bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 426: Identifying a predictive biomarker for chemotherapy (taxane) in patients with metastatic castration resistance prostate cancer
Authors: Rothchild Greg A. , Sandusky George , Temm Constance J. , Albany Costantine 
Published: July 2016

Abstract
In 2015, American Cancer Society predicts that 220,800 men will be diagnosed with prostate cancer (PC). Patients diagnosed with metastatic PC are first treated with androgen deprivation therapies (ADT) in order to lower testosterone to castration levels. Unfortunately, it is only a matter of time before becoming metastatic castration resistant prostate cancer (mCRPC). Subsequent treatments include combined androgen deprivation therapies such as (abiraterone, enzalutamide), immunotherapies, investigational drugs, and/or chemotherapy (docetaxel and cabazitaxel). Individualizing therapy for prostate cancer patients is an overarching goal of research. Currently, no valid practical biomarkers exist that can predict resistance to the taxane in PC. Identifying a marker that predicts taxane sensitivity would delineate patients who would benefit from taxane regimens from those who would suffer from added side-effects without any improved response. Previous studies have confirmed TLE3 is associated with a response to taxane therapy in breast and ovarian cancers. Preclinical studies have also shown that TLR4, RAGE, and HMGB1 confers chemo resistance to docetaxel on PC-3 human PC cells. After obtaining IRB approval (protocol IUCRO-0499), 8 metastatic castration resistant prostate cancer samples and 6 control samples were pulled for this study after scrutinous review of the H&E slides from clinical cases. This study then consisted of investigating the proteins TLE3, TLR4, RAGE, and HMBG1. Immunostaining was performed using the automated immunostainer, Dako FLEX System, and the slides were scanned into the whole slide Aperio Scanscope CS digital imaging system. Computer-assisted morphometric analysis of digital images was then performed using the Aperio ImageScope software. Review of the TLE3 and TLR4 expression in metastatic castration resistance prostate cancer samples showed a difference between the expressions of these two proteins. TLR4 positivity was found to be 43.88% higher than the expression of TLE3. This is suggestive of resistance to docetaxel treatments. Review of the RAGE and HMGB1 expression in metastatic castration resistance prostate cancer samples compared to normal prostate epithelium showed a 32.9% increase in RAGE and 36.6% increase in HMGB1 expression. The findings of this study are suggestive that there is a possible correlation between the overexpression of these protein biomarkers and the patient's response to a specific drug treatment.
Citation Format: Greg A. Rothchild, George Sandusky, Constance J. Temm, Costantine Albany. Identifying a predictive biomarker for chemotherapy (taxane) in patients with metastatic castration resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 426.
Abstract 4266: Reproducible spheroid formation using functionalized hyaluronan 3D scaffolds
Authors: Pannetier Pauline , Louis Fiona , Souguir Zied , Devaux Agathe , Le Cerf Didier , Vannier Jean-Pierre , Demange Elise , Vidal Guillaume 
Published: July 2016

Abstract
Extracellular matrix (ECM) characteristics, including stiffness, porosity, composition and spatial interaction with the surrounding cells and soluble factors are key components for cell growth in a tissue microenvironment. However, poor performance of 2D in vitro systems and animal models demands physiologically relevant well controlled 3D platforms for mechanistic assays, drug resistant phenotypes, new drug efficacy, toxicity assessment.
Technical limitations in the current use of multicellular spheroids prevent their widespread use in cancer research and drug development. Existing systems for spheroid formation require lengthy processing times, and make simple tasks like media exchange, cell retrieval and microscopy analysis challenging. An ideal 3D cell culture system would form spheroids in an in vivo like microenvironment, while being easy to handle and compatible with all analytical methods.
To address this unmet needs, we use a controlled hyaluronic acid-based scaffolds for spheroid formation. We have enriched 2 hyaluronan scaffolds with other components of the ECM such as collagen I, collagen IV, collagen VI, RGDs motif or galactosamine. Functionalised scaffolds overpass the 2D flat culture limitations by recreating cell/cell interactions and cell/matrix interaction to recreate a more physiologically authentic 3D architecture. The 2 functionalized scaffolds recapitulate the microenvironment for Hepatocyte and Adipocyte growth.
Once formed, the spheroids can be cultured long-term, the scaffold is transparent allowing reproducible High Content Screening, the spheroids and the cells can be retrieve, avoiding the technical issues of other 3D systems to retain samples. Moreover, the scaffold is compatible with fluorescence/luminescent kit and immunofluorescent microscopy.
We demonstrated this technology using cell lines, primary cells (adipocytes, hepatocytes). We assayed the spheroids over time using various endpoint spheroid morphology, growth and viability, resistance to anti-cancer drug, relevant cell organization formation and toxicity endpoint.
Thus, this study introduces functionalized HA scaffold for the use of in vitro culture model as that represent native cell environments is ready to ready to use and compatible with HTS and all analytical methods for drug development and compound screening.
Citation Format: Pauline Pannetier, Fiona Louis, Zied Souguir, Agathe Devaux, Didier Le Cerf, Jean-Pierre Vannier, Elise Demange, Guillaume Vidal. Reproducible spheroid formation using functionalized hyaluronan 3D scaffolds. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4266.
Abstract 4289: C-reactive protein and risk of lung cancer: A pooled analysis of 20 prospective cohorts
Authors: Muller David C. , Hodge Allison M. , Severi Gianluca , Cai Qiuyin , Meyer Klaus , Grankvist Kjell , Langhammer Arnulf , Brennan Paul , Johansson Mattias ,   Lung Cancer Cohort Consortium (LC3)
Published: July 2016

Abstract
Background: Inflammation may have an important role in the etiology of lung cancer, and several studies have reported that C-reactive protein (CRP) is associated with risk of lung cancer. To clarify this association, we conducted a pooled analysis of CRP and lung cancer risk using data from 20 prospective cohort studies.
Methods: Within the NCI Cohort Consortium, we designed a prospective nested case-control study. Controls were selected from appropriate risk sets and were matched to cases on smoking status, sex, and age at blood draw. This analysis included 5,299 case-control pairs nested within 20 cohorts. Rate ratios (RR) and their 95% confidence intervals associated with a doubling in concentration of CRP were estimated using conditional logistic regression models.
Results: Overall, higher circulating CRP was associated with an increased risk of lung cancer (RR 1.05, 95% CI [1.03, 1.08]). This association varied strongly by smoking status (p-heterogeneity &lt; 0.01), being similar for current (1.09 [1.05, 1.13]) and former smokers (1.09 [1.04, 1.14]), but not for never smokers (0.95 [0.91, 1.00]). The association was strongest for cancers diagnosed less than 2 years after blood draw (1.21 [1.13, 1.29], p-heterogeneity &lt; 0.01), and weakened as time between blood draw and diagnosis increased. The association was similar across all histological subtypes, with the exception of adenocarcinoma for which we observed no association.
Conclusions: CRP is associated with risk of lung cancer. The fact that the association is restricted to ever-smokers, and is most prominent for cancers diagnosed in the first 2 years of follow-up, strongly suggests that CRP is not a causal risk factor, but rather a distal marker of disease.
Citation Format: David C. Muller, Allison M. Hodge, Gianluca Severi, Qiuyin Cai, Klaus Meyer, Kjell Grankvist, Arnulf Langhammer, Paul Brennan, Mattias Johansson, Lung Cancer Cohort Consortium (LC3). C-reactive protein and risk of lung cancer: A pooled analysis of 20 prospective cohorts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4289.
Abstract 4306: Free IGFBP3 and the risk of liver cancer in a nested case-control study
Authors: Adachi Yasushi , Nojima Masanori , Mori Mitsuru , Matsunaga Yasutaka , Akutsu Noriyuki , Sasaki Shigeru , Endo Takao , Kurozawa Youichi , Wakai Kenji , Tamakoshi Akiko 
Published: July 2016

Abstract
Background: Insulin-like growth factor-1 (IGF1) is a potent mitogen, whereas IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 and low IGFBP3 are associated with increased risk of several cancers. Here we examined relations of those serum levels with the risk of hepatoma in a prospective case-control study nested in the JACC Study.
Methods: A baseline survey was conducted from 1988 to 1990 and 39,242 subjects donated blood samples. Those who had been diagnosed as hepatoma were regarded as cases for nested case-control studies. Ninety-one cases and 263 controls are eligible for the present analysis. A conditional logistic model was used to estimate odds ratios (OR) for incidence of hepatoma associated with serum IGF1 and IGFBP3 levels.
Results: Both IGF1 and molar ratio of IGF1/IGFBP3 were not correlated with the risk of hepatoma. After adjustment for hepatitis-viral infection, body mass index, smoking, and alcohol intake, higher molar difference of (IGFBP3 - IGF1) was associated with decreased risk of hepatoma (p for trend &lt; 0.001), and peoples in the highest quintile had a lower risk (OR = 0.098; 95%CI = 0.026-0.368). In subgroup analyses, both in male and female, high molar difference of (IGFBP3 - IGF1) was associated with decreased risk of hepatoma (p for trend &lt; 0.001). Both in the elderly and non-elderly, it was correlated inversely with risk of hepatoma (p for trend = 0.001, &lt; 0.001, respectively).
Conclusions: Molar difference of (IGFBP3 - IGF1) might associate inversely with the incidence of hepatoma.
Citation Format: Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Yasutaka Matsunaga, Noriyuki Akutsu, Shigeru Sasaki, Takao Endo, Youichi Kurozawa, Kenji Wakai, Akiko Tamakoshi. Free IGFBP3 and the risk of liver cancer in a nested case-control study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4306.
Abstract 4316: Pharmacological targeting of the TGF-beta-induced epithelial-mesenchymal transition by anthocyanidins in glioblastoma
Authors: Ouanouki Amira , Muhire Evelyne , Lamy Sylvie , Annabi Borhane 
Published: July 2016

Abstract
Introduction: Glioblastoma multiforme (GBM) is the most common primary brain tumor, known for its invasiveness and high resistance to standard treatments. Therefore, better understanding of the mechanisms that promote mesenchymal changes in GBM are of great clinical importance. Epithelial to mesenchymal transition (EMT) is a reversible biological process in which epithelial cells adopt mesenchymal properties. During EMT, migration, adhesion and cellular morphology are altered allowing benign tumor cells to infiltrate surrounding tissues and to metastasize to distant sites. Several growth factors have been shown to trigger EMT in tumor development; the Transforming Growth Factor-beta (TGF-b) is the most prominent inducer of EMT. Epidemiological studies have shown that diets rich in fruits and vegetables play an important role in preventing cancer due to their polyphenol content. Among polyphenols, the anthocyanidins, found in berries, red grapes, and other pigmented foods, plants and vegetables, have anti-inflammatory, cardioprotective, anti-angiogenic and anti-carcinogenic properties. Despite the well-known role of TGB-b in tumor progression, the impact of anthocyanidins on TGF-b-induced EMT remains misunderstood. Objectives: 1) Characterize the pharmacological effects of anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin and petunidin) on EMT, 2) identify the molecular targets leading to the inhibition of EMT modulated by anthocyanidins, and 3) characterize their effect on cellular activities involved in this tumor process. Methodology: The human U-87 glioblastoma (U-87 MG) cells were treated with anthocyanidins in pre-, co- and post-treatment with TGF-b. Results: Depending on the treatment, anthocyanidins affect differently the EMT induction by inhibiting U-87 MG cell migration. This inhibition resulted in a down-regulation of mesenchymal markers (fibronectin, snail), phosphorylation of Smad2 proteins and the mitogen-activated protein kinases (ERK, JNK) in a dose-dependent manner. Overall, delphinidin was the most potent inhibitor for all treatments. Conclusion: This study highlights a new antimetastatic action of anthocyanidins that supports the beneficial health and chemopreventive effects of dietary-based strategies against cancer.
Citation Format: Amira Ouanouki, Evelyne Muhire, Sylvie Lamy, Borhane Annabi. Pharmacological targeting of the TGF-beta-induced epithelial-mesenchymal transition by anthocyanidins in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4316.
Abstract 4317: Black raspberries show potent activity in prevention of experimental squamous cell esophageal cancer compared to a combination of selective COX-2 and iNOS inhibitors
Authors: Shi Ni , Riedl Kenneth M. , Schwartz Steven J. , Zhang Xiaoli , Steven Steven K. , Chen Tong 
Published: July 2016

Abstract
Esophageal squamous cell carcinoma (SCC) remains a major health threat worldwide and preventive strategies are needed. We previously reported that overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are correlated with nitrosamine-induced squamous carcinogenesis of the esophagus and the selective iNOS and COX-2 inhibitors significantly inhibit incidence and progression. We also demonstrated anti-cancer activity of black raspberries (BRB) in a rodent model of esophageal SCC. The objective of the current study was to compare the impact of BRB versus the combination of celecoxib, a selective COX-2 inhibitor, and S,S’-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), a selective iNOS inhibitor, in inhibition of SCC of the esophagus, and to elucidate molecular mechanism of an effective cancer prevention. We found that BRB is superior to the combination of two drugs in suppression of premalignant tissue growth in the rat esophagi. Moreover, rats fed BRB have lower tumor multiplicity than those fed celcecoxib + PBIT. Our data indicated that BRB also shows a potent inhibitory effect on esophageal iNOS and COX-2, in addition to modulating several associated oncogenic cell signaling pathways. We further conducted parallel mechanistic studies in vitro using BRB anthocyanins and the above two drugs. Our findings demonstrated that dietary BRB is superior to the combination of two chemopreventive pharmaceutical agents in prevention of experimental squamous cell esophageal cancer, suggesting the potential value of additional translational studies in developing food-based products using BRB for the prevention of esophageal SCC carcinogenesis in humans (Supported by NIH/NCI R01 CA131073).
Citation Format: Ni Shi, Kenneth M. Riedl, Steven J. Schwartz, Xiaoli Zhang, Steven K. Steven, Tong Chen. Black raspberries show potent activity in prevention of experimental squamous cell esophageal cancer compared to a combination of selective COX-2 and iNOS inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4317.
Abstract 432: Loss of MGMT promoter methylation and resistance to cisplatin in non-seminomatous germ cell tumors
Authors: Moutinho Cátia , Garcia-del-Muro Xavier , Guino Elisabet , Vidal August , Puertas Sara , Muñoz Clara , Piulats Josep , Villanueva Alberto , Esteller Manel 
Published: July 2016

Abstract
To explore if MGMT promoter methylation changes have a role in cisplatin chemoresistance, first we study its methylation status in cisplatin sensitive and resistant paired human non-seminomatous germ cancer cell lines. Secondly in xenograft paired tumors and after in human non-seminomatous germ cell primary tumors, from patients treated with cisplatin based chemotherapy. In general we found that cisplatin sensitive samples are related with MGMT promoter hypermethylation associated with its loss of expression. Resistance is present when MGMT promoter is not methylated and expressed. Clinically, the presence of MGMT promoter methylation is related with better overall survival (p = 0.025) in patients with testicular germ cell cancer. Inhibition of MGMT with O6-benzylguanine in vitro or in vivo increases the sensitivity to cisplatin and temozolomide, being this a possible chemotherapeutic approach to re-sensibilize human non-seminomatous germ cell refractory tumors.
Citation Format: Cátia Moutinho, Xavier Garcia-del-Muro, Elisabet Guino, August Vidal, Sara Puertas, Clara Muñoz, Josep Piulats, Alberto Villanueva, Manel Esteller. Loss of MGMT promoter methylation and resistance to cisplatin in non-seminomatous germ cell tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 432.
Abstract 4322: Maternal obesity increases tamoxifen resistance in female rat offspring
Authors: Zhang Xiyuan , Cruz Idalia , Zhang Hansheng , Hilakivi-Clarke Leena 
Published: July 2016

Abstract
More than 50% of pregnant women in the USA are overweight or obese, and over 40% gain more weight than recommended by the Institute of Medicine. We investigated if maternal obesity before and during pregnancy affects mammary cancer risk in the offspring, or alters response of the mammary tumors to antiestrogen therapy in a preclinical rat model of estrogen receptor positive (ER+) breast cancer.
Female Sprague-Dawley rats were fed an obesity-inducing high fat (OIHF) or control diet before and during pregnancy. Their offspring were all switched to a control AIN93G diet upon birth. Female offspring of control (n = 35) or OIHF (n = 40) diet fed dams were treated with a carcinogen DMBA on postnatal day 50 to induce ER+ mammary tumors. When mammary tumors reached a size of 13 mm in diameter, 337 ppm TAM citrate was added to the offspring's diet, resulting a daily intake of 15 mg/kg TAM. Responses of the tumors were categorized as de novo resistant (tumor kept growing), partial (size decreased but did not disappear), and complete (tumor disappeared). The animals with complete response were taken off from TAM and monitored for an additional 20 weeks to determine the risk of local recurrence.
The risk of developing mammary tumors was non-significantly increased in the OIHF group. Further, the OIHF exposed offspring had significantly more de novo resistant tumors than the control offspring. Although the percentage of completely responding tumors was similar in the two groups, local recurrence in the OIHF offspring was significantly higher than in the control offspring (90% vs 29%, respectively). To investigate the possible mechanisms of increased recurrence, we measured the protein levels of the members of unfolded protein response (UPR), inflammation and tumor immune pathways. We found that de novo TAM resistant and recurring tumors in the OIHF offspring exhibited significantly increased levels of Perk and Beclin-1, indicating activation of UPR. However, Nbr1 and p62 were also significantly increased in the OIHF offspring, suggestive of inhibition of autophagy in their mammary tumors. The levels of CD8a, a marker of cytotoxic T cells, were significantly reduced, whilst ERα, erBb2/Her2 and Vegfr2 were increased. Changes in the expression of these receptors could indicate increased inflammation.
We conclude that maternal obesity increased TAM resistance and the risk of mammary cancer recurrence in the female offspring. In addition, it induced changes in the UPR, autophagy and tumor immune responses in the offspring's mammary tumors.
Citation Format: Xiyuan Zhang, Idalia Cruz, Hansheng Zhang, Leena Hilakivi-Clarke. Maternal obesity increases tamoxifen resistance in female rat offspring. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4322.
Abstract 4329: The consequence of obesity and obstructive sleep apnea in liver cancer
Authors: Sweeney Nathan W. , Gomes Cecil J. , Pathasarthasy Sairam , Martinez Jesse D. 
Published: July 2016

Abstract
Primary liver cancer is the 3rd leading cause of cancer mortality worldwide. Eighty-five percent of liver cancers is comprised of hepatocellular carcinoma (HCC). Risk of developing HCC increases when patients have obesity related comorbidities, involving non-alcoholic steatohepatitis (NASH), hepatic inflammation, or lipid accumulation. Additionally, obesity is generally regarded as a prime risk factor for the development of obstructive sleep apnea (OSA), a repeated obstruction of the upper airway during sleep leading to oxygen deficiency (OD), which also increases the incidence of NASH. The connection of these morbidities presume that patients suffering from obesity induced OSA have an increased risk of developing HCC. To examine obesity and OSA's role in HCC we combined three generally accepted methods: A one-time injection of tumor initiator diethylnitrosamine followed by continuous administration of the promoter phenobarbital, a high fat diet, and a hypoxia chamber to house the mice for regulation of their oxygen intake, allowing us to mimic the OD seen in OSA. Utilizing these treatment methods and applying microCT imaging to non-invasively and repeatedly monitor the liver, we have been able to examine the effects of obesity and/or OD. Preliminary result indicate that a high fat diet results in obesity, lipidosis and liver damage. Interestingly, OD seems to inhibit obesity while still generating hepatic inflammation. Furthermore, we have observed that obesity and OD together cause severe damage to the liver, enhancing the risk of developing HCC. This study will be a significant preclinical step in distinguishing mechanisms that may explain obesities and OSA's combined consequence in HCC.
Citation Format: Nathan W. Sweeney, Cecil J. Gomes, Sairam Pathasarthasy, Jesse D. Martinez. The consequence of obesity and obstructive sleep apnea in liver cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4329.