bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2381: Neoangiogenesis correlates with increased breast density, calcitonin gene related peptide positivity and cell proliferation seeking radiotracer uptake in mixed invasive ductal associated with in situ, but not in pure invasive breast carcinoma
Authors: Papantoniou Vassilios , Tsaroucha Angeliki , Dimitrakakis Constantine , Marinopoulos Spyridon , Sotiropoulou Evangelia , Valsamaki Pipitsa , Fothiadaki Athina , Karianos Theodore , Archontaki Aikaterini , Sotiropoulou Maria , Syrgiannis Konstantinos , Antsaklis Aris 
Published: February 2011

Abstract
Aim: To assess neoangiogenesis in relation to breast density (BD), calcitonin gene related peptide (CGRP), cell proliferation seeking radiotracer 99mTc-(V)DMSA uptake (SMM) in invasive ductal associated with extensive in situ carcinoma (DCIS + IDC) and in pure invasive breast carcinoma (IDC).
Methods: 20 patients with histologically confirmed mixed DCIS + IDC (n=10) and pure IDC (n=10) were submitted preoperatively to mammography and scintimammography. The percentage of breast density (BD) and the percentage of tracer uptake (SMM) were calculated with computer assisted methods. CGRP and the number of newly formed blood vessels (NBV) were immunohistochemicaly assessed. NBV, BD, CGRP, and SMM were compared (t-test) between the two groups. Linear regression analysis was performed between NBV, BD, CGRP and SMM in both groups.
Results: NBV, BD, CGRP and SMM were significantly higher in mixed DCIS + IDC as compared to pure IDC (32.1±10.4 vs 24.3±5 p=0.048, 35.2 ± 6.9 vs 25.6±10.7 p=0.028, 25.5±7.6 vs 17±7.8 p=0.024, 26.75±4.09 vs 11.34±8.5 p=0.0009). NBV was strongly correlated with BD and CGRP in the DCIS component of the mixed group (r=0.933 p&lt;0.001, r=0.793 p&lt;0.01 respectively). BD was also significantly correlated with CGRP and SMM in the DCIS component of the same group (r=0.974 p&lt;0.001, r=0.728 p&lt;0.05 respectively). In contrast, no significant correlation(NS) was found between NBV and BD, CGRP or between BD and CGRP, SMM in both the IDC component of mixed group and pure IDC group (r=0.388 NS, r=0.391 NS, r= − 0.597 NS, r= − 0.352 NS in the IDC component of mixed group; r=0.584 NS, r= 0.297 NS, r= − 0.574 NS, r= −0.294 NS in pure IDC respectively).
Conclusion: Mixed DCIS + IDC lesions exhibit significantly increased NBV, BD, CGRP and SMM values as compared to those of IDC lesions. The strong correlation between neoangiogenesis and the other parameters in the mixed group indicates that the mixed DCIS + IDC constitutes a strictly different entity from pure IDC, more aggressive and probably originates from the stroma through the CGRP pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2381.
Abstract 2389: uPA and uPAR siRNA inhibits angiogenesis by blocking nuclear localization of angiogenin and angiopoietin1 signaling in glioblastoma cell lines
Authors: Raghu Hari , Song Ju Han , Fassett Daniel , Klopfenstein Jeffrey D. , Dinh Dzung H. , Gujrati Meena , Rao Jasti S. 
Published: February 2011

Abstract
Transcriptional inactivation of uPA and uPAR system in the glioblastoma cell line SNB19 inhibited angiogenesis both in vitro and in vivo. To decipher this mechanism and extend our studies to other glioblastoma cell lines, U87MG and U87 SPARC-overexpressing cell lines were subjected to uPA, uPAR and U2 (bicistronic construct against uPA and uPAR) downregulation by siRNA. In the present study, the bicistronic construct against uPA and uPAR caused significant inhibition of angiogenesis by in vitro angiogenesis assay and in vivo dorsal skin fold chamber models in both cell lines. Increased apoptosis was seen in siRNA downregulated gliomablastoma cells when compared with control cells by FACS analysis. MTT assay revealed significant inhibition of proliferation by U2 siRNA treatment in both cell lines. Transfection with siRNA against uPA and uPAR in co-cultures of glioma cells with endothelial cells showed significant inhibition of angiopoeitin1, IL-6, GRO and GM-CSF while SPARC-overexpressing U87 cells had decreased secretion of angiogenin, GRO, MCP-1, PDGFBB, VEGF and angiopoietin1 by protein array analysis. Bicistronic construct showed decreased levels of angiogenin by ELISA and Western blot in endothelial cells and in cocultures with cancer cells. Transcriptional inactivation of uPA and uPAR showed significant downregulation of angiogenin-induced phosphorylation of ERK, JNK and Akt signaling in endothelial cells. Nuclear translocation of angiogenin in semi-confluent human umbilical vein endothelial cells treated with conditioned medium from siRNA-transfected U87 SPARC-overexpressing cells was inhibited as shown by Western blot and immunofluorescence analyses. Conditioned medium from U87MG and U87 SPARC-overexpressing cells transfected with uPA, uPAR and U2 siRNA plasmids significantly inhibited the phosphorylation of Tie2 receptor in endothelial cells. uPA and uPAR downregulation significantly downregulated MMP-2 levels by gelatin zymography in co-cultures and in single cultures of cancer cells. Matrix metalloproteinase array analysis showed significant inhibition of MMP-3 in co-cultures of U2-transfected SPARC-overexpressing glioma cells. Overall, our results suggest that the simultaneous downregulation of uPA and uPAR inhibits angiogenesis by inhibition of nuclear localization of angiogenin, angiopoeitin 1 signaling and MMP-2 downregulation in endothelial cells. In summary, these results identify novel mechanisms by which the bicistronic construct against uPA and uPAR inhibits angiogenesis, thereby suggesting the potential use of U2 as an anti-angiogenic agent against glioblastoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2389.
Abstract 2413: Preventing the development of breast cancer by immunizing with multi-antigen vaccines targeting breast cancer proteins
Authors: Disis Mary L. , Gad Ekram , Herendeen Dan , Cecil Denise , Park Katie , Lai Vy , Lu Hailing , Lubet Ronald 
Published: February 2011

Abstract
Vaccines have been extremely successful in the prevention of infectious diseases. Although cancer vaccines have long been studied for the treatment of cancer, they have not been exploited as chemoprevention agents except in virally mediated malignancies. Human breast cancer is immunogenic and a variety of proteins involved in the malignant transformation or maintenance of the malignant phenotype have been identified as tumor antigens. Transgenic animal models are uniquely suited for evaluating the potential efficacy of preventative cancer vaccines. TgMMTV-neu mice, for example, develop neu-mediated breast cancer at about 150-200 days of life. Tumors are histologically similar to human breast cancer and have a molecular profile consistent with the luminal subtype. We have developed a multi-antigen vaccines targeting immunogenic proteins associated with oncogenesis and evaluated whether we could prevent the development of breast cancer in TgMMTV-neu mice. The vaccine is composed of 3 different antigens. Class II epitopes derived from antigenic proteins involved in growth factor pathways comprised the vaccine. The ability of active immunization to prevent breast cancer was evaluated in both older (18 week) and younger (5 week) mice. Vaccines were administered intradermally every two weeks for 3 immunizations and then monthly until the development of disease or 1 year had passed. The vaccine prevented breast cancer development in some older animals. 40% of peptide immunized older mice were cancer free at 1 year compared to 5% of controls (p=0.02). Protection from the development of cancer was mediated by T cells as evidenced by adoptive transfer of CD3+ cells purified from vaccinated and protected mice, sham immunized mice, and naïve mice. T cells from protected mice resulted in significant inhibition of tumor growth after a syngeneic tumor challenge (p=0.01 protected vs. sham vaccine). Prevention of breast cancer was more pronounced in the older animals when immunization was combined with oral chemoprevention agents. The cancer protective effect of immunization was more pronounced when vaccines were administered to the younger mice. The Class II epitope vaccine prevented cancer development in 65% of mice as compared to 5% of controls. These data suggest breast cancer vaccines targeting biologically relevant proteins may be an effective approach to the prevention of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2413.
Abstract 242: Analyses of novel genes encoding secreted and transmembrane proteins identified by CAST method: CDON is highly expressed in prostate cancer
Authors: Tetsutaro Hayashi , Oue Naohide , Anami Katsuhiro , Sakamotro Naoya , Sentani Kazuhiro , Ohara Shinya , Teishima Jun , Matsubara Akio , Yasui Wataru 
Published: February 2011

Abstract
Prostate cancer (PCa) is one of the most common human cancers. Identification of novel genes that encode membrane-spanning or secreted proteins expressed specifically in PCa has a great advantage to develop of ideal biomarkers for cancer diagnosis and therapeutics. Escherichia coli Ampicillin Secretion Trap (CAST) is a signal sequence trap method to identify genes encoding cell surface and secreted proteins. In this study, to identify novel diagnostic and therapeutic targets of PCa, CAST method was used. We generated cDNA libraries from normal prostate and two PCa cell lines, LNCaP and DU145. These CAST libraries were ligated into the pCAST which was plasmid with a mutant beta-lactamase lacking the endogenous signal peptide. Survival on ampicillin was observed only when various cDNA fragments encoding a signal sequence were inserted. We sequenced 960 ampicillin-resistant colonies for normal prostate CAST library, 1344 colonies for LNCaP CAST library and 960 colonies for DU145 CAST library. By comparing these sequences to those deposited in the public databases using BLAST (NCBI), 223 genes from normal prostate CAST library, 234 genes from LNCaP and 228 genes from DU145 were identified. To extract highly expressed genes in PCa, the genes expressed in normal prostate were excluded. Quantitative RT-PCR analyses of 64 candidate genes were performed and compared mRNA levels in 9 PCa tissues, 2 normal prostate tissues and 14 kinds of normal tissues. Quantitative RT-PCR analyses revealed that CDON was highly expressed in PCa. Overexpression of CDON (tumor/normal ratio &gt; 2) was observed in 8 (89%) of 9 PCa tissues. CDON is a cell surface receptor of the immunoglobulin /fibronectin type III repeat family. By western blot analysis, low to moderate CDON expression was noted in LNCaP cell extracts and moderate to high CDON expression was noted in DU145 cell extracts. The expression of CDON in LNCaP and DU145 was suppressed by treatment with CDON specific siRNA. Cell invasion assay and MTT assay revealed that knockdown of CDON in LNCaP cells did not inhibit both cell growth and invasion ability, but knockdown of CDON in DU145 cells inhibited both cell growth and invasion ability.
In conculusion, CAST is a robust and rapid method to identify cell surface and secreted proteins. CDON was up-regulated in PCa and participated in cell growth and invasion. These finding suggest that CDON may be a good therapeutic target.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 242.
Abstract 2427: Overexpression of insulin/IGF hybrid receptor as predictive biomarker of response to a humanized anti-insulin like growth factor-I receptor monoclonal antibody (CP751,871) in gastric and hepatocellular carcinoma cells
Authors: Kim Jun-Gyu , Kim Hwang Phill , Yoon Young Kwang , Han Sae Won , Im Seock-Ah , Oh Do-Youn , Bang Yung-Jue , Kim Tae You 
Published: February 2011

Abstract
Insulin-like Growth factor I receptor (IGF-IR) is highly expressed in many human cancers and plays a major role in proliferation, survival, and metastasis. Accordingly, abundant IGF-1R targeting drugs, especially monoclonal antibody drugs, have been focused and developed due to their safety and efficacy. In order to define biomarkers correlating with the drug sensitivity, we screened 10 gastric and 10 hepatocellular cancer cell lines, for in vitro response to CP-751,871, anti-insulin like growth factor type 1 receptor antibody. Our results show that CP-751,871 inhibits IGF-1 ligand-dependent IGF-1R phosphorylation and downstream signaling of the two major IGF-1R pathways, mitogen-activated protein kinase and phosphatidylinositol 3′-kinase/AKt. Moreover, long-term exposure to CP-751,871 also caused to decrease phospho-stat 3 as well as phospho-Akt level and induced G1 phase cell cycle arrest in dose-dependent manner preferentially in the sensitive cells. Surprisingly, among these 20 cell lines, cells with IGF-IR and insulin receptor (IR) were significantly inhibited by CP-751,871 compared to cells with IGF-IR or IR overexpression only. Considering their highly homologous structure, we thereby determined if the effect of CP-751,871 had relevance to the level of IR/IGF1R hybrid receptors through co-immunoprecipitation with either CP-751,871 or IGF1R antibody. Its immunoblot analysis revealed that not only did sensitive cell lines, such as SNU719, SNU368, and HepG2, show relatively higher levels of IR/IGF1R hybrid, but also superior ability of CP-751,871 to recognize their IR/IGF1R heterodimer complexes. Furthermore, we could observe that the hybrid forms were recruited by IGF1 ligands but this IGF-I ligand dependent formation was blockaded by CP-751,871. Lastly, the treatment of these sensitive cell lines with CP-751,871 caused dimer dissociation. Therefore, our data suggest that the antiproliferative effect by CP-751,871 requires the co-expression of IGF-1R and IR and may be related with the expression level of hybrid Insulin/IGF-1 receptors in gastric and hepatocellular carcinoma cell lines.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2427.
Abstract 2451: A novel humanized anti-CD40 RabMAb exhibits potent efficacy in preclinical models
Authors: Zhang Yongke , Dai Jihong , Ke Yaohuang , Li Wenjun , Yu Qiu , Li Mingzhen , Feng Lifeng , An Zhiqiang , Yu Guo-Liang , Zhu Weimin 
Published: February 2011

Abstract
Monoclonal antibodies directed against B cell antigens have shown clinical benefits to hematologic malignancies. CD40 is a member of the TNFR superfamily and is a target for potential treatment of B cell lineage hematological malignancies as well as certain carcinomas. To date, majority of the therapeutic monoclonal antibodies are of murine origin. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAb®), we generated functional RabMAbs against CD40 using Epitomics' RabMAb® platform. Here we report the characterization of EPI0050, a novel humanized anti-CD40 rabbit monoclonal antibody. EPI0050 specifically recognizes the CD40 ligand binding domain and selectively blocks the ligand binding to CD40. EPI0050 itself exhibits modest agonist effects as shown in the up-regulation of CD80, CD83 and CD86 in differentiated dendritic cells and direct inhibition of CD40 positive malignant B cells. EPI0050 bound CD40 strongly without much internalization, which conferred to a potent ADCC effect in vitro. In an established preclinical Ramos lymphoma model, EPI0050 significantly inhibited tumor growth with a long-term stabilization of the tumor post dosing as compared with Rituximab and another anti-CD40 antibody. EPI0050 was also able to regress established rebound tumors post Rituximab treatment. More animal models and MOA are being explored for EPI0050. Both in vitro and in vivo results support the preclinical and clinical development of EPI0050 as a bio-better tumor therapy.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2451.
Abstract 2452: Efficacy and toxicity of an anti-CD19 antibody drug conjugate
Authors: Rao Chetana , Pan Chin , Vangipuram Rangan , Huber Mary , Vemuri Kavitha , Stevens Alice , Chong Colin , Cortez Orville , Sung Janette , Derwin Dan , Passmore David , Zhang Qian , Gangwar Sanjeev , Cardarelli Pina , Deshpande Shrikant 
Published: February 2011

Abstract
CD19 is an attractive target for immunotherapy. The expression of CD19 is restricted to B cells and follicular dendritic cells. In B cells, expression is initiated at the point of B lineage commitment and continues through the pre B and mature B cell differentiation. Expression is lost during the terminal differentiation of B cells to plasma cells. CD19 expression continues in B-lineage cells that have undergone neoplastic transformation, making it a useful marker in diagnosis and treatment of B cell derived lymphomas and leukemias, including non-Hodgkin's lymphoma (NHL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL).
We have generated a fully human antibody to CD19 (MDX-1435) in transgenic mice for high binding affinity as well as the ability to rapidly internalize for drug delivery. The antibody was conjugated to a potent DNA alkylating agent related to Duocarmycin (MED-2460). This ADC (MDX-1206) shows anti-tumor activity in established Raji, Daudi and Ramos subcutaneous xenograft models at doses as low as 0.1 μmole/kg with no associated weight loss, or other overt toxicity. Efficacy was substantially superior to that of MDX-1435 and non-specific control antibody conjugates.
In addition, MDX-1435 binds to cynomologus monkey CD19 with similar affinity and tissue distribution as in humans. The intravenous administration of two doses at 0.4 μmole/kg was well tolerated in cynomologus monkeys and did not result in overt clinical or histological signs of toxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2452.
Abstract 2465: Gene expression, phenotypic and karyotypic analyses of stepwise prostate carcinogenesis in vitro
Authors: Ke Xi-Song , Li Wen-Cheng , Qu Yi , Hovland Randi , Liu Run-hui , Rotter Varda , Akslen Lars A. , Oyan Anne Margrete , Kalland Karl-Henning 
Published: February 2011

Abstract
The loss of epithelial characteristics and the acquisition of a migratory phenotype, referred to as epithelial to mesenchymal transition (EMT), is a crucial event in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to mesenchymal cells (EPT1) without malignant transformation. To achieve transformed prostate cells, EPT1 cells were kept growing in extended saturation density cultures to select for cells overriding quiescence. Following about 30 subconfluent passages and thereafter, foci appeared repeatedly in EPT1 monolayers following three to four weeks in confluent cultures. For comparison, in parallel experiments foci appeared neither in confluent cultures of EPT1 cells of early passage nor in confluent EP156T cells of either low or late passages.
Cells from the foci of EPT1 monolayers formed robust colonies in soft agar suggesting full malignant transformation. The transformed cells were named EPT2. In this stepwise transformation model, EPT2 cells showed much higher abilities to proliferate at confluence, migrated better, were less dependent on exogenous growth factors and were more resistant to staurosporine induced apoptosis than EP156T and EPT1 cells. Also, while EP156T cells and EPT1 cells remained diploid, chromosomal instability and aneuploidy were evident in EPT2 cells. Gene expression profiling and western blots showed progressive down-regulation of CDH1 from EP156T, through EPT1 to EPT2 together with a number of additional changes. Our findings provide a novel stepwise transformation model according to which EMT can occur independently of transformation, but is associated with subsequent malignant transformation in prostate carcinogenesis.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2465.