Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-294
Sanne Holt, Sophie C Vermond, M. Hazenoot, Rene J. McLaughlin, Marco Guadagnoli, M. Vlaming
{"title":"Abstract 294:In vitroefficacy studies to support engineered T cell therapies","authors":"Sanne Holt, Sophie C Vermond, M. Hazenoot, Rene J. McLaughlin, Marco Guadagnoli, M. Vlaming","doi":"10.1158/1538-7445.AM2021-294","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-294","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81215723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-328
Kelton A. Schleyer, Ben Fetrow, P. Z. Fatland, Jun Liu, Maya Chaaban, Biwu Ma, Lina Cui
{"title":"Abstract 328: Selective fluorogenic probe for rapid detection of cathepsin L activity","authors":"Kelton A. Schleyer, Ben Fetrow, P. Z. Fatland, Jun Liu, Maya Chaaban, Biwu Ma, Lina Cui","doi":"10.1158/1538-7445.AM2021-328","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-328","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81516118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-274
Michaela A. McCown, Carolyn Allen, Daniel Machado, S. Payne
{"title":"Abstract 274: Comparison of proteomics identification pipelines for lymphocyte characterization","authors":"Michaela A. McCown, Carolyn Allen, Daniel Machado, S. Payne","doi":"10.1158/1538-7445.AM2021-274","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-274","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76404770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-279
C. Brami, Ellaine Salvador, A. Kessler, M. Burek, T. Voloshin, M. Giladi, R. Ernestus, M. Löhr, C. Förster, C. Hagemann
{"title":"Abstract 279: Transient opening of the blood brain barrier by Tumor Treating Fields (TTFields)","authors":"C. Brami, Ellaine Salvador, A. Kessler, M. Burek, T. Voloshin, M. Giladi, R. Ernestus, M. Löhr, C. Förster, C. Hagemann","doi":"10.1158/1538-7445.AM2021-279","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-279","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"28 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91499976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-325
M. Dong, Karim Aljakouch, K. Böpple, Bernd Winkler, J. Schüler, F. Essmann, H. Kopp, J. Krijgsveld, W. Aulitzky
{"title":"Abstract 325: Nascent proteome analysis of tumor cells and their microenvironment in cultured human tumor tissues","authors":"M. Dong, Karim Aljakouch, K. Böpple, Bernd Winkler, J. Schüler, F. Essmann, H. Kopp, J. Krijgsveld, W. Aulitzky","doi":"10.1158/1538-7445.AM2021-325","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-325","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88006121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-284
V. Ouellette, Atziri Corin Chavez Alvarez, S. Fortin
{"title":"Abstract 284: Design, synthesis and biological evaluation of novel water-soluble salts of the antimitotic prodrugs 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides selectively bioactivated by cytochrome p450 1A1 in breast cancer cells","authors":"V. Ouellette, Atziri Corin Chavez Alvarez, S. Fortin","doi":"10.1158/1538-7445.AM2021-284","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-284","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82969909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-SY07-02
J. Barnholtz-Sloan
Glioblastoma (GBM) is the most common type of primary malignant tumor in adults and contributes disproportionately to cancer morbidity and mortality. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomics data on 99-treatment naive GBMs provided insights to GBM biology. Multiple key findings emerged that were not known from traditional genomic analyses: (1) Analysis of protein phosphorylation identified key signaling intermediates in the RTK/RAS path-way common to multiple RTK genomic alterations (PTPN11 and PLCG1), potentially offering common therapeutic targets for different oncogenic drivers in GBM. (2) Phosphoproteomics also identified potential druggable targets based on kinase-substrate pathway analysis, as well as novel phosphoprotein targets associated with the regulation of telomere length by ATRX in IDH mutants. (3) TP53 protein abundance in GBM is regulated by protein/phosphoprotein effectors (4) Four immune GBM subtypes exist, characterized by distinct immune cell population differences – Immune High and Immune Low phenotypes in GBM were driven by tumor-associated macrophage markers, and associated with distinct epigenetic modifications and histone acetylation patterns. (5) The mesenchymal subtype displays EMT signatures specific in tumor cells, distinct from infiltrating immune cells. (6) Histone H2B acetylation and immune-low GBM was driven largely by BRDs, CREBBP, and EP300. (7) Identification of key metabolic changes in IDH mutants facilitating the accumulation of onco-metabolite 2-HG were also associated with lipidomic changes. This work identifies additional therapeutic channels for GBM and novel information useful for more accurate stratification patients for effective treatment. Citation Format: Jill S. Barnholtz-Sloan. Gaining biologic insights into glioblastoma using proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY07-02.
胶质母细胞瘤(GBM)是成人中最常见的原发性恶性肿瘤类型，并对癌症发病率和死亡率有不成比例的贡献。了解其分子发病机制对提高诊断和治疗具有重要意义。对99次治疗的初始GBM的基因组学、蛋白质组学、翻译后修饰和代谢组学数据进行综合分析，为GBM生物学提供了新的见解。传统基因组分析中不知道的多个关键发现:(1)蛋白质磷酸化分析确定了多个RTK基因组改变(PTPN11和PLCG1)共同的RTK/RAS通路中的关键信号中间体，可能为GBM中不同的致癌驱动因素提供共同的治疗靶点。(2)磷酸化蛋白质组学还通过激酶-底物通路分析发现了潜在的可药物靶点，以及IDH突变体中与ATRX调节端粒长度相关的新型磷酸化蛋白靶点。(3) GBM中TP53蛋白丰度受蛋白/磷蛋白效应物调控。(4)GBM存在四种免疫亚型，其特征是免疫细胞群差异明显——GBM中的免疫高表型和免疫低表型由肿瘤相关巨噬细胞标志物驱动，并与不同的表观遗传修饰和组蛋白乙酰化模式相关。(5)间充质亚型在肿瘤细胞中表现出特异性的EMT特征，与浸润性免疫细胞不同。(6)组蛋白H2B乙酰化和免疫低GBM主要由brd、CREBBP和EP300驱动。(7) IDH突变体中促进肿瘤代谢物2-HG积累的关键代谢变化也与脂质组学变化有关。这项工作确定了GBM的额外治疗渠道和新信息，有助于更准确地分层患者进行有效治疗。引用格式:Jill S. Barnholtz-Sloan。利用蛋白质组学获得胶质母细胞瘤的生物学见解[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):SY07-02。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-319
A. DelaCourt, A. Mehta, Alyson P. Black, R. Drake, P. Angel, Y. Hoshida
{"title":"Abstract 319: MALDI-IMS of N-glycan profiles of molecular subclasses of human hepatocellular carcinoma","authors":"A. DelaCourt, A. Mehta, Alyson P. Black, R. Drake, P. Angel, Y. Hoshida","doi":"10.1158/1538-7445.AM2021-319","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-319","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91299719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-313
A. S. Bawadood, F. Al-Abbasi, A. El-Halawany, A. M. Al-Abd
Breast cancer is one of the most common female cancers and contributes 25.4% of the total diagnosed malignancies in women in 2018. Shogaol, paradol, and gingerol are obtained from many plants belonging to the family Zingiberaceae such as dried ginger and grain of paradise and shows different pharmacological activities. The current study evaluated the anticancer potential of these compounds in combination with chemotherapeutic platinum drugs against breast cancer cells. Cytotoxicity assay, apoptosis assay, immunofluorescent staining cell surface marker analysis, and wound healing assay were used for evaluating the cytotoxic potential of these compounds alone and in combination with platinum chemotherapeutics agents against naive and resistant breast cancer cell lines (MDA-MB-231 and MCF-7adr, respectively). Platinum drugs showed synergism in combination with shogaol and gingerol against the resistant breast cancer cells (MCF-7adr) with a Combination Index (CI) values of 0.39 and 0.54, respectively. A significant increase was observed in the percentages of early and late apoptotic cells for MDA-MB-231 cells treated with 6-shogaol for 24h. Significant decrease in CD44+/CD24- subpopulation was recorded in both cell lines using flowcytometric analysis. In the Wound healing assay, cells treated with the test compounds migrated significantly slower than control and needed a longer time to heal the scratch. In conclusion, gingerol, shogaol, and paradol compounds showed synergistic cytotoxicity with platinum-based drug and augmented their migration inhibitory activity, apoptotic effects, and tumor-associated stem cell suppressive the potential within naive and resistant breast cancer cells. Citation Format: Aziza S. Bawadood, Fahad A. Al-Abbasi, Ali M. El-Halawany, Ahmed M. Al-Abd. Synergistic interaction between gingerol, shogaol and paradol with platinum-based chemotherapeutic drugs against naive and resistant breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 313.
乳腺癌是最常见的女性癌症之一，占2018年女性确诊恶性肿瘤总数的25.4%。Shogaol、paradol和gingerol分别从姜科植物干姜和天堂粮中提取，具有不同的药理活性。目前的研究评估了这些化合物与化疗铂类药物联合治疗乳腺癌细胞的抗癌潜力。采用细胞毒性试验、细胞凋亡试验、免疫荧光染色细胞表面标记分析和伤口愈合试验来评估这些化合物单独使用和与铂类化疗药物联合使用对初发和耐药乳腺癌细胞系(分别为MDA-MB-231和MCF-7adr)的细胞毒性潜力。铂类药物联合shogaol、gingerol对耐药乳腺癌细胞MCF-7adr有协同作用，联合指数(CI)分别为0.39、0.54。6-shogaol作用24h后，MDA-MB-231细胞的早期和晚期凋亡细胞百分比显著增加。流式细胞术分析显示，两种细胞系中CD44+/CD24-亚群显著降低。在伤口愈合试验中，用测试化合物处理的细胞迁移速度明显慢于对照组，并且需要更长的时间来愈合划痕。综上所述，姜辣素、姜酚和酚类化合物与铂基药物表现出协同细胞毒性，增强了它们在初发和耐药乳腺癌细胞中的迁移抑制活性、凋亡作用和肿瘤相关干细胞抑制潜力。引文格式:Aziza S. Bawadood, Fahad A. Al-Abbasi, Ali M. El-Halawany, Ahmed M. Al-Abd。姜辣素、shogaol和paradol与铂类化疗药物对初发和耐药乳腺癌细胞的协同作用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要第313期。
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