bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A65: Activation of ERK1/2 using combination of aspirin, curcumin and sulforaphane regimen leads to NF-κB inhibition and apoptosis in pancreatic cancer cells
Authors: Thakkar Arvind , Sutaria Dhruvitkumar , Grandhi Karthik , Huang Ying , Wang Jeffrey , Prabhu Sunil 
Published: January 2014

Abstract
Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with approximately 37,000 deaths each year. Due to poor prognosis, attention has recently focused on the chemoprevention of this disease rather than on diagnosis and treatment. The present study aims to evaluate the combinatorial chemopreventive effects of low doses of aspirin (ASP), curcumin (CUR), sulforaphane (SFN) alone and in combination ACS (ASP+CUR+SFN) on two pancreatic cancer cell lines, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1mM), CUR (10μM) and SFN (5μM) alone did not reduce cell viability, whereas combination ACS reduced cell viability by ∼70% (P&lt;0.001). ACS treatment also induced cell apoptosis by ∼60% accompanied by activation of caspase- 3 and Poly (ADP-ribose) polymerase (PARP) proteins. The NF-κB DNA binding activity was inhibited by ∼45% (P&lt;0.01) and ∼75% (P&lt;0.001) in MIA PaCa-2 and Panc-1 cells respectively. The reduction in NF-κB activity was accompanied by down-regulation of phospho IκBα and phospho Akt proteins. Mechanistic studies revealed that ACS promoted reduction in cell viability, associated with increased expression of phospho extracellular signal-regulated kinase 1/2 (ERK1/2), phospho c-Jun, phospho p38 MAPK and phospho p53 proteins. Furthermore, to evaluate the significance of activation of ERK1/2 pathway on ACS induced reduction in cell viability and NF-κB, the cells were pretreated with U0126 (ERK1/2 inhibitor). The inhibition of ERK1/2 by U0126 pretreatment abolished the effect of ACS on cell viability and NF-κB DNA binding activity. Overall, our results for the first time, illustrate that low dose ACS combinations impart synergistic suppressive activity than chemopreventive agents alone thus confirming the importance of novel combination chemoprevention strategies against pancreatic cancer.
Citation Format: Arvind Thakkar, Dhruvitkumar Sutaria, Karthik Grandhi, Ying Huang, Jeffrey Wang, Sunil Prabhu. Activation of ERK1/2 using combination of aspirin, curcumin, and sulforaphane regimen leads to NF-κB inhibition and apoptosis in pancreatic cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A65.
Abstract A66: A Comparison of Helical Tomotherapy with Standard Radiotherapy Treatment Planning (AP/PA) in Patients with Wilms' Tumor and Ewing's Sarcoma
Authors: Sarfo-Kantanka Kofi , Crilly Richard , Moll Logan 
Published: January 2014

Abstract
Purpose/Objective: Radiation carries the risk of inducing complications directly linked to the amount absorbed by tissues. In this initial study, we compare the helical tomotherapy with standard(AP/PA) radiotherapy treatment for pediatric patients with lung metastasis associated with Wilms' tumor and Ewing's sarcoma. We hypothesize that helical tomotherapy will allow for more effective tumoricidal irradiation while minimizing harmful radiation to proximate sensitive structures.
Methods/Materials: The full body CT-scans from pediatrics patients were used to compare two radiotherapy techniques. Treatment plans were designed using HiArt- Tomotherapy and Eclipse planning systems for AP/PA traditional external beam radiotherapy with 12Gy/10x to PTV lung. Optimization was pushed for higher avoidance and data extracted for paired t–test analysis.
Results: The volume prescription dose (V12) in both plans showed no significant differences. However, doses of the lung and spinal column were more homogenous in the helical tomotherapy than the AP/PA. There was a statistical significance (p&lt;0.05) at V10 for the esophagus, breast buds, heart, l. kidney, spinal column and thyroid but no significance for r. kidney and spinal cord. At V5 there were no significance for r. kidney, l. kidney and esophagus but all other avoidant structures were statistically significant. The long term effects of these dose volumes is presently little studied.
Conclusion: Overall, it was observed that the helical tomotherapy is better for treating volumes that minimize dose to normal tissues and supply uniform doses when needed. As treatment techniques are refined, there is an increased need to understand the effects of lower doses on pediatric tissue.
Citation Format: Kofi Sarfo-Kantanka, Richard Crilly, Logan Moll. A comparison of helical tomotherapy with standard radiotherapy treatment planning (AP/PA) in patients with Wilms' tumor and Ewing's sarcoma. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A66.
Abstract A67: Syntheses and antitumor activities on NCI-60 human tumor cell line protocol of novel N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives with halo substitutions on ring-E
Authors: Kumar Ajay , Kumar Vineet , Alegria Antonio E. , Sanjay Malhotra V. 
Published: January 2014

Abstract
Podophyllotoxin is a natural product obtained from endangered Berberidaceae family species. Derivatives namely etoposide, etopophos and teniposide have been developed from podophyllotoxin and are currently used in clinic for the treatment of a variety of malignancies since five decades. Synthesis of podophyllotoxin is not feasible so far and due to this reason structural modification of podophyllotoxin could not be explored very well. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. In past we have developed synthetic analogues of podophyllotoxin i.e. aza-podophyllotoxin derivatives an important scaffold to address this chemistry.
We have developed some heterocyclic analogues of podophyllotoxin i.e. N-hydroxyethyl-4-aza-podophyllotoxin derivatives. Owing to their promising activity against 60 cell lines at NCI, we further developed a novel library of N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives substituted at ring-E by halogens. This was followed by a screen of in-vivo activity using a panel of tumor hollow-grafts implanted in mice consisting of breast (MDA-MB-231), non-small lung (NCI-H23 and NCI-H522), colon (SW-620 and COLO 205), melanoma (UACC-62, MDA-MB-435 and LOXIMVI), ovarian (OVCAR-5 and OVCAR-3) and CNS (U251 and SF-295) cell lines. These new compounds shows comparatively good activity against ovarian and melanoma cancer lines.
Citation Format: Ajay Kumar, Vineet Kumar, Antonio E. Alegria, Malhotra V. Sanjay. Syntheses and antitumor activities on NCI-60 human tumor cell line protocol of novel N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives with halo substitutions on ring-E. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A67.
Abstract A68: Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers
Authors: Tzeng Cherng-Chyi , Tseng Chih-Hua , Chen Yeh-Long 
Published: January 2014

Abstract
Chalcones are natural products which have displayed a wide variety of biological activities, including anti-malarial, anti-protozoal, anti-inflammatory, immunomodulatory, nitric oxide inhibition, tyronase inhibition, and anticancer activities. Due to their abundance in plants and ease of synthesis, the chalcone class of compounds has attracted extensive studies. On the other hand, quinoline skeleton is one of the key building elements for a large number of natural and synthetic heterocycles which possess a wide variety of biological effects such as antimalarials, bactericidal, antitumor, anti-inflammatory, antiproliferative, and antiviral activities. Therefore, a series of chalcone derivatives in which an aryl moiety was replaced with quinoline nucleus have been synthesized and evaluated for their antiproliferative activities. These newly synthesized chalcone derivatives were evaluated in vitro against a panel of six cancer cell lines including three non-small cell lung cancer cells (H1299, H460, and A549), three breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3), and a normal mammary epithelial cell (M10), Among them, (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (1) was active against the growth of H1299 and SKBR-3 with IC50 values of 0.71 and 0.52 μM respectively which was more active than the positive topotecan (IC50 values of &gt; 10.0 μM in each case). Compound 1 was the most active against the growth of MDA-MB-231 with an IC50 value of &lt; 0.1 μM and was not cytotoxic to the normal mammary epithelial cell (M10) with an IC50 value of 9.38 μM. Mechanism studies indicated that compound 1 induced cell cycle arrest at G2/M phase followed by DNA fragmentation via activation of caspase-3, cleavage of PARP, and consequently caused the cell death. Further structural optimization is currently ongoing.
Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A68.
Abstract A78: Broccoli-derived compounds down regulate C-C chemokine ligand 2 expression and monocyte attraction through androgen-dependent pathway in LNCaP prostate cancer cells
Authors: Wang Thomas , Kim Eun-Kyung , Milner John , Kim Young 
Published: January 2014

Abstract
Inflammation has an important role in prostate tumorigenesis. The recruitment of inflammatory monocytes to the tumor site is precipitated by increased levels of the chemo-attractant C-C chemokine ligand 2 (CCL2). In the present study, we test the hypothesis that broccoli-derived cancer protective compounds, indole-3-carbinol (I3C) and 3', 3'-diindolylmethane (DIM), exert anti-inflammatory effects by decreasing CCL2 levels and thereby down regulating CCL2 mediated pathways. Dihydrotestosterone (DHT) induced a time (0-72 hrs) and concentration-dependent (0-1 nM) increase in CCL2 mRNA levels in androgen-responsive LNCaP cells. Consistent with increase in CCL2 mRNA, we also observed increased secretion of CCL2 protein in the media of DHT-treated LNCaP cells. This effect of DHT was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction. Conditioned media from androgen-treated cells promoted human monocyte THP-1 cell migration and this effect was blocked by antibody against CCL-2. Both I3C and DIM inhibited promotional effects of DHT on CCL2 expression and monocyte migration in-vitro. These results indicate the effect of I3C and DIM on CCL2 and monocyte migration was androgen dependent. Hence, androgen appeared to stimulate CCL2 secretion and thereby promotes inflammatory micro-environments in prostate tumors. These results suggest that the androgen mediated inflammatory processes are modulated by broccoli-derived compounds.
Citation Format: Thomas Wang, Eun-Kyung Kim, John Milner, Young Kim. Broccoli-derived compounds down regulate C-C chemokine ligand 2 expression and monocyte attraction through androgen-dependent pathway in LNCaP prostate cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A78.
Abstract A84: ω3 rich diet protects against Kras-induced metaplasia via repression of NF-κB
Authors: Principe Daniel R. , Mascarinas Windel Emman T. , Chheda Chintan , Adrian Kevin , Mangan Riley , Boven Lindsay C. , Grippo Paul J. 
Published: January 2014

Abstract
Expression of mutant Kras is observed and often implicated in both pancreatitis and pancreatic cancer. Yet, the means by which inflammation occurs is relatively unexplored, although a previous report supports that induction of inflammation in the presence of oncogenic Kras initiates an NF-κB–mediated positive feedback loop that incorporates Cox-2 and production of PGE2 which further amplify mutant Kras. The involvement of PGE2 is interesting, as recent data suggests diets rich in ω6 fatty acids promote Kras induced pancreatic inflammation and neoplastic lesions. However, the precise mechanism and role of epigenetic events derived from diets rich in fatty acids have yet to be completely resolved. In this work, we demonstrate that a key step in this process is the induction and accumulation of NF-κB in pancreatic epithelia, a factor sufficient to promote chronic inflammation and progression to pancreatic adenocarcinoma. In HPDE cells, inhibition of NF-κB shows promise, as treatment with the IKK inhibitor Bay11-7085 noticeably reduced levels of the pro-proliferative factor pAkt. In EL-Kras mice fed a diet rich in ω6 fatty acids, NF-kB is upregulated in the pancreas, predominantly in metaplastic lesions. Conversely, these transgenic mice fed an ω3 fatty acid diet show little, if any, NF-kB expression, which is similar to the response in mice fed an intermediate, isocaloric high fat diet. pAkt is known to act upstream of NF-κB, implicating that NF-κB may be involved in a positive feedback loop with a variety of Kras effectors culminating in pancreatitis and eventually pancreatic neoplasia/adenocarcinoma. It has also been demonstrated that the ω6 Cox2-metabolite PGE2 is mediating this response, though in cultured human pancreatic epithelia, Cox-2 inhibition showed no significant change on levels of NF-κB. Yet, Cox2 inhibition in the stroma may be synergistic with epithelial inhibition of NF-κB, offering protection against the progression from inflammation to cancer. This data provides support to multiple targets of chemoprevention and therapy, including Ras and IKK/NF-κB, for pancreatic neoplasia and cancer.
Citation Format: Daniel R. Principe, Windel Emman T. Mascarinas, Chintan Chheda, Kevin Adrian, Riley Mangan, Lindsay C. Boven, Paul J. Grippo. ω3 rich diet protects against Kras-induced metaplasia via repression of NF-κB. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A84.
Abstract B100: Association between ambient ultraviolet radiation and risk of esophageal cancer
Authors: Tran Bich , Lucas Robyn , Kimlin Michael , Whiteman David , Rachel Neale 
Published: January 2014

Abstract
Background and Aims: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles and measures of ambient UVR over the life-course with risks of esophageal cancers.
Methods: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR and esophageal cancer risk.
Results: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC OR 0.59, 95% CI 0.35 – 0.99, EGJAC OR 0.55, 0.34 – 0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51 – 1.64). The associations were independent of age, sex, BMI, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H.pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls.
Conclusion: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.
Citation Format: Bich Tran, Robyn Lucas, Michael Kimlin, David Whiteman, Neale Rachel. Association between ambient ultraviolet radiation and risk of esophageal cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B100.
Abstract B107: The preclinical effects of purified mollusk extracts in a short term mouse model for early-stage colon cancer
Authors: Esmaeelian Babak , Benkendorff Kirsten , Leu Richard Le , Abbott Catherine 
Published: January 2014

Abstract
The Australian whelk, Dicathais orbita, is a novel source of bioactive compounds with anticancer properties. Crude extracts from this mollusk have been found to have anticancer activity against a range of cell lines in vitro and were also effective at inducing apoptosis in vivo in a short-term rodent model for colorectal cancer. However, one important limitation of the preclinical model was toxicity in the liver due to lack of purification in the extract. Consequently, the aim of this research was to purify the bioactive compounds tyrindoleninone, tyrindolenine and the oxidation product 6-bromoisatin from the crude extract of D.orbita using flash column chromatography. The retention times and mass spectrum of the isolated compounds were obtained by liquid chromatography-mass spectrometry. These compounds were then tested for anti-cancer activity using a short-term (2 weeks) in-vivo mouse model using azoxymethane injection. Distal colon epithelial proliferation and apoptosis were evaluated using immunohistochemical staining and hematoxylin staining. Liver toxicity was assessed using serum alanine aminotransferase (AST), aspartate aminotransferase (ALT) and alkaline phosphatase (ALP) levels. Histopathology evaluation of liver was also performed by staining with hematoxylin and eosin. The results showed that the purified compounds had a greater anticancer effect than the crude extract, as evidenced by a significantly higher apoptotic index in the distal colon without any toxicity on liver. In conclusion this study has provided further scientific evidence for establishing the usefulness for this mollusk extract as a new medicine for the treatment or prevention of colon cancer.
Citation Format: Babak Esmaeelian, Kirsten Benkendorff, Richard Le Leu, Catherine Abbott. The preclinical effects of purified mollusk extracts in a short-term mouse model for early-stage colon cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B107.
Note: This abstract was not presented at the conference.
Abstract B20: Secreted Protein Acidic and Rich in Cysteines-Like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers
Authors: Hanguang Hu , Hang Zhang , Weiting Ge , Xiyong Liu , Jiaping Peng , Shujing Yu , Yun Yen , Shu Zheng 
Published: January 2014

Abstract
Background: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is an extracellular matrix glycoprotein with malignancy suppressing potential. The hypothesis that SPARCL1 reduces cancer invasiveness and predicts better survival in colorectal cancers (CRC) was investigated.
Material and Methods: Stable SPARCL1 transfectants, RKO-SPRCL1, and corresponding vector control were constructed and implanted into nude mice to generate a mouse xenograft model of liver metastasis. Also, a retrospective outcome study was conducted on the COH set (222 CRCs) and ZJU set (412 CRCs). The protein expression level of SPARCL1 was determined by immunohistochemistry. The Kaplan-Meier and COX analyses were employed for survival analysis. The association of SPARCL1 with MET was sought by RT-PCR and Western blot analysis.
Results: The ectopic expression of SPARCL1 significantly reduced the potential for anchorage-independent growth, migration and invasion, and it induced cell differentiation in RKO and SW620 cells. In mouse xenograft model, the expression of SPARCL1 significantly reduced the liver metastasis (P = 0.001). The patient-based studies revealed that the expression of SPARCL1 was related to better differentiation (P &lt; 0.01), less lymph node involvement (Odds Ratio, OR=0.67, 95% CI 0.45-1.00) and less distant metastasis (OR=0.38, 95% CI 0.18-0.79). The Kaplan-Meier and COX analysis demonstrated that the expression of SPARCL1 was associated with better overall survival (Log–rank P &lt; 0.01; hazard ratio, HR=0.57, 95% CI 0.39-0.84). Transfection of SPARCL1 induced MET of colon cancer cells.
Conclusion: SPARCL1 functions as a tumor suppressor promoting differentiation possibly via MET, which inhibits the aggressiveness of CRC.
Citation Format: Hu Hanguang, Zhang Hang, Ge Weiting, Liu Xiyong, Peng Jiaping, Yu Shujing, Yen Yun, Zheng Shu. Secreted protein acidic and rich in cysteines-like 1 suppresses aggressiveness and predicts better survival in colorectal cancers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B20.
Abstract B21: Comparative Analysis of Peptide Nucleic Acid (PNA)-Mediated Real-Time PCR Clamping and DNA Direct Sequencing for KRAS Mutation Detection in Malignant Effusion
Authors: Park Chan Kwon , Yeo Chang Dong , Lee Sang Haak , Yoon Hyoung Kyu , Kim Seung Joon 
Published: January 2014

Abstract
Detection of mutations in clinical cancer specimen is important, and malignant pleural effusion could be important clinical specimen for KRAS mutation study in non-small cell lung cancer (NSCLC) patients. Direct sequencing is known to be the standard for detecting KRAS mutations. However, peptide nucleic acids (PNA)-mediated PCR clamping method is a recently introduced method for analyzing KRAS mutations with increased sensitivity and stability. Therefore, we attempted to compare to both methods through serum, effusion, tissue, and cell block if it was available.
A total of 48 malignant effusion being mainly NSCLC was analyzed for KRAS mutations using the PNA-mediated PCR clamping technique and direct sequencing. Proportion of mutation between PNA and sequencing were 14.6% (6.07-27.76) and 10.4% (3.47-22.66) on each. Diagnostic accuracy of mutation detection was that sensitivity 100% (47.82-100.0), specificity 95.35% (84.19-99.43), positive predictive value 71.43%(29.04-96.33), and negative predictive value 100% (91.41-100.0).
In conclusion, we demonstrated the PNA is favorable source for KRAS mutation test in the malignant effusion.
Citation Format: Chan Kwon Park, Chang Dong Yeo, Sang Haak Lee, Hyoung Kyu Yoon, Seung Joon Kim. Comparative analysis of peptide nucleic acid (PNA)-mediated real-time PCR clamping and DNA direct sequencing for KRAS mutation detection in malignant effusion. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B21.