bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2433: Comparisons between an IRDye 800CW-labeled PSMA-targeted small molecule and antibody for preclinical small animal imaging
Authors: Kovar Joy L. , Cheung Lael L. , Simpson Melanie A. , Olive D Michael 
Published: August 2012

Abstract
Prostate cancer continues to be the second leading cause of cancer death in men in 2011. Deciphering the progression and mechanisms contributing to the metastatic spread of this disease is critical to our overall understanding of how to approach treatment and/or therapy. Prostate-specific membrane antigen (PSMA) is a possible therapeutic target for the disease and is the focus of several cancer therapies currently in clinical trials. Near infrared (NIR) fluorescence imaging for cancer diagnosis and treatment is gaining attention for preclinical as well as clinical applications. IRDye 800CW is a NIR fluorophore exhibiting superior target-to-background ratios when conjugated to targeting moieties such as antibodies, peptides, and small molecules. Here we assess two different PSMA-targeted compounds conjugated to IRDye 800CW: the small molecule YC-27 and a PSMA-specific antibody. In vitro binding kinetics for both compounds exhibit expected dose dependent increases with increasing concentrations. Both compounds were successfully blocked with their unlabeled counterpart; however, neither blocked the other suggesting different PSMA epitopes. Although direct comparisons are inappropriate due to differences in molecular structures and labeling density, assessment of their respective pharmacokinetics is possible. Microscopy of prostate tumor cells incubated with each probe revealed a slower internalization of the small molecule when compared to the internalization of the antibody. Specificity of the labeled compounds in vivo was determined in male athymic nu/nu mice implanted with 22Rv1 (PSMA positive) or PC3M-LN4 (PSMA negative) prostate cancer cells (106). Mice received either IRDye 800CW YC27 (1 nmole) or IRDye 800CW PSMA (50 µg) followed by non-invasive fluorescent optical imaging of 800nm signals on the Pearl Impulse Small Animal Imager. At the study endpoint, organs and tumors were excised and imaged to assess residual probe localization. In vivo clearance patterns for these labeled molecules differed with the YC27 clearing via the kidneys and the antibody clearing through the liver. These subtle differences between the two imaging agents provide valuable options to investigators with specific requirements in their animal research.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2433. doi:1538-7445.AM2012-2433
Abstract 2442: A precise orthotopic rectal tumor model for evaluating therapeutic response of cancer treatment
Authors: Kikuchi Satoru , Kishimoto Hiroyuki , Tazawa Hiroshi , Hashimoto Yuuri , Uno Futoshi , Nishizaki Masahiko , Kagawa Shunsuke , Urata Yasuo , Hoffman Robert M. , Fujiwara Toshiyoshi 
Published: August 2012

Abstract
We have previously reported a “true” orthotopic rectal model in which tumors start forming in the rectal mucosal tissue from which tumors actually arise. The model was generated by intrarectal transplantation of mouse rectal cancer cells stably expressing fluorescent protein, followed by disrupting the epithelial cell layer of the rectal mucosa by soaking with an acetic acid solution. Early stage tumor was detected on the rectal mucosa from as early as 6 days after transplantation, which then became invasive into the submucosal tissue. The tumor incidence on the rectal mucosa was 100%, and it was proved that this rectal tumor model reflects the natural course of rectal cancer accurately. Spontaneous lymph node metastasis and lung metastasis were observed 4 weeks after transplantation in over 90% of mice. In the present study, we will report whether this model is useful for evaluating therapeutic response of surgical local resection of tumor with combination of anticancer drugs such as a telomerase-specific replicating adenovirus designed for cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2442. doi:1538-7445.AM2012-2442
Abstract 2452: Tumor detection and measurement of responses to chemotherapy using human phosphatidylserine targeting antibody fragments
Authors: Gong Jian , Archer Rich , Peacock Matthew , Hughes Christopher , Chang Connie , Freimark Bruce 
Published: August 2012

Abstract
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors recruit immune cells and engage the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric anti-PS antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II trials. In the present study, we characterize the response to chemotherapy of human tumor xenografts in mice using near-infrared dye labeled PGN650, a human F(ab’)2 fragment that targets PS expression. NIR-PGN650 bound human PC-3luc prostate, BT474 breast and A549luc non-small cell lung tumors in SCID or nude mice in the absence of chemotherapy. Docetaxel treatment enhanced tumor targeting of NIR-PGN650 approximately 2-3-fold compared to imaging signals prior to chemotherapy. Peak tumor uptake of NIR-PGN650 was observed when docetaxel was delivered 24 hours prior to injection of NIR-PGN650. Using these parameters, NIR-PGN650 is able to detect responses to chemotherapy in both the primary tumor and metastases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2452. doi:1538-7445.AM2012-2452
Abstract 2548: Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver
Authors: Ross Jeffrey A. , Leavitt Sharon A. , Schmid Judith E. , Nelson Garret B. 
Published: August 2012

Abstract
We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue™ transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclobutanil was not mutagenic under the same conditions. DNA sequencing of the mutants recovered from each treatment group and from untreated control animals revealed that the mutations induced by propiconazole and triadimefon do not result from clonal expansion of background mutations. We hypothesized that these mutations arise from the accumulation of reactive electrophilic metabolic byproducts within the liver in vivo. We therefore measured the spectra of endogenous DNA adducts in the livers of mice from these studies in order to determine if quantitative or qualitative differences in DNA adducts correlated with mutagenicity and tumorigenicity. We resolved and quantitated 16 individual adduct spots by 32P postlabeling and thin layer chromatography using 3 solvent systems. Qualitatively, we observed the same DNA adducts in control mice as in mice receiving conazoles. However, the 13 adducts with the highest chromatographic mobility were, as a group, present at significantly higher amounts in the livers of mice treated with propiconazole and triadimefon than in their concurrent controls, whereas this same group of DNA adducts in the myclobutanil-treated mice was not different from controls. We hypothesize that this treatment-related increase in endogenous DNA adducts may explain the observed increased in vivo mutation frequencies previously reported to be induced by treatment with propiconazole and triadimefon. This abstract does not necessarily reflect EPA policy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2548. doi:1538-7445.AM2012-2548
Abstract 2553: A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5
Authors: Kuang Lisha , Kou Haiping , Xie Zhongwen , Zhou Ying , Wang Zhigang 
Published: August 2012

Abstract
DNA damage tolerance is a major cellular mechanism in response to unrepaired DNA lesions during replication. It allows replication to completion in the presence of DNA lesions that block replicative polymerases. Damage tolerance consists of two major mechanisms: template switching and translesion DNA synthesis. Translesion synthesis directly copies damaged sites of the DNA template during replication. Consequently, error-prone translesion synthesis constitutes the major mechanism of base damage-induced mutagenesis. In eukaryotes, translesion synthesis is carried out by the Rev1-Polα pathway. Rev1 possesses a dCMP transferase activity, and is a member of the Y family of DNA polymerases. Additionally, it is widely believed that Rev1 plays non-catalytic functions in translesion synthesis. However, the non-catalytic function of Rev1 is not clearly defined. Using the yeast model system, we have investigated non-catalytic functions of Rev1 in translesion synthesis and base damage-induced mutagenesis. Specifically, we examined the role of Rev1-Rad5 interaction in translesion synthesis of UV damage and a site-specific 1, N6-ethenoadenine (a DNA lesion of lipid peroxidation products). Although Rad5 is better known for its role in template switching, it stably interacts with Rev1. Interaction domains in the Rev1 and Rad5 proteins were defined. Translesion synthesis and mutagenesis required Rad5 in cells. Disrupting the Rev1-Rad5 interaction by mutating Rev1 did not affect the dCMP transferase of Rev1, but led to inactivation of the translesion synthesis pathway. These results show that Rad5 is an indispensible component of the Rev1-Pol ≤ pathway for translesion synthesis and base damage-induced mutagenesis, and a non-catalytic function of Rev1 in translesion DNA synthesis is mediated by its stable interaction with Rad5.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2553. doi:1538-7445.AM2012-2553
Abstract 2555: Aberrantly expressed AURKC increases tumorigenicity in cancer cells
Authors: Hung Liang-Yi 
Published: August 2012

Abstract
Aurora-C (AURKC) belongs to the Aurora kinase family, which regulates many important events of the cell cycle. Aberrantly expressed Aurora kinases were demonstrated to be correlated with tumorigenesis. Recently, overexpression of AURKC was detected in human primary colorectal cancers, thyroid carcinoma, and several cancer cell lines. However, the regulation of and clinical index for overexpressed AURKC in somatic cancer cells are unclear. Herein, we showed that AURKC has an augmented expression in human cervical cancer with a statistical significance in its development. Overexpressed AURKC increases the proliferation, transformation, and migration activities in cultured cancer cells and in a xenograft model. Importantly, the kinase activity of AURKC is required for its ability of tumorigenesis. A reporter assay and Western blot analysis further demonstrated that PLZF, a transcriptional repressor, serves as a negative regulator for AURKC. The expressions of PLZF and AURKC mRNA in human cervical cancer displayed opposite patterns. Ectopically expressed HA-PLZF specifically repressed the expression of human AURKC, but not other Aurora kinase members, through recruitment to its promoter region. Taken together, our results provide important insights into human cervical cancer and AURKC expression, which may serve as a potential target for human cervical cancer therapy in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2555. doi:1538-7445.AM2012-2555
Abstract 2569: Lyc-O-Mato causes cell cycle arrest and apoptosis in human bladder transitional carcinoma cells
Authors: Bhaskaran Natarajan , Shukla Sanjeev , Ponsky Lee E. , Cherullo Edward E. , Gupta Sanjay 
Published: August 2012

Abstract
Approximately two thirds of new bladder cancer cases in the United States are superficial papillary transitional cell carcinoma (TCC), the majority of which are low-grade neoplasms. Data suggest that bladder carcinogenesis is a multi-step, multi-focal (field effect) process, possibly involving the spread of pre-malignant clones-all of which are prerequisites for effective preventive and/or interventional approaches. Epidemiological data suggests an inverse relationship between serum levels of carotenoids and risk of bladder cancer which has encouraged further investigation. In this study, we evaluated the effect of Lyc-O-Mato® (a crude tomato extract containing 10% lycopene and other tomato phytonutrients viz. tocopherols, phytoene, phytofluene, beta-carotene, phospholipids and phytosterols) on human bladder cancer cell growth, cell cycle modulation, induction of apoptosis, and associated molecular alterations. Treatment of bladder cancer cell lines (T-24, high-grade TCC and TCC-SUP, high-grade invasive tumor) with Lyc-O-Mato® at doses of 1-60µM resulted in inhibition of cell growth along with a G1 arrest in T24 cells and G2/M arrest in TCCSUP cells at 24 h post-treatment. In other studies, Lyc-O-Mato® treatment strongly induced the expression of p21/waf1 and p27/kip1, and resulted in a decrease in cyclin-dependent kinases (CDKs) and cyclins involved in G1 and G2/M progression in T24 and TCC SUP cells. Lyc-O-Mato® exposure to these cells showed an increased interaction between cyclin dependent kinase inhibitors (CDKIs)-cyclin-dependent kinases (CDKs) and decrease in the interaction of cyclins and CDKs with their respective stages of the cell cycle. Furthermore, Lyc-O-Mato® treatment significantly reduced the phosphorylation of Retinoblastoma at Serine780, although no significant changes were observed in the total levels of this protein. In additional studies, Lyc-O-Mato® showed a dose- and time-dependent apoptotic death in both T24 and TCC SUP cells which was associated with significant downregulation of survivin along with the enhancement of pro-apoptotic protein, Bax. These observations provide a strong rationale for further evaluating preventive and/or intervention strategies for Lyc-O-Mato® in pre-clinical models of bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2569. doi:1538-7445.AM2012-2569
Abstract 257: PARP inhibitor induces cytotoxicity in primary lung cancer through caspase induction
Authors: Gangopadhyay Nupur N. , Luketich James D. , Opest Amy , Landreneau Rodney , Schuchert Matthew J. 
Published: August 2012

Abstract
Considering the fact that lung cancer has a high incidental rate among all cancer types, our investigation was aimed to see if PJ34, a PARP inhibitor, could independently exert cytotoxicity in primary lung cancer cells. In the past this PARP inhibitor has been used in combination with other DNA targeted chemotherapeutics or in patients with DNA repair defects (e.g. BRCA mutation), however, based on our published findings we hypothesize that PJ34 can target lung cancer using alternative mechanisms where defects in DNA repair or synthetic lethality are not required. Additionally, we wanted to reveal the specific mechanisms of PARP inhibitor mediated cytotoxicity in lung cancer cells. Anti-cancerous effects of PJ34 were evaluated on six non-small cell lung cancer cell lines developed from surgically resected tissue. Using WST-1 dye and BrdU assay, 30uM (ED50) of PJ34 treatment showed a variable amount of cell survival and DNA synthesis among cultures used herein. Cellular morphological changes in response to the PJ34 treatment were investigated using annexin-V expression, nuclear fragmentation staining, and PARP specific protein in Western blot. Mitochondrial membrane potential changes were measured through JC-1 dye staining and indicated increased stress upon PJ34 treatment. The abundance of Caspase-9 further proves the role of mitochondrial stress in PJ34 treated cells. Immunofluorescent staining for Caspase-3 clearly showed changes towards apoptosis under PJ34 treated vs. untreated conditions. Additionally, a Caspase-3 specific protein band in PJ34 treated cells indicates the possibility of apoptosis through a caspase dependent pathway. Furthermore, lower expressions of PAR in PJ34 treated cells were indicative of PARP inhibition. This study has brought a new paradigm for using PJ34 as a potential therapeutic against lung cancer because of its ability to work regardless of a patient's genetic makeup as well as the possibility of using this group of compounds as independent chemotherapeutic agents.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 257. doi:1538-7445.AM2012-257
Abstract 2570: Role of PPAR gamma in chemoprevention of renal cell carcinomas by omega-3 fatty acids
Authors: Taub Mary L. , Cutuli Facundo 
Published: August 2012

Abstract
Renal Clear Cell Carcinoma (RCC) is the tenth most prevalent cancer, accounting for 80% of all renal cancers. Recent results of a 15.3 year epidemiological study indicate that a diet of fatty fish offers significant protection against RCC, results which were attributed to omega-3 fatty acids. The question arises as to the molecular mechanisms by which such omega-3 fatty acids exert their protective effect. Our hypothesis is that omega-3 fatty acids exert their protective effects by activating Peroxisome Proliferator-Activated Receptors (PPARs), which in turn reduce the level of expression of Hypoxia Inducible Factor (HIF). The level of HIF increases as a consequence of mutations in the von Hippel Lindau (VHL) gene, which is key to the development of RCCs. In order to begin to examine this hypothesis, primary cultures of renal proximal tubule cells have been examined with regards to their growth responses to PPAR agonists (as the RCC is of renal proximal tubule origin). Fibrate drugs and thiazolidinediones (TZDs) have been identified which have a high affinity for two different classes of PPARs, PPAR alpha and PPAR gamma, respectively. We have observed that troglitazone, a PPAR gamma agonist, caused a 4-fold increase in growth a concentration range of 10-6 to 5 x 10-6 M. A physiologically produced PPAR gamma agonist, Prostaglandin J2 (PGJ2), was also growth stimulatory, albeit to a lesser extent. In contrast, fenofibrate, a PPAR alpha agonist, had no significant affect. In order to examine our hypothesis that PPAR gamma activation affects signaling through HIF, transient transfection studies were conducted with HRE-Luc, a HIF regulatory element/reporter construct. The level of expression of HRE-Luc increases during hypoxia, leading to metabolic changes that promote tumorigenesis. Our studies with HRE-Luc indicate that 5 x 10-6 M troglitazone reduces the increase in HRE-Luc gene expression by over 50%. Similarly, troglitazone prevented the increase in HIF which occurs under normoxia in the presence of the hydroxylase inhibitor dimethyloxalylglycine (DMOG).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2570. doi:1538-7445.AM2012-2570
Abstract 2585: Resveratrol induces autophagy in prostate cancer cells and intervention suppresses the progression of PIN in animals
Authors: Li Guiming , Ghosh Rita , Rivas Paul , Reddick Robert Lee , Kumar Addanki Pratap 
Published: August 2012

Abstract
Resveratrol (3,4′-trihydroxystilbene), a natural product is present in significant concentrations in red wine, peanuts, walnuts etc. Emerging evidence indicates that resveratrol exerts antitumorigenic activity in various tumor models including prostate. Although multiple biological effects on proliferation, apoptosis and activation of SIRT1 have been demonstrated to be associated with resveratrol-induced activities, the precise mechanism associated with resveratrol-induced SIRT1 activation and cancer cell growth inhibition remains unclear. In addition, whether resveratrol intervention suppresses the development and progression of PIN (Prostatic Intraepithelial Neoplasia) is unknown. In this study, we examined the role of SIRT1 and the underlying mechanism involved in resveratrol-mediated biological effects. Our results show that although resveratrol significantly inhibited proliferation of multiple prostate cell lines including RWPE-1, C42B, PC3 and DU145 at higher concentrations (&gt; 50 µM); however, at lower concentrations (&lt; 25 µM), resveratrol prompted cell proliferation. Interestingly androgen responsive LNCaP cells exhibited resistance to resveratrol-mediated inhibition of cell proliferation. Under these experimental conditions, we also observed significant increase in autophagy without remarkable increase in apoptosis. Given the role of Akt/mTOR signaling pathway as a negative regulator of autophagy, we investigated whether resveratrol induce autophagy via modulation of Akt/mTOR signaling. Our data indicate that resveratrol-induced autophagy was associated with decreased levels of mTORC1 activity and increased SIRT1 expression. Knockdown of SIRT1 enhanced prostate cell proliferation and attenuated resveratrol-induced autophagy. Using prostate specific PTEN−/− mice, we found that dietary administration of resveratrol reduced the incidence of high-grade PIN lesions significantly. These findings implicated an important role for mTORC1/SIRT1 signaling axis in mediating resveratrol-induced upregulation of autophagy and inhibition of apoptosis. [Supported by NIH CA137578 (APK)]
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2585. doi:1538-7445.AM2012-2585