bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 354: Conditional inactivation of Pten and overexpression of EGFR in Schwann cells results in early high-grade peripheral nerve sheath tumor development.
Authors: Keng Vincent W. , Watson Adrienne L. , Rahrmann Eric P. , Li Hua , Tschida Barbara R. , Moriarity Branden S. , Choi Kwangmin , Rizvi Tilat A. , Collins Margaret H. , Wallace Margaret R. , Ratner Nancy , Largaespada David A. 
Published: August 2014

Abstract
It is hypothesized that many genetic changes are required for the transformation process of sporadic malignant peripheral nerve sheath tumor (MPNST). Currently, Schwann cells and/or their precursor cells are believed to be the primary pathogenic cell source in peripheral nerve sheath tumor (PNST) formation and malignant progression. Recently, it has been shown that phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) both play important roles in the initiation of peripheral nerve sheath tumors (PNSTs). In human MPNSTs, PTEN expression is often reduced, while EGFR expression is often induced. We tested if these two genes cooperate in the evolution of PNSTs, because genetically modified mouse models for each gene alone resulted in the formation of low-grade PNSTs. Transgenic mice were generated carrying conditional floxed alleles of Pten, EGFR was expressed under the control of the 2′,3′-cyclic nucleotide 3’ phosphodiesterase (Cnp) promoter and a desert hedgehog (Dhh) regulatory element driving Cre recombinase transgenic mice (Dhh-Cre). Transgenic mice with EGFR overexpression and Pten inactivated have an early postnatal lethality (median survival age of 26-days) and displayed various peripheral nervous system phenotypes. These mice had multiple enlarged dorsal root ganglia, with high incidence of enlarged brachial plexus and trigeminal nerves at various stages of PNST tumorigenesis. In vitro experiments using immortalized human Schwann cells demonstrated that loss of PTEN and overexpression of EGFR cooperate to increase cellular proliferation and anchorage-independent colony formation. Taken together, our data suggests that reduced PTEN expression, together with EGFR overexpression, can drive malignant progression of low-grade to high-grade PNSTs. Importantly, our novel mouse model recapitulates sporadic human MPNST and will be useful for testing therapies to prevent or reverse tumor progression.
Citation Format: Vincent W. Keng, Adrienne L. Watson, Eric P. Rahrmann, Hua Li, Barbara R. Tschida, Branden S. Moriarity, Kwangmin Choi, Tilat A. Rizvi, Margaret H. Collins, Margaret R. Wallace, Nancy Ratner, David A. Largaespada. Conditional inactivation of Pten and overexpression of EGFR in Schwann cells results in early high-grade peripheral nerve sheath tumor development. [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 354. doi:10.1158/1538-7445.AM2013-354
Abstract 3543: TOP2A is a therapeutic target for adrenocortical carcinoma .
Authors: Jain Meenu , Zhang Lisa , He Mei , Zhang Ya-Qin , Nilubol Naris , Shen Min , Kebebew Electron 
Published: August 2014

Abstract
Adrenocortical carcinoma (ACC) represents one of the most resistant human cancers to systemic chemotherapy and a major clinical challenge in the field of endocrine oncology. Recent molecular characterizations of ACC suggest new opportunities for targeted therapy. The current study aimed to evaluate expression and function of TOP2A in human adrenocortical neoplasm, and anticancer activity of agents that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112 adrenocortical tissue samples. In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI-H295R and SW13) was used to determine its effect on cellular proliferation, cell cycle, anchorage-independent growth and cellular invasion. We screened 14 TOP2A inhibitors for their anticancer activity in ACC cell lines. TOP2A mRNA expression was significantly higher in ACC than in benign and normal adrenocortical tissue samples (p &lt; 0.001); likewise, TOP2A protein expression was significantly higher in ACC (p &lt; 0.05). Knockdown of TOP2A gene expression decreased cell proliferation, anchorage-independent growth and invasion (p &lt; 0.05). Aclarubicin had the most potent antiproliferative activity out of 11 active TOP2A inhibitors, which significantly decreased proliferation and tumor spheroid size in ACC cell lines (p&lt; 0.05). Our data indicate that most TOP2A inhibitors are effective compounds for ACC, with aclarubicin having the best anticancer activity. Thus, TOP2A inhibitors should be tested in future clinical trials for patients with locally advanced and metastatic ACC.
Citation Format: Meenu Jain, Lisa Zhang, Mei He, Ya-Qin Zhang, Naris Nilubol, Min Shen, Electron Kebebew. TOP2A is a therapeutic target for adrenocortical carcinoma . [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 3543. doi:10.1158/1538-7445.AM2013-3543
Abstract 3544: The gastric mucosal tissue interleukin-8 mRNA expression level is a promising prognostic marker for prognosis prediction in advanced gastric cancer treatment.
Authors: Chakrabandhu Bandhuphat 
Published: August 2014

Abstract
Background : The Interleukin-8 is one of the potent chemokine that plays the major role in cancer inflammatory and vascular growth pathway. We conduct this experiment to determine how difference of its level between non-cancer and cancer location, and its possibility to predict prognosis and result of advance gastric cancer treatment .
Method : We collected 309 gastric tissue samples from 129 Thai advance gastric cancer patients during January 2007 to March 2012 . Clinical information was prospective collected on electronic data base. The Interleukin-8 expression levels were detected by relative quantitation RT-PCR method with Taqman probe for Interleukin-8 on 7500 series machine, Applied Biosystem . Test of difference of Mean was done with independent and paired t-test by SPSS version 17th. Test of difference was considered significant by p value ≤0.05.
Result : The gastric mucosal tissue IL-8 mRNA expression level was significantly higher in tumor specimen than benign specimen by level of 5469.35 and 565.42 respectively (p =0.13). Its level in diffuse histologic type,metastatic disease and positive lymph node group are higher without significant difference. In subgroup analysis for 50 neo- adjuvant chemotherapy patients, the responder group (partial response and complete response) had a lower IL-8 expression level than non-responder group by the means level of1904.02, 24269.31,respectively (p=0.209).
Conclusion : Gastric mucosal tissue IL-8 mRNA expression level was remarkable increased in advance gastric cancer and signet ring cell type. We found that the higher expression level is directly correlated with more advance of histological grading and prognosis of disease treatment. The chemotherapy response rate was poorer in extremely high expression. High interleukin-8 expression could be considered as poor clinical prognostic factor for gastric cancer treatment, and it may be helpful tool to predict the chemotherapy response in future.
Citation Format: Bandhuphat Chakrabandhu. The gastric mucosal tissue interleukin-8 mRNA expression level is a promising prognostic marker for prognosis prediction in advanced gastric cancer treatment. [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 3544. doi:10.1158/1538-7445.AM2013-3544
Abstract 3567: Estrogen signaling promotes effective progesterone receptor engagement with DNA in breast cancer cells.
Authors: Swinstead Erin E. , Trotta Andrew P. , Smith Eric , Grover Phulwinder K. , Need Eleanor F. , Buchanan Grant 
Published: August 2014

Abstract
Estrogens and progesterone (PROG) are key mediators of breast cancer aetiology and progression. The predominant actions of these hormones in the breast are mediated via their respective cognate steroid receptors, estrogen receptor alpha (ERα) and progesterone receptor (PGR). As ERα upregulates PGR expression, both are currently measured in clinical breast cancer samples to determine the utility of anti-estrogen therapy. Although the molecular actions of estrogens have been extensively studied, the role of PROG and PGR need further elucidation, particularly in the context of activated ERα signaling. Here, we treated ZR75-1 cells with 17β-estradiol (E2) alone or in combination with PROG and assessed global transcriptional responses by microarray expression profiling and receptor binding profiles by chromatin immunoprecipitation-sequencing (ChIP-seq).
PROG treatment alone significantly altered the regulation of only seven genes, whereas long term E2 treatment increased the PROG transcriptional response altering 785 genes (p value ≤ 0.05), and regulated pathways involved in ErbB signalling and cell proliferation. Consistent with these findings, ChIP-seq identified 10 times more PGR binding sites following long term E2 treatment (4566 at equivalent peak threshold) compared with PROG treatment alone. Candidate PGR ChIP validated these findings at 100% (12/12) sites tested. The long term E2-treated PGR cistrome was highly conserved amongst species, and enriched for progesterone receptor response elements (PREs) and FOXA1 binding sites. E2 enhancement of PGR binding could be abrogated by long term (72h) but not short term (4h) tamoxifen co-treatment. In T-47D cells, long term E2 treatment was not required for efficient interaction of PGR with DNA and FOXA1 silencing resulted in decreased PGR DNA occupancy at several sites. These data suggests that the combination of E2 and PROG regulated a distinct transcriptional response in breast cancer cells, perhaps due to the dependence of PGR on E2 signaling for maintenance of cellular PGR levels, and via the receptors sharing mutual collaborators and coregulators, such as FOXA1. ERα and PGR collectively shape a mitogenic response in breast cancer cells that is dependent on the combined presence of E2 and PROG.
Citation Format: Erin E. Swinstead, Andrew P. Trotta, Eric Smith, Phulwinder K. Grover, Eleanor F. Need, Grant Buchanan. Estrogen signaling promotes effective progesterone receptor engagement with DNA in breast cancer 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 3567. doi:10.1158/1538-7445.AM2013-3567
Abstract 3571: Inhibition of Cdk9 blocks ligand induced phosphorylation of Estrogen receptor alpha at Ser294.
Authors: Scott Gary K. , Kaur Ravneet , Rothschild Daniel , Benz C. C. 
Published: August 2014

Abstract
In response to ligand binding, the estrogen receptor (ER, alpha isoform) becomes phosphorylated on several serines including Ser294 and Ser118 to initiate an estrogenic transcriptional program that has been well studied. On the other hand, growth factor stimulation of ER also promotes serine phosphorylation at several sites including Ser305 and Ser118, but not Ser294, to drive a transcriptional program different from that induced by estrogenic ligands. Our previous work demonstrated that following estrogen or tamoxifen stimulation, cyclin dependent kinase (Cdk) mediated phosphorylation of the ER hinge region at Ser294 was essential for full transcriptional activation of ER. Current studies, using a recently developed rabbit monoclonal antibody to phospho-Ser294 ER, show that the Cdk9 inhibitor SCH727956/Dinaciclib, now in phase II clinical trials, completely prevents Ser294 phosphorlyation induced by estrogen stimulation of MCF-7 cells without influencing phospho-Ser118 formation which remains robust. Immunoprecipitation of ER from MCF-7 cells following estrogen treatment results in the co-immunoprecipitaton of cdk9. Further SCH727965/Dinaciclib has no influence upon epidermal growth factor (EGF) induced ER phosphorylation at Ser305, consistent with previous studies linking phospho-Ser305 formation to the activated kinases PKA and PAK. Ongoing studies evaluating siRNA induced knockdown of Cdk9 in MCF-7 cells followed by estrogen and/or EGF stimulation are designed to confirm the specific role of Cdk9 in mediating ligand-induced ER phosphorylation at Ser294. As Cdk9 is essential to promote transcriptional elongation by RNA polymerase II, the Ser294 specific recruitment of Cdk9 to ER following ligand stimulation offers rationale for the clinical use of Cdk9 inhibitors such as SCH727965/Dinaciclib in the treatment of ER-positive breast cancers. In particular, for those ER-positive breast cancers responsive to endocrine therapy the combined use of a Cdk9 inhibitor with antiestrogenic therapy is likely to prove clinically beneficial.
Citation Format: Gary K. Scott, Ravneet Kaur, Daniel Rothschild, C. C. Benz. Inhibition of Cdk9 blocks ligand induced phosphorylation of Estrogen receptor alpha at Ser294. [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 3571. doi:10.1158/1538-7445.AM2013-3571
Abstract 3582: Licochalcone-A, a natural inhibitor of c-Jun N-terminal kinase 1.
Authors: Yao Ke , Chen Hanyong , Lee Mee-Hyun , Li Haitao , Ma Weiya , Lee Ki Won , Bode Ann M. , Dong Zigang 
Published: August 2014

Abstract
The c-Jun N-terminal kinases (JNKs) pathway plays an important role in many physiological processes induced by a variety of stress signals. Each JNK protein appears to have a distinct function in cancer, asthma, diabetes, or Parkinson's disease. JNK1 is a key contributor for breast cancer and gastric cancer. Herein, we found that licochalcone-A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity, but had little effect on JNK2 in vitro. Although licochalcone-A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone-A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone-A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both ex vivo and in vitro systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expression compared with normal cell lines. In these cell lines, treatment with licochalcone-A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. These results demonstrate that licochalcone-A is a selective JNK1 inhibitor. Therefore, we suggest that because of JNK1’s critical role in colon cancer and pancreatic carcinogenesis, licochalcone-A might have therapeutic potential against this devastating disease.
Citation Format: Ke Yao, Hanyong Chen, Mee-Hyun Lee, Haitao Li, Weiya Ma, Ki Won Lee, Ann M. Bode, Zigang Dong. Licochalcone-A, a natural inhibitor of c-Jun N-terminal kinase 1. [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 3582. doi:10.1158/1538-7445.AM2013-3582
Abstract 3591: The role of T-cell protein tyrosine phosphatase (TC-PTP) in UVB-induced epidermal cell proliferation and survival.
Authors: Lee Young S. , Shin Jun W. , Morales Liza D. , Slaga Thomas J. , Kim Dae J. 
Published: August 2014

Abstract
Ultraviolet (UV) radiation is the primary cause of human skin cancer. Signal transducer and activator of transcription 3 (Stat3) is one of the key regulators of epidermal cell survival and proliferation during the development of UV-induced skin cancer. We have previously shown that T-cell protein tyrosine phosphatase (TC-PTP) contributes to the rapid dephosphorylation /deactivation of Stat3 in response to UVB irradiation in keratinocytes. In the current work, we investigated the functional role of TC-PTP in keratinocyte survival and proliferation following UVB exposure. Knockdown of TC-PTP in mouse keratinocytes using siRNA significantly reduced apoptosis following UVB irradiation in comparison with control keratinocytes as evidenced by the decreased levels of activated caspase-3 and PARP cleavage. This reduction corresponded with an increased level of phososphorylated Stat3 in TC-PTP-deficient keratinocytes. Knockdown of TC-PTP in keratinocytes also significantly increased cell proliferation following UVB irradiation compared with control keratinocytes. Similar with these results, overexpression of TC-PTP in keratinocytes significantly increased apoptosis and decreased cell proliferation in response to UVB irradiation compared with control keratinocytes, which corresponded with a decreased level of phosphorylated Stat3. Further studies using TC-PTP-deficient keratinocyte cell lines showed that cell viability was increased in TC-PTP-deficient cells following UVB irradiation. Treatment of TC-PTP-deficient keratinocytes with specific Stat3 inhibitor, STA21 significantly reduced cell viability, upon UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, which suggests that the effect of TC-PTP on cell viability is mediated by Stat3 dephosphorylation. Combined, our results indicated that TC-PTP plays an important role in the regulation of keratinocyte proliferation and survival after UVB exposure via modulation of Stat3 signaling. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer.
Citation Format: Young S. Lee, Jun W. Shin, Liza D. Morales, Thomas J. Slaga, Dae J. Kim. The role of T-cell protein tyrosine phosphatase (TC-PTP) in UVB-induced epidermal cell proliferation and survival. [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 3591. doi:10.1158/1538-7445.AM2013-3591
Abstract 3593: GABA counteracts ethanol induced stimulation of pancreatic cancer cells and normal pancreatic duct epithelia .
Authors: Al-Wadei Mohammed H. , Al-Wadei Hussein A.N. , Schuller Hildegard M. 
Published: August 2014

Abstract
Pancreatic cancer has a high mortality rate and alcoholism is a risk factor independent of smoking. We have shown that nicotinic acetylcholine receptors (nAChRs) regulate pancreatic ductal epithelia and pancreatic ductal adenocarcinoma (PDAC) cells in an autocrine fashion by stimulating their production of the stress neurotransmitters noradrenaline and adrenaline that signal through beta-adrenergic receptors (β-ARs). Our current study has investigated the modulation of this autocrine regulatory loop by chronic ethanol and explored the potential prevention of these effects by γ-amino butyric acid (GABA).
Treatment for seven days with ethanol at a concentration equivalent to the legal blood alcohol limit in the United States induced protein expression and sensitivity of nAChRs α3, α5 and α7 resulting in increased production of noradrenaline and adrenaline which drive proliferation and migration via cAMP-dependent signaling downstream of β-ARs. Treatment with GABA prevented all of these responses to chronic ethanol, reducing cell proliferation and migration below base levels in untreated cells.
Our findings suggest that alcoholism induces multiple cAMP-dependent PDAC stimulating signaling pathways by up-regulating the protein expression and sensitivity of nAChRs that regulate stress neurotransmitters production. Moreover, our data identify GABA as a promising agent for the prevention of PDAC in individuals at risk due to chronic alcohol consumption.
Supported by R01CA042829 and R01CA130888 with the National Cancer Institute
Citation Format: Mohammed H. Al-Wadei, Hussein A.N. Al-Wadei, Hildegard M. Schuller. GABA counteracts ethanol induced stimulation of pancreatic cancer cells and normal pancreatic duct epithelia . [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 3593. doi:10.1158/1538-7445.AM2013-3593
Abstract 3597: Further studies on cadmium-adapted lung epithelial cells: evidence for the attenuation of general stress response, enhancement of metallothionein-induction response, and loss of p53 expression.
Authors: Xu Yan-Ming , Zhou Yuan , Huang Dong-Yang , Zhang Jian , Chiu Jen-Fu , Lau Andy T. Y. 
Published: August 2014

Abstract
Adaptation is a cellular process in which cells are progressed from the starting sensitive state to the later adapted state to the exposing agent. Acute exposure of cells to cadmium (Cd) can cause cell death; however, chronic exposure of Cd can develop acquired tolerance where cell death is suppressed. We previously reported that during Cd adaptation in lung epithelial cells, cells develop tolerance to cell death, generally due to perturbation of the c-Jun N-terminal kinase (JNK) signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells (1, 2). In this study, we further studied the properties of these Cd-adapted cells. Our results indicate that Cd-adapted cells, when compared with Cd-treated parental Cd-sensitive cells, show negligible general stress response to the same dosage of cadmium exposure. Moreover, although metallothionein (MT) is induced in both Cd-sensitive and Cd-adapted cells, Cd-adapted cells show enhanced MT-induction response and this was not due to MT gene amplification. Lastly, we showed that the tumor suppressor p53 protein level is severely abrogated in these Cd-adapted cells, suggesting that the normal p53 function is lost and may account for the death tolerance, genome instability, as well as the progression of carcinogenesis.
Citation Format: Yan-Ming Xu, Yuan Zhou, Dong-Yang Huang, Jian Zhang, Jen-Fu Chiu, Andy T. Y. Lau. Further studies on cadmium-adapted lung epithelial cells: evidence for the attenuation of general stress response, enhancement of metallothionein-induction response, and loss of p53 expression. [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 3597. doi:10.1158/1538-7445.AM2013-3597