tbuckley/cabot-search huggingface dataset:
420. Improvement of Antitumor Activity in Intraperitoneal Ovarian Cancer Model by a Noble Cloned Carrier Cell Infected with Oncolytic Adenovirus
Authors: Katsuyuki Hamada, Kazuko Takagi, Takashi Sugiyama
Journal: Molecular Therapy (2016)

Infection inhibition of virus by antiviral antibodies is one of the major problems that cancer gene therapy has never shown the significant antitumor activity in human clinical trial. Oncolytic adenovirus-infected A549 carrier cells develop cell fragments and exosomes containing oncolytic adenoviral particles and could infect target cancer cells by overcoming antiadenoviral immunogenicity. A549 carrier cells induce complete tumor reduction in syngeneic subcutaneous mouse tumor model by direct antitumor activity of oncolytic adenovirus, antiadenoviral cytotoxic T lymphocyte and antitumor immunity but not in syngeneic intraperitoneal ovarian cancer mouse model. In this study, we cloned and established a noble carrier cell by limiting dilution to induce the complete tumor reduction of the intraperitoneal ovarian tumor by increasing antitumor activity of carrier cells. Oncolytic adenovirus AdE3-midkine driven by midkine promoter and non-replicative adenovirus Ad-mGM-CSF were used in this study. We cloned a nobel carrier cell from EHMK adenocarcinoma cells by limiting dilution, which were established in our laboratory. EHMK cells were infected with AdE3-midkine and co-cultured with ovarian adenocarcinoma HEY cells with or without antiadenoviral antibodies. In vitro antitumor activity of cloned EHMK carrier cells was calculated by IC50 and compared with that of A549 carrier cells infected with AdE3-midkine. B6C3F1 mouse and cognate ovarian cancer OVHM cell line were used in this study. Mice were injected intraperitoneally with OVHM cells after immunization with adenovirus and treated by carrier cells infected with AdE-midkine with or without Ad-mGM-CSF. Antitumor activity of carrier cells was analyzed by Kaplan Meier survival curve. In vitro antitumor activity of EHMK carrier cells was 1.0±0.1 and 1.1±0.2 that of A549 carrier cells with or without antiadenoviral antibodies, respectively. In vitro antitumor activity of EHMK-51 carrier cells after limiting dilution of EHMK cells was 4.5±1.1 and 3.4±1.9 that of A549 carrier cells with or without antiadenoviral antibodies, respectively. EMHK-51 cells were further cloned by limiting dilution. In vitro antitumor activity of EHMK-51-35 carrier cells was 3.1±1.5 and 2.8±0.9 that of EHMK-51 carrier cells with or without antiadenoviral antibodies, respectively. In comparison with A549 carrier cells, in vitro antitumor activity of EHMK-51-35 carrier cells was 12.5±4.3 and 10.5±5.0 that of A549 carrier cells with or without antiadenoviral antibodies, respectively. In mouse intraperitoneal tumor model, A549 carrier cells infected with AdE3-midkine ± Ad-mGM-CSF did not show any antitumor effect but EHMK carrier cells infected with AdE3-midkine with or without Ad-mGM-CSF showed 40% and 70% complete tumor reduction, respectively. From these results, it is concluded that EHMK-51-35 carrier cells might be potent to treat intraperitoneally metastasized ovarian cancer
Abstract 2260: Defining molecular mechanisms linking Endophilin A2 to metastasis in human breast cancer models
Authors: Tomas Baldassarre, Kathleen Watt, Peter Truesdell, Mark Schneider, Sandip Sengupta, Andrew WB Craig
Journal: Cancer Research (2015)

Abstract Breast cancers in the human epidermal growth factor receptor 2 (HER2) and triple-negative breast cancer (TNBC) subtypes have high rates of tumor metastasis. Tumor metastasis is driven by formation of invadopodia that degrade extracellular matrix (ECM) in basement membranes to spread locally and colonize distant sites. Endophilin A2 (Endo II) is an adaptor protein that coordinates internalization and trafficking of receptors that drive invadopodia formation and breast cancer metastasis. We have recently identified Endo II as a positive regulator of human TNBC metastasis, invadopodia formation, epidermal growth factor receptor (EGFR) internalization and signaling. Here, we extend these studies of Endo II to HER2 breast cancers, and define molecular mechanisms that link Endo II to invadopodia formation and cell invasion. Analysis of Endo II expression in human invasive ductal carcinomas revealed significantly high expression of Endo II in HER2 primary tumors, and significantly higher expression in paired lymph node metastases compared to other subtypes. We also observed that high levels of Endo II mRNA was associated with reduced rates of relapse free survival in patients with lymph node positive, estrogen receptor negative tumors. This correlates with our findings that Endo II promotes invadopodia formation and breast cancer cell invasion. Mechanistically, these defects may be due to reduced EGFR signaling and lowered expression of epithelial-mesenchymal transition (EMT) signature genes observed in Endo II knock-down (KD) cells. We are currently validating these results in mammary orthotopic tumor xenograft models of HER2 and TNBC cell models with stable Endo II KD. Together, these findings identify high levels of Endo II in high risk breast cancer subtypes, with high expression of EMT genes, and a potential link between Endo II levels and poor prognosis in breast cancer patients. Citation Format: Tomas Baldassarre, Kathleen Watt, Peter Truesdell, Mark Schneider, Sandip Sengupta, Andrew WB Craig. Defining molecular mechanisms linking Endophilin A2 to metastasis in human breast cancer models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2260. doi:10.1158/1538-7445.AM2015-2260
Factors predictive of leg-ulcer healing in sickle cell disease: a multicentre, prospective cohort study
Authors: P. Senet, C. Blas-Chatelain, P. Levy, E.M. Manea, M. Peschanski, T. Mirault, K. Stankovic-Stojanovic, C. Debure, K. Debbache, R. Girot, J.-M. Bureau, C. Bachmeyer, C. Baldeschi, F. Galacteros, F. Lionnet, J. Gellen-Dautremer
Journal: British Journal of Dermatology (2016)

BackgroundLeg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking.
Abstract 1311: The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment
Authors: Kilian Wistuba-Hamprecht, Benjamin Weide, Alexander Martens, Graham P. Pawelec
Journal: Cancer Research (2015)

Abstract Recently, there has been a resurgence of interest in the possibility of using γ/δ-T cells in cancer immunotherapy, because these cells can kill melanoma cells in vitro, and IL-2 and zoledronate treatment can expand some human γδ cells in vitro and in animal models in vivo. The presence of the main subsets of γ/δ-T cells in late-stage melanoma patients and relationship with survival has not been extensively explored, although relatively lower percentages of Vδ2-positive cells has been reported in melanoma. Here, we present preliminary data on associations between the major γ/δ-T cell subsets and survival in melanoma patients, and whether baseline data are informative for predicting responses to ipilimumab treatment. We used a carefully validated set of monoclonal antibodies to assess γ/δ-phenotypes, because we found that certain commercial reagents were not behaving as specified (Wistuba-Hamprecht et al. OMIP-020: phenotypic characterization of human γδ T-cells by multicolor flow cytometry. Cytometry A. 2014; 85:522-4). Comparing a total of 39 stage IV melanoma patients with 27 controls, we found no overall differences in Vδ1 or Vδ2 T-cell frequencies, or in proportions of naïe (CD27, CD28-double positive, CD45RA+)-vs -late-differentiated (CD27,CD28-double negative, CD45RA+) γ/δ cells. However, Kaplan-Meier plots stratifying individual patients into groups with Vδ1 or Vδ2 frequencies above or below the median showed that the presence of Vδ1 but not Vδ2 cells negatively correlated with longer survival (p = 0.033 log-rank; p = 0.047 Breslow). In a subgroup of 9 patients, ipilimumab treatment resulted in an increase of peripheral Vδ1+ T-cells (p = 0.0391, Wilcoxon) but not of Vδ2+ T-cells (p = 0.375, Wilcoxon). We are currently analyzing data from a larger prospective study of ipilimumba treatment with over 100 patients, to confirm or refute these results. Citation Format: Kilian Wistuba-Hamprecht, Benjamin Weide, Alexander Martens, Graham P. Pawelec. The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1311. doi:10.1158/1538-7445.AM2015-1311
Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death
Authors: Rong Na, S. Lilly Zheng, Misop Han, Hongjie Yu, Deke Jiang, Sameep Shah, Charles M. Ewing, Liti Zhang, Kristian Novakovic, Jacqueline Petkewicz, Kamalakar Gulukota, Donald L. Helseth Jr, Margo Quinn, Elizabeth Humphries, Kathleen E. Wiley, Sarah D. Isaacs, Yishuo Wu, Xu Liu, Ning Zhang, Chi-Hsiung Wang, Janardan Khandekar, Peter J. Hulick, Daniel H. Shevrin, Kathleen A. Cooney, Zhoujun Shen, Alan W. Partin, H. Ballentine Carter, Michael A. Carducci, Mario A. Eisenberger, Sam R. Denmeade, Michael McGuire, Patrick C. Walsh, Brian T. Helfand, Charles B. Brendler, Qiang Ding, Jianfeng Xu, William B. Isaacs
Journal: European Urology (2016)
The Brd-Inhibitor OTX015 Is Active in Pre-Clinical Models of Mature B-Cell Lymphoid Tumors
Authors: Paola Bonetti, Michela Boi, Maurilio Ponzoni, Maria Grazia Tibiletti, Anastasios Stahis, Giorgio Inghirami, Kay Noel, Emanuele Zucca, Francesco Bertoni
Journal: Blood (2012)
ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate Use Criteria for Coronary Revascularization in Patients With Acute Coronary Syndromes
Authors: Manesh R. Patel, John H. Calhoon, Gregory J. Dehmer, James Aaron Grantham, Thomas M. Maddox, David J. Maron, Peter K. Smith
Journal: Journal of the American College of Cardiology (2016)
Role of gefitinib (G) in heavily pretreated non-small cell lung cancer (NSCLC)
Authors: E. Tamburini, D. Tassinari, E. Pasquini, M. Papi, C. Possenti, F. Drudi, C. Castellani, C. Santelmo, F. Carloni, A. Ravaioli
Journal: Journal of Clinical Oncology (2009)

e19102 Background: To assess the role of a palliative treatment with gefitinib in advanced and heavily pre-treated NSCLC. Methods: The records of all the consecutive patients treated with G in our department were reviewed; all the patients pre-treated with at least one courses of a platinum-containing regimen were considered eligible and enrolled into the trial. All the patients were treated with G 250 mg/die until progression of the disease or intractable toxicity. All the patients were evaluated every 21 days for toxicity and every 2 months for survival. Primary end point was time to progression (TTP); secondary ones were overall survival (OS) and safety. A sub-analysis comparing TTP and OS on the basis of sex (male/female), smoker status (smoker/never-smoker) and histology (adenocarcinoma/non-adenocarcinoma) was performed using the Log-Rank test. Results: Till today 63 patients were considered eligible and enrolled into the trial; the results are summarised in the table . Toxicity was mild with no haematological side effects, and no grade III-IV non-haematological toxicity. Conclusions: G seems to represent an interesting options in patients with NSCLC heavily pre-treated with chemotherapy. Our data seems to confirm that G is active mainly in female, no-smoker patients with adenocarcinoma, suggesting the need of reintroducing the molecule in the treatment of such a subset of patients. [Table: see text] No significant financial relationships to disclose.
High-Sensitivity Mutational Analysis of BCR-ABL Mutations in the Kinase Domain Using Pyrosequencing Could Provides Alternative Methodology for Monitoring the Proportion of Mutant Alleles in Patient with Chronic Myelogenous Leukemia.
Authors: Il-Kwon Lee, Ju Hyun Yun, Yeo-Kyeoung Kim, Hee Nam Kim, Kyeong-Soo Park, Myung Geun Shin, Chan Choi, Hyeoung Joon Kim
Journal: Blood (2006)
Abstract A91: Stage-specific transcriptome analysis of human pancreatic cancer progression
Authors: Jungsun Kim, Greg Donahue, Wenli Yang, Kenneth S. Zaret
Journal: Cancer Research (2016)

Abstract Our goals are to discover gene networks that control the progression of pancreatic intraepithelial neoplasias (PanINs) to invasive stage pancreatic ductal adenocarcinoma (PDAC) and to understand how the pluripotency regulatory network can temporarily suppress the transition. Certain cancer cells are amenable to reprogramming to pluripotency by somatic cell nuclear transfer (SCNT) or defined transcription factors (iPS). Prior work showed that SCNT-cancer cells develop into normal appearing blastocysts, but later the cancer genome in SCNT-chimeric mice was reactivated during embryogenesis, re-expressing the cancer phenotype of the lineage from which they originated. We previously showed that when an iPS-like line, designated 10-22, derived from human pancreatic ductal adenocarcinoma (PDAC), was injected into immunodeficient mice, they consistently recapitulated pre-invasive, PanIN to invasive stages of PDAC (Kim et al., 2013 Cell Reports). Specifically, the PDAC-iPS cells differentiated into a ductal, PanIN2/3 epithelium with a collagen basement membrane, followed by progression to an invasive stage phenotype with basement membrane breakdown. Furthermore, the ductal cell lesions were surrounded by stroma that co-differentiated from the pluripotent 10-22 cells, indicative of signaling interactions with the epithelium. With this system, we now ask: 1) What gene regulatory networks for pluripotency can transiently attenuate the cancer genome; 2) Upon loss of pluripotency and differentiation, what are the regulatory network transitions during human PDAC progression? 3) What are the reciprocal signals between the PDAC epithelial cells and their surrounding stromal cells during pancreatic cancer progression? To address these questions, we have genetically tagged the PDAC-iPS 10-22 line with a lentiviral vector expressing a ubiquitous promoter driving GFP and a ductal K19 promoter driving infrared protein (iRFP), so that cells can be retrieved by FACS. While GFP+iRFP- cells include stroma derived from the 10-22 cells, GFP+iRFP+ allows isolation of precursor and invasive stages of PDAC. The tagged lines were injected into immunodeficient mice, the lesions were monitored in vivo by iRFP flourescence, and RNA was isolated in triplicate at multiple time points and subjected to RNA-Seq analysis. The human PDAC 10-22 cell system is being used to discover effectors and networks whereby pluripotency can dominate over cancer and new features of human PDAC progression, which would be ultimately used for developing novel cancer therapies. Citation Format: Jungsun Kim, Greg Donahue, Wenli Yang, Kenneth S. Zaret.{Authors}. Stage-specific transcriptome analysis of human pancreatic cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A91.
Abstract 5508: Fucoidan from <i>Turbinaria conoides</i> attenuates pancreatic cancer progession by regulating p53 - NFκB crosstalk
Authors: Caroline R. Delma, Guru Prasad Srinivasan, Nune Raviprakash, Sunil K. Manna, Somasundaram T. Somasundaram, Natarajan Aravindan
Journal: Cancer Research (2015)

Abstract Poor prognosis of pancreatic cancer (PC) has been attributed to its resistance to apoptosis and propensity for early systemic dissemination. Existing therapeutic strategies are often circumvented by the molecular crosstalk between cell signaling pathways. The fact that p53 is mutated in more than 50% of PC tissues and NFκB is constitutively activated in therapy resistant residual PC accounts for the evaded cell death and dissemination. In this study, we examined the benefit of fucoidan from a marine brown alga, Turbinaria conoides against PC progression. Five fractions of fucoidan isolated and fractionated using ion exchange chromatography were tested for their potential in this setting using two (MiaPaCa-2, Panc-1) genetically diverse human PC cell-lines. All fractions investigated exerted significant dose dependent and time dependent regulation of cell survival. Coherently, fucoidans induced apoptosis and activated caspase -3, -8 and -9 and cleaved PARP. Pathway-specific transcriptional analysis (QPCR profiling) recognized inhibition of 57 and 38 NFκB pathway molecules with fucoidan-F5 in MiaPaCa-2 and Panc-1 cells, respectively. In addition, fucoidan-F5 was also found to inhibit both the constitutive and TNFα mediated NFκB DNA-binding activity (EMSA) in PC cells. Upregulation of cytoplasmic IκB levels and significant reduction of NFκB dependent luciferase activity further substantiate inhibitory potential of seaweed fucoidans on NF-κB. Moreover, fucoidan(s) treatment increases cellular p53 in PC cells. Together, the results suggests that fucoidan regulates PC progression and further imply that fucoidans may selectively target p53-NFκB crosstalk and dictate apoptosis in PC cells. Citation Format: Caroline R. Delma, Guru Prasad Srinivasan, Nune Raviprakash, Sunil K. Manna, Somasundaram T. Somasundaram, Natarajan Aravindan. Fucoidan from Turbinaria conoides attenuates pancreatic cancer progession by regulating p53 - NFκB crosstalk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5508. doi:10.1158/1538-7445.AM2015-5508
Association of weekend effect with early mortality in severe sepsis patients over time
Authors: Yu-Ning Shih, Yung-Tai Chen, Chia-Jen Shih, Shuo-Ming Ou, Yen-Tao Hsu, Ran-Chou Chen, Imoigele P. Aisiku, Raghu R. Seethala, Gyorgy Frendl, Peter C. Hou
Journal: Journal of Infection (2016)
Abstract 5393: Evaluation of compounds developed against the TAM family kinases
Authors: Hong Zhang, Zaihui Zhang, Xiaoqing Shi, Erica Lee, Rick Li, Yuxiang Hu, Jun Yan, Jasbinder Sanghera
Journal: Cancer Research (2015)

Abstract The TAM family receptor tyrosine kinases, consisting of Tyro3, Axl and Mer, are implicated in a diverse range of cellular processes such as cell survival, proliferation, migration, angiogenesis, and inflammatory response. Despite the debates over their role as a driver in carcinogenesis owing to some recent findings, their link to human cancer is strongly supported by direct correlation of the level of expression/activity with tumor grade and prognosis. In particular, Axl was found to underlie metastasis as an essential regulator of the epithelial-mesenchymal transition (EMT) process and also to confer acquired resistance to the TKI-mediated targeted therapies by up-regulation of associated kinases. Currently, none of FDA-approved kinase drugs were developed for the TAM family kinases. In our effort to develop such small-molecule inhibitors targeting the TAM kinases for oncology indications, we uncovered a series of novel potent compounds with low nM potency against Axl and Tyro3. Effect of these compounds in human cancer cell lines of different tissue origins was mediated mainly through the Axl-dependent signaling pathways. Detailed analysis of signaling proteins downstream of Axl revealed different mechanisms of action for these compounds. In addition to suppression of cell proliferation, these compounds inhibited anchorage-independent colony formation, cell migration and invasion. Four compounds were selected to be evaluated in pharmacokinetic studies in mice and the results indicated that these compounds possess reasonable PK properties with high exposure, reasonably long half-life, and good bioavailability. The results of the efficacy studies in suppressing tumor growth in a xenograft and an orthotropic mouse models will be discussed. Citation Format: Hong Zhang, Zaihui Zhang, Xiaoqing Shi, Erica Lee, Rick Li, Yuxiang Hu, Jun Yan, Jasbinder Sanghera. Evaluation of compounds developed against the TAM family kinases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5393. doi:10.1158/1538-7445.AM2015-5393
Bortezomib in Patients with Relapsed-Refractory Multiple Myeloma (MM). Clinical Observations.
Authors: Marie-Christine Kyrtsonis, Sotirios Sachanas, Theodoros P. Vassilakopoulos, Nikoletta Kafassi, Tatiana Tzenou, Argyro Papadogiannis, Christina Kalpadakis, Antonios G. Antoniadis, Maria N. Dimopoulou, Maria K. Angelopoulou, Marina P. Siakantaris, Evangelia M. Dimitriadou, Styliani I. Kokoris, Eleni Plata, Panagiotis Tsaftaridis, Panayiotis Panayiotidis, Gerassimos A. Pangalis
Journal: Blood (2005)
Optimal NK Cell Expansion Depends on Accessory Cells, Synergy between Physiologic Concentrations of IL-2 and IL-15, and Umbilical Cord Blood (UCB) NK Cell Precursors Expand Better Than Adult NK Cells.
Authors: Purvi Gada, Michelle Gleason, Valarie McCullar, Philip B. McGlave, Jeffrey S. Miller
Journal: Blood (2006)