Experimental and Molecular Therapeutics最新文献

{"title":"Abstract 924: PROTECT, a novel antibody platform for integrating tumor-specific immune modulation and enhancing the therapeutic window of targeted multispecific biologics","authors":"S. Dixit, Florian Heinkel, Anna von Rossum, Harsh Pratap, Sifa Arrafi, Javairia Rahim, P. Bhojane, Liz Stangle, L. Stenberg, G. Volkers, Eric Escobar-Cabrera, T. Spreter","doi":"10.1158/1538-7445.AM2021-924","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-924","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91483256","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}

{"title":"Abstract 1014: Repurposing the anti-rheumatic gold compound auranofin for high-grade serous ovarian cancer therapy","authors":"Farah H. Abdalbari, A. Goyeneche, Elvis Martinez-Jaramillo, S. Sabri, C. Telleria","doi":"10.1158/1538-7445.AM2021-1014","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1014","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91488785","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}

{"title":"Abstract 1411: LAMC2 promotes progression and gemcitabine resistance through modulation of EMT and ATP-binding transporters in pancreatic ductal adenocarcinoma","authors":"Yasuyuki Okada, S. Nishiwada, N. Takahashi, T. Takayama, A. Goel","doi":"10.1158/1538-7445.AM2021-1411","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1411","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90047232","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}

{"title":"Abstract 1185: PRMT5 inhibition epigenetically regulates DNA damage response pathways in cancer cells and sensitizes to chemotherapy and PARP inhibition","authors":"Koichi Ito, Jack Carter, V. Thodima, Youyou Zhang, Monisha Sivakumar, Mu Xu, N. Bhagwat, J. Rager, Jacob Spruance, Lin Zhang, Bruce R Ruggeri, P. Scherle, K. Vaddi","doi":"10.1158/1538-7445.AM2021-1185","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1185","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91441466","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}

{"title":"Abstract 1021: Investigating the mechanism of PARP7 inhibition in type I interferon signaling by arrayed CRISPR screening","authors":"B. Gui, R. Abo, Patrick Flynn, A. Lu, Jan-Rung Mo, J. Gozgit, M. Vasbinder, Zacharenia A. Varsamis, Andrew G. Santospago, V. Richon, K. Kuntz, H. Keilhack, T. Mitchison, M. Niepel","doi":"10.1158/1538-7445.AM2021-1021","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1021","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80710139","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}

{"title":"Abstract 1213: PDE10A as a novel target to suppress Wnt/β-catenin signaling and other oncogenic pathways in ovarian cancer","authors":"Rebecca Barber, E. Gavin, A. Musiyenko, Wito Richter, Kevin J. Lee, A. Wilhite, J. Andrews, S. McClellan, I. Aragon, Antonio Ward, Xi Chen, A. Keeton, K. Berry, G. Piazza, J. Scalici, Luciana Madeira da Silva","doi":"10.1158/1538-7445.AM2021-1213","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1213","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83266560","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}

{"title":"Abstract 39: APOBEC3A drives acquired resistance to targeted therapies in non small cell lung cancer","authors":"H. Isozaki, Ammal Abbasi, Naveed Nikpour, Adam Langenbucher, Wenjia Su, Marcello Stanzione, L. Sequist, R. Buisson, M. Lawrence, A. Hata","doi":"10.1158/1538-7445.AM2021-39","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-39","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83540675","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}

{"title":"Abstract 1273: Discovery of a potent, selective, and orally bioavailable SOS1 inhibitor, RMC-023, anin vivotool compound that blocks RAS activation via disruption of the RAS-SOS1 interaction","authors":"A. Buckl, E. Quintana, Grace J. Lee, N. Shifrin, Mengqi Zhong, L. Garrenton, David C. Montgomery, Carlos Stahlhut, F. Zhao, D. Whalen, Severin Thompson, Arlyn Tambo-ong, Micah J. Gliedt, J. Knox, Cregg James Joseph, N. Aay, Jong Choi, Bao Nguyen, Atti Tripathi, Ruiping Zhao, Mae Saldajeno-Concar, Abby Marquez, Daphne Hsieh, Laura L. McDowell, E. Koltun, Alun Bermingham, D. Wildes, Mallika Singh, Zhengping Wang, R. Hansen, Jan Smith, A. Gill","doi":"10.1158/1538-7445.AM2021-1273","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1273","url":null,"abstract":"","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88636122","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}

{"title":"Abstract 966: Lenvatinib induces apoptosis and inhibits metastasis through downregulate Wnt/GSK3β/NF-κB in hepatocellular carcinoma","authors":"Tsu-Lan Chao, Zhao-Lin Tan, I-Tsang Chiang, Y. Chiang, Fei-Ting Hsu","doi":"10.1158/1538-7445.AM2021-966","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-966","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a prevalent cancer type and also the leading cause of cancer death among Taiwanese. The current treatments for liver cancer include eradication, chemical, targeted and radiotherapy… etc. Unfortunately, radiation therapy is quite harmful to patients and results in hepatic injury. Other treatment methods can only prolong patient9s life for few months, and has considerable side effects; therefore, it is extremely important to find other more effective drugs for HCC. HCC patients with higher expression level of ASPM (abnormal spindle-like microcephaly associated) have significantly lower survival rate than those of patients with lower expression level. ASPM is the co-activator of Wnt, which can activate the Wnt/β-catenin signaling pathway to increase the performance of GSK3β (Glycogen synthase kinase 3 beta) and regulate angiogenesis. In addition, studies have also found that GSK3β can also activate the transcription factor NF-κB, causing a large number of downstream proteins upregulation and thus triggered tumor growth and metastasis. Recent studies suggested that sorafenib has ability to inhibit the activation of transcription factor NF-κB and the expression of its downstream related proteins. Lenvatinib is also a multi-kinase inhibitor and had been approved by FDA for HCC treatment, which is more effective and with fewer skin side effects than sorafenib. However, whether the anti-tumor efficacy of lenvatinib in HCC was associated with the regulation of Wnt/GSK3β/NF-κB in HCC is remaining unclear. We aim to investigate whether the effect of lenvatinib in HCC, such as apoptosis induction and tumor metastasis inhibition, were associated with the inactivation of Wnt/GSK3B/NF-κB. Our studies demonstrated that lenvatinib can induce cytotoxicity of human HCC Hep3B and Huh7 cells. Lenvatinib may induce apoptosis effect via activated extrinsic- and intrinsic-apoptosis related molecules, including cleaved caspase-3, -8 and -9. Lenvatinib also significantly inhibited metastasis through the reduction of NF-κB-mediated metastasis associated proteins expression (MMP-2, MMP-9 and VEGF) and inhibition of invasion/migration ability in HCC cells. In addition, the inhibition of ASPM, Wnt and GSK3β were found after lenvatinib treatment in both in vitro and in vivo models. NF-κB activation was also effectively suppressed by lenvatinib in cells and animal model. Tumor growth inhibition was also found in lenvatinib treatment group. In conclusion, lenvatinib induces apoptosis and suppresses metastasis was associated with Wnt/GSK3β/NF-κB inactivation. Citation Format: Tsu-Lan Chao, Zhao-Lin Tan, I-Tsang Chiang, Yuan Chiang, Fei-Ting Hsu. Lenvatinib induces apoptosis and inhibits metastasis through downregulate Wnt/GSK3β/NF-κB in hepatocellular carcinoma [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):Abstrac","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89317672","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}

{"title":"Abstract 1307: Assessment of long IVT mRNA fragments with the Fragment Analyzer system","authors":"Kyle D. Luttgeharm, Solange Borg, C. Pocernich","doi":"10.1158/1538-7445.AM2021-1307","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1307","url":null,"abstract":"Quality control analysis of long in vitro transcribed (IVT) RNAs is challenging due to the lack of commercially available kits for sizing RNA over 6,000 nt, thus, to analyze long IVT RNAs, an extended separation method was developed for the Agilent 5200 Fragment Analyzer using a commercially available RNA ladder. IVT mRNA was produced using the RiboMAX Large Scale RNA Production System (Promega). RNA transcripts 9,000 and 10,000 nt in length were diluted in nuclease-free water and separated on the Agilent 5200 Fragment Analyzer system with the Agilent RNA kit (15 nt) (p/n DNF-471) with the following modifications. The Lonza RNA marker (Lonza) (long RNA Ladder) replaced the Agilent RNA Ladder and was diluted in nuclease-free water to 96 ng/μL. The long RNA Ladder was added to the Agilent RNA Diluent Marker (15 nt) (p/n DNF-369-0004) according to the RNA kit protocol. The standard separation method (8 kV for 45 minutes) for the RNA kit (15 nt) was manually altered to the extended RNA method (4 kV for 90 minutes) in the Agilent 5200 Fragment Analyzer software for fragments greater than 6,000 nt. The extended RNA method with the long RNA Ladder was employed for all subsequent runs. The long RNA Ladder separated with the extended method displayed enhanced resolution compared to separation with the standard method as seen by the increased spacing between the ladder peaks and the increased sharpness of the 9,000 nt peak. The extended RNA method reported a lower average sizing percent error (-0.7 %) over the entire concentration range of the kit compared to the standard RNA method (8.4 %) for the 9,000 nt sample. The 10,000 nt IVT mRNA average percent sizing error was similar between the two separation methods throughout the dilution series. Using the extended method, the 9,000 and 10,000 nt IVT mRNA samples were successfully analyzed with good sizing precision and accuracy, demonstrating that a commercially available RNA ladder can be used with the Fragment Analyzer system to provide accurate sizing of large IVT mRNA samples. The extended RNA method is recommended when extremely accurate sizing or high resolution is needed for determining the presence of degradation or sizing differences from incomplete transcription in IVT mRNA samples longer than 6,000 nt. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Kyle D. Luttgeharm, Solange Borg, Chava Pocernich. Assessment of long IVT mRNA fragments with the Fragment Analyzer system [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 1307.","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84781794","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}