bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 339: Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer (CRC) cells, enhances the efficacy of BH3 mimetics and inhibits clonogenicity
Authors: Mattoo Abid R. , Zhang Jingyu , Espinoza Luis A. , Thorgeirsson Snorri S. , Jessup J. M. 
Published: May 2015

Abstract
Combining lentiviral (LV) delivered shRNA against NANOG (shNG-1) or NANOGP8 (shNp8-1) with BH3 mimetics (ABT-737 and ABT-199) was undertaken to determine whether inhibition of NANOG/NANOGP8 enhances the cytotoxic effect of these BH3 mimetics in Colorectal Cancer (CRC) cells. NANOG is a key transcription factor important for both pluripotency in embryonic stem cells and malignant transformation and progression of colorectal carcinoma (CRC). Inhibition of NANOG or its paralog NANOGP8 reduces the proliferation, stemness and tumorigenicity of CRC cells. The cytotoxic potential of ABT-737 or ABT-199, as single agents, was tested in the CRC cell lines- Clone A, CX-1 and LS174T that have high levels of anti-apoptotic BCL-2 family proteins. Treatment with ABT-737 or ABT-199 showed variable cytotoxicity in the three CRC lines with LS174T being the most resistant. Inhibition of NANOG and NANOGP8 with LVshNG-1 or LVshNp8-1 in these cell lines decreased expression of MCL-1. The combination of LVshNG-1 and/or LVshNp8-1, with ABT-737 produced enhanced killing of the CRC cells by caspase-dependent apoptosis. These results were were confirmed when LV shNG-1 or LV shNp8-1 was used in combination with ABT-199. siRNA targeting MCL-1 reproduced the effects of NANOG/NANOGP8 inhibition. The CRC cells that survived the combination treatment showed lower regrowth potential and reduced clonogenicity when re-plated in fresh media. These results demonstrate that inhibition of NANOGP8 or NANOG enhances the cytotoxicity of BH3 mimetics that target BCL-2 family members through inhibition of MCL-1 expression.
Citation Format: Abid R. Mattoo, Jingyu Zhang, Luis A. Espinoza, Snorri S. Thorgeirsson, J. M. Jessup. Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer (CRC) cells, enhances the efficacy of BH3 mimetics and inhibits clonogenicity. [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 339. doi:10.1158/1538-7445.AM2014-339
Abstract 3408: FOXM1 regulates doxorubicin resistance through the non homologous end joining pathway and is associated with recurrence of bladder cancer
Authors: Roh Yun-Gil , Lee Se-Ra , Kim Won-Tae , Kim Seon-Kyu , Chu In-Sun , Leem Sun-Hee 
Published: May 2015

Abstract
Non-muscle invasive bladder cancer (NMIBC) remains a very troublesome cancer to care because of high recurrence rates. In the previous study, we characterized a gene expression dataset from 102 NMIBC patients of the Korean cohort to identify a signature associated with disease recurrence. In recurrent bladder cancers, the expression of FOXM1 (Forkhead Box M1) was increased compared to primary cancers. Although there is a relationship between DNA repair pathway and FOXM1, it remains unclear whether FOXM1 is associated with DNA repair mediated cancer recurrence. To investigate this association, we used five different human bladder cancer cell lines to examine the expression level of FOXM1. Two cancer cell lines (5637 and EJ cells) showed the increased level of FOXM1 than other three cancer cell lines (UC5, LD611 and UC9 cells). We examined the chemoresistance with chemotherapy reagent (Doxorubicin) and checked the possible regulation of DNA repair pathway by FOXM1 in these cell lines. The cell lines which elevated FOXM1 expression showed high expression levels of Non-homologous end joining (NHEJ) pathway genes (Ku70, Ku80, LIG4 and XRCC4). To examine the direct interaction between the FOXM1 and NHEJ pathway genes, the binding activity was checked by a promoter assay and chromatin immunoprecipitation. We revealed that the expression levels of NHEJ pathway genes are elevated on activation of exogenous FOXM1. Therefore, we suggest a novel activity of FOXM1 has a role in cancer recurrence through the NHEJ pathway in bladder cancer cells.
Citation Format: Yun-Gil Roh, Se-Ra Lee, Won-Tae Kim, Seon-Kyu Kim, In-Sun Chu, Sun-Hee Leem. FOXM1 regulates doxorubicin resistance through the non homologous end joining pathway and is associated with recurrence of bladder 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 3408. doi:10.1158/1538-7445.AM2014-3408
Abstract 3417: The genomic landscape of canine melanoma reveals broad mutational heterogeneity and recurrent patterns of structural variation
Authors: Hendricks William P. , Zismann Victoria , Button Berry , Legendre Christophe , Tembe Waibhav , Yin Holly , Bittner Michael , Berry Donald , Huentelman Matthew , Khanna Chand , LoRusso Patricia , Breen Matthew , Sekulic Aleksandar , Trent Jeffrey 
Published: May 2015

Abstract
Despite remarkable therapeutic advances in malignant melanoma, an incomplete understanding of melanoma's extraordinary genetic diversity, complex disease course and ability to resist treatment continues to impede rational, curative clinical intervention. This is particularly true for the understudied “dark matter” of the melanoma genome, i.e. cases that lack mutations in the three most commonly-mutated melanoma genes (BRAF, NRAS, NF1) and that display extensive mutational heterogeneity. Clearly a pressing need exists for transformative approaches to melanoma medicine. We have therefore broadened our traditional focus on melanoma in human patients to include canine melanoma as a model of human disease. Given canine melanoma's clinicopathological resemblance to human non-cutaneous triple-negative subtypes, study of this disease in each species may inform the other. Further, the accelerated clinical course of canine melanoma and flexibility in veterinary clinical trial design may allow for evaluation of novel treatment designs that would not be possible in human cancer trials. Thus, we have undertaken a first-in-dog genomic characterization study of canine melanomas from a cohort of 37 dogs to further explore the landscape of this comparative model. This analysis combines comprehensive genomics (whole genome, whole genome long-insert, RNA sequencing, and array comparative genomic hybridization) in 7 matched canine melanoma/normal tissues with targeted analysis in an additional 27 tumors and 3 cell lines. These canine tumors display striking patterns of mutation and subtype heterogeneity resembling that of their non-cutaneous human counterparts with the majority being BRAF, NRAS, and NF1 wild type and lacking recurrent single nucleotide variants. Despite heterogeneity at the single nucleotide level, shared patterns of structural variation and gene expression exist and these patterns suggest core pathways that may define therapeutic vulnerabilities in these disease subtypes. These data provide the genomic framework for further clinical pursuit of melanoma in the canine model as a paradigm for drug development.
Citation Format: William P. Hendricks, Victoria Zismann, Berry Button, Christophe Legendre, Waibhav Tembe, Holly Yin, Michael Bittner, Donald Berry, Matthew Huentelman, Chand Khanna, Patricia LoRusso, Matthew Breen, Aleksandar Sekulic, Jeffrey Trent. The genomic landscape of canine melanoma reveals broad mutational heterogeneity and recurrent patterns of structural variation. [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 3417. doi:10.1158/1538-7445.AM2014-3417
Abstract 3420: TERT promoter mutations are rare in uveal melanoma
Authors: AMARO Adriana Agnese , Gualco Marina , Dono Maria , Pfeffer Ulrich , Maric Irena , Mosci Carlo 
Published: May 2015

Abstract
Uveal melanoma is the most frequent primary tumor of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight UV-exposure on the etiology of uveal melanoma is matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma. We also analyzed the frequency of other recently discovered uveal melanoma specific mutations in the genes GNAQ, GNA11, BAP1, SF3B1, and EIFAX1, and we analyzed the association of these mutation with histopathological and clinical features including progression free survival. Finally, we analyzed TERT expression in these tumors.
The mutation frequencies observed confirmed the prevalence of GNAQ mutations in cases with disomy of chromosome 3 that have a better prognosis whereas GNA11 was more frequent in monosomic cases. Together these two mutations account for more than 85% of the cases. BAP1 mutations are associated with chromosome 3 monosomy but not with progression free survival. SF3B1 and EIF1AX mutations occur in 10.3 and 22.5% of uveal melanomas, in disomic cases only. We detected a TERT mutation in only one case of a 57-year old white male with clinical and histo-pathological features typical for uveal melanoma. The tumor showed mutations in GNA11 and EIF1AX. No mutations were detected in GNAQ, BAP1, and SF3B1. Both copies of chromosome 3 were retained. Several tumors among which the one carrying the TERT promoter mutation showed elevated TERT expression.
These data indicate that TERT mutations are rare in uveal melanoma, consistent with a reduced etiological influence of sunlight. No conclusion can be drawn on the potential influence of TERT mutations on tumor progression.
Citation Format: Adriana Agnese AMARO, Marina Gualco, Maria Dono, Ulrich Pfeffer, Irena Maric, Carlo Mosci. TERT promoter mutations are rare in uveal melanoma. [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 3420. doi:10.1158/1538-7445.AM2014-3420
Abstract 3428: Validation and utilization of next generation sequencing in the clinical assessment of gliomas
Authors: Nasrallah MacLean P. , Martinez-Lage Maria , Fox Alan , Sukhadia Shrey , Desai Arati , O'Rourke Donald M. , Brem Steven , Roth David , Morrissette Jennifer J.D. , Daber Robert D. 
Published: May 2015

Abstract
Background. Identifying prognostic and potentially therapeutic genetic alterations in gliomas is crucial to improve clinical outcome and guide future targeted therapies in this devastating disease. Here, we establish the feasibility of next generation sequencing (NGS) profiling of glioma samples in a clinical setting.
Methods. We optimized and validated a 47 gene panel for use on both fresh and Formalin Fixed Paraffin embedded (FFPE) tissue specimens in a CLIA-certified laboratory. Validation was performed in 27 samples by comparing mutation detection on two different NGS platforms, and we have since incorporated routine molecular tumor profiling into the standard workup of glioma patients seen at our institution.
Results. From analysis of 120 clinical samples, we found disease-associated changes in 90 patients (75%). Overall 184 changes including disease-associated point mutations and variants of unclear significance were identified across 98 samples, resulting in an average of 1.85 mutations per sample and a range of 1- 6 mutations. This included 49 amplifications across several genes (EGFR, PDGFRA and KIT).
Conclusions. The final validated assay allows for a cost effective and efficient analysis of a spectrum of clinically relevant and actionable biomarkers including point mutations, insertions, deletions and gene amplifications. Given the high fraction of tumors presenting with known disease associated changes, routine genomic profiling has the promise of improving patient outcomes and allow for access to targeted therapies.
Citation Format: MacLean P. Nasrallah, Maria Martinez-Lage, Alan Fox, Shrey Sukhadia, Arati Desai, Donald M. O'Rourke, Steven Brem, David Roth, Jennifer J.D. Morrissette, Robert D. Daber. Validation and utilization of next generation sequencing in the clinical assessment of gliomas. [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 3428. doi:10.1158/1538-7445.AM2014-3428
Abstract 3452: N-glycosylation on lung cancer cell-secreted IL-6 prolongs its activation on JAK/STAT pathway
Authors: Hung Chun-Hua , Yeh Hsuan-Heng , Wang Hao-Chen , Lin Chien-Chung , Tsai Tsung-Lin , Huang Wei-Lun , Chang Chuan-Fa , Su Wu-Chou 
Published: May 2015

Abstract
Interleukin-6 (IL-6) is overexpressed in various cancer cells, intriguingly contributing to both tumor growth and modulating anti-tumor immunity. Cell-type-specific glycosylations on IL-6 have been deduced in early studies; however, the glycosylation pattern and biological function of cancer cell-secreted IL-6 remain unclear. Here, we describe the glycosylation pattern of lung cancer cell-secreted IL-6 and its impact on the activation of JAK/STAT pathway. IL-6 molecules with different molecular weights were detected in the conditional media of IL-6-overexpressed lung cancer cell lines by immunoblot. Because in NetNGlyc 1.0 Server, one possible N-glycosylation site has been predicted at N73 on IL-6, we used treatment of N-glycosylation-specific inhibitors and site-directed mutagenesis on N73 to demonstrate that lung cancer cell-secreted IL-6 is modified by N-glycosylation. To examine which glycotransferases may participate in the modification, we had screened the expression of glycosyltransferases using qPCR and found that the expression of fucosyltransferase 8 (FUT8), responsible for core fucosylation on N-glycosylated proteins, was higher in lung cancer cells compared to normal bronchial cell. We then reduced core fucosylation on lung cancer cell-secreted IL-6 by silencing FUT8 with shRNA transduction. Subsequently, cells were treated with conditional media containing fully-glycosylated or core fucose-depleted IL-6 to uncover the potential influences on cellular signaling from glycosylation on IL-6. The fully-gycosylated IL-6 induced prolonged STAT3Y705 phosphorylation and distinct gene population compared to core fucose-depleted IL-6. The nuclear retention of STAT3 was concordant with the prolonged STAT3 activation in cells treated with fully-gycosylated IL-6. In paired normal (N) and tumor (T) tissues from lung cancer patients, higher FUT8 mRNA was detected in tumor part than normal part. Besides, we found similar glycosylation pattern in the secreted IL-6 of short-term cultured lung cancer cells derived from malignant pleural effusions. Together, we report the presence of specific IL-6 glycoforms secreted from lung cancer cell lines and lung cancer cells from clinical samples. Moreover, the glycosylation on IL-6 changes its activity on the regulation of JAK/STAT pathway.
Citation Format: Chun-Hua Hung, Hsuan-Heng Yeh, Hao-Chen Wang, Chien-Chung Lin, Tsung-Lin Tsai, Wei-Lun Huang, Chuan-Fa Chang, Wu-Chou Su. N-glycosylation on lung cancer cell-secreted IL-6 prolongs its activation on JAK/STAT pathway. [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 3452. doi:10.1158/1538-7445.AM2014-3452
Abstract 3490: Measurement of Gifinitib (ZD1839) effect on electrophysiological properties of head and neck cancer cells using Dielectrophoresis (DEP)
Authors: Mahabadi Sina , Hughes Michael Pycraft , Labeed Fatima Hanna 
Published: May 2015

Abstract
Introduction:
Dielectrophoresis (DEP) is a physical phenomenon which can be used to determine the dielectric properties of the cells through applying a non-uniform electric field. Electrophysiological properties such as the conductivity and permittivity of the membrane and cytoplasm can be determined by this method, which has already been applied in cancer research.
Gifinitib (Iressa) or ZD1839 is one of the most commonly used drugs for treatment of cancer such as breast and head and neck. This drug damages the local tumours through blocking the activity of EGFR (epidermal growth factor receptor) which is one of the most common factors in proliferation of the cancer cells. In this study, the effect of Gifinitib (Iressa) treatment was investigated through analysis of the electrophysiological properties of the HN5 (Head and Neck Carcinoma cells) using a DEPtech 3DEP dielectrophoresis analysis device.
Results:
The cell membrane capacitance for HN5 cells post twenty two hours of drug treatment became substantially lower. Significant changes were also observed in the cytoplasm over the 22-hour period.
Conclusion:
The results indicated a substantial reduction in the membrane parameters of HN5 cells, and these results can be attributed to the interaction between the drug and the EGFR in these cells. DEP appeared to be a reliable method for assessing the action of EGFR inhibitors for drug discovery.
Citation Format: Sina Mahabadi, Michael Pycraft Hughes, Fatima Hanna Labeed. Measurement of Gifinitib (ZD1839) effect on electrophysiological properties of head and neck cancer cells using Dielectrophoresis (DEP). [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 3490. doi:10.1158/1538-7445.AM2014-3490
Abstract 3540: Overexpression of incrna h19 enhances development and metastasis of gastric cancer
Authors: Li Jiangfang , Li Hao , su Liping , Zhu Zheng-gang , Liu Bingya 
Published: May 2015

Abstract
Background: Long non-coding RNAs (lncRNAs) have been shown to play key roles in the progression and metastasis in some carcinomas in recent studies. We found that the expression of long non-coding RNA H19 (H19) was much higher in gastric cancer tissues than that in paired noncanerous tissues. But its mechanism in gastric cancer remains unknown. The object of this study is to explore the role of H19 and it derived miR-675 in gastric cancer and to discover the downstream target genes. Methods: We detected the expression of H19 in 74 gastric tissues together with paired noncancerous tissues and followed-up median 27 months. Then, we investigated the role of H19 and miR-675 by knock-down their expression in MKN45 cell line and ectopic expression in SGC7901 cell line in vitro and in vivo. Finally, we built the co-expression network of H19 and demonstrate the target genes by RIP and DLR. Results: The overall survival (OS) in the patients with low H19 expression (ratio&lt;6) is much longer than that with high H19 expression (ratio≥6). Overexpression of H19 can enhance the characteristics of gastric cancer cells such as proliferation, migration, invasion Tumor formation and metastasis. We built the co-expression network of H19 and demonstrated ISM1 was the binding protein of H19. The expression of ISM1 was positive correlated with that of H19. CALN1 was the target gene of miR-675. The expression of CALN1 was negative correlated with that of miR-675. Conclusion: Overexpression of H19 correlates with bad prognosis in gastric cancer. H19 acts as an oncogene in gastric cancer to enhance the proliferation, migration, invasion, and metastasis. MiR-675 also can enhance gastric cancer progression and metastasis. In additional, H19 RNA is actively bind to protein ISM1 however miR-675 targets the protein CALN1. These suggested that H19 effect on GC both through encoding miR-675 and up-regulation ISM1.
Citation Format: Jiangfang Li, Hao Li, Liping su, Zheng-gang Zhu, Bingya Liu. Overexpression of incrna h19 enhances development and metastasis of gastric 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 3540. doi:10.1158/1538-7445.AM2014-3540
Abstract 3546: Transcriptional activation of Thioredoxin interacting protein by small activating RNA exerts cell growth inhibition in A549 human lung cancer cells
Authors: Park Ki Hwan , Kang Moo-Rim , Han Sang-Bae , Yun Jieun , Lee Chang Woo , Oh Soo Jin , Kim Youngsoo , Kang Jong Soon 
Published: May 2015

Abstract
TXNIP (also known as VDUP1 or TBP-2) has been identified as a tumor suppressor gene (TSG) and downregulated in various solid tumors and hematological malignancies. In recent years, a therapeutic application of small activating RNA for cancer treatment has been suggested. Therefore, we designed small activating RNA targeting TXNIP promoter (hsaTXNIP-834) and investigated the effect of hsaTXNIP-834 on cell growth inhibition in A549 human lung carcinoma. Transfection of hsaTXNIP-834 induced transcriptional activation of TXNIP gene and protein expression in a dose dependent manner in A549 cells. Transfection of hsaTXNIP-834 also stimulated demethylation of CpG island region of TXNIP gene promoter. In addition, hsaTXNIP-834 leaded to cell growth inhibition in a dose dependent manner. Further study demonstrated that hsaTXNIP-834 induces G0/G1 and G2/M phase cell cycle arrest. Moreover, hsaTXNIP-834 induced p53 expression and reduced phosphorylation of RB protein. However, co-transfection of TXNIP or Ago2 siRNA reversed cell growth inhibition by hsaTXNIP-834. Collectively, our results suggest that hsaTXNIP-834 inhibits the growth of A549 lung carcinoma cells by inducing G0/G1 and G2/M phase cell cycle arrest and this is mediated, at least in part, by transcriptional activation of TXNIP by hsaTXNIP-834.
Citation Format: Ki Hwan Park, Moo-Rim Kang, Sang-Bae Han, Jieun Yun, Chang Woo Lee, Soo Jin Oh, Youngsoo Kim, Jong Soon Kang. Transcriptional activation of Thioredoxin interacting protein by small activating RNA exerts cell growth inhibition in A549 human lung 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 3546. doi:10.1158/1538-7445.AM2014-3546
Abstract 4436: Neddylation of ribosomal protein S27-like and RPS27 regulates survival of breast cancer cells
Authors: Zhao Yongchao , Xiong Xiufang , Sun Yi 
Published: May 2015

Abstract
Neddylation plays a distinct role in stabilization of a subset of ribosomal proteins. How ribosomal proteins are neddylated and whether their neddylation plays any biological roles in cell growth and survival remains elusive. Here we report that ribosomal protein S27-like (RPS27L) and its family member RPS27 is subjected to neddylation by MDM2 E3 ubiquitin ligase, and deneddylation by NEDP1. Disrupting neddylation with MLN4924, a newly discovered small molecule inhibitor of neddylation pathway, destabilized RPS27L and RPS27. Moreover, silencing of RPS27L and RPS27 sensitized breast cancer cells to MLN4924-induced apoptosis. Our results suggest that neddylation stabilizes RPS27L and RPS27, and confers the survival of breast cancer cells.
Citation Format: Yongchao Zhao, Xiufang Xiong, Yi Sun. Neddylation of ribosomal protein S27-like and RPS27 regulates survival of breast 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 4436. doi:10.1158/1538-7445.AM2014-4436