bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2881: Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment
Authors: Li Jingjing , Zhang Jinming , Leung George Pak-Heng 
Published: September 2020

Abstract
To avoid the narrow therapeutic window and take advantage of the anticancer efficacy of triptolide (TP), a major active component of Tripterygium wilfordii Hook.F., a novel thermo-responsive nano-micelle hydrogel was fabricated in present study for the sustained release of TP in breast tumor tissue. Briefly, the amphiphilic poloxamer 188-g-poly (N-isopropylacrylamide-co-acrylic acid) copolymer was synthesized by atomic transfer radical polymerization reaction and self-assembled into micelles in aqueous solution with CMC value of 2.6×10-3 mg/mL. TP encapsulated nanogel (TP/F68-g-(PNIPAAm-co-AAC)) exhibited the sol-gel phase transition at 32°C with a narrow size distribution (about 50.16 nm) and sustained drug release in vitro. And then, the TP-loaded nanogel significantly inhibited the cell proliferation against human breast cancer MDA-MB-231 and MCF-7 cells, as well as the induction of cell apoptosis and cell cycle arrest activity. Moreover, we also found the superior anti-angiogenic activities of TP nanogel in both HUVEC and rat aortic ring model when compared to free TP. As expected, mediated by the 4T1 mouse breast cancer model, we demonstrated that a single injection of the TP-loaded nanogel system resulted in the long detention time in tumor tissue due to its thermo-responsive capacity. Moreover, the novel nanogel remarkably enhanced anticancer efficacy and reduced the side effects, when compared with the multiple injections of free TP. Therefore, the injectable thermo-responsive nanogel provided a potential strategy for the efficient delivery of TP with a sustained release manner in breast cancer treatment.
Citation Format: Jingjing Li, Jinming Zhang, George Pak-Heng Leung. Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2881.
Abstract 2883: A transformable delivery system for the effective treatment of pediatric central nervous system tumors
Authors: Lin Tzu-yin 
Published: September 2020

Abstract
Malignancies of the central nervous system (CNS) are the most common type of solid tumor affecting children and a leading cause of cancer-related death in children. With the deterioration of brain tumors, blood-brain barrier (BBB)/blood-brain tumor barrier (BBTB) with poor permeability, and relatively weak enhanced permeability and retention effect become major obstacles in delivering therapeutics to brain tumors. Vincristine (VCR) is a mainstay of treatment of a variety of cancers including brain tumors due to its well-defined mechanism of action and demonstrated anticancer activity. However, the clinical application of VCR in brain tumors was limited by its neurotoxicity and inability to penetrate BBB/BBTB resulting in unsatisfactory anti-cancer efficacy. In this project, we developed a transformable nanoparticle, named Ninja-nanoparticle, which is capable overcoming several important barriers for drug delivery to CNS tumors resulting in better efficacy and toxicity profile. Ninja-NP was stable during circulation due to crosslinking and could transpass BBB/BBTB through glucose receptor-mediated transcytosis. Ninja-NP could further transform into smaller nanoparticle upon encountering acidic microenvironment and revealed hidden moiety to target tumor surface overexpressed sialic acid. Ninja-NP employed a unique strategy which could sequentially target BBB/BBTB and brain tumor cells. Our study confirmed that VCR loaded Ninja-NP significantly accumulated at the orthotopic brain tumor sites, and exhibited superior anti-cancer efficacy in orthotopic diffuse intrinsic pontine glioma (DIPG), the most deadly pediatric CNS tumor, then free VCR or Liposomal VCR with limited systemic toxicity. Ninja-NP addresses multiple challenges for CNS tumor treatment and exhibits great potential to be translated into an effective theranostic nano-platform which could be seamlessly integrated into standard human brain tumor management (imaging-guided drug delivery) with reduced long term toxicity.
Citation Format: Tzu-yin Lin. A transformable delivery system for the effective treatment of pediatric central nervous system tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2883.
Abstract 2902: Antibody-drug conjugate targeting c-kit/CD117 suppresses imatinib resistant cancer cells
Authors: Kim Jin-Ock , Kim Kwang-Hyeok , Park Sang Gyu 
Published: September 2020

Abstract
c-Kit(CD117) is a type III receptor tyrosine kinase that mediates cell proliferation, survival, and differentiation. Gene amplification of c-kit is found in various cancers, including, glioblastoma (GBM) low grade glioma(LGG), gastrointestinal stromal tumor (GIST), sarcoma, melanoma, and small cell lung carcinoma (SCLC), leading to poor prognosis. In addition, the activation of c-kit as a cancer stem cell marker induces resistance of anti-cancer drug by increasing the expression of ABCG2. Imatinib is a first generation RTK inhibitor targeting BCR-ABL, c-kit, and PDGFR and currently using for the treatment of various cancers. Of note, the activating mutation of c-kit is found in various cancers, leading to resistance of imatinib. In this study, we have generated a human antibody targeting c-kit and developed antibody-drug conjugate using SMCC-DM1 to assess the therapeutic efficacy in vitro and in vivo.
Citation Format: Jin-Ock Kim, Kwang-Hyeok Kim, Sang Gyu Park. Antibody-drug conjugate targeting c-kit/CD117 suppresses imatinib resistant cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2902.
Abstract 2927: Targeted combination treatment for B-cell acute lymphoblastic leukemia
Authors: Kane Shriya , Ding Yali , Gowda Chandrika , Payne Jonathon Lee , Iyer Soumya , Dhanyamraju Pavan K. , Song Chunhua , Desai Dhimant , Sharma Arati , Payne Kimberly J. , Dovat Sinisa 
Published: September 2020

Abstract
The CCND3 gene encodes Cyclin D3–a protein that is essential for G1/S cell cycle progression and proliferation of malignant cells. Targeting Cyclin D3 is used to treat B-cell acute lymphoblastic leukemia (B-ALL); however, the mechanisms that regulate expression of the CCND3 gene in B-ALL are largely unknown. Here, we present evidence that oncogenic Casein Kinase II (CK2) regulates expression of CCND3 and G1/S cell cycle progression via direct phosphorylation of Ikaros, a transcription regulator and tumor suppressor protein. Global genome-wide DNA-binding analysis using ChIP-seq, show that Ikaros binds the promoter of CCND3 in primary human B-ALL. The role of Ikaros in regulating CCND3 expression in B-ALL was tested using gain-of-function and loss-of-function experiments. Ikaros knock-down with shRNA results in increased transcription of CCND3 in B-ALL. Overexpression of Ikaros in human B-ALL was associated with reduced expression of CCND3. Since Ikaros activity in leukemia is regulated by pro-oncogenic Casein Kinase II (CK2), we tested whether CK2 regulates expression of CCND3 in B-ALL. Increased expression of CK2 in B-ALL results in increased expression of the CCND3 gene. This was associated with a loss of Ikaros binding to the promoter of the CCND3 gene. Inhibition of CK2 with shRNA, and/or a specific CK2 inhibitor, CX-4945, resulted in increased Ikaros binding to the CCND3 promoter and reduced expression of Cyclin D3 in B-ALL. Treatment with CX-4945 showed strong therapeutic activity in preclinical models of B-ALL. A combination treatment with CX-4945 and dexamethasone that targets G1/S cell cycle progression shows a strong synergistic effect on B-ALL cells. In conclusion, presented data show that CK2 and Ikaros regulate G1/S cell cycle progression via transcriptional regulation of the CCND3 gene in B-ALL and that CK2 inhibition represses CCND3 expression by enhancing Ikaros tumor suppressor function. Results demonstrate the synergistic efficacy of a combination treatment with CK2 inhibitor and dexamethasone and provide a rationale for the use of this combination treatment as a novel therapeutic approach for B-cell acute lymphoblastic leukemia.
Citation Format: Shriya Kane, Yali Ding, Chandrika Gowda, Jonathon Lee Payne, Soumya Iyer, Pavan K. Dhanyamraju, Chunhua Song, Dhimant Desai, Arati Sharma, Kimberly J. Payne, Sinisa Dovat. Targeted combination treatment for B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2927.
Abstract 294: Altered ARID1A expression in colorectal cancer
Authors: Erfani Mehran , Vahid Seyed , Mokhtari Maral , Zamani Mozhdeh , Tahmasebi Kamran , Alizadeh Mahvash , Taghavi Alireza , Carethers John , Koi Minoru , Brim Hassan , Mokarram Pooneh , Ashktorab Hassan 
Published: September 2020

Abstract
Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined.
Aim: To investigate the role ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC.
Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. And used MSP to evaluate methylation of ARID1A. We used (IHC) to ARID1A protein expression, and, evaluate both MSI and EMAST status in 18 paired CRC and adjacent normal tissues. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters.
Results: Among the 18 CRC tumors studied, 7 (38.8 %) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) of cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines.
Conclusion: ARID1A expression is downregulated in CRC tissues correlate with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contribute to CRC tumorigenesis. There was no significant association between the ARID1A loss of expression and clinicopathological characteristics. ARID1A might be a useful biomarker for colorectal cancer. Future in- vivo analysis is warranted to further established this role.
Citation Format: Mehran Erfani, Seyed Vahid, Maral Mokhtari, Mozhdeh Zamani, Kamran Tahmasebi, Mahvash Alizadeh, Alireza Taghavi, John Carethers, Minoru Koi, Hassan Brim, Pooneh Mokarram, Hassan Ashktorab. Altered ARID1A expression in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 294.
Abstract 2948: Anti-tumor effect of C. orbiculata is modulated by alternative splicing
Authors: Makhafola Tshepiso , Bates David , Dlamini Zodwa 
Published: September 2020

Abstract
Recent research has revealed that alternative splice products can be linked to various genetic diseases and also play a role in carcinogenesis. It therefore appears that targeting splicing in cancer could offer novel effective cancer treatments. The aim of this study was to investigate the effects of a South African medicinal plant C. orbiculata on alternatively spliced genes in cancer cells. The effects of the crude extract on cell proliferation of colon (HCT116), esophageal (OE33 and KYSE70) and cervical (CASKI and C33A) cancer cell lines were evaluated using WST-1 assay. We also investigated the effects of this plant on splicing of hnRNPA2B1 and BCLx using RT-PCR and apoptosis induction via caspase-3-cleavage. Our data revealed that the crude C. orbiculata dose dependently decreased viability and also modulated splicing of hnRNPA2B1 and BCLx resulting in a decrease in hnRNPB1 splice variant and an increase in BCLxs splice variant in all 5 cancer cell lines. Additionally, the extract resulted in an increase in caspase-3-cleavage, an indication of apoptosis induction. We used siRNA knockdown of hnRNPB1 in HCT116 specifically to assess its functional role in cell proliferation and apoptosis. These cells had decreased viability and increased caspase-3-cleavage. We therefore concluded that in part, modulating hnRNPA2B1 splicing could be responsible for regulating the balance between pro/anti-apoptotic splice variants e.g. BCLxl/s resulting in apoptosis induction in colon cancer cells treated with C. orbiculata.
Citation Format: Tshepiso Makhafola, David Bates, Zodwa Dlamini. Anti-tumor effect of C. orbiculata is modulated by alternative splicing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2948.
Abstract 2960: Anti-cancer activity of NCTD: promotion of pro-apoptosis and anti-invasion in human oral cancer cells
Authors: Ahn Chi-Hyun , Hong Kyoung-Ok , Shin Ji-Ae , Hong Seong Doo , Cho Sung-Dae 
Published: September 2020

Abstract
Norcantharidin (NCTD), a demethylated analog of cantharidin isolated from blister beetles, has been used as a promising anticancer agent; however, the anti-tumor potentials of NCTD against human oral cancer has not been fully understood. Here, this study was aimed to investigate the pro-apoptotic and anti-invasive effect and its molecular targets of NCTD in human oral cancer cell lines. Trypan blue exclusion assay, live/dead assay, western blotting, 4-6-Diamidino-2-Phenylindole staining, flow cytometric analysis, Terminal Deoxynucleotidyl Transferase dUTP Nick end Labeling (TUNEL) assay, immunohistochemistry and tumor xenograft mice models were performed to investigate the pro-apoptotic effect of NCTD. Clonogenic, wound healing, invasion, zymography, western blotting and immunocytochemistry assays were performed to investigate the anti-invasive effect of NCTD. NCTD significantly inhibited cell growth and increased the number of dead cells in oral cancer cell lines. It induced the following apoptotic phenomena: (1) the cleavages of poly (ADP-ribose) polymerase and casepase-3; (2) increase in apoptotic morphological changes (nuclear condensation and fragmentation); (3) increase in annexin V-positive cells or sub-G1 population of cells. NCTD significantly activated the p38 mitogen-activated protein kinase (MAPK) pathway. A p38 MAPK inhibitor (SB203580) partially attenuated NCTD-induced apoptosis in oral cancer cell lines. NCTD strongly suppressed tumor growth in the tumor xenograft bearing HSC-3 cells, and the number of TUNEL-positive cells increased in NCTD-treated tumor tissues. Also, NCTD markedly suppressed the colony formation, migration, and invasion of YD-15 cells as well as the activities of MMP-2 and MMP-9. It disrupted F-actin reorganization through suppressing the FAK/Paxillin axis. Moreover, NCTD exhibited a powerful anti-invasive effect compared with that of PF-562271. Collectively, these results suggest that NCTD has a potential pro-apoptotic and anti-invasive activity against oral cancer cell lines. Therefore, these results suggest that NCTD could be a potential anticancer drug candidate for the treatment of human oral cancer. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning [2017R1D1A1B03029317, 2018R1D1A1B07043080, and 2019R1A2C1085896].
Citation Format: Chi-Hyun Ahn, Kyoung-Ok Hong, Ji-Ae Shin, Seong Doo Hong, Sung-Dae Cho. Anti-cancer activity of NCTD: promotion of pro-apoptosis and anti-invasion in human oral cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2960.
Abstract 2961: Olaparib mediated DNA damage response and its resistant mechanism in cervical cancer cells
Authors: Tse Ka Yu , Liu Stephanie Si , Lee Horace Hok Yeung , Ip Philip Pun Ching , Chan Kin Tak 
Published: September 2020

Abstract
Cervical cancer is still the most common gynecologic cancer in developing countries. Olaparib is a poly-(ADR-ribose)-polymerase 1 (PARP1) inhibitor targeting at DNA strand break repair. However its efficacy in cervical cancer is unclear. This study aimed to evaluate the therapeutic potential of olaparib in cervical cancer. Olaparib remarkably reduced the PARylation activity and arrested cervical cancer cells at G2/M phase, and was associated with reduced level of a mitosis marker, phosphor-histone H3 as indicated by propidium iodide DNA staining and immunofluorescence. Cytotoxicity of olaparib against cervical cancer cells was determined by XTT assay with IC50 ranged from 35.49µM in C4I to 87.17µM in SiHa. The difference in olaparib sensitivity between C4I and SiHa was consistently demonstrated in annexin V based apoptotic assay, where a higher level of apoptotic response was found in C4I (21.12%) compared to SiHa (6.37%). Immunofluorescent staining and western blot for gH2AX clearly showed DNA double-strand break accumulation in both cell lines upon PARP1 blockade. Lower expression level of RAD51, a homologous recombination (HR) repair factor, was also observed in C4I, when compared to SiHa. Besides, gH2AX/RAD51 foci co-immunofluorescent line scan image analysis showed that there was reduced level of DNA damage recognition by RAD51 (26.80%), compared to SiHa (65.31%). These findings suggested that there was a reduced HR activity in C4I and might explain the higher sensitivity to olaparib compared to SiHa. We also demonstrated the therapeutic potential of olaparib in cervical cancer, and the rationale of using RAD51 as a predictive biomarker for olaparib sensitivity.
Citation Format: Ka Yu Tse, Stephanie Si Liu, Horace Hok Yeung Lee, Philip Pun Ching Ip, Kin Tak Chan. Olaparib mediated DNA damage response and its resistant mechanism in cervical cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2961.
Abstract 2968: BPM31510, a Coenzyme Q10 (CoQ10) containing lipid nanodispersion, enhances radiation effects to prolong survival in a rodent glioblastoma model
Authors: Sun Jiaxin , Merchant Milton , Diers Anne R. , Kazerounian Shiva , Gesta Stephane , Narain Niven R. , Sarangarajan Rangaprasad , Nagpal Seema , Recht Lawrence 
Published: September 2020

Abstract
BPM31510 is a Coenzyme Q10 (CoQ10)-containing lipid nanodispersion in clinical development for the treatment of glioblastoma. Prior results demonstrate that high doses of CoQ10 delivered via BPM31510 differentially increases oxidative stress in glioblastoma relative to non-tumor cells in vitro and extends long-term survival (LTS) in an in vivo glioblastoma model. Since a primary consequences of tumor irradiation is induction of oxidative stress, we hypothesized that BPM31510 treatment would result in an enhanced radiation response and influence survival outcomes.1 x 106 luciferase labeled C6 cells were implanted into the right striatum of Sprague Dawley rats. 4 days post-implantation, rats were randomized into one of four groups: (i) Saline injection ip bid; (ii) BPM31510 50 mg/kg ip bid to continue up to 35 days; (iii) 12 Gy radiotherapy (RT) to be administered on Day 8 post-implant with saline injection; and (iv) BPM31510 + RT. Tumor-bearing rats were monitored until death or Day 50. Log rank survival analysis indicated a marked enhancement of median survival with the addition of BPM31510 to RT. While neither RT nor BPM31510 enhanced median survival relative to saline, the combination was markedly more effective (median survival of 17, 19, 24 and &gt;50 days for saline, BPM31510, RT and combination, respectively, p &lt; 0.001). This was also reflected in increase in frequency of LTS, which was over 70% (11 of 14 rats) in the combination group (p &lt; 0.01 compared to control). BPM31510 significantly enhanced the therapeutic efficacy of radiation in this model of glioblastoma. Effects on median survival and an enhancement of LTS with combination treatment were observed. While the mechanistic underpinnings are under investigation, the low toxicity profile of BPM31510 and its potential protective effects on normal cells may offer a unique strategy with which to enhance radiation.
Citation Format: Jiaxin Sun, Milton Merchant, Anne R. Diers, Shiva Kazerounian, Stephane Gesta, Niven R. Narain, Rangaprasad Sarangarajan, Seema Nagpal, Lawrence Recht. BPM31510, a Coenzyme Q10 (CoQ10) containing lipid nanodispersion, enhances radiation effects to prolong survival in a rodent glioblastoma model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2968.