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Prostate cancer treatment with electrochemotherapy (ECT): safety, efficacy and clinical experience in 144 patients. 144例前列腺癌电化疗的安全性、有效性及临床体会。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0061
Mara Stevanovic, Mathias Heringer, Mohammad Hjouj, Alessandro Zanasi, Francesca de Terlizzi, Michael K Stehling

Background: Prostate cancer (PCa) is a common cancer in men in developed countries. PCa treatment depends on the disease's stage; focal therapy provides an intermediate approach, with lower toxicity compared to radical prostatectomy, and better tumor control than active surveillance. We report the first retrospective analysis of prostate cancer patients treated with ECT at our institution.

Patients and methods: A cohort of 144 men with prostate cancer who were ineligible for or refused standard therapies were included and treated with ECT. Routine follow-up included PSA tests and MRI scans, as well as toxicity and genitourinary function evaluation by means of standard questionnaires. Local response was evaluated with MRI at 3 months after treatment, following the RECIST criteria for solid tumors.

Results: The procedure was technically successful in all patients and was well tolerated, with mild and temporary adverse events. Urinary and erectile functions were mostly preserved. A complete response was observed in 75% of evaluated patients, a partial response in 18%, stable disease in 5%, and disease progression in 2%. Short-term response was associated with TNM stage (p < 0.05), Gleason score (p = 0.0066), and pre-ECT PSA levels (p = 0.0070). During follow-up, 18 patients (13%) experienced disease progression; 1-year PFS was 88% (95% CI: 80%-97%) and was found to be significantly associated with tumor stage and pre-treatment PSA levels.

Conclusions: ECT is a feasible, safe, and effective treatment for prostate cancer, with extremely low toxicity and side effects. Preliminary results suggest that it offers promising outcomes in terms of local disease control in early-stage tumors, but also in locally advanced cases where other treatments may not be viable.

背景:前列腺癌(PCa)是发达国家男性常见的癌症。前列腺癌的治疗取决于疾病的分期;局灶性治疗提供了一种中间方法,与根治性前列腺切除术相比毒性更低,并且比主动监测更好地控制肿瘤。我们报告了在我院接受ECT治疗的前列腺癌患者的首次回顾性分析。患者和方法:144名不符合或拒绝接受标准治疗的前列腺癌患者接受了ECT治疗。常规随访包括PSA检测和MRI扫描,以及通过标准问卷进行毒性和泌尿生殖功能评估。在治疗后3个月用MRI评估局部反应,遵循实体瘤的RECIST标准。结果:手术在技术上是成功的,所有患者都有良好的耐受性,有轻微和暂时的不良事件。泌尿和勃起功能基本保留。75%的患者完全缓解,18%的患者部分缓解,5%的患者病情稳定,2%的患者病情进展。短期疗效与TNM分期(p < 0.05)、Gleason评分(p = 0.0066)和ect前PSA水平(p = 0.0070)相关。随访期间,18例患者(13%)出现疾病进展;1年PFS为88% (95% CI: 80%-97%),与肿瘤分期和治疗前PSA水平显著相关。结论:ECT治疗前列腺癌可行、安全、有效,毒副作用极低。初步结果表明,在早期肿瘤的局部疾病控制方面,它提供了有希望的结果,但在局部晚期病例中,其他治疗方法可能不可行。
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引用次数: 0
Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitro. 体外可逆电穿孔后患者源性胶质母细胞瘤细胞的侵袭特性。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0058
Anja Blazic, Bernarda Majc, Metka Novak, Barbara Breznik, Lea Rems

Background: Electroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells.

Materials and methods: Five patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electroporation using transwell assay and RNA transcriptome analysis, respectively.

Results: Reversible electroporation at 1.0 kV/cm enhanced invasion in a cell line-dependent manner. NIB140 CORE showed a consistent and pronounced increase, with a median of 3.74-fold (274%) higher number of invading cells compared to sham control. In contrast, NIB216 CORE exhibited only a modest increase in invasion (1.30-fold; 30%). Transcriptomic profiling identified modulation of genes linked to extracellular matrix organization and ion channel activity in NIB140 CORE, and cytoskeletal remodelling in NIB216 CORE, indicating the activation of invasion-related pathways.

Conclusions: These findings highlight a potential risk of pro-invasive responses in GB cells. In tumour ablation with irreversible electroporation, this concern relates to cells in the peripheral zone that may experience only sublethal electric fields, while in electrochemotherapy, a similar risk may arise if permeabilized cells are not effectively eliminated due to insufficient local drug delivery. Nevertheless, the two tested cell lines responded differently, underscoring patient-specific heterogeneity and the need for validation in more physiologically relevant models.

背景:在胶质母细胞瘤(GB)治疗中,以电穿孔为基础的疗法正在被探索,作为增强药物传递或实现非热消融的手段。然而,对于亚致死暴露如何影响GB肿瘤细胞的侵袭行为知之甚少。材料与方法:初步筛选5株患者源性GB细胞系的内在侵袭电位,选择两株最具侵袭性的NIB140 CORE和NIB216 CORE进行进一步的电穿孔实验。悬浮细胞暴露在高频双相电脉冲下,产生电场强度为1 kV/cm,对应于可逆电穿孔条件。电穿孔24小时后,分别用transwell实验和RNA转录组分析评估细胞侵袭和基因调控的变化。结果:1.0 kV/cm的可逆电穿孔以细胞系依赖的方式增强了侵袭。NIB140 CORE表现出一致且明显的增加,与假对照组相比,入侵细胞数量中位数增加了3.74倍(274%)。相比之下,NIB216 CORE仅表现出轻微的侵袭性增加(1.30倍;30%)。转录组学分析鉴定了NIB140 CORE中与细胞外基质组织和离子通道活性相关的基因调控,以及NIB216 CORE中与细胞骨架重塑相关的基因调控,表明入侵相关途径的激活。结论:这些发现强调了GB细胞的前侵入性反应的潜在风险。在不可逆电穿孔的肿瘤消融中,这种担忧与可能只经历亚致死电场的外周区细胞有关,而在电化疗中,如果渗透细胞由于局部药物递送不足而不能有效消除,则可能出现类似的风险。然而,两种被测试的细胞系反应不同,强调了患者特异性的异质性,需要在更多生理学相关的模型中进行验证。
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引用次数: 0
The influence of periodontal disease and periodontal treatment on colorectal cancer. 牙周病及牙周治疗对结直肠癌的影响。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0025
Ursa Potocnik Rebersak, Erik Brecelj, Rok Schara

Background: Periodontal disease (PD) is associated with more than 50 diseases and conditions, including colorectal cancer. The study aimed to investigate if periodontal treatment influences the blood levels of C-reactive protein (CRP) in colorectal cancer patients. In addition, the aim was to isolate periodontal pathogenic bacteria Fusobacterium nucleatum (FN) and Porphyromonas gingivalis (PG), which are most linked to colorectal cancer (CRC), from the mucosa of the cancer-affected intestine.

Patients and methods: To assess the effect of periodontal treatment on colorectal cancer, we measured the CRP levels in the blood during cancer therapy on the day of the initial examination by the oncological surgeon, two days following surgery, and at the first follow-up appointment. We compared the CRP levels between two groups: the group of subjects who underwent periodontal treatment and the patients who did not receive periodontal disease treatment. An attempt was made to isolate the periodontal pathogenic bacteria FN and PG from the mucosa of the cancerous tissue in the colon by using quantitative culture.

Results: We found no statistically significant difference between the groups in the initial CRP measurements before starting cancer treatment. There was no statistically significant difference between the groups in the CRP measurements taken 1st and 2nd day after surgery and at the follow-up appointment. We could not isolate periodontal pathogenic bacteria FN and PG from cancer-altered intestine mucosa using the quantitative culture method.

Conclusions: Our study did not find any correlation between periodontal treatment and CRC.

背景:牙周病(PD)与50多种疾病和病症有关,包括结直肠癌。该研究旨在调查牙周治疗是否会影响结直肠癌患者血液中c反应蛋白(CRP)的水平。此外,目的是分离牙周致病菌核梭菌(FN)和牙龈卟啉单胞菌(PG),这两种细菌与结直肠癌(CRC)最相关,来自受癌症影响的肠道粘膜。患者和方法:为了评估牙周治疗对结直肠癌的影响,我们在肿瘤外科医生首次检查当天、手术后两天以及第一次随访预约时测量了癌症治疗期间血液中的CRP水平。我们比较了两组之间的CRP水平:接受牙周病治疗的一组和未接受牙周病治疗的一组。采用定量培养的方法从结肠癌组织粘膜中分离出牙周致病菌FN和PG。结果:我们发现两组在开始癌症治疗前的初始CRP测量无统计学差异。两组患者术后第1天、第2天及随访时的CRP测量值无统计学差异。用定量培养法无法从癌变肠黏膜中分离出牙周致病菌FN和PG。结论:我们的研究没有发现牙周治疗与结直肠癌之间的任何相关性。
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引用次数: 0
The influence of catheter type, the number of sutures and patients' age on percutaneous nephrostomy displacement. 导管类型、缝线次数及患者年龄对经皮肾造口移位的影响。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0037
Dimitrij Kuhelj, Ana Sustersic, Urban Zdesar

Background: Percutaneous nephrostomy displacement results in procedure failure, reducing quality of life in patients with hydronephrosis. Scarce data about factors influencing displacement led to evaluation of our data in order to give better insight into this topic.

Patients and methods: Patients admitted for percutaneous nephrostomy (PCN) exchange between March 3rd and October 3rd 2023 were included in our prospective observational study aiming to determine possible factors influencing PCN displacement. Catheter type, number of sutures and patients' age over 70 years were analyzed. Descriptive statistics and Pearson's chi-square test were used; value less than 0.05 was determined as statistically significant.

Results: We included 57 patients (35 males; mean age 71.4 years) in the study. Loop catheters with strings were implanted 58 times and without strings 17 times. Fixation was achieved by 55 single and by 20 double sutures. 17 PCN (22.7%) were displaced in designated period. The mean time from PCN implantation to exchange was 4.16 months. Neither catheter type, number of sutures or patients' age significantly influenced PCN displacement (chi-square 0.57, 0.34 and 0.61, respectively).

Conclusions: No significant difference in PCN displacement between two types of catheters and the number of fixing sutures was detected. Elderly patients had similar rates of PCN displacements as younger ones. The most important causes of PCN displacement remained probably patients' activity and a care for PCN during months after the implantation. Proper patients' education and care of the PCN are possibly the keys for long-term success.

背景:经皮肾造口移位导致手术失败,降低肾积水患者的生活质量。关于影响位移因素的稀缺数据导致对我们的数据进行评估,以便更好地了解这一主题。患者和方法:我们的前瞻性观察研究纳入了2023年3月3日至10月3日期间接受经皮肾造口术(PCN)置换的患者,旨在确定影响PCN移位的可能因素。分析导管类型、缝合次数及患者年龄≥70岁。采用描述性统计和Pearson卡方检验;值小于0.05为有统计学意义。结果:我们纳入了57例患者(男性35例;平均年龄71.4岁)。带线环形导管植入术58次,无线环形导管植入术17次。55个单缝线和20个双缝线完成固定。17名PCN(22.7%)在指定时间内流离失所。从PCN植入到交换的平均时间为4.16个月。导管类型、缝线数和患者年龄对PCN移位均无显著影响(卡方分别为0.57、0.34和0.61)。结论:两种导管PCN移位及固定线数无显著差异。老年患者的PCN移位率与年轻患者相似。PCN移位的最重要原因可能仍然是患者的活动和植入后数月对PCN的护理。适当的患者教育和护理PCN可能是长期成功的关键。
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引用次数: 0
Baseline and dynamic changes in skeletal muscle mass as predictive biomarkers in patients with metastatic renal cell carcinoma treated with Nivolumab. 基线和动态变化骨骼肌质量作为转移性肾细胞癌患者接受尼武单抗治疗的预测性生物标志物。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0065
Erdem Ozkan, Murathan Koksal, Bunyamin Ece, Mustafa Koyun, Omer Faruk Kuzu, Yusuf Acikgoz, Efnan Algin

Background: Low skeletal muscle mass has been increasingly recognized as a negative prognostic factor in oncology. According to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), sarcopenia is defined as a progressive and generalized skeletal muscle disorder characterized by the loss of muscle strength and muscle mass, which can lead to impaired physical performance. This study aimed to investigate whether baseline low muscle mass and dynamic changes in muscle mass during immunotherapy could predict treatment response and survival in patients with metastatic renal cell carcinoma (mRCC) treated with Nivolumab.

Patients and methods: This retrospective cohort study included 50 mRCC patients (35 men, 15 women; mean age 59.1 ± 10.2 years) who received Nivolumab between 2019 and 2022 and underwent abdominal computed tomography (CT) before and during treatment. Muscle mass was assessed by calculating the skeletal muscle index (SMI) at the third lumbar vertebra using standard Hounsfield unit thresholds (-29 to +150 HU). Treatment response was evaluated according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and Cox regression models.

Results: Low muscle mass was identified in 60% of patients and was significantly associated with multiple organ metastases (p = 0.003). Patients with baseline low muscle mass or a negative change in SMI during treatment demonstrated poorer treatment response (p = 0.027 and p = 0.021, respectively). Both OS and PFS were significantly shorter in patients with low muscle mass and those with declining muscle mass during treatment.

Conclusions: Pre-treatment low muscle mass and muscle mass decline during immunotherapy were independently associated with inferior survival and treatment response in mRCC patients receiving Nivolumab. CT-based muscle mass assessment may serve as an imaging-based prognostic biomarker in this population.

背景:低骨骼肌质量越来越被认为是肿瘤预后不良的因素。根据欧洲老年人肌肉减少症工作组2 (EWGSOP2),肌肉减少症被定义为一种进行性和广泛性骨骼肌疾病,其特征是肌肉力量和肌肉质量的丧失,这可能导致身体机能受损。本研究旨在探讨基线低肌肉量和免疫治疗期间肌肉量的动态变化是否可以预测Nivolumab治疗的转移性肾细胞癌(mRCC)患者的治疗反应和生存。患者和方法:这项回顾性队列研究包括50名mRCC患者(35名男性,15名女性,平均年龄59.1±10.2岁),他们在2019年至2022年期间接受了尼武单抗治疗,并在治疗前和治疗期间接受了腹部计算机断层扫描(CT)。采用标准Hounsfield单位阈值(-29至+150 HU)计算第三腰椎骨骼肌指数(SMI)来评估肌肉质量。根据实体瘤免疫反应评价标准(iRECIST)评价治疗反应。采用Kaplan-Meier曲线和Cox回归模型分析总生存期(OS)和无进展生存期(PFS)。结果:60%的患者存在低肌肉量,且与多器官转移显著相关(p = 0.003)。基线肌量低或治疗期间SMI呈负变化的患者表现出较差的治疗反应(分别为p = 0.027和p = 0.021)。在治疗期间,低肌肉质量患者和肌肉质量下降的患者的OS和PFS都明显较短。结论:在接受Nivolumab治疗的mRCC患者中,治疗前低肌肉量和免疫治疗期间肌肉量下降与较差的生存期和治疗反应独立相关。在这一人群中,基于ct的肌肉质量评估可以作为一种基于成像的预后生物标志物。
{"title":"Baseline and dynamic changes in skeletal muscle mass as predictive biomarkers in patients with metastatic renal cell carcinoma treated with Nivolumab.","authors":"Erdem Ozkan, Murathan Koksal, Bunyamin Ece, Mustafa Koyun, Omer Faruk Kuzu, Yusuf Acikgoz, Efnan Algin","doi":"10.2478/raon-2025-0065","DOIUrl":"10.2478/raon-2025-0065","url":null,"abstract":"<p><strong>Background: </strong>Low skeletal muscle mass has been increasingly recognized as a negative prognostic factor in oncology. According to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), sarcopenia is defined as a progressive and generalized skeletal muscle disorder characterized by the loss of muscle strength and muscle mass, which can lead to impaired physical performance. This study aimed to investigate whether baseline low muscle mass and dynamic changes in muscle mass during immunotherapy could predict treatment response and survival in patients with metastatic renal cell carcinoma (mRCC) treated with Nivolumab.</p><p><strong>Patients and methods: </strong>This retrospective cohort study included 50 mRCC patients (35 men, 15 women; mean age 59.1 ± 10.2 years) who received Nivolumab between 2019 and 2022 and underwent abdominal computed tomography (CT) before and during treatment. Muscle mass was assessed by calculating the skeletal muscle index (SMI) at the third lumbar vertebra using standard Hounsfield unit thresholds (-29 to +150 HU). Treatment response was evaluated according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and Cox regression models.</p><p><strong>Results: </strong>Low muscle mass was identified in 60% of patients and was significantly associated with multiple organ metastases (p = 0.003). Patients with baseline low muscle mass or a negative change in SMI during treatment demonstrated poorer treatment response (p = 0.027 and p = 0.021, respectively). Both OS and PFS were significantly shorter in patients with low muscle mass and those with declining muscle mass during treatment.</p><p><strong>Conclusions: </strong>Pre-treatment low muscle mass and muscle mass decline during immunotherapy were independently associated with inferior survival and treatment response in mRCC patients receiving Nivolumab. CT-based muscle mass assessment may serve as an imaging-based prognostic biomarker in this population.</p>","PeriodicalId":21034,"journal":{"name":"Radiology and Oncology","volume":"59 4","pages":"624-634"},"PeriodicalIF":2.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human papillomavirus-related oropharyngeal squamous cell carcinoma exhibits enhanced radiosensitivity despite limited activation of cytosolic DNA sensing pathways and innate immune responses. 人乳头瘤病毒相关口咽鳞状细胞癌表现出增强的放射敏感性,尽管胞质DNA感应途径和先天免疫反应的激活有限。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0057
Kristina Levpuscek, Tanja Jesenko, Tilen Komel, Simona Kranjc Brezar, Gregor Sersa, Maja Cemazar, Primoz Strojan

Background: Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key role in the etiology of oropharyngeal squamous cell carcinoma (OPSCC). HPV16-related OPSCC exhibits enhanced radiosensitivity compared to HPV16-unrelated PSCC, yet the underlying mechanisms remain poorly understood. As HPV16 oncoproteins E6 and E7 are known to interfere with innate immune signaling, we investigated how modulation of cytosolic DNA sensing pathways and innate immune responses changes after irradiation (IR) and whether this contributes to enhanced radiosensitivity in HPV16-related OPSCC.

Materials and methods: Using HPV16-related and -unrelated PSCC models, we examined baseline expression levels of DNA sensors and cytokines and assessed the effects of IR on double-stranded DNA (dsDNA) accumulation, activation of cytosolic DNA sensors, cytokines, and immune cell infiltration both in vitro and in vivo. Analyses were performed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescent staining.

Results: HPV16-related OPSCC exhibited a distinct baseline expression profile of DNA sensors and cytokines, consistent with suppression of the stimulator of interferon genes (STING) pathway. While IR-induced activation of DNA sensors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cyclic GMP-AMP synthase (cGAS) and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infiltration following IR.

Conclusions: The key finding was that the involvement of cytosolic DNA sensing pathways and innate immune system do not increase radiosensitivity of HPV16-related OPSCC. In PSCC models, DNA sensor and cytokine expression varied depending on IR dose and fractionation.

背景:咽鳞状细胞癌(PSCC)是一个重要的健康问题,人乳头瘤病毒16 (HPV16)在口咽鳞状细胞癌(OPSCC)的病因学中起着关键作用。与hpv16无关的PSCC相比,hpv16相关的OPSCC表现出更高的放射敏感性,但其潜在机制尚不清楚。由于已知HPV16癌蛋白E6和E7干扰先天免疫信号,我们研究了辐照(IR)后胞质DNA传感途径和先天免疫反应的调节如何改变,以及这是否有助于增强HPV16相关OPSCC的放射敏感性。材料和方法:使用hpv16相关和不相关的PSCC模型,我们检测了DNA传感器和细胞因子的基线表达水平,并评估了IR对体外和体内双链DNA (dsDNA)积累、胞质DNA传感器激活、细胞因子和免疫细胞浸润的影响。采用实时定量聚合酶链反应(RT-qPCR)和免疫荧光染色进行分析。结果:hpv16相关的OPSCC显示出明显的DNA传感器和细胞因子的基线表达谱,与干扰素刺激因子(STING)途径的抑制一致。ir诱导的DNA传感器的激活是剂量和时间依赖的,而hpv16相关的OPSCC显示环GMP-AMP合成酶(cGAS)和STING的选择性激活,没有明显的细胞因子上调或免疫激活。相比之下,hpv16相关和不相关的PSCCs在IR后表现出多个DNA传感器的激活,细胞因子表达增加,免疫细胞浸润增强。结论:关键发现是细胞质DNA传感途径和先天免疫系统的参与不会增加hpv16相关OPSCC的放射敏感性。在PSCC模型中,DNA传感器和细胞因子的表达随IR剂量和分离而变化。
{"title":"Human papillomavirus-related oropharyngeal squamous cell carcinoma exhibits enhanced radiosensitivity despite limited activation of cytosolic DNA sensing pathways and innate immune responses.","authors":"Kristina Levpuscek, Tanja Jesenko, Tilen Komel, Simona Kranjc Brezar, Gregor Sersa, Maja Cemazar, Primoz Strojan","doi":"10.2478/raon-2025-0057","DOIUrl":"10.2478/raon-2025-0057","url":null,"abstract":"<p><strong>Background: </strong>Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key role in the etiology of oropharyngeal squamous cell carcinoma (OPSCC). HPV16-related OPSCC exhibits enhanced radiosensitivity compared to HPV16-unrelated PSCC, yet the underlying mechanisms remain poorly understood. As HPV16 oncoproteins E6 and E7 are known to interfere with innate immune signaling, we investigated how modulation of cytosolic DNA sensing pathways and innate immune responses changes after irradiation (IR) and whether this contributes to enhanced radiosensitivity in HPV16-related OPSCC.</p><p><strong>Materials and methods: </strong>Using HPV16-related and -unrelated PSCC models, we examined baseline expression levels of DNA sensors and cytokines and assessed the effects of IR on double-stranded DNA (dsDNA) accumulation, activation of cytosolic DNA sensors, cytokines, and immune cell infiltration both <i>in vitro</i> and <i>in vivo</i>. Analyses were performed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescent staining.</p><p><strong>Results: </strong>HPV16-related OPSCC exhibited a distinct baseline expression profile of DNA sensors and cytokines, consistent with suppression of the stimulator of interferon genes (STING) pathway. While IR-induced activation of DNA sensors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cyclic GMP-AMP synthase (cGAS) and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infiltration following IR.</p><p><strong>Conclusions: </strong>The key finding was that the involvement of cytosolic DNA sensing pathways and innate immune system do not increase radiosensitivity of HPV16-related OPSCC. In PSCC models, DNA sensor and cytokine expression varied depending on IR dose and fractionation.</p>","PeriodicalId":21034,"journal":{"name":"Radiology and Oncology","volume":"59 4","pages":"566-578"},"PeriodicalIF":2.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiotoxicity in low-to-moderate cardiovascular risk patients undergoing anti-HER2 therapy: a prospective cardiac magnetic resonance study. 接受抗her2治疗的低至中度心血管风险患者的心脏毒性:一项前瞻性心脏磁共振研究
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0043
Sainan Cheng, Mei Deng, Linlin Qi, Fenglan Li, Jiaqi Chen, Shulei Cui, Yawen Wang, Jianing Liu, Yang Fan, Lizhi Xie, Jianwei Wang

Background: The study aimed to investigate cardiotoxicity among individuals undergoing anti-human epidermal growth factor receptor 2 (HER2) therapy with a low-to-moderate risk of cardiovascular complications. Cardiac magnetic resonance (CMR) imaging was employed in the investigation.

Patients and methods: HER2-positive breast cancer patients who underwent CMR examinations both before and during therapy (first follow-up: 3-5 months; second follow-up: 6-12 months) between January 2021 and December 2022 were prospectively included. Each patient was evaluated for the risk of cardiovascular toxicity.

Results: Thirty-five HER2-positive breast cancer patients were included (48.86 ± 10.34 years). Eighty-nine percent of patients had low cardiovascular toxicity risk, and 11% had moderate cardiovascular toxicity risk. At follow-up CMR, nine (25.71%) patients developed cardiac dysfunction. At follow-up 1, there was a notable decrease in left ventricular ejection fraction, stroke volume index, cardiac output index, and absolute strain values, accompanied by higher T1 and T2 values as well as end-systolic volume index compared to baseline (p ≤ 0.002). At follow-up 2, the T1 and T2 values recovered to near baseline. The cardiac output index exhibited a continuous decline (p ≤ 0.022), while other variables were similar (p > 0.05). Furthermore, at follow-up 1, the T1 value displayed a marked increase in patients with 1-3 points in cardiovascular toxicity risk factors compared to those with no risk factors (p ≤ 0.043).

Conclusions: It is common for patients with low-to-moderate cardiovascular risk to experience early cardiotoxicity during anti-HER2 therapy. T1 mapping was a valuable approach for quantifying the specific extent of subtle tissue damage.

背景:本研究旨在调查接受抗人表皮生长因子受体2 (HER2)治疗且心血管并发症风险中低的个体的心脏毒性。采用心脏磁共振(CMR)成像进行研究。患者和方法:前瞻性纳入2021年1月至2022年12月期间在治疗前和治疗期间接受CMR检查的her2阳性乳腺癌患者(第一次随访:3-5个月;第二次随访:6-12个月)。对每位患者进行心血管毒性风险评估。结果:纳入35例her2阳性乳腺癌患者(48.86±10.34岁)。89%的患者心血管毒性风险较低,11%的患者心血管毒性风险中等。在随访CMR中,9例(25.71%)患者出现心功能障碍。随访1时,左室射血分数、卒中容积指数、心输出量指数、绝对应变值均显著降低,T1、T2值及收缩期末期容积指数均高于基线(p≤0.002)。随访2时,T1和T2恢复到接近基线。心输出量指数持续下降(p≤0.022),其他变量相似(p < 0.05)。随访1时,心血管毒性危险因素有1-3分的患者T1值明显高于无危险因素的患者(p≤0.043)。结论:低至中度心血管风险患者在抗her2治疗期间早期出现心脏毒性是常见的。T1映射是量化细微组织损伤具体程度的一种有价值的方法。
{"title":"Cardiotoxicity in low-to-moderate cardiovascular risk patients undergoing anti-HER2 therapy: a prospective cardiac magnetic resonance study.","authors":"Sainan Cheng, Mei Deng, Linlin Qi, Fenglan Li, Jiaqi Chen, Shulei Cui, Yawen Wang, Jianing Liu, Yang Fan, Lizhi Xie, Jianwei Wang","doi":"10.2478/raon-2025-0043","DOIUrl":"10.2478/raon-2025-0043","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to investigate cardiotoxicity among individuals undergoing anti-human epidermal growth factor receptor 2 (HER2) therapy with a low-to-moderate risk of cardiovascular complications. Cardiac magnetic resonance (CMR) imaging was employed in the investigation.</p><p><strong>Patients and methods: </strong>HER2-positive breast cancer patients who underwent CMR examinations both before and during therapy (first follow-up: 3-5 months; second follow-up: 6-12 months) between January 2021 and December 2022 were prospectively included. Each patient was evaluated for the risk of cardiovascular toxicity.</p><p><strong>Results: </strong>Thirty-five HER2-positive breast cancer patients were included (48.86 ± 10.34 years). Eighty-nine percent of patients had low cardiovascular toxicity risk, and 11% had moderate cardiovascular toxicity risk. At follow-up CMR, nine (25.71%) patients developed cardiac dysfunction. At follow-up 1, there was a notable decrease in left ventricular ejection fraction, stroke volume index, cardiac output index, and absolute strain values, accompanied by higher T1 and T2 values as well as end-systolic volume index compared to baseline (p ≤ 0.002). At follow-up 2, the T1 and T2 values recovered to near baseline. The cardiac output index exhibited a continuous decline (p ≤ 0.022), while other variables were similar (p > 0.05). Furthermore, at follow-up 1, the T1 value displayed a marked increase in patients with 1-3 points in cardiovascular toxicity risk factors compared to those with no risk factors (p ≤ 0.043).</p><p><strong>Conclusions: </strong>It is common for patients with low-to-moderate cardiovascular risk to experience early cardiotoxicity during anti-HER2 therapy. T1 mapping was a valuable approach for quantifying the specific extent of subtle tissue damage.</p>","PeriodicalId":21034,"journal":{"name":"Radiology and Oncology","volume":" ","pages":"510-521"},"PeriodicalIF":2.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 comparison of transcatheter aortic valve prosthesis platforms: Myval, Sapien, and Evolut in severe symptomatic aortic stenosis and low-moderate risk patients. 经导管主动脉瓣假体平台:Myval、Sapien和Evolut在重度症状性主动脉狭窄和中低危患者中的比较
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0046
Matjaz Bunc, Klemen Steblovnik, Simon Terseglav, Jana Ambrozic, Mojca Bervar, Ljupka Dimitrovska, Miha Cercek, Ana Kovac, Patricija Pleskovic, Polonca Kogoj, Zlatko Fras, Miha Sustersic, Bojan Vrtovec

Background: This article compares the real-world performance and safety of the three transcatheter aortic valve implantation (TAVI) platforms: Myval, Sapien, and Evolut in patients with severe symptomatic aortic stenosis and low to moderate surgical risk.

Patients and methods: Between September 2019 and September 2023, 1053 TAVI procedures were performed in the University Medical Centre Ljubljana, Slovenia. We used propensity-score match analysis to compare the Myval, Sapien, and Evolut platforms. 180 patients were enrolled in the propensity-score matching study, 60 for each platform. The study endpoints included haemodynamic outcomes compared to baseline, in-hospital clinical safety outcomes, and all-cause mortality at 30 days and one year.

Results: Changes in peak aortic valve velocity, mean aortic gradient, effective orifice area, and left ventricular ejection fraction were comparable between the platforms. After propensity score matching (tri-match), the rates of stroke (3.4% vs. 3.4% vs. 0.0%, p = 0.548), life-threatening bleeding (1.7% vs. 1.7% vs. 1.7 %), periprocedural myocardial infarction (3.3% vs. 0.0% vs. 0.0%, p = 0.330), postprocedural permanent pacemaker implantation rate (11.9% vs. 10.2% vs. 15.0%, p = 0.719), all-cause mortality at 30 days (3.3% vs. 5.0% vs. 3.3%; p = 1.000) and at 1 year (8.3% vs. 8.3% vs. 10.0%, p = 0.934) were comparable between the Myval, Sapien, and Evolut series, respectively. 2 cases of moderate paravalvular regurgitation were reported, one in Myval, and one in Sapien series.

Conclusions: The tri-match analysis of the real-world aortic stenosis patients with low to moderate surgical risk treated with the Myval, Sapien, and Evolut series showed comparable performance, safety, efficacy, and survival.

背景:本文比较了三种经导管主动脉瓣植入术(TAVI)平台:Myval、Sapien和Evolut在重度症状性主动脉狭窄和中低手术风险患者中的实际性能和安全性。患者和方法:2019年9月至2023年9月,在斯洛文尼亚卢布尔雅那大学医学中心进行了1053例TAVI手术。我们使用倾向得分匹配分析来比较Myval、Sapien和Evolut平台。180名患者参加了倾向评分匹配研究,每个平台60名。研究终点包括与基线相比的血流动力学结果、住院临床安全性结果以及30天和1年的全因死亡率。结果:两个平台间主动脉瓣峰值流速、平均主动脉梯度、有效开口面积和左室射血分数的变化具有可比性。倾向评分匹配(三匹配)后,卒中发生率(3.4% vs. 3.4% vs. 0.0%, p = 0.548)、危及生命的出血发生率(1.7% vs. 1.7% vs. 1.7%)、术中心肌梗死发生率(3.3% vs. 0.0% vs. 0.0%, p = 0.330)、术后永久起搏器植入率(11.9% vs. 10.2% vs. 15.0%, p = 0.719)、30天全因死亡率(3.3% vs. 5.0% vs. 3.3%;p = 1.000)和1年后(8.3% vs. 8.3% vs. 10.0%, p = 0.934) Myval、Sapien和Evolut系列之间分别具有可比性。报告中度瓣旁反流2例,Myval组1例,Sapien组1例。结论:对Myval、Sapien和Evolut系列治疗的低至中等手术风险的主动脉瓣狭窄患者的三配对分析显示,其性能、安全性、有效性和生存率相当。
{"title":"A comparison of transcatheter aortic valve prosthesis platforms: Myval, Sapien, and Evolut in severe symptomatic aortic stenosis and low-moderate risk patients.","authors":"Matjaz Bunc, Klemen Steblovnik, Simon Terseglav, Jana Ambrozic, Mojca Bervar, Ljupka Dimitrovska, Miha Cercek, Ana Kovac, Patricija Pleskovic, Polonca Kogoj, Zlatko Fras, Miha Sustersic, Bojan Vrtovec","doi":"10.2478/raon-2025-0046","DOIUrl":"10.2478/raon-2025-0046","url":null,"abstract":"<p><strong>Background: </strong>This article compares the real-world performance and safety of the three transcatheter aortic valve implantation (TAVI) platforms: Myval, Sapien, and Evolut in patients with severe symptomatic aortic stenosis and low to moderate surgical risk.</p><p><strong>Patients and methods: </strong>Between September 2019 and September 2023, 1053 TAVI procedures were performed in the University Medical Centre Ljubljana, Slovenia. We used propensity-score match analysis to compare the Myval, Sapien, and Evolut platforms. 180 patients were enrolled in the propensity-score matching study, 60 for each platform. The study endpoints included haemodynamic outcomes compared to baseline, in-hospital clinical safety outcomes, and all-cause mortality at 30 days and one year.</p><p><strong>Results: </strong>Changes in peak aortic valve velocity, mean aortic gradient, effective orifice area, and left ventricular ejection fraction were comparable between the platforms. After propensity score matching (tri-match), the rates of stroke (3.4% <i>vs</i>. 3.4% <i>vs</i>. 0.0%, p = 0.548), life-threatening bleeding (1.7% <i>vs</i>. 1.7% <i>vs</i>. 1.7 %), periprocedural myocardial infarction (3.3% <i>vs</i>. 0.0% <i>vs</i>. 0.0%, p = 0.330), postprocedural permanent pacemaker implantation rate (11.9% <i>vs</i>. 10.2% <i>vs</i>. 15.0%, p = 0.719), all-cause mortality at 30 days (3.3% <i>vs</i>. 5.0% <i>vs</i>. 3.3%; p = 1.000) and at 1 year (8.3% <i>vs</i>. 8.3% <i>vs</i>. 10.0%, p = 0.934) were comparable between the Myval, Sapien, and Evolut series, respectively. 2 cases of moderate paravalvular regurgitation were reported, one in Myval, and one in Sapien series.</p><p><strong>Conclusions: </strong>The tri-match analysis of the real-world aortic stenosis patients with low to moderate surgical risk treated with the Myval, Sapien, and Evolut series showed comparable performance, safety, efficacy, and survival.</p>","PeriodicalId":21034,"journal":{"name":"Radiology and Oncology","volume":" ","pages":"498-509"},"PeriodicalIF":2.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Induction chemotherapy and concurrent chemoradiotherapy for larynx preservation in laryngeal and hypopharyngeal cancer. 诱导化疗及同步放化疗对喉及下咽癌的保喉效果。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0055
Primoz Strojan, Gaber Plavc, Robert Sifrer, Simona Jereb, Bostjan Lanisnik, Marko Kokalj, Ales Groselj, Cvetka Grasic Kuhar

Background: To test the hypothesis that clinical tumor response after a single cycle of induction chemotherapy (ICT) can reliably differentiate between chemo-/radiosensitive and resistant tumors in the larynx preservation setting.

Patients and methods: Treatment consisted of docetaxel/cisplatin/5-fluorouracil (TPF) ICT followed by concurrent chemoradiotherapy (cCRT) with weekly cisplatin. The response of the primary tumor was assessed by transnasal endoscopy after the first ICT cycle.

Results: 37/39 (95%) patients with laryngeal (46%) or hypopharyngeal (54%) carcinoma responded to one cycle of ICT, and two patients were referred for salvage surgery. Laryngectomy-free survival at 2 and 5 years was 87% and 75%, respectively. The corresponding rates for locoregional control (and also for disease-free survival) were 79% and 70% and for overall survival 92% and 82%.

Conclusions: Clinical assessment of tumor response to one cycle of TPF ICT serves as a valid and easy-to-use predictor of tumor sensitivity to platinum-based cCRT.

背景:为了验证在喉保存环境下,单周期诱导化疗(ICT)后的临床肿瘤反应可以可靠地区分化疗/放射敏感和耐药肿瘤的假设。患者和方法:治疗包括多西紫杉醇/顺铂/5-氟尿嘧啶(TPF) ICT,随后同步放化疗(cCRT)每周顺铂。在第一个ICT周期后,通过经鼻内窥镜评估原发肿瘤的反应。结果:39例喉癌(46%)或下咽癌(54%)患者中有37例(95%)对1个周期的ICT有应答,2例患者转诊行挽救性手术。2年和5年无喉切除术生存率分别为87%和75%。相应的局部区域控制率(以及无病生存率)分别为79%和70%,总生存率分别为92%和82%。结论:临床评估肿瘤对一个周期TPF ICT的反应可作为肿瘤对铂基cCRT敏感性的有效且易于使用的预测指标。
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引用次数: 0
Heterogenous mitochondrial ultrastructure and metabolism of human glioblastoma cells: differences between stem-like and differentiated cancer cells in response to chemotherapy. 人胶质母细胞瘤细胞的异质线粒体超微结构和代谢:干细胞样和分化癌细胞对化疗反应的差异
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-12-01 DOI: 10.2478/raon-2025-0056
Urban Bogataj, Metka Novak, Simona Katrin Galun, Klementina Fon Tacer, Milos Vittori, Cornelis J F Van Noorden, Barbara Breznik

Background: Glioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells.

Materials and methods: Patient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis.

Results: We found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae are indicating increased biogenesis and mitochondrial fusion and corresponds to a more oxidative phosphorylation (OXPHOS)-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced ultrastructural mitochondrial damage in differentiated GBM cells.

Conclusions: We demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.

背景:胶质母细胞瘤干细胞样细胞(GSCs)有助于胶质母细胞瘤(GBM)肿瘤对标准治疗的抗性。在细胞代谢和线粒体作用的背景下,GSCs对化疗药物替莫唑胺耐药的背景尚未完全了解。本研究的目的是对替莫唑胺暴露前后的GSCs线粒体进行详细的超微结构表征,并将其与分化的GBM细胞进行比较。材料和方法:采用患者源性和已建立的GBM细胞系进行研究。透射电镜观察各组细胞系线粒体超微结构。显微分析是补充和比较细胞代谢分析使用海马细胞外通量分析。结果:我们发现GSCs的代谢谱是静止的和有氧的。它们细长的线粒体和高度组织化的嵴表明生物发生和线粒体融合增加,并对应于更依赖氧化磷酸化(OXPHOS)的代谢。GSCs的代谢依赖于OXPHOS,替莫唑胺治疗后,缺陷线粒体部分没有变化。相比之下,分化后线粒体碎片化的GBM细胞,嵴组织较少,更有活力和糖酵解能力。替莫唑胺诱导分化的GBM细胞超微结构线粒体损伤。结论:我们发现GSCs与分化的GBM细胞对替莫唑胺的线粒体超微结构和细胞代谢存在差异,提示线粒体在GSCs对替莫唑胺的耐药中起重要作用。本研究为进一步研究线粒体结构和功能背景下的GSC化疗耐药提供了基础。
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