bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2140: Efficacy of aerosolized pioglitazone in lung carcinogenesis in A/J mice
Authors: Seabloom Donna , Galbraith Art , Wuertz Beverly , Haynes Anna , Antonides Jenny , fujita alisha , Steele Vernon , Wattenberg Lee , Ondrey Frank G. 
Published: May 2015

Abstract
Pioglitazone is a PPAR gamma agonist commonly utilized clinically in the treatment of diabetes. There have been clinical trials with this agent in oral cancer prevention and we sought to potentially expand its use in lung cancer in a B[a]P mouse model. Directed epithelial delivery in lung cancer is an attractive treatment approach and we felt pioglitazone would be amenable to aerosol delivery. Initially, a maximum tolerated dose experiment examining standard toxicity parameters, including animal behavior characteristics, weight, general health, and increases in markers of cytotoxicity in bronchoalveolar lavage was conducted. We found no statistically significant indications of increased toxicity in the animals with administration of aerosolized pioglitazone and proceeded with the prevention protocol. We utilized 192 seven week old female A/J mice. All groups received Benzo[a]pyrene by oral gavage in 3 doses of 3mg/kg body weight over the course of 1 week. Animals were then randomized into 8 groups of 24 mice per group based on weight. Experimental diets, 0, 50, 150, and 450µg/kg body weight pioglitazone formulated into 0.6µm average diameter respiratory particles, were started 1 week or 8 weeks after last dose of B[a]P. Animals were continued on the feeding schedule, weighed weekly, and monitored for weight loss, attenuation, rough hair coat, or other signs of ill health. The study was concluded 16 weeks after administration of B[a]P. The agent was well tolerated for the duration of the experiment and there was no observable toxicity. The average number of adenomas per animal in the late treatment group was 10.69 ± 1.685 in the control, 12.27 ± 1.761 in the 50µg, 6.000 ± 0.6359 in the 150 µg, and 7.267 ± 1.071 in the 450µg groups but low control tumor counts in the early treatment group precluded analysis. The same tumor initation protocol was used with 72 mice. Animals were randomized into 3 groups of 24 animals and treated with 0, 150, or 450µg/kg body weight aerosol pioglitazone for 16 weeks starting 1 week after the last B[a]P dose. The average number of adenomas per animal was 9.217 ± 1.004 in the control, 7.957 ± 0.9440 in the in the 150 µg, and 6.304 ± 0.8653 in the 450µg groups. We conclude aerosol pioglitazone is well tolerated in the A/J mouse model and a promising chemoprevention agent in the aerodigestive tract.
Citation Format: Donna Seabloom, Art Galbraith, Beverly Wuertz, Anna Haynes, Jenny Antonides, alisha fujita, Vernon Steele, Lee Wattenberg, Frank G. Ondrey. Efficacy of aerosolized pioglitazone in lung carcinogenesis in A/J mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2140. doi:10.1158/1538-7445.AM2014-2140
Abstract 2141: Dietary feeding of Kava root extract inhibits prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model
Authors: Li Xuesen , Blair Christopher A. , Zi Xiaolin 
Published: May 2015

Abstract
Kava kava has been traditionally used to prepare beverages and herbal medicines in the Pacific Islands. Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. To determine the chemopreventive efficacy of kava root extracts, TRAMP mice were fed with commercial kava root extract supplemented food. In the prevention protocol, TRAMP mice were fed with 3 or 6 g (0.3% or 0.6%) kava root extract /kg food starting at 6 weeks of age and ending at 12 weeks of age, resulting in decreased numbers of high-grade prostatic intraepithelial neoplasia and moderately differentiated adenocarcinomas in kava root extract fed mice compared to the mice fed with control food (p&lt;0.01). In the intervention protocol, in which TRAMP mice were fed with 0.3% or 0.6% kava root extract food starting at 6 weeks of age and ending at 24 weeks of age, the average genitourinary (GU) weight of 0.6% kava root extract fed mice was significantly reduced when compared to control food fed mice (1.98±2.07 gram vs.3.63±4.28 gram, p&lt;0.05, Mann-Whitney U and Kolmogorov-Smirnov test). The percentages of large tumors (GU weight &gt; 0.9 gram) were also decreased from 86.4% in the control group to 52.2% and 43.5% in 0.3 and 0.6 % kava food groups, respectively. In addition, we showed that kawain, the main component of kava root extracts, inhibited LSD1 enzyme activity, enhanced H3K9 dimethylation and decreased the mRNA expression of androgen receptor target genes, including PSA and TMPRSS2, in LNCaP cells. Taken together, these results suggested that dietary consumption of kava products have the potential to reduce the risk of prostate cancer development.
Citation Format: Xuesen Li, Christopher A. Blair, Xiaolin Zi. Dietary feeding of Kava root extract inhibits prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2014-2141
Abstract 215: Aminoflavone exhibits in vivo efficacy on cancer stem cells in a spontaneous estrogen-dependent breast cancer murine model
Authors: Callero Mariana , Berardi Damian , Todaro Laura , Simian Marina , Brantley Eileen J. , Soto Ubaldo , Loaiza-Perez Andrea 
Published: May 2015

Abstract
Stem-cell populations have been identified in a range of solid tumors and possess the capacity to self renew. It is thought that these cancer stem cells (CSCs) play an important role in cancer establishment, progression, and resistance to current treatments. CSCs have been identified in primary breast cancer tissues and cell lines derived from metastatic tumors. Traditional cancer therapies are effective at debulking some tumors but often fail to produce long-term clinical remissions, presumably due to their inability to eradicate the cancer stem cell population. Therefore, novel treatments aimed at targeting this population can potentially enhance treatment of both primary and metastatic tumors. Aminoflavone (AF; NSC 686288) is a novel anticancer agent. Previous work from our research group demonstrated that AF is a ligand of the aryl hydrocarbon receptor (AhR) and displays cytotoxicity in the MCF-7 breast cancer cell line. A prodrug formulation of AF (AFP464, NSC710464), recently entered phase II clinical trials. Moreover, we previously found that AF disrupts MCF-7 mammosphere formation via AhR signaling activation to inhibit alpha 6-integrin expression. To investigate the efficacy of AF in vivo, we used an estrogen dependent, Tamoxifen-sensitive spontaneous M05 model system involving 1-year-old virgin female BALB/c mice developed in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. After AF treatment (12 mg/kg, i.p., QD × 5 days) tumor size and growth rate decreased substantially compared to control animals. Cytometric analyses of cells obtained from AF-treated and control animals revealed that Lin (-)/ CD29 (Hi)/CD24 (+) cancer stem cells were lower in animals treated with AF than in the vehicle control group. We also observed a diminished capacity for mammosphere formation in cells obtained from tumors treated with AF. These data suggest AF diminishes the quantity of breast cancer stem cells as well as their integrity and capacity to form mammospheres in vitro and in vivo. These findings shed additional insight into the molecular mechanism of anticancer action for this novel anticancer agent to strengthen the rationale for its inclusion in breast cancer treatment regimens.
Citation Format: Mariana Callero, Damian Berardi, Laura Todaro, Marina Simian, Eileen J. Brantley, Ubaldo Soto, Andrea Loaiza-Perez. Aminoflavone exhibits in vivo efficacy on cancer stem cells in a spontaneous estrogen-dependent breast cancer murine model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 215. doi:10.1158/1538-7445.AM2014-215
Abstract 2150: Chemopreventive effects of black raspberries in endometrial cancer
Authors: Chen Jo-Hsin , Aguilera-Barrantes Irene , Kuo Chieh-Ti , Hilakivi-Clarke Leena , Stoner Gary D. , Rader Janet S. , Huang Yi-Wen 
Published: May 2015

Abstract
Endometrial cancer is the most common type of gynecologic cancer and annually comprises 3% of all cancer deaths of women in the United States. Additionally, ∼80% of cases are type I endometrial cancer, mainly associated with Pten abnormalities. It was estimated that up to 90% of type I endometrial cancer patients are overweight/obese. Therefore, a regimen to prevent obesity associated tumorigenesis is the most important for type I endometrial cancer. In the current study, the Pten heterozygous (+/-) female mice were used as the model, to study the potentially chemopreventive effects by black raspberries (BRBs). At 3-4 weeks old, Pten (+/-) and wild type female mice were divided into four treatment groups, fed with either AIN-93G control diet (CD), CD with 5% BRBs, 58% fat to induce obesity (HF),or HF with 5% BRBs. All of mice were euthanized at 28 weeks old. In wild type mice, no malignant lesion was identified. In Pten (+/-) mice, HF diet increased 10% focal glandular hyperplasia with atypia lesions when compared with CD diet. Dietary administration of BRBs decreased 19% focal glandular hyperplasia with atypia lesions when compared with CD group. Specifically, BRBs in HF diet inhibited 32% obesity-induced endometrial malignant lesions and significantly lowed lesion multiplicity. Furthermore, cytokine profiles in plasma by Bio-Plex Assay revealed dietary BRBs decreased IL-1β and IL-17A, and lowed TNF-α and GM-CSF when compared with CD and HF group, respectively. In conclusion, this study for the first time suggested BRBs are chemopreventive for obesity-induced endometrial tumorigenesis.
Citation Format: Jo-Hsin Chen, Irene Aguilera-Barrantes, Chieh-Ti Kuo, Leena Hilakivi-Clarke, Gary D. Stoner, Janet S. Rader, Yi-Wen Huang. Chemopreventive effects of black raspberries in endometrial cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2150. doi:10.1158/1538-7445.AM2014-2150
Abstract 2152: Akt/survivin pathway inhibition synergizes the apoptotic cell death induced by A-santalol in prostate cancer cells
Authors: Bommareddy Ajay , Lockus Lauren , Seward Jonathan , Eggelston William , Prelewicz Stacy , Antal Andrea , Fillman Sarah , Castro Christian , VanWert Adam L. , Santha Sreevidya , Dwivedi Chandradhar 
Published: May 2015

Abstract
α-santalol, a major component of sandalwood oil inhibits growth of cultured prostate cancer cells in vitro by causing apoptosis. The present study was undertaken to investigate the mechanistic details associated with the induction of apoptosis by α-santalol in cultured prostate cancer cells (LNCaP and PC-3). Expressions of major proteins studied in the present investigation were determined using standard Western blot protocol and analyzed by LICOR-Odyssey infra-red scanner. Activity of survivin was confirmed employing survivin ELISA kit. The cell viability was determined by trypan blue dye exclusion assay and caspase-3 activity was confirmed using caspase-3 (active) ELISA kit. Treatment of prostate cancer cells with α-santalol (20, 40 µM) resulted in the down regulation of survivin, XIAP and p-AKT (s-473) levels. Furthermore, α-santalol significantly reduced the activity of survivin as evidenced by survivin ELISA assay. Inhibition of PI3K/Akt by pharmacological inhibitor LY294002 synergized the apoptotic cell death induced by α-santalol as determined by cell viability, active caspase-3 activity and expression of cleaved PARP, caspase-3 levels. In conclusion, the present study reveals that α-santalol downregulates activity and expression of survivin and that inhibition of PI3K/Akt pathway synergize the apoptotic cell death by downregulating survivin. This study was supported by Mentoring Task Force, Type I grant by Wilkes University and by Translational Cancer Research Center funded by South Dakota Governor's Office of Economic Development.
Citation Format: Ajay Bommareddy, Lauren Lockus, Jonathan Seward, William Eggelston, Stacy Prelewicz, Andrea Antal, Sarah Fillman, Christian Castro, Adam L. VanWert, Sreevidya Santha, Chandradhar Dwivedi. Akt/survivin pathway inhibition synergizes the apoptotic cell death induced by A-santalol in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2152. doi:10.1158/1538-7445.AM2014-2152
Abstract 2155: Novel combinations of nano-formulated ferulic acid and aspirin show high potential for chemoprevention of pancreatic cancer
Authors: Thakkar Arvind , Wang Jeffrey , Prabhu Sunil 
Published: May 2015

Abstract
Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with about 37,000 deaths each year. This study evaluated the chemopreventive potential of combinations of free and nano-encapsulated mixtures of ferulic acid (FA) and aspirin (ASP) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Cell lines were tested according to published protocols wherein cells were seeded in 96-well microplates and incubated with the unmodified and modified combinations for 72 h and analyzed using MTS cell viability assay method. Apoptosis was measured by flow cytometry. Results demonstrated that free FA (200 µM) and ASP (1 mM) combinations on average reduced cell viability by 60% (P&lt;0.001), and also induced cell apoptosis by 47% (P&lt;0.001) on the two cell lines. However, when individual agents (FA 200 μM; ASP 1mM) were tested, they were virtually ineffective in reducing cell viability, thus indicating an additive/synergistic effect of the two agents in combination. Subsequently, nano-formulations of FA and ASP (nano-FA and nano-ASP) were prepared by encapsulating the agents within solid lipid nanoparticles (SLNs) and tested on the same cell lines. Prior to this, nano-FA and nano-ASP were evaluated for particle sizes and encapsulation efficiencies. Initial particle sizes were 183± 46 nm (nano-FA) and 229±67 nm (nano-ASP), respectively. Furthermore, the encapsulation efficiencies were high for both nano-FA (86%) and nano-ASP (78%). The combination mixture of nano-FA (25 µM) and nano-ASP (25 µM) reduced the cell viability of MIA PaCa-2 and Panc-1 cells by 70% (P&lt;0.001), and also induced cell apoptosis by 30% (P&lt;0.01), thus reducing the dosage of FA by 8-fold and that of ASP by 40-fold to elicit a comparable response as the mixture of the free FA and ASP. Finally, a trans-AM NF-κB transcription factor assay kit was used to help understand the mechanism. Our results demonstrate that nano-FA and nano-ASP combinations significantly down-regulated NF-κB DNA binding activity in MIA PaCa-2 and Panc-1 cells. In conclusion, convincing evidence is provided of the chemopreventive potential of combinations of FA and ASP against pancreatic cancer, especially when formulated within a nanotechnology-based delivery system.
Citation Format: Arvind Thakkar, Jeffrey Wang, Sunil Prabhu. Novel combinations of nano-formulated ferulic acid and aspirin show high potential for chemoprevention of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2155. doi:10.1158/1538-7445.AM2014-2155
Abstract 2163: Height, weight and weight changes during adulthood and thyroid cancer risk
Authors: Hwang Yunji , Lee Kyu-Eun , Park Young Joo , Park Do Joon , Youn Yeo-Kyu , Yeo Yohwan , Ma Seung-Hyun , Kang Daehee , Yoo Keun-Young , Park Sue K. 
Published: May 2015

Abstract
BACKGROUND: Incidence of thyroid cancer has been rapidly increased, in not only small sizes with improved detection devices but also large size of tumors whose underlying mechanisms remain unclear. Body size and weight change in adulthood were examined as the potential risk factors for thyroid cancer development.
METHODS: A large scale case-control study was conducted with constructed questionnaire for their height, weight (current, 2 years ago, at the age of 20 and 35 years old) and confounders. Medical charts were reviewed for cancer histology, tumor aggressiveness and BRAF mutation status. A total of 2,003 cases (1,611 females and 392 males) and individually matched 17,700 controls (13,983 females and 3,717 males) by age, sex, 12-year education and birth year were included. Logistic regression model were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: Having a tall height and heavy weight was associated with increased risk in both females [OR and 95%CI for height and weight: 1.46 (1.25-1.71) and 2.66 (2.24-3.15), respectably] and males [OR and 95%CI for height and weight: 1.71 (1.25-2.34) and 2.80 (2.00-3.92), respectably] compared to those in the lowest quartile for the body sizes. This study observed approximated tripled the risk of thyroid cancer [OR and 95%CI: 3.03 (2.10-4.37)] when female subjects gained 10kg or more within recent 2 years. Males who gained 10 kg or more after 35 years old were more likely to have a greater tumor size [&lt;1cm vs. ≥1cm: 3.76 (2.62-5.38) vs. 6.87 (4.38-10.77)]. However, other factors were not significantly related to increased tumor aggressiveness (tumor size, lymph node metastasis, and mutlifocality) and BRAF mutation affected carriers.
CONCLUSION: The results support plausible hormonal and metabolic factors related height, weight, and rapid weight gain in adulthood increase thyroid carcinogenesis.
Citation Format: Yunji Hwang, Kyu-Eun Lee, Young Joo Park, Do Joon Park, Yeo-Kyu Youn, Yohwan Yeo, Seung-Hyun Ma, Daehee Kang, Keun-Young Yoo, Sue K. Park. Height, weight and weight changes during adulthood and thyroid cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2163. doi:10.1158/1538-7445.AM2014-2163
Abstract 2179: Relationship between daily habits and risk of death in patients with biliary tract cancer: a large-scale cohort study in Japan
Authors: Otani Shinji , Kurozawa Youichi , Hosoda Takenobu , Mu Haosheng , Onishi Kazunari , Yokoyama Yae , Watanabe Joji , Sakamoto Teruhisa , Endo Kanenori , Ikeguchi Masahide 
Published: May 2015

Abstract
Objective: Biliary tract cancer is one of the deadliest diseases in East Asia. Death due to this disease comprises 5% of total cancer deaths in Japan. This study was conducted to evaluate the relationship between biliary tract cancer and daily habits using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Japanese Ministry of Education (JACC study).
Methods: In the JACC study, a cohort of 110,792 subjects aged 40-79 from 19 prefectures in Japan completed the baseline survey during 1988-1990. The subjects were followed up until 2009. The endpoint for the present study was death due to biliary tract cancer, coded as C22.1 (intrahepatic bile duct carcinoma, CCC), C23 (malignant neoplasm of the gallbladder, GB cancer), and C24 (malignant neoplasm of other and unspecified parts of the biliary tract, BD cancer) in the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The hazard ratio (HR) of biliary tract cancer mortality for smoking and drinking habits, high intake of fatty food, body mass index, and the job category (office job, field work, and others) was evaluated. All results were considered to be significant at the 5% critical level.
Results: High intake of fatty food, smoking habit, and field work showed a significant positive association with death in female patients due to BD cancer in females [HR = 1.87, 95% confidence interval (CI): 1.03-3.39; HR = 1.56, 95% CI: 1.02-2.39; and HR = 2.23, 95% CI: 1.03-4.84, respectively]. No significant relationship was observed between daily habits and death due to CCC and GB cancer.
Conclusion: High intake of fatty food is often a key factor in the risk of death due to biliary tract cancer, and it is well known that smoking can cause various other cancers. Our findings support the results of a previous research. Moreover, our results suggest that occupational differences may have an effect on mortality in female patients with biliary tract cancer. Therefore, a more detailed analysis of the job category is required for a more meaningful interpretation of the data.
Citation Format: Shinji Otani, Youichi Kurozawa, Takenobu Hosoda, Haosheng Mu, Kazunari Onishi, Yae Yokoyama, Joji Watanabe, Teruhisa Sakamoto, Kanenori Endo, Masahide Ikeguchi. Relationship between daily habits and risk of death in patients with biliary tract cancer: a large-scale cohort study in Japan. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2179. doi:10.1158/1538-7445.AM2014-2179
Abstract 2192: Defective calcium signaling pathway highlights the mutational landscapes of liver metastasis from colorectal and breast cancer
Authors: Song Fangfang , Li Miao , Liu Yuexin , Song Fengju , Zhang Wei , Chen Kexin 
Published: May 2015

Abstract
Few therapeutic options are currently available to treat metastasis to distant organs (e.g., liver) in colorectal cancer (CRC) and breast cancer (BC) patients. To gain insight into the genetic and molecular underpinnings of metastasis, we performed whole-exome sequencing on paired primary and metastasis samples from 5 CRC and 2 BC patients and focused sequencing on additional 13-paired tumors to identify and validate somatic genetic alterations. The results showed that the mutational spectra of metastases were highly heterogeneous. Nevertheless, genetic aberrations in calcium signaling pathway genes (GPR98, SYT6, TACR3, CYSLTR1, RYR3, and CACNA1A) were somatically mutated in liver metastases in 25% of CRC and BC cases, indicating that calcium-dependent signaling plays a key role in distant metastasis. These results begin to define the genetic basis underlying liver metastasis from CRC/BC and identify potential therapeutic targets.
Citation Format: Fangfang Song, Miao Li, Yuexin Liu, Fengju Song, Wei Zhang, Kexin Chen. Defective calcium signaling pathway highlights the mutational landscapes of liver metastasis from colorectal and breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2192. doi:10.1158/1538-7445.AM2014-2192