bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1945: Inhibition of PTK6 kinase activity reduces proliferation and migration of tumor cells
Authors: Wang Yan , Malkowski Michael , Jin Weihong , Belanger David , Zeng Hongbo , Curran Patrick J. , Siddiqui M. Arshad , Miao Hua , Shipps Gerald W. , Hailey Judith , Maxwell Eugene , Carr Donna , Seidel-Dugan Cynthia 
Published: August 2014

Abstract
Protein kinase 6 (PTK6) is a member of the Frk family of non-receptor tyrosine kinase that is overexpressed in several types of cancers with the highest overexpression observed in breast tumors. PTK6 shows sequence homology to the src tyrosine kinase family. Its functional domains, including a SH3, a SH2 and a kinase domain, are arranged similarly with src family kinases although PTK6 lacks a myristoylation domain. We have identified a potent small molecule PTK6 kinase inhibitor from kinase cross screens that inhibits PTK6 autophosphorylation and phosphorylation of its substrate Sam68, a member of the KH domain containing RNA binding proteins. In cell culture, the compound inhibited proliferation, soft agar growth and migration of tumor cells. The compound inhibited soft agar growth of breast tumor cells more potently than dasatinib. A specific PTK6 kinase inhibitor may provide a novel approach to inhibit the growth of selected tumors, sensitize the response of the tumor cells to other chemotherapeutics and prevent/inhibit metastasis of cancer in a wide range of cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1945. doi:10.1158/1538-7445.AM2011-1945
Abstract 1946: Detecting protein-protein interactions between MUC16 CDΔ102 (80AA) and a SKOV-3 cDNA library using yeast two-hybrid screening
Authors: Polterauer Stephan , Parlett Ryan , Thapi Dharmarao , Rosales Nestor , Spriggs David R. , Yan Xiu J. 
Published: August 2014

Abstract
MUC16 is a membrane-bound mucin that extends from the surface of ovarian cancer cells. Recent studies suggest that MUC16 influences carcinogenesis and metastasis of ovarian cancer cells. It is expected that protein-protein interactions play a crucial role in MUC 16 signaling and oncogenic transformation.
To define the mandatory molecular partners for MUC16 signaling and transformation, we investigated potential protein binding partners, using a classic yeast two-hybrid screening. The 80AA MUC16-CDΔ102 construct (ectodomain deletion mutant) was cloned into the bait plasmid pGBKT7 and transformed into Y2HGold yeast cells, allowing expression of MUC16-CDΔ102 fused to the Gal4 DNA-binding domain (BD). A SKOV-3 cDNA library was generated and cloned into the prey plasmid pGADT7 and transformed into yeast cells, allowing expression of cDNAs fused to the Gal4 activation domain (AD). Bait and prey yeast cells were allowed to bind to potential partners and bringing the BD and AD into proximity to each other, which then activated transcription of three reporter genes. An array of diploid yeast clones was produced, by co-culturing the two strains overnight, each co-expressing the bait with a different library prey protein. The clone pool was plated on selective media (basic SD-/Trp with Agar) and incubated to screen for individual clones that express the appropriate reporter genes and markers, indicating the presence of interacting hybrid protein pairs. Prey plasmids were then isolated from yeast cells and DNA fragments of the positive clones were amplified by PCR to determine the interacting binding partner.
Seven potential binding proteins (no. of colonies), i.e. TTC1 (4), DARS (1), MAPK1IP1L (1), FAM175B (1), SEPT2 (1), CAMLG (4), and SKAP2 (3), were identified. Protein-complex immuno-precipitation analysis is planned to confirm the interactions between the seven potential binding proteins in human ovarian cancer cell lines, in order to verify that each identified member of the protein complex was a valid identification.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1946. doi:10.1158/1538-7445.AM2011-1946
Abstract 1949: Proliferation of cell lines from pancreatic ductal adenocarcinomas and ductal epithelia are stimulated by acute and chronic exposure to nicotine and ethanol via modulation in neurotransmitter production
Authors: Al-Wadei Mohammed H. , Al-Wadei Hussein A. , Schuller Hildegard M. 
Published: August 2014

Abstract
Pancreatic cancer is the leading cause of cancer mortality in both men and women in western countries due to its unresponsiveness to available therapeutics. It is well documented that smoking, diabetes and pancreatitis from chronic alcohol consumption are risk factors for this type of cancer. More than 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDACs) that arise from pancreatic ductal epithelia. Our lab has previously shown that nicotine stimulates the proliferation and migration of human small airway epithelial cells and the adenocarcinomas derived from them in vitro due to nicotine induced changes in the sensitivity of the nicotinic acetylcholine receptors. Such changes caused an increase in the production and secretion of excitatory neurotransmitters, but decreased the production and secretion of inhibitory neurotransmitter γ-aminobutyric acid (GABA). In analogy to these findings in lung cells, both nicotine and ethanol stimulated cell proliferation in PDAC cell lines Panc-1 and BXPC-3 and in immortalized pancreatic duct epithelial cells HPDE6-C7. Acute and chronic treatment of all cell lines with nicotine or ethanol alone and in combination significantly increased the production of noradrenaline and adrenaline by the cells while significantly reducing GABA production. Western blots are currently underway to assess the potential modulation of nicotinic receptor protein expression as well signaling pathways. Our findings suggest a potential role for these pathways contributing to the development of smoking and alcohol related pancreatic carcinogenesis and may result in the identification of novel targets for the prevention and therapy of this malignancy.
Supported by R01CAo42829 with the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1949. doi:10.1158/1538-7445.AM2011-1949
Abstract 195: Cell death pathway activation during monocytic / macrophagic differentiation of hematopoietic tumor cell lines
Authors: de Séllos João , Caetano Mauricio S. , Carvalho Erika , Amarante-Mendes Gustavo P. , Ferreira Carlos G. , Sternberg Cinthya 
Published: August 2014

Abstract
Apoptosis is a phenomenon of cellular degeneration highly conserved evolutionarily, being observed not only during development, but also associated with a number of diseases. Apoptosis is regulated by a complex set of proteins and accomplished by biochemical mechanisms that act to initiate and complete the destruction of the cell. Recently, typical biochemical and morphological changes associated to cell death were correlated with other vital cellular events, such as proliferation and differentiation. Despite the general tendency to treat apoptosis and cell differentiation as the result of different signaling pathways, several studies have shown that there is a high degree of morphological similarity between these events. The molecules involved in the regulation of apoptosis-like processes of differentiation have not been fully described. Since the main endogenous inhibitor of caspase-3 is the protein XIAP, which in turn is regulated by XAF1, we analyzed the expression of these proteins in the context of differentiation of different cell lines. The objective of this study was to evaluate the activation pathways of cell death in the process of monocytic/macrophage differentiation.
We have observed that the expression of XAF1 protein decreases during monocytic/macrophage differentiation of HL60 cell line induced by PMA, but levels of its mRNA do not change. Interestingly, we have found that HL60 cell lines overexpressing either Bcl-XL or Bcl-2 cell lines have decreased expression of XAF1 due to methylation of its promoter. Also, besides rendering cells resistant to apoptosis as expected, HL60 cells overexpressing either Bcl-XL or Bcl-2 were more prone to differentiate by PMA treatment than parental cells. The correlation between high levels of mRNA expression of Bcl-2 with low expression of XAF1 mRNA was also observed in the analysis of samples from patients with follicular lymphoma retrieved from Oncomine database (www.oncomine.com). These results demonstrate the differential activation of pathways of cell death in monocytic / macrophagic differentiation, suggesting that a descrease in XAF1 expression is a necessary event during this process. Furthemore, our results reveal a transcriptional regulatory loop exerted by Bcl-2 family of proteins that had not yet been described.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 195. doi:10.1158/1538-7445.AM2011-195
Abstract 1950: The effects of combination treatment of NO-donor and MEK inhibitor on proliferation and invasion of cancer cell lines
Authors: Furuhashi Satoshi , Sugita Hiroki , Takamori Hiroshi , Horino Kei , Nakahara Osamu , Okabe Hirohisa , Abe Shinya , Tanala Hiroshi , Beppu Toru , Baba Hideo 
Published: August 2014

Abstract
[Background] Nitric oxide (NO) possesses cytostatic and cytotoxic actions on cancer cells. MAPK and PI3K/Akt signaling pathways, those exist downstream of IGF-IR and EGFR, are two major pathways of oncogenic transformation and tumor maintenance in many kinds of cancer cells. Several studies demonstrated that NO inhibits PI3K/Akt pathway, on the other hand, NO enhances activates MAPK pathway by means of activation of H- and N-Ras. MEK inhibitor blocks MAPK pathway. Hence, we hypothesized that combination of NO-donor and MEK inhibitor inhibits proliferation and invasion of cancer cells in comparison with NO-donor or MEK inhibitor alone. [Methods and Results] We assessed effects of combination of GSNO (NO-donor) and U0126 (MEK inhibitor) on phosphorylation of Akt, and Erk1/2 after stimulation of IGF-I and EGF using Western blotting analyses. Combination of GSNO (500 μM) and U0126 (10 μM) down-regulates phosphorylation of Akt, and Erk1/2 after stimulation of IGF-I (25 nM) and EGF (100 ng/ml) more strongly in comparison with GSNO or U0126 alone in MIAPaCa-2 cells and HCT-116 cells. Combination of GSNO (200, 500 μM) and U0126 (10 μM) also inhibited cell proliferation of MIAPaCa-2 cells and HCT-116 cells more strongly in comparison with NO-donor or MEK inhibitor alone. Furthermore, combination of these compounds inhibited invasion of MIAPaCa-2 cells and HCT-116 cells more strongly in comparison with NO-donor or MEK inhibitor alone in vitro. [Discussion] Recent reports revealed that inhibition of PI3K/Akt or MAPK pathway alone was insufficient to robustly induce tumor shrinkage. It indicated that a feedback pathway between intracellular signalings might be up-regulated, if one main signaling pathway was inhibited. Concomitant inhibition of both PI3K/Akt and MAPK pathway by means of NO-donor and MEK inhibitor could inhibit not only cell growth but also invasion to suppress feedback loops. These results suggest that the combination treatment of NO-donor and MEK inhibitor may be useful for cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1950. doi:10.1158/1538-7445.AM2011-1950
Abstract 1951: Inhibition of aurora kinase using VX-680 enhances the radiation response in glioma cells
Authors: Jane Esther P. , Premkumar Daniel R. , Pollack Ian F. 
Published: August 2014

Abstract
The central role of aurora kinases in cell cycle regulation coupled with overexpression of aurora A and B kinases in a wide variety of human malignancies that led to the development of pharmacological inhibitors of aurora kinases. New generations of aurora inhibitors, including VX-680, has been evaluated preclinically and are in phase I and II trials for the treatment of solid tumors and leukemia. In this study, we investigated the role of VX680, Aurora kinase inhibitor in malignant human glioma cells with different p53 statuses as well as cytotoxicity of glioma cells to irradiation. VX-680 inhibits aurora A and B kinases and cell proliferation with nanomolar to low micromolar potency. Endoreduplication, the re-replication of DNA in the absence of mitotic division, ultimately results in polyploidy and inhibition of cell proliferation. VX680 treatment led to an increase in the number of multinucleated cells and the ratios of G2/M phase in p53-mutant (LN229) and p53-deleted cells (LNZ308), but minimal in p53-wild type (A172) glioma cells. FACS analysis revealed that the increase in nuclear size correlated with polyploidization, reaching a &gt;16 DNA content on day 2. During mitosis, the cells rounded normally, condensed their chromosomes on a metaphase-like plate. Our results demonstrate that pretreating cells with VX-680 prior to ionizing radiation led to an enhancement of radiation -induced apoptosis. Accordingly, our results suggested that Aurora kinase inhibition followed by irradiation increases in the appearance of multinucleated cells and increase apoptosis, and this treatment may become a potential therapy against malignant human gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1951. doi:10.1158/1538-7445.AM2011-1951
Abstract 1958: Glypican-3 (GPC3) modulates senescence, homotypic adhesion and migration of tumor mammary cells through the inhibition of the canonical Wnt pathway
Authors: Lago Huvelle María A. , Buchanan Cecilia , Romero Silvina A. , de Kier Joffé Elisa Bal , Peters María Giselle 
Published: August 2014

Abstract
The Wnt pathway is involved in regulating cell proliferation and differentiation. Alterations of this pathway have been identified as key event in neoplastic development.
Previously, we have demonstrated that the restatement of Glypican-3 (GPC3), a proteoglycan downregulated in breast cancer, is able to induce an inhibition of the canonical Wnt pathway in the murine mammary adenocarcinoma LM3 cells. We also reported that GPC3 reexpression induces an inhibition of the in vivo metastatic capacity and an in vitro reversion of the epithelial to mesenchymal transition (EMT). GPC3 reexpressing clones are less viable in stress conditions, more senescent, more homotypic adherent, less migrants and their actin is mainly localized in cortical position.
The aim of this study was to analyze whether the effects of GPC3 on these cellular parameters are dependent on the inhibition of canonical Wnt pathway. As a strategy, two LM3-GPC3 clones and two LM3-vector ones were treated with LiCl (activator of the Wnt pathway canonical) or NaCl as control. We determined that LiCl was able to partially reverse the LM3-GPC3 cell senescence (X-gal positive senescent cells: LM3-GPC3+NaCl=85% vs +LiCl=65%, ANOVA-Bonferroni p &lt;0.05). In contrast, no changes were observed on the susceptibility to death by serum starving (ANOVA, ns). Although there were no effects on the actin cytoskeleton organization, we established by a wound healing assays that LM3-GPC3 cells treated with LiCl regain their ability to migrate (Wound coverage: LM3-GPC3+NaCl=15% vs +LiCl=75%, ANOVA-Bonferroni p&lt;0.05). Interestingly, LiCl significantly reduced the homotypic adhesion of LM3-GPC3 cells, reaching control levels (ANOVA-Bonferroni p&lt;0.05).
These results suggest that inhibition of the canonical Wnt pathway induced by GPC3 mediates the effects of this glypican on senescence, migration and cell aggregation, while survival and actin cytoskeleton organization would be modulated through other pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1958. doi:10.1158/1538-7445.AM2011-1958
Abstract 1959: Identification of inhibitors specific for torc2 as strategy to overcome feedback erk activation in multiple myeloma cells when treated with second generation mtor inhibitors
Authors: Hoang Bao , Benavides Angelica , Bernath Andrew , Cloninger Cheri , Artinian Nicholas , Bashir Tariq , Gera Joe , Lichtenstein Alan 
Published: August 2014

Abstract
Recent data indicate that the second generation mTOR inhibitor, pp242, which inhibits TORC2 as well as TORC1, is much more effective against multiple myeloma (MM) cells than rapamycin, a first generation inhibitor which only curtails TORC1 activity. A major reason for this improved efficacy may be that pp242 prevents the feedback activation of AKT that results from rapamycin's inhibition of TORC1. It does this by inhibiting TORC2-induced AKT phosphorylation on S473. However, an additional feedback cascade that results from TORC1 inhibition is activation of MEK/ERK. Indeed, our data show that ERK activation is significant in MM cells exposed to either rapamycin or pp242. Pp242 was comparably potent for activating ERK in rictor-knocked down MM cells, supporting the contention that feedback activation was due to TORC1 inhibition. To examine whether this pp242-induced activation of ERK antagonizes pp242's cytotoxic effects, we co-exposed MM cells with pp242 + the ERK inhibitor U0126, using concentrations of the latter that abrogated ERK phosphorylation in pp242-treated MM cells. There was a marked synergistic effect, indicating ERK feedback activation is a mechanism of resistance to pp242. To address this problem, we performed a drug screen in a yeast-two hybrid system to identify compounds that prevented an interaction between rictor and mTOR. Our reasoning was that such an agent could be a specific TORC2 inhibitor without effects on TORC1 and, thus, without induction of feedback ERK activation. We identified several potential compounds and have begun to characterize their molecular activity. One of the most active agents in the drug screen is capable of inducing cytoreduction of MM cells in MTT assays with ED50s of approx 0.7-0.9 uM and significant MM cell apoptosis when used at 1 uM. This cytotoxic effect was accompanied by a down-regulation of TOR activity which was specific for TORC2 (ie., decreased S473 AKT phosphorylation). Most importantly, there was no activation of ERK in cells treated with this TORC2-specific agent. These data indicate feedback ERK activation may be a resistance mechanism when second generation mTOR inhibitors are used and suggest a strategy for preventing activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1959. doi:10.1158/1538-7445.AM2011-1959
Abstract 1961: PKCΔ mediates glycodelin-induced differentiation of breast cancer cells
Authors: Hautala Laura C. , Koistinen Riitta , Koistinen Hannu 
Published: August 2014

Abstract
Glycodelin is a secreted lipocalin family glycoprotein, expressed mainly in differentiated epithelia in reproductive tissues. The expression of glycodelin in breast and endometrial cancer cells induces cell differentiation. We have found that transfection of glycodelin cDNA into MCF-7 breast cancer cells changes cellular morphology and gene expression towards less malignant direction. In pre-clinical xenograft mouse model glycodelin-producing cells formed significantly smaller tumors with lower proliferation rate than control cells. This is in keeping with the association of glycodelin with well-differentiated and less proliferative tumors in sporadic breast cancer patients. The aim of the present study is to elucidate the mechanism(s) mediating glycodelin-induced differentiation of breast cancer cells.
The gene expression changes between glycodelin-producing and control cells were compared using a cDNA micro array. The cells were grown on Matrigel with and without protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA), PKCΔ inhibitor Rottlerin and various other kinase inhibitors. PKCΔ was also down-regulated with RNAi. The levels of PKCΔ were measured using Western Blotting.
The gene expression changes induced by glycodelin were enriched in several pathways, including mitogen-activated protein kinase (MAPK) -pathway. Among various studied proteins of MAPK-pathway, we found that phosphorylated PKCΔ was down-regulated in glycodelin-producing cells. Further studies with activators and inhibitors indicated that addition of PKC activator PMA to cell culture medium induced dramatic morphological changes and increased motility of the control cells, while glycodelin-producing cells were unresponsive. The effect of PMA was abolished by Rottlerin, an inhibitor of PKCΔ, as well as by using siRNA for PKCΔ. These results suggest that the glycodelin-induced differentiation of breast cancer cells is mediated by PKCΔ, which in other studies has been proposed to be a potential target for cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1961. doi:10.1158/1538-7445.AM2011-1961
Abstract 1962: Helicobacter pylori cytotoxin associated protein CagA represses TGF-β signaling through interaction with Smad proteins
Authors: Lee Ho-Jae , Nguyen Thuy Trang , Cho Han-Yang , Kim Kyoung-Mi , Kim Cho-Rong , Hahm Ki-Baek 
Published: August 2014

Abstract
Helicobacter pylori infection causes chronic gastric inflammation and peptic ulceration, and is the strongest risk factor for the development of gastric cancer. The cagA (cytotoxin-associated gene A) gene which is one of the most important virulence factors of H. pylori, is believed to contribute to the gastric tissue injury and cancer development. Transforming growth factor-β (TGF-β) signaling plays a pivotal role in modulating gastric mucosal inflammatory responses. Recently, H. pylori infection has been associated with attenuated TGF-β signaling in gastric mucosa. However, the precise underlying mechanism of H. pylori infection on TGF-β signaling and inflammatory response remains unclear. In this study, we examined the mechanism of inhibition of TGF-β signaling by H. pylori CagA protein. CagA suppressed TGF-β/Smad transcriptional responses. CagA interacted constitutively with Smad proteins, and most strongly with Smad3. Expression of CagA on AGS cells inhibited TGF-β-induced down-regulation of proinflammatory chemokines, such as CXCL1, CXCL3 and IL-8, as well as TGF-β-induced transcription of target genes. These results suggest that the attenuated TGF-β signaling associated with cagA-positive H. pylori infection could be an important determinant for the degree of inflammation provoked by H. pylori.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1962. doi:10.1158/1538-7445.AM2011-1962