bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1689: Impact of pre-treatment body mass index on patients with head and neck cancer treated with radiation
Authors: Tsang Ngan M. 
Published: August 2012

Abstract
Purpose: Radiation therapy (RT) may lead to difficulty in swallowing and subsequently weight loss in patients with head and neck cancer. We investigated the association of pre-treatment body mass index (preT BMI) with outcomes of head and neck cancer in patients treated with radiation. Methods: All 1562 patients diagnosed with head and neck cancer and treated with curative-intent RT to a dose of 60Gy or higher between 1994 and 2004 were retrospectively studied. Body weight was measured both at entry and at the end of RT. cancer-specific survival (CSS), overall survival (OS), locoregional control (LRC) and distant metastasis (DM) were analyzed by preT BMI (&lt; 25 Kg/m2 vs ≤ 25Kg/m2). The median follow-up was 8.6 years. Results: Patients with higher preT BMI appeared to have earlier T and N stage. Patients with lower preT BMI were statistically significantly associated with poor CSS (p = 0.023) and OS (p &lt; 0.0001) than those with higher preT BMI. There is no significant difference between high and low preT BMI in LRC and DM. Body weight loss (BWL) during radiation did not influence survival outcomes. However, in the group of higher preT BMI, CSS, OS and DM-free survival of patients with less BWL during radiation was statistically longer when compared with greater BWL (p = 0.002, &lt; 0.0001, and 0.033). Conclusion: This study demonstrates preT BMI greater than or equal to 25 Kg/m2 positively influenced survival outcomes for patients with head and neck cancer. Patients with higher preT BMI who were able to maintain their weight during radiation had significantly better survival and distant outcomes than patients experiencing greater BWL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1689. doi:1538-7445.AM2012-1689
Abstract 1690: Tumor-educated macrophages promote tumor growth and peritoneal metastasis in an orthotopic nude mouse model of human pancreatic cancer
Authors: Menen Rhiana , Hassanein Mohamed K. , Momiyama Masashi , Suetsugu Atsushi , Moossa Abdool R. , Bouvet Michael , Hoffman Robert M. 
Published: August 2012

Abstract
There is a strong association between poor survival and increased macrophage density in many cancers. In the current study, we determined whether macrophages from tumor-bearing mice (tumor-educated macrophages) had greater tumor-promoting capability than macrophages from non-tumor-bearing mice. Ten transgenic nude mice ubiquitously-expressing GFP were injected subcutaneously with the human pancreatic cancer cell line, BXPC3 stably expressing RFP. GFP-expressing macrophages from tumor-bearing transgenic GFP mice were harvested and defined as “tumor-educated macrophages”. Macrophages were also harvested from transgenic GFP mice (n=10) without subcutaneous tumors and identified as “naïve macrophages.” Three groups of mice were studied: 1) A control group without addition of macrophages (n=10); 2) A naïve group, with weekly intraperitoneal (ip) injection of 106 naïve macrophages per mouse (n=10); and 3) A tumor-educated group, with weekly ip injection of 106 tumor-educated macrophages per mouse (n=10). The study ended with termination of the tumor-educated group after 8 weeks due to a pre-morbid state identified in all mice. At this time, all mice in each of the three study arms were terminated, imaging was performed, and total tumor weight was obtained. In the control group, the average primary tumor weighed 668 mg; only three mice (30%) developed peritoneal metastases with an average weight of 241 mg. The naïve-macrophage group had an average tumor weight of 823 mg (p=0.51); 50% developed peritoneal metastases with an average weight of 975 mg (p=0.029). The tumor-educated-macrophage group had an average primary tumor weight of 2095 mg (p=0.001); 75% of mice developed peritoneal metastases with an average weight of 2135 mg (p=0.008). When comparing naïve- to tumor-educated- groups, primary tumor weight was significantly greater in the tumor-educated group (p=0.003), and the average weight of metastasis was 2.2 times greater in the tumor educated group, however this did not reach statistical significance (p = 0.17). When comparing naïve- to tumor-educated-groups, there was no statistically significant difference with regard to body weight (p=0.87), or weight of metastasis (p=0.68); however primary tumor weight was significantly greater in the tumor-educated group (p=0.013). Tumor-educated-macrophages specifically promote tumor growth progression in an orthotopic nude mouse model of pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1690. doi:1538-7445.AM2012-1690
Abstract 1704: AC electrokinetic isolation of cell free high molecular weight DNA (CF-HMW DNA) from serum
Authors: Lu Jerry , Hanna William , Kumosa Lucas S. , Bhalla Megha , Cheung Veronica W. , Turner Robert P. , McCanna James P. , Tu Eugene , Charlot David J. , Krishnan Rajaram 
Published: August 2012

Abstract
Recent reports of CF-HMW DNA in a variety of diseases has led to interest in its use as a prognostic biomarker, a diagnostic or screening tool for cancer. Apoptotic DNA (&lt;200bp) is present in the circulation of normal healthy individuals. In cancer, unregulated cell growth leads to uncontrolled cell death, or necrosis, which produces HMW DNA (&gt;500bp) that is then trafficked into circulation. Dielectrophoresis, or DEP (movement of particles in a non-uniform AC electric field), based electrokinetic techniques have been used for protein biomarker screening, cell separation, and DNA manipulation. Using specific DEP frequencies, analytes are moved to known locations (high or low field region) based on their inherent dielectric properties. The process allows specific nano-sized particles to be highly concentrated into high field regions, while micron-size cells are held weakly in low field regions. With fluidic washing, cells can be removed while nano-sized particles are held in high field regions. This method can effectively act as a CF-HMW DNA enrichment process for biological fluids. Unfortunately, DEP does not work well in (high conductance) physiological buffers, requiring significant dilution of the sample and, as a result, the target analyte concentration. Here, we describe a novel AC electrokinetic (ACE) technique using a custom microelectrode array and AC parameters to isolate and analyze CF-HMW DNA from high conductance serum. DNA from normal serum samples and the A549 cell line were isolated using Qiagen kits to determine initial DNA quantities. Normal sera were spiked with A549 cell line DNA at concentrations from 0 to 500 ng/ml and subjected to a 20 minute ACE protocol. DNA isolation was visualized in situ using SYBR Green I fluorescence and then eluted for use in secondary analyses. Results showed minimal fluorescence from samples without spike whereas A549 DNA spiked samples showed concentration-dependent fluorescence on the microelectrodes. After elution, levels of DNA were quantitated using ALU-sequence based qPCR and K-ras mutational status was confirmed by ABI CastPCR. Future experiments will compare CF-HMW DNA levels from normal and cancer patients across a variety of solid tumors. The ACE technique enables rapid isolation and detection of CF-HMW DNA directly from biological fluids without prior sample prep and has broad utility for diagnosis and monitoring of cancer and other diseases in which CF-HMW DNA may be used as a marker.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1704. doi:1538-7445.AM2012-1704
Abstract 1719: Significance of thymidylate synthase copy numbers for resistance to pemetrexed in lung cancer
Authors: Kasai Daishi , Oguri Tetsuya , Ozasa Hiroaki , Uemura Takehiro , Kunii Eiji , Takakuwa Osamu , Ohkubo Hirotsugu , Miyazaki Mikinori , Maeno Ken , Sato Shigeki 
Published: August 2012

Abstract
Pemetrexed is a multitargeted antifolate with promising clinical activity in non-squamous lung cancer. It targets the folate-dependent enzymes thymidylate synthase (TS), reduced folate carrier, and folylpolygamma-glutamate synthetas, all of which are involved in the de novo biosynthesis of thymidine and purine nucleotides.The primary mechanism of the action of pemetrexed is inhibition of TS, which results in a decrease in the available thymidine necessary for DNA synthesis. We have previously established pemetrexed -resistant lung cancer cell line, and have shown that overexpression of TS resulted in increased pemetrexed resistance. We have also examined that TS copy numbers by quantitative real-time PCR, were increased in pemetrexed-resistant cells. Therefore we investigated TS copy numbers in lung cancer cell lines and clinical samples to examine whether TS copy numbers are the biomarker for pemetrexed sensitivity. First, we examined the correlation of TS copy numbers and 50% cell survival of pemetrexed for 14 lung adenocarcinoma cell lines, and a meaningful relationship was accepted. In addition, we examined TS copy number in 20 bronchoscopic specimens of non-squamous lung cancers, and found that the correlation was also confirmed between TS copy numbers and clinical response. Our study suggests that TS copy number may be a predictive marker for pemetrexed sensitivity in lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1719. doi:1538-7445.AM2012-1719
Abstract 1723: Can histologic patterns of pulmonary adenocarcinoma reflect histologic grade, one of the most important factors of cancer prognosis?
Authors: Hwang Ilseon , Park Keon Uk , Kim Jin Young , Ha Eunyoung 
Published: August 2012

Abstract
Background: Pulmonary adenocarcinoma shows highly heterogeneous histologic pattern. Histologic pattern is suggested to be an important prognostic factor, therefore predominant histologic pattern is emphasized in 2010 IASLC/ATS/ERS classification of pulmonary adenocarcinoma. However, there are a few papers on the prognosis of pulmonary adenocarcinoma according to histologic patterns, especially in various stages. The aim of this study is to evaluate prognosis according to histologic patterns in pulmonary adenocarcinoma with various stages. Methods: We examined 125 cases of surgically resected pulmonary adenocarcinomas with various stages from January 1998 to December 2007. Invasive adenocarcinomas were classified into histologic subtypes which are lepidic, papillary, acinar, solid and micropapillary patterns by 2010 IASLC/ATS/ERS classification. Invasive adenocarcinoma was divided into 2010 classification (I), predominant and second predominant pattern (II), predominant and the worst pattern (III), and modified predominant pattern (IV). Results: Proportions of predominant lepidic, papillary, acinar, solid and micropapillary patterns were 11 (9.3%), 8 (6.8%), 54 (45.8%), 38 (32.2%) and 7 (5.9%), respectively. All histologic classification systems were not correlated with clinical manifestations including age, tumor size, T stage, N stage or recurrence. However, all histologic classification systems were significantly correlated with overall survival rates (p=0.010, 0.044, 0.001, and 0.013) by Kaplan-Meier survival test. In Cox proportional hazard model, histologic pattern was independent factor of prognosis on classification according to I, III, IV (p=0.017, 0.006 and 0.023). Conclusion: Histologic pattern is an independent prognostic factor in pulmonary adenocarcinoma with various stages and histologic patterns of pulmonary adenocarcinoma reflect the degree of histologic differentiation, one of the most important prognostic factor.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1723. doi:1538-7445.AM2012-1723
Abstract 173: Targeting the MUC1-C oncoprotein blocks activation of FLT-3/ITD and induces death of acute myeloid leukemia cells
Authors: Liu Suiyang , Kharbanda Surender , Kufe Donald , Stone Richard 
Published: August 2012

Abstract
Acute myeloid leukemia (AML) is an intrinsically resistant disease especially in the 30 % of patients whose blasts have a FLT3-ITD mutation (constitutively activated transmembrane tyrosine kinase due to insertion of between 3 and 300 base pairs in the juxta-membrane coding region). The MUC1 oncoprotein is aberrantly expressed in AML cells; however, there has been no evidence for involvement of MUC1 in FLT3-ITD signaling. We show that the FLT3-ITD associates with the MUC1 oncoprotein thereby leading to a new therapeutic target. We have synthesized MUC1-C peptide inhibitors that penetrate cells and bind to the MUC1-C cytoplasmic domain blocking its oncogenic function. In the present study, we demonstrate that MUC1-C peptide inhibitor treatment of the FLT3-ITD positive human MOLM-14, MV4-11 AML cell lines, and primary blasts from patients with AML, leads to growth arrest and induction of late apoptosis/necrosis. MUC1-C inhibitor-induced cell death of these cells is associated with significant downregulation of phospho-FLT3-ITD, indicating that inhibition of MUC1-C blocks FLT3-ITD activation. Taken together, these findings provide support for the evaluation of the MUC1-C inhibitor, GO-203-2C (an agent now undergoing Phase I evaluation in solid tumors), in the treatment of patients with AML harboring the FLT3-ITD activating mutation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 173. doi:1538-7445.AM2012-173
Abstract 1734: Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC
Authors: Guo Chengcheng , Shao Ruping , Correa Arlene M. , Behrens Carmen , Fang Bingliang , Roth Jack A. , Wistuba Ignacio I. , Swisher Stephen G. , Lin Tongyu , Pataer Apar 
Published: August 2012

Abstract
RNA-dependent protein kinase (PKR) is an independent prognostic variable in patients with non-small cell lung cancer (NSCLC). In the present study, we investigated the correlation between PKR and 25 other biomarkers for NSCLC, identified the markers that could further improve the prognostic significance of PKR, and elucidated the mechanisms of interaction between these markers and PKR. Tissue microarray samples obtained from 218 lung cancer patients were stained with an anti-PKR antibody and antibodies against 25 biomarkers. Immunohistochemical expression was scored and used for Kaplan-Meier survival analysis. The interaction between PKR and EphA2 in NSCLC cell lines was examined. We found that PKR was associated with EphA2 and that the prognostic information regarding NSCLC provided by the combination of PKR and EphA2 (P/E) was significantly more accurate than that provided by either marker alone. The 5-year overall survival rate in PKRlow/EphA2high patients (20%) was significantly lower than that of PKRhigh/EphA2low patients (74%), PKRhigh/EphA2high patients (55%), and PKRlow/EphA2low patients (55%) (P &lt; 0.0001). We also found that the PKR:EphA2 (P/E) ratio was significantly associated with prognosis (P &lt; 0.0001). Univariate and multivariate Cox analyses revealed that this P/E combination or ratio was an independent predictor of overall survival. In addition, induction of PKR expression reduced EphA2 protein expression levels in NSCLC cell lines. PKR/EphA2 is a significant predictor of prognosis for NSCLC. PKR/EphA2 may be a promising approach to improving screening efficiency and predicting prognosis in NSCLC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1734. doi:1538-7445.AM2012-1734
Abstract 1740: Inverse association of depletion of interferon-induced protein with tetratricopeptide repeats 2 with increased distant metastasis in patients with oral squamous cell carcinoma
Authors: Lai Kuo-chu , Liu Chung-Ji , Chang Kuo-Wei , Lee Te-Chang 
Published: August 2012

Abstract
Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), one of most responsive interferon-stimulated genes, is inversely associated with prognosis of patients with oral cancer. In the present study, we further demonstrated that IFIT2 mRNA and protein expression was positively associated with E-cadherin expression in tissue specimens of oral squamous carcinoma cancer (OSCC). Loss of E-cadherin and IFIT2 was observed at the invasive front, suggesting that loss of IFIT2 may induce EMT and lead to metastasis in OSCCs. Accordingly, we found that OSCC patients with lower IFIT2 (IFIT2 &lt; 50%) levels had higher distant metastatic rates and poorer prognoses compared to OSCC patients expressing higher levels of IFIT2 (IFIT2 ≤ 50%). In stable IFIT2-depleted OSCC cells, we observed epithelial-mesenchymal transition (EMT) and found enhanced cell motility and invasiveness when compared to control cells. Furthermore, our results indicated that atypical protein kinase C (aPKC) signaling was activated in IFIT2-depleted cells. Inhibition of aPKC by a specific myristoylated PKC∈ pseudosubstrate or aPKC siRNA abolished IFIT2 depletion-induced EMT, migration, and invasion, indicating that activation of aPKC signaling plays an essential role in the cellular activities induced by IFIT2 depletion. Our study demonstrates that IFIT2 depletion activates the aPKC pathway and hence induces EMT, cell migration, invasion and metastasis. Taken together, IFIT2, a protein responsible for interferon stimulation, may prevent OSCC from metastasizing and may serve as a prognostic marker.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1740. doi:1538-7445.AM2012-1740
Abstract 1757: Elesclomol (STA-4783) is a potent inhibitor of topoisomerase II
Authors: Wu Xing , Yalowich Jack C. , Hasinoff Brian B. 
Published: August 2012

Abstract
Elesclomol (STA-4783; N’1, N’3-dimethyl-N’1, N’3- bis(phenylcarbonothioyl)propanedihydrazide) is an anticancer drug that has received both fast track and orphan drug status from the FDA and is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with copper(II) and may exert its anticancer activity through the induction of oxidative stress. In the studies reported here elesclomol was assessed for its ability to inhibit: 1) the growth of the human erythroleukemic K562 cell line and an etoposide-resistant K/VP.5 cell line; 2) the decatenation activity of DNA topoisomerase IIα; and 3) the relaxation activity of DNA topoisomerase I. Elesclomol was also evaluated for its ability to induce topoisomerase IIα-mediated double strand cleavage of pBR322 DNA and to form topoisomerase IIα-DNA covalent adducts in the cell-based ICE assay. Elesclomol inhibited K562 cell growth in the submicromolar concentration range. However, K/VP.5 cells were not cross-resistant. Elesclomol also strongly inhibited the decatenation activity of topoisomerase IIα in the low micromolar concentration range. Elesclomol may also act as topoisomerase IIα poison because it induced formation of linear DNA, though not as strongly as etoposide. In conclusion, these results show that elesclomol may, in part, inhibit cell growth through the targeting of topoisomerase II. Support: CIHR, a Canada Research Chair in Drug Development to B.B.H., a National Institutes of Health grant CA090787 to J.C.Y.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1757. doi:1538-7445.AM2012-1757
Abstract 1759: Novel naphthalimide analogs elicit their anti-tumor activity through a dual inhibition of topoisomerase II and Akt signaling pathway
Authors: Gowda A.S. Prakasha , Sk Ugir Hossain , Spratt Thomas E. , Amin Shantu , Sharma Arun K. 
Published: August 2012

Abstract
Naphthalimide derivatives such as mitonafide, a topoisomerase II inhibitor, have shown antitumor activity both in preclinical studies and in phase I and phase II clinical trials. However, it suffers from severe toxicity issues, especially central nervous system (CNS) toxicity. We have recently reported promising naphthalimide analogs designed by incorporating functional groups such as a isothiocyanate (ITC) group which is present in chemicals found in cruciferous vegetables, in place of N, N-dimethyl group in mitonafide. Some of these agents effectively induced apoptosis in melanoma cells and inhibited cell proliferation, and inhibited melanoma tumor growth by ∼60% without any apparent systemic toxicity issues. The ITC group was incorporated in the structure in an attempt to lower the toxicity associated with mitonafide and also because this functionality has been shown to block PI3K/Akt pathway which is activated in majority of cancer types; Akt3 is activated in 70% of sporadic melanomas. The idea was to generate a compound capable of inhibiting not only topoisomerase II similar to mitonafide but also PI3K kinase. In order to evaluate the underlying mechanism of action, we first evaluated topoisomerase-II inhibitory activity of agents relative to mitonafide to check if the new agents retained this property. Relaxation activity of DNA topoisomerase II was determined by measuring the conversion of supercoiled pBR322 plasmid DNA to its relaxed form. Our results indicate that the ITC analogs, NNITC-2 and NITC-6, exhibited significant inhibition for DNA-topoisomerase II similar to mitonafide. Interestingly, corresponding isoselenocyanate (ISC) analog NISC-6 was less effective compared to NITC-6 as a topoisomerase II inhibitor; NNISC-2 on the other hand was equally good as NNITC-2. Furthermore, to test our hypothesis that the addition of ITC group into the structure would make it capable of inhibiting PI3K/Akt pathway, we examined the ability of naphthalimide derivatives to inhibit the total cellular content of human Akt pathway proteins, by Western blot analysis using polyclonal antibodies, in human melanoma cancer cells (UACC903). UACC903 cells treated with ITC derivatives at 0.5, 1 and 5 μM, showed a rapid decrease in Akt pathway proteins level in a dose-dependent manner. In comparison, ISC analogs were less effective. Detailed results of these investigations will be presented.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1759. doi:1538-7445.AM2012-1759