bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3487: Distant delivery of glioma-restricted oncolytic adenovirus loaded into a neural stem cell-based carrier prolongs the survival of animals with human glioblastoma
Authors: Ahmed Atique U. , Thaci Bart , Tobias Alex , Alexiades Nikita G. , Han Yu , Ulasov Ilya I. , Aboody Karen , Lesniak Maciej S. 
Published: August 2012

Abstract
Despite recent advancements in the treatment of brain tumors, the prognosis for patients with malignant glioblastoma (GBM) still remains poor due to the invasive nature of these tumors. In this context, our lab and others have investigated the unique inherent tumor tropic properties of neural stem cells (NSCs) as a novel platform for the targeted delivery of oncolytic adenovirus for anti-glioma therapy. NSCs hold great promise for glioma therapy because of their inherent ability to target satellite tumor foci throughout the brain. In this study, we report that the infection/loading of NSCs with oncolytic adenovirus upregulate various chemoattractant receptors such as CXCR4 (10-fold, P=0.0054), VEGFR2 (5-fold, P=0.0143) and significantly enhances glioma specific migration of NSCs both in vitro and in vivo. In a human glioma xenograft animal model, virus loaded NSCs retain a majority of their tumor homing capacity with minimal effect on their viability, and are capable of delivering a therapeutic payload to tumor cells located far from the original implanted site. Moreover, NSC-based cell carriers significantly reduce the non-specific distribution of therapeutic virus in the animal brain. Finally, distance delivery of NSCs-loaded with CRAd-S-pk7, a glioma restricted oncolytic adenovirus, in multiple orthotropic xenograft models of human glioma have shown the ability to inhibit tumor growth and increase median survival by about 38 days (54%) as compared to the animal group treated with the CRAd-S-pk7 alone (P=0.0416). Our data suggest that NSC-based cell carriers have the potential to improve the therapeutic efficacy of anti-glioma virotherapy by not only protecting the therapeutic virus from the host immune system, but also by enhancing targeted delivery of therapeutic virus at disseminated tumor sites.
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 3487. doi:1538-7445.AM2012-3487
Abstract 351: 2-Methoxyestradiol targets RON kinase and FLIP to inhibit epithelial-mesenchymal transition in prostate cancer
Authors: Batth Izhar Singh , Gong Jingjing , Bedolla Roble G. , Weintraub Susan T. , Kumar Addanki Pratap 
Published: August 2012

Abstract
Prostate Cancer (PCA) is the second leading cause of cancer-related deaths among men in the United States. Despite significant progress in our understanding of prostate biology, early detection and treatment, the five-year survival for hormone refractory metastatic prostate cancer (HRPCA) patients is less than 30%. Current therapies targeting PCA are not effective against the metastatic stage. 2-Methoxyestradiol (2-ME2) is a metabolic product of 17-β-estradiol and is found in trace amounts in the body; it has shown anti-tumorigenic properties in multiple cancer models. Previous studies from our lab have shown that 2-ME2 can induce apoptosis in PCA cells by blocking cell cycle progression, and also inhibits PCA growth and progression in TRAMP mice. However, the precise mechanism of action of 2-ME2 has not yet been elucidated. In order to classify the mechanism behind PCA inhibition by 2-ME2, we tested its effectiveness on an array containing genes associated with epithelial-mesenchymal transition (EMT). We identified Recepteur d'Origine Nantais (RON) as one of the most significantly downregulated genes in response to 2-ME2 treatment. RON has been shown to promote cell invasiveness, migration, survivability, and proliferation in many cancers such as breast, colon, lung, and pancreatic. However, very little is known about RON's signaling mechanism in PCA. We've found RON to be highly increased in advanced stage PCA cell lines. RON knockdown shows a concomitant decrease in the expression of FLICE-like inhibitory protein (FLIP). FLIP is an anti-apoptotic protein which prevents death receptor-induced apoptotic signaling. FLIP has been found to promote EMT as well as androgen-independent PCA growth. Stimulation with the RON ligand HGF yielded elevated expression of RON and FLIP in PCA cell lines while treatment with 2-ME2 caused downregulation. Immunoprecipitation experiments showed RON to be associated with the androgen-induced proliferation inhibitor (APRIN) in PCA cells. Our data suggest that RON/FLIP crosstalk plays a role in prostate cancer. Therefore, targeting RON/FLIP signaling could have potential therapeutic benefit for metastatic PCA. Supported by NIH CA 135451 (APK).
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 351. doi:1538-7445.AM2012-351
Abstract 3512: Expanded human regulatory iNKT cells exhibit direct cytotoxicity against hematolymphoid tumor targets
Authors: Luszczek Wioleta , Morales-Tirado Vanessa , van der Merwe Marie , Kudo Ko , Campana Dario , Pillai Asha 
Published: August 2012

Abstract
CD1d-restricted invariant natural killer T (iNKT) cells are rare but potent innate regulatory cells capable of immune modulation via robust production of Th1/Th2 cytokines, as well as tumor immunosurveillance via direct cytotoxicity. Protocols to expand iNKT cells and augment their cytotoxicity would broaden their application in allogeneic transplantation and adjuvant anti-tumor immunotherapy. We have optimized a protocol for ex vivo expansion of highly purified human CD3+CD4negVα24+ iNKT cells from human peripheral blood mononuclear cells (PBMC). PBMCs were stimulated with an iNKT-specific glycolipid (α-GalCer), recombinant IL-2 and IL-7 and sorted to &gt; 98% purity at day 7. Sorted iNKT cells were further expanded in the presence of irradiated allogeneic PBMCs, Vα24-specific TCR stimulation, and low-dose IL-2 and IL-7 for 21 days. This results in roughly 10^3-fold expansion, with peak yields of at day 21-28 of expansion (range 1.5 x 10^5 - 10.6 x 10^6 iNKT cells from 1 x 10^8 - 3.5 x 10^8 starting PBMC). At 28 days, these iNKT cells secrete high levels of IL-13, TNF-α, GM-CSF, and IL-4, moderate IL-2 and IFN-γ in anti-CD2/CD3/CD28 bead-stimulated Luminex supernatant assay. Day 28 expanded iNKT cells are dose-dependent suppressors of sorted autologous CD3+CD8+ effector T cells in 72-hr mixed leukocyte reaction (MLR). Anti-CD2/CD3/CD28 activation of these iNKT cells induced expression of high levels of key cytolytic effector molecules, including granzyme B. We therefore measured cytotoxicity of activated day 28 iNKT cells against various hematolymphoid tumor targets following co-incubation of iNKT cells versus control effector populations with firefly luciferase-transduced RS4:11 and Nalm6 (B-ALL), U937 (monocytic), and K562 (CML) targets. iNKT cell effectors (E) demonstrated dose-dependent cytotoxicity against B-lymphoid tumor targets (T) (e.g.: Nalm6: 37.7% at E:T 2:1, 17.7% at E:T 1:1, 7.7% at E:T 0.5:1), with no significant cytotoxicity against myeloid targets (e.g.: K562: 11.8% at E:T 2:1, 6.7 at E:T 1:1, 1.8 at E:T 0.5:1). Our results indicate that human iNKT cells expressing high levels of Th2 and regulatory cytokines can be potently expanded ex vivo and manifest cytotoxicity against B-ALL targets, supporting their potential application in tailored immunotherapy in the pre- and post-transplant setting.
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 3512. doi:1538-7445.AM2012-3512
Abstract 3534: Human Th17 cells have stem cell-like features and promote long-term tumor immunity
Authors: Kryczek Ilona , Zhao Ende , Liu Yan , Wang Yin , Vatan Linda , Szeliga Wojciech , Moyer Jeffrey , Klimczak Aleksandra , Lange Andrzej , Zou Weiping 
Published: August 2012

Abstract
Th17 cells play a role in multiple pathological scenarios. However, their functional phenotype, survival pattern and the underlying controlling mechanisms are poorly investigated in humans. This significantly hampers clinical application of targeting Th17 cells. Now we have studied Th17 cells in the pathological microenvironments of graft-versus-host disease, ulcerative colitis and cancer in humans. Th17 cells are increased in the chronic phase of these diseases. Th17 cells phenotypically resemble to terminally differentiated memory T cells, but are different from central memory, exhausted and senescent T cells. Despite their phenotypic markers of terminal differentiation, in vivo adoptive transfusing experiments demonstrate that Th17 cells mediate and promote long-term anti-tumor immunity. Furthermore, Th17 cells have important functional features including high capacity of proliferative self-renewal, potent persistence and apoptotic resistance in vivo, and the plasticity of converting into other types of T helper cells. These features are accompanied with relatively specific gene signature in Th17 cells including abundant anti-apoptotic genes. Moreover, we investigated the molecular mechanisms controlling their functional characters. We demonstrate that hypoxia inducible factor (HIF)1α and Notch collaboratively control key anti-apoptosis Bcl-2 family gene expression and function in Th17 cells. Altogether, the data indicate that human Th17 cells may be a long-lived proliferating effector memory T cell population with unique genetic and functional characters. These characters may be important determinants in Th17 cell biology. Targeting Th17-associated signaling pathway would be therapeutically meaningful for treating patients with autoimmune disease and advanced tumor.
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 3534. doi:1538-7445.AM2012-3534
Abstract 3538: The HIF-1α hypoxia response in mouse tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy
Authors: Palazon Asis , Martinez-forero Ivan , Teijeira Alvaro , Morales-Kastresana Aizea , Alfaro Carlos , Sanmamed Miguel Fernandez de , Hervas-Stubbs Sandra , Jure-Kunkel Maria , Aragones Julian , Melero Ignacio 
Published: August 2012

Abstract
The response to hypoxia modulates the expression of multiple genes. The tumor microenvironment of transplanted and spontaneous mouse tumors is profoundly deprived of oxygenation as confirmed by PET imaging. CD8 and CD4 tumor-infiltrating T lymphocytes (TILs) of transplanted colon carcinomas, melanomas and spontaneous breast adenocarcinomas are CD137 (4-1BB) positive, as opposed to their counterparts in tumor draining lymph nodes and spleen. Expression of CD137 on activated T lymphocytes is markedly enhanced by hypoxia and the prolyl-hydroxilase inhibitor DMOG. Importantly, hypoxia does not up-regulate CD137 in inducible HIF-1α knock-out T cells, and such HIF-1α-deficient T cells remain CD137-negative even when becoming TILs, in clear contrast to co-infiltrating HIF-1α-sufficient T cells. The fact that CD137 is selectively expressed on TILs was exploited to confine the effects of immunotherapy with agonist anti-CD137 monoclonal antibodies (mAb) to the tumor tissue, thereby avoiding liver inflammation, while still permitting synergistic therapeutic effects with PD-L1/B7-H1 blockade.
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 3538. doi:1538-7445.AM2012-3538
Abstract 3540: Prostate cancer-infiltrating mast cells suppress anti-tumor immunity through a TGFβ and IL-13 dependent mechanism
Authors: Watkins Stephanie K. , Hurwitz Arthur A. 
Published: August 2012

Abstract
Immune suppression is a major obstacle in the design of successful immune-based therapies for cancer. Using an experimental model of prostate cancer, we previously demonstrated the rapid induction of tolerance and suppressive activity in adoptively transferred tumor antigen-specific cytotoxic T cells. The mechanism of this tolerance induction involved T cell interactions with tumor-associated dendritic cells (TADCs) which express elevated levels of the forkhead box protein, FOXO3. We now propose a mechanism by which tumor-infiltrating mast cells exert immune suppressive activity on both T cells and DCs. Mast cells were identified as approximately 30% of the total CD45+ tumor-infiltrating leukocytes and were capable of degranulation and promoting immune suppression. Purified tumor-associated mast cells (TA-MC) spontaneously secreted IL-13 and TGF-β which were further increased by FcαR cross-linking or LPS stimulation. The suppression of Ag-specific T cells and the development of tolerogenic DC were found to be dependent on TA-MC secretion of TGF-β and IL-13 during in vitro co-culture. Further, blocking IL-13 and TGF-β in vivo prevented the induction of DC tolerogenicity and the induction of T cell tolerance, which, in turn, resulted in reduced tumor burden. Our findings reveal novel mast cell-mediated mechanisms that favor immune tolerance over anti-tumor immunity and therefore provide promising targets for the enhancement of cancer immunotherapy.
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 3540. doi:1538-7445.AM2012-3540
Abstract 3544: Role of tumor-infiltrating gammadelta T lymphocytes in breast cancer
Authors: Ma Chunling , Zhang Qunyuan , Ye Jian , Zhang Yanping , Wevers Eric , Schwartz Theresa , Hunborg Pamela , Vavares Mark A. , Hoft Daniel F. , Hsueh Eddy C. , Peng Guangyong 
Published: August 2012

Abstract
Breast cancer is the second leading cause of cancer-related deaths in women worldwide. Increasing evidence suggests that immunotherapy is a promising strategy for treating breast cancer, and understanding of the roles of different subtypes of tumor-infiltrating lymphocytes (TILs) in the tumor immunosuppressive microenvironment may be essential to cancer treatment and elimination. We recently discovered that enriched gammadelta1 T cell populations in the breast cancer TILs can suppress naïve and effector T cell responses and block the maturation and activities of dendritic cells (DC). In order to investigate the functional role of tumor-infiltrating gammadelta T cells in the immune pathogenesis of breast cancer, we further performed immunohistochemical staining to analyze gammadelta T cells, as well as CD4+, CD8+, IL-17-producing and FoxP3+ T cells in 50 freshly frozen tumor tissues from different stages of identified primary breast cancer and paired normal breast tissues. We found that the numbers of gammadelta T cells among tumor tissues were significantly increased compared with those in normal breast tissues in breast cancer patients. High numbers of gammadelta T cells were present in the patients with high tumor grades and lymph node metastases. Importantly, the patients with a high proportion of gammadelta T cells showed poorer survival rates in comparison to those with a low proportion of gammadelta T cells in breast cancer. These results indicate that gammadelta T cells constitute a dominant population existing in the breast tumor suppressive microenvironment that is negatively associated with clinical outcome, which may be an important cancer immunotherapeutic target for breast 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 3544. doi:1538-7445.AM2012-3544
Abstract 3573: Urine and serum biomarkers as early detection tools for ovarian cancer
Authors: Nolen Brian M. , Lomakin Aleksey , Bast Robert , Lu Karen , Marrangoni Adele , Lokshin Anna E. 
Published: August 2012

Abstract
Background: The measurement of biomarkers present in the bodily fluids of ovarian cancer patients represents an emerging strategy for early detection. To date, a great deal of related work has been devoted to blood, given its systemic exposure and extensive availability through tissue banks. However, blood is a dynamic biofluid with a proteome under continuous metabolic and homeostatic regulation. Alternatively, urine represents a biofluid that is inherently quiescent in that all molecular and proteolytic activity is largely complete upon sampling. Additional characteristics of urine, including its high level of temperature stability and low-complexity matrix resulting from renal filtration, suggest that this biofluid may serve as an effective alternative or companion to blood in biomarker analyses. Methods: A set of urines obtained from over 700 women, including patients diagnosed with ovarian cancer, patients diagnosed with benign pelvic lesions, and healthy donors, was tested for 39 biomarkers which demonstrated previous associations with ovarian cancer. In an effort to identify additional useful biomarkers, 122 candidate biomarkers were evaluated in a separate set of 150 sera obtained from ovarian cancer patients along with benign and healthy controls. Significantly altered biomarkers were identified in each analysis and the full biomarker dataset was examined by multivariate analysis to identify multianalyte panels capable of discriminating ovarian cancer patients from controls with high accuracy. Results: Numerous significantly altered biomarkers were identified in both urine and serum. The classification performance of several biomarkers was found to differ in urine vs. serum with an overall trend in favor of urine biomarkers. Separate urine and serum biomarker panels consisting of 3-4 analytes were identified which could discriminate ovarian cancer from healthy controls at a sensitivity of 96-97% at 95% specificity. Improvement upon this classification efficiency was observed when the best urine and serum biomarkers were combined into a single panel. The combination of urine HE4 and serum CA 125 was most effective in the discrimination of ovarian cancer from benign controls. Conclusions: Urine and serum biomarkers offer complementary information regarding ovarian cancer status. Their combined use may lead to the development of effective early detection tools.
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 3573. doi:1538-7445.AM2012-3573
Abstract 3577: A decade of changed behavior: Trends in screening adherence and incidence 2000-2010
Authors: Clarke Tainya C. , Ocasio Manuel A. , Caban-Martinez Alberto J. , Lee David J. , Arheart Kristopher L. 
Published: August 2012

Abstract
Background: Cancer is still one of the most prominent diseases of all times claiming more than 569,490 lives in 2010. Over the past decade the United States (U.S.), like many other industrialized and developed nations have seen a significant decrease in the incidence of cancers and have experienced an increase in the number of cancer survivors. The decrease in incidence can be attributed to an increase in the number of persons adhering to recommended cancer screenings. In 2012, there will be an estimated 1 million newly diagnosed Americans, 75% of who would have adhered to recommended cancer screening in the previous year. Methods: We used incidence data from the Surveillance Epidemiology and End Results database (2000 -2008) to assess the trend in incidence rates of some of the most common cancers in the United States. Using SAS version 9.2, we pooled data from the National Health Interview Survey (NHIS) - Cancer Supplements (2000, 2005 and 2010) and analyzed adherence to recommended screening (n= 90,959). The guidelines provided by the American Cancer Society were used to guide analyses. Screening compliance was measured among the appropriate age and sex cohort within the U.S. population. Results: There has been a 17.22% decrease in the incidence of colorectal cancers and a11.06% decrease in lung cancer incidence between 2000 and 2008. While Bladder and Cervical cancer showed no significant time trends, gender specific cancers, namely prostate and breast also showed significant decreases; 16.21% and 6.78% respectively. There was an 18.12% increase in the incidence of Melanoma cases. There was a significant increase in adherence to recommended screening between 2000 and 2010. Adherence to mammography screening guidelines increased two fold between 2000 and 2010 as represented by women interviewed in the NHIS. Similar trends were observed for pap smears and colorectal screenings; 2010 analyses showed 70.48% compliance for mammography, 72.80% for colorectal screening and 68.19% for pap smears. Conclusion: Though screening compliance is below the preferred level, there has been an increase in adherence to recommended screening in the U.S. population over the past decade. This has translated into decreased cancer incidence and an increased prevalence as more persons live beyond the five year survivor mark. Identification of cancers with high incidence rates is needed to direct targeted interventions and public health campaigns.
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 3577. doi:1538-7445.AM2012-3577
Abstract 359: Longitudinal monitoring of autotaxin-expressing tumors in vivo using an activatable near-infrared fluorescent probe
Authors: Madan Damian 
Published: August 2012

Abstract
Autotaxin (ATX) and its product lysophosphatidic acid are involved in numerous biological functions that generally involve cell proliferation and motility. Their dysregulation is associated with several diseases, including many cancers, with ATX reportedly being among the forty most upregulated genes in highly metastatic cancers. Until now there have been no methods to visualize or measure the activity of ATX in living organisms. Here, we monitor tumor progression in vivo using ATX-Red, a biosensor that reports on ATX activity. We show that ATX-Red is specifically activated by ATX to fluoresce in the near-infrared, the optimal spectral window for in vivo fluorescence imaging. While minimal fluorescence activation is seen when ATX-Red is administered systemically to healthy mice, ATX-Red is strongly activated in MDA-MB-231 xenografts, which are known to over-express ATX. Longitudinal imaging of mice bearing these xenografts shows that ATX-Red fluorescence correlates with tumor size. Our data demonstrate that ATX-Red is an effective and non-invasive in vivo imaging tool that enables real time visualization and quantitation of ATX-expressing tumor progression.
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 359. doi:1538-7445.AM2012-359