bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B41: Investigating ARID3B regulation of ovarian cancer metastasis
Authors: Gellerman Katrina , Samyesudhas Serene , Joseph Stancy , Dahl Karen Cowden 
Published: August 2014

Abstract
Over 60% of ovarian cancer cases are detected with widespread metastases. In an effort to define the associated molecular mechanisms of metastasis in ovarian cancer, recent findings have implicated a novel DNA-binding protein, ARID3B, as a contributor to ovarian cancer growth and metastasis. We recently demonstrated that increased expression of ARID3B promotes metastatic growth of ovarian cancer cells in a xenograft mouse model. The purpose of this study is to identify target genes of ARID3B, with the goal of elucidating a mechanism for this metastatic support. ChIP-on-chip analysis comparing ovarian cancer cells in the presence and absence of exogenous overexpression of ARID3B revealed a multitude of potential gene targets. These targets have been functionally sorted into 21 distinct groups and among these groups, 21 genes were selected for further analysis. Validation of these targets via RT-PCR has identified c-Myc, a known regulator of metastasis, as a putative target of ARID3B. Our results reveal an increase in c-Myc mRNA levels in response to ARID3B, implicating c-Myc as putative direct target of ARID3B. We used chromatin immunoprecipitation to study the potential interaction of ARID3B with the c-Myc promoter. The specifics of the regulation of c-Myc are currently under investigation. In conjunction with gene regulation, metastasis-associated phenotypes were examined, as well. ARID3B overexpression increases extracellular matrix adhesion and vitronectin haptotaxis. Specifically, we investigated the contribution c-Myc to ARID3B induced adhesion and motility as a means for promoting metastatic progression. We accomplished this via adhesion and haptotaxis assays using ovarian cancer cells exogenously overexpressing ARID3B, followed by siRNA knockdown of c-Myc. Further study will serve to define how ARID3B regulation of c-Myc contributes to ovarian cancer progression. Should c-Myc prove to be a biologically relevant target, ARID3B regulation of c-Myc could represent an important mechanism for the associated advancement of ovarian cancer metastasis.
Citation Format: Katrina Gellerman, Serene Samyesudhas, Stancy Joseph, Karen Cowden Dahl. Investigating ARID3B regulation of ovarian cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B41.
Abstract C74: Temozolomide-perillyl alcohol conjugate is cytotoxic for glioma cancer stem cells
Authors: Jhaveri Niyati , Agasse Fabienne , Hofman Florence M. , Chen Thomas C. 
Published: August 2014

Abstract
Glioblastoma multiforme (GBM), the most malignant glioma, is a highly invasive tumor which is usually fatal within 2 years. The chemotherapeutic agent of choice is temozolomide (TMZ); however glioma patients inevitably become resistant to TMZ and tumors recur. Tumor recurrence has been associated with highly invasive, chemoresistant cancer stem cells (CSC) which is resistant to TMZ. We have constructed a new chemical entity by conjugating TMZ to perillyl alcohol (POH) via a carbamate bond. This compound, TMZ-POH, contains POH, a naturally occurring monoterpene that reduces tumor cell migration and has anti-tumor properties against gliomas as well as other cancers. In the studies presented here we demonstrate that TMZ-POH is cytotoxic to CSCs without affecting normal stem cells. The mechanism of TMZ-POH induced cytotoxicity is mediated in part through the DNA damage response pathway and apoptosis. Furthermore, the TMZ-POH conjugate is 5 to 10 fold more effective in inducing cell death compared to TMZ, POH or the mixture of these agents. Our data show that TMZ-POH is a promising novel compound directed against cancer stem cells and therefore important for the treatment of drug resistant, recurrent gliomas.
Citation Format: Niyati Jhaveri, Fabienne Agasse, Florence M. Hofman, Thomas C. Chen. Temozolomide-perillyl alcohol conjugate is cytotoxic for glioma cancer stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C74.
Abstract C91: PyVmT luminal and EMT cell lines exhibit characteristic patterns of orthotopic and tail vein metastasis
Authors: Ellies Lesley G. , Kuo Christopher 
Published: August 2014

Abstract
Understanding pathways leading to metastasis remains a primary goal of breast cancer research. Epithelial to mesenchymal transition (EMT) is thought to be critical in this process as tumor cells migrate through the stroma and undergo deformation while passing endothelial cells to enter the circulation. To examine the role of EMT in tumor metastasis, we have developed a number of stable cell lines in polyomavirus middle T (PyVmT) mammary tumors congenic in the C57Bl/6 background. In this study we characterized the metastatic properties of a luminal cell line Py230 and an EMT cell line Py8119, both of which have cancer stem cell properties of self-renewal, differentiation and tumor initiation. Py230 cells form well-differentiated epithelial adenocarcinomas typical of the spontaneous PyVmT model when injected orthotopically. Injection of 1-10 cells at a single site can give rise to 1-2 metastases over a period of approximately 20 weeks, however the number of metastases can be increased and the duration of the experiment reduced, by injecting 106 cells at 4 sites and removing the tumors at 5-6 weeks when they reach 7-8 mm diameter. After an additional 4-5 weeks multiple lung metastases are visible. Multiple lung metastases can also be achieved by tail vein injection of 5 x 105 cells and inflammation plays a role in the growth at this site as a significant reduction in metastasis is observed in mice lacking the inducible nitric oxide synthase. No Py230 tumor metastases are found in other tissues such as liver, kidney or spleen either with orthotopic or tail vein injection. In contrast, Py8119 cells form highly invasive, poorly differentiated claudin low EMT tumors upon injection into the mammary fat pad. The tumors grow rapidly, but excision does not result in lung metastasis despite their highly invasive phenotype, indicating that EMT alone is not sufficient for metastasis from the mammary fat pad. However, when the cells are injected into the tail vein, metastases develop at multiple tissue sites including lung, liver, kidney and spleen. Py8119 cells upregulate markers of EMT including twist, sna1, sna2 and MMP2 in comparison to Py230 cells, but whether Py230 cells undergo transient EMT and MET during metastasis is currently unknown. Additional luminal or EMT cell lines exhibit similar patterns of metastasis to the Py230 and Py8119 cell lines respectively. Since the majority of human breast cancers are luminal and the less frequent claudin low tumors have a poor prognosis, both the Py230 and Py8119 cell lines should be a useful in dissecting pathways of metastasis relevant to human breast cancer.
Citation Format: Lesley G. Ellies, Christopher Kuo. PyVmT luminal and EMT cell lines exhibit characteristic patterns of orthotopic and tail vein metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C91.
Abstract PR10: High angiogenic capacity of inflammatory neutrophils and polarized M2 macrophages is determined by production of MMP-9 unencumbered by its natural inhibitor TIMP-1
Authors: Zajac Ewa , Schweighofer Bernhard , Casar Berta , Kupriyanova Tatyana , Rimann Ivo , Juncker-Jensen Anna , Deryugina Elena , Quigley James P. 
Published: August 2014

Abstract
By delivering a potent matrix metalloproteinase, MMP-9, inflammatory neutrophils and macrophages play an important role in tumor angiogenesis. We have previously demonstrated that high angiogenic capacity of neutrophil MMP-9 (nMMP-9) is determined by its TIMP1-free status. In this study, we compared biochemically and functionally nMMP-9 with the MMP-9 produced by monocytes and macrophages of innate (M0), tumor-suppressing (M1) and tumor-promoting (M2) phenotypes. The angiogenic potential of a specific leukocyte type correlated with amount of TIMP-1 complexed with secreted proMMP-9. Similar to neutrophils, M2-macrophages produce proMMP-9 complexed with very low amounts of TIMP-1, rendering its high angiogenic capacity. In contrast, M0 macrophages and M1-polarized macrophages secrete non-angiogenic proMMP-9 complexed with TIMP-1 at near stoichiometric ratios. However, silencing of TIMP-1 in M0- and M1-macrophages results in induction of their angiogenic potential, thereby supporting a biochemical mechanism for unique angiogenic capacity of proMMP-9 delivered by neutrophils and a distinct subset of pro-tumorigenic macrophages.
This abstract is also presented as Poster B89.
Citation Format: Ewa Zajac, Bernhard Schweighofer, Berta Casar, Tatyana Kupriyanova, Ivo Rimann, Anna Juncker-Jensen, Elena Deryugina, James P. Quigley. High angiogenic capacity of inflammatory neutrophils and polarized M2 macrophages is determined by production of MMP-9 unencumbered by its natural inhibitor TIMP-1. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr PR10.
Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis
Authors: Nelson Erik Russell , Wardell Suzanne E. , Howe Matthew K. , Carver Nicole J. , Umetani Michihisa , McDonnell Donald P. 
Published: August 2014

Abstract
Breast cancer remains the most common cancer and is the second leading cause of cancer death in women. The magnitude of this problem provides strong rationale for studies that may lead to the development of new chemopreventative strategies and/or lifestyle changes that reduce cancer incidence. It is of significance, therefore, that circulating cholesterol has been correlated to the development of breast cancer, and patients taking lipophilic inhibitors of 2-hydroxy-3-methylglutaryl coenzyme A (statins) demonstrate significantly lower breast cancer incidence, and decreased breast cancer recurrence. Therefore, our recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, exerts partial agonist activity on both the estrogen receptors (ERs) and liver X receptors (LXRs) suggests a potential, mechanistic link between hypercholesterolemia and breast cancer incidence. Importantly, the enzyme responsible for the conversion of cholesterol to 27HC (CYP27A1) is primarily expressed in macrophages, and it is well established that tumor infiltrating macrophages are associated with more aggressive tumors and worse patient outcome. Therefore, we initiated a series of studies to determine the impact of 27HC on breast cancer pathophysiology. Here, we demonstrate that (1) macrophage produced 27HC increases breast cancer cell proliferation, (2) elevation of exogenous 27HC increases in vivo tumor growth and lung metastases, and (3) genetic ablation of the enzyme responsible for 27HC synthesis increases latency, and reduces tumor growth and metastasis. Our ongoing work is aimed at identifying the mechanisms responsible for the 27HC induced increase in metastasis. In summary, our data thus far strongly indicate a role for macrophage produced 27HC in breast cancer pathophysiology and metastasis. The results provide additional support for the exploration of potential chemopreventative benefits of lower cholesterol diets, pharmacological inhibitors of HMG-CoA reductase or CYP27A1, and macrophage ablative strategies.
DOD Postdoctoral Award BC085585 (ERN), NIH 5R37DK048807 (DPM).
This abstract is also presented as Poster B50.
Citation Format: Erik Russell Nelson, Suzanne E. Wardell, Matthew K. Howe, Nicole J. Carver, Michihisa Umetani, Donald P. McDonnell. The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr PR3.
Abstract A21: Active immunotherapy with PROSTVAC® demonstrates potent antitumor efficacy in a mouse model of prostate cancer.
Authors: Rountree Ryan B. , Mandl Stefanie J. , Cote Joseph , Cruz Tracy dela , Giffon Thierry , Gordon Evan , Foy Susan P. , Lombardo John R. , Trent Erica , Laus Reiner , Delcayre Alain 
Published: August 2014

Abstract
BN ImmunoTherapeutics (BNIT) specializes in developing novel active immunotherapies for cancer. These therapies use recombinant poxviruses engineered to express tumor-associated antigens (TAAs), with the intent of generating effective immune responses against the patients' cancer. PROSTVAC® is a candidate product for the treatment of prostate cancer for which a global Phase III clinical trial (PROSPECT) was recently initiated. This product is composed of two different viral vectors derived from a recombinant vaccinia virus (PROSTVAC™-V) and a recombinant fowlpox virus (PROSTVAC™-F). Both vectors contain transgenes encoding prostate-specific antigen (PSA) and a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), designated as TRICOM™. Patients are immunized using a prime-boost strategy consisting of an initial treatment with PROSTVAC™-V followed by repeated boosting with PROSTVAC™-F to maximize the immune responses against the PSA tumor-antigen.
Here we show preclinical data characterizing PROSTVAC® activity in mice. Treatment with either PROSTVAC™-V or PROSTVAC™-F induced PSA-specific antibody and T cell responses; however, PSA-specific responses were further increased by the prime/boost strategy, particularly with respect to the frequency of responding CD8 T cells. These CD8 T cells produced IFN-gamma and degranulated in an antigen-specific manner. Furthermore, PROSTVAC® treatment resulted in strong efficacy in a mouse model of prostate cancer. In this model, treatment with PROSTVAC resulted in anti-tumor efficacy accompanied by a Th1-biased response against PSA. In contrast, growth of tumors in control mice induced only non-protective PSA-specific responses with strong Th2 bias.
Overall, these animal studies help define the activity and mechanism of action of PROSTVAC® which is currently being evaluated in the clinic.
R.B. Rountree and S.J. Mandl contributed equally to this work.
Citation Format: Ryan B. Rountree, Stefanie J. Mandl, Joseph Cote, Tracy dela Cruz, Thierry Giffon, Evan Gordon, Susan P. Foy, John R. Lombardo, Erica Trent, Reiner Laus, Alain Delcayre. Active immunotherapy with PROSTVAC® demonstrates potent antitumor efficacy in a mouse model of prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A21.
Abstract A33: Combination immunotherapy with anti-CD40 mAb and MPL results in T cell-independent antitumor effects against B16 melanoma in mice.
Authors: Voort Tyler Van De , Sondel Paul , Felder Mildred , Young Richard , Kalogriopoulos Nicholas , Rakhmilevich Alexander 
Published: August 2014

Abstract
Combination immunotherapies are promising candidates for clinical testing. In this study, monophosphoryl lipid A (MPL), a nontoxic derivative of LPS and agonist of Toll-like receptor (TLR) 4, was tested in combination with an agonistic anti-CD40 monoclonal antibody (anti-CD40) to assess the antitumor synergy between the two agents. We show that anti-CD40 is capable of priming mouse macrophages for subsequent ex vivo activation by MPL to an extent comparable to a TLR9 agonist, CpG. When given intratumorally (i.t.) to C57BL/6 mice bearing subcutaneous B16 melanoma, anti-CD40 and MPL induced synergistic antitumor effects. When administered i.t. into a primary tumor, anti-CD40 and MPL also slowed the growth of a secondary tumor growing simultaneously at a distant site in both immunocompetent mice and mice depleted of T cells. Taken together, our results show that the antitumor effects of anti-CD40 are enhanced by subsequent treatment with MPL, even in T cell-deficient hosts. These data suggest that anti-CD40+MPL could be a clinically promising immunotherapy for immunosuppressed cancer patients.
Citation Format: Tyler Van De Voort, Paul Sondel, Mildred Felder, Richard Young, Nicholas Kalogriopoulos, Alexander Rakhmilevich. Combination immunotherapy with anti-CD40 mAb and MPL results in T cell-independent antitumor effects against B16 melanoma in mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A33.
Abstract A36: Treatment of established dermal murine B16F10 melanoma with an attenuated Toxoplasma gondii eliminates the treated tumor and stimulates systemic antitumor immunity.
Authors: Fiering Steven , Baird Jason R. , Byrne Katelyn , Lizotte Patrick , Mullins David , Jo turk Mary 
Published: August 2014

Abstract
While the surgical removal of dermal melanoma cures that lesion, it does nothing to stimulate antitumor immunity that could potentially identify and eliminate occult metastatic disease. An immune based treatment that eliminates the primary dermal melanoma could also potentially generate systemic immunity that will protect against metastatic disease. We have utilized an attenuated strain of Toxoplasma gondii (cps) to break tumor-mediated immunosuppression, stimulate an antitumor immune response that eliminates the dermal tumor, and generate systemic antitumor immunity that leads to rejection of subsequent dermal or intravenous challenges with B16F10. T. gondii is an obligate intracellular eukaryotic parasite that infects virtually any mammalian species. The cps strain is a uracil auxotroph that can be grown in vitro but is unable to replicate in vivo. Despite its lack of infectivity, it enters cells and stimulates a strong T-cell mediated immune response characterized by long lasted CD8 effector cells. The presence of cps in the tumor microenvironment modifies the phenotype of tumor infiltrating leukocytes, and along with the expected anti-Toxoplasma immune response there is antigen-spreading so that tumor antigens are responded to and the immune system recognizes subsequent tumor challenges when there is no associated cps. The treatment requires CD8 and NK cells for efficacy but does not require CD4 cells. The treatment also requires that the host express IL-12 and Ifn-g. The treatment requires live cps for efficacy and is effective in mice that are latently infected with another strain of T. gondii, so it could function in the high percentage of humans with latent T. gondii infection and an established immune response against T. gondii.
Citation Format: Steven Fiering, Jason R. Baird, Katelyn Byrne, Patrick Lizotte, David Mullins, Mary Jo turk. Treatment of established dermal murine B16F10 melanoma with an attenuated Toxoplasma gondii eliminates the treated tumor and stimulates systemic antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A36.
Abstract A43: Therapeutic efficacy of antitumor monoclonal antibodies combined with chemotherapy depends on innate immunity and NK1.1- innate lymphoid cells.
Authors: Moskalenko Marina , Pan Michael , Hashimoto Daigo , Mortha Arthur , Bernardo Sebastian G. , Leboeuf Marylene , Houghton Alan , Wolchok Jedd , Burakoff Steven , Merad Miriam , Saenger Yvonne M. 
Published: August 2014

Abstract
Combination regimens incorporating chemotherapy and anti-tumor monoclonal antibodies are in wide clinical use but mechanisms of action are unknown. A better mechanistic understanding would enhance clinical protocols. We treated established melanomas with cyclophosphamide (CY) in combination with an antibody targeting tyrosinase related protein 1 (TRP1), a melanoma differentiation antigen. Therapeutic activity is immune mediated as Fc gamma receptors are required for efficacy. Immune responses can be innate or adaptive and, using Rag 1-/- mice deficient in B and T lymphocytes, we find that the innate immune system is sufficient for tumor clearance. Classic effector cells of the innate immune system include lymphocytes, of which the largest population is NK1.1+ natural killer (NK) cells, and macrophages. NK cells, surprisingly, are not critical as depletion of NK1.1+ cells did not significantly impair anti-tumor effect. In contrast, elimination of non-classical NK1.1- innate lymphocytes, through deletion of the Interleukin 2 (IL2) receptor common gamma chain required for their development, or depletion via antibody targeting pan lymphocyte marker Thy1.2 in Rag 1-/- mice, impairs efficacy of combination therapy. Non-classical NK1.1-Thy1.2+ innate lymphocytes have been implicated in leukocyte infiltration into tissues. We find that depletion of Thy1.2+ cells diminishes entry of Thy 1.2- leukocytes into melanomas treated with chemotherapy and alters the phenotype of infiltrating myeloid cells. Thus, our data highlights a novel role for non-classical innate lymphocytes in the treatment of solid malignancies with monoclonal antibody and chemotherapy.
Citation Format: Marina Moskalenko, Michael Pan, Daigo Hashimoto, Arthur Mortha, Sebastian G. Bernardo, Marylene Leboeuf, Alan Houghton, Jedd Wolchok, Steven Burakoff, Miriam Merad, Yvonne M. Saenger. Therapeutic efficacy of antitumor monoclonal antibodies combined with chemotherapy depends on innate immunity and NK1.1- innate lymphoid cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A43.