bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2948: c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in local anesthetics-induced apoptosis in human thyroid cancer cells.
Authors: Cheng Shih-Ping , Chang Yuan-Ching , Hsu Yi-Chiung , Huang Shih-Yuan , Hu Meng-Chun , Chi Chin-Wen , Yu Sung-Liang 
Published: August 2014

Abstract
Local anesthetics are known to induce apoptosis in clinically relevant concentrations. However, it is unknown whether the effects are also present in thyroid cancer cells and the mechanisms are not well uncharacterized. We sought to explore the effects of lidocaine and bupivacaine on thyroid cancer cells in terms of cell growth, colony formation, cell cycle, induction of apoptosis, and mitochondrial injury. At 24 hour, lidocaine had an IC50 value of 6.8 mM to 7.3 mM, whereas bupivacaine had an IC50 value of 1.3 mM to 3.1 mM. In search for a molecular mechanism, based on microarray and pathway analysis, we determined that apoptotic activity is mediated by the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK). Our data suggest that induction of apoptosis by local anesthetics has the potential to improve the regional control of thyroid cancer.
Citation Format: Shih-Ping Cheng, Yuan-Ching Chang, Yi-Chiung Hsu, Shih-Yuan Huang, Meng-Chun Hu, Chin-Wen Chi, Sung-Liang Yu. c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in local anesthetics-induced apoptosis in human thyroid 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 2948. doi:10.1158/1538-7445.AM2013-2948
Abstract 295: PPARγ-induced KLF4 in regulation of cell growth and migration in human hepatoma cells.
Authors: Hsu Hui-Tzu , Sung Ming-Ta , Chi Chin-Wen 
Published: August 2014

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recently, a zinc finger transcription factor Krüppel-like factor 4 (KLF4) was found to be reduced in tumors of HCC patients. Additionally, results from our laboratory showed that overexpressed KLF4 repressed epithelial-mesenchymal transition (EMT) process and cell motility by induction of E-cadherin expression and reduction of EMT markers in hepatoma cells. Interestingly, it has been found that PPARγ agonists upregulated KLF4 in colorectal cancer cells. However, the mechanism of PPARγ-induced KLF4 in the EMT process of HCC remains unclear. In this study, Hep3B, PLC/PRF/5, and Mahlavu human hepatoma cells were treated with PPARγ agonists rosiglitazone, troglitazone, and PPARγ antagonist GW9662, respectively. After rosiglitazone or troglitazone treatment for various time periods, growth inhibition was observed in both Hep3B and PLC/PRF/5 cells at 48 hours by surforhodamine B assay. Mahlavu cells showed less response to rosiglitazone and troglitazone treatment as compared to the other two cell lines. However, pretreatment of GW9662, a PPARγ antagonist, prior to PPARγ agonists treatment did not block the PPARγ agonists-induced cell growth inhibition. Moreover, cotreatment of PPARγ agonist and antagonist showed additive growth inhibition effect. In addition, rosiglitazone and troglitazone inhibited the migration of Hep3B, PLC/PRF/5 and Mahlavu cells differentially in transwell assay. Western blotting analysis showed upregulation of KLF4 and E-cadherin in Hep3B and PLC/PRF/5 cells after rosiglitazone and troglitazone treatment. Interestingly, decreased KLF4 and E-cadherin were observed in Hep3B, PLC/PRF/5, and Mahlavu cells after GW9662 treatment, indicating that the regulation of KLF4 and E-cadherin were PPARγ-dependent. Moreover, GW9662 also inhibited cell migration of Hep3B, PLC/PRF/5, and Mahlavu cells, with a concomitant decrease of vimentin. These results together suggested that PPARγ agonists and antagonist not only inhibited the growth but also decreased migration of hepatoma cells. Modulation of the PPARγ agonists induced expression of KLF4 and E-cadherin played important role in migration of hepatoma cells.
Citation Format: Hui-Tzu Hsu, Ming-Ta Sung, Chin-Wen Chi. PPARγ-induced KLF4 in regulation of cell growth and migration in human hepatoma 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 295. doi:10.1158/1538-7445.AM2013-295
Abstract 2961: The N-terminal projection domain of the microtubule associated protein tau inhibits TNFα signaling.
Authors: Debnath Shawon , Hannon Peter , Toropova Kristina , Rodriguez Nelson Nunez , Alonso Alejandra , Fata Jimmie Eugene 
Published: August 2014

Abstract
Tumor Necrosis Factor-alpha (TNFα) is a multifunctional pro-inflammatory cytokine implicated in inducing both tumor promotion and tumor inhibition. This paradoxical effect can be partly explained by the fact that TNFα acts as a regulator of both proliferation and apoptosis; however the mechanisms and factors associated with how or whether a tumor cell responds to a microenvironment rich in TNFα have not been fully resolved. Here we provide evidence that the microtubule associate protein Tau inhibits TNFα signaling through its N-terminal domain and implicate it as a novel regulator of the cellular response to this key cytokine. Our findings indicate that over-expression of Tau in the human breast cancer cell lines MCF7, SkBr3 and in the pheochromocytoma cell line PC12 suppresses TNFα induced apoptosis evident in the control cells. TNFα induced cell apoptosis in control cells is triggered as early as 6 hrs post-treatment with hallmark features of cell shrinkage, membrane blebbing, disruption of tubulin architecture and caspase-3 activation. While over-expression of wild type full length Tau isoform in these cell lines, completely abrogates all TNFα associated apoptotic phenotypes. Aside from inhibiting TNFα induced apoptosis, Tau over-expression also interferes with TNFα induced NFκB activation. This is evident by a significant decrease in NFκB nuclear translocation in Tau over-expressed cells compared to controls. Suppression of TNFα signaling by Tau is not associated with its tubulin interaction since a truncated N-terminal projection domain lacking all microtubule binding domains still provides resistance to TNFα induced apoptosis and NFκB activation. These findings lead us to conclude that the functional domain of Tau that regulates TNFα response lies within its N-terminal region and current mechanistic studies indicate this region inhibits TNFα receptor clustering, which is needed for signaling. Our data provide direct evidence that the N-terminal domain of the microtubule associated protein Tau can inhibit TNFα signaling in tumor cells. These findings indicate a novel function for Tau and add to our knowledge of how a tumor cell responds to TNFα signaling.
Citation Format: Shawon Debnath, Peter Hannon, Kristina Toropova, Nelson Nunez Rodriguez, Alejandra Alonso, Jimmie Eugene Fata. The N-terminal projection domain of the microtubule associated protein tau inhibits TNFα signaling. [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 2961. doi:10.1158/1538-7445.AM2013-2961
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2978: DNA methylation changes during epithelial-to-mesenchymal transition in ovarian cancer cells.
Authors: Cardenas Horacio , Goswami Chirayu , Nephew Kenneth P. , Matei Daniela 
Published: August 2014

Abstract
Epithelial-to-mesenchymal transition (EMT) is a required step in the process of metastasis and has been linked to cancer cell stemness. We hypothesized that aside from defined genetic changes associated with EMT, epigenetic mechanisms are also involved. We determined DNA methylation changes in SKOV3 ovarian cancer (OC) cells undergoing TGFβ-induced EMT by using the Infinium HumanMethylation450 array. Methylation of sites was expressed as ß-values ranging from 0 (completely unmethylated) to 1 (completely methylated). Methylation of 468 and 390 sites changed significantly (P&lt;.01, ANOVA and FDR&lt;0.05) after 48h and 120h of TGFβ stimulation, of which 31 and 72 sites changed &gt;1.25-fold. The majority of changes (∼66%) reflected TGFβ-induced demethylation. Methylation of 160 sites changed similarly at 48 and 120h indicating that approximately 40% of changes were sustained. PCA analysis demonstrated that the removal of TGFβ was associated with reversal of DNA methylation changes at most sites and restitution of the baseline methylome. Pathway analysis identified DNA methylated genes involved in functional networks relevant to EMT and cancer progression, including: 1) cell morphology and development (39 genes), 2) cell growth and proliferation, and cell death and survival (34 genes), 3) cellular assembly and organization (22 genes), 4) DNA replication, recombination and repair (17 genes), and 5) gene expression, cell signaling, and cellular movement (15 genes). Validation of the relevant genes is ongoing. Treatment of OC cells with the DNA methyl transferase inhibitor SGI-110 prevented TGFβ-induced EMT and reduced by two-fold the number of cells with stem cell characteristics (ALDH1+). These results demonstrate that DNA methylation is a dynamic process involved in regulation of genes implicated in EMT and metastasis.
Citation Format: Horacio Cardenas, Chirayu Goswami, Kenneth P. Nephew, Daniela Matei. DNA methylation changes during epithelial-to-mesenchymal transition in ovarian 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 2978. doi:10.1158/1538-7445.AM2013-2978
Abstract 2985: The histone demethylase JMJD1A induces neuroblastoma cell migration and invasion.
Authors: Ling Dora , Tee Andrew , Nelson Charlotte , Xu Ning , Atmadibrata Bernard , Liu Pei Y. , Pasquier Eddy , Marshall Glenn M. , Suzuki Takayoshi , Zhang Yi , Liu Tao 
Published: August 2014

Abstract
Patients with neuroblastoma due to N-Myc oncogene-amplification die of tumour metastasis. However, little is known about how N-Myc induces cell migration, invasion and metastasis. The histone demethylase JMJD1A activates target gene transcription by demethylating lysine
9 residues of histone H3 (H3K9). Here we demonstrated that N-Myc up-regulated the expression of JMJD1A in N-Myc oncogene-amplified human neuroblastoma cells by directly binding to JMJD1A gene promoter. Affymetrix gene array studies revealed that the gene most significantly up-regulated by JMJD1A was the long intergenic noncoding RNA Metastasis-associated Lung Adenocarcinoma Transcript 1 (MALAT1).
Consistent with this finding, chromatin immunoprecipitation showed that JMJD1A bound to MALAT1 gene promoter. Importantly, JMJD1A siRNAs, MALAT1 siRNAs and small molecule JMJD1A inhibitors impeded neuroblastoma cell migration and invasion. Taken together, our data identify a novel pathway through which N-Myc causes neuroblastoma cell migration, invasion and potentially metastasis.
Citation Format: Dora Ling, Andrew Tee, Charlotte Nelson, Ning Xu, Bernard Atmadibrata, Pei Y. Liu, Eddy Pasquier, Glenn M. Marshall, Takayoshi Suzuki, Yi Zhang, Tao Liu. The histone demethylase JMJD1A induces neuroblastoma cell migration and invasion. [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 2985. doi:10.1158/1538-7445.AM2013-2985
Abstract 2989: Loss of methylation in a regulatory region of BCL2 in MDS/AML.
Authors: Lee Sangmin , Galili Naomi , Nimer Stephen , Minden Mark D. , Murty Vundavalli V. , Jhanwar Suresh , Raza Azra , Tycko Benjamin 
Published: August 2014

Abstract
Background:
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and increased risk of progression to acute myeloid leukemia (AML). A hallmark of MDS is increased apoptosis, while AML undergoes decreased apoptosis and increased proliferation. BCL2, an anti-apoptotic protein, is overexpressed in high grade MDS and AML and may confer poor prognosis and increased chemotherapy resistance. In this study we examined the DNA methylation status of BCL2 in MDS and AML.
Methods:
We conducted DNA methylation profiling on genomic DNA extracted from bone marrows of 22 refractory anemia with ringed sideroblasts (RARS), 8 refractory anemia with excess blasts (RAEB), 21 de novo AML, 21 therapy related AML, and 7 normal volunteers. We used both Illumina 27K BeadChip and 450K BeadChip methylation arrays to assess CpG methylation. Standard student T-test was used to screen differentially methylated MDS and AML CpG sites compared to normal samples. We validated the microarray data by combined bisulfite restriction analysis (COBRA) and bisulfite sequencing.
Results:
We identified a region in the BCL2 gene body that was among the most differentially methylated in MDS and AML versus normal bone marrow. Within that amplicon, BCL2 in both RARS, a low grade MDS, and RAEB, a high grade MDS, were hypermethylated compared to normal bone marrow (43% vs 18%, 48% vs 18%, respectively, p&lt;0.05). BCL2 in de novo AML and therapy related AML were hypomethylated compared to normal bone marrow (12% vs 35%, 13% vs 35%, respectively, p&lt;0.05). We validated these results by COBRA and bisulfite sequencing. This region coincided with H3K27ac and H3K4m1 enhancer type marks in ENCODE data in normal cells.
Conclusions:
Our study identifies a region of BCL2 that is hypermethylated in both low and high risk MDS while hypomethylated in AML compared to normal bone marrows. We hypothesize aberrant epigenetic modification of BCL2 plays a key role in apoptosis and transformation from MDS to AML, and our data support the idea of combining demethylating drugs with BCL2 antagonists. We are currently investigating whether BCL2 protein expression correlates with methylation, and plan to map the histone marks with CHIP-seq to correlate chromatin accessibility and DNA methylation in BCL2.
Citation Format: Sangmin Lee, Naomi Galili, Stephen Nimer, Mark D. Minden, Vundavalli V. Murty, Suresh Jhanwar, Azra Raza, Benjamin Tycko. Loss of methylation in a regulatory region of BCL2 in MDS/AML. [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 2989. doi:10.1158/1538-7445.AM2013-2989
Abstract 3: Molecular markers of prostate cancer: Investigation of microRNA profiles as a marker in patients with high-risk prostate cancer.
Authors: Stegmaier Petra , Kirste Simon , Mo Xiaokui M. , Zynger Debra L. , Chakravarti Arnab , Hlavin Bell Erica 
Published: August 2014

Abstract
Purpose:
The aim of this study was to investigate the microRNA (miRNA) profile in prostate carcinoma as biomarkers to identify high-risk prostate cancer patients who may benefit from post-prostatectomy radiation therapy using global miRNA profiling.
Method:
Tumor from Formalin-Fixed Paraffin-Embedded (FFPE) tissues were obtained from 9 radical prostatectomy specimens resected for high-risk prostate cancer, to perform a pilot study using the Nanostring miRNA platform from isolated RNA. An optimized protocol utilizing the Ambion RecoverAll digestion buffer and the Qiagen miRNeasy FFPE kit was used to isolate total RNA. Each prostatectomy specimen was marked by a genitourinary pathologist and 1 mm cores of enriched areas of tumor or normal epithelial or stromal tissue were obtained. To analyze global miRNA expression, the Nanostring nCounter human miRNA Expression Assay Kit was used. The data was further analyzed in collaboration with The Ohio State University Center for Biostatistics.
Results:
The expression of miRNA in prostate tumor samples was compared to normal epithelium. It showed that seven miRNAs (miR-375, miR-18a, miR-25, miR-183, miR-641, miR-15b, miR-548a-3p) that were &gt;1.5-fold upregulated and 4 miRNAs (miR-660, miR-1915, miR-200b, miR-205) &lt;1.5-fold downregulated. Three (miR-375, miR-183, miR-205) were in accordance with previous studies published on prostate cancer. Expression of six up-regulated miRNAs (miR-205, miR-877, miR-K12-4-5p, miR-548b-3p, miR-34c-5p, ebv-miR-BART10) correlated with high risk (T&gt;3 and/or Gleason score ≥ 8) and five miRNAs (up-regulated: miR-10b, miR-205; down-regulated: miR-574-5p, miR-30c, miR-499-5p) with pathological tumor stage 2 and 3.
Conclusion:
Our results suggest great potential for the use of miRNA profiling as a novel diagnostic and prognostic biomarker in defining the signatures of prostate cancer at different stages. We are currently completing the RNA isolation and downstream analyses in correlation with clinical data for 80 additional high-risk prostate cancer cases from the University hospital of Freiburg, Germany.
Citation Format: Petra Stegmaier, Simon Kirste, Xiaokui M. Mo, Debra L. Zynger, Arnab Chakravarti, Erica Hlavin Bell. Molecular markers of prostate cancer: Investigation of microRNA profiles as a marker in patients with high-risk prostate cancer. [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 3. doi:10.1158/1538-7445.AM2013-3
Abstract 3005: Cdca7l is a sex-specific modifier of astrocytoma and glioblastoma.
Authors: Reilly Karlyne M. , Lee Min-Hyung , Schaick Jessica Amlin-Van 
Published: August 2014

Abstract
Astrocytoma and glioblastoma-multiforme (GBM) are the most common primary brain tumors and are currently incurable. Both astrocytoma and GBM show male-predominance, with a male-to-female ratio of 1.3:1, respectively. Previously, our lab has demonstrated that astrocytoma/GBM-tumorigenesis in the Nf1-/+;Trp53-/+cis (NPcis) mouse model shows gender-bias in certain genetic contexts. Using linkage-analysis in the NPcis mouse, we have identified a male-specific genetic modifier locus on distal chromosome 12, named Arlm1 for Astrocytoma-resistance-locus-in-males1. To identify candidate genes for the Arlm1 modifier of glioma risk, we used combinational bioinformatics approaches and cross-species comparisons, identifying Cell-division-cycle-associated-7-like (CDCA7L) as a strong candidate for a male-specific astrocytoma susceptibility gene among 503 candidate genes. To investigate the role of CDCA7L in astrocytoma/GBM, we analyzed CDCA7L in both human and mouse astrocytoma cell lines in both genders. CDCA7L expression was upregulated in astrocytoma cells compared to normal brain with male-predominance. shRNA-mediated CDCA7L-silencing in male-derived astrocytoma cells led to decrease of both cell growth and viability in both human and mouse. Further mechanistic study revealed that CDCA7L-depletion in male-derived astrocytoma cells was connected with the induction of Caspase3-activation and reduction of CyclinD1-expression, suggesting the oncogenic role of CDCA7L in astrocytoma/GBM. On the other hand, CDCA7L-overexpression in female-derived astrocytoma cells showed less degree of cell proliferation and viability increases. Strikingly, CDCA7L-depletion in human female-derived astrocytoma cell line, U87MG caused increase of both cell growth and viability. These data highlight the sex-specificity of CDCA7L in astrocytoma/GBM tumorigenesis and provide evidence for the first modifier of male-specific susceptibility to brain tumors.
Citation Format: Karlyne M. Reilly, Min-Hyung Lee, Jessica Amlin-Van Schaick. Cdca7l is a sex-specific modifier of astrocytoma and glioblastoma. [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 3005. doi:10.1158/1538-7445.AM2013-3005
Abstract 3007: Down-regulation of HOXC6 in serous ovarian cancer.
Authors: Tait David L. , Bahrani-Mostafavi Zahra , Vestal Carol , Richardson Christine , Mostafavi M. Taghi 
Published: August 2014

Abstract
Objective: The Homeobox (HOX) family of genes consists of 39 genes encoding transcription factors important to morphogenesis and cell differentiation. Usually inactive in normal differentiated tissues, dysregulation of HOX genes has been reported in several malignancies. HOX genes have been linked to genes important in malignant transformation including vascular endothelial growth factor, Ras, interleukin-8, and fibroblast growth factor. We have previously reported up-regulation of HOXA2, HOXA7 and HOXB7 in ovarian cancer. Little is known about HOXC6 gene expression in ovarian cancer. In this study we evaluated HOXC6 expression in normal and malignant human ovarian tissue to characterize expression of HOXC6 in serous ovarian cancer.
Methods: Microarray analysis of mRNA from LCM captured cells from human ovarian tissues was performed on 11 samples of normal, and malignant ovarian tissues. These samples were analyzed using the Affymetrix Human EXON 1.0 ST microarray to distinguish the differential pattern of mRNA expression between malignant and normal samples. Real-time reverse transcription PCR was utilized to confirm down-regulation of HOXC6 genes as determined by microarray analysis. HOXC6 protein in tissue was evaluated by immunohistochemistry.
Results: Microarray analysis demonstrated significant down-regulation of the HOXC6 gene in malignant serous ovarian tumor samples compared to normal ovarian epithelial cells of control samples. RT-PCR and immunohistochemistry confirmed HOXC6 down-regulation in malignant samples. A 115-fold difference in malignant and normal primary tissue samples and cell lines was seen in the RT-PCR analysis. By immunohistochemistry nuclear staining of HOXC6 protein was seen in the nuclei of normal ovarian surface epithelial tissues but significantly reduced or absent in malignant ovarian samples.
Conclusion: HOXC6 is significantly differentially expressed comparing normal ovarian tissue and serous malignant ovarian tissue based on both tissue mRNA and protein analysis. This finding of HOXC6 down-regulation in ovarian cancer is unique and opposite of the up-regulation of other HOX genes previously reported. Down-regulation of HOXC6 in serous ovarian cancer may be an important finding relative to oncogenic pathways and biomarker development. This suggests dysregulation of HOXC6 genes may be an early event in malignant transformation and additional studies to validate the role of the HOXC6 gene in ovarian cancer are warranted.
Citation Format: David L. Tait, Zahra Bahrani-Mostafavi, Carol Vestal, Christine Richardson, M. Taghi Mostafavi. Down-regulation of HOXC6 in serous ovarian cancer. [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 3007. doi:10.1158/1538-7445.AM2013-3007