bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3925: Optical coherence tomography imaging in cancer research.
Authors: Vakoc Benjamin J. , Fukumura Dai , Padera Timothy P. , Jain Rakesh K. , Bouma Brett E. 
Published: August 2014

Abstract
Optical coherence tomography (OCT) is an established imaging technology with a greater than 10 year history in the clinic. Over the past 5 years, an increasing number of cancer investigators have employed OCT in preclinical studies and have found that its unique capabilities address some of the gaps left by existing intravital imaging approaches. However, because OCT is relatively new to the cancer research community, these capabilities and limitations are not broadly known. Therefore, to facilitate translation, we will summarize OCT to the cancer research community. This will include a description of how it works, what its capabilities are, and what its role in preclinical cancer research is now and what it is likely to become over the next decade.
The basic principles of OCT will be summarized to allow investigators to compare it with alternative imaging technologies and identify investigations where OCT is best suited. The imaging modes of OCT will be described and examples of use in cancer investigations will be given. The use of OCT for angiography at spatial and temporal scales not accessible to other technologies will be described. We will also present anatomical imaging of tumors using OCT and highlight its ability to assess tumor volume and to map tumor viability. Finally, the advantages of OCT-based label-free lymphangiography will be described and compared with existing approaches for lymphatic vessel imaging.
We will end our discussion by communicating briefly some of the innovations in OCT that are happening now in research and engineering laboratories and the new capabilities that such innovations are likely to enable. Through this presentation, we hope to establish dialogues to drive technology development toward answering critical problems in cancer research.
Citation Format: Benjamin J. Vakoc, Dai Fukumura, Timothy P. Padera, Rakesh K. Jain, Brett E. Bouma. Optical coherence tomography imaging in cancer research. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3925. doi:10.1158/1538-7445.AM2013-3925
Abstract 393: Clinical impact of pentraxin family expression on prognosis in pancreatic carcinoma.
Authors: Kondo Shunsuke , Ueno Hideki , Morizane Chigusa , Hosoi Hiroko , Koizumi Fumiaki , Tamura Kenji , Okusaka Takuji 
Published: August 2014

Abstract
Background: Inflammatory mediators may play decisive roles at different stages of tumor development. PTX3, a mediator that is a member of the pentraxin family, may be a biomarker for the early prognostic stratification of advanced pancreatic carcinoma patients.
Methods: Enzyme-linked immunosorbent assay and cellular migration assay were performed to determine PTX3 concentrations in pancreatic carcinoma cell lines (ASPC-1, BXPC-3, MIAPACA-2 and PANC-1) PTX3 levels and other inflammatory mediators (IL-1beta, IL-6, CCL2, CCL3, CCL4, CCL7, CXCL9, and MIF) were validated in a subgroup of pancreatic carcinoma patients. Univariate and multivariate Cox analysis were performed to investigate the extent of PTX3 production in the cell lines and the differences in outcomes between patients with high and low levels of inflammatory mediators, who had been divided into high and low groups based on mean values.
Results: In two cell lines (MIAPACA-2 and PANC-1), elevated PTX3 production was observed. A direct relationship was identified between migration activity and PTX3 level. In pancreatic carcinoma patients, median PFS was 76 days (95% confidence interval [CI], 43-109) in the PTX3high group and 150 days (95% CI, 131-197; P = 0.002) in the PTX3low group. Median OS was 117 days (95% CI, 82-152) in the PTX3high group and 357 days (95% CI, 239-475) in the PTX3low group (P &lt; 0.001). Univariate and multivariate Cox model analysis of the pancreatic carcinoma clinical specimens revealed a strong correlation between pentraxin family member expression and PFS as well as OS. Examination of the relationship between PTX3 expression and the expression of other pro-inflammatory mediators indicated that PTX3 level is positively correlated with level of CRP, IL-6, and MIF.
Conclusion: Thus, pentraxin family member, especially PTX3, is a promising biomarker for the prognosis of pancreatic carcinoma, and its expression can promote pancreatic carcinoma progression.
Citation Format: Shunsuke Kondo, Hideki Ueno, Chigusa Morizane, Hiroko Hosoi, Fumiaki Koizumi, Kenji Tamura, Takuji Okusaka. Clinical impact of pentraxin family expression on prognosis in pancreatic carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 393. doi:10.1158/1538-7445.AM2013-393
Abstract 3935: AnnexinA2 regulates invasion and metastasis of pancreatic ductal adenocarcinoma through Semaphorin3d.
Authors: Foley Kelly , Zhou Donger , Xiao Qian , Rucki Agnieszka , Mo Guanglan , Huang Lanqing , Maitra Anirban , Jaffee Elizabeth , Zheng Lei 
Published: August 2014

Abstract
Pancreatic ductal adenocarcinoma (PDA), a devastating disease with a median survival of less than six months, is characterized by its high metastatic ability and a lack of effective therapies. The mechanisms involved in promoting metastasis of PDA have yet to be elucidated. We recently identified AnnexinA2 (AnxA2) as a PDA-associated antigen. Tyr23 phosphorylated AnxA2 promotes metastasis of PDA cells, while shRNA knockdown, knockout or therapeutic inhibition of AnxA2 prevents metastasis to the liver in a mouse model.
To identify downstream mediators of AnxA2 signaling, we evaluated gene expression differences in cell lines derived from the primary tumors of mice that express AnxA2 (KPC) and are metastatic or lack AnxA2 expression (KPCA) and are unable to metastasize. Using microarray analysis, we observed that expression of the ligand-receptor pair Semaphorin3d (Sema3d) and PlexinD1 (PlxnD1) was significantly down regulated in the non-metastatic KPCA cells. Sema3d and PlxnD1 were first identified as axon guidance genes. However, recently, axon guidance genes, including Sema3d and PlxnD1, were recently found by the International Cancer Genome Consortium to be among the cellular pathways that are most frequently altered by genetic mutations and amplification in human PDA (Biankin 2012). Therefore, we hypothesized that AnxA2 interacts with Sema3d and PlxnD1 in PDA to induce metastasis.
We confirmed by RT-PCR and immunofluorescence analysis in multiple independent tumors from KPC and KPCA mice that Sema3d and PlxnD1 expression is down regulated in the absence of AnxA2 expression. AnxA2, Sema3d and PlxnD1 colocalize at the cell surface during pancreatic tumor development when AnxA2 is expressed. Interestingly, co-immunoprecipitation analysis demonstrated a direct interaction between Sema3d and AnxA2 in PDA cells supporting our hypothesis that AnxA2 regulates the secretion of Sema3d from PDA cells to enable its paracrine interaction with PlxnD1 resulting in invasion of PDA cells.
Clinically, we have found that Sema3d expression correlates with increased lymphovascular invasion, increased perineural invasion, poor survival and increased metastatic potential in human PDA patients. Therefore, understanding the pathways that lead to metastasis of PDA will enable the development of more effective therapeutics and better clinical outcomes.
Citation Format: Kelly Foley, Donger Zhou, Qian Xiao, Agnieszka Rucki, Guanglan Mo, Lanqing Huang, Anirban Maitra, Elizabeth Jaffee, Lei Zheng. AnnexinA2 regulates invasion and metastasis of pancreatic ductal adenocarcinoma through Semaphorin3d. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3935. doi:10.1158/1538-7445.AM2013-3935
Abstract 3937: Collagen prolyl hydroxylases are essential for breast cancer metastasis.
Authors: Gilkes Daniele M. , Chaturvedi Pallavi , Bajpai Saumendra , Hubbi Maimon , Wirtz Denis , Semenza Gregg 
Published: August 2014

Abstract
Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix in the metastatic process may lead to the development of improved therapies to treat cancer patients. Intratumoral hypoxia is found in the majority of breast cancers and is associated with an increased risk of metastasis and patient mortality. Here we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced cancer cell invasion and metastasis to lymph nodes and lungs. We establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and evaluate the novel use of ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, which decreases tumor fibrosis and metastasis in a mouse model of breast cancer.
Citation Format: Daniele M. Gilkes, Pallavi Chaturvedi, Saumendra Bajpai, Maimon Hubbi, Denis Wirtz, Gregg Semenza. Collagen prolyl hydroxylases are essential for breast cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3937. doi:10.1158/1538-7445.AM2013-3937
Abstract 3949: Hypoxia induces the conversion of tumor initiating cells from stationary to invasive by promoting cell surface trafficking of matrix metalloproteinase-14.
Authors: Cao Jian 
Published: August 2014

Abstract
Emerging experimental and clinical evidence has demonstrated that quiescent, stationary tumor initiating cells (TICs) can become invasive and metastatic. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. A better understanding of this conversion is crucial for the design of inhibitors aimed at preventing cancer metastasis. We report here for the first time that hypoxia, a low oxygen environment that often occurs in solid tumors, induces translocation of the membrane anchored protease, matrix metalloproteinase-14 (MMP-14) from the cytoplasmic storage pool to the cell surface resulting in conversion of stationary TICs to invasive TICs. Exposure of minimally invasive breast cancer TICs, SK-3rd, that displays CD44high/CD24low with high mammosphere-forming and tumorigenic capacities, to hypoxic conditions (1% O2) results in markedly enhanced cell invasive ability. This phenotypic change is also observed in SK-3rd TICs in the presence of cobalt chloride (CoCl2), an agent that mimics hypoxia. Given the role of MMP-14 in cancer invasion/metastasis, we explored a possible involvement of MMP-14 in hypoxia-induced TIC invasion. Silencing of MMP-14 by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. When SK-3rd cells were cultured under hypoxic conditions, MMP-14 redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MMP-14. Interestingly, cell surface MMP-14 gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MMP-14 in cytoplasmic storage pools under normoxic conditions. We demonstrated a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MMP-14 expression in SK-3rd TICs. These observations suggest that MMP-14 is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis.
Citation Format: Jian Cao. Hypoxia induces the conversion of tumor initiating cells from stationary to invasive by promoting cell surface trafficking of matrix metalloproteinase-14. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3949. doi:10.1158/1538-7445.AM2013-3949
Abstract 3964: Appropriate conditioning of CD4+T cells for antitumor immunotherapy.
Authors: Tanaka Tomohiro 
Published: August 2014

Abstract
It is now evident that lymphodepleting cytotoxic regimens augment antitumor immunity. We and others have demonstrated that transfer of naïve T cells after sublethal whole body irradiation induces antitumor effector T cells and inhibits tumor progression. We recently reported that CD4+CD25+Foxp3+ regulatory T cells (Treg) largely increased after whole body irradiation and suppressed the development of antitumor immune responses during recovery from lymphopenia. Depletion of these radio-resistant Treg following lymphodepletion significantly enhanced antitumor immunity (Baba J, et al. 2012, Blood). The combination of lymphodepletion and transfer of naïve T cells seems to be a promising approach for antitumor immunotherapy. But harvesting sufficient number of T lymphocytes from tumor-bearing patients is difficult. To obtain enough number of T cells that were capable of recognizing tumor-antigens, we expanded naïve T cells in vitro with culturing in CM containing several cytokines. CD4 or CD8 T cells from naïve spleens were activated with immobilized anti-CD3 mAbs for 2 days. Stimulated cells were maintained in CM with the combination of IL-2 (16 U/ml), IL-7 (10 ng/ml), IL-15 (10 ng/ml) and IL-23 (2 ng/ml) for additional 7 days. TCR-Vβ expressions of cultured T cells revealed that they maintained TCR diversity. To evaluate antitumor effects of these cells, mice were irradiated with 500 cGy to deplete lymphocytes and were transferred i.v. with the cultured T cells (4 x 107). On the same day, mice were inoculated s.c. with MCA205 tumor cells (1 x 105). We found that expanded CD4+ T cells mediated regression of s.c. tumors. In contrast, CD8+ T cells alone did not have therapeutic effects even combined with depletion of Treg. Next, we examined T cells proliferation by labeling with the CFSE and evaluated IFN-γ production after stimulation with specific tumor cells. Cultured CD4+ T cells proliferated rapidly and developed into tumor-specific effector T cells after transfer into lymphopenic hosts. Because CD4+ T cells from OT-II mice, that recognize Ovalbumin peptide specifically, did not show any antitumor effects after transfer into lymphopenic mice, this antitumor activity of CD4+ T cells is more likely to be tumor-antigen specific. Interestingly, using irradiated Rag-2 knockout mice as recipient abrogated antitumor effects of transferred cultured CD4+ T cells. Our results indicated that the combination of lymphodepletion and transfer of in vitro expanded CD4+ T cells has a potent antitumor efficacy, and recipient cells from irradiated hosts play a role in this treatment model.
Citation Format: Tomohiro Tanaka. Appropriate conditioning of CD4+ T cells for antitumor immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3964. doi:10.1158/1538-7445.AM2013-3964
Abstract 3966: Development of a fully-human chimeric antigen receptor against PSCA for the treatment of pancreatic cancer.
Authors: Abate-Daga Daniel , Lagisetty Kiran H. , Gattinoni Luca , Yu Zhiya , Restifo Nicholas P. , Rosenberg Steven A. , Morgan Richard A. 
Published: August 2014

Abstract
Pancreatic cancer represents the fourth leading cause of cancer-related death in developed countries. Despite remarkable advances in the understanding of its molecular pathophysiology, treatment options remain scarce, highlighting the need for novel therapies. Adoptive cell transfer (ACT) of lymphocytes engineered ex vivo to express chimeric antigen receptors (CAR) has come of age as a safe and clinically efficacious treatment for advanced cancers.
We sought to develop a CAR specific for prostate stem cell antigen (PSCA), a glycoprotein with restricted expression in normal tissues that is over-expressed in pancreatic cancer cells starting at early stages of malignant transformation.
In order to establish the optimal CAR design, we generated constructs containing antigen-recognition domains derived from mouse or human antibodies, and intracellular domains containing one or two co-stimulatory domains, in addition to CD3zeta. We compared multiple constructs and found that a CAR based on human monoclonal antibody Ha1-4.117 had greater reactivity in vitro. Using a murine model of ACT we observed that CAR-engineered human lymphocytes induced an antitumor effect on HPAC xenografts. Interestingly, unlike what has been described for other CARs, a second generation PSCA CAR (containing CD28 signaling domain) induced a more potent antitumor effect than its third generation counterpart (containing CD28 and 41BB domains).
Our results provide evidence to support PSCA as a target antigen for immunotherapy of pancreatic cancer, using adoptively transferred autologous lymphocytes engineered to express an Ha1-4.117-based CAR.
Citation Format: Daniel Abate-Daga, Kiran H. Lagisetty, Luca Gattinoni, Zhiya Yu, Nicholas P. Restifo, Steven A. Rosenberg, Richard A. Morgan. Development of a fully-human chimeric antigen receptor against PSCA for the treatment of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3966. doi:10.1158/1538-7445.AM2013-3966
Abstract 397: Increased Rho GTPase and reduced glycolysis activity in metastatic cancer cells.
Authors: Su Pei-Fen , Chang Shu-Hao , Ho Chia-Hsin , Huang Wei-Li 
Published: August 2014

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. Metastases are resistant to conventional therapies and are responsible for 90% of tumour-related death. Better understanding on the molecular mechanism of metastasis may shed light on prevention and treatment of disease. We have established a systemic cellular model for metastases investigation. The parental SAS cells, a low tumorigenic HNSCC cell line; SASVO3 (VO3) cells, a highly tumorigenic cells derived from SAS; and SASVO3M-1 (M1) and SASVO3M-5 (M5) cells, two lines of pulmonary metastatic cells derived from SASVO3 cells using mice model. Transcriptome analysis revealed that M1 and M5 shared the most similar transcription signature and their common genes were designated common M. The profiles of VO3 and common M were distinct from that of parental SAS. Biological pathway analyses showed the signaling of cell movement such as integrin, RhoA, Cdc42, Rac, and actin polymerization were identified in metastatic cells. Of oncogenic properties, metastatic cells possess increased activities of foci formation, filopodia formation, wound healing, and in vivo pulmonary metastases. Interestingly, metabolism assay revealed that the glycolysis activity was increased in highly tumorigenic VO3 cells compare to parental SAS. Yet it was decreased in metastatic M5 cells compared to VO3 cells. “Reverse Warburg effect," which indicating a lowered glycolysis in tumor cells, has been demonstrated by others in metastatic breast cancer by in situ immunohistochemistry stain. The correlation of metabolism and metastasis of HNSCC cells will be discussed.
Citation Format: Pei-Fen Su, Shu-Hao Chang, Chia-Hsin Ho, Wei-Li Huang. Increased Rho GTPase and reduced glycolysis activity in metastatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 397. doi:10.1158/1538-7445.AM2013-397
Abstract 3982: Immuno-sensitization of malignant gliomas by natural polyphenols.
Authors: Mandalaparty Chandramouli , Huang Andrew , Mittal Sandeep , Rimando Agnes M. , Dou Q. Ping , Parajuli Prahlad 
Published: August 2014

Abstract
Malignant gliomas are the most common primary brain tumors with approximately 22,000 cases per year. In spite of aggressive surgery, radiotherapy and chemotherapeutic regimens, the median survival of patients with malignant gliomas is a dismal 15 months. The objective of our study was to explore the adjuvant therapeutic potential and associated molecular mechanisms of natural polyphenols stilbenes in malignant gliomas. Recent studies have demonstrated the efficacy of stilbenes in extracranial tumor models. Stilbenes, including resveratrol, were bioavailable in the brain even after low dose oral administration and there was no toxicity to normal tissue. On the contrary, these compounds were found to be neuroprotective in Alzheimer's disease models. Mechanistically, stilbenes modulate NF-κB, STAT3, wnt/β-catenin signaling and also inhibits antiapoptotic protein Bcl-xl. While these molecules are critical in imparting chemoresistance, they are also pivotal in inducing immune-resistance and pro-tumor immune infiltration in gliomas. We hypothesized that stilbenes enhance the efficacy of chemotherapy while also inhibiting immune-suppression and -resistance in malignant gliomas via overlapping molecular mechanisms. We observed significant positive interaction between Temozolomide and Resveratrol for inhibition of glioma proliferation. Resveratrol induced apoptosis in gliomas via inhibition of Bcl-2 and Bcl-xl, while STAT3 activity was also inhibited. Importantly, Resveratrol significantly enhanced the expression of TRAIL-R2 and MIC A/B in gliomas, making them vulnerable to lysis by CTLs and NK cells. Studies are underway to determine combined effect of DC-based immunotherapy and stilbenes against malignant gliomas using syngeneic, orthotopic mouse glioma models. The results can have significant impact in developing novel adjuvant studies to improve survival in patients with malignant gliomas.
Citation Format: Chandramouli Mandalaparty, Andrew Huang, Sandeep Mittal, Agnes M. Rimando, Q. Ping Dou, Prahlad Parajuli. Immuno-sensitization of malignant gliomas by natural polyphenols. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3982. doi:10.1158/1538-7445.AM2013-3982