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Research advances on TIL therapy for colorectal cancer. TIL 治疗结直肠癌的研究进展。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-28 DOI: 10.1007/s12094-024-03530-4
Jiaojiao Jiang, Wenxi Shu, Qinghua Yao

Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy. Tumor-infiltrating lymphocyte (TIL) therapy, a form of adoptive cellular therapy (ACT), involves isolating T lymphocytes from tumor tissues, in vitro expansion, and reintroduction into the body to target and eliminate tumor cells. This article presents an overview of the development and application of TIL therapy in CRC, as well as the associated challenges.

结直肠癌(CRC)是一种常见的胃肠道恶性肿瘤。肿瘤浸润淋巴细胞(TIL)疗法是一种领养细胞疗法(ACT),包括从肿瘤组织中分离出T淋巴细胞,进行体外扩增,然后重新导入体内靶向清除肿瘤细胞。本文概述了 TIL 疗法在 CRC 中的发展和应用,以及相关挑战。
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引用次数: 0
A retrospective analysis of the clinicopathological features and prognostic value of MAPK12 protein expression in diffuse large B-cell lymphoma. 弥漫大 B 细胞淋巴瘤的临床病理特征和 MAPK12 蛋白表达预后价值的回顾性分析。
IF 4.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-21 DOI: 10.1007/s12094-024-03515-3
Yue Liu, Han Zhang, Shu Zhao, Yue Zhang

Purpose: Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL).

Methods: Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates.

Results: We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes.

Conclusion: DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.

目的:丝裂原活化蛋白激酶12(MAPK12)又称p38γ,是p38 MAPK家族的成员之一,在肿瘤发生和侵袭过程中起着至关重要的作用。然而,MAPK12在弥漫大B细胞淋巴瘤(DLBCL)中的参与情况仍不确定:我们的研究采用生物信息学分析方法调查了 MAPK12 mRNA 在各种类型癌症中的表达情况。此外,我们还通过免疫组化(IHC)检测了MAPK12在DLBCL患者中的表达情况,并比较了临床指标和生存率:结果:我们发现,MAPK12在DLBCL患者中的高表达率为43.1%。包括IPI评分、Hans分类、LDH水平和Ki-67表达在内的多项临床指标与MAPK12的表达密切相关。生存期分析显示,MAPK12的高表达与DLBCL患者较短的无进展生存期(PFS)和总生存期(OS)显著相关。此外,单变量和多变量分析表明,IPI评分、MAPK12表达和利妥昔单抗的使用是独立的OS风险因素(P 结论:DLBCL患者的预后较差:MAPK12水平高时,DLBCL患者预后较差,有望成为治疗靶点和预后因素。
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引用次数: 0
Hyperprogressive disease in patients with advanced cancer treated with immune checkpoint inhibitors. 接受免疫检查点抑制剂治疗的晚期癌症患者病情过度进展。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-03 DOI: 10.1007/s12094-024-03696-x
Gülin Alkan Şen, Nihan Şentürk Öztaş, Ezgi Değerli, Murad Guliyev, Günay Can, Hande Turna, Mustafa Özgüroğlu

Background: Hyperprogressive disease (HPD) is a new phenomenon developing in the era of immune checkpoint inhibitor (ICI) therapy. HPD is characterized by an unexpected and fast progression in tumor volume and poor survival. There is no standardized definition for HPD and clinicopathological variables associated with HPD are unclear. Herein, we assessed incidence, treatment outcomes and factors predictive of HPD in patients treated with ICIs.

Methods: We retrospectively analyzed patients with advanced cancer treated with ICI at one academic center between 2014 and 2021. We used the Lo Russo's adopted criteria combined with clinical and radiologic parameters for the definition of HPD. All patients who underwent their first tumor evaluation according to RECIST1.1 were included.

Results: Of 155 patients, 147 were eligible for analysis. The median age was 61 and 83% were male. The cancer types were; lung 67.3%, bladder 12.9%, gastric 9.5%, 5, colon 5.4% and renal cell carcinoma 4.8%. 59.9% of patients were treatment-naive and others had one or more lines of chemotherapy. 19 (12.9%) patients had HPD. In patients who had HPD, progression-free survival (PFS) was significantly shorter (1.5 vs 9.8 months, (HR 9.56; 95% CI (5.51-16.57), p < 0.001). The median overall survival (OS) was also shorter for HPD patients than non-HPD (3.0 vs 23.1 months, respectively, HR 12.03, 95% CI (6.64-21.81), p < 0.001). Gastric cancer, larger sum of target lesion diameters at baseline, liver metastases, higher LDH level and higher neutrophil-lymphocyte ratio (NLR) were significantly associated with HPD.

Conclusion: Our findings demonstrated that HPD was a rapid phenomenon with significantly poor survival rates. Several clinicopathological factors and tumor characteristics might indicate HPD.

背景:超进展性疾病(HPD)是免疫检查点抑制剂(ICI)治疗时代出现的一种新现象。HPD的特点是肿瘤体积出乎意料地快速进展,生存率低。HPD尚无标准化定义,与HPD相关的临床病理变量也不明确。在此,我们评估了接受 ICIs 治疗的患者中 HPD 的发生率、治疗结果和预测因素:我们回顾性分析了2014年至2021年间在一家学术中心接受ICI治疗的晚期癌症患者。我们采用 Lo Russo 采用的标准结合临床和放射学参数来定义 HPD。所有根据RECIST1.1进行首次肿瘤评估的患者均被纳入其中:在 155 名患者中,有 147 名符合分析条件。中位年龄为 61 岁,83% 为男性。癌症类型包括:肺癌 67.3%、膀胱癌 12.9%、胃癌 9.5%、结肠癌 5.4%、肾细胞癌 4.8%。59.9%的患者未接受过治疗,其他患者接受过一次或多次化疗。19名患者(12.9%)患有HPD。在患有HPD的患者中,无进展生存期(PFS)明显较短(1.5个月 vs 9.8个月,HR 9.56; 95% CI (5.51-16.57), p 结论:我们的研究结果表明,HPD是一种快速现象,其生存率明显较低。一些临床病理因素和肿瘤特征可能预示着 HPD。
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引用次数: 0
Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01). 放疗加顺铂或西妥昔单抗治疗局部晚期头颈癌患者的晚期毒性生物标志物研究指出皮肤巨噬细胞的相关性(TOX-TTCC-2015-01)。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-23 DOI: 10.1007/s12094-024-03526-0
Antonio Rullan, Juan A Marín-Jiménez, Alicia Lozano, Oriol Bermejo, Lorena Arribas, Nuria Ruiz, Isabel Linares, Miren Taberna, Xavi Pérez, María Plana, Marc Oliva, Ricard Mesía

Purpose: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity.

Methods/patients: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC).

Results: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68.

Conclusions: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

目的:放疗(RT)联合顺铂(CRT)或西妥昔单抗(ERT)是治疗局部晚期头颈部鳞状细胞癌(LA-SCCHN)的公认治疗方案。长期不良反应(AEs)对患者的生活质量有很大影响。本研究探讨了有助于预测晚期毒性的组织生物标志物:单机构前瞻性研究,包括年龄≥18岁、组织学确诊的新诊断LA-SCCHN患者,根据机构方案接受RT治疗,并同时接受顺铂q3w或每周西妥昔单抗治疗。所有患者都在治疗前和治疗后对临床目标体积内的颈部区域进行了皮肤活检。通过免疫组化(IHC)对血管生成、巨噬细胞和细胞外基质(ECM)标记物进行了评估:从2016年4月15日至2017年12月11日,共对31名患者进行了评估[CRT=12(38.7%),ERT=19(61.3%)]。27名患者(87%)接受了诱导化疗。所有患者都按计划完成了 RT。CRT 和 ERT 两组患者的血管(CD34)和胶原(Masson's Trichrome)的 IHC 表达没有显著差异。相反,治疗后观察到 CD68 和 CD163 巨噬细胞浸润表达增加,但治疗方式无明显影响。晚期毒性较高的患者与晚期毒性较低的患者相比,治疗前样本中巨噬细胞标记物的表达较低,其中CD68的差异有统计学意义:血管生成和ECM生物标志物在CRT和ERT之间没有显著差异。结论:CRT 和 ERT 的血管生成和 ECM 生物标志物无明显差异,两种治疗后巨噬细胞标志物均增加,值得进一步研究,以预测 LA-SCCHN 患者的晚期毒性。[协议代码:TOX-TTCC-2015-01TOX-TTCC-2015-01/西班牙临床研究登记处(REec):2015-003012-21/注册日期:2016年1月27日]。
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引用次数: 0
Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis. 甲氧口服长春瑞滨及其联合疗法作为晚期非小细胞肺癌二线和三线治疗方案的疗效和安全性:一项回顾性分析。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-09 DOI: 10.1007/s12094-024-03543-z
ShiJie Chen, ZhiYong He, MeiFang Li, LiHong Weng, JingHui Lin

Objective: This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC).

Methods: NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared.

Results: Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4 months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2 months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6 months (95% CI 4.8 to 6.4 months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3 months (95% CI 0.1 to 12.5 months) and DCR of 86.7%.

Conclusion: Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.

研究目的该回顾性分析旨在评价甲氧口服长春瑞滨及其联合治疗作为晚期非小细胞肺癌(NSCLC)二线及二线以上治疗方案的疗效及不良反应:入选2018年10月至2022年10月在福建省肿瘤医院接受甲氧口服长春瑞滨作为二线及二线以上治疗方案的NSCLC患者,收集患者的人口学特征和临床特征。比较甲氧口服长春瑞滨单药及其联合治疗方案的疗效和安全性:57名研究对象中,63.2%接受了三线及三线以上治疗,中位无进展生存期(mPFS)为4个月,总反应率(ORR)为10.5%,疾病控制率(DCR)为80.7%。与治疗相关的不良反应发生率为42.1%,只有一例出现3级和4级不良反应(1.8%)。在驱动基因阴性的参与者中,长春瑞滨联合治疗方案的mPFS时间更长(4.6个月对1.2个月,危险比=0.11,P 结论:长春瑞滨联合治疗方案的mPFS时间更长:甲氧口服长春瑞滨及其联合治疗方案是晚期NSCLC患者二线和三线治疗的有利选择,具有可接受的疗效和可耐受的毒性。相对于甲硝唑口服长春瑞滨,长春瑞滨联合治疗方案显示出更高的疗效和相似的毒性,而且甲硝唑口服长春瑞滨可能与免疫疗法和表皮生长因子受体-TKI靶向疗法具有协同作用。
{"title":"Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.","authors":"ShiJie Chen, ZhiYong He, MeiFang Li, LiHong Weng, JingHui Lin","doi":"10.1007/s12094-024-03543-z","DOIUrl":"10.1007/s12094-024-03543-z","url":null,"abstract":"<p><strong>Objective: </strong>This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared.</p><p><strong>Results: </strong>Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4 months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2 months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6 months (95% CI 4.8 to 6.4 months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3 months (95% CI 0.1 to 12.5 months) and DCR of 86.7%.</p><p><strong>Conclusion: </strong>Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3202-3210"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retrospective registry of patients with locally advanced/metastatic HR+/HER2- breast cancer treated in clinical practice in Andalusia. 对在安达卢西亚接受临床治疗的局部晚期/转移性 HR+/HER2- 乳腺癌患者进行回顾性登记。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-03 DOI: 10.1007/s12094-024-03510-8
Natalia Chavarría Piudo, Isabel Blancas, Encarna González Flores, Fernando Henao Carrasco, Pilar López Álvarez, David Morales Pancorbo, Salvador Gámez Casado, María de la Cabeza Lomas Garrido, José Manuel Rodríguez García, Antonia Martínez Guisado, Adrián Sánchez Vega, Manuel Ruíz Borrego

Background: Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC).

Objective: To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis.

Methods: Physicians from 12 centers participated in selecting demographic and clinical characteristics, treatment, and outcome data from women with HR + /HER2- MBC treated with or without CDK4/6i in addition to hormonal in the first-line setting, in a 3:1 proportion. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs).

Results: A total of 212 patients were included, of whom 175 (82.5%) were in the CDK4/6i treatment group and 37 (17.5%) were in the non-CDK4/6i treatment group (control group). Patients in the CDK 4/6i treatment group were younger (p = 0.0011), the biopsies of the metastatic site at the moment of the relapse were most commonly performed (p = 0.0454), and had multiple metastatic sites (p = 0.0025). The clinical benefit rate (CBR) was 82.3% in the CDK4/6i group and 67.8% in the control group. Median time to a progression event or death (PFS) was 20.4 months (95%CI 15.6-28) in the CDK4/6i group and 12.1 months (95%CI 7.9-not reached) in the control group.

Conclusions: Younger patients, biopsies of metastatic disease and with multiple metastatic sites were more frequently treated with CDK4/6i in our daily clinical practice.

背景:有关细胞周期蛋白依赖性激酶4/6抑制剂(CDK4/6i)(palbociclib/ribociclib)作为激素受体阳性/人表皮生长因子受体2阴性(HR + /HER2-)转移性乳腺癌(MBC)患者一线治疗的实际有效性和安全性的数据有限:评估在2017年11月至2020年4月期间,安达卢西亚自治区(西班牙)的临床实践中,临床或人口统计特征是否限制了CDK4/6i一线治疗的获得。此外,还将对有效性进行探索性分析:来自12个中心的医生以3:1的比例参与了对HR + /HER2- MBC女性患者的人口统计学和临床特征、治疗和结果数据的筛选,这些患者在一线治疗中除激素治疗外还接受或不接受CDK4/6i治疗。卡普兰-梅耶尔分析估计了无进展率(PFR)和生存率(SR):共纳入212例患者,其中175例(82.5%)为CDK4/6i治疗组,37例(17.5%)为非CDK4/6i治疗组(对照组)。CDK 4/6i治疗组患者更年轻(p = 0.0011),最常在复发时对转移部位进行活检(p = 0.0454),并且有多个转移部位(p = 0.0025)。CDK4/6i组的临床获益率(CBR)为82.3%,对照组为67.8%。CDK4/6i组患者出现进展事件或死亡的中位时间(PFS)为20.4个月(95%CI 15.6-28),对照组为12.1个月(95%CI 7.9-未达到):结论:在我们的日常临床实践中,年轻患者、转移性疾病活检结果和多个转移部位的患者更常接受CDK4/6i治疗。
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引用次数: 0
Proteo-genomic characterization of cirrhosis-associated liver cancers reveals potential subtypes and therapeutic targets. 肝硬化相关肝癌的蛋白质基因组特征揭示了潜在亚型和治疗靶点。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-28 DOI: 10.1007/s12094-024-03517-1
Yi-Fan Gao, Yang-Qing Liu, Hui Zhang, Meng-Yi Zhang

Background: This study aimed to identify potential subtypes of hepatocellular carcinoma (HCC) associated with cirrhosis and to investigate key markers using bioinformatic analysis of gene expression datasets-0.

Methods: Three data sets (GSE17548, GSE56140, and GSE87630) were extracted from the Gene Expression Omnibus (GEO) database and normalized using the Limma package in R. Principal component analysis (PCA) and cluster analysis was performed to examine data distribution and identify subtypes. Differential gene expression analysis was performed using the Limma software package. Protein-protein interaction analysis and functional annotation were performed using the STRING database and Cytoscape software. Important signaling pathways and processes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis.

Results: The analysis revealed different subtypes of HCC associated with cirrhosis and identified several key genes, including CCNB2, MCM4, and CDC20, with strong binding power and prognostic value. Functional annotation indicated involvement in cell cycle regulation and metabolic pathways. ROC analysis showed high sensitivity and specificity of these genes in predicting HCC prognosis.

Conclusion: These results suggest that CCNB2, MCM4, and CDC20 may serve as potential biomarkers for predicting HCC prognosis in patients with cirrhosis and provide insights into the molecular mechanisms of HCC progression.

背景:本研究旨在确定与肝硬化相关的肝细胞癌(HCC)的潜在亚型,并利用生物信息学分析方法研究关键标记物:本研究旨在确定与肝硬化相关的肝细胞癌(HCC)的潜在亚型,并利用生物信息学分析基因表达数据集-0研究关键标记物:从基因表达总库(GEO)数据库中提取了三个数据集(GSE17548、GSE56140和GSE87630),并使用R语言中的Limma软件包进行了归一化处理。使用 Limma 软件包进行差异基因表达分析。使用 STRING 数据库和 Cytoscape 软件进行了蛋白质-蛋白质相互作用分析和功能注释。使用基因本体(GO)和京都基因和基因组百科全书(KEGG)途径分析确定了重要的信号通路和过程:结果:分析揭示了与肝硬化相关的不同亚型HCC,并确定了几个关键基因,包括CCNB2、MCM4和CDC20,它们具有很强的结合力和预后价值。功能注释表明,这些基因参与了细胞周期调控和代谢途径。ROC分析表明,这些基因在预测HCC预后方面具有很高的灵敏度和特异性:这些结果表明,CCNB2、MCM4 和 CDC20 可作为预测肝硬化患者 HCC 预后的潜在生物标志物,并为 HCC 进展的分子机制提供了见解。
{"title":"Proteo-genomic characterization of cirrhosis-associated liver cancers reveals potential subtypes and therapeutic targets.","authors":"Yi-Fan Gao, Yang-Qing Liu, Hui Zhang, Meng-Yi Zhang","doi":"10.1007/s12094-024-03517-1","DOIUrl":"10.1007/s12094-024-03517-1","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify potential subtypes of hepatocellular carcinoma (HCC) associated with cirrhosis and to investigate key markers using bioinformatic analysis of gene expression datasets-0.</p><p><strong>Methods: </strong>Three data sets (GSE17548, GSE56140, and GSE87630) were extracted from the Gene Expression Omnibus (GEO) database and normalized using the Limma package in R. Principal component analysis (PCA) and cluster analysis was performed to examine data distribution and identify subtypes. Differential gene expression analysis was performed using the Limma software package. Protein-protein interaction analysis and functional annotation were performed using the STRING database and Cytoscape software. Important signaling pathways and processes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis.</p><p><strong>Results: </strong>The analysis revealed different subtypes of HCC associated with cirrhosis and identified several key genes, including CCNB2, MCM4, and CDC20, with strong binding power and prognostic value. Functional annotation indicated involvement in cell cycle regulation and metabolic pathways. ROC analysis showed high sensitivity and specificity of these genes in predicting HCC prognosis.</p><p><strong>Conclusion: </strong>These results suggest that CCNB2, MCM4, and CDC20 may serve as potential biomarkers for predicting HCC prognosis in patients with cirrhosis and provide insights into the molecular mechanisms of HCC progression.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3085-3099"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LC-MS metabolomics analysis of serum metabolites during neoadjuvant chemoradiotherapy in locally advanced rectal cancer. 局部晚期直肠癌新辅助放化疗期间血清代谢物的LC-MS代谢组学分析
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-03 DOI: 10.1007/s12094-024-03537-x
Qiliang Peng, Lili Jiang, Yi Shen, Yao Xu, Xinan Shen, Li Zou, Yaqun Zhu, Yuntian Shen

Background: This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis.

Methods: 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves.

Results: The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability.

Conclusion: This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.

研究背景本研究旨在利用液相色谱-质谱(LC-MS)代谢组学分析方法,研究局部晚期直肠癌(LARC)患者新辅助化放疗(NCRT)期间的血清代谢物谱。方法:从放疗前、放疗中和放疗后的 20 名 LARC 患者中采集 60 份血清样本,进行 LC-MS 代谢组学分析,以确定代谢物的变化。应用功能注释发现代谢途径的改变。筛选出关键代谢物,并利用随机森林和 ROC 曲线计算其预测放疗敏感性的能力:结果表明,NCRT 导致血清代谢物谱发生显著变化。血清代谢谱在不同时间点和不同敏感性组之间有明显的分离。此外,功能注释显示,不同的代谢物与一系列重要的代谢途径相关。放疗前的(3Z,6Z)-3,6-壬二烯纳和放疗前的1-羟基布洛芬在区分NCRT敏感组和非敏感组方面显示出良好的预测性能,AUC分别为0.812和0.75。重要的是,不同代谢物的组合能显著提高预测能力:这项研究证明了 LC-MS 代谢组学在揭示 LARC NCRT 期间血清代谢物谱方面的潜力。鉴定出的代谢物可作为治疗该疾病的潜在生物标记物和治疗靶点。此外,了解受影响的代谢途径有助于为 LARC 患者设计更加个性化的治疗策略。
{"title":"LC-MS metabolomics analysis of serum metabolites during neoadjuvant chemoradiotherapy in locally advanced rectal cancer.","authors":"Qiliang Peng, Lili Jiang, Yi Shen, Yao Xu, Xinan Shen, Li Zou, Yaqun Zhu, Yuntian Shen","doi":"10.1007/s12094-024-03537-x","DOIUrl":"10.1007/s12094-024-03537-x","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis.</p><p><strong>Methods: </strong>60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves.</p><p><strong>Results: </strong>The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3150-3168"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance? 与血液病患者 PICC 相关的血栓形成和感染,其意义何在?
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-12 DOI: 10.1007/s12094-024-03548-8
Manuel Sánchez Cánovas, Esmeralda García Torralba, Noel Blaya Boluda, Ana Sánchez Saura, Gabriel Puche Palao, Ana Sánchez Fuentes, Lorena Martínez Montesinos, Carmen Poveda Ganga, Lucía García Tomas, Josefa Bayona Jiménez, Ángeles Cos Zapata, Carmen María Muñoz Jurado, Inmaculada Pina Mingorance, María Amor Caravaca Hernández, Vicente Vicente García, Francisco Ayala de la Peña

Purpose: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions.

Material and methods: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events.

Results: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy.

Conclusions: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

目的:肿瘤血液病患者的外周置入中心静脉导管(PICC)可能与血栓形成或感染有关,并可能造成中短期影响:对前瞻性收集的队列进行单中心回顾性分析。主要目的是确定 PICC 血栓和感染的发生率。次要目标是分析这些并发症患者的概况以及与发生这些事件的可能性增加相关的变量:共招募了 549 名患者。58.5%(n = 321)为肿瘤科患者,41.5%(n = 228)为血液科患者。与 PICC 相关的血栓形成发生率为 3.5%(n = 19)。10.6%的病例(n = 2)的血栓形成与潜在恶性病变的进展有关。所分析的临床变量与血栓形成之间没有关联。与 PICC 相关的感染发生率为 7.65%(42 例)。在 PICC 感染前的 30 天内,57.1%(n = 24)的患者出现过其他病灶的发热综合征,73.8%(n = 11)的患者曾住院治疗,49.5%(n = 25)的患者中性粒细胞计数为 0-500 cells/mm3,47.6%(n = 20)的患者曾出现过中性粒细胞减少性发热。与感染发生明显相关的变量包括血液病患者、高流量PICC、3-lm PICC或因接受膀胱造瘘剂治疗而插入PICC:结论:PICC 相关血栓形成的发生率较低,与其他形式的癌症相关血栓形成相比,其预后的侵袭性显然较小,但没有确定预测因素。感染的发生率较高,在我们的系列研究中找出风险因素有助于预防感染。
{"title":"Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?","authors":"Manuel Sánchez Cánovas, Esmeralda García Torralba, Noel Blaya Boluda, Ana Sánchez Saura, Gabriel Puche Palao, Ana Sánchez Fuentes, Lorena Martínez Montesinos, Carmen Poveda Ganga, Lucía García Tomas, Josefa Bayona Jiménez, Ángeles Cos Zapata, Carmen María Muñoz Jurado, Inmaculada Pina Mingorance, María Amor Caravaca Hernández, Vicente Vicente García, Francisco Ayala de la Peña","doi":"10.1007/s12094-024-03548-8","DOIUrl":"10.1007/s12094-024-03548-8","url":null,"abstract":"<p><strong>Purpose: </strong>Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions.</p><p><strong>Material and methods: </strong>Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events.</p><p><strong>Results: </strong>549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy.</p><p><strong>Conclusions: </strong>Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3226-3235"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology. 2024 年乳腺癌生物标志物:西班牙肿瘤内科学会和西班牙病理学会最新共识声明。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1007/s12094-024-03541-1
Ramon Colomer, Blanca González-Farré, Ana Isabel Ballesteros, Vicente Peg, Begoña Bermejo, Belén Pérez-Mies, Susana de la Cruz, Federico Rojo, Sonia Pernas, José Palacios

This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX®, MammaPrint®, Prosigna®, or EndoPredict®) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

这份由西班牙肿瘤内科学会(SEOM)和西班牙病理解剖学会(SEAP)修订的共识声明更新了我们于 2018 年首次发布的关于在乳腺癌诊断和治疗中使用生物标志物的建议。专家组建议在早期乳腺癌中确定雌激素受体(ER)、孕激素受体(PR)、Ki-67和人表皮生长因子受体2(HER2),以及高危HER2阴性乳腺癌中的乳腺癌(BRCA)基因,以辅助预后并帮助指明治疗方案,包括激素治疗、化疗、抗HER2治疗和其他靶向治疗。现有的四种基因预后平台(Oncotype DX®、MammaPrint®、Prosigna® 或 EndoPredict®)之一可用于ER阳性的早期乳腺癌患者,以确定预后类别,并帮助患者决定辅助治疗是否仅限于激素治疗。在二线晚期乳腺癌中,此外,对激素敏感的病例应检测磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚基α(PIK3CA)和雌激素受体 1(ESR1),对 HER2 阴性的癌症应检测 BRCA 基因突变,对三阴性乳腺癌(TNBC)应检测程序性细胞死亡-1 配体(PD-L1)。包括肿瘤浸润淋巴细胞(TILs)、同源重组缺陷(HRD)检测、丝氨酸/苏氨酸激酶(AKT)通路激活和新一代测序(NGS)在内的新型生物标记物和技术目前尚处于研究阶段。
{"title":"Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.","authors":"Ramon Colomer, Blanca González-Farré, Ana Isabel Ballesteros, Vicente Peg, Begoña Bermejo, Belén Pérez-Mies, Susana de la Cruz, Federico Rojo, Sonia Pernas, José Palacios","doi":"10.1007/s12094-024-03541-1","DOIUrl":"10.1007/s12094-024-03541-1","url":null,"abstract":"<p><p>This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX<sup>®</sup>, MammaPrint<sup>®</sup>, Prosigna<sup>®</sup>, or EndoPredict<sup>®</sup>) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2935-2951"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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Clinical & Translational Oncology
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