bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5248: Pioglitazone prevents hepatocellular carcinoma development in a rat model of cirrhosis
Authors: Li Shen , Ghoshal Sarani , Arora Gunisha , Erstad Derek J. , Lanuti Michael , Tanabe Kenneth K. , Fuchs Bryan C. 
Published: July 2017

Abstract
Introduction: Advanced hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide with limited treatment options. There is a readily identifiable cohort of cirrhosis patients at risk and they are ideal candidates for chemoprevention. Anti-hyperglycemic agents have garnered interest for their potential anti-fibrotic as well as chemo-preventive effects. Pioglitazone, a selective PPAR-γ agonist, has been shown to reduce non-alcoholic steatohepatitis (NASH), but its role as an anti-fibrotic and chemopreventive agent has yet to be elucidated. The hypothesis of this study is that Pioglitazone reduces cirrhosis and subsequent HCC development in rats with diethylnitrosamine (DEN)-induced cirrhosis.
Methods: Male Wistar received DEN 50mg/kg by intraperitoneal injection. DEN injury reliably recapitulates histological and molecular features of human HCC development with induction of hepatic fibrosis at 8 weeks, cirrhosis at 12 weeks, and HCC by 18 weeks. DEN-injured rats were randomized to receive oral gavage of pioglitazone at 3mg/kg/day (n=9) or vehicle control (n=9). Initiation of pioglitazone coincided with the development of liver fibrosis at 8 weeks. All animals were sacrificed at 18 weeks.
Results: As expected, repeated injections of DEN in rats resulted in progressive fibrosis, cirrhosis, followed by HCC formation. Treatment with pioglitazone resulted in a 56% reduction of surface nodules relative to treatment with vehicle (7.4±4.9 vs. 17±7; p&lt;0.005). Liver sections were stained by picrosirius red to assess fibrosis and pioglitazone significantly reduced collagen deposition in DEN-injured rats (collagen proportional area = 3.2±1.8% vs. 9.2±2%; p&lt;0.035). This histologic observation was further confirmed by gene expression analysis with reductions in collagen-I, α-smooth muscle actin, and transforming growth factor beta in rats treated with pioglitazone. Finally, weekly injection of DEN also caused a significant decrease in overall body weight in comparison to untreated rats (398.1±60 vs. 598±46 grams; p&lt;0.015), and pioglitazone treatment resulted in a trend for better protection of body weight relative to vehicle (398.1±60 vs. 427.5±56.3 grams).
Conclusion: Overall our data supports the hypothesis that the anti-diabetic agent pioglitazone may be repurposed as a drug to reduce fibrosis and prevent HCC. This could be beneficiary in patient management given the low cost as well as minimal side effects.
Citation Format: Shen Li, Sarani Ghoshal, Gunisha Arora, Derek J. Erstad, Michael Lanuti, Kenneth K. Tanabe, Bryan C. Fuchs. Pioglitazone prevents hepatocellular carcinoma development in a rat model of cirrhosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5248. doi:10.1158/1538-7445.AM2017-5248
Abstract 5252: Quercetin inhibits prostate cancer by modulating ROS and key regulators of apoptosis and cell survival
Authors: Ward Ashley B. , Mir Hina , Kapur Neeraj , Sonpavde Guru , Singh Shailesh 
Published: July 2017

Abstract
Long latency and indolent nature of prostate cancer (PCa) provides a window of opportunity for preventive interventions using natural and synthetic agents. Hence, the focus of this study was to ascertain the chemopreventive role of Quercetin, a bioflavonoid, commonly used to treat prostatitis. Human PCa cells (LNCaP, DU145 and PC3) were treated with different concentrations of Quercetin and its effect on cell survival and apoptosis was determined by MTT assay. Human PCa cells treated with Quercetin showed significant reduction in cell viability and proliferation compared with untreated controls, which was dose and time dependent. In addition to this our FACS analysis showed higher percentage of apoptotic cells after Quercetin treatment compared to untreated cells. Quercetin induced apoptosis in PCa cells is a cumulative effect of modulation of key apoptotic proteins, changes in mitochondrial membrane potential and ROS production. Our results demonstrate that Quercetin is a potent chemopreventive agent, which may improve outcomes of PCa by inhibiting mechanisms involved in tumor progression.
Citation Format: Ashley B. Ward, Hina Mir, Neeraj Kapur, Guru Sonpavde, Shailesh Singh. Quercetin inhibits prostate cancer by modulating ROS and key regulators of apoptosis and cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5252. doi:10.1158/1538-7445.AM2017-5252
Abstract 5266: The mechanisms of apoptosis induction by deubiquitylatinase inhibitor b-ap15 in esophageal squamous cell carcinoma cells
Authors: Li Pei , Chen Ping , Chen Xiao-Yu , Zhang Jing-Yang , Sha Bei-Bei , Hu Tao , Zhang Yi-Lin , Du Ying , Dong Zi-Ming 
Published: July 2017

Abstract
Deubiquitinases (DUBs) act on ubiquitinated substrates to catalyze the removal of ubiquitin moieties which can reverse the process of protein degradation, and further affect or regulate cell metabolism, proliferation and differentiation. As a novel small molecular inhibitor, b-AP15 can specifically inhibit the deubiquitinating activity of 19S regulatory subunit UCHL5(ubiquitin C-terminal hydrolase 5) and USP14(ubiquitin-specific peptidase 14) in cancer cells. In this study, we aimed to check whether b-AP15 have anti-tumor activity in esophageal cancer cells in vitro and try to explore the underling mechanisms.
Results: CCK-8 assay, colony formation assay and morphological observation results indicate that b-AP15 can significantly inhibit the proliferation activity of EC1 and Kyse 450 esophageal cancer(EC) cell lines in a concentration-dependent manner in vitro studies. Flow cytometry results show cells were arrested in G2/M phase after being treated with b-AP15. Western blot results show that the expression of G2/M phase related proteins p21, p27 and pWee1 significantly increased while the expression of the G1/S phase marker proteins including cyclinA, cyclinD show no significant change after being treated with b-AP15. FITC annexin V Apoptosis detection kit with PI and Caspase 3 Assay kit results show that b-AP15 treatment can significantly induce apoptosis in two EC cell lines. The results from western blot show that the expression of apoptotic protein c-PARP and c-caspase 3 significantly increased and was dose-dependent. JC-1 flow cytometry analysis show that b-AP15 treatment can significantly decrease mitochondrial membrane potential. All these results suggest that b-AP15 can induce EC cells apoptosis and may play certain role in mitochondrial control of apoptosis signaling pathway.
Conclusion: b-AP15 shows a significantly anti-tumor activity in vitro models of ESCC and the results confirm that b-AP15 can inhibit proliferation of EC cell lines by inducing cell-cycle arrest and promoting cell apoptosis.
Key words: b-AP15;esophageal cancer;deubiquitylatinase(DUBs);apoptosis;
Citation Format: Pei Li, Ping Chen, Xiao-Yu Chen, Jing-Yang Zhang, Bei-Bei Sha, Tao Hu, Yi-Lin Zhang, Ying Du, Zi-Ming Dong. The mechanisms of apoptosis induction by deubiquitylatinase inhibitor b-ap15 in esophageal squamous cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5266. doi:10.1158/1538-7445.AM2017-5266
Abstract 5267: Chemoprevention of lung carcinogenesis by dietary nicotinamide and inhaled budesonide
Authors: Seabloom Donna , Wuertz Beverly , Galbraith Art , Antonides Jenny , Steele Vernon , Wattenberg Lee , Ondrey Frank G. 
Published: July 2017

Abstract
Nicotinamide, the amide form of vitamin B3, and budesonide, a synthetic glucocorticoid used in the treatment of asthma, were evaluated for efficacy of chemoprevention of lung adenoma formation in a benzo(a)pyrene murine carcinogenesis model. Female A/J mice were given three doses of 3 mg benzo[a]pyrene three days apart and started on experimental diets either 1 week (early stage intervention) or 8 weeks (late stage) after last carcinogen dose. Aerosol treatments were delivered 5 days per week starting 1 or 8 weeks post carcinogen. Nicotinamide, fed at a dietary concentration of 0.75% starting 1 week after last carcinogen administration, inhibited adenoma formation by 54%, and by 39% when begun 8 weeks post final carcinogen. Nicotinamide fed at 0.25% of the diet was not found to effect adenoma formation . Dietary nicotinamide under the same conditions with budesonide administered via aerosol administration at 25μg/kg, reduced lung adenoma formation by 90% at early stage intervention and 49% at late stage intervention. Budesonide alone administered at the same dose level gave 77% inhibition at early stage and 41% inhibition at late stage. Decreases in adenoma formation were statistically significant via ANOVA analysis at both early and late interventions. Combination therapy decreased adenoma formation significantly over either individual therapy at the early stage and significantly compared to nicotinamide alone at the late stage. However, administration of nicotinamide by aerosol inhalation at doses up to 15 mg/kg/day did not result in a statistically significant reduction in tumor multiplicity at 1 or 8 weeks post last carcinogen administration . There is a high level of clinical interest in minimal toxicity lung cancer chemoprevention strategies. We feel administration of a safe dietary agent such as nicotinamide when combined with direct epithelial delivery of a glucocorticoid such as budesonide, commonly used for asthma therapy, is a promising approach for aerodigestive chemoprevention.
Citation Format: Donna Seabloom, Beverly Wuertz, Art Galbraith, Jenny Antonides, Vernon Steele, Lee Wattenberg, Frank G. Ondrey. Chemoprevention of lung carcinogenesis by dietary nicotinamide and inhaled budesonide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5267. doi:10.1158/1538-7445.AM2017-5267
Abstract 5268: Nexrutine and palmatine mediated effects on the STAT3/EP4/IL-6 axis in pancreatic cancer
Authors: Munoz Amanda R. , Bedolla Roble G. , Rivas Paul , Chakravarthy Divya , Reddick Robert L. , Hanes Martha A. , Halff Glenn A. , Ghosh Rita , Kumar Addanki P. 
Published: July 2017

Abstract
With a 5 year survival of less than 8%, the poor prognosis of pancreatic cancer (PanCA) underlines the importance of improving therapies for effective management of this disease. In previous studies, we identified the tumor cell growth inhibitory activities for Nexrutine® (Nx, a bark extract from Phellodendron amurense) and palmatine (PMT) which is a constituent of Nx. These studies revealed an important role for downregulation of KRAS downstream effectors including GLI, STAT3 and NF-κB in mediating growth inhibitory effects. Remarkably, both Nx and PMT exerted synergistic growth inhibitory effects in combination with the conventional chemotherapeutic agent, Gemcitabine (GEM). Despite such promising in vitro observations, the in vivo efficacy of Nx or PMT had not been established. In this investigation, we evaluated the ability of Nx and PMT to (i) prevent the development of pancreatic tumors; and (ii) inhibit the growth of patient derived pancreatic cancer tissue in short term ex vivo cultures. Studies were also conducted to investigate the underlying molecular mechanism using cell culture models. Our results show that both Nx and PMT are well tolerated in vivo as evidenced by a lack of significant changes in the body weights of athymic mice implanted with Capan-2 cells. Interestingly, both Nx and PMT showed a significant decrease in the circulating levels of inflammatory molecules including IL-6 and CXCL1. In this first proof-of-concept study, PMT treated animals demonstrated a trend towards decreased pancreatic tumor weight with associated histopathogical changes. Remarkably, both Nx and PMT inhibited the growth of patient derived pancreatic cancer cells. Mechanistic investigations identified downregulation of STAT3, TrkA, Src, and RPS6 activities as potential contributors to Nx or PMT-induced synergistic growth inhibitory effects with GEM. Further investigation of STAT3 signaling revealed the involvement of the prostaglandin receptor, EP4, in a potential feedback loop with STAT3 and in asserting STAT3-mediated inhibition of autophagy. Taken together these data support potential utility for Nx and/or PMT in the management of PanCA and suggest that these agents use multiple mechanisms to affect growth of pancreatic tumors. Supported by NCCIH (R01 AT007448; APK) and VA-MERIT Award (I01 BX 000766; APK).
Citation Format: Amanda R. Munoz, Roble G. Bedolla, Paul Rivas, Divya Chakravarthy, Robert L. Reddick, Martha A. Hanes, Glenn A. Halff, Rita Ghosh, Addanki P. Kumar. Nexrutine and palmatine mediated effects on the STAT3/EP4/IL-6 axis in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5268. doi:10.1158/1538-7445.AM2017-5268
Abstract 5272: Chemopreventive activities of a polyphenol rich purified extract from olive oil processing on colon cancer cells
Authors: Bassani Barbara , Rossi Teresa , Stefano Daniela De , Pizzichini Daniele , Corradino Paola , Bruno Antonino , Noonan Douglas M. , Albini Adriana 
Published: July 2017

Abstract
Epidemiological studies showed that diet can play a relevant role in reducing the risk of developing colon cancer (CC) and lower rate of CC insurgence has been observed amongst populations living within the Mediterranean basin. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of waste material, termed ‘olive mill wastewaters’ (OMWW), that have been reported to be enriched in polyphenols as well. Given the beneficial activity of polyphenols on human health, we investigated whether the use of different batches of purified extracts from OMWW, termed A009, might be effective in exerting chemopreventive activities in vitro and in vivo, on CC cell lines.
Cell proliferation and survival were evaluated on A009 treated cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the induction of apoptosis was assessed by flow cytometry. Further, functional studies to investigate the ability of A009 to interfere with CC cell line adhesion, migration, sprouting and invasion were performed. Finally, the ability of A009 to interfere with CT-26 CRC tumour cell growth was assessed in vivo. Purified hydroxytyrosol, the major component in the A009 extracts, was used as a control.
A009 inhibited cell proliferation, migration, invasion, adhesion and sprouting of CC cells along with the release of pro-angiogenic and pro- inflammatory cytokines (VEGF, IL-8) similar to hydroxytyrosol alone. In vivo, A009 inhibited CT-26 tumour growth in a significant manner over that of hydroxytyrosol alone.
Our results show that A009 extracts exert promising chemopreventive properties, suggesting that different polyphenols act synergistically, improving their single component effects in CC cell lines. Finally, our results support the idea of repositioning a waste derived material for nutraceutical employment, with environmental and industrial cost management benefits.
Citation Format: Barbara Bassani, Teresa Rossi, Daniela De Stefano, Daniele Pizzichini, Paola Corradino, Antonino Bruno, Douglas M. Noonan, Adriana Albini. Chemopreventive activities of a polyphenol rich purified extract from olive oil processing on colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5272. doi:10.1158/1538-7445.AM2017-5272
Abstract 5273: Detection of sessile serrated adenomas/polyps in African Americans
Authors: Atefi Nazli , Singh Sanmet , Shokrani Babak , Lee Edward , Afsari Ali , Nouraie Mehdi , Laiyemo Adeyinka , Mathews Joseph , Williams Carla , Brim Hassan , Ashktorab Hassan 
Published: July 2017

Abstract
Introduction: The majority of colorectal cancers (CRCs) develop through the adenoma-carcinoma sequence, while 15-20% develop via the serrated pathway. Sessile Serrated Adenoma/Polyps (SSA/P) are more difficult to detect during colonoscopy and generally require a shorter time follow-up than other lesions (3 vs. 5 years). These polyps lead to cancer faster than conventional adenomas. In order to better define patients at risk for these lesions, we performed a retrospective study to evaluate clinicopathological features of patients diagnosed with SSA/P.
Methods: We reviewed pathology reports of patients at Howard University Hospital from 2010-2015. We identified 5,900 patients with colorectal lesions, of whom 312 (5.3%) were diagnosed with SSA/P. We analyzed the specific clinical, pathological and demographic features of patients with SSA/P lesions.
Results: We identified 312 cases with SSA/P. The incidence of SSA/P over the 5 years period was 5.3%: 198/312 (63.4%) patients had 2 or more polyps, 54.5% of the SSA/P patients were females, 70.5% of patients were 50-64 years of age and 18% were older than 65. SSA/P lesions’ locations were as follows: rectal: 32.1%; rectosigmoid: 18.6%; sigmoid: 16.8%; Ascending Colon: 13.2 % and Descending Colon: 7.1%. Reasons for colonoscopy were as follows: Screening: 43.6 %; GI bleeding: 15.1%; Abdominal Pain: 13.1%and Change in Bowel Habits: 10.2%.
Conclusion: Our results show that there is a slightly increased predominance of SSA/P occurrence in females. Most SSA/P occurred in patients 50 to 64 years old. This age range is younger in comparison to patients with conventional adenomas. SSA/Ps were predominantly distal (rectal, rectosigmoid, sigmoid) whereas previous literature reports a proximal location. Most patients in our study were diagnosed in screening colonoscopies; however, other patients presented with symptoms such as GI bleeding, abdominal pain, or change in bowel habits.
Citation Format: Nazli Atefi, Sanmet Singh, Babak Shokrani, Edward Lee, Ali Afsari, Mehdi Nouraie, Adeyinka Laiyemo, Joseph Mathews, Carla Williams, Hassan Brim, Hassan Ashktorab. Detection of sessile serrated adenomas/polyps in African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5273. doi:10.1158/1538-7445.AM2017-5273
Abstract 5279: Association of Vitamin D deficiency with breast cancer in African-American and Hispanic women in south Los Angeles
Authors: Wu Yanyuan , Sarkissyan Marianna , Clayton Sheilah , Vadgama Jay 
Published: July 2017

Abstract
Background: Experimental evidence supports a protective role of Vitamin D level in breast carcinogenesis, but epidemiologic evidence is inconsistent. African Americans have high prevalence of Vitamin D deficiency and the African American women with breast cancer have the highest mortality rate. The aim of this study is to investigate the association of Vitamin D levels with breast cancer risk and disease progression in African American and Hispanic women.
Methods: This is a cases-control study of 660 African American and Hispanic women with and without breast cancer in South Los Angeles. Blood samples were collected prior cancer treatment and the serum 25-hydroxyvitamin D (25(OH) D was measured by Quest Diagnostics. Information regarding BMI and clinical factors were obtained by medical record abstraction. Logistic Regression with multivariate analysis was used for determining the association of Vitamin D deficiency (&lt;20ng/ml) with breast cancer. Kaplan-Meier survival analysis and Cox Regression with multivariate analysis were used to assess disease-free survival and the relative risk of disease progression.
Results: Our data shows that 69.2% of African American women and 37.8% of Hispanic women suffer from Vitamin D deficiency in our cohort. African American women had significant lower level of Vitamin D3 compared with Hispanic women in all age groups. The lower Vitamin D3 level was observed among age groups of 31 to 50 in African Americans. The deficiency in Vitamin D levels was significantly associated with breast cancer in both African Americans (OR=2.5, p=0.007) and Hispanics (OR=1.9, p=0.009). Interestingly, we found that a significant association of Vitamin D deficiency with trip negative breast cancer (TNBC) in African Americans (OR=3.2, p=0.04), but not in Hispanics. The lowest Vitamin D3 level was observed in African American women with TNBC. There was no significant association of Vitamin D deficiency with tumor size, lymph node involvement and tumor stage. The deficiency of Vitamin D3 level was not associated with disease progression in this cohort of women.
Conclusion: Our data suggests that a significant association of Vitamin D deficiency with breast cancer in both African Americans and Hispanics, especially more associated with type of TNBC in African American women in our cohort.
Citation Format: Yanyuan Wu, Marianna Sarkissyan, Sheilah Clayton, Jay Vadgama. Association of Vitamin D deficiency with breast cancer in African-American and Hispanic women in south Los Angeles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5279. doi:10.1158/1538-7445.AM2017-5279
Abstract 5284: Gastric cancer in Alaska Native people: A cancer health disparity
Authors: Martinson Holly , Alberts Steven , Olnes Matthew 
Published: July 2017

Abstract
Gastric cancer in the Alaska Native (AN) people occurs at a 3-fold higher incidence and 4-fold higher mortality rate compared to Non-Hispanic Whites (NHW), representing one of the largest cancer disparities in the AN population. We aimed to review the AN gastric cancer burden and identify clinicopathological factors that are associated with cancer outcomes. Patient information was collected from 132 AN gastric cancer patients diagnosed between 2006-2015 at the Alaska Native Medical Center. The Surveillance, Epidemiology and End Result database 18 was used to collect comparison United States NHW gastric cancer patient data. Compared to NHW patients, AN gastric cancer patients have a higher incidence rate, are significantly younger, 60 versus 69 years, and have a poorer 5-year overall survival rate of 10% compared to 22%. AN patients differ from NHW patients in gastric cancer anatomic location, subtype, and higher presence of signet ring cell carcinomas. Forty-one percent of AN patients were positive at the time of diagnosis for Helicobacter pylori, 77% had chronic gastritis, 30% had a family history of a first-degree relative with gastrointestinal cancers, and 82% were current or former tobacco users. Using univariate analysis, diminished overall survival was observed with anatomic site, increasing stage, no treatment, the number of lymph nodes examined during resection, blood type, and chronic gastritis. Multivariable analysis revealed stage and treatment type were independently associated with improved overall survival. AN gastric cancer cases vary in their clinical and epidemiologic features, relative to NHW.
Citation Format: Holly Martinson, Steven Alberts, Matthew Olnes. Gastric cancer in Alaska Native people: A cancer health disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5284. doi:10.1158/1538-7445.AM2017-5284