bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5095: Biochanin A, a natural isoflavone inhibits angiogenesis in glioma.
Authors: Jain Aditi , Lai James C.K. , Bhushan Alok 
Published: August 2014

Abstract
Malignant gliomas like glioblastoma multiforme are the most lethal form of adult brain tumor. Patients with this disease survive for only 12-15 months after diagnosis. Angiogenesis, a process of formation of new blood vessels is a pathological hallmark of glioblastoma and plays an important role in tumor growth and survival. Although angiogenesis holds promise as a drug target, recent studies have highlighted that glioblastoma acquires aggressive invasive characteristics when treated with anti-angiogenic monotherapy. Therefore, there is an urgent demand for therapies which effectively target angiogenesis and limit invasion in glioblastoma. Previously, our laboratory has found that biochanin A, a dietary isoflavone inhibits invasion in human glioblastoma cells. In this study, we determined the effects of biochanin A on brain tumor angiogenesis using rat brain tumor cells (C6) and endothelial (bEnd.3) cells. Our cell survival data indicate a dose dependent decrease in cell survival of both C6 and bEnd.3 cells treated with biochanin A (5μM-70μM) for 72 hours. Biochanin A also inhibited ERK and AKT pathway in these cells. Zymography invasion assay demonstrated a decrease in enzymatic activity of MMP's in biochanin A treated C6 and bEnd.3 cells. Apart from these signaling molecules, angiogenesis is also driven by hypoxia through upregulation of hypoxia inducible factor (HIF-1α) which releases vascular endothelial growth factor (VEGF), a key player of angiogenesis. We found that biochanin A at 35 μM inhibited protein expressions of both HIF-1α and VEGF in C6 cells treated with cobalt chloride, a chemical inducer of hypoxia. Biochanin A was also effective in inhibiting angiogenesis in an ex vivo chick chorioallantoic membrane model. These findings indicate that we may use biochanin A as a dual targeted agent that inhibits two processes, invasion and angiogenesis at similar concentrations. Thus, our study will allow the formulation of new and improved therapies for glioblastoma and ultimately enhance patient survival. (This study was supported by NIH INBRE grant #P20R16454, University Research Committee grant and Mountain States Tumor and Medical Research Institute grant).
Citation Format: Aditi Jain, James C.K. Lai, Alok Bhushan. Biochanin A, a natural isoflavone inhibits angiogenesis in glioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5095. doi:10.1158/1538-7445.AM2013-5095
Abstract 5102: Analysis of CTCs enriched from whole blood samples of Breast, Lung and Colorectal cancer patients with a flexible microspring array device.
Authors: Harouaka Ramdane , Zhou Ming-Da , Yeh Yin-Ting , Truica Cristina , Das Avisnata , Kaifi Jussuf , El-Deiry Wafik , Liu Xin , Belani Chandra , Baney Tara , Allerton Jeffrey , Zheng Si-Yang 
Published: August 2014

Abstract
The process by which metastatic cancers release cells that detach from a primary tumor, spread through the circulatory system and invade distant organs accounts for over 90% of cancer related deaths. A fundamental challenge with analysis of these circulating tumor cells (CTCs) in blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. We have developed a flexible micro spring array (FMSA) that employs mechanical separation to effectively enrich CTCs in a nondestructive manner that does not compromise cell viability. The FMSA device geometric design and applied filtration pressures have been optimized to maximize capture efficiency, enrichment against leukocytes, and tumor cell viability. We have successfully enriched and detected varying numbers of CTCs (min=1, max=101) in 7.5mL whole blood samples obtained from Breast, Lung and Colorectal cancer patients. CTCs were analyzed qualitatively and quantitatively based on immunocytochemical determination of phenotype and cell morphological characteristics. Aggregate clusters of cells were observed in all assayed cancer types that comprised of multiple attached CTCs (min=2, max=20) and occasionally leukocytes as well.
Citation Format: Ramdane Harouaka, Ming-Da Zhou, Yin-Ting Yeh, Cristina Truica, Avisnata Das, Jussuf Kaifi, Wafik El-Deiry, Xin Liu, Chandra Belani, Tara Baney, Jeffrey Allerton, Si-Yang Zheng. Analysis of CTCs enriched from whole blood samples of Breast, Lung and Colorectal cancer patients with a flexible microspring array device. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5102. doi:10.1158/1538-7445.AM2013-5102
Abstract 5131: Modeling of EMT/MET transitions in breast cancer stem cells.
Authors: Sehl Mary E. , Shimada Miki , Lange Kenneth , Wicha Max S. 
Published: August 2014

Abstract
Background: Recent studies suggest that breast cancer stem-like cells (BCSCs) exist in two freely interconvertible states: an EMT- and an MET-like state, and that conversion between these two states is regulated by both intracellular and microenvironmental signaling (Liu et al. 2012, Korkaya et al. 2012). Using a mathematical model, we quantify rates of transition between the EMT and MET-like states. We further explore BCSC behavior in response to alterations in microenvironmental signaling and examine key regulators of BCSC population dynamics.
Methods: We employ a continuous-time Markov chain model to quantify rates of transition between the EMT and MET-like state for BCSCs. Our data-based modeling approach employs parameter estimates derived from mouse xenograft experiments from the Wicha laboratory (Liu et al. 2012) to estimate the equilibrium EMT- and MET-like state distributions. We expand our model to simulate BCSC population counts and EMT and MET state transitions in response to alterations in the complex regulatory network involving IL-6, HER2, miRNA, NF-κB, and TGF-β signaling.
Results: We estimate the rate of BCSC transition from an EMT- to MET-like state to be 0.08 per cell per day, and the rate of transition from an MET- to EMT-like state to be 0.013 per cell per day. Simulation studies examining the effects of abrogating microenvironmental signals individually and in combinations revealed that slowing both self-renewal rate and the rate of transition from an MET- to EMT-like state is essential to eradicating the total BCSC population. The fastest decline in the BCSC population was observed when IL-6 is inhibited and the activation of NF-κB via HER2 signaling and IL-6 feedback was blocked.
Conclusions: Rates of transition between EMT- and MET-like states are estimated to occur frequently and these events are much more likely than dedifferentiation. Predictions from our mathematical model match experimental data (Korkaya et al. 2012) showing the efficacy of combined HER2 and IL-6 blockade in reducing the BCSC population.
Citation Format: Mary E. Sehl, Miki Shimada, Kenneth Lange, Max S. Wicha. Modeling of EMT/MET transitions in breast cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5131. doi:10.1158/1538-7445.AM2013-5131
Abstract 5132: Interactively exploring patterns in TCGA data: a web-based compendium of ‘next-generation’ clustered heat maps.
Authors: Weinstein John N. , Kane David W. , Akbani Rehan , Dodda Deepti , Nguyen Lam , Ryan Michael C. , Wakefield Chris , Broom Bradley M. 
Published: August 2014

Abstract
Each of the 5 TCGA marker paper published in Nature to date has included at least one clustered heat map (CHM). We introduced CHMs in the early 1990’s for pharmacogenomic analysis (1) and later for integrated visualization of genomic, transcriptomic, proteomic, pharmacological, and functional data (1). As the ubiquitous first-order way of visualizing omic data, CHMs have appeared in many thousands of publications (3–9), including those from TCGA. We have elsewhere summarized their limitations (10).
One such limitation is that CHMs are generally static images. We therefore initiated the next-generation CHM (NG-CHM) project, using an image-tiling technology similar to that in Google Maps for navigation and extreme drill-down without loss of resolution. Once the CHM has been zoomed sufficiently, labels (e.g., gene, protein, or drug names) appear on the image's axes. Clicking on a label produces a menu of link-outs (e.g., to GeneCards, Google, PubMed). For gene vs. gene maps, each pixel can represent a color-coded Pearson correlation coefficient. Clicking on the pixel pulls up the corresponding data scattergram, bootstrap statistics, literature references, or pathway relationships. Strong usability features include floating windows, flexible search tools, cluster selection tools, customizable re-coloring of the CHM, and high-quality PDF's suitable for publication. NG-CHMs are a major resource for exploratory analysis and visualization in multiple projects of TCGA and other large-scale molecular profiling programs. Explore interactive versions for TCGA breast, colorectal, lung squamous, and glioblastoma data at http://bioinformatics.mdanderson.org/main/TCGA/NGCHM.
Supported in part by NCI Grant No. U24CA143883, by a gift from the Mary K. Chapman Foundation, and by a grant from the Michael and Susan Dell Foundation honoring Lorraine Dell.
Citation Format: John N. Weinstein, David W. Kane, Rehan Akbani, Deepti Dodda, Lam Nguyen, Michael C. Ryan, Chris Wakefield, Bradley M. Broom. Interactively exploring patterns in TCGA data: a web-based compendium of ‘next-generation’ clustered heat maps. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5132. doi:10.1158/1538-7445.AM2013-5132
Abstract 5156: Upstream activation of PTEN.
Authors: Naguib Adam , Bencze Gyula , Faehnle Christopher R. , Schalch Thomas , Lazar Zsolt , Ruse Cristian I. , Joshua-Tor Leemor , Pappin Darryl J. , Trotman Lloyd C. 
Published: August 2014

Abstract
The PTEN tumor suppressor is among the most frequently altered genes of cancer. PTEN suppression at the protein level is critically associated with disease since PTEN is haploinsufficient in many cancer types, including prostate. We have recently shown strong cooperation between protein phosphatases and PTEN to suppress PI 3-Kinase and AKT signaling in prostate cancer. Intriguingly, our findings showed that PTEN status orchestrates a PHLPP2 response by controlling the protein levels of this phosphatase.
Yet, little is known about genes that control the levels and activity of PTEN to a degree that they critically maintain its function in disease. Therefore, it is assumed that PTEN is constitutively active in normal cells.
Here we identify the upstream activation mechanism of PTEN and discuss the consequences for cancer diagnosis and therapy with PI 3-Kinase pathway inhibitors.
Citation Format: Adam Naguib, Gyula Bencze, Christopher R. Faehnle, Thomas Schalch, Zsolt Lazar, Cristian I. Ruse, Leemor Joshua-Tor, Darryl J. Pappin, Lloyd C. Trotman. Upstream activation of PTEN. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5156. doi:10.1158/1538-7445.AM2013-5156
Abstract 5171: FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes p53-dependent checkpoint response.
Authors: Li Zheng , Yan Shuangshuang , Qiu Li , Zhang Jun , Ma Ke , Zhang Xifeng , Hao Xishan 
Published: August 2014

Abstract
Ubiquitin linkage is critical in directing the cellular fate of a ubiquitinated protein. Although K48-linked polyubiquitination of p53 leads to its degradation, whether polyubiquitination of p53 has a positive role in its activation remains unknown. Here, we show that FATS, a cancer-associated gene susceptible to DNA damage, acts as a p53 activator through binding to p53 and polyubiquitnating p53. Knockdown of FATS impairs p53 activation in response to DNA damage. Moreover, FATS is a unique ubiquitin ligase (E3) that assembles non-linear ubiquitin chains through K11-, K29- and K63-linkages, independently of ubiquitin-conjugating enzyme (E2). The expression of NH2-terminal FATS is sufficient to polyubiquitinate and stabilize p53, which is associated with increased transcriptional activity of p53 and stronger effect on p53-mediated cell cycle arrest. Importantly, FATS-catalyzed polyubiquitination of p53 is required for robust activation of p53 upon DNA damage. Our findings uncover a new mechanism of p53 activation in response to DNA damage and establish the functional linkage between non-linear polyubiquitination and checkpoint response.
Citation Format: Zheng Li, Shuangshuang Yan, Li Qiu, Jun Zhang, Ke Ma, Xifeng Zhang, Xishan Hao. FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes p53-dependent checkpoint response. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5171. doi:10.1158/1538-7445.AM2013-5171
Abstract 5182: MSP58 regulates telomerase activity and cell proliferation via interaction with TEIF.
Authors: Hsu Che-Chia 
Published: August 2014

Abstract
Telomerase expression is essential for cell proliferation and survival, which also plays a role in development, senescence and cancer. In our previous studies, we demonstrated that ectopic expression MSP58 regulates cell proliferation in context-dependent manner and induces premature senescence in HT1080 cells and normal human diploid fibroblasts through p53/p21 senescence pathway. In addition, we also demonstrated that MSP58 overexpression significantly suppressed telomerase activity in HT1080 cells. Currently, we identified a novel MSP58 interacting protein, TEIF (Telomerase transcription element-interacting factor) by yeast-two hybrid screening. TEIF has been reported to up-regulate the hTERT gene expression and telomerase activity. Interestingly, we found that MSP58 represses the TEIF-mediated activation of telomerase. Furthermore, overexpression of MSP58 represses TEIF promoted anchorage-independent growth in HT1080 cells. In contrast, knockdown MSP58 expression increases TEIF promoted anchorage -independent growth in HT1080 cells. These results suggest that MSP58 regulates telomerase activity via interaction with TEIF and contributes to control cell proliferation.
Citation Format: Che-Chia Hsu. MSP58 regulates telomerase activity and cell proliferation via interaction with TEIF. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5182. doi:10.1158/1538-7445.AM2013-5182
Abstract 5187: The membrane traffic regulator PACS-1 mediates genome stability at S-phase of the cell cycle.
Authors: Veena Mysore S. , Basak Saroj K. , Venkatesan Natarajan , Zinabadi Alborz , Thomas Laurel , Thomas Gary , Srivatsan Eri S. 
Published: August 2014

Abstract
We previously mapped a 5.5 kb homozygous deletion in cervical cancer cell lines and primary tumors to chromosome 11q13 within the 1st intron of PACS-1 gene, which encodes a membrane traffic regulator. This deletion correlates with elevated expression of 120 kDa PACS-1 in primary cervical tumors compared to normal tissues as well as the expression of a 140 kDa immunoreactive isoform in the nucleus specifically in cervical cancer cell lines. Inspection of the PACS-1 mRNA sequence revealed a target site for miR449a, which mediates cell fate. Northern blot analysis showed miRNA 449a expression was reduced in cervical cancer cell lines and primary tumors suggesting that dysregulation of miRNA449a or the intronic deletion contributed to aberrant PACS-1 expression and that the increased expression of PACS-1 may mediate cell viability and cell cycle progression. Consistent with this possibility, siRNA knockdown of PACS-1 or increased expression of miR449a caused cells to accumulate in S phase and induced expression of γH2AX. By contrast, overexpression of PACS-1 or expression of antimiR 449a reduced γH2AX expression. Whereas PACS-1 mediates secretory pathway trafficking, the effect of PACS-1 expression on genome stability suggested PACS-1 might shuttle between the cytoplasm and the nucleus to mediate genome stability. Consistent with this possibility, the PACS-1 sequence contains canonical NLS and NES motifs. Indeed, confocal microscopy studies revealed GFP-tagged PACS-1 accumulated in the nucleus in a leptomycin B-dependent manner. We hypothesize that aberrant expression of PACS-1 in cervical cancer cells results in the stabilization and replication of rearranged DNA sequences leading to tumor development.
Citation Format: Mysore S. Veena, Saroj K. Basak, Natarajan Venkatesan, Alborz Zinabadi, Laurel Thomas, Gary Thomas, Eri S. Srivatsan. The membrane traffic regulator PACS-1 mediates genome stability at S-phase of the cell cycle. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5187. doi:10.1158/1538-7445.AM2013-5187
Abstract 519: Attenuation of mammary tumor growth by gap junction enhancer.
Authors: Shishido Stephanie N. , Nguyen Thu A. 
Published: August 2014

Abstract
Normal cells have functional gap junctional intercellular communication (GJIC), while cancer cells exhibit many defects in cellular communication that contribute to the loss of tissue homeostasis. It is believed that restoring GJIC is linked to drug sensitivity and reduction of tumorigenicity. Previous studies show that GJIC and neoplastic cellular growth are inversely related and small molecule targeting gap junction can alter tumor growth. A dose of 25 mg/kg gap junction enhancer (PQ) can cause a 77% decrease of xenograft T47D breast tumors. In addition these small molecules can induce a decrease of tumor growth by 110%, 129%, and 73% in the pre, early, and late stages of tumor development of the transgenic mouse strain, FVB/N-Tg(MMTV-PyVT)634Mul/J. Western blot analysis shows that the gap junction protein, Cx43, was highly expressed in the PQ-treated tumors compared to the controls. Data suggests that enhancement of GJIC attenuates tumor growth; specifically Cx43 plays a significant role in tumorigenesis. Establishment of a continuous line of mammary tumor cells from the malignant neoplasm of a female transgenic mouse demonstrates that PQs can cause an increase of Cx43 expression and subsequently trigger a decrease of cell viability. Overall, targeting gap junction by small molecule PQ has shed light to the dynamic of connexins and gap junctions in mammary tumors.
Citation Format: Stephanie N. Shishido, Thu A. Nguyen. Attenuation of mammary tumor growth by gap junction enhancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 519. doi:10.1158/1538-7445.AM2013-519
Abstract 5194: Pim2 is required for maintaining Multiple Myeloma cell proliferation through modulating mTORC1 pathway.
Authors: Lu Jing , Zavorotinskaya Tatiana , Dai Yumin , Niu Xiaohong , Castillo Joseph , Sim Janet , Yu Jianjun , Shannon Kevin , Garcia Pablo 
Published: August 2014

Abstract
Multiple Myeloma (MM) is the second most common hematological malignancy. Despite the advances of therapeutic regimens over the last decade, nearly all patients eventually relapse, highlighting the need for additional therapeutic agents. Pim kinases, a family of serine/threonine kinase, are reported to be oncogenic and required for the maintenance of hematological malignancies. Here, consistent with previous reports, we show that Pim2 kinase expression is most highly elevated in MM. Importantly, shRNA knockdown of Pim2 leads to a significant inhibition of MM cell growth, suggesting that Pim2 is critical in maintaining MM malignancy. We developed a potent and specific small molecule inhibitor for the Pim kinases. Inhibition of Pim2 by this molecule suppresses
MM cell growth. We find that Pim inhibitor treatment results in the suppression of cell proliferation, but not induction of apoptosis, in all MM cell lines tested. Further, we identified mTORC1 signaling, which is critical for cell proliferation, as significantly repressed by Pim2 inhibition. The two major mTORC1 downstream effectors: P70S6K and 4EBP1 are rapidly dephosphorylated upon Pim inhibitor treatment of MM cells. We are currently investigating the potential signaling modules that may mediate Pim2’s regulation on mTORC1 pathway. Taken together, our findings strongly support
Pim2 as a promising therapeutic target in MM, given its distinct expression in
MM and essential role in maintaining proliferation.
Citation Format: Jing Lu, Tatiana Zavorotinskaya, Yumin Dai, Xiaohong Niu, Joseph Castillo, Janet Sim, Jianjun Yu, Kevin Shannon, Pablo Garcia. Pim2 is required for maintaining Multiple Myeloma cell proliferation through modulating mTORC1 pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5194. doi:10.1158/1538-7445.AM2013-5194