bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2931: The compounding effects of coenzyme q10 and radiation treatment on glial fibrillary acidic protein network of glioma in vitro
Authors: Liao Chong-Chun , Jhunjhunwala Megha , Chung Li-Han , Chen Chi-Shuo 
Published: August 2019

Abstract
Introduction: Astrocytoma is an aggressive primary malignant brain tumor in adults. Radiation therapy is an effective medical treatment, but one of its undesired side-effects is the induced genomic instability of surrounding astrocytes, which can lead abnormal distribution of GFAP and associates with severe brain injury (BI).
Purpose: In order to cope with this serious difficulty, various antioxidants have been applied with radiation therapy. Among antioxidants, Coenzyme Q10 (Q10) is one of the few candidates without double-edged sword effect. However, the understand about Q10 therapeutic effect on radiological protection is limited. In this study, we aimed to investigate the potential therapeutic effects of Q10 on brain tumor radiation treatment.
Materials and Methods: Astrocyte and glioma cell lines were cultivated with Q10 (10μM~ 50 μM) and exposed to 10 Gy single dose from Cobalt-60 (60Co). After the radiation exposure, cell viability was analyzed using MTT assay, GFAP responses was examined by immunofluorescence staining and qPCR, and other cell phenotype indexes, such as the morphology, migration, and invasion in vitro, were observed by microscopy.
Results: Our results indicated that Q10 treatment was capable of maintaining GFAP network of astrocyte after radiation exposure. Besides, Q10 synergistically eliminated glioma proliferation after radiation treatment. By extending horizontally along the base of GFAP remodeling, we further investigated the ability of 3D tumor invasion in co-culture model which simulated the microenvironment composed of reactive astrocyte and glioma in clinical research. Results indicated that radiation therapy with Q10 can further suppress the invasive ability in vitro.
Conclusions: In sum, our results demonstrated the potential radiological protection of Q10 on astrocyte and amplified the therapeutic effectiveness for brain tumor therapy.
Citation Format: Chong-Chun Liao, Megha Jhunjhunwala, Li-Han Chung, Chi-Shuo Chen. The compounding effects of coenzyme q10 and radiation treatment on glial fibrillary acidic protein network of glioma in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2931.
Abstract 2939: Developing new therapeutic strategy to bladder cancer by targeting CK1 delta
Authors: Lin Yu-Chen , Chen Mei-chuan , Liou Jing-Ping , Chen Chun-Han 
Published: August 2019

Abstract
Bladder cancer is a common malignancy with high recurrent rate, but targeted therapy other than immune checkpoint inhibitors is currently unavailable. Hence, there is an unmet medical need for the discovery of new therapeutic approach to bladder cancer. By investigating Oncomine database, the mRNA level of CK1 delta is higher in bladder cancer compared to normal tissue, which correlates with survival rate. The aim of this study is to develop new CK1 delta inhibitors and examine their therapeutic potential to bladder cancer as well as the pharmacological mechanisms. Cell viability, cell cycle progression, apoptosis, migration and downstream signaling pathway were analyzed. The results showed that treatment of CK1 delta inhibitors decreased cell viability and inhibited wnt/β-catenin pathway in bladder cancer cell lines. CK1 delta inhibitors increased the accumulation of sub-G1 phase by flow cytometry analysis, as well as the activation of caspase-3, 8, 9 and PARP cleavage by western blot, indicating the promotion of cell apoptosis. Meanwhile, necroptosis was also involved as evident by the rescuing effects by knocking down MLKL in bladder cancer cells. In conclusion, this study demonstrates that CK1 delta is a potential target for bladder cancer therapy in the future.
Note: This abstract was not presented at the meeting.
Citation Format: Yu-Chen Lin, Mei-chuan Chen, Jing-Ping Liou, Chun-Han Chen. Developing new therapeutic strategy to bladder cancer by targeting CK1 delta [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2939.
Abstract 2942: Cathepsin S inhibition alleviates oxaliplatin-induced peripheral neuropathy through regulation of Ca2+ homeostasis
Authors: Chen Szu-Jung , Shen Meng-Ru , Chen Li-Hsien , Lin Hsiao-Han , Hsu Shih-Han , Chang Jang-Yang 
Published: August 2019

Abstract
Chemotherapeutic drug oxaliplatin is frequently causing chemotherapy-induced peripheral neuropathy. Currently, there is no effective drug to prevent neuropathy in the clinic. Therefore, identification of the potential target to treat to alleviate oxaliplatin-induced neuropathy is urgent. Previously, the release of cathepsin S (CTSS) from microglial cells, which causes neuropathic pain, has been reported, but the detailed mechanism remains unclear. In this study, we discovered that oxaliplatin treatment triggers CTSS expression accompanies with prompted calcium influx from SOCE in vitro. And, the oxaliplatin treated mice displayed increased tail-withdrawal temperature hyperalgesia and impaired locomotor activity along with the loss of neuromuscular function. Furthermore, oxaliplatin-induced peripheral neuropathy was inhibited by the highly selective CTSS inhibitor, 58, which significantly improved the thermal sensitivity and alleviated mechanical allodynia on the heat tail-withdrawal and von Frey tests in oxaliplatin-treated mice, respectively. The grip strength test showed that 58 significantly improved the motor strength and neuromuscular function of oxaliplatin-treated mice. The ultrastructure of sciatic nerve myelin integrity through G ratio quantification supported the observations in our oxaliplatin-induced peripheral neuropathy mouse behavioral tests. Also, inhibition of CTSS enzymatic activity by 58 resulted in the suppression of STIM1 aggregation and decreasing the oxaliplatin-induced calcium influx from SOCE. These results revel a novel molecular mechanism of CTSS in the involvement of oxaliplatin-induced peripheral neuropathy. (This study was supported by the following grants: the National Health Research Institutes (CA-107-PP-22), the Ministry of Science and Technology (MOST 106-2314-B-006-076-MY3)
Citation Format: Szu-Jung Chen, Meng-Ru Shen, Li-Hsien Chen, Hsiao-Han Lin, Shih-Han Hsu, Jang-Yang Chang. Cathepsin S inhibition alleviates oxaliplatin-induced peripheral neuropathy through regulation of Ca2+ homeostasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2942.
Abstract 2948: Novel cell line barcoding method reveals tepoxalin as a selective drug against MDR1-high tumor cells
Authors: Corsello Steven M. , Spangler Ryan D. , Nagari Rohith T. , Kocak Mustafa , Rossen Jordan , O'Hearn Patrick , Roth Jennifer , Gonzalez Alfredo , Dumont Nancy , Doench John , Boehm Jesse S. , Vazquez Francisca , Tsherniak Aviad , Golub Todd R. 
Published: August 2019

Abstract
Drug repurposing for cancer therapy has seen notable success, such as the reintroduction of thalidomide. To discover new indications, all existing drugs known to be safe should be systematically evaluated for anti-cancer properties. However, given cost and throughput considerations, phenotypic screens are typically limited along the cell line (e.g., NCI-60 cell lines) or compound dimension (e.g., testing only several hundred cancer drugs). To identify new repurposing opportunities at scale, we tested more than 4,600 existing drugs for cytotoxicity against 578 diverse cancer cell lines using PRISM, a recently developed multiplexed cell viability assay. High gene expression of the ABCB1 transporter (MDR1/p-glycoprotein) was strongly correlated with resistance to numerous approved cancer therapeutics including taxanes, anthracyclines, vinca alkaloids, and proteasome inhibitors. Surprisingly, we identified a single drug, tepoxalin, with the opposite profile: selective activity against MDR1-high cancer cell lines.
Tepoxalin, an oral cyclooxygenase inhibitor, is FDA-approved for treatment of osteoarthritis in dogs and was previously found to be safe in human trials. To evaluate for alternative mechanism of action and genomic mediators of tepoxalin resistance, we conducted pooled genome-wide CRISPR-Cas9 modifier screens in the LS1034 colorectal cancer cell line. The CRISPR knockout screen revealed ABCB1 as the top enriched gene mediating tepoxalin resistance, while the CRISPR activation screen revealed ABCB1 as the top depleted gene. Overexpression of ABCB1 in ovarian cancer cell lines also sensitized to tepoxalin killing. Small molecule combination testing demonstrated rescue of tepoxalin killing by known ABCB1 inhibitors. Future studies will include biophysical characterization of the interaction between tepoxalin and the ABCB1 protein as well as in vivo efficacy testing. Our results demonstrate that tepoxalin or related derivatives may be useful in the treatment of chemotherapy-resistant colorectal cancer, ovarian cancer, lymphoma, and other malignancies.
Citation Format: Steven M. Corsello, Ryan D. Spangler, Rohith T. Nagari, Mustafa Kocak, Jordan Rossen, Patrick O'Hearn, Jennifer Roth, Alfredo Gonzalez, Nancy Dumont, John Doench, Jesse S. Boehm, Francisca Vazquez, Aviad Tsherniak, Todd R. Golub. Novel cell line barcoding method reveals tepoxalin as a selective drug against MDR1-high tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2948.
Abstract 2959: Deoxysappanchalcone inhibits cell growth by regulation of TOPK signaling pathway in colon cancer
Authors: Zhao Ran , Huang Hai , Choi Bu Young , Song Mengqiu , Yin Fanxiang , Fu Xiaorong , Chen Hanyong , Shim Jung Hyun , Lee Mee-Hyun , Dong Zigang 
Published: August 2019

Abstract
Background: Colorectal cancer is one of the most common cancer death causes in the worldwide. Still systemic chemotherapies are limited to many complications and relapse. T-lymphokine-activated killer cell-originated protein kinase (TOPK) is highly expressed and activated in colon cancer, and plays important roles in inflammation, proliferation and survival of cancer cells. Therefore, suppression of the TOPK activity and its downstream signaling cascades is considered to be a rational therapeutic/preventive strategy of colon cancers.
Purpose: Deoxysappanchalcone (DSC), a component of Caesalpinia sappan L., is a natural oriental medicine. In the present study, we investigated the effects of DSC on colon cancer cell growth and elucidated its underlying molecular mechanism by targeting TOPK.
Study Design and Methods: To evaluate the effects of DSC on colon cancers, we performed cell proliferation assay, propidium iodide- or annexin V-staining analysis and western blotting. Targeting TOPK by DSC was identified by kinase/binding assay and computational docking models. Results: DSC inhibited the kinase activity of TOPK but not mitogen-activated protein kinase (MEK). The direct binding of DSC with TOPK was explored using a computational docking model and binding assay in vitro & ex vivo. DSC inhibited colon cancer cell proliferation, anchorage-independent cell growth, and induced G2/M cell cycle arrest and apoptosis. Treatment of colon cancer cells with DSC induced protein expressions which are involved in cell cycle (cyclin B1) and apoptosis (cleaved-PARP, cleaved-caspase-3 and cleaved-caspase-7), and suppressed protein expressions of extracellular signal-regulated kinase (ERK)-1/2, ribosomal S6 kinase (RSK) or cellular jun (c-Jun) which are regulated by the upstream kinases TOPK.
Conclusion: DSC suppresses colon cancer cell growth by direct targeting TOPK-mediated signaling pathway.
Citation Format: Ran Zhao, Hai Huang, Bu Young Choi, Mengqiu Song, Fanxiang Yin, Xiaorong Fu, Hanyong Chen, Jung Hyun Shim, Mee-Hyun Lee, Zigang Dong. Deoxysappanchalcone inhibits cell growth by regulation of TOPK signaling pathway in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2959.
Abstract 2976: A comparative study between the therapeutic efficacy of vitamin D3 and its analogue, paricalcitol, in the treatment of colon cancer in rat
Authors: Baghdadi Mohammed Abbas , Aslam Mohammed , Ahmad Jawwad , Idris Shakir , Refaat Bassem 
Published: August 2019

Abstract
Background: Vitamin D3 (VD) and its analogue, Paricalcitol (Pcal), have previously shown anti-tumorigenic activities against colorectal cancer (CRC). Hence, this study compared the therapeutic efficacy of both VD types with or without chemotherapy (5-FU) in azoxymethane (AOM)-induced CRC in rat.
Methods: seventy male Wistar rats were equally allocated into 7 groups: Control, AOM, VD, Pcal, 5-FU, 5-FU/VD and 5-FU/Pcal. AOM was subcutaneously injected for 2 weeks (15mg/kg/week). The study duration was 25 weeks. VD (500 IU/rat/day; 3 days/week) and Pcal (2.5 μg/kg/day; 3 days/week) were injected subcutaneously from week-15 till the end of the study. 5-FU intraperitoneal injections started in week-21 (12 mg/kg/day; 4 successive days) and continued in week-22 (6 mg/kg/4 doses every other day). The colons were collected for gross and histopathological examination. The expression of VD signalling system, Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, smad4, p21 and p27 proteins was measured by immune-histochemistry/fluorescence. The mRNA expression of Wnt, β-catenin, DKK-1 and COX-2 genes was measured by Quantitative RT-PCR. ELISA was used to measure the concentrations of TGF-β1, VEGF and COX-2 proteins in tissues.
Results: The AOM and 5-FU groups showed marked inhibitions in the VD receptor and binding protein compared with controls (P &lt; 0.05). VD and Pcal monotherapies significantly increased the expression of the VD molecules and the VD group showed the utmost elevations. Moreover, the tumour numbers and sizes were equally and significantly reduced in the 5-FU, VD and Pcal groups compared with the AOM group (P &lt; 0.05). Interestingly, the 5-FU/VD and 5-FU/Pcal resulted in significantly lower numbers of tumours compared with the remaining study groups and the highest significant reduction was observed in the former group. At the molecular level, the 5-FU/VD markedly inhibited the pro-oncogenic molecules (Wnt, β-catenin, NF-κB, COX-2, iNOS & VEGF) as well as significantly upregulated the anti-tumorigenic molecules (DKK-1, TGF-β1, smad4, p21 and p27) compared with the other study groups (P &lt; 0.05).
Conclusions: Vitamin D3 showed a better synergism than Pcal with 5-FU. The enhanced anti-tumorigenic actions of 5-FU/VD involved the modulation of the Wnt/β-catenin and TGF-β1/smad4 pathways, angiogenesis and cell cycle arrest. Further studies are required to elucidate the therapeutic significance of VD in clinical settings
Citation Format: Mohammed Abbas Baghdadi, Mohammed Aslam, Jawwad Ahmad, Shakir Idris, Bassem Refaat. A comparative study between the therapeutic efficacy of vitamin D3 and its analogue, paricalcitol, in the treatment of colon cancer in rat [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2976.
Abstract 2989: An all-in-one transcriptome-based assay to identify therapy-related biomarkers in lung cancer
Authors: Kok Klaas , Wei Jiacong , Rybczynska Anna A. , Meng Pei , Terpstra Martijn M. , Wekken Anthonie J. van der , Hiltermann Jeroen T. , Schuuring Ed , Groen Harry J. , Berg Anke van den 
Published: August 2019

Abstract
Background. In the past decade, treatment of advanced stage lung cancer patients guided by somatic aberrations has become routine practice. Different molecular tests are being applied to detect all targetable mutations and fusions. However, in most cases tissue biopsies are small, hampering multiple independent diagnostic tests. To optimize diagnostic testing we developed an all-in-one transcriptome-based assay.
Methods. We have developed a targeted next generation sequencing protocol that uses total RNA as input and is based on the Single Primed enrichment Technology (SPET). We included 11 cell lines, four frozen biopsies, 12 pleural effusion samples and 32 FFPE samples with in total 41 known mutations (including EGFR n=15; KRAS n=11; BRAF n=2; PIK3CA n=3 ), 21 fusion genes (including ALK n=15; ROS n=3) and 3 cases of MET exon14 skipping.
Results. We confirmed presence of 32 out of 41 mutations, 19 out of 23 fusions and all three cases of exon skipping by our assay. Besides confirming the fusions, we were also able to identify the fusion gene partner for all detected fusion transcripts. For the samples for which we failed to detect the mutations or fusions, the read depth of the target region was less than four, indicating low expression, low tumor content or insufficient unique reads. Independent RNA-based ddPCR on six unconfirmed mutations were all positive, albeit with low numbers of mutant droplets in some cases. One of three undetected fusions was positive in a NanoString fusion gene detection assay. For one of two negative cases, the fusion was most likely false positive by FISH, as this patient was FISH-break positive for both ALK and RET, which is never reported before.
Conclusions. This study proved feasibility of this targeted all-in-one transcriptome-based assay for simultaneous detection of mutations and fusions even in relatively small FFPE tissue biopsies. Moreover, we were able to detect the fusion partner genes in all positive cases. We expect that for routine diagnostic testing using an enrichment for tumor cell-rich areas of recently prepared FFPE blocks, the success rate of the all-in-one transcriptome approach will reach similar sensitivity as currently used diagnostic tests.
Citation Format: Klaas Kok, Jiacong Wei, Anna A. Rybczynska, Pei Meng, Martijn M. Terpstra, Anthonie J. van der Wekken, Jeroen T. Hiltermann, Ed Schuuring, Harry J. Groen, Anke van den Berg. An all-in-one transcriptome-based assay to identify therapy-related biomarkers in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2989.
Abstract 299: Synergistic activity of mebendazole and chemotherapeutic agents for rare cancers
Authors: Samizadeh Mahta , Chakrabarti Debashree , Zhu Yuhan , Treuting Robert Louis , Kaplan Johanne , Siders William , Barber Jamie D. 
Published: August 2019

Abstract
Depending upon the definition used, as many as half of all cancers diagnosed are considered rare cancers, and most rare cancer patients would greatly benefit from additional therapies. Repurposing of drugs for use in oncology represents an attractive strategy for the rapid development of therapies that address the significant unmet medical need that remains for rare cancers. The FDA-approved anti-helminthic drug mebendazole (MBZ) has been reported to affect several biological pathways involved in tumor growth and metastasis. Based on this activity, multiple rare cancer tumor cell lines including neuroblastoma, carcinoid tumors, esophageal adenocarcinoma, gastrointestinal stromal tumors, leiomyosarcoma, pheochromocytoma, and mesothelioma were analyzed for their susceptibility to MBZ treatment alone or in combination with standard chemotherapeutic agents in vitro. Cultured cells exposed to increasing concentrations of MBZ alone showed a significant decrease in cell viability with IC50s ranging from 0.09-2.2 μM. To evaluate efficacy of MBZ in an additional model system, an ex vivo 3D assay using gastric cancer primary cells isolated from two patient-derived xenograft (PDX) models was performed. Cells were seeded in 3D cultures and treated for seven days with MBZ at nine different doses in triplicate. IC50s were determined to be 0.74 and 0.76 μM indicative of significant potency. These results along with the in vitro data generated using cell lines suggest that MBZ may represent an effective anti-cancer agent across multiple rare cancer indications. However, since tumor cells can often evade or develop resistance to single agent therapy, the potential for synergistic combinations with chemotherapeutic agents was also explored in vitro. Cells were plated in triplicate and treated with a range of concentrations of MBZ and relevant chemotherapeutic agents in a complete Latin square. Combination indexes (CI) were determined based on the method described by Chou and Talalay. Several synergistic drug combinations were identified with CI values ranging from 0.008 to 0.428 (CI &lt; 0.9 indicates synergy). Overall, our results indicate that synergistic combinations of MBZ and chemotherapy agents represent a promising strategy for the treatment of rare cancers.
Citation Format: Mahta Samizadeh, Debashree Chakrabarti, Yuhan Zhu, Robert Louis Treuting, Johanne Kaplan, William Siders, Jamie D. Barber. Synergistic activity of mebendazole and chemotherapeutic agents for rare cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 299.