bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4316: Suppression of Sp protein expression with Tolfenamic Acid inhibits oral Squamous Cell Carcinoma
Authors: Madero Rafael A. , Lee Chriss M. , Basha Riyaz M. , Abdelrahim Maen A. , Baker Cheryl H. , Shellenberger Thomas D. 
Published: July 2012

Abstract
OBJECTIVE: Upregulation of members of the Sp protein family is associated with cell proliferation and metastasis in multiple cancer types. Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug shown to inhibit the expression of Sp proteins. We tested the hypothesis that TA inhibits Sp protein expression in human head and neck squamous cell carcinoma lines to suppress cell growth.
METHODS: An oral Squamous cell carcinoma cell line (UMSCC-1) was screened for Sp-1 expression, a known target for Tolfenamic Acid (TA). To assess the effect of TA on UMSCC-1 cells, in vitro cell proliferation assays were performed at 24, 48, 72, 96 and 120Hrs, in order to correlate the cell growth response to different drug concentrations (25, 50, 75 and 100 µM). In parallel, Western blot analyses were use to measure Sp-1 expression after 72hrs of drug treatment. In subsequent experiments, we analyzed the effect of TA and radiation on UMSCC-1 under two conditions. Experiment 1: Tolfenamic acid was added 24 hrs after the cells were seeded, and underwent different doses of radiation (5, 10 or 20 Gy) 24 hrs after drug treatment was started. Experiment 2: 24 hrs after seeding UMSCC-1 cells were exposed to different doses of radiation (5, 10 and 20 Gy) and TA was added 24 hrs post-radiation. Cell growth was measure ATP assays.
RESULTS: Preliminary results confirmed the presence of Sp-1 expression in the head and neck squamous cell carcinoma cell line, UMSCC-1. In vitro growth analysis showed a direct correlation between cell death and TA concentration. Additionally a synergistic effect was observed when using TA and radiation. Sp-1 has been identified as a transcription factor for the production of Survivin, a protein which is known to be overexpressed in most cancer cells and has been directly linked to the radiation-resistant phenomenon. By regulating the expression of SP-1 using tolfenamic acid, we have demonstrated a reduction and/or complete inhibition of the cancer cells capability to produce Survivin, sensitizing them to radiation.
CONCLUSIONS: Our study suggests that TA bears potential in the treatment of oral squamous cell carcinomas as a concomitant agent for traditional chemotherapeutic regimens. In parallel, preliminary data suggest that TA potentiates radiation sensitivity in human head and neck cancer cells. Animal's studies are warranted to further investigate TA in squamous cell carcinoma.
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 4316. doi:10.1158/1538-7445.AM2011-4316
Abstract 432: A tissue engineered human extra cellular matrix (hECM) inhibits tumor growth
Authors: Pinney Emmett , Schenone Aaron , Montes-Camacho Mayra , Suetsugu Atsushi , Easter David , Hoffman Robert M. , Naughton Gail 
Published: July 2012

Abstract
A human extracellular matrix (hECM) was extracted from deposits made by neonatal dermal fibroblasts that were seeded on dextran microspheres and cultivated in a stirred bioreactor. The resulting hECM is high in collagen content with reduced hydroxylation as well as proteins found primarily in fetal ECM. These include high concentrations of SPARC, fibulin-2, tenascin, decorin, lumican, and fibromodulin. This hECM was used to treat tumor lines that were introduced onto the CAM of the fertilized chicken egg or growing subcutaneously in the nude mouse. In the CAM model significant tumor inhibition by hECM was seen with the following tumor lines: B16 melanoma was reduced 67%, C6 glioma 58% and MDA-MB-435 breast cancer 78%. Histology indicated that where the cells are in contact with hECM the cells appeared apoptotic. In the nude mouse models similar inhibition by hECM was observed: B16 melanoma was reduced 61%, C6 glioma 60% and MDA-MB-435 breast cancer reduced 58%. Apoptotic pathway activation was confirmed with caspase 9 upregulation in a dose-dependent response to hECM. These data indicate that an ECM rich in fetal proteins is capable of retarding tumor growth.
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 432. doi:10.1158/1538-7445.AM2011-432
Abstract 4324: Loss of TGF-beta receptor I and PTEN promotes HNSCC
Authors: Bian Yansong , Hall Bradford , Sun Zhi-Jun , Molinolo Alfredo , Chen Wanjun , Van Waes Carter , Kulkarni Ashok 
Published: July 2012

Abstract
The precise molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been clearly delineated. Here, we report that defects in the TGF-β and PI3K/Akt signaling pathways are common in human HNSCCs. Activation of the PI3K/Akt pathway due to PTEN deletion gives rise to hyperproliferation in the head and neck epithelia, but only a few lesions progressed to HNSCCs. Strikingly, PTEN deletion, in combination with a loss of Tgfbr1, caused HNSCC with complete penetrance. Molecular analysis revealed enhanced cell proliferation, increased expression of CCND1 and decreased expression of CDKN1A in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/PTEN double conditional knockout (2cKO) mice. These tumors displayed pathology and multiple molecular alterations that resembled human HNSCCs. Furthermore, the neoplastic transformation was due to senescence evasion and was associated with an increased number of putative (CD44+, CD133+) cancer stem cells. In addition, myeloid derived suppressor cell (MDSC) infiltration, angiogenesis and immune suppression in the tumor microenvironment also accompanied mouse head and neck carcinogenesis. The Tgfbr1/PTEN 2cKO mouse model is suitable for preclinical intervention and has significant implications in the development of diagnostic cancer biomarkers as well as effective preventive and therapeutic strategies for the treatment of HNSCCs.
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 4324. doi:10.1158/1538-7445.AM2011-4324
Abstract LB-161: A complete regression and therapeutic vaccination against aggressive malignant rat mesenchymal tumors with “stemness” characteristics obtained by intratumoral injection of LTX-315 (Oncopore®)
Authors: Rekdal Øystein , Wang MengYu , Camilio Ketil , Sveinbjornsson Baldur , Rolstad Bent , Kvalheim Gunnar 
Published: July 2012

Abstract
Background: In order to develop more effective anticancer agents there is a shift from not only treating the bulk of cells in a tumor but also to target the self renewing cancer stem cells (CSCs). Standard treatment with chemotherapy and radiotherapy is unable to eradicate CSCs and therefore other treatment modalites against CSCs are needed. LTX-315 (Oncopore®) is a chemically modified cytolytic peptide which is equally active against drug-sensitive and drug-resistant cancer cells. Earlier animal studies have demonstrated that treatment of syngenic murine A20 B-lymphomas and CT26WT carcinomas with intratumoral (i.t.) injection with LTX-315 resulted in complete tumor regression. The present study was undertaken to investigate whether LTX-315 induced an antitumor response in vivo in a novel malignant rat mesenchymal tumor model with “stemness” properties. Methods: Following long-term culturing of bone marrow-derived rat mesenchymal cells, a transformed mesenchymal cell line (rTMSC) has been been developed. rTMSC has, as the non-malignant rMSC, maintained osteogenic and adipose differentation properties and side population cells from rTMSC are highly clonogenic both in vitro and in vivo. Previously we have shown that s.c. as well as i.v. or i.p. injection of rTMSCs form immature solid sarcomas both in nude rats as well as in PVG rats. In this study the rTMSCs were marked with a dual reporter gene GFP and Luciferase and a CCD camera was used for dynamic living imaging. rTMSCs (5×105 cells) were subcutaneously inoculated into PVG rats and established tumors treated i.t. with LTX-315. Results: Intratumoral treatment with LTX-315 resulted in a complete regression in the majority of the treated animals. Successfully treated mice were protected against s.c. or i.p. re-challenge with rTMSCs. Conclusions: Taken together, our results suggest that LTX-315 treatment induced complete regression and long-term, specific cellular immunity against malignant rat mesenchymal tumor cells with “stemness” properties”. Thus, intratumoral administration of a cytolytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against established cancers containing CSCs
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 LB-161. doi:10.1158/1538-7445.AM2011-LB-161
Abstract LB-178: Analysis of restored FFPE samples on Infinium methylation arrays
Authors: Le Jennie , Pokholok Dmitry , Teo Wei Wen , Barnes Brett , Steemers Frank , Hansen Mark , Fan Jian-Bing , Ronaghi Mostafa , Shen Richard , Helm Alex , Fackler Mary Jo , Umbricht Chris , Bibikova Marina , Sukumar Saraswati , Gunderson Kevin L. 
Published: July 2012

Abstract
Millions of Formalin Fixed Paraffin Embedded (FFPE) cancer tissue samples currently present in the US and worldwide provide an enormous, invaluable repository to the discovery of biomarkers in cancer research, drug development, diagnosis and treatment of diseases. However, the processes of fixation and storage of FFPE samples leads to degradation and base modification with chemical residues. This degraded FFPE DNA is inefficiently amplified by the Infinium® whole genome amplification (WGA) step leading to poor performance in genome wide methylation analysis. In this study, purified FFPE DNA or crude lysates (200–500 ng input) were bisulfite converted and restored through Illumina's Infinium HD DNA Restoration kit consisting of a combination of treatment with a DNA polymerase, a repair enzyme, and a ligase. Results of methylation analysis on high density HumanMethylation450 BeadChip®, featuring over 450,000 assays indicated that even highly degraded samples which show initial call rates (genes detected p =0.01) of 50–70% can be successfully restored to a state that achieved call rates of greater than 90%. Direct comparison of frozen and FFPE samples from the same tumors showed an R2 correlation of beta values of greater than 95.0% between fresh frozen (FF) and FFPE samples. We also developed a method to assess FFPE sample quality based on a 90 bp qPCR assay (Infinium HD FFPE QC kit). In this assay FFPE samples exhibiting a Ct (Cq) difference of less than six relative to an intact standard are considered to pass the QC test and generally perform well in the assay.
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 LB-178. doi:10.1158/1538-7445.AM2011-LB-178
Abstract LB-424: A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility to bladder cancer
Authors: Gu Jian , Chen Meng , Shete Sanjay , Amos Christopher I. , Kamat Ashish , Ye Yuanqing , Lin Jie , Dinney Colin P. , Wu Xifeng 
Published: July 2012

Abstract
Telomeres play a critical role in maintaining genome integrity. Telomere shortening is associated with the risk of many aging-related diseases. Classic twin studies have shown that genetic components may contribute up to 80% of the heritability of telomere length. In the study we report here, we used a multi-stage genome-wide association study (GWAS) to identify genetic determinants of telomere length. The mean telomere length in peripheral blood leukocytes was measured by quantitative real-time polymerase chain reaction. We first analyzed 300,000 single-nucleotide polymorphisms (SNPs) in 459 healthy controls, finding 15,120 SNPs associated with telomere length at P &lt; 0.05. We then validated these SNPs in two independent populations comprising 890 and 270 healthy controls, respectively. Four SNPs, including rs398652 on 14q21, were associated with telomere length across all three populations (pooled P-values of &lt; 10−5). The variant alleles of these SNPs were associated with longer telomere length. We then analyzed the association of these SNPs with the risk of bladder cancer in a large case-control study. The variant allele of rs398652 was associated with a significantly reduced risk of bladder cancer (odds ratio = 0.81; 95% confidence interval, 0.67–0.97; P = 0.025), consistent with the correlation of this variant allele with longer telomeres. We then conducted a mediation analysis to examine whether the association between rs398652 and reduced bladder cancer risk is mediated by telomere length, finding that telomere length was a significant mediator of the relationship between rs398652 and bladder cancer (P = 0.013) but that it explains only 14% of the effect. In conclusion, we found that the SNP rs398652 on 14q21 was associated with longer telomere length and a reduced risk of bladder cancer and that a small portion of the effect of this SNP on bladder cancer risk was mediated by telomere length.
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 LB-424. doi:10.1158/1538-7445.AM2011-LB-424
Abstract LB-463: Proteomic patterns of colonic submucosa delineates the inflammatory colitides. This could aid understand IBD-related colorectal malignancy
Authors: Schäffer Michael W. , Smith Joan C. , Roy Tanusri Ghosh , Wise Paul E. , Seeley Erin H. , Washington Mary K. , Schwartz David A. , Adunyah Samuel E. , Muldoon Roberta L. , Herline Alan J. , Moses Harold L. , Caprioli Richard M. , M'Koma Amosy E. 
Published: July 2012

Abstract
Purpose: Differentiating Crohn's colitis (CC) and ulcerative colitis (UC) can be challenging even in combination of clinical, endoscopic, radiologic and histopathology examination. Biomarker studies have thus far been unsuccessful for disease delineation. We aim to use unique tissue proteomic methods to evaluate colonic tissue layers for potential biomarkers to identify CC vs. UC. Methods: Fresh-frozen colon specimens from resections for IBD and/or colorectal cancer were retrospectively retrieved. Colitis diagnoses were histologically re-confirmed by a blinded gastrointestinal pathologist. Three sample groups (n=5 each group) were examined: normal colon from CRC specimens (control), UC & CC. MALDI-MS was used to profile mucosal and submucosal compartments individually. Frozen tissues were sectioned at ∼10–15 μm for mounting onto either metal or conductive glass target plates (the glass plates allowing for histologic and MALDI-MS analysis on the same section). Sinapinic acid (20 mg/mL in 50:50 acetonitrile: 0.1% TFA in water) was used to give the best combination of uniform crystal coverage and signal quality for direct tissue protein analysis. Results: MALDI-MS achieved high mass accuracy (±0.01 Daltons) in the lower mass range (&lt;15 kDa). There was distinguishable isotopic resolution of mass-to-charge ratio (m/z) values between normal vs the IBD and more strikingly between CC vs. UC (p&lt; 0.0009) of SAM and FDR tests. There were 5 statistically significant discriminative m/z peaks observed in CC vs UC submucosa. The mucosa did not yield such distinctive peaks. Both the mucosa and submucosa provided signatures that differentiated IBD (CC or UC)) from control tissues (p&lt; 0.001). Conclusions: MALDI-MS tissue profiling as described distinguished the colitides. The methodology revealed 5 m/z peaks of interest. Analyses are underway to identify these IBD discriminative proteins. We hypothesize that these biomarker candidates that distinguish UC from CC will allow delineation of indeterminate colitis into UC or CC. Whether these protein fingerprints play a role in colonic carcinogenesis remains to be elucidated.
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 LB-463. doi:10.1158/1538-7445.AM2011-LB-463
Abstract LB-48: Cooperation of NF-κB, STAT3 and p300 on the growth and survival of plasma-cell neoplasia
Authors: Han Seong-Su , Son Dong-Ju , Duncan Kaylia , Janz Siegfried 
Published: July 2012

Abstract
Collaboration of pro-inflammatory cytokine, interleukin 6 (IL-6), with oncogenic transcription factor, MYC, has been implicated in the natural history of human B-cell and plasma-cell neoplasms such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). To generate a mouse model of IL-6/MYC-driven B-lineage tumors, we intercrossed strain C.H2-Ld-IL6 mice, which carry a human IL6 cDNA gene under control of the major histocompatibility complex (MHC) H2-Ld promoter, with strain C.iMycEμ and C.iMycCα mice, which harbor a gene-insertion mutation that recapitulates the chromosomal T(12;15) translocation leading to deregulated expression of MYC in mouse plasmacytoma (PCT). Double-transgenic C.IL6/iMycEμ and C.IL6/iMycCα mice develop PCT with full penetrance (100% tumor incidence), short latencies (3–6 months) and remarkable phenotypic consistency. To test the hypothesis that nuclear factor-κB (NF-κB) signaling plays a role in malignant plasma-cell transformation in these mice, we performed electrophoretic mobility shift assays (EMSA) using splenic B cells from C.IL6/iMycΔEμ mice. We found that the splenocytes contained elevated levels of NF-κB and signal transducer and activator of transcription 3 (STAT3) DNA-binding activities compared to normal splenic B cells used as control. Super-shift assays demonstrated that in addition to p50, p65 and c-Rel (indicators of canonical NF-κB pathway activation), RelB was involved. This suggested the additional activation of alternative NF-kB signaling. NF-kB, pSTAT3 and co-transcription factor, p300, were shown to be physically associated in transgenic B cells. Ongoing studies are aimed at elucidating whether NF-κB/STAT3/p300 signaling underlies up-regulation of c-myc level in the course of PCT development. Using qPCR we also found that p21 – which is usually known as a tumor suppressor and direct target of NF-κB, STAT3, p53 and MYC – exhibited increased p53-independent expression in B cells obtained from C.IL6/iMycΔEμ mice, but not from C.IL6 or iMycΔEμ mice. In contrast, the expression of Aurora kinase A, a direct upstream regulator of both NF-kB and E2F1, was strongly up-regulated in B cells from C.IL6/iMycΔEμ, C.IL6 and iMycΔEμ mice. Likewise, E2F1, a direct upstream regulator of p21, and E2F3, a direct upstream regulator of both p21 and Aurora kinase A, were upregulated. Our findings suggest that p21 is up-regulated, either directly or indirectly, through Aurora kinase A and/or NF-κB/STAT3/p300 complex. Furthermore, they indicate the usefulness of the newly developed IL-6/MYC mouse tumor model for identifying potential targets for the treatment and prevention of MM and WM.
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 LB-48. doi:10.1158/1538-7445.AM2011-LB-48
Abstract LB-52: Integrative protein and transcriptomic analysis identified an EMT-associated secretory phenotype that correlates with metastasis and predicts survival in lung adenocarcinoma patients
Authors: Reka Ajaya Kumar , Chen Guoan , Jones Richard , Kim Sinae , Michailidis George , Kuick Rork , Pisano Michael , Beer David , Omenn Gilbert , Keshamouni Venkateshwar 
Published: July 2012

Abstract
The epithelial-mesenchymal transition (EMT) confers many clinicaly relevant properties to cancer cells, including migratory and invasive capacity, resistance to apoptosis, drug resistance, evasion of host immune surveillance, and tumor stem cell traits. Therefore, we reasoned that characterizing the secretome of cultured cells in EMT may identify biomarkers which allow monitoring of EMT in tumors and provide a signature to predict metastasis and survival in patients with cancers. Utilizing aTGF-β-induced EMT model with A549 lung adenocarcinoma cells, we harvested serum-free conditioned media from control and EMT cells (5 ng/ml TGF-β, 72h) to quantitatively profile differentially expressed proteins by GeLC-MS/MS and spectral counting. We identified &gt;2000 proteins, &gt;70% of which were putative secretory proteins. Corresponding transcriptomic analysis was performed by Affymetrix U133-plus microarray which identified ∼3,500 genes as differentially expressed. By integrating these two data sets we derived an EMT-associated secretory phenotype (EASP) comprising 97 genes of secretory proteins that were differentially up-regulated by at least two-fold during EMT both for protein and mRNA levels. Several of these proteins were validated by MRM. Analysis of EASP expression in a gene expression dataset from 443 human lung adenocarcinoma tumors revealed strong positive correlations with lymph node metastasis (p&lt;0.05), advanced tumor stage (p=0.006) and histological grade (p&lt;0.00001). After splitting the 443 tumors into a training (n=254) and test (n=189) sets, random forest survival analysis, including age, sex and stage as variables, stratified the test-set into low, medium and high-risk groups with significant differences in overall survival (p=0.0002). For further validation we tested EASP in two independent histologically distinguished lung cancer data sets. Interestingly, EASP predicted survival only in the dataset with adenocarcinomas (n=111, p=0.03), not in the dataset with squamous tumors (n=130). This result indicates that integrative analysis of relevant biological processes in cell-culture models may provide mechanism-related, tumor type-specific, clinically-relevant biomarkers with significant prognostic value.
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 LB-52. doi:10.1158/1538-7445.AM2011-LB-52