列腺癌与良性前列腺增生的生物标志物的基础上,本研究建立了一种放射转录组学模型,通过将对比增强超声(CEUS)放射组学与分期特异性转录组学特征相结合,来区分T3b期和T2c期的前列腺癌,解决了精确分期的关键知识空白。方法和结果:本前瞻性研究经中国人民解放军总医院审查委员会批准(S2021-565-01),所有参与者均提供书面知情同意。回顾性分析48例经直肠活检证实的前列腺癌患者(T2c期35例,T3b期13例)的经直肠b超及两个成像平面的超声增强图像。采用微血管超声和增强超声对纹理特征进行评价。然后从所有模式中检索放射学数据。在两个PCa阶段也进行了mRNA和miRNA表达的全面调查。鉴定出6种生物标志物(卷曲4、核糖体蛋白S7、核糖体蛋白L29、miR-374c、miR-9和miR-6510)用于区分T3b期和T2c期。联合集(随机森林、naïve贝叶斯和支持向量机的AUC分别为0.887、0.956和0.996)和放射组学特征(AUC分别为0.921、0.957和0.998)的曲线下面积(AUC)值比单独使用转录组学数据(AUC分别为0.583、0.716和0.898)或单独使用临床特征(AUC分别为0.585、0.675和0.953)的曲线下面积(AUC)值更准确。由四种mirna (miR-148、miR-141、miR-342和miR-210)组成的PCa基因调控网络可能有助于加速肿瘤进展。结论:通过解码阶段特异性成像-基因组串扰,我们建立了专门用于区分T3b期和T2c期的新的放射转录组学特征。这种新方法可能克服TNM分期的限制。
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引用次数: 0
The Efficacy of Radiofrequency Ablation in Treating Nonmetastatic Medullary Thyroid Carcinoma: A Case Study 射频消融治疗非转移性甲状腺髓样癌的疗效:一例研究。
IF 1.9 Q4 ONCOLOGY Pub Date : 2025-12-10 DOI: 10.1002/cnr2.70419
Hojat Ebrahiminik, Hossein Chegeni, Haleh Chehrehgosha

Background

Radiofrequency ablation (RFA) can be an alternative management method for patients who are not candidates for surgery or who refuse it. There are limited data concerning the role of RFA in patients with medullary thyroid carcinoma (MTC). This case is presented to discuss the efficacy of RFA in the management of nonmetastatic MTC.

Case

In this report, we present the case of an 83-year-old male with MTC who refused thyroidectomy. RFA was performed and he was followed for 1 year. In this case, RFA resulted in significant reductions in tumor size and calcitonin levels without any significant complications.

Conclusion

This research indicates that Radiofrequency Ablation (RFA) can yield acceptable results in the management of Medullary Thyroid Cancer (MTC). However, ongoing investigation remains crucial to clarify long-term outcomes and to compare RFA's efficacy against conventional management methods.

背景:射频消融(RFA)可以作为不适合手术或拒绝手术的患者的另一种治疗方法。关于RFA在甲状腺髓样癌(MTC)患者中的作用的数据有限。本病例是为了讨论RFA在非转移性MTC治疗中的疗效。病例:在本报告中,我们报告一例83岁男性MTC患者拒绝甲状腺切除术。术后随访1年。在这个病例中,RFA导致肿瘤大小和降钙素水平的显著减少,没有任何明显的并发症。结论:射频消融(RFA)治疗甲状腺髓样癌(MTC)疗效满意。然而,正在进行的研究对于澄清长期结果和比较RFA与传统管理方法的疗效仍然至关重要。
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引用次数: 0
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