bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4591: Comparison of the inhibitory effects of unmodified and modified combinations of chemopreventive agents on MIA PaCa-2 and Panc-1 human pancreatic cancer cell lines
Authors: Sutaria Dhruvitkumar , Huang Ying , Prabhu Sunil 
Published: June 2012

Abstract
Pancreatic cancer is the fourth leading cause of death in the United States with approximately 40,000 estimated deaths in 2010. The objective of our study was to compare the effectiveness of chemopreventive combination regimens of aspirin, curcumin and sulforaphane (ACS) administered in unmodified (free drug) and in modified forms, encapsulated within solid lipid nanoparticles (SLNs), on the MIA PaCa-2 and Panc-1 human pancreatic cancer cell lines. MTS cell proliferation and apoptosis assay studies were conducted on cultured cells. For the MTS assay, upon 75 % confluence, 2.5 × 103 cells for MIA PaCa-2 and 4 × 103 cells for Panc-1 were transferred into each well of 96-well plates. The ACS chemopreventive agents alone or in combination were added to the cells and incubated for 72 h. Absorbance was recorded at 490 nm using an ELISA plate reader. For the apoptosis assay, 3 × 105 cells were cultured in 6-well plates for both Panc-1 and MIA PaCa-2 cell-lines. ACS, individual or combinations, were added and the plates were incubated for 72 h. Cells were analyzed using flow cytometry, measuring the fluorescence emission at 530 nm (FL1) and &gt;575 nm (FL3). IC50 values obtained for the respective unmodified and modified forms of aspirin were (2.05mM/L; 66.08µM/L), curcumin (16.05µM/L; 4.93µM/L) and free sulforaphane at 11.82 µM/L for MIA PaCa-2 cells. Similarly, for Panc-1 cells, the IC50 values for unmodified and modified aspirin were (2.42mM/L; 90.23µM/L), curcumin (24.01 µM/L; 7.5µM/L) respectively and free sulforaphane at 17.81µM/L. For MIA PaCa-2 cell line, unmodified combinations of aspirin (1mM/L) with curcumin (10µM/L) and sulforaphane (5µM/L) showed significant reduction in cell viability of &gt;60% using MTS assay. In comparison, aspirin SLN (25µM/L), curcumin SLN (2.5µM/L) and free sulforaphane (5µM/L) mixtures showed cell viability of &gt;55%. Flow cytometry analysis demonstrated apoptosis of 63% (unmodified) and 50% (modified) for the combinations, at the same concentration ranges as above. For the Panc-1 cell line, treatment with similar concentrations of unmodified and modified SLN combinations showed a &gt;75% and &gt;60% decrease in cell viability (MTS assay) and 63% and 54% induction of apoptosis cells, respectively. Our results demonstrated that the drugs when encapsulated in SLNs at lower concentrations exhibited decreasing cell proliferation and increased induction of apoptosis within the pancreatic cancer cell lines. This data provides compelling evidence of the potential of the SLN carrier system in designing in-vivo studies for the pancreatic cancer chemoprevention.
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 4591. doi:10.1158/1538-7445.AM2011-4591
Abstract 4605: Consumption of S-allylcysteine inhibits the growth of human non-small cell lung carcinoma in a mouse xenograft model
Authors: Tang Feng-Yao , Chiang En-Pei Isabel , Pai Man-Hui 
Published: June 2012

Abstract
Lung cancer is one of the leading causes of cancer death in the world. Human non-small cell lung carcinoma (NSCLC) accounts for almost 80 percent of lung cancer cases. Aberrant phosphoinositide 3-kinase (PI3K)/ Akt /mTOR signaling pathways play important roles and have been widely observed in the development of NSCLC. Previous studies indicated that garlic extracts such as diallyl disulfide (DADS) and diallyl trisulfide (DATS) could inhibit the proliferation of several types of cancer in vitro. However, the inhibitory effects of S-allylcysteine (SAC) on the growth of NSCLC have not been demonstrated yet. Therefore, we investigated whether consumption of SAC could prevent the growth of NSCLC in both in vitro and in vivo models. In the current study, SAC significantly inhibited the proliferation of human NSCLC A549 cells in vitro. Treatment of NF-κB inhibitor, Bay-11-7082, could significantly inhibit the proliferation of NSCLC A549 cells. Our results demonstrated that SAC significantly suppressed the activation of mTOR, NF-κB and cyclin D1 molecules in vitro. Furthermore, our results demonstrated that consumption of SAC significantly inhibited the growth of highly metastatic human NSCLC cells in tumor bearing mice. Bioluminescence imaging, pathological and immunohistochemical (IHC) staining results also indicated that SAC could effectively suppress the growth and malignant progression of human NSCLC in vivo. The chemopreventive effects of SAC were associated with suppression of mTOR and NF-κB molecules in vivo. These results suggested that SAC could act as an effective agent against the malignant progression of human non small cell lung cancer in both in vitro and in vivo models.
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 4605. doi:10.1158/1538-7445.AM2011-4605
Abstract 4608: Hydrogen sulfide-releasing aspirin inhibits the growth of leukemic Jurkat cells and modulates β-catenin expression
Authors: Gan Zong Yuan , Chattopadhyay Mitali , Kodela Ravinder , Boring Daniel , Crowell James A. , Kashfi Khosrow 
Published: June 2012

Abstract
Introduction: Acute leukemia is the primary cause of cancer-related mortality in children. ß -catenin, a regulator of cell-cell adhesion and transcription, is expressed in T-acute lymphoblastic leukemia cells, tumor lines of hematopoietic origin and primary leukemia cells but not in normal peripheral blood T cells. ß -catenin may promote leukemia cell proliferation, adhesion, and survival. Hydrogen sulfide-releasing aspirin (HS-ASA) is a novel compound with significant potential for the control of cancer. It consists of a traditional ASA molecule covalently bound to an H2S-releasing moiety (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione). Here we examined the effect of HS-ASA on the growth of Jurkat T-acute lymphoblastic leukemia cells and on the fate of ß -catenin.
Methods: HS-ASA was synthesized and purified at our lab with 1H-NMR verification. Cell line: Jurkat T-leukemia. Quantification of cell growth: MTT assay. Cell kinetics: cell cycle phase distribution by flow cytometry; apoptosis by subdiploid (sub-G0/G1) peak in DNA content histograms; and proliferation by PCNA. ß-Catenin and caspase-3 expression was assayed by immunoblotting in cells treated with HS-ASA at 24 hr. Caspase-3 enzyme activity, and H2S levels was also measured.
Results: 1) The IC50 for HS-ASA was 1.5 ± 0.2 µM, whereas that of ASA was &gt;5000 µM strongly suggesting that HS-ASA is at least 3000-fold more potent than traditional ASA. 2) At 0.5xIC50, 1xIC50, and 2xIC50 the following observations were made: Proliferation was inhibited by 88 ± 2%, 63 ± 2%, 42 ± 3%; apoptosis was increased by 15 ± 2%, 39 ± 3%, 54 ± 4%; and cells in the G0/G1 phase increased dose-dependently whereas those in the S and G2/M phases decreased, suggesting a G0/G1 block. 3) HS-ASA dose-dependently reduced the levels of ß-catenin, whereas ASA up to 5 mM had no effect on ß-catenin expression. HS-ASA also increased caspase-3 protein levels and increased its activity dose-dependently, at 0 (no treatment), 0.5xIC50, 1xIC50, and 2xIC50 the values were 3.9 ± 0.3, 12.3 ± 0.5, 23.3 ± 0.7, and 42.6 ± 1.2 pmol/min/mg protein. H2S levels also increased as a function of HS-ASA concentration.
Conclusion: HS-ASA strongly inhibits the growth of Jurkat T cells and causes inhibition of ß-catenin expression. These studies suggest one mechanism by which HS-ASA inhibits the growth of Jurkat T cells.
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 4608. doi:10.1158/1538-7445.AM2011-4608
Abstract 4613: Serum levels of antioxidants in college aged, elderly, and cancer patients
Authors: Bluemel Trevor S. , Sanderson Michael Q. , Jensen Jacob R. , Garrett Andrew R. , Alegre Melissa M. , Robison Richard A. , O'Neill Kim L. 
Published: June 2012

Abstract
Antioxidants are able to prevent the oxidation of biomolecules. Free radicals are oxidants known to be agents which damage DNA. This damage can lead to cancer. Antioxidants neutralize free radicals and are an effective defense system. It has been shown that consumption of fruits, nuts, vegetables, and seeds increases the body's total antioxidant capacity.1 Performing a study that provides data on antioxidant levels in serum will offer insight on potential improvements that can be made in the diets of various populations. In this study we used the oxygen radical absorbance capacity assay (ORAC) to compare serum antioxidant status in three different groups, college age, elderly, and cancer patients. Serum was obtained from 15 college age students (18-21) at Brigham Young University, 15 age matched elderly persons (over the age of 55), and 15 cancer patients. 10 ml of blood was drawn, allowed to clot, centrifuged to separate the cells from the serum, and then diluted to a 1/128 concentration. The ORAC assay was utilized as a way to determine the ability of serum to prevent the oxidation of fluorescein. The results of the experiment surprisingly demonstrate that cancer serum has the highest level of antioxidant status with 99200.97 trolox equivalents per Liter (TE/L) and a standard deviation (STDEV) of 17838.13. The elderly presented the second highest levels of serum antioxidants with 37837.75 TE/L and a STDEV of 7947.08. The college age group had the lowest TE/L with 19051.82 and a STDEV of 2113.36. The elderly compared to the youthful had a p-value &lt; 0.0001, and the cancer patients compared to the healthy possessed a p-value &lt; 0.0001. These results have brought forth more questions than answers. The elderly and cancer patients may have a greater concern for proper dietary intake compared to college age individuals. The cells of the youthful also may be more capable of intaking the antioxidants from the bloodstream. Further studies on these two conclusions may reveal more on the data retrieved.
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 4613. doi:10.1158/1538-7445.AM2011-4613
Abstract 4621: Zfra regulates protein degradation and provides strong prevention against skin cancer
Authors: Chang Nan-Shan 
Published: June 2012

Abstract
Zinc finger-like protein for regulating apoptosis (Zfra) is a 31-amino-acid protein, which participates in the mitochondrial pathway of apoptosis and affects the functions of tumor suppressors WWOX and p53. Here, synthetic full-length Zfra1-31, or truncated Zfra4-10, undergoes ladder-like self-polymerization by greater than 20-100 fold when phosphate ions are present in solutions (without catalytic enzymes). Upon encountering with Zfra, certain cellular proteins become “zfrated” and undergo degradation independently of the ubiquitin/proteasome system. Transiently overexpressed Zfra induces apoptosis of many types of cancer cells. Most strikingly, pre-injection of Zfra1-31 or Zfra4-10 via tail veins protects nude mice from growing cancer xenografts (e.g. melanoma and skin basal cell carcinoma cells). Alteration of Ser8 abolishes self-polymerization and cancer prevention, suggesting an essential role of Ser8 in protein zfration and degradation and cancer prevention.
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 4621. doi:10.1158/1538-7445.AM2011-4621
Abstract 4628: PBISe, an iNOS/Akt inhibitor for colon cancer chemoprevention
Authors: Desai Dhimant H. , Irby Rosalyn , Aliaga Cesar , Amin Shantu G. 
Published: June 2012

Abstract
Colorectal cancer (CRC) is one of the leading causes of premature death in people worldwide. Conversion of normal colonic cells to malignant lesions requires several steps and therefore often proceeds over considerable time periods, on average, 10-15 years, thus providing a window of opportunity for effective intervention and prevention. In 2010 it was estimated that in USA alone about 150,000 people will be diagnosed with colorectal cancer and that about 50,000 people will die of the disease. Today, there is handful of truly effective drugs for colon cancer is available for the patients giving a variety of chemotherapy cocktails. Preventive therapies are promising approach for treatment of cancer, and it has a potential to be a major component of colorectal cancer control. Inducible nitric oxide synthase (iNOS) deregulation and PI3K pathways are such events occurring in colon cancer development. Currently known iNOS inhibitors, such as, S,S’-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), require high concentration for clinical efficacy in colon cancer prevention causing systemic toxicity. It is known in the literature that by replacement of sulfur with selenium in the molecule provide a higher inhibitory potency to the compound. Therefore, to develop more potent agent effective at significantly lower concentration, a novel isosteric selenium analog, namely; Se,Se’-1,4-phenylene-bis(1,2-ethanediyl)bis-isoselenourea (PBISe) was developed. Preliminary investigation from our laboratory indicates that PBISe is 25 fold more potent than PBIT in four colon cancer cell lines in MTS assay. Western blot analysis showed decrease pAkt and Akt2 levels, and downstream pPRAS40 levels, and increase in cleaved PARP an apoptosis markers that are specific for Colon cancer. The results from our investigation on maximum tolerated dose (MTD) in FBV mice and male F344 rat when feed with PBISe in a diet as well as tumorigenicity in male (heterozygous) C57BL/6J-APCmin mice and in vitro studies will be discussed. These investigations are highly significant providing insight into the chemoprevention potential and mechanisms based development of PBISe that will inhibit colon cancer. This study was supported by NCI grant CA137763 (DD).
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 4628. doi:10.1158/1538-7445.AM2011-4628
Abstract 4641: Cumulative body burdens of polycyclic aromatic hydrocarbons associate with estrogen bioactivation in pregnant women: Protein adducts as biomarker of exposure
Authors: Lin Po-Hsiung , Wang Tzu-Wen , Tsai Chen-His , Wei Hz-Han , Chen Guan-Jie , Chen Dar-Ren , Chen Shou-Tung , Wang Shu-Li , Lin Che 
Published: June 2012

Abstract
The objective of this research was to develop a biochemical assay to simultaneously analyze protein adducts of quinonoid metabolites of polycyclic aromatic hydrocarbons (PAHs) and endogenous estrogen in pregnant women in Taiwan and to explore the correlations among them. The methodology, which employs trifluoroacetic acid anhydride (TFAA) and methanesulfonic acid (MSA) to selectively cleave cysteinyl adducts, had previously been applied to measure benzene and naphthalene adducts in albumin (Alb). In this study, we refined the assay to allow measurements of both naphthoquinone- and estrogen quinone-derived adducts in serum albumin derived from pregnant women in Taiwan. The isomeric forms of cysteinyl adducts of naphthoquinones, including 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) as well as estrogen quinones, including estrogen-2,3-quinones (E2-2,3-Q) and estrogen-3,4-quinones (E2-3,4-Q), are characterized by using isotopically-labelled bound internal standards after adducts cleavage by the TFAA/MSA derivatization procedure. We applied this method to analyze the background levels of cysteinyl adducts of naphthalene- and estrogen-derived quinones on human serum albumin(Alb)derived from healthy pregnant women (n=40) and their respective umbilical cords (n=40). Results showed that the background levels of cysteinyl adducts of 1,2-NPQ and 1,4-NPQ on human serum albumin were at levels ranging from 89-941 and 33-615 pmol/g, respectively. Logged levels of 1,2-NPQ-Alb were correlated with logged levels of 1,4-NPQ-Alb (correlation coefficient r=0.500, p&lt;0.001). In addition, cysteinyl adducts of E2-2,3-Q-1-S-Alb, E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb were detected in most of the subjects with median levels at 325, 457, and 592 pmol/g, respectively. We also found a significantly positive relationship between logged levels of E2-2,3-Q-4-S-Alb and those of E2-3,4-Q-2-S-Alb (r = 0.537, p&lt;0.001). We noticed that logged levels of 1,2-NPQ-Alb are positively and significantly associated with increasing logged levels of E2-3,4-Q-2-S-Alb (r = 0.539, p&lt;0.001). This evidence suggests that environmental exposure to PAHs may enhance the production of reactive quinone species of endogenous estrogen in human. Overall, we conclude that the methodology developed in this study may be applied to epidemiological study to serve as biomarkers of environmental exposure to PAHs and other modulators of estrogen homeostasis. (This work was supported by the National Science Council, Taiwan, through grant NSC99-2314-B-005-001-MY3)
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 4641. doi:10.1158/1538-7445.AM2011-4641
Abstract 4643: Epstein-Barr virus infection (EBV) and expression of B-cell oncogenic markers in HIV+ diffuse large B-cell lymphoma (DLBCL)
Authors: Chao Chun R. , Abrams Donald , Silverberg Michael J. , Haque Reina , Zha Hongbin D. , Martinez-Maza Otoniel , McGuire Michelle , Chi Margaret , Castor Brandon , Xu Lanfang , Leyden Wendy , Habel Laurel , Said Jonathan 
Published: June 2012

Abstract
Background: Lymphomagenicity of EBV in the setting of HIV infection has been widely accepted. However, the underlying carcinogenic mechanism of EBV is largely unknown and warrants further study. We sought to investigate the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV+ DLBCL.
Methods: HIV+ DLBCL cases diagnosed between 1996-2007 within the Kaiser Permanente California Health Plan were identified. Archived tumor specimens were retrieved and H&E slides were reviewed to identify representative tumor blocks for tissue microarray (TMA) construction. Immunohistochemistry staining was performed on TMA cores to analyze the expression of selected B-cell oncogenic markers in the following categories: (1) mutagenic molecule (that induce mutation/translocation), (2) cell cycle promoter, (3) B-cell activator and (4) anti-apoptotic protein. Percent of DLBCL cells with visible marker staining was scored on a scale from 0-4 (0-9%, 10-24%, 25-49%, 50-74% and ≥75%). EBV infection was determined by in situ hybridization of EBV encoded RNA and was considered positive if ≥10% of the DLBCL cells had detectable EBV. Correlations between EBV and marker expression were examined using Spearman's correlation coefficient.
Results: We identified 194 HIV+ DLBCL cases. Of these, 117 lacked sufficient tissue; another 7 had undetermined EBV status; and 70 were included in the study. Marker expressions are shown in the table:

Conclusion: There was a suggestion that Cyclin E and PKC-β2 were more commonly expressed in EBV+ DLBCL, and that FOXP1, BCL2, and Survivin were more commonly expressed in EBV- DLBCL. However, none of these associations reached statistical significance. These findings provide limited support that the underlying carcinogenic mechanism of EBV involves the mediation of the expression of oncogenic markers examined here. However, our study power was limited, thus requiring confirmation in larger studies.
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 4643. doi:10.1158/1538-7445.AM2011-4643
Abstract 4666: Genetic polymorphisms in the pre-microRNA flanking region and non-small cell lung cancer survival
Authors: Shen Hongbing , Hu Zhibin Zhibin , Chen Jiaping 
Published: June 2012

Abstract
Rationale: Previously, we reported that common variants in pre-miRNA sequences played a role in the prediction of non-small-cell lung cancer (NSCLC) survival.
Objectives: To assess whether variants in the pre-miRNA flanking region can influence the clinical behavior of NSCLC.
Methods: we conducted a two-stage study to examine the impact of a panel of 85 SNPs on the overall survival of 923 NSCLC patients (568 in the screening set and 355 in the validation set) in China.
Measurements and Main Results: Eleven single nucleotide polymorphisms (SNPs) were primarily associated with the NSCLC survival in the univariate analysis. However, in the validation set, only miR-30c-1 rs928508 was consistently a NSCLC survival predictor and the protective role of rs928508 AG/GG genotypes were more pronounced among early stage (stage I/II) patients and patients treated with surgery. The area under curve (AUC) at year 5 was significantly increased from 0.658 to 0.741 after adding the miR-30c-1 rs928508 risk score to the traditional clinical risk score (stage and surgery). Furthermore, in the genotype-phenotype correlation analysis, rs928508 AG/GG genotypes were associated with a significantly decreased expression of precursor and mature miR-30c (P=0.009 and 0.011), but not with that of its primary miRNA. The expression of the host nuclear transcription factor Y (NFYC) gene was correlated with pri-mir-30c-1, but not with rs928508 genotypes, implicating the co-regulation of the transcription of NFYC and pri-mir-30c-1.
Conclusions: Our data indicated, for the first time, that genetic polymorphisms in the pre-miRNA flanking region may be prognostic biomarkers of NSCLC, and rs928508 is such a potential candidate.
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 4666. doi:10.1158/1538-7445.AM2011-4666