bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5196: Histologic and whole slide quantitative image analysis of lung metastases in a mouse breast cancer model using carboplatin and Nutlin 3A alone and in combination
Authors: Strack Margaret , Tonsing-Carter Eva , Sinn Tony , Spragin Tiaishia , Peterson Kacie , Bailey Barbara , Pollok Karen , Sandusky George 
Published: August 2015

Abstract
Breast cancer will affect 1 in 8 women in their lifetime. Approximately 20-30% of all breast cancer cases become metastatic. This study was designed to evaluate the effect of tumor met knockdown with individual and combination drug therapy. In this mouse model, with 3 per group, we used the following chemotherapeutic agents: a vehicle control, carboplatin (20mg/kg i.p.), Nutlin-3a (200mg/kg p.o.) and a combination group with the same doses. Nutlin-3 is a small-molecule inhibitor that binds to the p53-binding pocket of MDM2, and activates the p53 pathway. This has been shown to be effective in mouse models of cancer that have a wild-type p53, including prostate, leukemia and multiple myeloma.
The lungs were removed and examined for metastatic lung lesions, fixed in 10% neutral buffered formalin (NBF), processed into a paraffin block, microtomed, and slides were stained with H&E. Ki67 immunostain was performed to clearly define the met lesions and the whole slide was imaged with an Aperio Digital Imaging System. The Image Scope positive pixel algorithm was used to quantitate the met lesions in the lungs. The data revealed upon drug treatment the number of mets in the lungs were unchanged in the carboplatin and nutlin-3a individual treatment groups compared to the vehicle group. The lungs in the combination group had the lowest number of tumors with both visual and quantitative image analysis compared to the vehicle control group.
The Aperio automated positive pixel count for Ki67 immunostain was consistent with the H&E pathology read. The values decreased with combination treatment (control vs. combination 20mg/kg carboplatin, 200mg/kg nutlin 3a) and were 6% and 1.7% respectively.
It was concluded that mice treated with carboplatin and Nutlin-3a combination therapy had fewer metastatic breast cancer mets in the lungs. The individual drug doses were low compared to previous studies and did not have an effect as was expected. This finding suggests that the combination of a traditional chemotherapy with a small protein inhibitor could inhibit the spread of metastatic breast cancer.
Citation Format: Margaret Strack, Eva Tonsing-Carter, Tony Sinn, Tiaishia Spragin, Kacie Peterson, Barbara Bailey, Karen Pollok, George Sandusky. Histologic and whole slide quantitative image analysis of lung metastases in a mouse breast cancer model using carboplatin and Nutlin 3A alone and in combination. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5196. doi:10.1158/1538-7445.AM2015-5196
Abstract 5202: Magnolin suppresses cell migration by abrogation of ERK-mediated RSK2/NF-κB signaling pathway
Authors: Lee Cheol-Jung , Lee Mee-Hyun , Song Ji-Hong , Yoo Sun-Mi , Cho Yong-Yeon 
Published: August 2015

Abstract
Our previous study demonstrated that RSK2 directly phosphorylated IκBα at ser 32, resulted in its degradation which leads to promote NF-κB activation and might be an important role in metastasis. Therefore, it is reasonable the discovery of chemotherapeutic and/or chemopreventive agent. Magnolin, an ingredient of magnolia species, suppressed EGF-induced neoplastic cell transformation by targeting of ERK 1 and 2. In this study, we found that magnolin inhibited cell migration and invasion of normal cell and human lung cancer cells. Further, we demonstrated that magnolin suppressed epidermal growth factor-induced ERK/RSK2 signaling pathway, resulting in suppression of NF-κB activity in JB6Cl41 cells. The EGF-induced NF-κB activity was abrogated up-regulation of COX-2 mRNA expression and COX-2 protein levels by co-treatment of EGF and magnolin. Interestingly, magnolin suppressed ERK-mediated MMP-2 and NF-κB-mediated MMP-9 expression. In addition, we found that the protein expression of N-cadherin involved in metastasis was markedly attenuated upon treatment with magnolin. Notably, magnolin suppressed the migration and invasion of lung cancer cells in a dose-dependent manner. Taken together, these results demonstrated that magnolin is beneficial for the anti-invasion and -migration in cancer metastasis.
Citation Format: Cheol-Jung Lee, Mee-Hyun Lee, Ji-Hong Song, Sun-Mi Yoo, Yong-Yeon Cho. Magnolin suppresses cell migration by abrogation of ERK-mediated RSK2/NF-κB signaling pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5202. doi:10.1158/1538-7445.AM2015-5202
Abstract 524: Assessing the interaction between acetylenic tricyclic bis-(cyano enone) and cysteine residues of actin to inhibit non-small cell lung cancer cell migration
Authors: Chan Eddie , Saito Akira , Honda Tadashi , Di Guglielmo John 
Published: August 2015

Abstract
During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their cell-cell junctions, apical-basal polarity, and reorganize their actin cytoskeleton. These changes, among others, increase the motility of individual cells and promote a highly invasive phenotype. The actin cytoskeleton is also key in cell migration and invasion, as the polymerization of actin at the leading edge provides the necessary driving force for translocation and protrusions. Therefore, the actin cytoskeleton is a potential target for inhibiting tumour progression. In this study we characterized a novel tri-cyclic synthetic triterpenoid derivative, TBE-31, in its ability to associate with actin and inhibit cell migration. Using a pull-down approach, we demonstrate that TBE-31 binds directly to actin. Furthermore, TBE-31 inhibited branched and linear actin polymerization in vitro, and stress fibre formation in cultured cells. Actin cytoskeleton reorganization and stress fiber formation was also inhibited in TGFβ-dependent EMT of non-small cell lung cancer cells. We next used SwissDock software to investigate the potential molecular interaction between TBE-31 and actin. Swissdock predicted that TBE-31 would have a high affinity for binding to the same cleft as Cytochalasin D, a bona-fide actin polymerization inhibitor. As triterpenoids associate with cysteine residues in target proteins, we generated cysteine to alanine mutants of actin and verified TBE-31 binding using pull-down assays. Finally, we observed that TBE-31 inhibited fibroblast and non-small cell lung tumor cell migration with an IC50 of 1.0 and 2.5 μM, respectively. Taken together, our results suggest that TBE-31 targets actin polymerization to alter cell morphology and inhibit cell migration.
Citation Format: Eddie Chan, Akira Saito, Tadashi Honda, John Di Guglielmo. Assessing the interaction between acetylenic tricyclic bis-(cyano enone) and cysteine residues of actin to inhibit non-small cell lung cancer cell migration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 524. doi:10.1158/1538-7445.AM2015-524
Abstract 528: PP4C plays a braking role in Akt-driven cancer migration/invasion
Authors: Ho Ming-Yi , Liang Shu-Mei , Liang Chi-Ming 
Published: August 2015

Abstract
Treatment of lung cancer cells with growth factors and PGE2 activates phospho-AktS473 to transiently up-regulate phosphorylation of IKK and NF-κB within 1 hour, resulting in the elevation of cellular COX-2/PGE2, E-cadherin suppressor Snail and epithelial-mesenchymal transition (EMT) 24-31 hours later. In this study, we further found that in the cells treated with PGE2 or growth factors, the activated phospho-AktS473 declined to basal level 2 hours after treatment and increased again to reach a plateau 24-31 hours later but this resurgence of phospho-AktS473 was no longer associated with phosphorylation of IKK and NF-κB. To identify which factors or proteins cause dephosphorylation of IKK and NF-κB during phospho-AktS473 resurgence, we used immunoprecipitation, immunoblotting and activity assay approaches. Our results showed that during 12-31 hours of PGE2 treatment, the activity of protein phosphatase (PP) 4C and its association with IKK was increased. In comparison, there was no association between PP1, PP2A and PP5 with IKK. PP4C knockdown in PGE2 treated lung cancer cells increased their IKK/IκB/NF-κB signaling leading to the sustainment of COX-2 and Snail for much longer time. Knockdown of PP4C also increased the cellular EMT, migration and invasion of the lung cancer cells significantly. These findings demonstrated that PP4C downregulates IKK/IκB/NF-κB signaling to play a braking role in the Akt-driven lung cancer migration/invasion.
Citation Format: Ming-Yi Ho, Shu-Mei Liang, Chi-Ming Liang. PP4C plays a braking role in Akt-driven cancer migration/invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 528. doi:10.1158/1538-7445.AM2015-528
Abstract 5282: A 3q amplification gene signature associated with triple negative breast cancer lung-specific metastasis
Authors: Qian Jun , Chen Heidi , Massion Pierre P. 
Published: August 2015

Abstract
Triple negative breast cancers (TNBC), devoid of expression of the estrogen, progesterone and HER2 receptors, are among the most aggressive and deadly breast cancers, with high rates of tumor recurrence and metastatic spread. New prognostic markers are needed to identify patients who are at the highest risk for developing metastases, which might assist in tailoring treatment strategies. We previously identified 20 candidate driver genes in Chromosome 3q26-29, a critical amplified region in many human cancers including breast and lung cancer. The aim of this study was to assess the prognostic power of this 20-gene signature in TNBC patients. 855 breast tumors combined from four breast cancer cohorts (GSE12276, GSE2603, GSE2034 and NKI295) were used to evaluate the signature for prediction of organ-specific distant metastasis free survival (DMFS). The predictive ability of the 20-gene signature was evaluated by Cox proportional hazards model and was compared against other published breast cancer gene signatures including MammaPrint (70-gene), Veridex (76-gene), PAM50, 54 lung metastasis signature genes, HIF1 hypoxia pathway (8-gene), TGF β pathway (153-gene), BACH1 pathway metastasis gene signature (25-gene) and Gene Expression Prognostic Index Using Subtypes (GENIUS). The 20-gene signature was strongly associated with worse lung-specific metastasis-free survival (HR, 2.0, 95%CI, 1.4 to 2.87, P=0.00014) in TNBC patients (n = 131), independently of intrinsic subtype or published gene signatures and less so in non-TNBC patients (n = 724, HR, 1.3, 95%CI, 1.01 to 1.69, P=0.04). In conclusion, we discovered an amplified 20-gene signature in 3q26-29 that are associated with lung metastasis in patients with TNBC, suggesting on a potential role of 3q genes in the mechanism of lung-specific metastasis and incriminating cancer driver genes in this location as potential attractive novel therapeutic targets in this disease. The work is supported by the NIH Grant R01 CA102353 to PPM.
Citation Format: Jun Qian, Heidi Chen, Pierre P. Massion. A 3q amplification gene signature associated with triple negative breast cancer lung-specific metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5282. doi:10.1158/1538-7445.AM2015-5282
Abstract 5286: Expression of cancer type amino acid transporter LAT1 is a prognosis prediction factor in breast carcinoma: comparison between triple-negative and non-triple-negative types
Authors: Ichinoe Masaaki , Mikami Tetsuo , Hana Kiyomi , Yanagisawa Nobuyuki , Endou Hitoshi , Okayasu Isao , Murakumo Yoshiki 
Published: August 2015

Abstract
Purpose: Amino acid transporters play important roles in cell survival and proliferation. L-Type amino acid transporter 1 (LAT1) is one of the major Na+-independent neutral amino acid transporters. LAT1 has an aspect of oncofetal protein. Recently, high levels of LAT1 expression have been reported in various tumors, such as prostate cancer, pancreas cancer, bile duct cancer, lung cancer and stomach cancer.We revealed LAT1 expression is an independent prognosis marker in stomach cancer, prostate cancer and pancreas cancer. The purpose of the present study was to investigate the LAT1 expression in breast carcinoma and relationship between LAT1 expression and prognosis.
Materials & Methods: We enrolled 290 patients with invasive breast carcinoma surgically resected between 2006 and 2010 at Kitasato University Hospital and Toho University Omori Medical Center, Japan. We investigated LAT1 expression in the enrolled breast carcinoma cases by immunohistochemical staining. All cases were divided into two groups, 78 cases of triple negative carcinoma (TNBC) and 212 cases of non-triple negative carcinoma (NTNBC), with immunohistochemistry of estrogen and progesterone receptors and Her2. After LAT1 expression was compared between TNBC and NTNBC, correlations among LAT1 expression, Ki-67 labeling index (LI), CD98 expression, and clinicopathological findings was assessed.
Results: TNBC showed significantly higher LAT1 expression than NTNBC. TNBC also showed significantly higher CD98 expression rather than NTNBC. LAT1 expression of extraductal invasive cancer cells was significantly higher than those of intraductal carcinoma cells. A significantly positive correlation was observed between LAT1 expression and CD98 expression. Further, a positive correlation between LAT1 expression and Ki-67 LI was found. Log-rank test in overall breast cancers revealed that high LAT1 expression group showed significantly poor prognosis, compared to low LAT1 group. In NTNBC, high LAT1expression cases possessed poorer prognosis than low LAT1 expression cases.
Conclusion: In invasive ductal carcinoma of breast, LAT1 expression has a potential for a prognosis prediction factor. LAT1 offers a potential target for anti-cancer therapy by its inhibitor JPH203 which has been developed by us.
Citation Format: Masaaki Ichinoe, Tetsuo Mikami, Kiyomi Hana, Nobuyuki Yanagisawa, Hitoshi Endou, Isao Okayasu, Yoshiki Murakumo. Expression of cancer type amino acid transporter LAT1 is a prognosis prediction factor in breast carcinoma: comparison between triple-negative and non-triple-negative types. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2015-5286
Abstract 5290: Identification of novel prognostic genes associated with risk of recurrence in early breast cancer patients
Authors: Kwon Mi Jeong 
Published: August 2015

Abstract
Introduction : In order to determine the need for adjuvant chemotherapy in early estrogen receptor-positive breast cancer, especially luminal A, it is important to identify patients at high risk of recurrence. This study was performed to identify novel prognostic genes associated with the recurrence risk of patients with lymph node-negative luminal A (LN−/LumA) breast cancer.
Methods : RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. The expression levels of 16 candidate genes identified from our previous study were measured using quantitative real-time reverse transcription-PCR in 926 FFPE samples. We used Cox proportional hazards models to assess the prognostic value of clinical and gene variables for recurrence.
Results : Of the 796 patients with recurrence-free survival (RFS) and 826 patients with overall survival (OS), 24.4% (194/796) and 24.0% (198/826), respectively, had LN−/LumA breast cancer. Univariate analysis showed that clinical variables such as tumor size, involvement of lymph nodes, and tumor stage were not significantly associated with RFS and OS of patients with this subtype. In contrast, there was a significant association between gene expression and patient outcomes. Higher expression of 4 proliferation-related genes (F4, M4, R3, and U4) was significantly correlated with shorter OS and RFS. Importantly, in multivariate analyses, high expression of R3 and U4 remained significantly associated with RFS. While not significantly related to RFS in univariate analysis, immune response-related B5 expression had a significantly lower harzard ratio in the multivariate analysis (P = 0.004), indicating it was an independent positive prognostic factor. Higher expression of M4 (P = 0.014) and R3 (P = 0.01) was independently associated with shorter OS. When tested using gene variables, prognostic models for risk of recurrence included M4, R3, U4, and B5. Moreover, patients with low B5 and high U4 expressions had a significantly shorter RFS than those with high B5 and low U4 expressions.
Conclusions : Novel prognostic genes identified in our study give more significant information on the risk of recurrence than clinical variables in patients with LN−/LumA breast cancer. Multigene expression signatures, including immune response-related genes, can be used to identify patients at high risk of recurrence in this subtype of breast cancer.
Citation Format: Mi Jeong Kwon. Identification of novel prognostic genes associated with risk of recurrence in early breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5290. doi:10.1158/1538-7445.AM2015-5290
Abstract 5304: A serum protein test for improved prognostic stratification of patients with myelodysplastic syndrome (MDS)
Authors: Roder Joanna , Löffler-Ragg Judith , Stauder Reinhard , Germing Ulrich , Sperr Wolfgang R. , Valent Peter , Roder Heinrich , Steingrimsson Arni , Zwierzina Heinz 
Published: August 2015

Abstract
While existing scoring systems provide physicians with methods of assessing prognosis of patients with MDS and help with the choice of appropriate treatment regimens, some patients defined as lower risk still have poor outcomes and tests which can refine current stratifications are of clinical interest.
Serum samples, clinical and survival data were available from 106 MDS patients with refractory anemia (RA) (n = 46), RA with excess blasts (n = 29), RA with ring sideroblasts (n = 14), and chronic myelomonocytic leukemia (n = 17). The international prognostic scoring system (IPSS) score distribution 0/0.5/1/&gt;1 was n = 36/23/24/12. Matrix assisted laser desorption/ionization (MALDI) mass spectra were acquired from the samples using the deep MALDI method1, allowing a deep probing of the proteome. The spectra were preprocessed and spectral features defined. The integrated intensities of these features were combined with the survival data using deep learning based machine learning techniques to create classifiers able to stratify patients into groups with better and worse survival.
Patients in the good prognosis group had median survival of 52 months, compared with 23 months in the poor prognosis group (hazard ratio = 0.37, p &lt; 0.001). Within the subgroup of patients with refractory anemia (n = 46) it was possible to identify a group of patients with no death events before 30 months, while median survival in the other patients was only 25 months. Multivariate analysis stratified by MDS subtype found that the mass spectral (MS) classification was a significant independent predictor of survival even when adjusted for international prognostic scoring system (IPSS) score and cytogenetic status. MS classification was able to separate low to intermediate risk (IPSS 0-1) and good karyotype subgroups into groups with significantly better and worse survival.
If validated in an independent dataset, this serum test would provide complementary information for physicians to consider in addition to existing scoring systems to aid in planning treatment for MDS patients.
1. M Duncan et al, Proceedings of the 61st ASMS Conference on Mass Spectrometry and Allied Topics. Minneapolis, MN June 8-9, 2013 MP 181.
Citation Format: Joanna Roder, Judith Löffler-Ragg, Reinhard Stauder, Ulrich Germing, Wolfgang R. Sperr, Peter Valent, Heinrich Roder, Arni Steingrimsson, Heinz Zwierzina. A serum protein test for improved prognostic stratification of patients with myelodysplastic syndrome (MDS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2015-5304
Abstract 531: lncRNA profiling and its potential usage as thyroid cancer biomarker
Authors: Tian Song , Rulli Samuel , Fahey Thomas J. , Lader Eric 
Published: August 2015

Abstract
Thyroid nodules are detected in as high as 67% of the population. Distinguishing thyroid cancers from benign lesions is crucial for determining appropriate and timely treatment. Fast and accurate detection using a simple screening method could greatly contribute to minimizing unnecessary surgery while increasing the accuracy of cancer detection. Several long non-coding RNAs (lncRNAs) have been linked to cancer development as either oncogenes or tumor suppressors, and their potential use as cancer biomarkers has been suggested. Unfortunately, limited analyses have been performed on the expression of lncRNA in thyroid cancer. Here, we explored the possible use of lncRNA as a specific thyroid cancer biomarker. The expression of 84 human cancer-related lncRNAs were evaluated in RNA samples from 9 thyroid cancer (PTC and FVPTC) patients and 13 non-cancer controls (NH and FA) with a simple real-time RT-PCR strategy. PTCSC1, an lncRNA previously linked to thyroid cancer, was found to be down regulated in patient 3.4 fold (p&lt;0.005). In addition, we observed dysregulation of other lncRNA such as BANCR (down 3 fold, p&lt;0.005) and SNHG16 (down 2 fold, p&lt;0.005). We next used the lncRNA expression data for signature panel development to classify benign and malignant thyroid patient tissue samples. With a random forest classification model, a fine tuned classification signature of 16 target genes was reasonably successful (Accuracy 95%, sensitivity 92%, PPV = 90% and NPV = 100%). Our results suggested that in addition to the role that lncRNA plays in thyroid cancer, analysis of lncRNA expression represents a promising path towards a simple test for thyroid cancer detection.
Citation Format: Song Tian, Samuel Rulli, Thomas J. Fahey, Eric Lader. lncRNA profiling and its potential usage as thyroid cancer biomarker. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 531. doi:10.1158/1538-7445.AM2015-531