bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 834: Formation of DNA double-strand breaks in colon tumors after targeted alpha therapy with 211At-mAb
Authors: Eriksson Sophie E. , Elgström Erika , Lindegren Sture , Bäck Tom 
Published: July 2017

Abstract
Introduction: Targeted alpha therapy has shown promising results in preclinical and clinical studies. Alpha particle irradiation gives a high fraction of DNA double-strand breaks (DSB), as shown in vitro, resulting in a high probability of cell death. We have previously examined the therapeutic effects of 211At on solid colon carcinoma tumors (diameter approximately 1 cm), with tolerable activities (5 MBq/animals) resulting in non-palpable tumors within one week p.i. The aim of the present study was to investigate the formation of DNA DSB during tumor regression after radioimmunotherapy with 211At-mAb in a syngeneic rat colon carcinoma model. Methods: 18 rats bearing solid colon tumors (1 cm in diameter) between peritoneum and the abdominal muscle were injected intravenously with 5 MBq/animal 211At-BR96. Tumors were excised and paraffin-embedded after 10 min, 2 h, 8 h, 18 h, 24 h, and 48 h p.i. (3 tumors per time point). 53BP1 was stained by immunohistochemistry and used as a marker for DNA DSB. Untreated tumors were used as controls (n=9). DNA DSB were counted in central and peripheral tumor areas selected at random. Results: A few DNA DSB were detected in untreated tumors. Already 10 min p.i., the number of DNA DSB had increased slightly in peripheral tumor tissue. The number peaked 8 h p.i., when the number of DNA DSB had increased 50 times in the tumor periphery and 24 times in the tumor center. The number of DNA DSB then declined, but the difference between center and periphery remained, as expected considering the intratumoral distribution of radioimmunoconjugate. This correlates with the 211At half-life of 7.2 h. Conclusion: DNA DSB are formed early after injection of 211At-mAb and follows the intratumoral distribution of mAbs.
Citation Format: Sophie E. Eriksson, Erika Elgström, Sture Lindegren, Tom Bäck. Formation of DNA double-strand breaks in colon tumors after targeted alpha therapy with 211At-mAb [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 834. doi:10.1158/1538-7445.AM2017-834
Abstract 837: PSMB8 as a candidate marker of responsiveness to preoperative radiotherapy in rectal cancer patients
Authors: Ha Yejin , Tak Ka hee , Kim Chan wook , Roh Seon Ae , Choi Eun Kyung , Cho Dong Hyung , Kim Jeong-Hwan , Kim Seon-Kyu , Kim Seon-Young , Kim Yong Sung , Kim Jin-Cheon 
Published: July 2017

Abstract
Prediction of individual responsiveness is urgently needed, specifically in locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT). The present study, RNA-Seq was used to compare the basal expression profile between responders and non-responders to preoperative CRT, in correlation with the tumor regression grade (TRG) among 22 LARC patients. Eight differentially expressed genes (B3GALT4, HSPA1B, KRBOX1, PPBP, PPP1R18, PSMB8, SLC39A7, and TAP2) associated with preoperative CRT responses were primarily identified among the 22 LARC patients by RNA-Seq (p&lt;0.0005 and &gt;16-fold difference). Among these genes, PSMB8 and SLC39A7 were upregulated in the responsive group in the other 40 LARC patients (p&lt;0.05). PSMB8 overexpression significantly reduced colony formation and increased apoptosis-inducing molecules like cleaved caspase-3 and cleaved PARP in irradiated CRC cells after 6 Gy irradiation. PSMB8 knockdown increased colony formation and decreased caspase-3 activation and cleaved PARP levels after irradiation. In mice treated with ionizing radiation, tumor growth suppression was significantly greater in HCT116/PSMB8-xenografts (81%) than in HCT116/vector-xenografts (53%) (p=0.001). However, SLC39A7 overexpression had no significant effect on irradiated CRC cells. These results suggest that PSMB8 appears to predict radiosensitivity in LARC patients with preoperative CRT, although further clinical validation is needed in a larger cohort.
Citation Format: Yejin Ha, Ka hee Tak, Chan wook Kim, Seon Ae Roh, Eun Kyung Choi, Dong Hyung Cho, Jeong-Hwan Kim, Seon-Kyu Kim, Seon-Young Kim, Yong Sung Kim, Jin-Cheon Kim. PSMB8 as a candidate marker of responsiveness to preoperative radiotherapy in rectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 837. doi:10.1158/1538-7445.AM2017-837
Abstract 838: Effect of tumor treating fields on cell proliferation and synergistic antitumor efficacy in combination with ionizing radiation
Authors: Kim Eun Ho , Jo Yunhui , Sung Jiwon , Song Hyo Sook , Yoon Myonggeun 
Published: July 2017

Abstract
Alternating electric fields at an intermediate frequency (100~300 kHz), called tumor treating fields (TTFs), are reported to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the presence of an antimitotic effect of TTFs has been widely reported, the efficacy of TTFs is still controversial issue among medical experts. To resolve this controversial issue, the comparison study between the effects of TTFs and the effect of other conventional cancer treatment techniques need to be carried out. In this study, experimental evidence of the synergistic antimitotic effect of TTFs in combination with ionizing radiation (IR) is reported. For these experiments, aggressive brain cancer cells, glioblastoma multiforme (GBM) cells (U373 and U87), were treated either with TTFs alone, with IR alone or with TTFs followed by ionizing radiation (IR). The percentages of cell apoptosis, DNA damage, and mitotic abnormalities were increased by the application of TTFs alone and its quantity was markedly increased when TTFs were combined with IR. Our results also suggested that radiotherapy together with TTFs may be clinically beneficial since the combination treatment seemed to synergistically suppress both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.
Citation Format: Eun Ho Kim, Yunhui Jo, Jiwon Sung, Hyo Sook Song, Myonggeun Yoon. Effect of tumor treating fields on cell proliferation and synergistic antitumor efficacy in combination with ionizing radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 838. doi:10.1158/1538-7445.AM2017-838
Abstract 84: CCN1/Cyr61 regulation of gemcitabine-resistant phenotype in pancreatic cancer: involvement of CTGF and dCK
Authors: Gupta Vijayalaxmi G. , Maity Gargi , Haque Inamul , Banerjee Sushanta K. , Banerjee Snigdha 
Published: July 2017

Abstract
With an estimated half a million new cases and similar mortality rates for 2016, pancreatic ductal adenocarcinoma (PDAC) remains a life-threatening and challenging disease to diagnose and treat. As per American Cancer Society (ACS), varying efficacy in different patients has led to an increase in the mortality rate of PDAC. Gemcitabine (GEM) remains the drug of choice either alone or in combination, but is unsuccessful in reducing or curing PDAC in most patients. The limited efficacies of these drugs are due to the acquisition of chemo-resistant characteristics of PDAC. Although several molecular and physiological factors have been shown to correlate with the GEM-resistance, defined molecular mechanism(s) of GEM-resistance remains a mystery. Previous studies have shown that CCN1, which is overexpressed in PDAC and known to associate with PDAC progression, is critical for drug resistance. Here, we found that while the pancreatic cancer cell lines (i.e., Panc-1 and AsPC-1) in which CCN1 is overexpressed are typically GEM-resistant, the knocking down of CCN1 makes them sensitive to GEM. Mechanistic studies revealed that CCN1 regulates two important genes that are directly involved in regulation GEM-sensitivity in PDAC. These include cancer cell-secreted connective tissue growth factor (CTGF), a regulator of desmoplasia, and Deoxycytidine kinase (dCK), an enzyme that enhances gemcitabine sensitivity and efficacy in cancer cells. The deletion of CCN1 in PDAC cells blocks CTGF expression and under co-cultured conditions prevent the growth of alpha-smooth muscle actin (α-SMA)-positive stellate cells, which are required for desmoplastic growth in pancreatic cancers. CCN1 ablation upregulates dCK expression in PDAC cell lines as compared to CCN1 expressed PDAC cells. These two events enhance the anti-proliferative effect of GEM and can be rescued by CTGF-treatment or blocking dCK. In conclusion, CCN1 promotes GEM-resistance in PDAC cell through the regulation of CTGF and dCK and the mechanistic insights provided by these studies may help in designing future therapeutic strategies to combat PDAC.
Citation Format: Vijayalaxmi G. Gupta, Gargi Maity, Inamul Haque, Sushanta K. Banerjee, Snigdha Banerjee. CCN1/Cyr61 regulation of gemcitabine-resistant phenotype in pancreatic cancer: involvement of CTGF and dCK [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 84. doi:10.1158/1538-7445.AM2017-84
Abstract 841: UTR analysis identifies Musashi1 as a translational regulator of radiation-induced Golgi-related gene expression
Authors: Lehman Stacey L. , O'Neill John W. , Camphausen Kevin , Tofilon Philip J. 
Published: July 2017

Abstract
The cellular radioresponse is regulated by post-translational modification of constitutively expressed proteins and by changes in gene expression. Although the role of constitutively expressed proteins, such as those involved in the DNA damage response and cell cycle checkpoints, is well-understood in the context of the radioresponse, radiation-induced changes in gene expression are not as clearly defined. We have previously demonstrated that glioblastoma stem-like cells (GSCs) alter their gene expression at the translational level in response to ionizing radiation (IR). In particular, the NSC11 GSC line demonstrated thousands of genes differentially translated at one hour after a dose of 2 Gy, while considerably fewer were modified at the transcriptome level. Furthermore, there was little overlap between the transcriptome and the translatome. Genes undergoing translational regulation in response to IR fell into distinct functional categories, including mitochondrial structure and function, Golgi function, and translational regulation. Here, we aimed to elucidate the mechanism by which IR induces translational changes in the NSC11 GSC line. NSC11 cells were either exposed to 2 Gy or mock irradiated, and polysomes were isolated by sucrose gradient fractionation one hour later. Polysome-bound mRNA was purified and analyzed by microarray. The 5’ and 3’ untranslated regions (UTRs) of the top 75 up- and down-regulated genes were analyzed for the presence of regulatory elements. The most frequently occurring element in the UTRs of both the top up- and down-regulated genes was the Musashi1 binding site. Musashi1 is an RNA binding protein that typically binds to 3’ UTRs to regulate mRNA translation. It is a neural stem cell marker, and its expression is correlated with the grade of malignancy in glioma. GO term analysis of known Musashi1 target genes that were translationally regulated in response to IR revealed an enrichment of genes involved in Golgi function and vesicular trafficking. Knockdown of Musashi1 prevented IR-induced Golgi dispersal in NSC11 cells. Musashi1 knockdown also radiosensitized NSC11 cells, indicating a role for the protein in the cellular radioresponse. Together, these data demonstrate that in the NSC11 GSC line, Musashi1 contributes to radiation-induced translational regulation, specifically in the context of Golgi-related genes, and suggests that Musashi1 is a novel target for radiosensitization.
Citation Format: Stacey L. Lehman, John W. O'Neill, Kevin Camphausen, Philip J. Tofilon. UTR analysis identifies Musashi1 as a translational regulator of radiation-induced Golgi-related gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 841. doi:10.1158/1538-7445.AM2017-841
Abstract 843: CLDN1 mediates tumor invasion in HNSCC by regulation of EMT through AMPK-TGF-β signalling
Authors: Chang Jae Won , Jung Seung-Nam , Liua Lihua , Kim Jin Man , Ban Myung Jin , Kim Yeon Soo , Lee Bok-Soon , Kim Yang Eun , Won Ho Ryun , Kim Chul-Ho , Koo Bon Seok 
Published: July 2017

Abstract
Background: Claudin-1 (CLDN1), a major component of tight junction complexes in epithelium, maintains cellular polarity and plays critical roles in cell-to-cell communication and epithelial cell homeostasis. Although, the role of CLDN1 in cancer has been generally studied in cancers, the exact regulatory mechanisms and downstream pathways in cancer have been controversial and are not completely understood.
Materials and Methods: After, analysed mutational profiling of tumor/non-tumor paired tissue in the patients with head and neck squamous cell carcinoma (HNSCC) by next-generation sequencing (NGS), CLDN1 expression levels were measured in human HNSCC cell lines and tissues from HNSCC patients using next-generation sequencing. For functional in vitro analysis, cell proliferation testing using a WST-1 assay, an invasion assay, and Western blotting was performed after CLDN1 expression regulation. In vivo validations were performed using nude mouse and patient-derived tumor xenograft (PDTX) model.
Results: Mutational profiling of tumor/non-tumor paired HNSCC tissue by NGS revealed that HNSCC tumor tissues and cell lines had relatively high levels of CLDN1 expression. Although, CLDN1 regulation did not affect proliferation of HNSCC cell lines, knock down of CLDN1 inhibited invasive characteristics (migration/invasion) with down-regulation of EMT associated proteins (vimentin and slug). We also found that CLDN1 negatively correlated with AMPK phosphorylation and AMPK activator (AICAR) showed the same effect with CLDN1 suppression on HNSCC cells without change in CLDN1 expression which lead to inhibition of TGF-β-induced Smad phosphorylation and their transcriptional activity, suggesting that CLDN1/AMPK/TGF-β cascade. Then, we confirmed antitumorigenic effects of suppression of CLDN1 in HNSCC in a nude mouse and PDTX model.
Conclusions: Our findings suggest that CLDN1 acts as oncogenic driver in HNSCC via regulating EMT through AMPK/TGF-β signalling and if validated in further studies, a CLDN1-targeting agent partnered with an existing anti-TGF-β modality could be a novel tactic to overcome HNSCC.
Citation Format: Jae Won Chang, Seung-Nam Jung, Lihua Liua, Jin Man Kim, Myung Jin Ban, Yeon Soo Kim, Bok-Soon Lee, Yang Eun Kim, Ho Ryun Won, Chul-Ho Kim, Bon Seok Koo. CLDN1 mediates tumor invasion in HNSCC by regulation of EMT through AMPK-TGF-β signalling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 843. doi:10.1158/1538-7445.AM2017-843
Abstract 85: Establishment of cabazitaxel-resistant prostate cancer cell lines
Authors: Mizokami Atsushi , Machioka Kazuaki , Izumi Kouji , Aerken Maolake , Natsagdorji Ariunbold , Kadono Yoshifumi , Takezawa Yuta , Iwamoto Hiroaki , Keller Evan T. 
Published: July 2017

Abstract
Background: The final treatment for castration-resistant prostate cancer (CRPC) is generally cabazitaxel treatment. However, once CRPC becomes resistant to cabazitaxel, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. We already established paclitaxel/docetaxel-resistant prostate cancer, PC-3-TxR and DU145-TxR cells, and characterized those cell lines previously. Then we further tried to establish cabazitaxel-resistant prostate cancer cell lines, and characterized those cell lines.
Materials and Methods: We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR by increasing concentration of cabazitaxel from 1 nM to 30 nM gradually when PC-3-TxR and DU145-TxR cells were passaged. We confirmed the IC50 of docetaxel and cabazitaxel of these cells. Next we purified total RNA and performed cDNA microarray (Agilent and compared gene expression profiles among these cells.
Results and Conclusion: IC50 of PC-3-TxR and PC-3-TxR/CxR for cabazitaxel was 1.3 nM and 15.4 nM, respectively. IC50 of DU145-TxR and DU145-TxR/CxR was 7.0 nM and 30. 8 nM, respectively. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that 4,470 genes in PC-3-TxR/CxR, and 1,345 genes in DU145-TxR/CxR cells were upregulated more than 3-fold and 4,683 genes PC-3-TxR/CxR and 1,537 genes were downregulated less than 0.3-fold, respectively. Especially, although expression of ABCB1 (MDR) gene was upregulated in DU145-TxR by 500-fold compared with DU145 cells, it was not upregulated in not upregulated in DU145-TxR/CxR cells any more. In contrast, expression of ABCB1 gene was upregulated in PC-3-TxR by 20-fold compared with PC-3 cells and it was further upregulated in PC-3-TxR/CxR by 40-fold compared with PC-3-TxR. In conclusion, various genes were regulated in cabazitaxel-resistant PCa cells and different mechanisms might be involved in this resistance in different cell lines.
Citation Format: Atsushi Mizokami, Kazuaki Machioka, Kouji Izumi, Maolake Aerken, Ariunbold Natsagdorji, Yoshifumi Kadono, Yuta Takezawa, Hiroaki Iwamoto, Evan T. Keller. Establishment of cabazitaxel-resistant prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 85. doi:10.1158/1538-7445.AM2017-85
Abstract 855: Ube2v1 promotes epithelial mesenchymal transition and metastasis in colorectal cancer by epigenetically transcriptional suppression of autophagy
Authors: Shen Tong , Cai Dong Ling , Liu Hong Yu , Gan Juan Wen , Li Ming , Wang Ru Jing , Guo Da Peng , Zhou Qun , Lu Xing Xing , Li Shi , Sun Na Li , Li Ming Jian 
Published: July 2017

Abstract
Ubiquitination is one of the basic post-translational modifications for cellular homeostasis. The conjugating enzyme (E2) family plays as a bridge linking the first step mediated by E1 with the final step mediated by E3 in the ubiquitin-proteasomesystem. However, the role of Ube2v1, one of Ubiquitin-conjugating E2 enzyme variant proteins (Ube2v), in colorectal cancer (CRC) and autophagy is unclear. Here, we found that Ube2v1 is elevated in tumor samples of CRC patients and correlated with poorer survival of CRC patients. Furthermore, Ube2v1 promotes migration and invasion of CRC cells in vitro and boosts tumor growth and metastasis of CRC cells in vivo. Interestingly, Ube2v1 suppresses autophagy program and promotes EMT and metastasis of CRC cells in an autophagy dependent pattern in vitro and in vivo. Moreover, Rapamycin attenuates the enhanced in vitro migration and invasion and in vivo lung metastasis of Ube2v1 overexpression by inducing the autophagy pathway. Mechanistically, Ube2v1 increases histone H4 lysine 16 acetylation by down-regulating expression of Sirt1 and epigenetically suppresses gene expression of autophagy genes in colorectal cancer. In conclusion, Ube2v1 functions as a globalregulator for autophagy by epigenetically transcriptional suppression of autophagy, and consequently promotes EMT and metastasis of CRC. Our study functionally links Ube2v1, one member of E2 family in the ubiquitin-proteasome system toautophagy program in CRC progression and metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Tong Shen, Dong Ling Cai, Hong Yu Liu, Juan Wen Gan, Ming Li, Ru Jing Wang, Da Peng Guo, Qun Zhou, Xing Xing Lu, Shi Li, Na Li Sun, Ming Jian Li. Ube2v1 promotes epithelial mesenchymal transition and metastasis in colorectal cancer by epigenetically transcriptional suppression of autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 855. doi:10.1158/1538-7445.AM2017-855
Abstract 869: Mesenchymal identity of breast cancer promotes brain metastases and therapeutic resistance through MLK4/NFkB signaling Pathway
Authors: Alsheikh Heba Allah M. , Minata Mutsuko , Yamaguchi Shinobu , Nakano Ichiro 
Published: July 2017

Abstract
Patients with breast cancer brain metastases (BCBM) suffer from a devastating outcome despite recent progress in a variety of therapeutic modality. Among the four major molecular subtypes, breast cancers that are either human epidermal growth factor receptor (HER) 2- positive or triple-negative breast cancer (TNBC) patients have a higher risk of BCBM compared with the luminal cancer patients. The mechanisms by which the disseminated cancer cells overcome the multistep defense mechanism in the brain, adapt the microenvironment, and subsequently initiate metastasis remain elusive. Recently, we identified a set of genes that contribute to initiate Glioblastoma (GBM) and at least some of them are functionally essential for GBM establishment and the therapy resistance. Mixed lineage kinase 4 (MLK4) is a relatively poorly characterized serine/threonine kinase, which is largely expressed in various cancers including GBM. We recently found a critical role of MLK4 in controlling the mesenchymal identity in GBM stem cells and plays a role in GBM initiation through direct activation of NF-kB signaling. Our preliminary data indicates MLK4 is also highly expressed in patient-derived hormone receptor (HR)-negative breast cancer cells in comparison with the other HR-positive counterparts. For therapeutic development purpose, we performed the structure-based drug design, which has led to identify two small molecule MLK4 inhibitor candidates to test efficacy on a set of patient-derived breast cancer cells in vitro and their xenografted tumors in vivo. Results will be presented in the conference.
Citation Format: Heba Allah M. Alsheikh, Mutsuko Minata, Shinobu Yamaguchi, Ichiro Nakano. Mesenchymal identity of breast cancer promotes brain metastases and therapeutic resistance through MLK4/NFkB signaling Pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 869. doi:10.1158/1538-7445.AM2017-869