bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4375: UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models
Authors: Hiroshima Yukihiko , Maawy Ali , Sato Sho , Murakami Takashi , Yamamoto Mako , Uehara Fuminari , Miwa Shinji , Yano Shuya , Momiyama Masashi , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: May 2015

Abstract
The aim of this study was to determine the efficacy of UVC irradiation in combination with fluorescence-guided surgery (FGS) in an orthotopic model of pancreatic cancer. Two weeks after orthotopic implantation of human MiaPaCa-2-GFP pancreatic cancer cells, bright-light surgery (BLS) was performed on all tumor-bearing mice (n=24). Postoperatively, the surgical resection bed was imaged with the OV100 variable magnification imaging system with a magnification of 0.56x to detect residual tumor. The mice which underwent BLS were randomized into 3 groups; BLS only (n=8) or FGS (n=8) or FGS-UVC (n=8). The residual tumors were resected with FGS using a portable, hand-held imaging system. After FGS, the surgical resection bed was imaged with the OV100 with a magnification of 0.89x, to detect minimal residual tumor and was irradiated with 2700 J/m2 UVC (emission peak 254 nm) from the bottom of a chamber using a Benchtop 3UV transilluminator (UVP, LLC, Upland, CA). The average residual tumor area after FGS was significantly smaller than BLS (0.135 ± 0.137 mm2 and 3.338 ± 2.929 mm2, respectively; p=0.007). Relapse-free survival (RFS) and overall survival (OS) were determined in 3 groups. Three-month RFS in the BLS, FGS and FGS-UVC were 0%, 50% and 100%, respectively. Five-month OS in BLS, FGS and FGS-UVC was 10%, 90% and 100%, respectively. FGS and FGS-UVC resulted in significantly increased survival compared to BLS for both RFS and OS. FGS-UVC showed significantly increased survival compared to the FGS for both RFS and OS (p=0.008 and p=0.025, respectively). These results suggests that UVC irradiation in combination with FGS could be a curative strategy for human pancreatic cancer.
Citation Format: Yukihiko Hiroshima, Ali Maawy, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2014-4375
Abstract 438: Long non-coding RNA AK023948 enhances breast cancer progression by activating AKT
Authors: Koirala Pratirodh 
Published: May 2015

Abstract
The role of long non-coding RNAs (lncRNAs) in various physiological and pathological conditions has been increasingly appreciated, however, given the large number of lncRNAs, little is known for the vast majority of lncRNAs for their potential role in breast cancer. In this study, using real-time PCR-based lncRNA profiling array, we identified a set of lncRNAs that were differentially expressed in breast cancer tissues of patients as compared to the normal breast tissue. Among them, AK023948 was upregulated in breast cancer; it was also upregulated in breast cancer cell lines (MCF-7 and MDA-MB-231) as compared to human mammary epithelial cells (HMLE). This was further supported by breast cancer tissue microarray by in situ hybridization. Moreover, ectopic expression of AK023948 in MCF-7 cells promoted the proliferation and anchorage independent cell growth, implying its potential oncogenic role in breast cancer progression. In consistent with this finding, we found that while ectopic expression of AK023948 activated, AK023948-siRNA suppressed Akt activation. To determine the underlying mechanism of AK023948-mediated activation of Akt, we performed RNA pull-down assay with biotin-labeled AK023948 RNA probe. Mass spectrometry analysis of the pulled down proteins identified ATP dependent RNA helicase A (RHA/DHX-9) as a potential binding partner for AK023948, which was confirmed by western blot. Gene silencing of DHX-9 in MCF-7 cells suppressed AKT phosphorylation, suggesting that AK023948 may activate AKT activation through interacting with DHX-9 and modulating its function. Together, these results suggest that AK023948 may function as an oncogenic lncRNA in breast cancer and thus, it may represent a novel target for breast cancer therapy.
Citation Format: Pratirodh Koirala. Long non-coding RNA AK023948 enhances breast cancer progression by activating AKT. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 438. doi:10.1158/1538-7445.AM2014-438
Abstract 4384: Targeting miR-124 inhibits growth of prostate cancer xenografts and sensitized prostate cancer cells to anti-androgen
Authors: Shi Xu-Bao , Ma Aihong , Xue Lingru , White Ralph W. deVere 
Published: May 2015

Abstract
Increasing evidence has shown that miR-124 is a tumor suppressor and plays an important role in pathogenesis of many types of human cancer. We previously found that miR-124 directly targets the androgen receptor (AR) and is significantly downregulated in clinical prostate cancer (CaP) samples. Moreover, overexpression of miR-124 induced apoptosis and inhibited cell proliferation and xenograft growth of CaP. In this study, we determined whether restoration of miR-124 may represent an adjunctively therapeutic option for CaP treatment. For this purpose, WST-1 and clonogenic assays were performed to evaluate the effects of miR-124 or miR-124 plus enzalutamide (one new androgen antagonist) on CaP cell proliferation. In animal experiment, male nude mice were inoculated s.c with CWR22 CaP cell suspensions. When tumor sizes reached ∼50 mm3, mice were treated with polyethylenimines (PEI)-complexed miR-124 (i.v., 10µg/day, thrice a week for 4 weeks) or PEI-miR-124 (i.v.) plus enzalutamide (p.o., 10mg/kg/day for 5 weeks). PEI can increase internalization and facilitate miRNA release into cytoplasm. After treatment, tumors were harvested for analyzing apoptosis and measuring miR-124 target levels. In in vitro experiment, 22Rv1 cells were separately treated with miR-124, enzalutamide or both. It was found that the combined treatment significantly increased growth inhibition of 22Rv1 cells. In addition, we established enzalutamide-resistant 22Rv1 subline (22Rv1-MDVR) by clone-selection in gradually increased doses (from 5μM to 40μM within four months). Treatment with miR-124 obviously inhibited clone formation of 22Rv1-MDVR cells. In mice receiving miR-124 or enzalutamide treatment, we observed tumor-inhibitory effects. However, the combination of miR-124 and enzalutamide exhibited more significant inhibition of tumor growth when compared to the single treatment. We examined the expression of AR and its variant 7 (AR-V7) that are targets of miR-124. Reduced levels of AR and AR-V7 were found in miR-124-treated tumors, indicating that PEI facilitates entry of miR-124 into the tumor cells. We also observed increased apoptosis in miR-124-treated tumors. Data from in vitro and in vivo studies show that miR-124 inhibited growth of CaP cells and sensitized CaP cells to anti-androgens, suggesting that miR-124 can be used as an adjunctively therapeutic agent for improved CaP treatment.
Citation Format: Xu-Bao Shi, Aihong Ma, Lingru Xue, Ralph W. deVere White. Targeting miR-124 inhibits growth of prostate cancer xenografts and sensitized prostate cancer cells to anti-androgen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4384. doi:10.1158/1538-7445.AM2014-4384
Abstract 439: Mitochondrial uncoupling protein 2 promotes skin carcinogenesis
Authors: Li Wenjuan , Zhang Chunjing , Shi Runhua , Gu Xin , Zhao Yunfeng 
Published: May 2015

Abstract
Mitochondrial uncoupling uncouples mitochondrial respiration and ATP production. There are five uncoupling proteins (UCPs), UCP2 is ubiquitous expressed and plays an important role in the reprogramming of cancer cell metabolism. However, little is known about at what stage of cancer development mitochondrial uncoupling occurs and what the role of UCP2 in cancer etiology. We will try to address these puzzles in present study.
The well-established chemically-induced skin carcinogenesis mouse model was used and UCP2 wide-type (WT) and homozygous knockout (KO) mice were added to this study as direct evidence for the role of UCP2 during skin carcinogenesis. After forty-week treatment with chemical carcinogens, the incidence of papillomas in WT and KO TPA mice was 92.3% and 77.8%, respectively; and tumor multiplicity was 2.6 and 1.3, respectively. The incidence of carcinomas in WT and KO TPA treatment was 76.9% and 22.2%, respectively, and tumor multiplicity was 0.9 and 0.2, respectively. We next detected how the mitochondrial function and ATP generation would be changed in this model. UCP2 knockout slightly increased oxygen consumption compared with WT, whereas tumor promoter treatment suppressed oxygen consumption in both UCP2 KO and WT group. As for ATP generation, there was no significant change between WT and KO, or between vehicle and tumor promoter treatment.
We next examined the mechanisms of tumor promotion by mitochondrial uncoupling by overexpressing UCP2 in JB6 P+ cells, which are the only characterized skin cell model to study tumor promotion. Anchorage-independent growth assay was performed and the results showed that overexpression of UCP2 enhanced colony formation in response to tumor promoter treatment. In addition, overexpression of UCP2 induced the upregulation of the oncoprotein Fra-1 whereas inhibited the increase in p53 expression.
In summary, this study will add new knowledge to the understanding of the role of mitochondrial uncoupling in cancer etiology, and many help design a mitochondrial uncoupling-targeted approach for the suppression of cancer development.
Citation Format: Wenjuan Li, Chunjing Zhang, Runhua Shi, Xin Gu, Yunfeng Zhao. Mitochondrial uncoupling protein 2 promotes skin carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 439. doi:10.1158/1538-7445.AM2014-439
Abstract 4396: MicroRNA MIR551B amplified at 3q26.2 locus activate c-KIT expression and causes resistance to anoikis of ovarian cancer cells
Authors: Chaluvally-Raghavan Pradeep , Zhang Fan , Liu Wenbin , Tyler Moss , Yu Shuangxing , Pradeep Sunila , Ram Prahlad , Lu Yiling , Sood Anil , Mills Gordon 
Published: May 2015

Abstract
Background and Hypothesis
The 3q26.2 loci amplification is present in at least 35% of high grade serous ovarian cancer (HGSEOC). Recently we identified a microRNA, MIR551B located in the 3q26 amplicon. However, the potential role of microRNAs amplified at 3q26 amplicon and their functions in ovarian tumorigenesis has not been studied previously. Thus, our studies have the potential to provide novel mechanism underlying MIR551B oncogenesis in ovarian cancer.
Results
The 3q26.2 locus is large and structurally complex suggesting that multiple coding genes located in the amplicon could contribute to tumor initiation and progression alone or through cooperative activity. High-resolution SNP-based copy number analysis of 533 high-grade serous ovarian cancer samples demonstrated that MIR551B is highly amplified as a consequence of the 3q26.2 amplicon. Expression analysis in the Cancer Genome Atlas (TCGA) data sets showed that amplification of MIR551B is associated with increased expression of maturedmicroRNA miR551b in the recently defined proliferative subtype of ovarian cancer. Reverse phase protein array (RPPA) demonstrated that enforced expression of miR551b-5p increased the expression c-KIT oncogene and activated the ERK signaling pathway. Our target search analysis identified a potential novel mechanism whereby miR551b-5p could bind to a target site in the promoter of c-KIT oncogene and increase the transcription of c-Kit mRNA. Strikingly, enforced expression of miR551b-5p induced the survival and proliferation of ovarian surface epithelial cells detached from extracellular matrix. Of note, miR551b-5p expression in recurrent ovarian tumors are higher than the primary ovarian cancers.
Summary
Our results show that copy number alterations (CNAs) of MIR551B are associated with increased levels of mature microRNA, miR551b. Mechanistic studies revealed a novel role of microRNA miR-551b-5p to induce transcriptional activation by interacting with the promoter of the c-Kit oncogene, which in turn renders cells resistant to anokis a critical component of the survival and spread of ovarian cancer in the peritoneal cavity. Our results propose the c-KIT transcriptional activation induced by miR551b-5p is a key mechanism of survival of ovarian cancer cells in the ascitic fluid in the peritoneal cavity.
Citation Format: Pradeep Chaluvally-Raghavan, Fan Zhang, Wenbin Liu, Moss Tyler, Shuangxing Yu, Sunila Pradeep, Prahlad Ram, Yiling Lu, Anil Sood, Gordon Mills. MicroRNA MIR551B amplified at 3q26.2 locus activate c-KIT expression and causes resistance to anoikis of ovarian cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4396. doi:10.1158/1538-7445.AM2014-4396
Abstract 4397: Therapeutic microRNA agaisnt KRAS mutant colorectal cancer
Authors: Hiraki Masayuki , Nishimura Junichi , Uemura Mamoru , Hata Taishi , Takemasa Ichiro , Mizushima Tsunekazu , Yamamoto Hirofumi , Doki Yuichiro , Mori Masaki 
Published: May 2015

Abstract
Background:
The anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are the molecular target drugs, dependent on v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations status in metastatic colorectal cancer (mCRC). Anti-EGFR monoclonal antibody based chemotherapy is the standard treatment for mCRC with KRAS wild-type. However, the issue of resistance to this therapy in CRC with KRAS mutations (approximately 50% of CRC) remains unresolved. The aim of this study is to identify microRNAs (miRNAs) that govern the resistance to anti-EGFR monoclonal antibody in CRC with KRAS mutations.
Experimental Design:
We first established the KRAS mutant cell model using HEK293 and MRC5 cells by introducing KRASG12V plasmid. The miRNA expression profiles were compared between these cells using miRNA microarray analysis. We selected the candidate a miRNA which down-regulates the downstream signal of KRAS using luciferase reporter assays. Assessment of target genes of the candidate a miRNA was performed in vitro. Next, anti-tumor effects by supplement of a miRNA were evaluated in vitro and in vivo.
Results:
We picked up miRNAs, of which expressions decreased in both HEK293 and MRC5 cells by introduction of KRASG12V plasmid in miRNA array analysis. Among them, administration of mature-miR-X suppressed SRE and AP1 activity in KRAS mutant CRC cell lines such as DLD1G13D, SW480 G12V, and HCT116 G13D using dual luciferase reporter assay. Furthermore, miR-X regulated not only Ras/Raf/MAPK pathway but also suppressed PI3K/Akt pathway in vitro. Administration of mature-miR-X suppressed proliferation and induced apoptosis of the CRC cell lines with KRAS mutations in vitro. Systemic mature-miR-X administration into tail veins of nude mice significantly inhibited the growth of pre-established DLD1G13D xenografts. miR-X level was significantly lower in tumor tissues compared to normal mucosa.
Conclusions:
miR-X may overcome anti-EGFR therapy resistance in CRC with KRAS mutations by regulating Ras/Raf/MAPK pathway and PI3K/Akt pathway. Our data suggests that miR-X could be suitable for a novel therapy for mCRC patients with KRAS mutations.
Citation Format: Masayuki Hiraki, Junichi Nishimura, Mamoru Uemura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori. Therapeutic microRNA agaisnt KRAS mutant colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4397. doi:10.1158/1538-7445.AM2014-4397
Abstract 4401: A novel drug suppresses proliferation of lung cancer cells via increasing the CBL activity and down-regulating epidermal growth factor receptor
Authors: Huang Kuo-Yen , Pan Szu-Hua , Wang Wen-Lung , Chen Ching-Shih , Hong Tse-Ming , Yang Pan-Chyr 
Published: May 2015

Abstract
Aberrant epidermal growth factor receptor (EGFR) signaling is one of the most critical oncogenic pathways in NSCLC that may trigger the tumor progression. Thus, how to suppress the EGFR downstream signaling cascade or to reduce the EGFR expression level has long been considered an important therapeutic approach for cancer interventions. Here, we found a regulatory mechanism by which the degradation of EGFR is enhanced by a novel promising drug, compound 22. First, the exposure to compound 22 induced cell death via apoptosis in lung cancer cell lines, including EGFR wild type A549 as well as EGFR mutant PC9 and H1975 cells. Compound 22 decreased the EGFR protein level in a dose-dependent manner and facilitated dephosphorylation of its downstream targets, including AKT and ERK, both of which play a critical role for cancer cell survival. Second, we observed that compound 22 induced EGFR degradation through proteasome degradation in the cycloheximide chase plus MG132 assay. Additionally, compound 22 increased the CBL (the ubiquitin E3 ligase)-mediated ubiquitination of EGFR, which was accompanied by the enhancement of Y1045 phosphorylation in the EGFR kinase domain. Overall, these pieces of evidence suggest that compound 22 is a novel class of anticancer drug which is able to inhibit the TKI-resistant NSCLC cells by inducing the degradation of EGFR.
Citation Format: Kuo-Yen Huang, Szu-Hua Pan, Wen-Lung Wang, Ching-Shih Chen, Tse-Ming Hong, Pan-Chyr Yang. A novel drug suppresses proliferation of lung cancer cells via increasing the CBL activity and down-regulating epidermal growth factor receptor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4401. doi:10.1158/1538-7445.AM2014-4401
Abstract 4402: Synergistic cell death in nedd8 and hrb27c mutant cells under an rbf-negative background is dependent on EGFR/MAPK signaling
Authors: Zhang Robin , Zhang Tianyi , Sheng Zhentao , Du Wei 
Published: May 2015

Abstract
The Rb (retinoblastoma) protein is highly functionally conserved between the Drosophila, and deregulation and mutations in the Rb pathway are common events across a wide range of cancers. Here, we identify two novel synthetic lethal interactions between Rb and mutant alleles of Nedd8 and Hrb27c that were identified through an unbiased genetic screen in Drosophila that resulted in apoptosis in both the wing disc pouch and the region of the eye disc posterior to the morphogenetic furrow. However, the molecular mechanisms behind the apoptotic phenotypes in both synthetic lethal double mutants have yet to be elucidated. It is known that wild-type Rb normally sequesters and can prevent the E2F1 transcription factor from promoting transcription of hid, the major pro-apoptotic regulator in imaginal discs. Synthetic lethality is therefore likely to be contingent on EGFR/hid signaling, and I will determine if such is the case through a series of genetic epistasis tests. Interestingly, preliminary evidence also suggests that EGFR/MAPK signaling may be ablated in both mutants of Nedd8 and Hrb27c. However, this observation is completely novel and therefore the molecular mechanisms behind downregulation of MAPK signaling have yet to be elucidated in both these mutants. I will again perform a series of epistasis experiments to determine how Nedd8 and Hrb27c mutations mechanistically affect EGFR/MAPK signaling. This will be achieved first by determining if signaling is downregulated either during EGFR ligand processing or downstream of the EGFR receptor. This will be followed by subsequent experiments to determine which specific element in either pathway is being affected by Nedd8 or Hrb27c ablation. I therefore hypothesize that inhibition of both nedd8 and hrb27c synergistically induce cell death in Rb-negative cells in a process that is dependent on both E2F1 activity and downregulation of MAPK signaling. Many existing treatment regimens fail to take into account the unique biological properties of cancer cells compared to their normal counterparts, thus often resulting in off-target effects and limitations in dosage. This proposal is therefore both novel and significant because the mechanisms behind both the Rb/Hrb27c and Rb/Nedd8 synthetic lethal interactions have yet to be elucidated and characterization of such interactions such as these have the potential to catalyze the development of new therapeutic strategies in the treatment of cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Robin Zhang, Tianyi Zhang, Zhentao Sheng, Wei Du. Synergistic cell death in nedd8 and hrb27c mutant cells under an rbf-negative background is dependent on EGFR/MAPK signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4402. doi:10.1158/1538-7445.AM2014-4402
Abstract 4416: IKBKE is a key mediator of Ras activation of NF-κB and Ras oncogenic function
Authors: Kim Donghwa , Guo Jianping , Challa Sridevi , Coppola Domenico , Cheng Jin Q. 
Published: May 2015

Abstract
Accumulating evidence indicates that the NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. IKBKE has been shown to activate NF-κB through both canonical and non-canonical pathways. Here we show that activating mutations of Ras significantly induce IKBKE kinase activity and that depletion of KRas results in decrease of IKBKE activity only in KRAS mutant but wild-type cells. KRas-induced NF-κB DNA-binding and transcription activity was abrogated by knockdown of IKBKE. In addition, we demonstrated significant decrease of lung tumor development in Ikbke-/-;KRasLA1 mice when compared to Ikbke+/-;KRasLA1 and Ikbke+/+;KRasLA1 animals. Furthermore, depletion of IKBKE selectively reduces cell survival and tumor growth in K-Ras mutant non-small cell lung cancer cells. These data identify IKBKE as a downstream effector of Ras which mediates RAS activation of NF-κB and Ras tumorigenic activity.
Citation Format: Donghwa Kim, Jianping Guo, Sridevi Challa, Domenico Coppola, Jin Q. Cheng. IKBKE is a key mediator of Ras activation of NF-κB and Ras oncogenic function. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4416. doi:10.1158/1538-7445.AM2014-4416