bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5288: Tumor-endothelial 3D spheroids for dynamic imaging of cancer progression
Authors: Upreti Meenakshi 
Published: June 2012

Abstract
The increasing use of anti-angiogenic drugs for the treatment of cancer has emerged from the explosion of knowledge about the process of tumor angiogenesis. However, the clinical results of using such drugs have been relatively modest and new agents are likely needed. A robust pre-clinical model of cellular mechanisms governing tumor angiogenesis may improve our ability to develop strategies for tumor specific drug delivery with superior pharmacokinetics, controlled biodistribution, efficacy, and safety profiles. We have developed a system to grow 3D-cultures of tumor and endothelial cells in hanging drops of medium. Subsequently, we transplant these spheroidal cultures into the dorsal skin fold window chamber of mice for intravital multiphoton imaging of neovasculature and disease progression. Our initial observation was that there was a marked difference in neovascularization from the GFP-tumor-endothelial spheroids in comparison to GFP-tumor spheroids in the window chamber mouse model. Molecular analysis using an antibody array showed a pronounced upregulation of angiogenic factors in the tumor tissue derived from the tumor-endothelial spheroid compared to the spheroid grown with tumor cells alone. Interleukin-1α, FGF-1α, CCN3/NOV, PIGF-2, MMP-3, MMP-8 and MMP-9 were seven identified proteins that showed distinct differences in expression between the two spheroid types. Further, the relative increase in tumor growth of tumor-endothelial spheroids implanted on the rear hind limb was much faster than the tumor cell alone spheroid and resulted in evidence of greater metastasis to the lung. We thus strongly believe that the 3D tumor-endothelial spheroid implanted in the dorsal fold window chamber of mice is a more realistic and informative model for dynamic imaging of critical aspects of tumor angiogenesis and the study of metastasis. Efforts are underway to monitor molecular and cellular events related to radiation exposure combined with anti-angiogenic agents of varying mechanisms of action to determine prudent new avenues for therapeutic success.
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 5288. doi:10.1158/1538-7445.AM2011-5288
Abstract 5288A: Multivalent fluorescent probes for in vivo tumor targeting
Authors: Zhang Ning , Kim Jae-Beom , Lim Ed , Ansaldi Dan , Ang Angel , Singh Raj 
Published: June 2012

Abstract
Conventional fluorescence probes are monovalent molecules that interact with cellular or extra-cellular target molecules through affinity binding. To improve the binding affinity and sensitivity of detection of the fluorescence probe, we describe a novel strategy for the synthesis designed to contain multiple targeting moieties and a near infrared fluorescent dye Iflour750 for optimal in vivo detection. In this study, we applied several multivalent probes to in vivo tumor targeting and monitored the targeting process using fluorescence imaging. Deoxyglucose based fluorescence probes have been applied to tumor labeling as the high metabolic rate of the tumor cells causes preferential labeling of the tumor mass. With a multivalent 2-deoxy-D- glucose Iflour750 (2-DG-IF750) probe, we demonstrated sensitive in vivo targeting as compared to a control mono-valent 2DG probe in several tumor models, including PC3M-luc2 prostate tumor cells, MDA-MB-231-luc2 mammary fat tumor cells as well as LL/2-luc and H460-luc2 lung cancer cells. Distinct tumor signal was visualized within a few hours after intravenous delivery and reached the peak of signal/background ratio between 6-24 hours. With a multivalent cyclooxygenase (COX) binding fluorescence probe Indomethacin-IF750, we observed an interesting targeting of COX2 negative colon tumor cells HCT116-luc2, but not the COX2 positive HT29-luc2, hypothetically due to selective binding to COX1. We also tested a multivalent RGD probe for targeting integrin avb3, the expression of which is associated with tumor angiogenesis and metastasis. With our iFlur750-(RGD)4 probe, we demonstrated in vivo targeting of U87-MG-luc2, HCT116-luc2 and HT29-luc2 tumor cells. Finally, we demonstrated that optical imaging was conveniently applied to evaluating the PK/PD profile of the probes. Our multivalent probes showed a fast clearance with a half life of less than 1 hour, which is a desirable feature for achieving maximal tumor/background contrast. In summary, we have developed a new class of multi-valent fluorescence probes with improved specificity and sensitivity of tumor targeting as compared to mono-valent analogs. Utility of this class of multivalent probes is likely to pass beyond pre-clinical models, as imaging guided tumor surgery is on the verge of clinical applications.
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 5288A. doi:10.1158/1538-7445.AM2011-5288A
Abstract 5293: Mixed micelles of triblock copolymers enhance delivery of indocyanine green for fluorescent tumor imaging
Authors: Mount Christopher , Kim Tae Hee , Dulken Benjamin , Li Xingde , Gombotz Wayne , Pun Suzie 
Published: June 2012

Abstract
The goal of this study is to develop formulations for non-invasive, near-infrared detection of tumors. Indocyanine green (ICG) is an FDA-approved near-infrared (NIR) imaging agent that is clinically used for angiography and evaluation of liver function. ICG could potentially be used as a NIR fluorescence imaging agent for shallow tumors such as breast cancers. To fulfill this potential, formulations that improve the stability of ICG and direct its accumulation in tumors are necessary. We have previously described Pluronic F127 copolymer micelles that stabilize ICG, enhance its stability, and facilitate tumor accumulation in vivo after systemic administration. A major advantage of Pluronic F127 is its temperature-sensitive behavior that results in more stable micelle formulations at body temperature. However, Pluronic F127 micelles are not stable at room temperature, making micelle preparation and handling challenging. We hypothesized that mixed micelles formed from both Pluronic F127 and a temperature insensitive triblock copolymer composed of poly(ethylene oxide) and poly(3-hydroxybutyrate) (PEO-PHB-PEO), would result in micelles that are both easy to formulate at room temperature and that demonstrate increased stability at body temperature. Micelle formulations with various ratios of Pluronic F127: PEO-PHB-PEO were prepared and loaded with ICG. The micelle stability was determined by assessment of critical micelle concentration measurements, and time-course fluorescence assays were conducted to assess the ability of each micelle formulation to stabilize ICG fluorescence in buffer conditions. The ICG-loaded micelles were administered to tumor-bearing mice by tail vein injection and tumor localization was monitored by non-invasive fluorescence imaging in live mice. The polymer ratio used in micelle formulation was found to play a significant role in the ability of each preparation to stabilize ICG fluorescence Mixed micelles were found to enhance the stability of ICG fluorescence in buffer conditions, and CMC was shown to be dependent on polymer ratios. In vivo, mixed micelles were found to be more effective at maintaining ICG fluorescence in the bloodstream and achieved higher fluorescence signals in the tumor tissues compared with either PEO-PHB-PEO or Pluronic 127 micelles. These results suggest that the mixed micelle formulations offer a promising route to stabilizing these nanoparticles for improved delivery of NIR fluorescent contrast agents to tumors for imaging applications.
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 5293. doi:10.1158/1538-7445.AM2011-5293
Abstract 5294: Real-time optical imaging of nanoparticle biodistribution in vivo
Authors: van de ven-Moloney Anne L. , Haley O'Hara , Kim Pilham , Yun Seok-Hyun , Ferrari Mauro , Decuzzi Paolo 
Published: June 2012

Abstract
High-resolution optical imaging provides the opportunity to visualize the transport of systemically injected nanoparticle systems along a series of biophysical barriers to their site of action. Data collected using this approach can be used to simulate, predict, understand, and improve the delivery of therapeutics and/or contrast agents to solid tumors. Here we present evidence that tailoring the physical properties of nanoparticle systems can improve their accumulation at disease sites. Using confocal technologies, we investigated the dynamics of nanoporous silicon particles in the microvasculature of normal and tumor-bearing mice. The biodistribution of intravenously injected particles of different size, shape, and surface properties were monitored in real-time. In organs of the reticuloendothelial system (RES), the rate of particle accumulation, as well as the total number of particles accumulated, was highly dependent on particle shape. Particles which preferentially accumulated in tumors were different than those which accumulated in the RES organs, suggesting that particle shape is an important design parameter for organ-specific delivery. The importance of modifying particle surface was evaluated in melanoma-bearing mice by systemically administering particles with and without endothelial-specific targeting moieties. The addition of targeting moieties was found to improve tumor-specific accumulation as much as changing particle shape. We have independently validated these in vivo findings and begun to elucidate the mechanisms of particle accumulation using inductively coupled plasma atomic emission spectrometry, immunocytochemistry, immunohistochemistry, and mathematical modeling.
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 5294. doi:10.1158/1538-7445.AM2011-5294
Abstract 5304: A genetically engineered mouse model for GBM wherein Akt kinase activity can be monitored non-invasively in real-time
Authors: Galbán Stefanie , Lemasson Benjamin , Lafferty Michael J. , Li Fei , Heist Kevin , Galban Craig J. , Ross Brian D. , Rehemtulla Alnawaz 
Published: June 2012

Abstract
Approximately 30-40% of human gliomas exhibit mutations in the tumor suppressor gene PTEN resulting in deregulation of the phosphoinositide 3-kinase/Akt survival signaling pathway. In a significant number of GBMs tumor initiation is additionally driven by an oncogenic signal stemming from the gene locus amplification of the Platelet derived growth factor receptor (PDGFR), also leading to Akt and mammalian target of rapamycin (mTOR) activation. Phosphorylated, active Akt controls a plethora of cellular responses by regulating a large number of substrates, such as GSK-3, BAD, Forkhead transcription factors (FOXO), and MDM2. Elevated Akt activity increases tumor cell growth, survival and impairs apoptosis. Thus blocking Akt phosphorylation to treat cancer in particular gliomas has therapeutic potential. Here we demonstrate the pre-clinical use of a bioluminescent molecular reporter to evaluate Akt kinase inhibition in real time in a genetically engineered PDGF-driven PTEN-deficient mouse model of GBM. Glial cell specific delivery of the bioluminescent reporter was achieved by RCAS-TVA technology. In brief, we utilized genetically engineered PTEN loxP/loxP,
Ink4a-Arf -/-, nestin-TVA transgenic animals and delivered the Akt reporter along with Cre recombinase and PDGF by intracranial implantation of chicken cells expressing avian virus containing the specific cargo. PTEN deletion in nestin positive cells resulted in increased Akt kinase phosphorylation as demonstrated by western blotting. Tumor growth was monitored by MRI and Bioluminescence imaging (BLI) technology. The design of the previously described Akt reporter allows for detectable bioluminescence only in the absence of Akt kinase activity due to the reconstitution of the wt luciferase enzyme. To evaluate the therapeutic potential of PI3-kinase- and Akt inhibitors in this pre-clinical GBM model, tumors were treated with either perifosine or API-2. Increased bioluminescence activity was observed in gliomas in a time- and dose-dependent manner with both inhibitors. These findings demonstrate that the Akt reporter provided a quantitative surrogate for Akt activity in PTEN-deficient gliomas. In conclusion we have provided a novel approach of pairing molecular imaging with a murine GBM model to investigate targeted agents. This may aid the future identification of most efficacious drug combinations impinging on PI3-kinase/Akt signaling in gliomas.
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 5304. doi:10.1158/1538-7445.AM2011-5304
Abstract 5312: Near-infrared multichannel Raman spectroscopy with a 1064-nm excitation wavelength for ex vivo diagnosis of gastric cancer
Authors: Kikuchi Hirotoshi , Kawabata Toshiki , Okazaki Shigetoshi , Hiramatsu Yoshihiro , Baba Megumi , Ohta Manabu , Kamiya Kinji , Tanaka Tatsuo , Konno Hiroyuki 
Published: June 2012

Abstract
Background: Gastric cancer is one of the major causes of death in Japan. Endoscopic submucosal dissection (ESD) has been developed for the treatment of early cancers. ESD needs accurate diagnosis of the demarcation line, pathological type and depth of cancer lesions. We have previously reported, using biopsy specimens, the usefulness of the 1064-nm near-infrared multichannel Raman spectroscopy (RAS) system as a novel diagnostic modality for gastric cancer (J Gastroenterol.43(4), 2008). However, our study might not have reflected in vivo use of RAS due to a lack of tissue other than the mucosal layer in the biopsy specimens. Here, we used the 1064-nm near-infrared multichannel RAS ex vivo for optical diagnosis of gastric cancer in surgically resected stomach.
Methods: A total of 213 Raman spectra were obtained from 12 cancer lesions and their corresponding non-neoplastic areas in 10 stomachs following resection for gastric cancer. Without any pretreatment, the fresh specimens were measured with a near-infared multichannel Raman spectroscopic system with an excitation wavelength of 1064nm, and Raman spectra specific for the specimens were obtained. To develop optical diagnostic systems for gastric cancer, principal component analysis (PCA) of all the Raman spectra was performed.
Results: The averaged Raman spectra of the cancer lesions could be distinguished from those of the non-neoplastic regions. Discrimination analysis of cancer from non-neoplastic regions with 10 principal components revealed that sensitivity, specificity and accuracy of cancer diagnosis was 73%, 73% and 72%, respectively. RAS discriminated between differentiated and undifferentiated cancers, early and advanced cancers, as well as T1a (M) and T1b (SM) cancers with high accuracy (98%, 93% and 98%, respectively).
Conclusions: The 1064-nm near-infrared multichannel RAS system is useful not only for gastric cancer detection, but also for discrimination between differentiated and undifferentiated, as well as early and advanced cancers. RAS could help establish indications for endoscopic treatment by eliminating cancer lesions with an undifferentiated component or submucosal invasion.
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 5312. doi:10.1158/1538-7445.AM2011-5312
Abstract 5315: PET imaging with the proliferation tracer 18F-FLT as early, non-invasive predictor of everolimus effect on tumor growth: Studies in human neuroendocrine tumor xenografts in mice
Authors: Johnbeck Camilla Bardram , Jensen Mette Munk , Hag Anne Mette Fisker , Madsen Jacob , Knigge Ulrich , Kjaer Andreas 
Published: June 2012

Abstract
Background and aim: Everolimus (RAD001), an oral mTOR inhibitor has shown promising results in the treatment of several types of cancer including neuroendocrine tumors. With the expanding numbers of clinical treatment protocols there is a need for early, non-invasive predictors of treatment response. We hypothesized that PET imaging with the proliferation tracer 3′-Deoxy-3′-[(18)F]fluorothymidine (FLT) could serve as such a predictor. Therefore, we studied in human neuroendocrine tumor xenografts in mice whether PET imaging with FLT could predict, at an early time-point, the effect of everolimus on tumor growth.
Methods: In vivo uptake of FLT in human neuroendocrine xenografts (H727) in mice was studied at baseline when tumors were on average 140 mm3. The mice were randomized into two groups. One group of mice (n=10 tumors) were treated with daily i.p. injections of everolimus (5 mg/kg) for 10 days while another group of mice (n=10 tumors) served as control and was given the same volume of vehicle i.p. The mice were FLT scanned at day 0, 1, 3, 7 and 10. Each PET scan was acquired over 15 min 1 h after injection in a tail vein of 10 MBq FLT. In addition, a CT-scan was performed for calculation of tumor volume. The tumors were defined on PET/CT images and FLT uptake was calculated as mean standardized uptake values (SUV).
Results: Everolimus treated mice showed a clear reduction in tumor growth compared to the vehicle group at day 7 and 10 (P&lt;0.0001). At day 7 the relative tumor volumes (day 7/day 0) were 1.78±0.10 in the everolimus group and 2.77±0.11 (407 mm3) in the control group. At day 10 the relative tumor volumes (day 10/day 0) were 2.17±0.15 (304 mm3) in the everolimus group and 3.50±0.13 (518 mm3) in the vehicle group. The relative FLT SUV value on day 10 showed significantly reduced uptake (P=0.003) in the everolimus group (0.91±0.06) compared to the control group (1.16±0.04). In the everolimus group FLT uptake at day 3 predicted relative tumor size both at day 7 (R2=0.53; P=0.017) and day 10 (R2=0.60; P=0.024). FLT uptake at day 1 also predicted tumor growth, although only borderline significant, at day 3 (R2=0.38; P=0.060), 7 (R2=0.39; P=0.055) and 10 (R2=0.45; P=0.069).
Conclusion: FLT-PET imaging as early as 1 or 3 days after treatment initiation with everolimus predicts neuroendocrine tumor growth over the first 10 days of treatment. We suggest that FLT-PET is a promising tool for early prediction of effect of everolimus in patients with neuroendocrine tumors and may be used for tailoring 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 5315. doi:10.1158/1538-7445.AM2011-5315
Abstract 5323: Staging of metastatic pancreatic cancer is facilitated by fluorescence laparoscopy
Authors: Metildi Cristina A. , Kaushal Sharmeela , Hardamon Chanae R. , Snyder Cynthia S. , Luiken George A. , Talamini Mark A. , Hoffman Robert M. , Bouvet Michael 
Published: June 2012

Abstract
The aim of this report was to improve the real-time imaging of fluorescence laparoscopy with the introduction of an LED light source. We also attempted to determine the optimal fluorophore to improve accurate identification and localization of tumor deposits without the loss of background illumination. Human pancreatic cancer orthotopic models were established with intraperitoneal injections of RFP-expressing FG or BxPC-3, or non-fluorescent BxPC-3 human pancreatic cancer cells into 6-week-old female athymic mice. One to 2 weeks post implantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail vein injection of Alexa 488-conjugated anti-CEA. An attempt was made to detect and localize all cancer lesions under each light mode. After laparoscopy, the animals were sacrificed and abdominal cavities exposed. Images of the lesions were obtained with the Maestro CRI Small Animal Imaging System serving as a positive control. Tumors were collected and processed for histologic review. Fluorescence laparoscopy with the use of a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor metastases in the peritoneal cavity. With adjustments to the LED light source, we could simultaneously detect tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Overall, fluorescence laparoscopy using the LED light source afforded accurate detection of more lesions compared to standard xenon bright field laparoscopy. In addition, several tumor deposits of less than 1mm were identified and localized under FL. Such lesions were not detected under bright field laparoscopy. All identified lesions, when possible, were verified histologically. In this study, we have thus demonstrated that using an LED light source with adjustments to the red, blue and green wavelengths, we can simultaneously identify fluorescent tumor metastases of different wavelengths without compromising background illumination. The further development of this technology can serve as a novel tool in the staging and treatment of 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 5323. doi:10.1158/1538-7445.AM2011-5323