bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2416: Neuropilin-2 is upregulated during EMT in lung cancer
Authors: Nasarre Patrick , Roche Joelle , Potiron Vincent A. , Nair-Menon Joyce , Gemmill Robert M. , Drabkin Harry A. 
Published: August 2012

Abstract
Neuropilins (NRP1 and NRP2) are high affinity receptors for the class-3 semaphorins, cell guidance molecules involved in tissue development, immune responses, angiogenesis and cancer. Semaphorins affect cell protrusion, spreading and adhesion, and can trigger migratory responses often in a repulsive manner depending on the cellular context. Interestingly, neuropilins are also receptors for galectin-1 and growth factors including VEGF, PlGF, EGF and TGFβ. We previously cloned the SEMA3F gene from chromosome 3p21.3, which undergoes homozygous deletion and frequent loss of heterozygosity in lung cancer. We found that SEMA3F levels were inversely correlated with tumor aggressiveness in human lung cancer and confirmed its tumor suppressor activity in experimental xenograft models. We subsequently discovered that SEMA3F is directly downregulated by ZEB1, a transcription factor involved in the epithelial to mesenchymal transition (EMT). In the present study, we asked whether SEMA3F specific receptor, NRP2, was also regulated during the EMT process. TGFβ, a physiologic EMT inducer, stimulated NRP2 expression in two NSCLC cell lines. Forced expression of ZEB1, but not Snail, also induced NRP2. Conversely, ZEB1 and Snail inhibition blocked NRP2 upregulation by TGFβ. Importantly, inhibiting NRP2 or ZEB1 expression reduced TGFβ-induced migration in an equivalent manner. In lung cancer tissue microarrays, NRP1 and NRP2 were preferentially expressed in the tumor compartment, whereas the EMT-related transcription factors, ZEB1 and Snail, were predominantly expressed in the stroma. Of note, NRP2 was also expressed in stromal cells and was significantly associated with both ZEB1 and a higher (worse) tumor grade. Since NRP2 is the highest affinity receptor for SEMA3F, our results suggest that loss of SEMA3F coupled with increased NRP2 would facilitate the binding of growth factors to NRP2 to further promote EMT and metastasis. Therefore, targeting NRP2 could be an important therapeutic approach against EMT in lung 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 2416. doi:1538-7445.AM2012-2416
Abstract 2423: Acute in vitro exposure to cigarette smoke particulate matter does not induce epithelial-mesenchymal transition in lung epithelial cells
Authors: Breheny Damien M. 
Published: August 2012

Abstract
The epithelial-mesenchymal transition (EMT) program was first identified from studies on embryogenesis and organ development, but has since been found to play vital roles in tissue remodelling and tumorigenesis. EMT is a biological process during which epithelial cells change their morphology to adopt fibroblast-like characteristics. During EMT, cell adhesion is lost while cells become more motile. A number of distinct molecular events are required for a cell to undergo EMT including transcription factor activation, cytoskeletal rearrangement, changes in cell adhesion molecule expression and increased production of extracellular matrix-degrading enzymes. EMT has recently been linked to chronic inflammation and cigarette smoke exposure in the lung and is believed to be involved in lung carcinogenesis. As the specific genes and proteins involved in EMT have been well defined, they can serve as markers to demonstrate the passage of cells through EMT in the context of cigarette smoking. The purpose of this study was to develop an in vitro model of EMT using immortalised human bronchial epithelial (BEAS-2B) cells. EMT was induced in BEAS-2B cells using a 72 hour treatment with 5 ng/mL TGF-β1. Expression of the following EMT markers were assessed at the transcript level using reverse transcription real time-polymerase chain reaction (RT-PCR): alpha smooth muscle actin (α-SMA), collagen 1, fibronectin, vimentin, e-cadherin, slug and snail. Protein levels of α-SMA, fibronectin, β-catenin, e-cadherin and zonular occludin-1 were evaluated using immunocytochemistry techniques. This model was then used to determine the effects of acute (72 hour) cigarette smoke particulate matter treatment on EMT in BEAS-2B cells. Cells were treated with particulate matter alone, and in combination with TGF-β1. Particulate matter did not induce EMT directly, nor did it influence EMT induced by TGF-β1 under the treatment conditions used in this study, based on marker expression. It is possible that a more prolonged exposure to particulate matter is required for EMT induction in BEAS-2B cells.
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 2423. doi:1538-7445.AM2012-2423
Abstract 2436: [18F]FDG accumulation in tumor microenvironment -Microautoradiographic study combined with immunohistochemistry in mice-
Authors: Sugita Sachi , Yamato Masanori , Kataoka Yosky , Watanabe Yasuyoshi 
Published: August 2012

Abstract
[Purpose] Tumor microenvironment is characterized by the conditions including hypoxia, low nutrition, stromal cell infiltration, and acidosis due to incomplete blood vessel network. Tumor microenvironment has been recognized as a major factor influencing not only the response to anti-cancer therapies but also malignant progression and metastasis. Non-invasive imaging of such a microenvironment by positron emission tomography (PET) will provide more therapeutic merits. Accumulation of FDG, 2-deoxy-2-[F-18]fluoro-D-glucose, a most-often used PET probe, in tumor has been reported to correlate with the metastasis and malignancy. However, the FDG uptake profile in the microenvironment has remained unknown. In this study, we simultaneously visualized the intratumoral FDG distribution and the microenvironment by using microautoradiography in microscopic spatial resolution combined with immunohistochemistry. [Methods] Human epidermoid carcinoma cell line A431 was transplanted into the back of female SCID mice, and FDG was injected into the mice 2 weeks after the transplantation. The tumors were removed from mice 45 minutes after the FDG administration and the frozen sections were obtained. Overall image of the intratumoral FDG distribution was obtained by conventional autoradiography. FDG distribution and microenvironment in microscopic levels were visualized by microautoradiography followed by immunohistochemical detection of hypoxic condition and cell-specific markers. [Result & Conclusion] Conventional autoradiography and microautoradiography showed the similar pattern in FDG distribution in the tumor. Furthermore, microautoradiographic study with immunohistochemistry revealed that grains at high-density were observed in pimonidazol (hypoxia marker)-accumulated areas showing infiltration of many S100A4-immunopositive fibroblasts. These results suggested that FDG accumulation was prominent in stromal cells involved in hypoxic condition in tumor microenvironment.
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 2436. doi:1538-7445.AM2012-2436
Abstract 2437: Fluorescent imaging in animal model of human tongue squamous cell carcinoma in vivo by Nimotuzumab conjugated near-infrared quantum dots and small molecule fluorescent dye
Authors: Huang Xuelei , Ren Yipeng , Xi Qing , Zhang Lei , Fu Chongjian , Bu Rongfa 
Published: August 2012

Abstract
Objectives:To explore near-infrared fluorescent imaging in vivo using quantum dots Qdot800 and Alexa680 dye labeling Nimotuzumab for human tongue squamous cell carcinoma diagnosis, location. Methods: Near-infrared fluorescent quantum dots Qdot800 and Alexa680 dye were respectively conjugated with Nimotuzumab. Subsequently, the probes were used to detect fixed or live human tongue squamous cell carcinoma cell line Tca8113. After Tca8113 subcutaneous xenografts grown in, the nude mice were injected intravenously with one of the conjugates followed by fluorescent imaging using small animal imaging system. The images of targeting tumor in vivo were required and analyzed. Results: Near-infrared fluorescent quantum dots Qdot800 and Alexa680 dye were successfully conjugated with Nimotuzumab. The conjugates were able to specifically and efficiently recognize fixed and live Tca8113 with intense fluorescence. Although Nimotuzumab labeled with Qdot800 could not be detected targeting the subcutaneous Tca8113 xenografts grown in vivo, Nimotuzumab labeled with Alexa680 performed very well with bright fluorescence in contrast to surrounding normal tissue. Conclusions: The fluorescent conjugates probes Nimotuzumab conjugated with Near-infrared fluorescent Qdot800 and Alexa680 dye were able to specifically target human tongue squamous cell carcinoma cell in vitro. Alexa680 labeling with Nimotuzumab was more suitable than Qdot800 to perform fluorescent imaging in vivo for the study of human tongue squamous cell carcinoma. [Key words] tongue squamous cell carcinoma, fluorescent imaging, fluorescent probe, Nimotuzumab
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 2437. doi:1538-7445.AM2012-2437
Abstract 2438: Bevacizumab treatment hampers tumor uptake of antibodies in human tumor bearing mice
Authors: Arjaans Marlous , Munnink Thijs H. Oude , Oosting Sjoukje F. , van Scheltinga Anton G. T. Terwisscha , Timmer-Bosscha Hetty , de Hooge Marjolijn N. Lub- , Schröder Carolina P. , de Vries Elisabeth G. E. 
Published: August 2012

Abstract
Background: Extensive angiogenesis, defective vascular architecture, impaired lymphatic drainage and increased vascular permeability are characteristics unique for solid tumors. These characteristics result in enhanced tumor permeability and retention (EPR) effect. The EPR effect has been recognized as an important factor for intratumoral delivery of macromolecular drugs, like antibodies. Rapid changes in tumor vasculature and permeability due to antiangiogenic treatment could possibly restrain the EPR effect and thereby lead to a decreased uptake of antibodies. This would have implications for combining antiangiogenic therapy with monoclonal antibodies. We therefore investigated the effect of bevacizumab treatment on the tumor uptake of antibodies by means of immunoPET imaging. Methods: The effect of bevacizumab treatment on the antibody tumor uptake was studied with in vivo PET imaging of 89Zr-trastuzumab, 89Zr-bevacizumab and 89Zr-IgG in a SKOV-3 human xenograft tumor model. PET images were made before and during bevacizumab (5mg/kg; 2qw) or placebo (normal saline) treatment. All animals also received trastuzumab, bevacizumab or IgG labeled with the near-infrared fluorescence dye IRDye 800CW as a co-injection. Immunohistochemistry was performed to determine the mean vascular density (MVD). Immunofluorescence was used to visualize trastuzumab-800CW, bevacizumab-800CW and IgG-800CW and to determine vessel normalization by vessel pericyte coverage. Results: Bevacizumab treatment decreased 89Zr-trastuzumab, 89Zr-bevacizumab and 89Zr-IgG tumor uptake with 41 ± 5% (P&lt;0.0001), 43 ± 4% (P&lt;0.0001) and 28 ± 6% (P=0.0004) respectively. Placebo treatment did not affect tumor uptake of 89Zr-IgG. Immunofluorescence showed less accumulation of IgG-800CW in bevacizumab treated tumor sections compared to placebo treated tumor sections. In all groups, bevacizumab treatment decreased the MVD (P&lt;0.0003). Remaining vessels in bevacizumab treated tumor sections showed an increase in the amount and degree of vessel pericyte coverage compared to placebo. Conclusion: Bevacizumab treatment reduces tumor uptake of trastuzumab, bevacizumab and IgG possibly by restraining the EPR effect through vessel normalization. This deserves attention in the design of clinical trials, when combining antiangiogenic treatment with antibodies.
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 2438. doi:1538-7445.AM2012-2438
Abstract 2447: Measurement of tumor vascular integrity changes in an orthotopic glioma model in rats induced by antiangiogenic treatment using DCE-MRI
Authors: Provent Peggy , Boisferon Marc Hillairet de , Koob Zina , Bichat Francis , Tizon Xavier 
Published: August 2012

Abstract
Background Glioblastoma is the most aggressive subtype of brain tumors. Antiangiogenic compounds are being tested in clinical trials, for this pathology, mostly in combination with other molecules. The availability of an imaging biomarker of efficacy could help optimize the dosing and scheduling of these combinations. The aim of this study was to validate DCE-MRI, using two contrast agents of different molecular weight, as an imaging biomarker of the efficacy of sorafenib (Nexavar®, BAY 43-9006) in an orthotopic glioma model in Nude rats. Methods U-87 MG human glioma cells were inoculated by stereotactic injection in the right caudate nucleus of 24 Nude rats. All rats were first imaged 10 days after cell injection to measure their baseline tumor volume (TV) using T2-weighted MRI (Bruker Pharmascan, 4.7T). Based on their TV, 20 rats were selected and imaged at D-1 (14 days after cell injection). The rats were then randomized into 2 groups of 8 rats according to their tumor vascular status following a full DCE-MRI protocol using either Gd-DTPA (Magnevist®) or P846 (two parameters: Ktrans from pharmaco-kinetic modeling of the contrast agent uptake curve, and iAUC60, the initial area under the gadolinium concentration time curve after 60 seconds). P846 is a medium-molecular weight, gadolinium-based contrast agent provided by Dr P. Robert (Guerbet). In both subgroups of 8 rats, each animal received a daily per os administration of either sorafenib (100 mg/kg/adm) or its vehicle. All 16 rats were then imaged at D1, D3 and D7. At each time point, voxelwise maps of DCE-MRI parameters were derived from imaging data and their distribution analyzed within regions of interest within the tumor and the contralateral lesion-free tissue. Results Sorafenib was well tolerated and it increased the median survival of tumor-bearing rats by 20%. At D7, despite no difference in tumor growth kinetics, DCE-MRI parameters (Ktrans and iUAC60) showed significant differences between sorafenib-treated and control groups using either Magnevist® or P846. Visual assessment showed that the heterogeneity of contrast agent uptake was reduced by antiangiogenic treatment with sorafenib. The quantification of this phenomenon by statistical analysis of the parameter distributions within the ROIs is pending. Conclusions In conclusion, we have shown that DCE-MRI, with either Magnevist® or P846 contrast agents, is a suitable non-invasive imaging technique to show changes of tumor vasculature integrity induced by antiangiogenic treatment such as sorafenib in orthotopically-implanted glioma in Nude rats.
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 2447. doi:1538-7445.AM2012-2447
Abstract 245: ST6Gal-I sialylation of the Fas (CD95) receptor provides protection against Fas mediated apoptosis
Authors: Swindall Amanda F. , Liu Zhongyu , Bellis Susan L. 
Published: August 2012

Abstract
The golgi glycosyltransferase, ST6Gal-I, adds the negatively-charged sugar, α2-6 sialic acid to membrane and secreted proteins. This enzyme has been shown to be upregulated in numerous human cancers including colon cancer. However, the function of ST6Gal-I in tumor progression remains unclear due to a dearth of knowledge regarding enzyme substrates, and the effect of sialylation on target function. Previously, we have shown ST6Gal-I to be upregulated by oncogenic-ras which leads to increased invasion in colon carcinoma cells. Recently a role for ST6Gal-I in the protection of tumors against apoptosis is emerging, as we have shown sialylation to block galectin-mediated apoptosis by inhibiting the binding of galectin-3. Here we identify the Fas (CD95) receptor as a target for ST6Gal-I sialylation, and show that Fas sialylation prohibits apoptotic signaling in two independent cell models. Specifically, in an shRNA knockdown of ST6Gal-I in cells with high endogenous ST6Gal-I (HD3), and in a forced expression of ST6Gal-I in cells with no endogenous sialyltransferases (SW48), we show the presence of ST6Gal-I impedes Fas apoptotic signaling. Upon treatment with both the activating antibody, CH11 and the endogenous ligand, FasL, cells expressing ST6Gal-I had decreased levels of cleaved caspases 3 and 8, as shown by western blot and immunofluorescent staining. However, there was no difference in DR4/DR5-mediated apoptosis induced by TRAIL, suggesting a specific effect of ST6Gal-I on Fas-mediated apoptosis. Additionally, we have shown ST6Gal-I sialylation of Fas decreases the binding of FADD to Fas cytoplasmic tails limiting DISC formation, and prohibits receptor internalization after activation, effectively blocking Fas apoptotic signaling. We have also shown Fas-mediated apoptosis driven by the agonistic antibody, Jo2, to be inhibited in primary macrophages from transgenic mice genetically engineered by our lab to over-express ST6Gal-I. Furthermore, we have shown ST6Gal-I to be upregulated in 7/9 human colon tumor samples, and despite Fas downregulation, the expressed Fas is hypersialylated in several human tumor tissues. In summary, these data identify ST6Gal-I sialylation of the Fas receptor as a novel mechanism in the self-protection of tumors against apoptosis, and further identify ST6Gal-I as an important regulator of apoptotic signaling.
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 245. doi:1538-7445.AM2012-245
Abstract 2454: In vivo binding of chTNT-1/B antibodies (Cotara) to DNA/histone complexes in tumors using near-infrared optical imaging
Authors: Gong Jian , Sevilla Roy , Nguyen Vince , Fisher Seth , Alldredge Jessica , Kinjo Jessie , Archer Rich , Peacock Matthew , Hughes Christopher , Chang Connie , Freimark Bruce 
Published: August 2012

Abstract
Tumors contain both microscopic and macroscopic areas of necrotic cells. These have abnormal cell membrane permeability, which allows passage of large macromolecules such as antibodies into the cell. 131I-chTNT-1/B antibody (Cotara) is a novel, single administration agent designed to target tumor necrosis that has completed a Phase II clinical trial for recurrent glioblastoma multiforme (GBM), showing 9.3 month median overall survival for patients. Since 131I-chTNT-1/B antibody is a high-molecular-mass protein, it cannot easily pass from the systemic circulation through the blood-brain barrier (BBB) and thus can only be delivered locally by an intratumoral catheter. We have developed a human ME-180 cervical carcinoma xenograft tumor model in nude mice to characterize the targeting of chTNT-1/B to necrotic areas using near infrared (NIR) optical imaging. The use of NIR optical imaging is a powerful translational tool to monitor in vivo antibody targeting. chTNT-1/B was labeled with a NIR fluorescent dye and kinetics of antibody retention in tumors was measured by NIR optical imaging following intratumoral injection of the NIR-chTNT-1/B. NIR-chTNT-1/B was retained in ME180 tumors for a longer duration compared to NIR dye alone. Labeling of chTNT-1/B with a low dye/protein ratio was necessary to demonstrate maximum specific targeting to tumor necrosis. Evaluation of in vivo antibody targeting to tumors using NIR imaging may facilitate improvements for treatment of patients with malignant glioma with Cotara.
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 2454. doi:1538-7445.AM2012-2454
Abstract 2558: VEGF-dependent suppression of prostaglandin transporter (PGT) expression in Kras mutant human bronchial epithelial cells
Authors: Lee Gina , Gardner Brian K. , Hazra Saswati , Kachroo Puja , Lee Mi-Heon , Krysan Kostyantyn , Walser Tonya C. , Larsen Jill E. , Girard Luc , Wistuba Ignacio I. , Minna John D. , Dubinett Steven M. 
Published: August 2012

Abstract
Prostaglandin transporters are expressed in cyclooxygenase-positive cells and provide the dominant mechanisms for transport of prostaglandins (PG) across the cell membrane. Specifically, the prostaglandin transporter PGT, expressed in many cell types including lung epithelia, is responsible for the uptake of prostaglandin E2 (PGE2) for intracellular metabolism and degradation by 15-prostaglandin dehydrogenase (15-PGDH). The regulation of prostaglandin transporters has not been fully explored in lung cancer. We hypothesize that loss of PGT expression is important in lung carcinogenesis and its loss may be enhanced in the presence of common mutations in premalignant bronchial epithelial cells and non-small cell lung cancer (NSCLC). Our preliminary studies show that PGT expression (protein and mRNA) and 15-PGDH are significantly downregulated in Kras mutant human bronchial epithelial cells (HBEC) and in NSCLC. It is well known that Kras mutant cancers are associated with increased production of VEGF, an important factor in tumor angiogenesis. In HBEC, we found significantly higher VEGF levels in Kras mutants compared to vector controls (2242 versus 628 pg/mg, p = 0.04). We proposed that VEGF modulates PGT expression and tested our hypothesis by treating HBEC and NSCLC with human recombinant VEGF. PGT expression is downregulated with exogenous VEGF treatment and neutralizing VEGF production (neutralizing VEGF antibody) prevented the loss of PGT expression. The MEK1/2 inhibitor PD98059 upregulated PGT expression in HBEC Kras. Our results suggest Kras mutation is associated with loss of PGT expression and may be dependent on VEGF production. Modulation of PGT expression may be important in lung carcinogenesis.
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 2558. doi:1538-7445.AM2012-2558