bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5229: Single, pre-labeled metastatic melanoma cells can be detected in the mouse brain using MRI
Authors: Daphu Inderjit K. , Wendelbo Ingvild , Immervoll Heike , Sykova Eva , Jendelova Pavla , Babic Michel , Bjerkvig Rolf , Thorsen Frits 
Published: June 2012

Abstract
In metastatic melanoma, brain metastases are clinically diagnosed in 40-60% of patients during the disease, but can be found in up to 90% at autopsy. The prognosis for these patients is poor, due to ineffective treatments and development of multiple brain metastasis. There is a limited knowledge about the biological mechanisms behind this development of multiple metastasis in the brain, which necessitates the development of clinically more relevant animal models.
The purpose of this study was to develop a multiple brain metastasis animal model which closely reflects the clinical setting, and specifically to determine the number of single melanoma cells able to arrest in the animal brain.
The H1 brain metastatic melanoma cell line was established from a patient melanoma brain metastases obtained during surgery. The H1 cells were pre-labeled with superparamagnetic iron oxide particles (Fedex; Babic et al, Bioconjugate Chem 2008) at a concentration of 10 μg/ml for 24 hrs. The viability of labeled cells was studied in vitro using cell proliferation assays, and Scanning/Transmission Electron Microscopy (SEM/TEM). One million pre-labeled tumor cells were then injected into the left ventricle of the heart in nod scid mice. 24 hrs after injections, T1 weighted (T1w), T2 weighted
(T2w) and T2* weighted (T2*w) MR imaging were performed. In addition, T1w and T2w MR images were obtained 5 weeks after injections. We also transfected the H1 melanoma cells with luciferase, and monitored the animals for up to 6 weeks using bioluminescence imaging (OI).
Pre-labeling of melanoma cells with Fedex did not affect cell proliferation. The SEM and TEM studies showed iron oxide particle attachment to the tumor cell membrane, as well as localisation of the labelling agents within vesicles in the cytoplasm. By encapsulating pre-labeled tumor cells at various concentrations in soft agar, we were able to detect less than 50 cell/μl using T2 mapping MRI. By pre-labeling the melanoma cells with Fedex, we were able to detect single tumour cells in the animal brains. Imaging studies (OI, MR) 4-6 weeks after injections confirmed multiple metastatic spread to the brain.
In conclusion, we have developed a melanoma metastasis model in immunodeficient mice, which reflects the metastatic tumor spread seen in patients. By using pre-labeling with Fedex, we were able to detect single tumour cells in the brain.
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 5229. doi:10.1158/1538-7445.AM2011-5229
Abstract 5238: Lung adenocarcinoma harboring EGFR L858R mutation has increased invasive ability through up-regulation of CXCR4
Authors: Chang Tzu-Hua , Yang Hsiao-Yin , Tsai Meng-Feng , Su Kang-Yi , Yang Pan-Chyr , Shih Jin-Yuan 
Published: June 2012

Abstract
Our previous study disclosed EGFR L858R mutation rate of lung adenocarcinoma with malignant pleural effusions of is higher than that of surgically resected lung adenocarcinoma (Wu et al, Eur Respir J 2008). The molecular mechanism is not clear. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Stable clones of wild type and mutant L858R EGFR from lung cancer cell line H1299 were obtained from Dr. Chen (Chen YR et al Oncogene 2006). The Invasive ability of L858R EGFR H1299 cells was higher than that of wild type EGFR H1299 cell. L858R EGFR H1299 cell had higher CXCR4 expression, which was required for L858R EGFR-mediated invasion in vitro. Up-regulation of CXCR4 in L858R EGFR H1299 cell promoted invasion via increased activity of ERK. These results provide a plausible mechanism for L855R EGFR-mediated lung tumor metastasis and establish a functional link between mutant EGFR and CXCR4 signaling pathways.
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 5238. doi:10.1158/1538-7445.AM2011-5238
Abstract 5239: Licoricidin present in licorice root extract inhibits metastatic capacity of 4T1 mouse mammary carcinoma cells in vitro and in vivo systems
Authors: Park So Young , Kwon Sujin , Lim Soon Sung , Kim Jin Kyu , Kim Jong-Sang , Lee Choonghwan , Park Jung Han Yoon 
Published: June 2012

Abstract
Licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and also to induce severe hypokalemia and hypertension. In our previous experiments, licoricidin was identified as an antimetastatic active component of a licorice root extract, which contains undetectable amounts of glycyrrhizin. In this study, we evaluated the effects of the licoricidin on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro model, licoricidin inhibited cell migration in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that licoricidin significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase-1 was reduced in licoricidin-treated cells. Licoricidin reduced the protein levels of vascular cell adhesion molecule but did not change intercellular adhesion molecule. To assess the effects of licoricidin on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. Starting 1 week after 4T1 cell injection, the mice were given daily intraperitoneal injection of licoricidin (2 or 4 mg/kg body weight/day) for 21 days. Licoricidin treatment did not affect solid tumor growth but significantly reduced the number and volume of pulmonary tumor nodules. The expression of interleukin (IL)-1ra, IL-16, interferon γ-inducible protein (IP)-10, chemokine (C-X-C motif) ligand (CXCL)-9, MMP-3, -8, -9, osteopontin, pentraxin-3, stromal cell-derived factor (SDF)-1, and plasminogen activator inhibitor (PAI)-1 was increased in the lung tissues of mice injected with 4T1 cells, which was suppressed by the repeated injections of licoricidin. By contrast, the expression of angiopoietin-1, insulin-like growth factor binding proteins (IGFBP)-9 and IGFBP-10 was decreased in lung tissues of mice injected with 4T1 cells and was increased by the licoricidin treatment. In the present study, using both in vivo and in vitro systems, we have demonstrated that licoricidin profoundly inhibits the metastatic capacity of 4T1 mammary carcinoma cells, which may be mediated via the regulation of several metalloproteases, adhesion molecules, cytokines, and chemokines.
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 5239. doi:10.1158/1538-7445.AM2011-5239
Abstract 5247: Expression and functional role of CCR9 in lung cancer
Authors: Singh Rajesh , Lillard James W. , Grizzle William E. , Singh Shailesh 
Published: June 2012

Abstract
Lung cancer is leading cause of cancer related deaths worldwide in both men and women. Metastasis is responsible for most lung cancer related deaths; therefore, a better understanding of the metastatic processes and therapies designed to prevent the spread of cancer cells are greatly needed. The specific mechanisms that promote metastases have not been fully elucidated. Among all known chemokine receptors involved in cancer progression, most cancer cells including lung cancer express CXCR4. Furthermore, involvement of CXCR4 and CCR7 in breast cancer and CXCR4, CCR9 and CX3CR1 in prostate cancer progression further indicates that multiple chemokine receptors are involved in dictating the multi-step process of metastasis. For the first time, we show that lung cancer cells and tissue form Non Small Cell Lung Carcinoma (NSCLC) express CCR9, which is the receptor for CCL25. CCR9 was highly expressed by NSCLC cell lines as compared to Small Cell Lung Carcinoma (SCLC) cell lines at mRNA and protein levels. Furthermore, we have shown that CCR9-CCL25 interaction plays a crucial role in lung cancer cell migration. It addition to these, serum levels of CCL25 was significantly elevated in lung cancer patents compared to normal healthy donor. The mechanism underlying these clinically and biologically important finding need to be further explored. Increased serum CCL25 in lung cancer patients with metastatic disease required further validation as a potential therapeutic target and/or diagnostic marker for lung 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 5247. doi:10.1158/1538-7445.AM2011-5247
Abstract 525: Functional screen of paracrine signals in breast carcinoma fibroblasts
Authors: Su Gui , Beebe David J. , Friedl Andreas 
Published: June 2012

Abstract
Stromal fibroblasts actively participate in normal mammary gland homeostasis and in breast carcinoma growth and progression by secreting paracrine factors. However, our knowledge about the identity of paracrine mediators operating in individual patients remains incomplete. The purpose of this study was to characterize paracrine signaling pathways between breast carcinoma cells and breast carcinoma-associated fibroblasts (CAF) or normal mammary fibroblasts (NF), respectively. CAF and NF were isolated from breast carcinoma tissue samples and adjacent normal mammary gland tissue of 28 patients. The fibroblasts were grown in 3D collagen gel co-culture with T47D human breast carcinoma cells and T47D cell growth was measured. CAF stimulated T47D cell growth to a significantly greater degree than NF. Collectively, neutralizing antibodies to fibroblast growth factor 2, heparin-binding epidermal growth factor, SDF1 and TGF- β1 and the enzymes heparanase-1 and MT1-MMP significantly abrogated CAF-stimulated T47D cell growth, although, a considerable degree of inter-individual heterogeneity was observed. CAF from low-grade but not high-grade carcinomas required IGF1 and TGF- β1 to stimulate carcinoma growth. CAF from estrogen or progesterone receptor negative carcinomas depended on HB-EGF activity for carcinoma growth. Paradoxically, blocking of MT1-MMP stimulated T47D cell growth in co-culture with NF. The results were largely replicated by treating the fibroblasts with siRNA oligonucleotides prior to co-culture, implicating the fibroblasts as principal production site for the paracrine mediators examined in this study. In summary, we characterize the paracrine signaling network of primary breast cancer fibroblasts with inhibitor screens. These findings have significant implications for the design of stroma-targeted therapies.
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 525. doi:10.1158/1538-7445.AM2011-525
Abstract 5252: Sequential biphasic changes in claudin1 and claudin4 expression correlate to colorectal cancer progression and liver metastasis
Authors: Georges Rania , Bergmann Frank , Adwan Hassan , Berger Martin R. 
Published: June 2012

Abstract
Terminal progression of colorectal cancer culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyze mRNA expression profiles of CC531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag-Rij rats and re-isolated after 3, 6, 9, 14 and 21 days. Compared to control CC531 cells, claudin1 and claudin4 were among the ≥8 fold initially down-regulated genes. The co-culture of tumor cells with isolated rat hepatocytes and Kupffer cells did not induce down-regulation of either claudin1 or 4. When the environment effective on circulating tumor cells was simulated by cell culture conditions favoring their adhesion, only claudin4 showed augmented expression. Knockdown of claudin1 and claudin4 mediated by siRNA caused significantly increased migration and decreased clonogenic growth of tumor cells (p&lt;0.05), but had no effect on their proliferation. These experimental results were paralleled by increased claudin1 and claudin4 expression in human colorectal cancer samples in UICC stages l-lll, as evaluated by real-time PCR. Increased claudin4 levels were correlated with significantly reduced overall survival (log-rank test, p=0.018). Further, significantly (p&lt;0.05) reduced expression of claudin1 and claudin4 was observed in stage IV and liver metastasis by immunohistochemistry. In conclusion, sequential biphasic changes in claudin1 and claudin4 expression occur during the homing of colorectal cancer cells to the liver.
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 5252. doi:10.1158/1538-7445.AM2011-5252
Abstract 5256: Osteopontin-c and Osteopontin-b splicing isoforms activate important hallmarks of cancer contributing to prostate carcinoma progression
Authors: Tilli Tatiana M. , Matos Aline , Goulart Luis Ricardo , Weber Georg F. , Gimba Etel Rodrigues Pereira 
Published: June 2012

Abstract
Introduction: Osteopontin (OPN) is a secreted glycophosphoprotein and is involved in tumorigenesis and metastasis in many solid tumors, including prostate cancer (PCa). Alternative splicing of OPN mRNA leads to the expression of 3 isoforms, named OPNa, OPNb and OPNc. However, the expression pattern and the roles of these isoforms have not been previously characterized in PCa. Objective and Methodology: Herein we evaluated the expression pattern of these OPN isofoms in PCa and BPH (benign prostate hyperplasia) tissue samples by using qRT-PCR. ROC curve analysis evaluated the performance of OPN isoforms tissue levels as compared to PSA serum levels for the diagnosis of PCa. Additionally, we investigated the roles of these isoforms on PCa progression using PC3 cells ectopically overexpressing each OPN isoform and in vitro and in vivo assays. Results: Our data demonstrate that these 3 isoforms are overexpressed in PCa in relation to BPH tissue samples and that OPNc presents the highest expression level. ROC curve analysis demonstrate that OPNa, OPNb and OPNc expression levels perform better (AUC 0,9; 0,81 and 0,88, respectively, p&lt; 0,0001) than PSA serum levels (AUC 0,52; p&lt; 0,0001) for the differential diagnosis of PCa and BPH patients. Furthermore, OPN isoforms expression levels are positively correlated to tumor Gleason Score (p &lt; 0,001). Cells overexpressing OPNc and OPNb, but not OPNa, significantly activate cell features typically related to key hallmarks of cancer, such as cell proliferation, migration, anchorage-independent growth and tumor formation in vivo in nude mice, reflecting the potential of these isoforms to active PCa tumor progression. Besides, OPNc seems also to in involved in PCa tumorigenesis, once stimulate the proliferation of RWPE1 prostate non- tumoral cells. Trying to describe the signaling pathways involved on OPNc and OPNb roles on activating PCa progression steps, we demonstrated that the use LY-294002 inhibitor significantly inhibited the proliferation of cells overexpressing OPNc and OPNb, suggesting that these OPN splicing isoforms on activating cell proliferation occurs via PI3K/Akt signaling pathways. Conclusions: Taken together, these results suggest that the evaluation of OPN splicing isoforms expression levels could be used as molecular parameter to improve the differential diagnosis of PCa in relation to BPH. Besides, we provide evidence that OPNc and OPNb activate important steps in PCa progression and hence could be important targets for the development of therapeutic approaches.
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 5256. doi:10.1158/1538-7445.AM2011-5256
Abstract 5279: Imaging of pancreatic cancer with activated cell penetrating peptide dendrimers
Authors: Metildi Cristina A. , Nguyen Quyen T. , Kaushal Sharmeela , Tran Cao Hop S. , Snyder Cynthia S. , Hoffman Robert M. , Tsien Roger Y. , Bouvet Michael 
Published: June 2012

Abstract
We have recently described novel activatable cell penetrating peptides attached to dendrimers (ACPPDs) which can selectively label tumors for real-time imaging during surgery. The aim of this study was to evaluate the ability of Cy5-labeled ACPPDs to visualize primary tumors and their margins in an orthotopic mouse model of pancreatic cancer. BxPC-3 or BxPC-3-RFP-expressing human pancreatic cancer cells were injected into the pancreas of 6-week old athymic mice to establish the orthotopic mouse models. ACPPs were synthesized on an automated peptide synthesizer by using standard protocols for fluorenylmethoxycarbonyl solid-phase synthesis. Peptides were cleaved off the resin, purified by HPLC, and conjugated to a generation 5 PAMAM dendrimer. Cy5 labeling was performed directly on the dendrimer. Dendrimers were then capped completely with Peg4 NHS ester. Tumor-bearing mice were injected with 20 nmoles of ACPPDs via tail vein 48 hours prior to imaging. Mice were first imaged non-invasively using OV-100 (Olympus) or Maestro (CRI) small animal imaging systems. Mice then underwent laparotomy. Resection of the primary pancreatic tumor using fluorescence guidance was performed using a MVX-10 fluorescence-dissecting microscope (Olympus) customized to allow the surgeon to see white-light reflectance, fluorescence, or the two superimposed in real time. At the conclusion of the experiments, H&E staining was used to confirm the pathological diagnosis of cancer in the resected specimens. We found that in the orthotopic BxPC3 mouse model of pancreatic cancer, intravenous injection of ACPPD showed bright fluorescence labeling of tumors compared to surrounding normal tissue. Co-localization studies showed a good correlation between ACPPD uptake and RFP tumor expression. Tumor margins were more clearly delineated with fluorescence imaging using ACPPDs compared to with white light reflectance alone. Post resection, the tumor bed was examined and imaged for residual tumor. With fluorescence-guided resection, the tumor bed was free of residual tumor, which was confirmed histologically. In this study, we have shown that ACPPDs can accurately and effectively label primary pancreatic tumors in an orthotopic mouse model of pancreatic cancer. This technology has the potential to improve surgical outcomes in patients with pancreatic 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 5279. doi:10.1158/1538-7445.AM2011-5279
Abstract 5282: Pretargeted immunoPET for imaging human colonic cancer in a mouse model
Authors: Schoffelen Rafke , Franssen Gerben M. , McBride William J. , Disselhorst Jonathan A. , Sharkey Robert M. , Laverman Peter , van der Graaf Winette T. A. , Oyen Wim J. G. , Goldenberg David M. , Boerman Otto C. 
Published: June 2012

Abstract
Objective: Molecular imaging with pretargeting bispecific antibodies allows rapid and specific targeting of tumors for PET imaging. In this study, pretargeted immunoPET with a bispecific monoclonal anti-carcinoembryonic antigen (CEA; CEACAM5) × anti-hapten antibody (bsMAb) and a small (1.5 kD) peptide labeled with a short-lived positron-emitter 68Ga was compared to FDG for detection of intraperitoneal CEA-expressing human colonic tumor xenografts in nude mice.
Methods: In BALB/c nude mice LS174T human colonic tumor cells were injected intraperitoneally. One group (n=5) received 5 MBq FDG i.v., and another group (n=5) received the bsMAb i.v. and 5 MBq of 68Ga-labeled peptide i.v. 16 h later. One hour after the injection of the peptide or FDG, PET/CT images were acquired. One day later the same procedure was repeated vice versa, and after microPET imaging the uptake of the 68Ga or 18F in dissected tissue was determined.
Results: Within one hour, specific tumor targeting of 68Ga-labeled peptide (23.4 ± 7.2% ID/g) combined with the low background activity levels resulted in the clear visualization of the small intra-abdominal tumor lesions (1.5-5 mm). High tumor/background radioactivity concentration ratios were obtained (e.g. tumor/intestines 57.5 ± 22.4). FDG localized efficiently in the tumors (8.7 ± 3.1 % ID/g), but with physiological uptake in various normal tissues (ratio tumor/intestines 4.0 ± 0.9).
Conclusion: Pretargeted immunoPET performs exceptionally well with short-lived radionuclides, and is a highly sensitive procedure for dectection of small tumor deposits that is also more specific than FDG-PET.
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 5282. doi:10.1158/1538-7445.AM2011-5282