首页 > 最新文献

Neoplasma最新文献

英文 中文
Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis. 氟司匹林通过抑制 FOXM1-KIF20A 轴发挥抗胶质母细胞瘤的作用。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_230909N479
Yang Kong, Wei Zhu, Zhen Zhang, Wei Sun, Guangqiang Cui, Hongguang Chen, Haiying Wang

Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

鉴于人类胶质母细胞瘤(GBM)的浸润性,鸡尾酒药物疗法仍将是治疗该疾病的重要工具。我们研究了氟嘧啶、培非那嗪和舒必利这三种经典的抗精神分裂症药物,并将其作为可能的抗 GBM 药物。CCK-8 试验表明,氟匹利林具有最突出的抗 GBM 作用。我们在体外和小鼠正位异种移植模型中进行了分子机制研究。氟螺利林抑制了 U87MG 和 U251 GBM 细胞株在体外的增殖和迁移。流式细胞术表明,治疗增加了细胞凋亡,细胞在 G2/M 期积累。我们分析了用该药物治疗的几种细胞系的公开表达数据,从而确定了包括 KIF20A 在内的几个基因会被氟螺利林下调,从而导致生长抑制/细胞凋亡。我们还证明了 siRNA 敲除驱动蛋白家族成员 KIF20A 可减轻 GBM 细胞和小鼠正位异种移植模型的细胞增殖。利用包含蛋白质相互作用网络的 String 数据库发现了 KIF20A 的调控因子--致癌转录因子 FOXM1。在氟螺利林处理的细胞中,FOXM1 蛋白减少,这表明由于 FOXM1 蛋白减少,KIF20A 在药物存在时被下调。这些结果表明,氟螺利林是一种有效的抗骨髓胶质瘤药物,它通过抑制 FOXM1-KIF20A 致癌轴而发挥作用。
{"title":"Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis.","authors":"Yang Kong, Wei Zhu, Zhen Zhang, Wei Sun, Guangqiang Cui, Hongguang Chen, Haiying Wang","doi":"10.4149/neo_2024_230909N479","DOIUrl":"10.4149/neo_2024_230909N479","url":null,"abstract":"<p><p>Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"333-346"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia. 斯洛伐克治疗人类乳头瘤病毒相关口咽癌的趋势。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240306N96
Michaela Švajdová, Pavol Dubinský, Branislav Jeremić, Vladimír Vojtek, Gabriela Barilíková, Iveta Selingerová, Tomáš Kazda

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

人乳头瘤病毒(HPV)相关口咽癌(OPC)的最佳治疗方法是目前临床研究的一个课题。这项问卷调查研究调查了斯洛伐克目前治疗人乳头瘤病毒相关(HPV+)口咽癌的趋势,并在临床试验之外将去强化肿瘤治疗纳入常规临床实践。斯洛伐克头颈部癌症合作小组(SCHNCG)编制了一份调查问卷,旨在确定斯洛伐克所有放射肿瘤学(RO)机构的 HPV+ OPC 肿瘤治疗趋势。放射肿瘤领域的专家们回答了有关各自机构特点的一般性问题,以及有关 HPV+ OPC 治疗的 4 个理论临床方案(病例报告),主要侧重于放射治疗(RT)的应用剂量、靶体积范围和同期化疗(CHT)类型。来自斯洛伐克 14 家机构的 35 位 RO 专家参与了问卷调查。关于 T1N1M0 HPV+ OPC 的初级放化疗 (CRT),16 位受访者(45.7%)会考虑将 RT 剂量降级为
{"title":"Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.","authors":"Michaela Švajdová, Pavol Dubinský, Branislav Jeremić, Vladimír Vojtek, Gabriela Barilíková, Iveta Selingerová, Tomáš Kazda","doi":"10.4149/neo_2024_240306N96","DOIUrl":"https://doi.org/10.4149/neo_2024_240306N96","url":null,"abstract":"<p><p>The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"402-413"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
A response to: Artificial immortalization, number of therapy lines, and survival of patients with advanced gastric and esophagogastric adenocarcinoma. 回应:晚期胃癌和食管胃腺癌患者的人工永生化、治疗次数和存活率。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240618N262-R
Vesna Bišof, Andrija Katić, Majana Soče, Marina Vidović, Jelena Viculin, Stjepko Pleština, Eduard Vrdoljak

N/A.

不适用。
{"title":"A response to: Artificial immortalization, number of therapy lines, and survival of patients with advanced gastric and esophagogastric adenocarcinoma.","authors":"Vesna Bišof, Andrija Katić, Majana Soče, Marina Vidović, Jelena Viculin, Stjepko Pleština, Eduard Vrdoljak","doi":"10.4149/neo_2024_240618N262-R","DOIUrl":"https://doi.org/10.4149/neo_2024_240618N262-R","url":null,"abstract":"<p><p>N/A.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"415-416"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer. 高组蛋白 H3K18 乳化水平与上皮性卵巢癌的不良预后相关。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240127N41
Jinyu Chao, Guan-di Chen, Shu-Ting Huang, Haifeng Gu, Yue-Yang Liu, Yiheng Luo, Zidan Lin, Zhi-Zai Chen, Xiaoli Li, Bin Zhang, Xifeng Xu, Shanyang He

Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.

蛋白质乳化在恶性肿瘤中预后较差,但它对上皮性卵巢癌(EOC)预后的影响仍不清楚。我们对 112 例 EOC 患者进行了分析。免疫组化染色法检测了EOC组织和正常卵巢组织中泛乳化(Pan Kla)和组蛋白H3K18乳化(H3K18la)的水平。结果显示,EOC组织的蛋白乳化水平高于正常组织。然后,我们分析了EOC的总生存期(OS)、无进展生存期(PFS)与乳酸化之间的关系。结果显示,组蛋白H3K18la水平高的患者OS(P=0.028)和PFS(P=0.028)均较差。
{"title":"High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer.","authors":"Jinyu Chao, Guan-di Chen, Shu-Ting Huang, Haifeng Gu, Yue-Yang Liu, Yiheng Luo, Zidan Lin, Zhi-Zai Chen, Xiaoli Li, Bin Zhang, Xifeng Xu, Shanyang He","doi":"10.4149/neo_2024_240127N41","DOIUrl":"https://doi.org/10.4149/neo_2024_240127N41","url":null,"abstract":"<p><p>Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"319-332"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Vitamin D supplementation in cancer prevention and the management of cancer therapy. 在癌症预防和癌症治疗管理中补充维生素 D。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240531N240
Ladislav Klena, Kristina Galvankova, Adela Penesova, Olga Krizanova

Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g., cancer. Vitamin D is involved in the regulation of cell proliferation, differentiation, energetic metabolism, and different types of cell death (e.g., apoptosis, autophagy, etc.). In physiological conditions, it is also able to modulate immune responses, angiogenesis, etc., which belongs to fundamental cancer-related processes. Vitamin D deficiency has been associated with an increased risk of some types of cancer, e.g., colorectal, breast, ovarian, prostate, pancreatic, etc. The role of vitamin D in cancer prevention, carcinogenesis, and cancer treatment is still under investigation and depends on the type of cancer. This review summarizes the role of vitamin D in all three above-mentioned aspects and discusses the mechanism of action and potential possibilities in cancer treatment.

维生素 D 是一种重要的类固醇激素,具有免疫调节作用,能控制钙和磷的平衡,并对人体健康产生重大影响。维生素 D 缺乏症是一个全球性的健康问题,影响着全球约 60% 的成年人,并与癌症等一系列不同类型的疾病有关。维生素 D 参与细胞增殖、分化、能量代谢和不同类型细胞死亡(如细胞凋亡、自噬等)的调节。在生理条件下,它还能调节免疫反应、血管生成等与癌症有关的基本过程。缺乏维生素 D 会增加罹患某些类型癌症的风险,如结直肠癌、乳腺癌、卵巢癌、前列腺癌、胰腺癌等。维生素 D 在癌症预防、致癌和治疗中的作用仍在研究中,并取决于癌症的类型。本综述总结了维生素 D 在上述三个方面的作用,并讨论了维生素 D 在癌症治疗中的作用机制和潜在可能性。
{"title":"Vitamin D supplementation in cancer prevention and the management of cancer therapy.","authors":"Ladislav Klena, Kristina Galvankova, Adela Penesova, Olga Krizanova","doi":"10.4149/neo_2024_240531N240","DOIUrl":"https://doi.org/10.4149/neo_2024_240531N240","url":null,"abstract":"<p><p>Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g., cancer. Vitamin D is involved in the regulation of cell proliferation, differentiation, energetic metabolism, and different types of cell death (e.g., apoptosis, autophagy, etc.). In physiological conditions, it is also able to modulate immune responses, angiogenesis, etc., which belongs to fundamental cancer-related processes. Vitamin D deficiency has been associated with an increased risk of some types of cancer, e.g., colorectal, breast, ovarian, prostate, pancreatic, etc. The role of vitamin D in cancer prevention, carcinogenesis, and cancer treatment is still under investigation and depends on the type of cancer. This review summarizes the role of vitamin D in all three above-mentioned aspects and discusses the mechanism of action and potential possibilities in cancer treatment.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"307-318"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The importance of sentinel lymph node intraoperative frozen analysis for indication of lateral neck dissection in patients with medullary thyroid cancer. 前哨淋巴结术中冰冻分析对甲状腺髓样癌患者颈侧清扫指征的重要性
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240521N228
Robert Kralik, Eva Takacsova, Iveta Waczulikova, Miguel Arciniegas, Martin Sabol, Stefan Durdik, Marianna Grigerova

Our research seeks to evaluate the utility of intraoperative frozen analysis of sentinel lymph nodes (SLNs) in the lateral cervical compartment (LCC) as a tool to inform decision-making regarding therapeutic neck dissection in patients with medullary thyroid carcinoma (MTC). This is particularly relevant due to the variability observed in guidelines regarding the indication for lateral neck dissection in this patient population. The study comprised 64 patients (25 males, 39 females) aged between 29 and 81 years, with a median age of 59, who underwent surgery for MTC at stage T1-3N0-1M0 between January 1, 2012, and December 31, 2020. A standardized surgical approach involving total thyroidectomy with central neck dissection was adopted. LCC dissection was reserved for patients with clinically apparent nodal metastases. In patients lacking clinical evidence of nodal involvement, SLNs were identified using patent blue dye, excised, and subjected to intraoperative frozen analysis. If metastasis was confirmed, LCC dissection was subsequently performed. Among the study participants, 14 individuals (21.9%) underwent therapeutic LCC dissection due to clinical lymph node (LN) metastases. This intervention resulted in clinical remission for 9 patients, while disease progression was observed in 5 cases, leading to 2 fatalities. In the remaining cohort of 50 patients clinically negative for nodal involvement, SLNs were successfully identified and examined in 38 cases, revealing metastases in 6 patients (15.8%). Among both subsets of patients with analyzed SLNs, irrespective of metastatic status, one patient each required repeat surgery due to disease recurrence; however, all patients eventually achieved clinical remission. Lymphatic mapping in the LCC plays a pivotal role in detecting early metastases, thereby aiding in the avoidance of unnecessary repeat neck surgeries, and ultimately improving the prognosis in patients with MTC.

我们的研究旨在评估术中对颈外侧区(LCC)前哨淋巴结(SLN)进行冷冻分析的效用,以此作为甲状腺髓样癌患者颈部治疗性切除的决策依据。由于指南中关于该患者群体颈侧切除术的适应症存在差异,因此这一点尤为重要。这项研究包括 64 名患者(25 名男性,39 名女性),年龄在 29 岁至 81 岁之间,中位年龄为 59 岁,他们都是在 2012 年 1 月 1 日至 2020 年 12 月 31 日期间接受手术治疗的 T1-3N0-1M0 期 MTC 患者。采用的标准化手术方法包括全甲状腺切除术和颈部中央切除术。临床上有明显结节转移的患者才会进行 LCC 切除术。对于无临床证据表明有结节受累的患者,使用专利蓝染料对SLN进行鉴定、切除并进行术中冷冻分析。如果证实有转移,则随后进行 LCC 剖检。研究参与者中有 14 人(21.9%)因临床淋巴结(LN)转移而接受了治疗性 LCC 切除术。9名患者的临床症状得到缓解,5名患者的病情恶化,其中2人死亡。在剩余的 50 例临床表现为结节受累阴性的患者中,有 38 例成功识别并检查了 SLN,发现 6 例患者(15.8%)有转移。在分析了SLNs的两个亚组患者中,无论转移状态如何,各有一名患者因疾病复发而需要再次手术;不过,所有患者最终都实现了临床缓解。LCC淋巴管图谱在检测早期转移灶方面起着关键作用,从而有助于避免不必要的颈部重复手术,最终改善 MTC 患者的预后。
{"title":"The importance of sentinel lymph node intraoperative frozen analysis for indication of lateral neck dissection in patients with medullary thyroid cancer.","authors":"Robert Kralik, Eva Takacsova, Iveta Waczulikova, Miguel Arciniegas, Martin Sabol, Stefan Durdik, Marianna Grigerova","doi":"10.4149/neo_2024_240521N228","DOIUrl":"https://doi.org/10.4149/neo_2024_240521N228","url":null,"abstract":"<p><p>Our research seeks to evaluate the utility of intraoperative frozen analysis of sentinel lymph nodes (SLNs) in the lateral cervical compartment (LCC) as a tool to inform decision-making regarding therapeutic neck dissection in patients with medullary thyroid carcinoma (MTC). This is particularly relevant due to the variability observed in guidelines regarding the indication for lateral neck dissection in this patient population. The study comprised 64 patients (25 males, 39 females) aged between 29 and 81 years, with a median age of 59, who underwent surgery for MTC at stage T1-3N0-1M0 between January 1, 2012, and December 31, 2020. A standardized surgical approach involving total thyroidectomy with central neck dissection was adopted. LCC dissection was reserved for patients with clinically apparent nodal metastases. In patients lacking clinical evidence of nodal involvement, SLNs were identified using patent blue dye, excised, and subjected to intraoperative frozen analysis. If metastasis was confirmed, LCC dissection was subsequently performed. Among the study participants, 14 individuals (21.9%) underwent therapeutic LCC dissection due to clinical lymph node (LN) metastases. This intervention resulted in clinical remission for 9 patients, while disease progression was observed in 5 cases, leading to 2 fatalities. In the remaining cohort of 50 patients clinically negative for nodal involvement, SLNs were successfully identified and examined in 38 cases, revealing metastases in 6 patients (15.8%). Among both subsets of patients with analyzed SLNs, irrespective of metastatic status, one patient each required repeat surgery due to disease recurrence; however, all patients eventually achieved clinical remission. Lymphatic mapping in the LCC plays a pivotal role in detecting early metastases, thereby aiding in the avoidance of unnecessary repeat neck surgeries, and ultimately improving the prognosis in patients with MTC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"387-391"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Artificial immortalization, number of therapy lines, and survival of patients with advanced gastric and esophagogastric adenocarcinoma. 晚期胃癌和食管胃腺癌患者的人工永生化、治疗次数和存活率。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240618N262
Ivan Krečak, Marko Skelin, Marko Lucijanić

Letter to the Editor Regarding 'Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia', published in Neoplasma 2024; 71: 201-208. https://doi.org/10.4149/neo_2024_231209N633.

致编辑的信,内容涉及《晚期胃癌和食管胃腺癌治疗线数量对生存期的影响--来自克罗地亚的真实世界回顾性分析》,发表于《Neoplasma 2024》;71: 201-208。https://doi.org/10.4149/neo_2024_231209N633。
{"title":"Artificial immortalization, number of therapy lines, and survival of patients with advanced gastric and esophagogastric adenocarcinoma.","authors":"Ivan Krečak, Marko Skelin, Marko Lucijanić","doi":"10.4149/neo_2024_240618N262","DOIUrl":"https://doi.org/10.4149/neo_2024_240618N262","url":null,"abstract":"<p><p>Letter to the Editor Regarding 'Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia', published in Neoplasma 2024; 71: 201-208. https://doi.org/10.4149/neo_2024_231209N633.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"414"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
HER2 status results in an unstable switch from primary to recurrent breast cancer. HER2 状态导致原发性乳腺癌向复发性乳腺癌的不稳定转换。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240229N89
Anjie Zhu, Nan Wang, Zehui Yun, Xiaoran Liu, Xu Liang, Ying Yan, Bin Shao, Hanfang Jiang, Lijun Di, Guohong Song, Huiping Li

Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression. We included patients who were HER2-2+ of primary or rebiopsy tumor samples, to evaluate the evolution of HER2-2+ expression. In the cohort with a total of 159 patients with HER2-2+ expression in either primary tumor or locoregional/distant metastasis samples, 44.0% had HER2-2+ in primary tumor and 88.8% in recurrent disease. Among patients with primary and recurrent HER2-2+ breast cancers, 18.5% and 15.2% of the patients, respectively, had HER2 gene amplification via ISH. The overall rate of discordance in HER2 IHC results was 67.1%. Among primary HER2-2+ patients, 74.6% were maintained in the HER2-2+ cohort at the recurrence. The discordance was mostly driven by patients switching from HER2-2+ to HER2-1+ (64.7%). Among HER2-2+ recurrent patients, discordance in the IHC results was mostly driven by switching from HER2-0 to HER2-2+ (47.1%). When HER2-low was added to the analysis, the overall rate of HER2 discordance was 40.4%. The proportion of patients with discordant HER2 expression was significantly greater among HR-positive patients than negative patients (44.1% vs. 21.7%, p=0.062). HER2 expression in primary and recurrent breast cancer samples was highly unstable. Discordance was more frequently observed in the HR-positive population.

通过免疫组化(IHC)准确区分HER2-2+肿瘤和HER2-0/1+肿瘤仍然非常具有挑战性。HER2 IHC 2+ 被认为表示中度表达,更容易区分,在以前和现在的临床实践中结果更可靠。我们以 HER2-2+ 患者为研究对象,评估了原发性和配对复发性疾病患者之间 HER2 状态的转换,以评价 HER2+ 表达的不一致性。我们还纳入了原发或复查肿瘤样本中HER2-2+的患者,以评估HER2-2+表达的演变情况。在原发肿瘤或局部/远处转移样本中均有HER2-2+表达的159例患者中,44.0%的患者在原发肿瘤中HER2-2+,88.8%的患者在复发疾病中HER2-2+。在原发性和复发性HER2-2+乳腺癌患者中,分别有18.5%和15.2%的患者通过ISH检测发现HER2基因扩增。HER2 IHC结果的总体不一致率为67.1%。在原发性 HER2+ 患者中,74.6% 的患者在复发时仍保持在 HER2+ 组群中。不一致的主要原因是患者从HER2-2+转为HER2-1+(64.7%)。在HER2-2+复发患者中,IHC结果不一致的主要原因是从HER2-0转为HER2-2+(47.1%)。如果将HER2-low加入分析,HER2不一致的总体比例为40.4%。HR阳性患者中HER2表达不一致的比例明显高于阴性患者(44.1% vs. 21.7%,P=0.062)。原发性和复发性乳腺癌样本中的HER2表达高度不稳定。在HR阳性人群中更常观察到不一致性。
{"title":"HER2 status results in an unstable switch from primary to recurrent breast cancer.","authors":"Anjie Zhu, Nan Wang, Zehui Yun, Xiaoran Liu, Xu Liang, Ying Yan, Bin Shao, Hanfang Jiang, Lijun Di, Guohong Song, Huiping Li","doi":"10.4149/neo_2024_240229N89","DOIUrl":"10.4149/neo_2024_240229N89","url":null,"abstract":"<p><p>Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression. We included patients who were HER2-2+ of primary or rebiopsy tumor samples, to evaluate the evolution of HER2-2+ expression. In the cohort with a total of 159 patients with HER2-2+ expression in either primary tumor or locoregional/distant metastasis samples, 44.0% had HER2-2+ in primary tumor and 88.8% in recurrent disease. Among patients with primary and recurrent HER2-2+ breast cancers, 18.5% and 15.2% of the patients, respectively, had HER2 gene amplification via ISH. The overall rate of discordance in HER2 IHC results was 67.1%. Among primary HER2-2+ patients, 74.6% were maintained in the HER2-2+ cohort at the recurrence. The discordance was mostly driven by patients switching from HER2-2+ to HER2-1+ (64.7%). Among HER2-2+ recurrent patients, discordance in the IHC results was mostly driven by switching from HER2-0 to HER2-2+ (47.1%). When HER2-low was added to the analysis, the overall rate of HER2 discordance was 40.4%. The proportion of patients with discordant HER2 expression was significantly greater among HR-positive patients than negative patients (44.1% vs. 21.7%, p=0.062). HER2 expression in primary and recurrent breast cancer samples was highly unstable. Discordance was more frequently observed in the HR-positive population.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"392-401"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The role of RRS1 in breast cancer cells metastasis and AEG-1/AKT/c-Myc signaling pathway. RRS1 在乳腺癌细胞转移和 AEG-1/AKT/c-Myc 信号通路中的作用。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240122N35
Jing He, Sijing Liu, Shajie Luo, Jiaojiao Fu, Zhengyue Liao, Junying Song, Jinlin Guo, Ya'nan Hua

Breast cancer is the most common malignant tumor in women. Recurrence, metastasis, and chemotherapy resistance are the main causes of death in breast cancer patients. The inhibition of breast cancer metastasis is of great significance for prolonging its survival. Ribosome biogenesis regulatory protein homolog (RRS1) is overexpressed in breast cancer tissues and is involved in regulating the carcinogenic process of breast cancer cells. However, the exact signaling pathway and molecular mechanism of RRS1 promoting breast cancer metastasis are not fully understood. Hence, the primary objective of our study is to investigate the correlation between RRS1 and breast cancer metastasis. Bioinformatic analysis was used to identify the expression levels and prognostic significance of RRS1 in breast cancer. Lenti-sh RRS1 lentivirus was constructed and employed to downregulate the RRS1 expression in MDA-MB-231 and BT549 cells, which had a high-level expression of RRS1. Subsequently, we assessed the impact of RRS1 downregulation on the proliferation, migration, and invasion of breast cancer cells using CCK-8, apoptosis, and cell cycle by flow cytometry, wound healing test, Transwell migration, and invasion experiments. Moreover, we utilized an in vivo imaging system to examine the metastatic potential of breast cancer cells after RRS1 knockdown. Picrate staining and hematoxylin-eosin staining were employed to evaluate the presence of metastatic lesions. To gain a deeper understanding of the molecular mechanism, we conducted co-immunoprecipitation and western blot. The significant overexpression of RRS1 in breast cancer indicates a worse prognosis, as determined through TCGA databases (p<0.01). Additionally, RRS1 exhibits upregulation in breast cancer (p<0.001), which is tightly linked to the occurrence of lymph node metastasis (p<0.001). Clinical breast cancer tissues and breast cancer cell lines also demonstrated a noteworthy upregulation of RRS1 (p<0.05). Loss-of-function experiment illustrated that the inhibiting of RRS1 expression reduced the rapid proliferation capacity of MDA-MB-231 and BT549 cells and hindered their migration and invasion capabilities (p<0.05). Importantly, the suppression of RRS1 significantly diminished lung metastasis in Balb/c nude mice that were injected with MDA-MB-231 cells (p<0.01). Mechanistically, RRS1 may interact with the AEG-1 to modulate the phosphorylation of AKT at T308 and S473, consequently impeding the activity of c-Myc (p<0.05). To conclude, RRS1 functions as a potential oncogene in breast cancer by leveraging the AEG-1/AKT/c-Myc signaling.

乳腺癌是女性最常见的恶性肿瘤。复发、转移和化疗耐药是乳腺癌患者死亡的主要原因。抑制乳腺癌转移对延长患者生存期具有重要意义。核糖体生物发生调控蛋白同源物(RRS1)在乳腺癌组织中过度表达,参与调控乳腺癌细胞的致癌过程。然而,RRS1 促进乳腺癌转移的确切信号通路和分子机制尚不完全清楚。因此,我们研究的主要目的是探讨 RRS1 与乳腺癌转移之间的相关性。研究采用生物信息学分析来确定 RRS1 在乳腺癌中的表达水平和预后意义。我们构建了Lenti-sh RRS1慢病毒,用于下调RRS1在MDA-MB-231和BT549细胞中的表达。随后,我们利用 CCK-8、流式细胞术、伤口愈合试验、Transwell 迁移和侵袭实验评估了 RRS1 下调对乳腺癌细胞增殖、迁移和侵袭的影响,以及细胞凋亡和细胞周期的影响。此外,我们还利用体内成像系统检测了 RRS1 基因敲除后乳腺癌细胞的转移潜力。我们还采用了毕赤染色和苏木精-伊红染色来评估转移病灶的存在。为了深入了解其分子机制,我们进行了共免疫沉淀和免疫印迹。根据 TCGA 数据库的测定,RRS1 在乳腺癌中的显著过表达表明预后较差(p
{"title":"The role of RRS1 in breast cancer cells metastasis and AEG-1/AKT/c-Myc signaling pathway.","authors":"Jing He, Sijing Liu, Shajie Luo, Jiaojiao Fu, Zhengyue Liao, Junying Song, Jinlin Guo, Ya'nan Hua","doi":"10.4149/neo_2024_240122N35","DOIUrl":"10.4149/neo_2024_240122N35","url":null,"abstract":"<p><p>Breast cancer is the most common malignant tumor in women. Recurrence, metastasis, and chemotherapy resistance are the main causes of death in breast cancer patients. The inhibition of breast cancer metastasis is of great significance for prolonging its survival. Ribosome biogenesis regulatory protein homolog (RRS1) is overexpressed in breast cancer tissues and is involved in regulating the carcinogenic process of breast cancer cells. However, the exact signaling pathway and molecular mechanism of RRS1 promoting breast cancer metastasis are not fully understood. Hence, the primary objective of our study is to investigate the correlation between RRS1 and breast cancer metastasis. Bioinformatic analysis was used to identify the expression levels and prognostic significance of RRS1 in breast cancer. Lenti-sh RRS1 lentivirus was constructed and employed to downregulate the RRS1 expression in MDA-MB-231 and BT549 cells, which had a high-level expression of RRS1. Subsequently, we assessed the impact of RRS1 downregulation on the proliferation, migration, and invasion of breast cancer cells using CCK-8, apoptosis, and cell cycle by flow cytometry, wound healing test, Transwell migration, and invasion experiments. Moreover, we utilized an in vivo imaging system to examine the metastatic potential of breast cancer cells after RRS1 knockdown. Picrate staining and hematoxylin-eosin staining were employed to evaluate the presence of metastatic lesions. To gain a deeper understanding of the molecular mechanism, we conducted co-immunoprecipitation and western blot. The significant overexpression of RRS1 in breast cancer indicates a worse prognosis, as determined through TCGA databases (p<0.01). Additionally, RRS1 exhibits upregulation in breast cancer (p<0.001), which is tightly linked to the occurrence of lymph node metastasis (p<0.001). Clinical breast cancer tissues and breast cancer cell lines also demonstrated a noteworthy upregulation of RRS1 (p<0.05). Loss-of-function experiment illustrated that the inhibiting of RRS1 expression reduced the rapid proliferation capacity of MDA-MB-231 and BT549 cells and hindered their migration and invasion capabilities (p<0.05). Importantly, the suppression of RRS1 significantly diminished lung metastasis in Balb/c nude mice that were injected with MDA-MB-231 cells (p<0.01). Mechanistically, RRS1 may interact with the AEG-1 to modulate the phosphorylation of AKT at T308 and S473, consequently impeding the activity of c-Myc (p<0.05). To conclude, RRS1 functions as a potential oncogene in breast cancer by leveraging the AEG-1/AKT/c-Myc signaling.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"347-358"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients. 生殖细胞肿瘤患者谷胱甘肽 S 转移酶 M1 表达与治疗效果之间的关系
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_240609N249
Michal Mego, Katarina Kalavska, Samuel Horak, Michaela Hyblova, Georgina Kolnikova, Vera Novotna, Kristina Majtanova, Gabriel Minarik, Lucia Kucerova, Zuzana Cierna

Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.

以顺铂为基础的化疗是治疗生殖细胞肿瘤(GCT)的主要方法。谷胱甘肽 S-转移酶(GST)是一种多态酶,可催化谷胱甘肽与烷化剂、铂化合物和化疗产生的自由基的结合,因此与治疗耐药性的产生有关。本研究旨在评估 GST mu 1(GSTM1)的表达水平及其与 GCT 患者治疗效果的关系。这项转化研究纳入了207名新确诊的GCT患者的肿瘤标本,以及顺铂敏感的GCT细胞系异种移植及其耐药变体,涵盖了GCT的所有组织学变体。GSTM1 的表达通过反转录定量 PCR 和使用单克隆抗体的免疫组织化学方法进行检测,并采用乘法快速评分(QS)法进行评分。GSTM1的表达与患者/肿瘤特征和治疗结果相关。精原细胞瘤的 GSTM1 表达量最高,其次是绒毛膜癌、胚胎癌和卵黄囊瘤,而畸胎瘤的 GSTM1 表达量最低(P<0.05)。
{"title":"Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients.","authors":"Michal Mego, Katarina Kalavska, Samuel Horak, Michaela Hyblova, Georgina Kolnikova, Vera Novotna, Kristina Majtanova, Gabriel Minarik, Lucia Kucerova, Zuzana Cierna","doi":"10.4149/neo_2024_240609N249","DOIUrl":"10.4149/neo_2024_240609N249","url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"374-386"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
期刊
Neoplasma
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1