bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1476: Cell surface nucleolin acts as a specific receptor of Tipα, a carcinogenic factor released from H. pylori
Authors: Suganuma Masami , Watanabe Tatsuro , Tsuge Hideaki , Hirano Kazuo , Beppu Masatoshi , Yamaguchi Kensei , Takahashi Atsushi , Fujiki Hirota 
Published: February 2011

Abstract
TNF-α inducing protein (Tipα), a unique carcinogenic factor of H. pylori, has the potential to transform Bhas 42 (v-H-ras transfected BALB/3T3) cells. Tipα directly binds to gastric cancer cells and then induces expression of TNF-α gene, an endogenous tumor promoter, in gastric epithelial cells. H. pylori obtained from gastric cancer patients release significant amounts of Tipα into the culture medium compared with H. pylori of gastritis patients, indicating that Tipα plays important role in gastric cancer development. Recently, Tipα vaccination was reported to significantly reduce the colonization of H. pylori in mice associated with high levels of Tipα-specific antibody: All the results indicate that Tipα is a suitable molecular target for gastric cancer prevention. We recently demonstrated that nucleolin is a specific binding protein for Tipα in mouse gastric cancer cells MGT-40 using FLAG pull-down assay. Although nucleolin is known to a be non-ribosomal protein in nucleoli, we found that nucleolin is present on the cell surface of MGT-40 cells and various human gastric cancer cell lines, such as KATOIII and AGS, as determined by flow cytometry with anti-NUC295 antibody (recognizing cell surface nucleolin), and by cell fractionation. Pretreatment with anti-NUC295 antibody induced the enhancement of Tipα incorporation into the MGT-40 cells, but pretreatment with tunicamycin, an inhibitor of N-glycosylation decreased the amounts of cell surface nucleolin and inhibited internalization of Tipα, resulting in down-regulation of TNF-α gene expression. We here present evidence that cell surface localized nucleolin acts as a receptor of Tipα and shuttles Tipα from cell surface to cytosol and nuclei, and we discuss the significant roles of cell surface nucleolin in gastric cancer development by H. pylori infection.
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 1476.
Abstract 1483: 15-Deoxy-D12,14-prostaglandin J2 upregulates 15-hydroxyprostaglandin dehydrogenase expression through activation of AP-1 signaling in human colon cancer cells
Authors: Park Jong-Min , Cho Kyung-Hwa , Myung Seung-Jae , Surh Young-Joon , Na Hye-Kyung 
Published: February 2011

Abstract
Abnormal up-regulation of cyclooxygenase-2 (COX-2) expression has been considered as a key oncogenic event in inflammation-associated human colon carcinogenesis. It was reported that 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a physiological antagonist of COX-2 in its catabolism, is ubiquitously lost in human colon cancer, and hence considered as a tumor suppressor. However, the molecular mechanisms underlying regulation of 15-PGDH expression in colon carcinogenesis remain largely unresolved. In the present study, we found that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the terminal products of COX-mediated arachidonic acid metabolism, upregulates the expression of 15-PGDH in the human colon cancer HCT116 cells in a time and concentration-dependent manners. 15d-PGJ2 treatment (10 μM) significantly upregulated the expression of 15-PGDH and its mRNA transcript. 15-PGDH activity was also elevated by 15d-PGJ2 treatment. In a subsequent experiment, we performed cDNA microarray analysis with HCT116 cells exposed to 15d-PGJ2 (10 µM) for 3 h. We observed that C/EBP delta, FOS-like antigen 1, and c-Jun (AP-1) were the most highly induced genes upon treatment with 15d-PGJ2. Based on these findings, we determined whether 15d-PGJ2 could activate the DNA binding of AP-1, a representative transcription factor that preferentially binds to the promoter region of 15-PGDH. 15d-PGJ2 caused increased DNA binding activity of AP-1 in HCT116 cells. Moreover, siRNA knock down of c-Jun, a major subunit of AP-1, significantly reduced 15-PGDH expression as well as AP-1 DNA binding induced by 15d-PGJ2. To elucidate the upstream signaling pathways responsible for AP-1 activation and 15-PGDH expression induced by 15d-PGJ2, we examined the effect of this cyclopentenone prostaglandin on the activation of mitogen-activated protein kinases (MAPKs), such as ERK, p38 and JNK, and also Akt. We observed that a pharmacological inhibition of Akt/PKB with LY294002 abrogated the 15d-PGJ2-induced 15-PGDH expression and AP-1 DNA binding activity, while inhibitors of MAPKs failed to affect these events. Taken together, these finding suggest that 15d-PGJ2 upregulates the expression of 15-PGDH via Akt-mediated AP-1 activation.
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 1483.
Abstract 1486: Increased expression and phosphorylation of eukaryotic initiation factor 4E (eIF4E) and 4E-binding protein (4E-BP1) correlates with disease progression and high risk clinical/pathological features in melanoma
Authors: Chakravarti Nitin , Warneke Carla L. , Johnson Marcella M. , Davies Michael A. , Prieto Victor G. 
Published: February 2011

Abstract
Cutaneous melanoma is an increasingly important public health problem, as the incidence of this disease has increased 15-fold during the last four decades, more than any other malignancy. There is a great need for biomarkers that can be used both for both diagnosis and prognosis in melanoma. Identification of such biomarkers may provide insight into the pathogenesis of this disease, and also suggest rational therapeutic approaches. Protein translation has been shown to play a significant role in carcinogenesis in various organ systems. Several pathways upstream of protein translation are deregulated during melanoma development, including the RAS-RAF-MAPK and the PI3K-AKT kinase cascades. It is unknown whether dysregulated translational machinery contributes to the pathogenesis of melanoma. In order to test the hypothesis that dysregulation of protein translation plays a significant role in melanoma, we have performed immunohistochemical analysis to evaluate expression of phospho-4E-BP1 (p4E-BP1), phospho-eIF4E (peIF4E) and total eIF4E in benign nevi (n=49), primary melanomas (n=130), and melanoma metastases (n=47 cases) specimens obtained from the Department of Pathology of The University of Texas M. D. Anderson Cancer Center. A significant positive correlation was observed between the percentage of positively staining cells and staining intensity for p4E-BP1 (p&lt;0.0001) and peIF4E (p&lt;0.0008) with progression from benign nevi to primary tumors, and from primary tumors to metastases. Significantly higher levels of p4E-BP1 (p=0.0085) and total eIF4E (p=0.0173) proteins were observed in samples with vertical growth phase than in samples with radial growth phase only. Higher levels of p4E-BP1 were also observed in samples with ulceration (p=0.0167), which is a well-established marker of poor clinical outcomes in patients with local and regional melanoma. Thus, total and phosphorylated eIF4E and phosphorylated 4E-BP1 correlate with disease progression and high risk clinical and pathological features in melanoma. These findings provide new insight into the molecular pathogenesis of melanoma, and suggest that protein translation machinery may be an important therapeutic target in this disease.
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 1486.
Abstract 149: DNA methylation biomarker discovery using the Methyl-Profiler PCR Array System
Authors: Shaffer Jonathan M. , Liu Chun-Xiang , Gu Xiujing , Liu GuoZhen , Xiang Yan , Lin Yuye , Han Rui , Quellhorst George J. , Boon Kathy 
Published: February 2011

Abstract
Histone modifications and DNA methylation are epigenetic events that can modulate gene expression patterns associated with normal development and disease pathology. Epigenetic alterations are clearly involved in breast cancer initiation and progression, as they silence tumor suppressor genes and activate proto-oncogenes. As a result, the profiling of gene promoter DNA methylation status can lead to the identification of novel biomarkers which can aid in the development and improvement of diagnostic, prognostic, and therapeutic treatments. The Methyl-Profiler PCR Array System proves to be quite useful for these purposes.
The Methyl-Profiler DNA Methylation technology method is designed for semi high-throughput gene/target-specific DNA methylation profiling. The method involves the selective digestion of sample DNA with methylation-specific restriction enzymes, followed by precise quantization of intact remaining target DNA by real-time PCR using assays specially designed and validated for high G/C content amplicons. Attesting to the power of this method, as little as one µg of genomic DNA can be used to profile the methylation status of up to 96 gene/target assays, and as low as five % hyper-methylated DNA copies can be reliably detected in a heterogeneous sample. In short, this technology yields quantitative data comparable to bisulfite sequencing, but without the need for bisulfite conversion.
Using the Methyl-Profiler assay, the methylation status of highly relevant methylation targets in breast cancer cell lines was profiled in an effort to discover novel DNA methylation biomarkers. Several putative markers were identified and compared with results as generated by Illumina® Infinium® Methylation Assay platform, demonstrating the viability of the Methyl-Profiler method in discovering DNA methylation biomarkers. In three short procedural steps, the Methyl-Profiler PCR System can efficiently and reproducible identify novel methylation-related targets that may prove to be valuable in developing breast cancer preventative and therapeutic strategies.
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 149.
Abstract 1491: CEA interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers
Authors: Cao Hong , Li Ying , Yao Wenguo , Jogunoori Wilma , Thenappan Arun , Mishra Lopa 
Published: February 2011

Abstract
Carcinoembryonic antigen (CEA) is a tumor marker for the clinical management of colorectal cancer (CRC). The elevated blood levels of CEA are associated with metastasis and poor prognosis in CRC. There is mounting evidence that CEA enhances the metastatic potential of cancer cells. CEA increases the ability of weakly metastatic CRC to colonize the liver and to develop spontaneous hematogeneous liver and lung metastases. CEA expression has also been related with resistance to cytotoxic chemotherapy and to anoikis, a form of apoptosis caused by detachment from cell matrix. Yet the mechanism of CEA mediated metastasis is only partially understood. The TGF-β (transforming growth factor beta) signaling pathway contributes to tumorigenesis by controlling several biological processes, including cell proliferation, differentiation, migration and apoptosis. It has been reported that TGF-β regulates CEA transcription and secretion, however, little is known about the effects of CEA on TGF-β signaling. Aims: Based on the above facts, we focused on the influence of CEA on the TGF-β signaling in both normal cells and colorectal cancer cells. Results: Our preliminary data showed that CEA directly interacted with TGF-β receptors. Overexpression of CEA blocked TGF-β induced SMAD3 phosphorylation, SMAD3 translocation to nuclear and the downregulation of c-myc transcription. Targeting CEA with anti-CEA antibody rescued TGF-β response in CRC cell lines with elevated CEA expression, thereby restoring the inhibitory effects of TGF-β on the proliferation of these cancer cells. Finally, in animal experiment, we found that CEA enhanced survival of colorectal cancer cell in both local colonization and liver metastasis. Conclusion: Since CEA is a well-characterized tumor-associated antigen that is frequently overexpressed in tumors, specific antibodies targeting CEA have been developed as a novel therapeutic approach for treatment of tumors expressing CEA on their surface. Based on our study, it may be helpful to combine CEA antibody and TGF-β to inhibit cancer cell proliferation and metastasis in some cases.
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 1491.
Abstract 1493: High-resolution comparative genomic hybridization of preneoplastic and invasive esophageal squamous cell carcinoma: Identification of the earliest preneoplastic changes
Authors: Killian Jonathan Keith , Roth Mark J. , Singh Parvati D. , Walker Robert , Zhu Jack , Suuriniemi Miia , Chen Yidong , Wang Guo-Qing , Hu Nan , Taylor Philip R. , Qiao You-Lin , Dawsey Sanford M. , Meltzer Paul S. 
Published: February 2011

Abstract
Background: Esophageal cancer causes &gt; 400,000 deaths/year in the world. Clinically useful early detection methods must identify these cancers and their precursor lesions at more curable stages. We conducted comparative genomic hybridization analyses of preneoplastic and invasive esophageal squamous cell carcinoma to look for gene copy number patterns that might be useful as early detection markers. The current effort focuses on aberrations associated with mild squamous dysplasia, the earliest histologic form of squamous preneoplasia.
Methods: DNA was extracted from either biopsies or surgical resections from 122 esophageal tissues spanning a spectrum including normal mucosa, squamous preneoplasia, and invasive squamous cell carcinoma. High-resolution micro-array based comparative genomic hybridization (Agilent) was used to measure regions of chromosomal gain or loss with an emphasis on identifying changes associated with the transition from normal to mild dysplasia.
Results: Chromosomal number aberrations were identified that involve several chromosomes, occur early in the neoplastic process, and progress with disease severity. Specific chromosomal number aberrations associated with mild squamous dysplasia, the earliest form of squamous preneoplasia, were uniquely identified.
Conclusions: Comparative genomic hybridization identifies patterns of chromosomal number aberrations that may distinguish patients with and without high-grade squamous dysplasia or cancer. The current effort also identifies specific changes associated with mild squamous dysplasia, the earliest form of preneoplasia, and this may help elucidate mechanisms related to the initiation of carcinogenesis.
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 1493.
Abstract 1498: The combination of immunosuppression and carrier cells significantly enhances poxvirus delivery and the efficacy of its oncolytic virotherapy in the pre-immunized host
Authors: Guo Zongsheng , Thirunavukkarasu Prag , Parimi Vamsi , O'Malley Mark E. , Austin Frances , Sathaiah Magesh , Bartlett David L. 
Published: February 2011

Abstract
The pre-existing anti-poxvirus immunity in cancer patients presents a hurdle to successful poxvirus-mediated oncolytic virotherapy. To overcome this hurdle, we have explored strategies of immunosuppression (IS) or/and immune evasion (IE) for successful delivery of an oncolytic vaccinia virus to tumor models in mice pre-vaccinated with a poxvirus. These include transient IS using a cocktail of three immunosuppressive drugs (IS drugs) (tacrolimus, mycophenolate mofetil and methylprednisolone sodium succinate) that have been used in organ transplant, carrier cells as a means of IE, or the combined strategy. The three drug cocktail, which targeted multiple components of innate and adaptive immunity, displayed no enhancing effects on viral infection in tumor tissue in the pre-immunized host. Using B cell knockout mice, we confirmed that B cells and the neutralizing antibodies, the later of which were not targeted by the drug cocktail, played a significant role in preventing poxvirus infection. Cancer cells as carrier cells alone were not effective to deliver the virus to tumor. Instead, the application of both IS drugs and carrier cells worked synergistically to promote the delivery to, viral infection, replication and spread inside the tumor mass and thus enhanced the efficacy of oncolytic virotherapy in an ovarian carcinomatosis model. The administraton of these IS drugs led to facilitated development of tumor-associated macrophages (TAMs) into immunosuppressive M2 phenotype (IL-10hi/IL-12low) in the tumor microenvironment. These results revealed a novel mechanism for induction of the immunosuppressive tumor microenvironment by the IS drugs, and demonstrated in principle that it is feasible to treat pre-vaccinated cancer patients with an oncolytic poxvirus when combined with both IS and IE strategies.
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 1498.
Abstract 15: Targeting cancer stem cells and vasculature by a novel anti-delta-like 4 ligand (DLL4) antibody inhibits triple-negative breast cancer tumor growth and delays tumor recurrence
Authors: Yen Wan-Ching , Fischer Marcus , Lewicki John , Gurney Austin , Hoey Timothy 
Published: February 2011

Abstract
Triple negative breast cancer (TNBC, ER−, PR− Her2−) accounts for about 10% of all types of breast cancer and is known to particularly aggressive and refractory to current therapies. Chemotherapeutic agents, such as taxanes, are currently the only treatment option for this type of breast cancer, however, these treatments often result in high rates of local and systemic relapse. It has been suggested that cancer stem cells drive tumor growth and progression and are preferentially resistant to many current therapies. Delta-like 4 ligand (DLL4) is an important component of the Notch signaling pathway which is known to mediate stem cell self-renewal and vascular development. We hypothesized that targeting cancer stem cells and the tumor vasculature by interfering with the DLL4/Notch pathway will improve treatment outcome. We developed anti-DLL4 antibodies that recognize either the human or murine protein and have potent binding and antagonist activities. We used these antibodies to investigate the role of DLL4 in triple negative breast cancer and to probe the mechanism in tumor and stromal cells in xenograft models derived from primary breast tumors. These studies showed that anti-DLL4 was efficacious as a single agent and in combination with paclitaxel (Taxol) against TNBC xenograft tumors. Gene expression analysis showed that anti-DLL4 affected vascular-related genes in the stroma and Notch target genes in the tumor and stroma. Inclusion of anti-DLL4 delayed breast tumor recurrence and decreased the growth rate of recurrent tumors following termination of paclitaxel treatment. Flow cytometric analysis showed that ESA+/CD44+/CD24low expressing breast cancer stem cells, BrCSC, were enriched followed by paclitaxel treatment, whereas the combination of anti-DLL4 and paclitaxel reversed paclitaxel-induced increase in this cell population. Further analysis indicated that blocking DLL4 signaling in tumor cells by anti-human DLL4 delayed tumor recurrence and decreased ESA+/CD44+/CD24low expressing BrCSC fraction and tumorigenic potential, whereas blocking DLL4 in host stroma and endothelial cells by anti-mouse DLL4 interfered with angiogenesis. The combination of both antibodies produced an additive effect. Our findings provide a rationale for targeting cancer stem cells and tumor vasculature through inhibition of the DLL4/Notch signaling for TNBC treatment.
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 15.
Abstract 1500: Modulation of recombinant vaccinia virus vector immunogenicity
Authors: Raafat Nermin , Mengus Chantal , Heberer Michael , Spagnoli Giulio C. , Zajac Paul 
Published: February 2011

Abstract
Recombinant poxviruses expressing tumor associated antigens (TAAs) are evaluated since 20 years as immunogenic vaccine vector in clinical trials. Possible limitation to recombinant viral vector is due to either prior systemic immunity to poxviruses or immunodominance of viral antigens which may reduce the induction of immune response against weaker tumor antigens. To address this issue, we developed a recombinant Vaccinia virus expressing HSV type I protein ICP47. This protein down-regulates MHC class-I antigen presentation by blocking the transporter associated with antigen processing (TAP), which translocates peptides, generated by proteasomal protein degradation, into the endoplasmic reticulum for loading onto MHC class I molecule.
Herpes simplex virus (HSV) US12 gene, coding for infected cell protein 47 (ICP47) was introduced into wild type vaccinia virus and into a r.VV expressing MART-1/Melan-A27–35 HLA-A201 endoplasmic reticulum (ER)-targeted epitope. Following infection with non-replicating recombinant virus, effect of ICP47 expression on cell surface MHC-class-I, MHC class-II and co-stimulatory molecules was characterized by antibody staining and FACS analysis. Human T-lymphocytes were stimulated in vitro with autologous CD14+ cells infected with r.VV-US12, r.VV-Mart-US12 or control virus. Responsiveness of specific CD8+ and CD4+ to viral proteins and recombinant epitopes were monitored by MHC-multimer staining and interferon gamma (IFNg) expression analysis.
Cells infected with HSV-US12-r.VV, demonstrated a decreased ability of presenting MHC class-I antigens to CD8+ T cells whereas MHC-class-II restricted presentation to CD4+ T cells remained unaffected. Co-expression of ER-Melan-A/Mart-126–35 appeared to partially compensate for the ICP47 related surface MHC class-I molecule down-regulation and preserve a strong capacity to induce CTL response against the TAA derived peptide.
Thus, viral vectors expressing ICP47 confirmed a diminished TAP-dependant processing of endogenous class-I restricted epitopes while the immunogenic potential of recombinant epitopes directly targeted to the ER was enhanced. Such reagents could become of high relevance especially in multiple-boost vaccine protocol required in cancer immunotherapy.
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 1500.