bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2191: GABA but not baclofen prevents gemcitabine resistance induced by low dose nicotine in pancreatic cancer xenografts.
Authors: Banerjee Jheelam , Al-Wadei Mohammed H. , Al-Wadei Hussein A. N. , Schuller Hildegard M. 
Published: August 2014

Abstract
Pancreatic ductal adenocarinoma (PDAC) is a leading cause of cancer deaths in developed countries. The nucleoside analog Gemcitabine, which induces apoptosis, is widely used for the therapy of pancreatic cancer. Smoking and alcoholism are risk factors for pancreatic cancer. Nicotine replacement therapy often accompanies chemotherapy while the GABA-B receptor (GABA-B-R) agonist Baclofen has recently been suggested as an effective agent for the treatment of alcohol dependence. Our laboratory has shown that the proliferation and migration of PDAC and pancreatic duct epithelial cells in vitro is regulated by the nicotinic receptor-mediated synthesis and release of stress neurotransmitters that bind to beta-adrenoreceptors (beta-ARs). We have additionally shown that nicotine in the drinking water at a high dose (432 μmole/L) comparable to nicotine exposure in heavy smokers significantly stimulated the growth of PDAC xenografts whereas identical exposure of mice to low dose nicotine (1 μmole/L) reduced gemcitabine-induced apoptosis, thus significantly increasing resistance to gemcitabine. In the current study, we have investigated the potential prevention of nicotine-induced gemcitabine resistance by γ-aminobutyric acid (GABA) and Baclofen in PDAC xenografts. We found that GABA significantly reduced nicotine-induce drug resistance. By contrast, Baclofen failed to reduce nicotine-induced resistance to gemcitabine while even slightly increasing xenograft growth in mice not exposed to nicotine. Investigation of xenograft tissues for the expression levels of the GABA-B-R, intracellular cAMP and signaling proteins associated with cell proliferation, apoptosis and metastasis by immunoassays and western blots revealed effective inhibition of cAMP-dependent signaling in xenografts of mice treated with GABA. By contrast, Baclofen did not inhibit cAMP-dependent signaling and decreased the protein expression of the GABA-R, suggesting downregulation of the receptor. Our findings identify GABA as a promising agent for the prevention of nicotine-induced resistance to gemcitabine in PDAC. On the other hand, our data suggest that treatment of alcohol dependence by Baclofen should be avoided in PDAC patients. Supported by grants RO1CA130888 and RO1CA042829 with the National Cancer Institute.
Citation Format: Jheelam Banerjee, Mohammed H. Al-Wadei, Hussein A. N. Al-Wadei, Hildegard M. Schuller. GABA but not baclofen prevents gemcitabine resistance induced by low dose nicotine in pancreatic cancer xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2191. doi:10.1158/1538-7445.AM2013-2191
Abstract 2198: Possible circadian modulation of dihydropyrimidine dehydrogenase by mir-27a and mir-27b.
Authors: Butterfield Gabriel L. , Offer Steven M. , Diasio Robert B. 
Published: August 2014

Abstract
5-fluorouracil (5-FU) is a commonly administered chemotherapy drug used for the treatment of various aggressive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate limiting enzyme of the 5-flourouracil (5-FU) catabolic pathway, and as such limits the amount of drug available for conversion into active metabolites. Reduced expression of DPD has been linked to severe adverse toxicity to 5-FU, including mucositis, diarrhea, hematological toxicities, and, in extreme cases, death. DPD has been previously shown to follow circadian patterns of expression in rodent models and in humans. Many microRNAs also exhibit circadian variations in expression and have been suggested to control oscillations in target protein expression. Using in silico prediction, we identified two putative binding domains for the microRNAs mir-27a and mir-27b within the DPYD gene. One of these sites is located in the 3’ untranslated region (UTR) and the other is located within the coding region just upstream from the stop codon. Using a reporter system, we show that mir-27a and mir-27b are able to bind to both predicted binding sites. Furthermore, over-expression of either microRNA reduced endogenous DPD protein levels in the HT-29 colon cancer cell line. To investigate mir-27a/b as a potential circadian regulator of DPD expression, expression was measured in livers collected at 4-hour intervals from chrono-synchronized mice. As expected, the circadian pattern of DPD enzyme activity closely matched that of DPD expression. The expression patterns for mir-27a and mir-27b were inverse of those for DPD expression and activity. These data suggest that mir-27a and mir-27b may direct circadian variations in DPD enzyme activity.
Citation Format: Gabriel L. Butterfield, Steven M. Offer, Robert B. Diasio. Possible circadian modulation of dihydropyrimidine dehydrogenase by mir-27a and mir-27b. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2198. doi:10.1158/1538-7445.AM2013-2198
Abstract 2199: Associations of genetic polymorphisms in VEGFR1 with progression-free and overall survival in patients with neuroendocrine tumors treated with the VEGFA inhibitor bevacizumab.
Authors: Ter-Minassian Monica , Qian ZhiRong R. , Chan Jennifer A. , Hooshmand Susanne M. , Brais Lauren K. , Heafield Rachel , Lin Xihong , Liu Geoffrey , Christiani David C. , Kulke Matthew H. 
Published: August 2014

Abstract
Background:
Neuroendocrine tumors (NET) have been shown to be responsive to treatment with VEGF pathway inhibitors. We hypothesized that genetic variation in VEGFA, VEGFR1 or VEGFR2 is associated with progression free survival (PFS) and/or overall survival (OS) in patients with metastatic NET treated with bevacizumab, a monoclonal antibody targeting VEGFA.
Methods:
We selected 61 functional and tagging SNPs with a minor allele frequency of 5% or greater, with full gene coverage of VEGFA, VEGFR1 and VEGFR2. We pooled data from two genotyped datasets, selecting 82 patients with metastatic NET who received bevacizumab administered either as a single agent or as part of a combination regimen. Using a Cox proportional hazards regression analysis, and an additive genetic model, we tested the SNPs’ associations with PFS and OS adjusting for age and stage at diagnosis, gender, tumor origin, grade of differentiation, and genotyping dataset.
Results:
We found that 4 intronic tagging SNPs in VEGFR1, rs7987649, rs9508021, rs9513095 and rs2104330 were associated with PFS at p&lt;0.05. The association between rs7987649 and PFS (multivariate Hazard Ratio 0.55 (0.38, 0.81) p=0.002) remained significant after adjusting for multiple testing. One of the four SNPs associated with PFS, rs7987649, as well as another SNP in VEGFR1, rs3794339, were associated with OS at p&lt;0.05 although these associations did not remain significant after multiple testing adjustment. No SNPs in either VEGFR2 or VEGFA were associated with PFS or OS.
Conclusions:
In patients with neuroendocrine tumors treated with bevacizumab, the VEGFR1 SNP rs7987649 appears to be associated with progression-free survival. We note that three SNPs identified in our analysis, rs9508021, rs9513095 and rs2104330, are in strong linkage disequilibrium with SNPs rs7993418 and rs9582036, which have been associated with increased VEGFR1 expression and with PFS and OS in pancreatic adenocarcinoma (Lambrechts, 2012). Further study of loci within this region of VEGFR1 is warranted to discover potential causal variants affecting NET survival.
Citation Format: Monica Ter-Minassian, ZhiRong R. Qian, Jennifer A. Chan, Susanne M. Hooshmand, Lauren K. Brais, Rachel Heafield, Xihong Lin, Geoffrey Liu, David C. Christiani, Matthew H. Kulke. Associations of genetic polymorphisms in VEGFR1 with progression-free and overall survival in patients with neuroendocrine tumors treated with the VEGFA inhibitor bevacizumab. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2199. doi:10.1158/1538-7445.AM2013-2199
Abstract 222: Anticancer effects of Withaferin A on UP-LN1 carcinoma cells through the inhibition of STAT3 phosphorylation and IFN-γ-mediated induction of metastatic cancer stem cells .
Authors: Yeh Chi-Tai , Wu Alexander TH , Chen Hung-Chang , Chuang Cheng-Keng , Pang See-Tong , Liao Shuen-Kuei 
Published: August 2014

Abstract
Cancer stem cells (CSCs) have been defined as a subpopulation of cancer cells with the ability of self-renewal, giving rise to different progenies, and transition between epithelial and mesenchymal status in response to the tumor microenvironment. Due to the lack of an appropriate cell model, our understanding of CSC biology remains poor and the development of CSC antagonists is challenging. We herein used the UP-LN1 cell line as a CSC model which was derived from a gastrointestinal tumor-to-lymph node metastasis lesion. UP-LN1 cells constitute two major components, the floating (F) and adherent (A) cells. F cells were identified as the primary niche of CSCs, and could be serially subcultured while maintaining their stem-like properties including high self-renewal potential, formation of suspended grape-like aggregates and/or spheres, resistance to multiple drugs and NK/LAK effectors, as well as an increased CDY1 (a novel iPS probe) dye retention. Using this cell model, we demonstrated that Withaferin A (WA) dramatically reduced the proliferation of F cells and their ability to form aggregates in vitro. WA also dose-dependently reduced the side population cells. Mechanistically, WA treatment resulted in the down-regulation of two axes, CXCR4 and STAT3, both instrumental in the acquisition of metastatic ability and the development/maintenance of CSCs. We validated the in vitro results using non-invasive imaging technique in a xenograft mouse model. WA-treated animals demonstrated a marked decrease in tumor burden and metastasis, indicating that WA is potentially an effective agent for targeting CSCs.
Citation Format: Chi-Tai Yeh, Alexander TH Wu, Hung-Chang Chen, Cheng-Keng Chuang, See-Tong Pang, Shuen-Kuei Liao. Anticancer effects of Withaferin A on UP-LN1 carcinoma cells through the inhibition of STAT3 phosphorylation and IFN-γ-mediated induction of metastatic cancer stem cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 222. doi:10.1158/1538-7445.AM2013-222
Abstract 224: Targeting reprogramming the stemness in breast carcinogenesis by 2-Methoxyestradiol.
Authors: Maity Gargi , Banerjee Snigdha , De Archana , Sarkar Sandipto , Das Amlan , Banerjee Sushanta 
Published: August 2014

Abstract
2-Methoxyestradiol (2ME2), a natural metabolite of estradiol is a potent antitumor and antiangiogenic agent. 2ME2 inhibits the proliferation of a wide variety of cancer cell and primary cultures and blocks tumor growth in the tumor xenograft model. 2-ME2 is currently undergoing Phase I and II clinical trial under the commercial name Panzem. Although various molecular targets have been proposed for this compound, the impact of 2ME2 on reprogramming of stemness is unknown. Thus, the purpose of this was to determine whether 2ME2 can modulate pathophysiological events like epithelial to mesenchymal transition (EMT), cell migration and stemness in breast cancer cell. Our study indicated that 2ME2 inhibits EMT by down regulating mesenchymal markers like vimentin, Snail, Twist and upregulating epithelial markers like keratin-19, E-cadherin in both low metastatic (MCF-7) and high metastatic (MDA-MB-231) breast cancer cells. We found that 2ME2 significantly reduced in vitro breast cancer cell proliferation and migration. We also showed that 2ME2 not only decreased expression of stem cell markers CD44 and oct4 and increased CD24 expression in breast cancer cells it also inhibits stemness or self -renewal property of breast cancer stem cell as observed from mammosphere assay. Overall our results may help to understand the role of 2ME2 in EMT process followed by stemness, which may facilitate to develop new therapeutic targets in breast cancer management.
Citation Format: Gargi Maity, Snigdha Banerjee, Archana De, Sandipto Sarkar, Amlan Das, Sushanta Banerjee. Targeting reprogramming the stemness in breast carcinogenesis by 2-Methoxyestradiol. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 224. doi:10.1158/1538-7445.AM2013-224
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2248: Anti-leukemic activities of alcoholic extracts of two traditional Indian medicinal plants.
Authors: Malhotra Hemant , Malhotra Bharti , Bhargava Shipra , Rathode Om Singh , Sharma Pratibha , Mathur Ashwin , Jasuja Sandeep , Chiplunkar Shubha V. 
Published: August 2014

Abstract
Background: In recent years there has been a re-awakening of interest in the identification of Medicinal plants and their derivatives for the treatment of human diseases including cancer. The present work aims to investigate the in-vitro activity of two plants used in traditional Indian medicine - Zingiber Officinale Rose(Rhizome) and Nerium Oleander L(Leaves) against a human leukemic cell line.
Method: The plants were extracted with methanol and ethanol using soxalate apparatus. In-vitro anti-cancer activity was screened against leukemic cell line K562 using the SRB and MTT assay. Apoptosis and DNA fragmentation were characterized by PI staining flow cytometry and Gel electrophoresis, respectively.
Results: Notable cancer cell growth inhibition was observed for extracts from Zingiber Officinale Rose and Nerium Oleander L with IC50 values ranging between 10 -28 μg/ml. Furthermore, treatment of cells with both the extracts was shown to produce cell cycle arrest and DNA damage indicating that the observed cytotoxicity was mediated via apoptosis.
Conclusion: Extracts of Ginger and Oleander has anti-cancer activity against the K572 cell line in an in-vitro system. Based upon this initial screening work reported here, further studies aimed at the identification of active components of these extracts are planned. The activity of these agents against cell lines developed from actual patient samples are also planned.
Citation Format: Hemant Malhotra, Bharti Malhotra, Shipra Bhargava, Om Singh Rathode, Pratibha Sharma, Ashwin Mathur, Sandeep Jasuja, Shubha V. Chiplunkar. Anti-leukemic activities of alcoholic extracts of two traditional Indian medicinal plants. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2248. doi:10.1158/1538-7445.AM2013-2248
Abstract 2249: Induction of PIAS3 by curcumin as a novel treatment strategy in mesothelioma.
Authors: Dabir Snehal , Wildey Gary , Dowlati Afshin 
Published: August 2014

Abstract
Curcumin, a natural drug derived from the spice turmeric, has been extensively studied as an anti-cancer agent. The mechanism of action behind this promising bioactivity of curcumin, previously unclear, is now beginning to emerge. Curcumin has been shown to inhibit STAT3 phosphorylation and activity in melanoma cells, ovarian and endometrial cancer cells and small-cell lung cancer cells. In many cancers constitutively activated STAT3 (Signal Transducers and Activators of Transcription 3) is essential for cell proliferation. In this study we demonstrate that four mesothelioma cell lines demonstrate high levels of active STAT3. The addition of curcumin can suppress mesothelioma cell growth and proliferation, demonstrating the STAT3-dependence of these cells. Interestingly, the inhibitory effect of curcumin on STAT3 appears to be mediated through an upregulation of an endogenous inhibitor of STAT3 called PIAS3 (protein inhibitor of activated STAT3). Thus, the significance of our results is that curcumin not only targets an effector of mesothelioma cell proliferation, STAT3, but does this by increasing the expression of its endogenous inhibitor, PIAS3. This result prompted ongoing studies to determine if PIAS3 levels are deficient in mesothelioma tumor specimens obtained from the National Virtual Mesothelioma bank. Taken together, our data support the idea that mesothelioma is a STAT3-driven cancer caused by a lack of PIAS3 expression and that strategies to increase endogenous PIAS3 expression will have tumor suppressor effects. The ability of curcumin to increase PIAS3 expression will give us a jump start on pursuing this strategy because it represents a bioactive lead compound with many available structural analogs.
Citation Format: Snehal Dabir, Gary Wildey, Afshin Dowlati. Induction of PIAS3 by curcumin as a novel treatment strategy in mesothelioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2249. doi:10.1158/1538-7445.AM2013-2249
Abstract 2266: The characterization of anti-breast cancer compounds isolated from the Juniperus communis.
Authors: Robichaud Gilles A. , Picot Nadia , Jean Stéphanie , Carpenter Caitlyn , Gray Chris A. 
Published: August 2014

Abstract
Breast cancer is the most common form of cancer in the female population worldwide where approximately 30% of these women will succumb to their disease. The identification of novel, efficacious and safe anticancer drugs is thus essential to mitigate the morbidity and mortality associated with this disease. More recently, the study of anticancer properties from natural products has regained popularity as natural entities provide more biodiversity of chemical structures with biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we have examined the anti-breast cancer properties of extracts from Juniperus communis (common juniper).
Using methanolic extracts from juniper needles and branches, we conducted bioassay-guided fractionation to assess growth inhibition of the highly malignant MB231 breast cancer cell line. The isolation and identification of active juniper constituents were performed through high performance liquid chromatography (HPLC) and standard spectroscopic analysis (1D- and 2D-nuclear magnetic resonance [NMR] and low-resolution and high-resolution mass spectrometry).
We characterized the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin as very potent inhibitors of cancer cell growth using dose-response and kinetic cell viability assays. Using a series of cellular and molecular tests, we also found that isocupressic acid and deoxypodophyllotoxin block MB231 cell cycling through the suppression of the ERK/MAPK and the NFκB signaling pathways. In addition to the blockade of the cell's survival cascade, both compounds concomitantly induced CASPASE-3-dependant apoptosis of MB231 cells within hours of treatment.
Our findings emphasize the potential and importance of natural products screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous natives will provide new candidate entities with desirable bioactivities to develop new cancer therapies.
Citation Format: Gilles A. Robichaud, Nadia Picot, Stéphanie Jean, Caitlyn Carpenter, Chris A. Gray. The characterization of anti-breast cancer compounds isolated from the Juniperus communis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2266. doi:10.1158/1538-7445.AM2013-2266
Abstract 2267A: Red beetroot dye inhibits proliferation in squamous cell carcinoma of the head and neck.
Authors: Lew Daniel , Wrege Kay , Stoner Gary , Bock Jonathan M. 
Published: August 2014

Abstract
Head and Neck Squamous Cell Carcinoma (SCCHN) comprises more than 90% of all head and neck cancers. Despite the many recent advancements in cancer therapy, SCCHN survival has had little improvement with a 5-year survival rate of less than 50%. SCCHN is currently the 6th most common form of cancer in the United States and is rapidly becoming one of the most frequent cancers in developing nations. Red beetroot dye is a commonly used food additive to add a deep red color to commonly consumed foods like ice cream and yogurt. It also contains active anticancer chemical compounds such as betanins and betalains. These compounds are prepared by crushing the beetroots and mixing with water, ascorbic acid, citric acid, and dextrin. Previous work has shown that red beetroot dye can be effective in suppressing the development of multiorgan tumors in animal experiments, including up to 70% prevention of esophageal cancer in a rat chemoprevention study. No previous studies have evaluated the ability of red beetroot dye to inhibit the growth and proliferation of SCCHN. SCCHN cells were treated with increasing dose concentration of red beetroot dye and assessed for proliferation, apoptosis, cell cycle changes, and G1 protein expression changes. We observed dose dependent toxicity in SCCHN following red beetroot dye treatment with concomitant cell cycle arrest in the G1 and G2 cell cycle phases. Cell cycle arrest appeared to be more significant with p53 mutation. Decreased cell counts were induced by cells undergoing apoptosis and necrosis. UMSCC-17b (mutant p53) treated with increasing doses of red beetroot dye expressed lower levels of p53 and p21 by western blot analysis. Taken together, these results suggest that red beetroot dye may have significant potential as a chemopreventive or adjuvant treatment for SCCHN.
Citation Format: Daniel Lew, Kay Wrege, Gary Stoner, Jonathan M. Bock. Red beetroot dye inhibits proliferation in squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2267A. doi:10.1158/1538-7445.AM2013-2267A