bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4263: Dopamine ameliorates hematological complications in tumor bearing animals
Authors: Sarkar Chandrani , Chakroborty Debanjan , Basu Sujit 
Published: July 2012

Abstract
One of the major complications of anti-VEGF-A (vascular endothelial growth factor-A) agents are their serious hematological toxicities. We had earlier shown that the catecholamine neurotransmitter dopamine is a potent inhibitor of VEGF-A induced tumor angiogenesis and thereby, tumor growth. Therefore, it is prudent to investigate the effects of dopamine on important hematological parameters in preclinical cancer models. Our study shows that in addition to inhibiting tumor angiogenesis and growth of colon and prostate cancer bearing animals, dopamine can also significantly improve hemoglobin concentration, RBC and platelet counts in these animals. Anemia and thrombocytopenia are the two most common hematological toxicities induced by anti-VEGF-A drugs, which in turn increases the morbidity in cancer patients treated with these agents. Our report here shows that the anti-angiogenic action of dopamine inhibits tumor angiogenesis and growth in preclinical models without adversely affecting hematopiesis; rather it ameliorates anemia associated with 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 4263. doi:10.1158/1538-7445.AM2011-4263
Abstract 4265: Bithionol as an inhibitor of tumor angiogenesis
Authors: Zhai Ling , Roy Anshu M. , Zamani Ali , Liu Ximeng , Wang Yimin , Li Rongbao , Qu Zhican 
Published: July 2012

Abstract
Tumor progression depends on angiogenesis. The clinical successes in recent years have demonstrated that antiangiogenic agents can be developed as effective treatment for cancer patients. However, the resistance to the current FDA approved antiangiogenic therapies is emerging, which presents challenges in cancer research and urgent needs for novel angiogenesis inhibitors with different mechanisms of drug actions to overcome the resistance. In our previous studies, we have identified a small molecule bithionol as a potential antiangiogenic agent through a chemical diversity library screening with a cell-based angiogenesis assay. Bithionol is a FDA approved and current clinically used anthelmintics, which has been found to directly inhibit activity of autotaxin, a secreted enzyme that catalyzes lysophosphatidic acid (LPA) production. LPA, as a lipid signaling molecule, is a potent angiogenic and cancer cell motility stimulating factor. Therefore, autotaxin plays important role in tumor angiogenesis and metastasis and has been recently identified as an attractive angiogenesis and cancer target. Our recent studies have shown that autotaxin is expressed at high levels in human endothelial and number of human cancer cell lines. Bithionol has demonstrated inhibitory activities against human endothelial cell proliferation, migration, and tube-formation as the three key cellular steps in angiogenesis process. The effect of bithionol on inhibition of tumor angiogenesis was also evaluated with an ex vivo xenograft chicken embryo chorioallantoic membrane (xenograft-CAM) model system. Bithionol is able to inhibit tumor-induced new blood vessel formation in a dose dependent manner and has demonstrated an additive inhibitory activity when it is applied in combination with Sutent, a current clinically used antiangiogenic drug. The results of this research suggest that bithionol provide a unique promising opportunity in developing new combinational treatment to increase the anticancer efficacy and minimize the resistance in cancer patients.
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 4265. doi:10.1158/1538-7445.AM2011-4265
Abstract 4267: Biomimetic anti-angiogenic peptide as therapeutic agent for breast cancer
Authors: Rosca Elena V. , Penet Marie-France , Koskimaki Jacob E. , Pandey Niranjan B. , Bhujwalla Zaver M. , Popel Aleksander S. 
Published: July 2012

Abstract
Despite the continuous research in novel therapeutics, globally each year more people succumb to cancer than HIV, TB and malaria combined. Angiogenesis, the development of neovasculature, has been a major focus of cancer research, and it resulted in the development, approval and clinical use of bevacizumab, an anti-VEGF monoclonal antibody. However, in the case of breast cancer, the results show gains in progression-free survival but not in overall survival. Other agents targeting VEGF receptors are under investigation with the premise that a cocktail of agents could be more effective.
Recently, there has been great interest in the development of peptides as therapeutic agents due to their high specificity and low toxicity, which are conducive for the development of new therapeutic cocktails. Identification of pharmacophores (minimal information content) allows for the introduction of non-natural amino acids in the peptide sequence to increase its stability while maintaining or improving its activity, thus creating optimized peptides for clinical applications. We present the application of a 20-mer biomimetic peptide derived from the α5 fibril of collagen IV in which a cysteine is replaced by a non-natural amino acid, i.e., amino-butyric acid, and investigate its mechanism of action as an anti-angiogenic agent in treatment of breast cancer. We demonstrated its activity in suppressing tumor growth in an orthotopic triple negative breast tumor model. In vivo magnetic resonance imaging (MRI) demonstrated reduction in vascular permeability and vascular volume. In vitro studies of receptor pulldown and cellular surface proximity staining demonstrate that this peptide interacts specifically with the αVβ1 integrin. This biomimetic stable peptide is a novel non-VEGF targeting agent active as a single agent, or that could be used in combination with chemotherapy or other therapeutic peptide-based cocktails.
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 4267. doi:10.1158/1538-7445.AM2011-4267
Abstract 4268: Interleukin-27 inhibits angiogenesis in non-small cell lung cancer
Authors: Kachroo Puja , Zhang Ling , Walser Tonya C. , Cui Xiaoyan , Hazra Saswati , Lin Qiang Ying , Minna John D. , Dubinett Steven M. , Lee Jay M. 
Published: July 2012

Abstract
Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Angiogenesis is a critical process during carcinogenesis. We investigated the role of IL-27 in tumor angiogenesis in lung cancer. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and human non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot after IL-27 exposure demonstrated activation of both pathways in these cell lines. Protein production of an important pro-angiogenic factor, vascular endothelial growth factor (VEGF), was measured by ELISA and Western analysis. After exposure to IL-27, there was a 60-80% decrease in VEGF protein expression of VEGF by ELISA (confirmed by Western analysis in the NSCLC lines but not in the HBECs or their genetically modified derivatives). The IL-27 down regulation of VEGF was not increased by the addition of a STAT3 inhibitor. In summary, IL-27 inhibits VEGF production in NSCLC through a mechanism independent of STAT3, suggesting that STAT1 may play a dominant role in IL-27 mediated angiogenesis suppression.
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 4268. doi:10.1158/1538-7445.AM2011-4268
Abstract 4272: Hexastatin is a potent therapeutic agent for targeting tumor angiogenesis and tumor growth
Authors: Akulapalli Sudhakar , Boosani Chandra Shekhar , Laknaur Archana , Gunda Venugopal 
Published: July 2012

Abstract
Peptides or short protein domains derived from the extracellular matrix are reported to possess anti-tumor properties. In the present study, one such molecule “Hexastatin or [α6(IV)NC1]” a non-collagenous domain of α6 chain of type (IV) collagen was derived from the carboxy terminal and was found to inhibit tumor growth, but the mechanism by which it inhibits the growth of solid tumors has not been reported yet. In the present study, we identified that the biological functions of hexastatin are attributed to its binding to different cell surface integrins. We identified that hexastatin binds to α3β1, αVβ3 and α5β1 integrins and inhibits p38-MAPK signaling. Hexastatin competes with human vascular endothelial cells in binding to α1β1 integrins on type IV collagen, and or with α5β1/αVβ3 integrins on fibronectin/vitronectin matrix, thus inhibiting endothelial migration and tube formation. Interestingly, p38-MAPK phosphorylation was not inhibited in α3 and β3 integrin null endothelial cells upon treatment with Hexastatin which confirms that the antiangiogenic functions of Hexastatin are possibly mediated through α3β1 and αVβ3 integrins. While both the integrins (α3β1 and α5β1) are required for the inhibition of tube formation by Hexastatin in endothelial cells, only α3β1 integrin was found to regulate endothelial cells migration. In addition we also demonstrate that Hexastatin inhibits tumor growth, tumor angiogenesis and circulating endothelial cells in-vivo. These in-vitro and in-vivo findings indicate that α3β1 and αVβ3 integrins are critical for Hexastatin mediated inhibition of angiogenic signaling and tumor progression. Collectively, our findings demonstrate that hexastatin is a potent therapeutic agent for targeting tumor angiogenesis and tumor growth.
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 4272. doi:10.1158/1538-7445.AM2011-4272
Abstract 4274: Characterization and drug sensitivity testing of HTS compatible cancer microtissues
Authors: Helbling Marianne M. , Drewitz Maren , Bieri Manuela , Lotz Carina , Wyder Lorenza , Lehembre Francois , Lichtenberg Jan , Moritz Wolfgang , Regenass Urs , Kelm Jens M. 
Published: July 2012

Abstract
The tumor microenvironment strongly effects the drug response. Although the advantages of organotypic 3D-cell-culture models are known for years, complex production and readout processes impede the implementation in an industrial setting. This study, presents for the first time a novel multi-well platform in a standard 96-well format to produce organotypic, scaffold-free cancer microtissues models and its implementation in an automated screening process. This technology allows to produce either homotypic or heterotypic tumor microtissues in a hanging-drop culture by liquid top-loading similar to standard 96-well plates. The core piece of the well is a microfluidic channel connecting an inlet funnel at the top and an outlet funnel at the bottom of the plate, where a hanging drop is formed and stabilized by a combination of capillary and surface-tension forces. The use of this technology enables the automated production of microtissues with a very narrow size distribution below 10% on plate and batch-to-batch.
3 cancer microtissue models were developed from two colon cancer and one breast cancer cell lines and characterized in terms of their proliferative capacity and growth characteristics. Process parameters for media exchange, addition of compounds, microtissue-size variances and implementation of cell-based viability assays (ATP, LDH and size) were established. As a proof of concept, a whole screening process using four reference compounds was performed in comparison to classical monolayer cultures underlining the different behavior of both cell-culture models. Finally, four novel compounds that inhibit tumor cell proliferation in monolayer cultures, were tested for their potential in a 3-D system.
Overall, we could demonstrate that organotypic microtissues can be implemented into an automated screening process using standard liquid-handling robotics. The use of this system in drug development may strengthen the predictive force of the in-vitro evaluation of novel drug candidates and reduce drug failure in clinics.
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 4274. doi:10.1158/1538-7445.AM2011-4274
Abstract 4275: A prostate cancer spheroid related gene and chemotherapy
Authors: Watanabe Masatoshi , Takagi Akimitsu , Hirokawa Yoshifumi , Shiraishi Taizo 
Published: July 2012

Abstract
Spheroid culture is one of the three-dimensional (3-D) culture models. We have constructed a spheroid culture model for prostate cancer therapy and characterized this model. The change of global gene expression profiles in spheroids and solid tumor tissues were also compared with monolayer cultures, leading to extraction of candidate genes in contexts that more closely mimic tumor growth in vitro under different in vitro growth conditions. It is possible that these genes may be specific to the construction of spheroids and reveal the possibilities of new mechanisms of acquiring anticancer drug resistance or sensitivity. The plk-2 was extracted as a candidate
e gene related with spheroid formation. A member of the polo-like kinase (PLK) family, PLK2 is one of highly conserved serine/threonine protein kinases. In this study, we analyzed effects of the PLK2 on the spheroid characterization and anticancer drug resistance in DU-145 spheroids by suppressing plk2 with RNAi. When docetaxel (DTX) was exposed for siRNA-transfected spheroids, the viability changed, the volume decreased at each concentration of DTX, and spheroids were collapsed at last. The result indicates that the plk2 may be involved in acquiring anticancer drug resistance.
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 4275. doi:10.1158/1538-7445.AM2011-4275
Abstract 4276: Characterization of an ex vivo primary multicellular renal cell culture as a potential model system for renal cell carcinoma tumorigenesis
Authors: Arreola Alexandra , Rathmell W. Kimryn 
Published: July 2012

Abstract
Sporadic and germline mutations or loss of the von Hippel-Lindau (VHL) tumor suppressor gene have been linked to varying levels of risk for Renal Cell Carcinoma (RCC). RCC is a highly prevalent malignancy that affects roughly 56,000 people annually in the United States. With no true murine model for RCC, patient derived renal carcinoma cell lines and mouse embryonic stem cell lines have been largely used for the study of this malignancy. The purpose of this study is to generate an ex vivo model for Renal Cell Carcinoma using primary neonatal epithelial kidney cells grown as multicellular cultures. To better understand the genetic changes associated with RCC tumor formation following VHL loss or inactivation, primary epithelial kidney cells from newborn conditional Vhl null and Vhl G518A mutant genetically engineered mouse lines are undergoing investigation. Analysis of primary neonatal epithelial kidney cells cultured under mild hypoxia show that these cells preferentially grow in an organized multicellular spherical culture. Additionally, these multicellular cultures, termed “renospheres”, display focal expression of progenitor cell marker CD133, and also globally express Oct4 while select cells in the renospheres express renal cell type markers as seen by immunohistochemistry. Current work is aimed at identifying the cellular makeup of these spheres and determining any role individual cellular components may have in tumorigenesis. Future plans will compare growth characteristics and cellular components of renospheres in the setting of VHL mutation or loss with those with an intact VHL network. This ex vivo system can provide insight into both the cellular characteristics and molecular events that contribute substantially to RCC tumor formation as growth conditions of the renospheres are meant to mimic as close to a physiological state as possible, a factor not currently being addressed by common practices in the field.
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 4276. doi:10.1158/1538-7445.AM2011-4276
Abstract 4281: Real-time imaging of the cell-cycle in vivo
Authors: Suetsugu Atsushi , Moriwaki Hisataka , Saji Shigetoyo , Pinney Emmett , Naughton Gail , Yano Shuya , Fujiwara Toshiyoshi , Hoffman Robert M. 
Published: July 2012

Abstract
FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator) cells are labeled orange in the G1 phase nuclei (monomeric Kusabira-Orange2: mKO2) and labeled green in the S/G2/M phases (monomeric Azami-Green1: mAG1) (Cell 132, 487-498, 2008). FUCCI-expressing MKN45 gastric cancer cells were used for imaging cell-cycle dynamics in vivo and in vitro. When a confluent monolayer of MKN45-FUCCI was scratched, the edge of the wound turned green within 24hr, indicating that healing of the wound required proliferation of MKN45 cells. FUCCI-expressing MKN45 cells were injected subcutaneously in the nude mice. The injected cells gradually grew and emitted both green and red fluorescence for 14 days, indicating cell cycle progression. In the chorioallantonic membrane (CAM) chick embryo model, green and red fluorescence FUCCI cells and blood vessels were observed for 5 days. FUCCI cells of the edge in the tumor migrated into the transparent egg membrane. Mouse and CAM FUCCI tumor models will be used to study the role of cell cycle dynamics in metastasis including dormancy.
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 4281. doi:10.1158/1538-7445.AM2011-4281
Abstract 4282: Real-time subcellular imaging of cancer cell nuclear dynamics in the brain of live mice
Authors: Momiyama Masashi , Suetsugu Atsushi , Tome Yasunori , Bouvet Michael , Chishima Takashi , Endo Itaru , Hoffman Robert M. 
Published: July 2012

Abstract
In order to visualize single cancer cell nuclear dynamics in the brain, U87 human glioma cells were injected into the brain stereotactically, or Lewis lung mouse carcinoma (LLC) cells were injected into the carotid artery of nude mice. Both cancer cells types express GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was made over the right parietal bone for real-time imaging of cancer cells on the brain. Mitotic and apoptotic cancer cells in the brain were imaged in real time. Temozolomide (TMZ) and UVC light were used for induction of cancer cell apoptosis. Imaging showed that approximately 86% of Lewis lung carcinoma cells irradiated with UVC light underwent apoptosis and died in contrast to U87 cells which were resistant to UVC. Real-time subcellular imaging in the brain showed TMZ-induced apoptosis of both U87 and LLC cells. Imaging could be carried out for at least two weeks through the craniotomy window enabling treatment to be evaluated on cancer cells in the brain at the subcellular level. The subcellular real-time imaging model of cancer cells in the brain will be of important use for discovery and evaluation novel drugs active against brain cancer and brain metastasis.
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 4282. doi:10.1158/1538-7445.AM2011-4282
Abstract 4284: Combined magnetic resonance and fluorescence-protein imaging to simultaneously assess the anti-tumor and anti-angiogenesis efficacy of selenium
Authors: Bhattacharya Arup , Turowski Steve G. , Martin Ivan Dominguez San , Rajput Ashwani , Rustum Youcef M. , Hoffman Robert M. , Seshadri Mukund 
Published: July 2012

Abstract
In this report, we determined the feasibility to combine fluorescent protein imaging (FPI) and magnetic resonance imaging (MRI) to demonstrate the efficacy of selenium on tumor progression and angiogenesis of colon cancer in an orthotopic model. GEO human colon carcinoma cells expressing green fluorescent protein (GFP), were implanted orthotopically into the colon of athymic nude mice. Beginning 5 days post implantation, whole body FPI was performed to monitor tumor growth in vivo. Upon visualization of tumor growth by FPI, animals were randomly assigned to either a control group or a treatment group. Treatment consisted of daily oral administration of the organoselenium compound, methyselenocysteine (MSC; 0.2 mg/day × 5 weeks). Longitudinal monitoring of tumor growth was performed using FPI and MRI. In addition, dynamic contrast-enhanced MRI was performed to examine the change in tumor blood volume following treatment. Changes in tumor vascularity visualized by imaging were correlated with immunohistochemical determination of microvessel density. Both FPI and MRI allowed non-invasive visualization of the longitudinal growth of orthotopic colon tumors. While T1- and T2-weighted MRI provided adequate contrast and volumetric assessment of GEO tumor growth, GFP imaging allowed for high-throughput visualization of tumor progression. Selenium treatment resulted in a significant reduction in blood volume and microvessel density of GEO tumors. A significant inhibition of tumor growth was also observed in selenium-treated animals compared to untreated control animals. Together, these results highlight the usefulness of multimodal imaging approaches to demonstrate antitumor and anti-angiogenesis efficacy and the potential of selenium treatment of colon 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 4284. doi:10.1158/1538-7445.AM2011-4284