bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1763: Activation of p53/miR-34a tumor suppressor network by Chinese herbal recipe JP-1 in human lung cancer cells
Authors: Yao Chih-Jung , Sheng Peter , Hu Tsai-Shu , Wang-Peng Jacqueline , Lai Gi-Ming 
Published: August 2015

Abstract
Non-small cell lung cancer (NSCLC) is one of the most common cancers worldwide. In spite of the recent progress in targeted therapy, most of the patients eventually expired due to the inevitable recurrence and drug resistance. New integrated therapeutics with evidence based molecular mechanism is urgently needed. MiR-34a, a direct target of p53, is a well-characterized tumor suppressor miRNA in a variety of cancers. How to restore the p53/miR-34a regulatory axis has becomes an important novel strategy for cancer therapy. Here, we show that a Chinese herbal recipe JP-1 activates p53/miR-34a tumor suppressor network in human NSCLC A549 cells (p53 wild type). Treatment of A549 cells with JP-1 extract (38% ethanol) induced profound apoptosis accompanied with marked elevation of p53 and its downstream p21 and Bax protein levels. Accordingly, increase of miR-34a was also observed. Analyzing the miR-34a downstream targets in JP-1-treated cells, we found the decrease of survival factors such as Sirt1 and survivn. Nevertheless, JP-1 also decreased Axl, an important invasion-related miR-34a downstream, while increased E-cadherin expression. The JP-1-activated p53/miR-34a tumor suppressor network coincided with mitochondrial-dependent apoptosis induction and EMT (epithelial-mesenchymal transition) inhibition. In agreement with this, JP-1 induced phospho-AMPKα but inhibited phospho-AKT protein level. Our results might interpret the clinical benefit observed in JP-1-treated patients and suggest its potential as a complementary medicine for NSCLC.
Note: This abstract was not presented at the meeting.
Citation Format: Chih-Jung Yao, Peter Sheng, Tsai-Shu Hu, Jacqueline Wang-Peng, Gi-Ming Lai. Activation of p53/miR-34a tumor suppressor network by Chinese herbal recipe JP-1 in human lung cancer cells. [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 1763. doi:10.1158/1538-7445.AM2015-1763
Abstract 1767: Anti-proliferative and anti-invasive action of omega-3 polyunsaturated fatty acids in stomach cancer cells
Authors: Shin Soyeon , Jeong Soyeon , Kim Soyeon , Heo Jun-Young , Kweon Gi-Ryang , Park Seung-Kiel , Park Jong-Il , Lim Kyu 
Published: August 2015

Abstract
The American Cancer Society has been reported that about 22,220 cases of stomach cancer will be diagnosed and about 10,990 patients will die from this type of cancer in 2014. Omega-3 polyunsaturated fatty acids (ω3-PUFA), including docosahexaenoic acid (DHA) have been suggested to have anti-cancer effects by epidemiological and clinical studies. However, their underlying anti-cancer mechanisms are still unclear in stomach cancer. This study was designed to examine the impact of ω3-PUFA on stomach cancer and the molecular mechanism of their action. DHA reduced cells viability in a dose- and time-dependent manner in human stomach cancer cells including AGS cells. The DHA-induced cells death was in part due to apoptosis, since the cells exhibited increases of apoptotic markers including cleaved PARP and TUNEL-positive cells. DHA also led to autophagic vesicle formation an increase levels of lipidated form LC3B and stimulated the autophagic flux, indicating the involvement of both apoptosis and autophagy in the cytotoxic effect of stomach cancer cells by ω3-PUFA. Moreover, AGS stable cell expressing the ω3-desaturase (fat-1) gene (AGS-fsc) or control vector stable cell (AGS-csc) were eatablished, and the effect of endogenous high level of ω3-PUFA was investigated in AGS cells. The cell proliferation, invasion and colony-formation were inhibited in AGS-fsc compared to AGS-csc. Taken together, these results indicate that ω3-PUFA induce anti-cancer action is related to anti-proliferation and anti-invasive action in stomach cancer cells. Thus, utilization of ω3-PUFA may represent a promising therapeutic approach for chemoprevention and treatment of human stomach cancer. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2014R1A1A2008915) and by the Korea government(MSIP) (No. 2007-0054932)]
Citation Format: Soyeon Shin, Soyeon Jeong, Soyeon Kim, Jun-Young Heo, Gi-Ryang Kweon, Seung-Kiel Park, Jong-Il Park, Kyu Lim. Anti-proliferative and anti-invasive action of omega-3 polyunsaturated fatty acids in stomach cancer cells. [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 1767. doi:10.1158/1538-7445.AM2015-1767
Abstract 1777: The characterization of the effects of the strigolactones on the heat shock response
Authors: Wang Victor S. , Kyin Nu Nu , Pollock Claire , Lee Hyjoung , Li Xin , Prandi Cristina , Kapulnik Yoram , Koltai Hinanit , Whitesell Luke , Yarden Ronit 
Published: August 2015

Abstract
Strigolactones (SLs) are a novel class of plant hormones that inhibit the self-renewal of undifferentiated meristem cells in shoots regulating above-ground plant architecture. Data from our lab have shown that SL analogues are able to inhibit the growth and survival of a wide array of cancer-derived cell lines including: prostate, colon, lung, breast and osteosarcoma (U2OS) while minimally affecting cultured normal cells. Treatment of cancer cells with SL analogues leads to the activation of stress-related signaling including p38MAPKs and JNK1/2, as well as the activation of the heat shock master regulator, heat shock transcription factor 1 (HSF1), and heat shock response (HSR) gene expression. We further show that SLs generate reactive oxygen species (ROS) and that SL treatments of cancer cells leads to the activation of GRP78, the master regulator of the unfolded protein response (UPR). To further characterize the relationship between SLs, HSR and UPR, several clones of HSF1 shRNA knockdown, in U2OS cells were generated and are currently being studied. Interestingly, while wild type mouse embryonic fibroblast (MEF) cells are refractory to SLs treatments, we demonstrate that HSF1 knockout in MEFs enhances the sensitivity of the cells to SLs treatments. Taken together, our data suggest that the HSR and UPR are recruited as cell survival mechanisms against the SLs treatments, giving rise to possible future chemotherapeutic combinatorial treatment options.
Citation Format: Victor S. Wang, Nu Nu Kyin, Claire Pollock, Hyjoung Lee, Xin Li, Cristina Prandi, Yoram Kapulnik, Hinanit Koltai, Luke Whitesell, Ronit Yarden. The characterization of the effects of the strigolactones on the heat shock response. [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 1777. doi:10.1158/1538-7445.AM2015-1777
Abstract 1799: Mithramycin A as a radiation sensitizer
Authors: Scroggins Bradley T. , Burkeen Jeffery F. , Chung Eun Joo , White Ayla O. , Chung Su I. , Hudak Kathryn E. , Citrin Deborah E. 
Published: August 2015

Abstract
Introduction: Radiation therapy (RT) is used in the treatment of many cancers to reduce or eliminate tumor burden. In many cases RT is not curative and recurrence often occurs. Therefore agents that enhance the effectiveness of RT are necessary to improve cancer management. We investigated the use of the DNA binding antibiotic mithramycin A as a radiosensitizer of solid tumors. Mithramycin A binds to GC rich regions of double stranded DNA displacing transcription factors, such as SP1. Mithramycin A has also been shown to inhibit DNA double strand break repair by mechanisms unrelated to its effect on transcription.
Methods: Human cancer cells (A549/lung, HT29/colon, DU145/prostate, and UM-UC3/bladder) were grown at 37°C and 5% CO2 in RPMI1640 media. Cells were treated with 25 nM mithramycin A 1 hour prior to radiation and then allowed to grow for 7-10 days after RT. Clonogenic colonies were counted to determine the effect of mithramyicn A on radiation sensitivity. The effects of mithramycin A treatment and RT on DNA damage repair was measured by counting nuclear gamma-H2AX foci and neutral Comet assay. Cell cycle changes induced by mithramycin A and RT were measured by flow cyctometry. Mitotic catastrophe was analyzed by nuclear fragmentation. In vivo radiosensitzation of mithramycin A (1mg/kg) was quantified using growth delay of A549 tumor xenografts in both single dose (4 Gy) and fractionated RT (4x 2Gy) dosing schedules.
Results: Mithramycin A treatment of cell lines in vitro prior to RT increased radiosensitivity with a range of dose modifying factors between 1.17-1.48. DNA damage repair after RT was not affected by mithramycin A treatment. Cell cycle distribution was altered by mithramycin A treatment with fewer cells in S-phase after treatment. Mitotic catastrophe after combined treatment with mithramycin A and RT was significantly elevated above the level of either agent alone. In vivo A549 tumor xenografts treated with both mithramycin A and a single dose RT had more than an additive growth delay compared to either agent alone.
Conclusion: Mithramycin A treatment sensitized human cancer cells to radiation therapy in in vitro assays and an in vivo model system through an increase in mitotic catastrophe. A more detailed analysis of the mechanism of action is ongoing.
Citation Format: Bradley T. Scroggins, Jeffery F. Burkeen, Eun Joo Chung, Ayla O. White, Su I. Chung, Kathryn E. Hudak, Deborah E. Citrin. Mithramycin A as a radiation sensitizer. [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 1799. doi:10.1158/1538-7445.AM2015-1799
Abstract 18: Prohibitin 1 regulates apoptosis via its interaction with XIAP
Authors: Xu Yingjie , Yang Wen , Guarani Virginia , Shi Jinjun , Harper J. Wade , Zetter Bruce R. 
Published: August 2015

Abstract
Prohibitin 1 (PHB1) belongs to an evolutionarily highly conserved family of proteins that share the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain. PHB1 has been implicated in the regulation of diverse cellular processes, including cell-cycle progression, transcriptional regulation, apoptosis, mitochondrial biogenesis, and as a cell-surface receptor. To better understand the function of PHB1, we analyzed PHB1 protein interactors using Immunoprecipitation followed by mass spectrometry analysis (IP-MS). We identified the X-linked inhibitor of apoptosis protein (XIAP) as a novel PHB1-binding partner. The interaction of PHB1-XIAP has been confirmed both in vitro and in vivo. Using immunofluorescence staining, We observed that PHB1 and XIAP colocalized upon induction of apoptosis. Using various XIAP mutant constructs, we showed that PHB1 binds principally to the BIR3 domain of XIAP. In addition, silencing of either PHB1 or XIAP sensitized cells to chemotherapeutic drug-induced cell apoptosis and partially rescued the chemosensitivity of resistant cancer cells. The observation that PHB1 silencing decreased XIAP levels with a concomitant increase in XIAP cleavage suggests that the formation of a PHB1-XIAP complex inhibits apoptosis by enhancing XIAP stability. Our findings indicate that the PHB1-XIAP complex promotes an anti-apoptotic response in cancer cells and reinforces the potential of PHB1 as a therapeutic target.
Citation Format: Yingjie Xu, Wen Yang, Virginia Guarani, Jinjun Shi, J. Wade Harper, Bruce R. Zetter. Prohibitin 1 regulates apoptosis via its interaction with XIAP. [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 18. doi:10.1158/1538-7445.AM2015-18
Abstract 1807: Nuclear targeted gold nanoparticles for radiation enhancement
Authors: Hainfeld James F. , Smilowitz Henry M. 
Published: August 2015

Abstract
Gold nanoparticles (AuNP) have been shown to enhance radiation dose (Hainfeld et al, 2004) resulting in significant improvement in tumor control (Hainfeld et al 2008, 2010, 2012). AuNPs that target nuclear DNA have the potential to greatly improve such radiation dose enhancement due to the utilization of the cascade of low energy Auger electrons that follow x-ray absorption. If the AuNP binds to the DNA, these high LET electrons should greatly augment double strand breaks and tumor cell killing. While positively charged peptides are known to take NP into the cell nucleus, they are expensive and subject to proteolytic degradation. We reasoned that just putting a positive charge on the AuNP might mimic enhanced cellular uptake, endothelial escape and nuclear translocation. Such three nm AuNPs had high cell uptake but were retained in the endosome with none getting into the nucleus whereas one nm positively charged AuNPs were found in the cell nucleus and nuclear membrane as well as the cytoplasm as evidenced by light and electron microscopy. Nuclear-localized positively charged AuNPs were found predominantly over regions of heterochromatin. Cells incubated with positively charged AuNPs in vitro and then irradiated showed an increased number of H2AX binding sites as evidenced by fluorescence. Cell metabolism assays using MTT, a surrogate for cell viability, performed one, two and three days following radiation therapy, showed that cells irradiated after loading with positively charged, nuclear targeted AuNPs manifested some decrease in cell viability.
Citation Format: James F. Hainfeld, Henry M. Smilowitz. Nuclear targeted gold nanoparticles for radiation enhancement. [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 1807. doi:10.1158/1538-7445.AM2015-1807
Abstract 1824: Predictive value of neutrophil-lymphocyte ratio for the efficacy of preoperative chemotherapy in triple-negative breast cancer
Authors: Asano Yuka , Kashiwagi Shinichiro , Morisaki Tamami , Noda Satoru , Kawajiri Hidemi , Takashima Tsutomu , Onoda Naoyoshi , Hirakawa Kosei 
Published: August 2015

Abstract
Purpose: Abnormalities in the subpopulations in white blood cells, such as neutrophilia and lymphopenia, have been reported in tumor-bearing patients, and the neutrophil/ lymphocyte ratio (NLR) has been found to associate with prognosis in patients following radical surgery. The NLR was reported to associate with prognosis in cancer patients by influencing both cancer progression and chemosensitivity. The correlation between NLR and the outcome of neoadjuvant chemotherapy (NAC) in breast cancer patients has not been elucidated yet. The aim of this study is to evaluate NLR as one of the possible markers to predict the outcome of NAC in patients with TNBC by a retrospective investigation of the consecutive patient series treated with a standardized single protocol in our institute.
Experimental Design: NLR was evaluated in a total of 177 patients with early-stage breast cancer treated with NAC consisting FEC (5-fluorouracil, epirubicin, and cyclophosphamide) followed by weekly paclitaxel followed by curative surgery. The correlation between NLR and the prognosis including the efficacy of the NAC was evaluated retrospectively. NLR was calculated from the preoperative blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. On the basis of previous studies, an NLR value of 3.0 was used as the cut-off value to discriminate between high-NLR (3.0 and over) and low-NLR (less than 3.0) groups.
Results: NLR distributed from 0.5 to 10.6 with a median of 2.0. Fifty-eight patients with low NLR (less than 3) had a higher pCR rate (p&lt;0.001), and more frequently diagnosed to have TNBC (p&lt;0.001) compared with those with high NLR (3 and over). Among TNBC patients who achieved pCR, DFS (p = 0.006) and OS (p&lt;0.001) were significantly longer in patients with low NLR than that with high NLR. Low NLR was associated with a significantly favorable prognosis in TNBC patients who achieved pCR, according to univariate analysis (p = 0.044, HR = 0.06).
Conclusions: Low NLR in patients with TNBC could be expected to show high efficacy, and favorable outcome after NAC.
Citation Format: Yuka Asano, Shinichiro Kashiwagi, Tamami Morisaki, Satoru Noda, Hidemi Kawajiri, Tsutomu Takashima, Naoyoshi Onoda, Kosei Hirakawa. Predictive value of neutrophil-lymphocyte ratio for the efficacy of preoperative chemotherapy in triple-negative breast cancer. [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 1824. doi:10.1158/1538-7445.AM2015-1824
Abstract 183: Oncogenic miRNA miR-130a-induced inhibition of the growth regulator protein ZAR2 in TNBC cells
Authors: Misra Smita , Snghal Ashutosh , Chaudhuri Gautam 
Published: August 2015

Abstract
ZAR2 is C4-type zinc-finger protein that we found to suppress the growth of breast tumor cells. In the dividing breast cancer cells ZAR2 is primarily located in the cytosol. It probably inhibits the growth of the tumor cells through sequence-specific capture and degradation of certain mRNAs which are critical for the growth of the cells. We found that the level of ZAR2 protein is significantly lower in the highly aggressive breast cancer cells of the triple negative subtype (TNBC). Forced expression of ZAR2 in the TNBC cells prevented the proliferation and invasiveness of these cells. Major objective of the research presented here is to understand the mechanism of suppression of ZAR2 level in the TNBC cells. As ZAR2 mRNA levels are very similar in the TNBC and non-TNBC cells, we postulated that ZAR2 protein levels are down-regulated in the TNBC cells due to the induction of a ZAR2-targeting miRNA in these cells. We used computational prediction to identify potential microRNAs down-regulating ZAR2 in the TNBC cells. One of the major miRNAs that is predicted by DIANA-Tools (http://diana.imis.athena-innovation.gr/DianaTools/index.php?r = MicroT_CDS/index) to target ZAR2 mRNA is hsa-miR-130a-5p. We found that the level of miR-130a-5p in the TNBC cells is inversely related to the level of ZAR2 protein in the TNBC cells. We validated the binding of miR130a-5p miRISC to several specific locations at the 3′-UTR of ZAR2 mRNA and the inhibition of translation of ZAR2 mRNA by this miRNA. We propose that targeted knockdown of miR130a-5p in the TNBC cells will elevate the level of ZAR2 protein resulting in the inhibition of the growth of these cells. This research is supported in part by NIH/NCIgrant1R21CA181920-01 to GC and NIH grant 1U54RR026140 to SM.
Citation Format: Smita Misra, Ashutosh Snghal, Gautam Chaudhuri. Oncogenic miRNA miR-130a-induced inhibition of the growth regulator protein ZAR2 in TNBC cells. [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 183. doi:10.1158/1538-7445.AM2015-183
Abstract 1830: Untargeted metabolomics reveals smokers’ characteristic profiles
Authors: Hsu Ping-Ching , Lan Renny S. , Brasky Theodore , Marian Catalin , Cheema Amrita K. , Ressom Habtom W. , Loffredo Christopher A. , Pickworth Wallace , Shields Peter G. 
Published: August 2015

Abstract
Introduction. Smoking-related biomarkers for lung cancer and other disease risks are needed to enhance early detection strategies and to provide a science base for FDA decision making for the regulation of tobacco products. Methods. An untargeted metabolomics approach was used in a cross-sectional study of smokers (n = 112) where subjects smoked 2 cigarettes one hour apart, and blood was collected immediately before and after each cigarette. The global metabolomic profiles from the two blood samples were determined using UPLC-Q-TOF/MS (n = 448 assays). The study design allows for the direct detection of smoking-related effects since each subject served as his/her own control. Results were analyzed by using a false discovery rate q value &lt;0.05. Results. Pair-wise comparisons of pre- and post-cigarettes showed 24 features (metabolites) significantly changed due to smoking. The analysis identified important changes in menthol-glucuronide (p = 6.99E-10) and endogenously occurring metabolites including glutamate and glycerophospholipids. Menthol-glucuronide was positively correlated with glutamate, and negatively correlated with oleamide, lysoPC(16:1(9Z)), and an unknown metabolite with m/z of 517.31+ (p &lt; 0.01), implying a menthol specific effect. Some shared and different metabolites were found by race and gender. Pathway analysis revealed smoking-related effects on carbohydrate metabolism, lipid metabolism, and small molecule biochemistry. Network analysis revealed eleven molecules involved in cancer, notably inhibition of cAMP. Conclusions. This first time identification of a menthol metabolite in blood samples from smokers serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers. This study also identified several endogenous non-smoke metabolites not previously related to smoking carcinogenesis that may serve as biomarkers of exposure and/or effect (e.g., glutamate), and provides new biological insights for the effects of tobacco smoke on cellular functions.
Citation Format: Ping-Ching Hsu, Renny S. Lan, Theodore Brasky, Catalin Marian, Amrita K. Cheema, Habtom W. Ressom, Christopher A. Loffredo, Wallace Pickworth, Peter G. Shields. Untargeted metabolomics reveals smokers’ characteristic profiles. [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 1830. doi:10.1158/1538-7445.AM2015-1830