bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 539: The expression of monocyte/macrophage-restricted scavenger receptor CD163 by malignant cells may be a consequence of cell fusion with tumor-associated macrophages: A novel target for cancer therapy
Authors: Maniecki Maciej B. , Damsky William E. , Ulhøi Benedicte P. , Steiniche Torben , Ørntoft Torben F. , Dyrskjøt Lars , Borre Michael , Kjeldsen Eigil , Bosenberg Marcus W. , Møller Holger J. 
Published: June 2012

Abstract
Solid tumors contain large a number of infiltrating macrophages, which are believed to play a key role in progression and metastasis. Recent research has indicated that malignant cells at times express molecular pathways normally only observed in myeloid cells such as macrophages, hence suggesting that macrophages may fuse with tumor cells. In the present work, we aimed to investigate tumor cell expression of the monocyte/macrophage-restricted scavenger receptor CD163. Initially, the tumor expression of CD163 was examined using a bladder cancer tissue microarray (TMA) containing 425 cores of tumor tissue from 425 patients and 43 paired metastatic lymph nodes. Tumor cells showed a characteristic pleomorphic and atypical morphology with large nuclei, and they were easily distinguished from macrophages. Immunohistochemical staining revealed that CD163-expressing tumor cells could be detected in 98% of the tumor cores, and CD163-expressing metastatic cells could be identified in 77% of the cores of lymph node biopsies. Quantitative real-time polymerase chain reaction and flow cytometric analysis showed that bladder cancer cell lines did not express CD163; however, when co-cultured with macrophages a significant induction of CD163 expression was observed. Utilizing the xCELLigence Real-Time Cell Analyzer System we showed that macrophage-tumor hybrid cells exhibited a significantly increased migratory capacity compared to non-hybrid tumor cells. Tracing the Y chromosome in co-cultures of male macrophages and female T24 cells, we found T24 cell nuclei to be fused with the macrophages. A Cre-inducible mouse model of melanoma expressing a fluorescent reporter system (GFP) was used to characterize hybrid cell formation of macrophages with GFP positive tumors cells in vivo. Flow cytometric analysis demonstrated that &gt;90% of the murine GFP positive tumor cells co-expressed CD163.
In conclusion, we show that the expression of the monocyte/macrophage scavenger receptor CD163 was not confined to tumor-associated macrophages. In fact, a significant portion of the tumor cells also expressed CD163, possibly as a result of heterotypic cell fusion between tumor cells and macrophages. Our findings identify CD163 as a possible target for novel cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 539. doi:10.1158/1538-7445.AM2011-539
Abstract 5443: A novel biosensor for monitoring intracellular cGMP in live cells
Authors: Sun Yanjie , Keeton Adam B. , Tinsley Heather N. , Butler Braeden L. , Binkowski Brock F. , Piazza Gary A. 
Published: June 2012

Abstract
The second messenger, cyclic guanosine 3’, 5’-monophosphate (cGMP) is a critical and multifunctional signaling molecule involved in many cellular processes. Intracellular cGMP is synthesized by guanylyl cyclase (GC) and is degraded by various phosphodiesterase (PDE) isozymes. Increased levels of cGMP can activate cGMP-dependent protein kinase (PKG), modulate cGMP-gated ion channels, or affect PDE activity. Since cGMP plays an important physiological role and may also be involved in various pathological conditions, including cancer, CNS disorders, and vascular deficiencies, cGMP-specific PDE isozymes represent an important class of drug targets. In order to measure intracellular cGMP levels in live cells, we constructed a novel genetically encoded cGMP biosensor with cGMP binding domains (from human PDE5A GAF-A domain) fused to a modified firefly luciferase. A lipid based reagent was used to transiently transfect HEK293 with this biosensor. Cells were then treated with the nitric oxide donors, sodium nitroprusside (SNP) or NOR-3, which are known to activate soluble GC. Bioluminescence was measured every 2 minutes for at least 60 minutes following treatment. Both SNP (50 µM) and NOR-3 (100 µM) caused a 3-fold increase in bioluminescence compared with vehicle treated cells, reaching a maximum within 10 to 20 minutes of compound addition. Co-transfection with soluble GC further increased the response up to 13-fold following SNP treatment. In addition, PDE inhibitors such as, zaprinast, dipyridamole and 3-isobutyl-1-methylxanthine amplified the response to SNP treatment. As expected, co-transfection with PDE5A decreased the basal level of cGMP and increased the sensitivity of the cGMP response to zaprinast and SNP, as well as the combination. These results suggest that this cGMP biosensor can be useful for studying drug effects on cGMP signaling in live cells. Methods to use the assay for high throughput screening are also being developed. Funding provided by NIH/NCI grants CA131378 and CA148817.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5443. doi:10.1158/1538-7445.AM2011-5443
Abstract 5568: Ginkgo biloba extract kaempferol induces apoptosis in human prostate cancer cells through downregulation of β-Catenin signaling
Authors: Zeng Yan , Xiao Dong 
Published: June 2012

Abstract
Kaempferol (Kae) is one of the most important constituents in ginkgo biloba extract which has been well known for its antioxidant and anti-inflammatory activities. Kae is also reported to suppress the growth of cancer cells but the mechanism of cell death induction is not fully understood. In the present study, we performed in vitro studies, for the first time to examine whether Kae induces apoptotic cell death in human prostate cancer cells and if β-Catenin signaling pathway is involved in the Kae-induced apoptosis. Kae treatment was found to decrease viability of human prostate cancer PC-3 (androgen independent, p53 null) and LNCaP (androgen responsive, wild-type p53) cells at pharmacologically achievable concentrations (10-40 µmol/L at 24 h). The anti-cancer activity by Kae was caused by apoptosis induction, which was determined by increased cytoplasmic histone-associated DNA fragmentation, caspase 3 activities and sub-G0/G1 cell phase in PC-3 and LNCaP cells treated with Kae compared with controls. Interestingly, a normal human prostate epithelial cell line (PrEC) is significantly more resistant to growth inhibition and apoptosis induction by Kae. Exposure of PC-3 and LNCaP cells to Kae resulted in significant inhibition of β-Catenin protein levels by Elisa assay, down-regulation of protein expression of β-Catenin as well as its down stream targets C-myc, Cyclin D1 and survivin, and alteration in nuclear/cytoplasmic distribution of β-Catenin by immunoblotting. Moreover, Kae treatment significantly inhibited the β-Catenin/TCF transcriptional activity in PC-3 and LNCaP cells transiently transfected with the TCF-4 reporter assay. We also found that apoptosis induction by Kae in human prostate cancer cells correlates with suppression of androgen receptor (AR), phosphor-AR and PSA protein levels. In conclusion, the present study indicates that β-Catenin as well as AR signaling pathways may be targets for Kae-induced apoptosis in human prostate cancer cells. This investigation was supported by USPHS grant R21 CA143104-02, awarded by the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2011-5568
Abstract 831: Chemopreventive effects of selective estrogen receptor modulator (SERM) raloxifene on intestinal neoplasia of APCMin/+ mice
Authors: Janakiram Naveena B. , Mohammed Altaf , Qian Li , Venkateshwar Madka , Reddy Manasa P. , Steele Vernon E. , Rao Chinthalapally V. 
Published: June 2012

Abstract
Estrogen receptor β (ER-β) has been implicated in several neoplastic diseases. Previously we have shown that ER-β is up-regulated in human and rodent colonic tumors, suggesting ER-β as a potential target for colon cancer prevention (Naveena et al., CaPR 2009). Thus, ER-β modualtors, SERMs are useful for colon cancer prevention. Hence, we tested raloxifene, an ER antagonist in APCMin/+ mice treated with azoxymethane (AOM), to enhance the colonic tumors. Six-week-old male and female APCMin/+ (9/group) were injected s.c., with AOM at 5 mg/kg BW, once a week for three weeks. APCMin/+ mice were then fed diets containing 0, 1.5, and 3.0 ppm raloxifene for 12 weeks before intestinal tumors and various markers of toxicity, cell proliferation and apoptosis were evaluated. Results suggest that dietary administration of 1.5 and 3.0 ppm raloxifene in male mice suppressed small intestinal polyp formation by 24% (p&lt;0.05) and 58% (p&lt;0.0001), respectively. In female mice, 1.5 and 3.0 ppm raloxifene suppressed small intestinal polyps by 58% (0&lt;0.0001) and 48% (p&lt;0.0001), respectively. Also, significant inhibition of colonic tumor suppression was observed in female mice fed the 1.5 and 3.0 ppm of raloxifene, whereas in male mice, only high-dose inhibited colonic tumors. Mice fed with raloxifene had &gt;70% less polyps with size of &gt;1-mm suggesting suppression of tumor volume/size. Also, we find that raloxifene treatment in female APCMin/+ mice showed significantly reduced serum creatine phosphokinase and cholesterol levels, and an increased alkaline phosphatase levels when compared to untreated control mice. Also, a dose-dependent increase in serum calcium was observed with raloxifene administration. Dietary raloxifene showed no liver enzyme toxicities as measured by aspartate aminotransferase levels in serum. However, raloxifene administered mice showed a modest decrease in serum glucose levels. The mRNA and protein expression levels for p21cip/waf1 were significantly higher with decreased expression of Cyclin D1 and PCNA in raloxifene treated colonic tumors and SI polyps compared to control diet fed mice tissues, suggesting estrogen's function in crypt cell proliferation. Overall, our results clearly suggest that raloxifene significantly suppresses small intestinal and colonic polyps formation by up-regulating p21cip/waf1 and has potential usefulness for human colon cancer prevention. (Supported by CN53300 and R01-94962)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 831. doi:10.1158/1538-7445.AM2011-831
Abstract 832: Effects of beta-cryptoxanthin on cigarette smoke-induced lung oxidative damage, inflammation and activation of NF-kappa B and AP-1
Authors: Liu Chun , Bronson Roderick T. , Russell Robert M. , Wang Xiang-Dong 
Published: June 2012

Abstract
In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which beta-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of beta-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of pro-inflammatory cytokine [tumor necrosis factor alpha (TNF-alpha)] and transcription factors [nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2′-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty six male ferrets were assigned to cigarette smoke exposure or to no exposure and to no dose, low-dose, or high-dose beta-cryptoxanthin supplementation (2 × 3 factorial design) for 3 months. Beta-cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. Beta-cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. Beta-cryptoxanthin also substantially reduced smoke-elevated TNF-alpha levels in alveolar, bronchial, bronchiolar and airway serous/mucous gland epithelial cells and in lung macrophages. Moreover, beta-cryptoxanthin decreased smoke-induced activation of NF-kappa B and expression of AP-1 and 8-OHdG. The beneficial effects of beta-cryptoxanthin were stronger for high-dose beta-cryptoxanthin than for low-dose beta-cryptoxanthin. Data from this study indicate that beta-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs. Beta-cryptoxanthin may prevent lung carcinogenesis through its inhibitive effects on lung inflammation and oxidative DNA damage.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 832. doi:10.1158/1538-7445.AM2011-832
Abstract 894: Pancreatic cancer screening by TLR phenotyping
Authors: Rosenberg Jonathan S. , Singh Sujay , Raul Sanjay , Tong Zhimin , Guha Sushovan 
Published: June 2012

Abstract
Background: Toll-like receptor (TLR) proteins play key roles in immune responses against infection. TLRs are normally associated with multiple chronic inflammatory diseases. As chronic inflammation often leads to development of neoplasia, we hypothesize that TLRs may promote neoplasia in distinct organ types. Elevated expression of some TLRs has been reported in many tumor tissues and/or tumor cell lines. It is known that in pancreatic ductal adenocarcinoma (PDAC), chronic inflammatory conditions often precede the tumorigenesis process. However, in this context a comprehensive analysis of expression of TLRs in PDAC is currently unknown.
Aim: To investigate the expression of multiple TLRs in PDAC cells.
Methods and Results: Multiple PDAC cell lines including AsPC-1, MIA PaCa2, PANC-1, PANC-28, and SW1990 were used for TLR phenotyping. The expression of TLRs including TLR2, 3, 4, 7 and 9 were analyzed by Flow Cytometry and Western Blotting techniques. We found that the expression of TLR2, 3, 4, 7 and 9 can be detected in MIA PaCa2, PANC-1, PANC-28, and SW1990 cells. However, the expression of TLR4 and TLR7 are very low in SW1990 cells when compared to MIA PaCa2, PANC-1, and PANC-28 cells. In AsPC-1 cells, the expression of TLR2, 4, and 7 are below the detection levels while the expression of TLR9 and TLR3 can be readily detected.
Conclusion: The expression profile of TLRs is distinct among multiple PDAC cells. Using the PDAC cell lines as a model system we are assessing potential predictive value of TLRs as biomarkers in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 894. doi:10.1158/1538-7445.AM2011-894
Abstract 92: Effects of p16 methylation on the efficacy of cetuximab in metastatic colorectal cancer
Authors: Kim Ki Hyang , Park Kyu Hyun , Chang Hyun , Kim Hyo Song , Shin Sang Joon , Rha Sun Young , Chung Hyun Cheol , Roh Jae Kyung , Ahn Joong Bae 
Published: June 2012

Abstract
Background: Promoter DNA methylation is an important epigenetic factor of gene inactivation in human carcinogenesis and gene silencing of tumor suppressor genes in colorectal cancer. Global DNA methylation, reflected by the status of LINE-1 methylation, plays an important role in genomic instability and carcinogenesis. We examined the role of p16 methylation and LINE-1 methylation in metastatic colorectal cancer patients treated with cetuximab chemotherapy.
Methods: The study was performed using fresh frozen specimens from 42 metastatic colorectal cancer patients treated with cetuximab. Samples were analyzed by bisulfied-based approaches to study the methylation status of p16 and LINE-1 by pyrosequecing. KRAS mutation was determined by pyrosequencing.
Results: Methylation of p16 was associated with decreased progression-free survival in all patients (n=42, 4.9 months in p16 methylated patients vs 15.7 months in p16 unmethylated patients, p=0.01). When proximal location tumors were analyzed separately, methylation of p16 was associated with decreased progression-free survival (n=11, 4 months vs 15.7 months, p&lt;0.01), and decreased overall survival (14.5 months vs 35 months, p&lt;0.01). Among KRAS wild type tumors (n=35), methylation of p16 demonstrated a tendency toward decreased progression-free survival (6.3 months in methylated patients vs 15.7 months in unmethylated patients, p=0.07). In 3rd line erbitux treatment patients (n=13), the median PFS was 4.0 months for p16 methylated patients and 9.6 months for unmethylated patients (p=0.25). In the response rate analysis, compared with KRAS wild type tumors, KRAS mutant tumors had a significantly lower response rate (0 % vs 45.7%, p=0.033). Compared with P16-methylated tumors, p16 unmethylated tumors demonstrated a tendency toward better response rate (10% vs 46.9%, p=0.061). LINE-1 methylation was not associated with either progression-free survival (p=0.53) or response rate (p = 0.53).
Conclusions: 16 methylation may be a factor other than KRAS mutation associated with resistance to anti-EGFR monoclonal antibodies. Because we analyzed heterogeneous population and our sample size was too small, we suggest that further studies are necessary to determine the predictive role of DNA methylation markers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 92. doi:10.1158/1538-7445.AM2011-92
Abstract 993: Enhanced EGFR activity of prostate cancer cells by low pH, low glucose environment
Authors: Bollu Lakshmi R. , Weihua Zhang 
Published: June 2012

Abstract
Background: Hypoxia, lack of nutrients and high aerobic glycolysis creates a microenvironment of high lactate, low glucose and low pH conditions within a solid tumor. The purpose of the current research is to study how the cancer cells adapt to a microenvironment with low pH, low glucose and high lactate levels with selective growth advantages.
Methods: We simulated solid tumor microenvironment conditions by making DMEM media with low glucose (2mM), high lactate (10mM) and low pH (6.5). To study the growth advantages of this microenvironment, we determined the effect of low pH, low glucose and lactate medium on EGFR activation. Prostate cancer (PC3) cells were grown in six-well plates in 10% serum containing DMEM and serum starved overnight before they were changed to experimental medium. Control cells were grown in normal DMEM. We treated PC3 cells growing in normal DMEM and experimental medium with EGF at 1ng/ml. Protein samples were collected at different time intervals and subjected to western blotting to observe the activation of EGFR by using phospho EGFR antibody. EGFR and actin antibodies were used as control and loading controls, respectively.
Results: Robust and sustained phosphorylation of EGFR for longer time was observed with EGF treatment when the cells were grown in low pH, low glucose and high lactate medium when compared with the cells grown in normal DMEM medium.
Conclusion: The robust activation of EGFR with low pH, low glucose and high lactate medium suggest that the microenvironment containing high lactate provides growth or survival advantages to the cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 993. doi:10.1158/1538-7445.AM2011-993
Abstract LB-12: Estrogen-induced redox signaling via NRF-1 is involved in the development of breast cancer
Authors: Okoh Victor , Felty Quentin H. , Roy Deodutta 
Published: June 2012

Abstract
The purpose of this study was to determine the role of estrogen-induced reactive oxygen species (ROS) signaling pathways in the development of breast cancer. Here we tested the postulate that activation of a redox sensitive transcription factor, nuclear respiratory factor-1 (NRF-1) signaling is essential for 4-hydroxyestradiol (4-OH-E2)-induced tumorigenesis. We observed that (i) 4-OH-E2 treatment of MCF-10A or MCF-7 cells increased the formation of ROS, (ii) Estrogen-induced ROS activated redox sensitive transcription factor NRF-1, (iii) 4-OH-E2 through activating a redox sensitive serine-threonine kinase AKT phosphorylated NRF-1, (iv) Overexpression of catalase and MnSOD, as well as silencing of NRF-1 prevented 4-OH-E2-induced anchorage-independent growth of MCF-10A and MCF-7 cells and xenograft tumor formation, and (v) 4-OH-E2-induced ROS through stimulating AKT kinase and histone acetyltransferase of CREB binding protein-associated factor (P/CAF), respectively, controlled phosphorylation and acetylation of NRF-1. The results also showed that 4-OH-E2-induced post-translational changes lead to NRF-1 activation, and silencing of NRF-1 and overexpression of MnSOD or catalase prevented 4-OH-E2-induced tumor formation. Taken together, these findings suggest a new paradigm for estrogen-induced breast carcinogenesis that deregulation of phosphorylation and aceytylation of NRF-1 may represent a major mechanism of 4-OH-E2-induced neoplastic transformation and tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-12. doi:10.1158/1538-7445.AM2011-LB-12