bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1921: The effect of Hoechst 33342 and Hoechst 33258 on side population (SP) cells or stem cell-like population
Authors: Tang Naimei , Zhang Crystal , Noraian Cyndi , Wali Anil , Pass Harvey , Harbut Michael , Zhang Xinbo 
Published: May 2015

Abstract
Hoechst 33342 side population (SP) analysis is widely used for identifying and sorting side population (SP) or stem cell-like population from a variety of tissues and species including cancer cell lines. However, Hoechst 33342, but not its derivative Hoechst 33258, is an apoptotic inducer. Our previous results showed that Hoechst 33342 induced apoptosis in seven mesothelioma cell lines through cytochrome C release, caspase activation and degradation of Poly (ADP-ribose) polymerase. We hypothesize Hoechst 33342 may cause SP cell death during Hoechst 33342 staining and Hoechst 33258 may be a safe indicator for identification and isolation of SP cells.
The aims of this study are 1) to detect the effect of H 33342 on SP cells, and 2) to identify if H33258 can be an indicator for stem cell isolation.
Procedure: The effect of Hoechst dyes on the tumorigenicity of H2373 mesothelioma cells was analyzed by soft agar clonogenic colony formation. MTT assay have been employed to estimate the effect of Hoechst dyes on cell growth in H2373 mesothelioma cells, and Hoechst 33342 and Hoechst 33258 SP analysis was performed on a FACSDiVa cell sorter.
Results: Our result demonstrated that Hoechst 33342 staining can causes SP cell damage and also decreases cell colony formation and cell proliferation after using the routine staining doses and intervals for SP cell analysis. In contrast, Hoechst 33258 has little effect on the cell colony formation and cell proliferation. We have found that verapamil, ABC transporter inhibitor, significantly inhibits the efflux of intracellular Hoechst 33258, which means Hoechst 33258 may be used as a marker in isolating ABC transporter positive cells, as Hoechst 33342 does.
Conclusion: 1) Hoechst 33342 can induce apoptosis of SP cells of mesothelioma cancer cells 2) Hoechst 33258 may be a safe indicator and replace Hoechst 33342 for identification and isolation of side population.
Future Studies: 1) More in vitro methods such as clonogenic assay, drug resistant assay, and invasion assay are required for further determination of stem cell-like properties of side population isolated by Hoechst 33258 when compared to that isolated by Hoechst 33342. 2) Xenograft (or animal) study is ultimately required to determine the capacity of in vivo tumor formation of the side population cells isolated by Hoechst 33258 after the completion of in vitro study
Note: This abstract was not presented at the meeting.
Citation Format: Naimei Tang, Crystal Zhang, Cyndi Noraian, Anil Wali, Harvey Pass, Michael Harbut, Xinbo Zhang. The effect of Hoechst 33342 and Hoechst 33258 on side population (SP) cells or stem cell-like population. [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 1921. doi:10.1158/1538-7445.AM2014-1921
Abstract 1934: Role of CDK1 in human stem cell biology
Authors: Wang Xiao Q. , Chen Lin , Norbury Chris 
Published: May 2015

Abstract
Self-renewal and pluripotency of stem cells (SC) is maintained by well-characterized transcriptional factors that assemble a core regulatory network, although less defined auto- and cross-regulatory signaling pathways are also critical. Accumulating evidence indicates that cell cycle regulators play an important role in control of pluripotency and differentiation that goes beyond their roles in cell cycle regulation. Cyclin-dependent kinase 1 (CDK1) is essential for cell cycle progression and embryonic development, and has recently been implicated in a signaling network with pluripotency proteins.
In this study, we investigated the potential role of CDK1 in regulation of pluripotency and differentiation. CDK1 expression is enriched in the pluripotent state of human embryonic stem cells (hESCs) and down regulated during differentiation. shRNA knockdown of CDK1 or a selective CDK1 inhibitor (RO-3306) promoted hESC differentiation, shown by the reduced expression of the pluripotency markers Oct4, Nanog, and Sox2, and the up-regulation of the mesendoderm transcripts Brachyury, Eomes, Goosecoid, and MixL1. Interestingly, down-regulation of CDK1 by both shRNA and RO-3306 could not block ES cells at G2/M or other phases of the cell cycle, suggesting that relatively milder knockdown of CDK1 did not induce hESC cell cycle arrest or impair overall proliferation but was enough to promote differentiation. Knockdown of CDK1 also decreased phosphorylation of Akt at Thr308 and Ser473, one of the key regulators of pluripotency signaling. Further, JNJ-770621, a dual inhibitor of CDK1/CDK2 and Aurora kinases but not Akt or Erk, induced human embryonal carcinoma cell (NCCIT) differentiation accompanied by reduced phosphorylation of Akt. Addition of UO126 and SB431542, which inhibit MEK/ERK and TGFβ/Smad2/ respectively (downstream of PI3K/Akt signaling), reversed the differentiation induced by shCDK1 or RO-3306 treatment. Moreover, phosphorylation of PDK1 (upstream of Akt) was notably reduced in CDK1 knockdown cells but not in serum-induced differentiation, indicating that the inhibition of activation of PDK1 or Akt could be the primary effect of CDK1 down-regulation. The results suggest that threshold levels of CDK1 might direct- or cross-regulate key signaling pathways, such as that operating through PI3K-PDK1-Akt.
In summary, CDK1 is required for maintenance of stem cell pluripotency, in a manner that is distinct from its role in regulation of cell cycle progression, potentially through direct or indirect cross-regulation of fundamental pluripotency signaling of PI3K/PDK1/Akt-ERK-GSK3β and TGFβ/Smad.
Citation Format: Xiao Qi Wang, Lin Chen, Chris Norbury. Role of CDK1 in human stem cell biology. [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 1934. doi:10.1158/1538-7445.AM2014-1934
Abstract 1944: Divergent effects of BRAF activation in neural stem and progenitor-like glioblastoma cells
Authors: Lerner Robin G. , Ihara Yuichiro , Lewis Kate , Griveau Amelie , Reichhold Brian , Qu Dian , McMahon Martin , Rowitch David , James Charles D. , Petritsch Claudia 
Published: May 2015

Abstract
Glioblastoma multiforme (GBM) are heterogeneous tumors that are refractory to radiation and traditional chemotherapeutics. Separate studies have identified populations of neural stem and progenitor -like GBM cells, however the contribution of these cells types to tumor progression and the response to targeted therapy are poorly understood. Small molecules (such as vemurafenib) targeting the most common MAPK-activating mutation, BRAFV600E, are currently entering clinical trials for treatment of high-grade glioma. Understanding the contribution of different cell types to treatment responses will be necessary for the design of effective adjuvant therapeutic strategies.
We show that activating MAPK pathway gene mutations in GBM correlate with elevated expression levels of oligodendrocyte precursor (OPC) and neural stem cell (NSC)-associated genes. Cells expressing CD133 and NG2 coexist in human GBM and BRafV600E expressing mouse neurosphere cultures, and maintain some of their respective neural stem and progenitor-like properties.
In isogenic mouse cells expressing BRafV600E, NG2+ cells expand rapidly and symmetrically, while rates of asymmetric division are unaffected in slow-proliferating CD133+ cells. Tracing of proliferation rate with the membrane-associated dye PKH-26 reveals heterogeneity in the proliferation rate of CD133+ cells, but not proliferative NG2+ cells. BRAF-targeted inhibition of human GBM cells with PLX4720, the tool compound of vemurafenib, reduces S-phase entry of NG2+ cells, yet CD133+ cells are less affected. Interestingly targeted inhibition of components of the asymmetric division machinery selectively disrupts G2-M progression in CD133+ cells. The functionally divergent populations of CD133-expressing NSC-like cells will likely be therapeutically problematic with mono-therapeutic approaches. These data point to a differential regulation of key cell cycle processes between CD133+ stem-like cells and NG2+ OPC-like cells, that will inform the intelligent design of compound treatment strategies.
Note: This abstract was not presented at the meeting.
Citation Format: Robin G. Lerner, Yuichiro Ihara, Kate Lewis, Amelie Griveau, Brian Reichhold, Dian Qu, Martin McMahon, David Rowitch, Charles D. James, Claudia Petritsch. Divergent effects of BRAF activation in neural stem and progenitor-like glioblastoma 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 1944. doi:10.1158/1538-7445.AM2014-1944
Abstract 1946: Inhibition of IKK/NF-κB impairs glioma stem cell function
Authors: Rinkenbaugh Amanda L. , Cogswell Patricia C. , Baldwin Albert S. 
Published: May 2015

Abstract
Glioma, the most frequently occurring primary brain tumor, has a median survival of less than 15 months, despite multimodal treatment combining surgery, radiation, and chemotherapy. It has been suggested that the presence of cancer stem cells (CSCs) within these tumors are responsible for resistance to treatment and high probability of recurrence. As a result, there is increasing interest in specifically targeting CSCs with new therapies to improve treatment of this disease. NF-κB has been implicated in numerous forms of cancer, as its target genes regulate hallmarks of cancer such as cell proliferation, survival, and invasion. Both glioma cell lines and tumor samples show high levels of phosphorylated p65, a marker of NF-κB activation. When comparing populations from tumor explants, NF-κB is preferentially activated in the CSC subset. We are examining the effects of IKK/NF-κB inhibition on both heterogeneous glioma explants and purified (CD133+) CSCs from these explants. Inhibition of NF-κB through either genetic or pharmacological means abrogates neurosphere formation, an in vitro measure of stem cell function. Additionally, real-time PCR analysis indicates that inhibition of NF-κB leads to a decrease in target genes implicated in glioma CSC biology, such as A20 and IL-6. We have also studied our glioma explants in both subcutaneous and intracranial xenografts to examine the role of NF-κB in vivo. We are utilizing microarrays to define the NF-κB-dependent gene expression signature in CD133+ cells. Our studies indicate a significant role for the NF-κB pathway in the biology of glioma CSCs, with possible parallels in CSCs of other tumor types.
Citation Format: Amanda L. Rinkenbaugh, Patricia C. Cogswell, Albert S. Baldwin. Inhibition of IKK/NF-κB impairs glioma stem cell function. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1946. doi:10.1158/1538-7445.AM2014-1946
Abstract 1953: The role of NR5a2 in pancreas development and carcinogenesis
Authors: Nissim Sahar , Wucherpfennig Julia , Wang Xiao-Xu , Kimmelman Alec , Goessling Wolfram 
Published: May 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers today. A recent genome-wide association study (GWAS) has implicated the nuclear receptor NR5A2 in modulating risk for pancreatic cancer. While a role for this gene in pancreatic cancer has not been previously recognized, it is known to have an important role in stem cell pluripotency and metabolism. Using the zebrafish model organism, we demonstrate that knockdown of nr5a2 results in absence of exocrine pancreas, while leaving endocrine pancreas unaffected, indicating an essential role in pancreas organ formation. Further, we localize expression of nr5a2 to the endodermal bud that gives rise to the exocrine pancreas, consistent with a role for nr5a2 in regulating differentiation of pancreas progenitors. In resected human PDAC specimens and in vitro cell lines, we find that NR5A2 expression is altered compared to normal ductal epithelium. Moreover, shRNA knockdown of NR5A2 dramatically alters proliferation of PDAC cell lines, supporting the hypothesis that NR5A2 is involved in pancreatic carcinogenesis. These data support a model that NR5a2 regulates the proliferation and differentiation of exocrine pancreas progenitor cells during development. Consistent with this model, we find that signaling through nr5a2 interacts with notch activity. We postulate that aberrant expression of NR5a2 results in dysregulation of these processes in the adult pancreas by driving ductal epithelial cells to acquire properties of progenitor cells, and therefore is an important step in pancreas oncogenesis.
Note: This abstract was not presented at the meeting.
Citation Format: Sahar Nissim, Julia Wucherpfennig, Xiao-Xu Wang, Alec Kimmelman, Wolfram Goessling. The role of NR5a2 in pancreas development and carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1953. doi:10.1158/1538-7445.AM2014-1953
Abstract 1980: Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma
Authors: Kasashima Hiroaki , Yashiro Masakazu , Go Yukie , Masuda Go , Kinoshita Haruhito , Tokumoto Mao , Morisaki Tamami , Fukuoka Tatsunari , Toyokawa Takahiro , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Ohira Masaichi , Hirakawa Kosei 
Published: May 2015

Abstract
Object: Lysyl oxidase (LOX) family is the extracellular matrix-modifying enzymes comprising of LOX and LOX-like (LOXL) 1-4. These enzymes have intracellular functions involved in the regulation of motility, migration, differentiation, and transcription in various types of cells. LOX is associated with mesenchymal reconstruction that is essential for cancer invasion and metastasis. LOX overexpression is crucial to promoting tumor growth and metastasis in several cancers such as breast cancer and colorectal cancer, however, role of LOX in gastric cancer remain unknown. Here, we investigated the clinicopathological significance of LOX and LOXL2 in gastric cancer.
Materials and Methods: A total of 549 patients who had undergone surgery for gastric cancer at Osaka-City University were enrolled. LOX and LOXL2 expressions were evaluated by intensity of staining and percentage of stained tumor cells at the invading tumor front. This study was approved by the Osaka City University ethics committee. Informed consent was obtained from all patients.
Results: LOX and LOXL2 expression were positive in 265 (48.3%) and 342 (58.5%) of the 549 gastric tumors. Both LOX and LOXL2 expression in cancer cells were significantly associated with macroscopic type (p&lt;0.01), histological type (p&lt;0.01), depth of invasion (p&lt;0.01), lymph node status (p&lt;0.01), vessel invasion (p&lt;0.01). The prognosis of patients with LOX-positive tumors or LOXL2-positive tumors was significantly (p&lt;0.001 or p&lt;0.001, log-rank) worse than that of patients with LOX-negative or LOXL2-negative tumors, respectively. A multivariate analysis indicated LOX and LOXL2 expression in cancer cells to be an independent prognostic factor (p=0.016 or p&lt;0.001).
Conclusions: LOX and LOXL2 expression might be associated with metastatic activity of gastric cancer cells. LOX and LOXL2 might be useful predictive prognostic factors for patients with gastric cancer.
Citation Format: Hiroaki Kasashima, Masakazu Yashiro, Yukie Go, Go Masuda, Haruhito Kinoshita, Mao Tokumoto, Tamami Morisaki, Tatsunari Fukuoka, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma. [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 1980. doi:10.1158/1538-7445.AM2014-1980
Abstract 1995: The Functional analyses of Oct4 in metastasis of human hepatocellular carcinoma
Authors: Dong Qiongzhu , Dai Chun , Jia Huliang , Qin Lunxiu 
Published: May 2015

Abstract
There is an increasing evidence that in a malignant bulk tumor, a small proportion of ‘cancer stem cells’ exist, leading to tumorigenesis,metastasis or recurrence by their plasticity. However, the functional status and significance of stem cell factors in hepatocellular carcinogenesis is unknown. In this study, we analyzed the expression of 3 stem cell factors: Oct4, Sox2 and Nanog in HCC patients, and found that Oct4 and Sox2, 3 stem cell factors, were expressed in HCCs. Expression of Oct4 correlated with HCC recurrence and metastasis. Through gain- and loss-of-function studies, Oct4 was demonstrated to significantly promote in vitro cell proliferation, invasion, transformation. In addition, Oct4 reduced chemosensitivity of HCC cells. Importantly, Oct4 enhanced in vivo tumor growth and metastasis in nude mice models bearing human HCC. Moreover, Oct4 dramatically stimulated expression of HCC stem cell markers, including Epcam,ELF, KLF4,CD44 and CD133 as well as stem cell signaling pathway (IL-6/surviving, TGF-beta and Wnt / beta-catenin passway). Conclusion: Oct4 plays a critical role in HCC development and progression and its deregulated signaling could be a promising new molecular target for designing novel preventive and therapeutic strategies to control this malignancy
Note: This abstract was not presented at the meeting.
Citation Format: Qiongzhu Dong, Chun Dai, Huliang Jia, Lunxiu Qin. The Functional analyses of Oct4 in metastasis of human hepatocellular carcinoma. [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 1995. doi:10.1158/1538-7445.AM2014-1995
Abstract 1998: Deficient expression of oncogenic Wip1 (PPM1D) negatively regulates melanoma progression and metastasis
Authors: Moon Bo-Hyun , Suman Shubhankar , Li Henghong , Yang Qian , Strawn Steven J. , LoBello Janine , Mazur Sharlyn J. , Appella Ettore , Chen Suzie , Fornace Albert J. 
Published: May 2015

Abstract
PPM1D belongs to the magnesium-dependent serine/threonine phosphatase family. It is well demonstrated that PPM1D amplification and overexpression is a frequent event in many human cancer types; however, its role in melanoma development and metastasis is not yet defined. The objectives of this study were to evaluate the role of Wip1 in melanoma progression and to evaluate correlations between Wip1 expression and clinical pathological parameters, such as grade and metastasis. In order to investigate the role of Wip1 in melanoma progression, we crossed Grm1 transgenic (TG3) mice, a well-characterized mouse model for melanoma, with Wip1 null mice (PPM1D-/-) to generate TG3:PPM1D-/- mice, and observed the rate of spontaneous melanoma formation. Compared with TG3 mice, TG3:PPM1D-/- mice exhibited dramatic reductions in melanoma incidence and metastasis to lymph nodes, lungs, liver and spleen. In addition, in-vitro down-regulation of Wip1 in Mass20 melanoma cells significantly decreased cellular proliferation and migration. Further, human melanoma tissue microarrays (TMAs) were used to determine PPM1D mRNA and protein expression levels in human tumors at different stages of progression. In situ staining of PPM1D mRNA and its corresponding protein Wip1 in human melanoma TMAs revealed higher expression levels in at least ∼50% of the metastatic tumors analyzed.
Overall, our results demonstrate abundant expression of Wip1 in late stage/high grade melanoma and suggest that therapeutic strategies targeting Wip1 in individuals with select tumor subtypes might improve the survival advantage in Wip1-positive melanoma patients. However, further studies are required to elucidate the interactions between Wip1 signaling and established pathways of melanoma progression.
Note: This abstract was not presented at the meeting.
Citation Format: Bo-Hyun Moon, Shubhankar Suman, Henghong Li, Qian Yang, Steven J. Strawn, Janine LoBello, Sharlyn J. Mazur, Ettore Appella, Suzie Chen, Albert J. Fornace. Deficient expression of oncogenic Wip1 (PPM1D) negatively regulates melanoma progression and metastasis. [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 1998. doi:10.1158/1538-7445.AM2014-1998
Abstract 2080: Plasma membrane fluidity drives metastasis in breast cancer
Authors: Zhao Weina , Tisza Michael , Sjol Jessie , Mani Sendurai , Chang Jeffrey T. 
Published: May 2015

Abstract
New therapeutic targets that can inhibit cancer metastasis are desperately needed. To address this issue, we have leveraged a computational approach and performed an unbiased screen for therapies that can inhibit an epithelial-to-mesenchymal transition (EMT) gene expression profile, a phenotype that is believed to promote metastases. This yielded predictions of drugs that can both promote and inhibit an EMT transcriptional profile. Following up on these predictions, we confirmed that these drugs can induce or repress an EMT in a range of breast cancer cell lines. Furthermore, we discovered that they do so by altering the fluidity of the plasma membrane. An increase in plasma membrane fluidity is necessary and sufficient to induce and maintain an EMT state, increased motility, and increased mammosphere forming ability. Finally, we found that human cancers can regulate their membrane fluidity through cholesterol homeostasis pathways. Human breast tumors with altered cholesterol profiles have a significantly shorter time to metastasis. These data demonstrate that plasma membrane fluidity is a cellular attribute that is leveraged by human tumors to increase metastatic capacity, and that it can, in principle, be targeted by therapeutics to prevent metastasis.
Citation Format: Weina Zhao, Michael Tisza, Jessie Sjol, Sendurai Mani, Jeffrey T. Chang. Plasma membrane fluidity drives metastasis in breast 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 2080. doi:10.1158/1538-7445.AM2014-2080