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The role of interleukin-6 classic and trans-signaling and interleukin-11 classic signaling in gastric cancer cells. 白细胞介素-6经典信号传导和白细胞介素-11经典信号传导在胃癌细胞中的作用
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-08-15 DOI: 10.5114/wo.2024.142211
Josephine Runge, Christoph Garbers, Juliane Lokau

Introduction: The cytokine interleukin-11 (IL-11) binds on its target cells to a membrane-bound IL-11R, which results in homodimerization of the signal-transducing β-receptor gp130. Recent studies have uncovered a pro- inflammatory role in several diseases, including different tumor entities, and mouse models have revealed a crucial role of the IL-11/IL-11R axis in gastric cancer. However, studies regarding human gastric cancer are sparse, and whether the results obtained in mouse models also hold true in the human situation is little investigated.

Material and methods: We analyzed gene expression of IL11RA, IL11, IL6R, IL6 and IL6ST in different gastric tumor and immune cell lines. Furthermore, we stimulated these cell lines with exogenous cytokines and determined intracellular signaling. Finally, we analyzed gene expression data of gastric tumor patients and correlated them with overall patient survival.

Results: This study showed that different gastric tumor cell lines respond to IL-6 classic and trans-signaling, but only slightly to stimulation with IL-11. We observed that monocyte-like cell lines expressed high levels of IL-6R and responded to IL-6, but not to stimulation with IL-11. Using gene expression data, we found that IL11RA and IL11 are not overexpressed in human gastric cancer tissue and do not correlate with patient survival. However, low IL6 expression is associated with higher overall survival.

Conclusions: We provided evidence for IL-6 but not IL-11 signaling in gastric tumor cells and demonstrated that IL6 expression in gastric tumors is associated with overall survival of patients.

简介细胞因子白细胞介素-11(IL-11)在其靶细胞上与膜结合的 IL-11R 结合,从而导致信号转导 β 受体 gp130 的同源二聚化。最近的研究发现,IL-11/IL-11R 轴在多种疾病(包括不同的肿瘤实体)中具有促炎症作用,小鼠模型也揭示了 IL-11/IL-11R 轴在胃癌中的关键作用。然而,有关人类胃癌的研究却很少,而且在小鼠模型中获得的结果是否也适用于人类情况也鲜有研究:我们分析了不同胃癌和免疫细胞系中 IL11RA、IL11、IL6R、IL6 和 IL6ST 的基因表达。此外,我们还用外源细胞因子刺激这些细胞系,并测定细胞内信号传导。最后,我们分析了胃肿瘤患者的基因表达数据,并将其与患者的总生存率相关联:这项研究表明,不同的胃肿瘤细胞株对 IL-6 经典信号和跨信号有反应,但对 IL-11 的刺激反应轻微。我们观察到单核细胞样细胞株表达高水平的 IL-6R 并对 IL-6 有反应,但对 IL-11 的刺激没有反应。通过基因表达数据,我们发现 IL11RA 和 IL11 在人类胃癌组织中并未过度表达,也与患者的生存期无关。然而,IL6的低表达与较高的总生存率相关:我们提供了胃肿瘤细胞中 IL-6 而非 IL-11 信号转导的证据,并证明胃肿瘤中 IL6 的表达与患者的总生存率有关。
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引用次数: 0
Psychological distress and coping strategies in parents of children receiving cancer therapy in Morocco - a correlational study. 摩洛哥接受癌症治疗儿童的父母的心理困扰和应对策略--一项相关研究。
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-10-15 DOI: 10.5114/wo.2024.144134
Asmaa Marrakchi, Miloud Chakit, Naoual Elmorabit, Maria El Kababri, Aboubaker El Hessni, Abdelhalim Mesfioui

Introduction: Treating a child with cancer in a family is a challenge that can have an impact on mental health. The study consists of determining the prevalence of psychological distress of parents of cancer children and exploring its correlations with their coping strategies.

Material and methods: The survey was conducted between March and July 2023 among parents or guardians of children with cancer. The data collection tool was a version of the general health questionnaire (GHQ12) to estimate the prevalence of psychological distress and the coping orientation to problems experienced, to explore coping strategies. The correlation between the mean GHQ12 score and adaptation strategies is assessed through bivariate analyses and multiple regression.

Results: 232 parents or guardians of children participated in the study. The average GHQ12 score (0-36) was 22 ±6.83. Regarding coping strategies, religion was the most frequently used strategy. The general health questionnaire score showed significant negative correlations with active coping strategies with r = -0.14; p = 0.03, and acceptance with r = -0.51; p < 0.001, and significant positive correlations with denial with r = 0.25; p < 0.001, and self-blame with r = 0.24; p < 0,001. In multivariate analysis, acceptance (β = -1.9, p < 0.001) and denial stra- tegy (β = 0.46, p = 0.02) are predictive factors of psychological distress.

Conclusions: The study highlights the significant impact of coping strategies on the psychological distress experienced by parents of children undergoing cancer treatment in Morocco, by facilitating a more resilient adaptation and improved psychological well-being. These findings could form the basis for the development of culturally adapted mental health support programs for parents in simi-lar contexts.

介绍:治疗家庭中的癌症患儿是一项挑战,会对心理健康造成影响。本研究旨在确定癌症患儿父母心理困扰的普遍程度,并探讨其与应对策略的相关性:调查于 2023 年 3 月至 7 月间在癌症儿童的父母或监护人中进行。数据收集工具是一份普通健康问卷(GHQ12),用于估算心理困扰的普遍程度,以及对所经历问题的应对取向,从而探讨应对策略。通过双变量分析和多元回归评估了 GHQ12 平均得分与适应策略之间的相关性。GHQ12 平均得分(0-36 分)为 22 ±6.83。在应对策略方面,宗教是最常用的策略。一般健康问卷得分与积极应对策略呈显著负相关(r = -0.14;p = 0.03),与接受呈显著正相关(r = 0.51;p < 0.001),与否认呈显著正相关(r = 0.25;p < 0.001),与自责呈显著正相关(r = 0.24;p < 0.001)。在多变量分析中,接受(β = -1.9, p < 0.001)和否认压力(β = 0.46, p = 0.02)是心理困扰的预测因素:本研究强调了应对策略对摩洛哥接受癌症治疗儿童的父母所经历的心理压力的重要影响,因为它有助于提高适应能力和改善心理健康。这些研究结果可作为在类似背景下为父母制定适应文化的心理健康支持计划的基础。
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引用次数: 0
Deep feature extraction and fine κ-nearest neighbour for enhanced human papillomavirus detection in cervical cancer - a comprehensive analysis of colposcopy images. 用于增强宫颈癌人类乳头状瘤病毒检测的深度特征提取和精细κ-近邻--阴道镜图像综合分析。
IF 1.8 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-04-26 DOI: 10.5114/wo.2024.139091

Introduction: This study introduces a novel methodology for classifying human papillomavirus (HPV) using colposcopy images, focusing on its potential in diagnosing cervical cancer, the second most prevalent malignancy among women globally. Addressing a crucial gap in the literature, this study highlights the unexplored territory of HPV-based colposcopy image diagnosis for cervical cancer. Emphasising the suitability of colposcopy screening in underdeveloped and low-income regions owing to its small, cost-effective setup that eliminates the need for biopsy specimens, the methodological framework includes robust dataset augmentation and feature extraction using EfficientNetB0 architecture.

Material and methods: The optimal convolutional neural network model was selected through experimentation with 19 architectures, and fine-tuning with the fine κ-nearest neighbour algorithm enhanced the classification precision, enabling detailed distinctions with a single neighbour.

Results: The proposed methodology achieved outstanding results, with a validation accuracy of 99.9% and an area under the curve (AUC) of 99.86%, with robust performance on test data, 91.4% accuracy, and an AUC of 91.76%. These remarkable findings underscore the effectiveness of the integrated approach, which offers a highly accurate and reliable system for HPV classification.Conclusions: This research sets the stage for advancements in medical imaging applications, prompting future refinement and validation in diverse clinical settings.

导言:本研究介绍了一种利用阴道镜图像对人类乳头瘤病毒(HPV)进行分类的新方法,重点关注其在诊断宫颈癌(全球女性第二大恶性肿瘤)方面的潜力。这项研究填补了文献中的一个重要空白,突出了基于阴道镜图像的宫颈癌 HPV 诊断这一尚未开发的领域。该研究强调阴道镜筛查适用于不发达和低收入地区,因为其设置小巧、成本效益高,无需活检标本,方法框架包括使用 EfficientNetB0 架构进行稳健的数据集扩增和特征提取:通过对 19 种架构进行实验,选出了最佳卷积神经网络模型,并使用精细κ-近邻算法进行微调,提高了分类精度,从而实现了单个邻域的详细区分:所提出的方法取得了杰出的成果,验证准确率达 99.9%,曲线下面积(AUC)达 99.86%,在测试数据上表现强劲,准确率达 91.4%,曲线下面积(AUC)达 91.76%。这些令人瞩目的发现强调了综合方法的有效性,它为 HPV 分类提供了一个高度准确和可靠的系统:结论:这项研究为医学影像应用的进步奠定了基础,促使未来在不同的临床环境中进行改进和验证。
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引用次数: 0
Quality of life of patients treated for stage IV breast cancer. Multidimensional assessment and examination of determining factors.
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2025-01-15 DOI: 10.5114/wo.2024.147006
Juan Ignacio Arraras, Jose Juan Illarramendi, Ana Manterola, Uxue Zarandona, Berta Ibañez, Andrew Bottomley, Lucia Teijeira, Ignacio Visus, Susana de la Cruz, Marta Barrado, Ruth Vera

Introduction: Metastatic breast cancer (MBC) can profoundly impact patients' lives. The health-related quality of life (HRQOL) of MBC metavivors remains a paramount concern. This study exa-mined the multifaceted aspects of HRQOL in MBC metavivors.

Material and methods: Ninety-eight participants with over 4 years of meta-static disease were evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30, QLQ-BR42 and QLQ-BM22 alongside the Assessment of Survivor Concerns (ASC) questionnaire.

Results: HRQOL scores were high (> 80/100 points) in some HRQOL areas, including role, cognitive and social functioning and breast symptoms. Moderate limitations (> 30 points) occurred in global QOL and financial impact (QLQ-C30); sexual functioning, sexual enjoyment, future perspective, breast satisfaction, upset by hair loss, skeletal symptoms, and weight gain (QLQ-BR42); and psychosocial aspects of QLQ-BM22. Worries were moderate in the two ASC factors (6.8 and 5.3) and the global scale (11.7). The multivariate model that best explains high risk of low global QOL included limiting comorbidity, financial impact, cancer worry and role functioning (R 2 = 0.692). Patients with only bone metastases showed higher cancer and health worries (ASC scale) than patients with soft tissues and visceral sites.

Conclusions: This study shows that MBC metavivors adapted well to their situation and underscores the persistent HRQOL challenges they face. In-depth analysis of the QLQ-C30 glo-bal score highlights the need to address not only medical aspects but also integrated psychosocial and economi-cal support in MBC metavivor care. HRQOL variations across metastatic sites underscore the need to tailor interventions to address site-specific challenges.

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引用次数: 0
Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours. 评估胃-肠-胰腺和支气管神经内分泌肿瘤中 IL-6 家族的部分循环细胞因子--白细胞介素 6、oncostatin M 和心脏营养素-1。
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-08-23 DOI: 10.5114/wo.2024.142584
Janusz Strzelczyk, Ksenia Janas, Joanna Katarzyna Strzelczyk, Elżbieta Chełmecka, Dariusz Kajdaniuk, Beata Kos-Kudła

Introduction: The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs.

Material and methods: The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, n = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, n = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA.

Results: The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant (p < 0.001). The concentration of OSM was significantly lower in the study group than in the control group (p < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference (p < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways.

Conclusions: These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.

简介近年来,神经内分泌肿瘤(NET)的发病率有所上升。这些肿瘤大多没有功能,病程长且无症状。这就导致了晚期诊断。我们的研究目的是评估白细胞介素-6家族的某些循环细胞因子--白细胞介素6(IL-6)、癌细胞生长因子M(OSM)和心肌营养素-1(CT1)--在NET中的作用:研究组由多个亚组的80名患者(56%)组成,包括胃肠胰腺肿瘤(GEPNETs,n = 64,80%)和支气管肺神经内分泌肿瘤(BPNETs,n = 16,20%)。用酶联免疫吸附法检测血清中IL-6、OSM和CT1的浓度:研究组 IL-6 的中位浓度为 41.5 pg/ml,对照组为 32.6 pg/ml,差异有统计学意义(P < 0.001)。研究组的 OSM 浓度明显低于对照组(p < 0.001),分别为 105.6 pg/ml 和 115.5 pg/ml。研究组(222.0 pg/ml)和对照组(267.2 pg/ml)的 CT1 浓度有明显差异(p < 0.01)。我们对选定的 IL-6 家族细胞因子进行的调查显示,信号转导通路受到不同程度的调节:这些研究结果表明,尽管IL-6家族细胞因子利用了一种共同的信号转导因子,但它们对神经内分泌肿瘤的发展产生了不同的生物学效应。值得注意的是,IL-6似乎能促进肿瘤发生,而OSM和CT1则对胃肠道-胰腺和支气管神经内分泌肿瘤的发展有抑制作用。要验证IL-6家族细胞因子在NET中的诊断作用,还需要进一步的研究。
{"title":"Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours.","authors":"Janusz Strzelczyk, Ksenia Janas, Joanna Katarzyna Strzelczyk, Elżbieta Chełmecka, Dariusz Kajdaniuk, Beata Kos-Kudła","doi":"10.5114/wo.2024.142584","DOIUrl":"https://doi.org/10.5114/wo.2024.142584","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs.</p><p><strong>Material and methods: </strong>The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, <i>n</i> = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, <i>n</i> = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA.</p><p><strong>Results: </strong>The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant (<i>p</i> < 0.001). The concentration of OSM was significantly lower in the study group than in the control group (<i>p</i> < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference (<i>p</i> < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways.</p><p><strong>Conclusions: </strong>These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.</p>","PeriodicalId":49354,"journal":{"name":"Wspolczesna Onkologia-Contemporary Oncology","volume":"28 2","pages":"114-120"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478918","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
Survival after docetaxel for metastatic castration-resistant prostate cancer in a rural health care setting. 农村医疗机构多西他赛治疗转移性耐阉割前列腺癌后的存活率。
IF 1.8 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-04-15 DOI: 10.5114/wo.2024.138842

Introduction: The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated.

Material and methods: Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed.

Results: In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76.

Conclusions: In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.

简介本研究旨在评估挪威诺德兰郡农村地区接受多西他赛全身治疗的转移性阉割抵抗性前列腺癌(MCRPC)男性患者的总生存率。研究还评估了与治疗相关的预后因素和其他变量:这项回顾性研究共纳入132名患者,时间跨度为2009年至2022年。研究进行了单变量和多变量生存分析:在这组老年患者(中位年龄 72 岁)中,每周一次的低剂量多西他赛是首选方案(44%)。73%的患者接受了一线治疗。只有11名患者(8%)在激素敏感期预先接触过多西他赛。中位生存期为14.3个月。延长生存期的预后因素包括血红蛋白较高、乳酸脱氢酶较低、多西他赛作为MCRPC的一线治疗药物,以及因合并症而使用的处方药较少。多西他赛的预暴露作用不大,P = 0.76:在这一农村医疗机构中,多西他赛治疗后的存活期短于其他团体的报告。血液检测结果被证实是重要的预后因素。在治疗顺序不断变化的今天,我们建议对真实世界的治疗结果进行监测。
{"title":"Survival after docetaxel for metastatic castration-resistant prostate cancer in a rural health care setting.","authors":"Carsten Nieder, Luka Stanisavljevic, Astrid Dalhaug, Ellinor Haukland","doi":"10.5114/wo.2024.138842","DOIUrl":"10.5114/wo.2024.138842","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated.</p><p><strong>Material and methods: </strong>Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed.</p><p><strong>Results: </strong>In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76.</p><p><strong>Conclusions: </strong>In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.</p>","PeriodicalId":49354,"journal":{"name":"Wspolczesna Onkologia-Contemporary Oncology","volume":"28 1","pages":"31-36"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11117159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155474","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
Treatment outcomes of patients with BRAFV600E-mutated metastatic colorectal cancer: a Polish retrospective cohort study.
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2025-01-15 DOI: 10.5114/wo.2024.146953
Jolanta Żok, Michał Bieńkowski, Barbara Radecka, Agata Kuchar, Szymon Borowiec, Joanna Streb, Michał Jurczyk, Anna Jakieła-Drąg, Marek Gełej, Patryk Zając, Małgorzata Ploch-Glapińska, Renata Duchnowska

Introduction: The BRAFV600E mutation is found in 6-11% of metastatic colo-rectal cancer (mCRC) patients. According to international guidelines for BRAFV600E-mutated mCRC, the triplet chemotherapy FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) or double chemotherapy with or without bevacizumab, and encorafenib plus cetuximab should be considered in the first- and second-line settings. We aimed to evaluate clinical practices in BRAFV600E-mutated mCRC patients treated at five Polish oncology centers.

Material and methods: We retrospectively analyzed the data of BRAFV600E- mutated mCRC patients treated between 2011 and 2023. Before starting the first-line treatment, all patients were tested for BRAF and RAS mutations.

Results: One hundred twenty-six patients (median age: 68 years; 55% female, 45% male) from five oncology centers were included. The majority of patients (69, 55%) had a right-sided primary tumor. The first line of chemotherapy was received by 100 patients (79.4%). The majority received doublet chemotherapy: FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin), FOLFIRI (folinic acid, 5-fluorouracil, irinotecan), XELOX (capecitabine, oxaliplatin), and FOLFIRI with bevacizumab: 30 (30%), 47 (47%), 5 (5%), and 3 (3%). Only three patients received FOLFOXIRI; one patient received bevacizumab. The median duration of first-line treatment was 5.26 months (95% CI: 0.03-18.9). Subsequently, 40%, 16%, 5%, and 1% of patients received second, third, fourth, and fifth-line therapy, retrospectively. During the median follow-up of 38.5 months, 96 (79.3%) patients died. The median overall survival from the time of mCRC diagnosis was 13.7 months (95% CI: 11.3-17.6).

Conclusions: This study highlights the unmet need for effective treatment strategies for patients with BRAFV600E-mutated mCRC in Poland.

{"title":"Treatment outcomes of patients with BRAF<sup>V600E</sup>-mutated metastatic colorectal cancer: a Polish retrospective cohort study.","authors":"Jolanta Żok, Michał Bieńkowski, Barbara Radecka, Agata Kuchar, Szymon Borowiec, Joanna Streb, Michał Jurczyk, Anna Jakieła-Drąg, Marek Gełej, Patryk Zając, Małgorzata Ploch-Glapińska, Renata Duchnowska","doi":"10.5114/wo.2024.146953","DOIUrl":"10.5114/wo.2024.146953","url":null,"abstract":"<p><strong>Introduction: </strong>The BRAF<sup>V600E</sup> mutation is found in 6-11% of metastatic colo-rectal cancer (mCRC) patients. According to international guidelines for BRAF<sup>V600E</sup>-mutated mCRC, the triplet chemotherapy FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) or double chemotherapy with or without bevacizumab, and encorafenib plus cetuximab should be considered in the first- and second-line settings. We aimed to evaluate clinical practices in BRAF<sup>V600E</sup>-mutated mCRC patients treated at five Polish oncology centers.</p><p><strong>Material and methods: </strong>We retrospectively analyzed the data of BRAF<sup>V600E</sup>- mutated mCRC patients treated between 2011 and 2023. Before starting the first-line treatment, all patients were tested for BRAF and RAS mutations.</p><p><strong>Results: </strong>One hundred twenty-six patients (median age: 68 years; 55% female, 45% male) from five oncology centers were included. The majority of patients (69, 55%) had a right-sided primary tumor. The first line of chemotherapy was received by 100 patients (79.4%). The majority received doublet chemotherapy: FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin), FOLFIRI (folinic acid, 5-fluorouracil, irinotecan), XELOX (capecitabine, oxaliplatin), and FOLFIRI with bevacizumab: 30 (30%), 47 (47%), 5 (5%), and 3 (3%). Only three patients received FOLFOXIRI; one patient received bevacizumab. The median duration of first-line treatment was 5.26 months (95% CI: 0.03-18.9). Subsequently, 40%, 16%, 5%, and 1% of patients received second, third, fourth, and fifth-line therapy, retrospectively. During the median follow-up of 38.5 months, 96 (79.3%) patients died. The median overall survival from the time of mCRC diagnosis was 13.7 months (95% CI: 11.3-17.6).</p><p><strong>Conclusions: </strong>This study highlights the unmet need for effective treatment strategies for patients with BRAF<sup>V600E</sup>-mutated mCRC in Poland.</p>","PeriodicalId":49354,"journal":{"name":"Wspolczesna Onkologia-Contemporary Oncology","volume":"28 4","pages":"297-303"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400533","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
Evaluation of outcome and safety profile in high-dose BEAM and Benda-EAM chemotherapy with subsequent autologous stem cell transplantation in lymphoma patients. 评估淋巴瘤患者接受大剂量 BEAM 和 Benda-EAM 化疗后进行自体干细胞移植的疗效和安全性。
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-07-26 DOI: 10.5114/wo.2024.141794
Kinga Krawiec, Piotr Strzałka, Olga Racińska, Marcin Kędzior, Hubert Sowul, Wojciech Salamon, Kacper Kościelny, Michał Kośny, Damian Mikulski, Agnieszka Pluta, Agnieszka Wierzbowska

Introduction: Autologous hematopoietic stem cell transplantation (auto- HSCT) preceded by high-dose chemotherapy is a mainstay in relapsed/refractory lymphoma. The study aimed to compare the efficacy and adverse event profile between BEAM and Benda-EAM (BeEAM) regimens and to evaluate prognostic factors for survival in lymphoma patients undergoing auto-HSCT.

Material and methods: We present a single-center retrospective analysis of 82 lymphoma patients (median age 52; IQR 38.2-62.2) who received BEAM (47.6%) or BeEAM (52.4%) followed by auto-HSCT between January 2015 and December 2021.

Results: During the post-HSCT period 58% of patients experienced febrile neutropenia (51.3% vs. 64.3% in BEAM and BeEAM, respectively; p = 0.27), 80.5% mucositis (69.2% vs. 90.7%; p = 0.02), 42.5% bacteremia (50% vs. 35.7%; p = 0.26), and 18.8% pneumonia (31.6% vs. 7.1%; p = 0.01). Patients who received bendamustine required more platelet transfusions (p = 0.02). In the multivariate Cox regression model, C-reactive protein level on the first day of hospitalization (hazard ratio - HR = 1.03, 95% CI: 1.01-1.06) and days of agranulocytosis (HR = 1.15, 95% CI: 1.00-1.32) were predictors of poorer overall survival (OS), whereas hemoglobin level at the auto-HSCT was a protective factor in terms of OS (HR = 0.43, 95% CI: 0.23-0.78) and progression-free survival (PFS) (HR = 0.66, 95% CI: 0.45-0.96). The median OS since auto-HSCT was 87 months, while the median PFS was 49 months. No differences in PFS and OS between BEAM and BeEAM regimens were proven.

Conclusions: Conditioning with BEAM and BeEAM regimens is associated with comparable post-transplant outcomes. The toxicity of these regimens is comparable; however, BEAM is associated with a higher risk of pneumonia, while BeEAM is associated with a higher risk of mucositis.

简介自体造血干细胞移植(auto- HSCT)前进行大剂量化疗是治疗复发/难治性淋巴瘤的主要方法。该研究旨在比较BEAM和Benda-EAM(BeEAM)方案的疗效和不良反应情况,并评估接受自体造血干细胞移植的淋巴瘤患者的生存预后因素:我们对2015年1月至2021年12月期间接受BEAM(47.6%)或BeEAM(52.4%)后进行自动HSCT的82名淋巴瘤患者(中位年龄52岁;IQR 38.2-62.2)进行了单中心回顾性分析:在HSCT后期间,58%的患者出现发热性中性粒细胞减少症(BEAM和BeEAM分别为51.3%和64.3%;P = 0.27),80.5%的患者出现粘膜炎(69.2%和90.7%;P = 0.02),42.5%的患者出现菌血症(50%和35.7%;P = 0.26),18.8%的患者出现肺炎(31.6%和7.1%;P = 0.01)。接受苯达莫司汀治疗的患者需要更多的血小板输注(p = 0.02)。在多变量 Cox 回归模型中,住院第一天的 C 反应蛋白水平(危险比 - HR = 1.03,95% CI:1.01-1.06)和粒细胞减少天数(HR = 1.15,95% CI:1.00-1.32)是总生存期(OS)较差的预测因素,而自体HSCT时的血红蛋白水平是OS(HR = 0.43,95% CI:0.23-0.78)和无进展生存期(PFS)(HR = 0.66,95% CI:0.45-0.96)的保护因素。自体HSCT后的中位OS为87个月,中位PFS为49个月。BEAM和BeEAM方案的PFS和OS没有差异:结论:采用BEAM和BeEAM方案进行调理可获得相似的移植后疗效。结论:BEAM和BeEAM方案的移植后疗效相当,毒性也相当,但BEAM方案发生肺炎的风险较高,而BeEAM方案发生粘膜炎的风险较高。
{"title":"Evaluation of outcome and safety profile in high-dose BEAM and Benda-EAM chemotherapy with subsequent autologous stem cell transplantation in lymphoma patients.","authors":"Kinga Krawiec, Piotr Strzałka, Olga Racińska, Marcin Kędzior, Hubert Sowul, Wojciech Salamon, Kacper Kościelny, Michał Kośny, Damian Mikulski, Agnieszka Pluta, Agnieszka Wierzbowska","doi":"10.5114/wo.2024.141794","DOIUrl":"https://doi.org/10.5114/wo.2024.141794","url":null,"abstract":"<p><strong>Introduction: </strong>Autologous hematopoietic stem cell transplantation (auto- HSCT) preceded by high-dose chemotherapy is a mainstay in relapsed/refractory lymphoma. The study aimed to compare the efficacy and adverse event profile between BEAM and Benda-EAM (BeEAM) regimens and to evaluate prognostic factors for survival in lymphoma patients undergoing auto-HSCT.</p><p><strong>Material and methods: </strong>We present a single-center retrospective analysis of 82 lymphoma patients (median age 52; IQR 38.2-62.2) who received BEAM (47.6%) or BeEAM (52.4%) followed by auto-HSCT between January 2015 and December 2021.</p><p><strong>Results: </strong>During the post-HSCT period 58% of patients experienced febrile neutropenia (51.3% vs. 64.3% in BEAM and BeEAM, respectively; <i>p</i> = 0.27), 80.5% mucositis (69.2% vs. 90.7%; <i>p</i> = 0.02), 42.5% bacteremia (50% vs. 35.7%; p = 0.26), and 18.8% pneumonia (31.6% vs. 7.1%; <i>p</i> = 0.01). Patients who received bendamustine required more platelet transfusions (<i>p</i> = 0.02). In the multivariate Cox regression model, C-reactive protein level on the first day of hospitalization (hazard ratio - HR = 1.03, 95% CI: 1.01-1.06) and days of agranulocytosis (HR = 1.15, 95% CI: 1.00-1.32) were predictors of poorer overall survival (OS), whereas hemoglobin level at the auto-HSCT was a protective factor in terms of OS (HR = 0.43, 95% CI: 0.23-0.78) and progression-free survival (PFS) (HR = 0.66, 95% CI: 0.45-0.96). The median OS since auto-HSCT was 87 months, while the median PFS was 49 months. No differences in PFS and OS between BEAM and BeEAM regimens were proven.</p><p><strong>Conclusions: </strong>Conditioning with BEAM and BeEAM regimens is associated with comparable post-transplant outcomes. The toxicity of these regimens is comparable; however, BEAM is associated with a higher risk of pneumonia, while BeEAM is associated with a higher risk of mucositis.</p>","PeriodicalId":49354,"journal":{"name":"Wspolczesna Onkologia-Contemporary Oncology","volume":"28 2","pages":"158-166"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478917","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
Metformin in the treatment of colorectal cancer and neuroendocrine tumours. 治疗结直肠癌和神经内分泌肿瘤的二甲双胍。
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2024-08-23 DOI: 10.5114/wo.2024.142553
Karolina Daniłowska, Natalia Picheta, Barbara I Krupska, Anna Rudzińska, Oliwia Burdan, Katarzyna Szklener

Colorectal cancer is being detected in increasingly younger age groups, and its incidence has been on the rise in recent years. Neuroendocrine tumors have also shown an increase in occurrence despite their rarity. Neuroendocrine tumors most commonly occur in the gastrointestinal tract and lungs. Therefore, new, better, and more effective treatment methods are being sought. Metformin, a drug commonly used in the treatment of type 2 diabetes, has demonstrated its ability to reduce the incidence and increase the efficacy of chemotherapy in colorectal cancer and neuroendocrine tumors. The biguanide works by inhibiting the mammalian target of rapamycin pathway, activating 5'AMP activated protein kinase, and reducing insulin-like growth factor 1. In studies conducted on human cells and xenografts, the drug has shown its positive effects in combating these tumors by reducing proliferation, slowing the growth of cancer cells, and inhibiting metastasis. The main goal of this review is to comprehensively summarize the current state of knowledge regarding metformin in the treatment of colorectal cancer and neuroendocrine tumors.

结直肠癌的发现年龄越来越年轻化,近年来发病率呈上升趋势。神经内分泌肿瘤尽管罕见,但其发病率也呈上升趋势。神经内分泌肿瘤最常发生在胃肠道和肺部。因此,人们正在寻求新的、更好的和更有效的治疗方法。二甲双胍是一种常用于治疗 2 型糖尿病的药物,它已证明能够降低结肠直肠癌和神经内分泌肿瘤的发病率,并提高化疗的疗效。双胍类药物通过抑制哺乳动物雷帕霉素靶点通路、激活 5'AMP 活化蛋白激酶和减少胰岛素样生长因子 1 发挥作用。在对人体细胞和异种移植物进行的研究中,这种药物通过减少增殖、减缓癌细胞生长和抑制转移,在抗击这些肿瘤方面发挥了积极作用。本综述的主要目的是全面总结二甲双胍治疗结直肠癌和神经内分泌肿瘤的知识现状。
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引用次数: 0
Prognostic value of FGFR2 in ER-positive breast cancer is influenced by the profile of stromal gene expression: an in silico analysis based on TCGA data.
IF 2.9 Q2 ONCOLOGY Pub Date : 2024-01-01 Epub Date: 2025-01-15 DOI: 10.5114/wo.2024.147003
Julia M Sołek, Zuzanna Nowicka, Wojciech Fendler, Rafal Sadej, Hanna Romanska, Marcin Braun

Introduction: Fibroblast growth factor receptor 2 (FGFR2) activation is associated with endocrine therapy resistance in luminal breast cancer (BC) in vitro, but clinical evidence remains inconsistent. Given the role of FGFRs in mediating tumour microenvironment (TME) interactions, the prognostic value of FGFR2 may depend on the stromal component. This study aimed to validate the association between FGFR-related profile of the stroma and FGFR2 prognostic value in oestrogen receptor-positive invasive ductal carcinoma (IDC).

Material and methods: An in silico gene expression analysis identified 12 stromal factors (FAP, CXCL12, PDGFRA, COL1A1, HSPG2, CCL2, MMP14, S100A4, MMP9, PDGFA, MCAM, IL6) forming an "FGFR-related profile of the stroma". A cohort of 257 ER+ IDC patients from The Cancer Genome Atlas (TCGA) was analysed. Tumours were clustered using k-means based on stromal gene expression, and Cox proportional hazards regression models were used to assess the association between FGFR2 and overall survival (OS).

Results: Two clusters of ER+ IDC tumours were identified based on the stromal gene expression profile. While both clusters had similar tumour stages and hormone receptor statuses, multivariable analysis adjusted for clinical factors revealed a significant association between FGFR2 expression and cluster assignment. In Cluster I (high expression of stromal genes), high FGFR2 was linked to poor prognosis, whereas in Cluster II (low expression), high FGFR2 indicated favourable prognosis. FGFR1, FGFR3, and FGFR4 showed no significant prognostic value.

Conclusions: Stromal profiles modulate the prognostic significance of FGFR2 in luminal breast carcinoma, highlighting the importance of TME profiling for biomarker assessment and explaining inconsistencies in FGFR2 studies.

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引用次数: 0
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Wspolczesna Onkologia-Contemporary Oncology
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