tbuckley/cabot-search huggingface dataset:
Abstract 3262: Mitochondrial haplotype effects on tumor formation and metastasis are both cell autonomous and non-cell autonomous
Authors: Amanda E. Brinker, Carolyn J. Vivian, Kyle P. Feeley, Scott W. Ballinger, Danny R. Welch
Journal: Cancer Research (2015)

Abstract Increasing data support roles for mitochondrial genomes in complex diseases, including cancer. We hypothesize that primary tumor formation and metastasis can arise from inherited mitochondrial differences. To test directly the role of mitochondrial DNA (mtDNA) in mammary cancer tumorigenicity and metastasis, we generated Mitochondrial Nuclear Exchange (MNX) mice. This unique animal model is created by moving the nucleus from an oocyte of one strain into an enucleated oocyte of a different strain. By exchanging the nucleus of mouse strains promoting or inhibiting metastatic efficiency, mtDNA effects can be distinguished from phenotypes which would occur due to nuclear admixing. To determine if a change in the mtDNA background impacts metastasis in a cell autonomous manner, two FVB transgenic mouse strains encoding either Her2 or PyMT oncogenes were crossed with MNX mice with FVB nuclear DNA and mtDNA from either BALB/cJ or C57BL6J strains. The mtDNA were chosen because of higher or lower metastatic efficiency, respectively (PMID9679770, PMID16491073). Latency of mammary tumor formation in MNX mice with C57BL/6 mtDNA is longer for both Her2 and PyMT. Lung metastases are smaller in C57BL6 but larger in BALB/c MNX crosses with the PyMT. Studies measuring metastasis efficiency in the MNX crosses with Her2 are still in progress. To determine whether the mitochondrial haplotype alters tumorigenicity or metastasis in a non-cell autonomous manner, syngeneic tumor cells were injected orthotopically and ectopically (i.v.). Tumor formation and metastasis differ in a tumor and mtDNA-dependent manner. For example, E0771 forms significantly more lung metastases in C57BL/6n:C3H/HeNmt mice compared to controls. To explore underlying mechanisms, metabolic differences were observed in MNX and matched wild type mouse embryonic fibroblasts using the Seahorse bioanalyzer. Conclusion: mtDNA affects mammary cancer development and progression via both genetic and non-cell autonomous mechanisms in the tumor microenvironment. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Steiner Family Fund for Metastasis Research, Kansas Bioscience Authority, CA134981, P30-CA168524 Citation Format: Amanda E. Brinker, Carolyn J. Vivian, Kyle P. Feeley, Scott W. Ballinger, Danny R. Welch. Mitochondrial haplotype effects on tumor formation and metastasis are both cell autonomous and non-cell autonomous. [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 3262. doi:10.1158/1538-7445.AM2015-3262
Flow Cytometric Examination of Non-Hematic Body Fluids in Hematologic Malignancies: A Comparison with Cytology.
Authors: Clara Cesana, Barbara Scarpati, Bruno Brando, Claudia Barba, Ursula Ferri, Linda Scampini, Pierluigi Oreste, Silvio Veronese, Annamaria Nosari, Enrica Morra, Roberto Cairoli
Journal: Blood (2007)
256. Pharmacokinetics of Natural and Engineered Secreted Factors Delivered by a Cell Therapeutic
Authors: Biju Parekkadan
Journal: Molecular Therapy (2015)

Cell therapy is an emerging drug class that requires new approaches for pharmacological monitoring during use. Human mesenchymal stem cells (MSCs) are a clinically-tested transient cell therapeutic that naturally secrete anti-inflammatory factors to attenuate immune-mediated diseases. MSCs were used as a proof-of-concept with the hypothesis that measuring the release of secreted factors after cell transplantation, rather than the biodistribution of the cells alone, would be an alternative monitoring tool to understand the exposure of a subject to MSCs. By comparing cellular engraftment and the associated serum concentration of secreted factors released from the graft, we observed clear differences between the pharmacokinetics of MSCs and their secreted factors. Exploration of the effects of natural or engineered secreted proteins, active cellular secretion pathways, and clearance mechanisms revealed novel aspects that affect the systemic exposure of the host to secreted factors from a cellular therapeutic. A combined consideration of cell delivery strategies and molecular pharmacokinetics may provide a more predictive model for outcomes of MSC transplantation and other cell therapeutics.
Concurrent chemoradiotherapy (cCTRT) with weekly cisplatin (wCDDP) in locally advanced cervical cancer (LACC) patients (pts): a monoinstitutional experience
Authors: V. Murgia, O. Caffo, A. Caldara, S. Brugnara, M. Dipasquale, A. Ferro, M. Frisinghelli, S. Macrini, F. Maines, M. Daniela, C. Trentin, F. Valduga, A. Veccia, E. Galligioni
Journal: Annals of Oncology (2015)
Abstract 1977: Elucidating heterogeneity within cancer cell populations using single cell RNA detection
Authors: Don Weldon, Yuko Williams, Victor Koong, Alex Ko
Journal: Cancer Research (2015)

Abstract As researchers continue to analyze the relationships between gene expression and biological processes involved in the development and progression of cancer, increasing importance is being placed on the study of genetic variation across single cells. However, traditional methods tend to measure RNA expression globally, with cell lysis and fixation steps resulting in a loss of key information about individual cells, making it challenging to properly assay the genetic heterogeneity within cell populations. We demonstrate the use of a single cell RNA detection technology that specifically measures gene expression in live cells without altering their viability or inherent biology. This enables researchers to not only detect heterogeneity within their samples, but also separate, enrich, and further characterize cell subpopulations based on RNA expression variation, when using techniques such as Fluorescent Activated Cell Sorting (FACS). Here, we describe live cell detection of cancer biomarkers within heterogeneous cell models. First, we co-cultured MCF-7 and SK-BR3 breast cancer cell lines in specific ratios to mimic heterogeneous breast cancer populations. Subsequent characterization of the populations was performed by both flow cytometry using fluorescent live-cell RNA detection probes, and quantitative real-time PCR. Next, we analyzed miR-221 expression in a mixture of T47D and MDA-MB-231 breast cancer cell lines, which allowed us to sort the two cell types based on differential expression of this microRNA and perform downstream immunohistochemical analysis of vimentin and E-cadherin, two protein markers known to be associated with the epithelial-to-mesenchymal transition during tumor progression. Use of a live cell RNA detection methodology in gene expression experiments allows scientists to formulate novel questions and design experiments that better address the importance of gene expression heterogeneity in normal and disease states, particularly in cancer, where individual cells within the tumor microenvironment may exhibit aberrant RNA expression profiles that render them invasive or metastatic. Note: This abstract was not presented at the meeting. Citation Format: Don Weldon, Yuko Williams, Victor Koong, Alex Ko. Elucidating heterogeneity within cancer cell populations using single cell RNA detection. [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 1977. doi:10.1158/1538-7445.AM2015-1977
Characterization of Patients with Multiple Myeloma Achieving Complete Response to Bortezomib: An Interim Report From An International Electronic Observational Study.
Authors: Michel Delforge, Hadewijch De Samblanx, Maria Roussou, Konstantinos Zervas, Eirini Katodritou, Kudrat M Abdulkadyrov, Deniz Sargin, Cyrille Hulin, Lucia Ahlberg, Javier de la Rubia, Rita Ganguly, Joris Diels, Ravinder Dhawan, Meletios A. Dimopoulos
Journal: Blood (2009)
Stereological Analysis Of The Peripheral Lung Anatomy In Patients With Alpha-1 Antitrypsin Deficiency Using Mdct And Micro-CT
Authors: D. M Vasilescu, D Kinose, A. B Phillion, Stijn Verleden, M Elliott, Bart Vanaudenaerde, Geert Verleden, Dirk Van Raemdonck, J. D Cooper, J. C Hogg
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Abstract 4743: A population-based approach to address clinical cancer care: The national genomics platform
Authors: Ogan Abaan, Amrita Basu, Noah Brown, Bret Light, David Deal, Michael Hultner
Journal: Cancer Research (2015)

Abstract Our understanding of the genetic basis for cancer is advancing at a rapid rate due to the application of next generation sequencing (NGS) technologies. It is becoming common to sequence tumors and patients in an attempt to find actionable mutations that could offer the patient a more targeted and effective treatment. However, the genomics of cancer is very complex and only a handful of actionable mutations have been characterized. Larger-scale studies are needed to understand the pathogenic spectrum of cancer variants and deliver reliable clinical decision-making support to providers. Several large-scale sequencing projects are underway to collect NGS data on tumors (e.g. TCGA, ICGC, and TARGET) but a national platform for analysis, interpretation, and reporting does not exist. We propose that a consolidated informatics platform for the collection of outcomes data with genomics and clinical data would accelerate research and provide patients with the opportunity for personalized cancer treatment. In addition, with 1,665,540 new cancer cases predicted in the US for 2014, a national-scale genomics platform is needed, capable of sequencing 3 million genomes per year, storing exabytes of data, while supporting over 20,000 oncologists, researchers, and analysts. At Lockheed Martin, we deliver highly scalable and reliable information systems for a variety of missions and citizen services. Here, we will present our vision for a national cancer genomics platform to include NGS data collection, cost-efficient storage, scalable and modular processing pipelines, and collaborative analytics and data sharing capabilities, within a compliant privacy and security framework. In conclusion, by leveraging the scale of clinical cancer sequencing and capturing these data into a case management system for translational research, this platform provides data at-scale needed for finding actionable mutations, designing effective treatments and implementing prevention strategies, faster. Citation Format: Ogan Abaan, Amrita Basu, Noah Brown, Bret Light, David Deal, Michael Hultner. A population-based approach to address clinical cancer care: The national genomics platform. [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 4743. doi:10.1158/1538-7445.AM2015-4743
Abstract 5309: The role of aquaporin-1 as the prognostic factor for triple negative breast cancer
Authors: Young Ah Lim, Lee-Su Kim
Journal: Cancer Research (2015)

Abstract Aquaporins(AQPs) area a large family of integral membrane water transport cannel proteins that facilitate the transport of water through the cell membrane. And in the subgroup of AQPs, AQP1 are expressed in many epithelia and endothelia such as kidney and lung. Recent studies revealed that AQPs were associated with human malignancies, since they are likely to play a role in the promotion of tumor progression and invasion. In this study, we evaluated the correlation with AQP1expression and invasive breast cancer, especially triple negative breast cancer(TNBC) and we analyzed AQP1 expression and the clinicopathologic factor. The present study was based on 277 patients of primary breast carcinomas who underwent surgery and treatment, presenting between Jan. 2003 and Dec. 2008. The immunohistochemical expression of AQP1 was investigated and compared with clinicopathologic factors. AQP1 expression was demonstrated in 17 tumors(6.1%) for all patinets. In 50 patients who were diagnosed with TNBC, 12 patients(24%) showed AQP1 expression. In the result, AQP1 expression was associated with TNBC. For all patients, AQP1 expression was associated with poor prognostic factor. In TNBC patients, AQP1 expression was not associated with prognostic factor. In consideration of AQP1 expression for TNBC patients, our results suggested AQP1 expression is a new prognostic factor of TNBC which is aggressive subgroup of breast carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Young Ah Lim, Lee-Su Kim. The role of aquaporin-1 as the prognostic factor for triple negative breast cancer. [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 5309. doi:10.1158/1538-7445.AM2015-5309
Abstract 2674: Activity of BAY1082439, a balanced PI3Kα/β inhibitor, in gastric cancer
Authors: Huynh T. Hung, Richard Ong, Katja Haike, Elissaveta Petrova, Mei Ling Chong, Marie Loh, Bhaskar Bhattacharya, Richie Soong, Ningshu Liu
Journal: Cancer Research (2015)

Abstract Background: Activation of the p110α and p110β subunits of PI3K by PIK3CA mutation (7% of cancers), PIK3CA amplification (36-60%) and/or PTEN loss (33-47%) is a frequent oncogenic event in gastric cancer. Here, we report on the activity, mode of action and biomarker analysis of BAY1082439, a balanced PI3Kα/β inhibitor, in cell lines and xenografts from Asian and Caucasian gastric cancer patients. Methods: Twenty cell lines were screened in vitro for the sensitivity to BAY1082439 using cell proliferation, cell cycle, migration and invasion assays. In vivo activity and mode of action of BAY 1082439 were further assessed by pathway inhibition, tumor growth inhibition, and effects on tumor stromal cells. Molecular features were assessed by Oncocarta analysis, gene expression arrays, and immunohistochemistry. Results: Seven cell lines were sensitive to BAY1082439, which included 6/7 cell lines with PIK3CA mutations and/or PTEN loss. In vivo study with 15 PDX and 2 cell line models revealed that tumors with genetic alteration of PIK3CA and PIK3CB, PTEN-loss, and/or HER2/HER3/FGFR overexpression were more sensitive to BAY 1082439 (tumor growth inhibition &amp;gt;90%), while tumors harboring KRAS mutation and/or overexpressing EGFR were insensitive or less responsive to BAY 1082439. Interestingly, BAY1082439 did not inhibit proliferation of MKN45 cells in-vitro (IC50&amp;gt;10μM), however it induced tumor stasis in this highly vascularized MKN45 xenografts. The anti-angiogenic activity BAY 1082439 was also demonstrated in patient derived gastric cancer models assessed by CD31 immunohistochemistry. BAY1082439 was also active in many tumors resistant to standard-of-care chemotherapy. Synergistic or additive effects on tumor growth and apoptosis were observed for BAY1082439 in combination with paclitaxel, 5-FU, and capecitabine/oxaliplatin. Conclusions: The PI3Kα/β balanced inhibitor BAY1082439 showed considerable anti-tumor activity including tumor regression in gastric cancer models with genetic alteration or activation of PI3Kα/β and/or PI3Kα/β as single agent or in combination. Citation Format: Huynh T. Hung, Richard Ong, Katja Haike, Elissaveta Petrova, Mei Ling Chong, Marie Loh, Bhaskar Bhattacharya, Richie Soong, Ningshu Liu. Activity of BAY1082439, a balanced PI3Kα/β inhibitor, in gastric cancer. [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 2674. doi:10.1158/1538-7445.AM2015-2674
Induction of PD-1 and PD-1 Ligand Expression by Hypomethylating Agents (HMA) in Myelodysplastic Syndromes and Acute Myelogenous Leukemia Suggest a Role for T Cell Function in Clinical Resistance to Hmas
Authors: Hui Yang, Carlos E. Bueso-Ramos, Simrit Parmar, Yue Wei, Zhihong Fang, Martin Nguyen, Michael Fernandez, Sherry A. Pierce, Qirong Geng, Hagop M. Kantarjian, Jorge E Cortes, Guillermo Garcia-Manero
Journal: Blood (2012)
Prognostic Value of<i>BRAF </i>and <i>KRAS</i> Mutations in MSI and MSS Stage III Colon Cancer
Authors: Julien Taieb, Karine Le Malicot, Qian Shi, Frédérique Penault-Llorca, Olivier Bouché, Josep Tabernero, Enrico Mini, Richard M Goldberg, Gunnar Folprecht, Jean Luc Van Laethem, Daniel J Sargent, Steven R Alberts, Jean Francois Emile, Pierre Laurent Puig, Frank A Sinicrope
Journal: JNCI Journal of the National Cancer Institute (2016)

The prognostic value of BRAF and KRAS mutations within microsatellite-unstable (MSI) and microsatellite-stable (MSS) subgroups of resected colon carcinoma patients remains controversial. We examined this question in prospectively collected biospecimens from stage III colon cancer with separate analysis of MSI and MSS tumors from patients receiving adjuvant FOLFOX +/- cetuximab in two adjuvant therapy trials.
Abstract 2500: Identification of promiscuous oncofetal antigen (IMP-3)-derived long peptides, bearing both Th cell and CTL epitopes
Authors: Masatoshi Hirayama, Akira Yuno, Yusuke Tomita, Mohammad Abu Sayem, Hirotake Tsukamoto, Atsushi Irie, Satoru Senju, Yoshihiro Yoshitake, Daiki Fukuma, Masanori Shinohara, Eiji Yuba, Kenji Kono, Koji Yoshida, Yusuke Nakamura, Hideki Nakayama, Yasuharu Nishimura
Journal: Cancer Research (2015)

Abstract We recently identified CTL epitopes derived from an oncofetal antigen, insulin-like growth factor II mRNA-binding protein 3 (IMP-3) which was frequently overexpressed in head-and-neck cancers (HNCs) and lung cancers, but not in many normal adult organs, by using genome-wide cDNA microarray analyses. Several phase I/II clinical trials using IMP-3-derived short peptides (SPs) vaccination against several types of malignant tumor are ongoing. Recently we reported the phase I/II clinical trial of multiple tumor-associated-antigen (TAA)-derived SPs vaccinations including IMP-3-SP for advanced HNC patients. In this trial, we observed the vaccinated SPs-specific CTL responses and the prolongation of overall survival of HNC patients (Clin Cancer Res; Nov. 12, 2014 in press). In order to further develop peptides-based cancer immunotherapy, we attempted to identify IMP-3-derived long peptides (LPs) containing both CTL and Th cell epitopes in this study. We successfully identified two promiscuous IMP-3-derived LPs, and one of them encompasses two natural CTL epitopes, and these LPs can stimulate IMP-3-LP-specific Th1 cells restricted by 7 frequent HLA class II molecules. We confirmed that Th cells induced by two LPs responded to autologous dendritic cells (DCs) loaded with IMP-3 protein, suggesting that these IMP-3-derived LPs were possibly naturally processed from IMP-3 protein and presented by DCs. We also demonstrated that one of the IMP-3-derived LPs could cross-prime IMP-3-SP-specific CTLs in vitro in human and in vivo in HLA-A2 transgenic mice. The same LP encapsulated in newly developed pH-sensitive liposome, that can deliver LPs from endosome to cytoplasm, was also found to be efficiently cross presented in vitro to stimulate IMP-3-SP-specific human CTLs. Furthermore, we could induce IMP-3-LP-specific Th cells from a HNC patient vaccinated with an IMP3-derived SP. Immune response to these LPs in many other HNC patients is now under investigation. Taken together, IMP-3-derived LPs may be applicable to cancer immunotherapy. Citation Format: Masatoshi Hirayama, Akira Yuno, Yusuke Tomita, Mohammad Abu Sayem, Hirotake Tsukamoto, Atsushi Irie, Satoru Senju, Yoshihiro Yoshitake, Daiki Fukuma, Masanori Shinohara, Eiji Yuba, Kenji Kono, Koji Yoshida, Yusuke Nakamura, Hideki Nakayama, Yasuharu Nishimura. Identification of promiscuous oncofetal antigen (IMP-3)-derived long peptides, bearing both Th cell and CTL epitopes. [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 2500. doi:10.1158/1538-7445.AM2015-2500
Abstract 4770: Levels of 5-methyl-cytosine and 5-hydroxymethyl-cytosine in hepatocellular carcinoma prognosis
Authors: Lissette Delgado-Cruzata, Hui Chen Wu, Tiffany Thomas, Abby B. Siegel, Jing Shen, Yu-Jing Zhang, Abhishek Goyal, Christine C. Hsu, Helen Remotti, Regina M. Santella
Journal: Cancer Research (2015)

Abstract Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. The US incidence of HCC has tripled between 1975 and 2005 and has been accompanied by improved long term survival rates, but as a result of HCC ‘s poor prognosis, 1-year survival remains lower than fifty percent. Therefore, a better understanding of the molecular mechanisms underlying the disease process is currently needed. Epigenetic alterations have been linked to HCC and global genomic hypomethylation is a well known hallmark of the disease. Less is understood about the role hydroxymethylation plays in HCC carcinogenesis. Here, we conducted a study to determine 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels by UPLC/MS/MS in HCC tumor (T) and non-tumor (NT) adjacent tissue DNAs of sixty six individuals treated at Columbia Presbyterian Medical Center in New York. We analyzed the association between demographic and clinicopathological characteristics and 5mC and 5hmC levels, as well as performed a Cox-survival analysis to determine which factors better predicted survival. Mean levels of 5mC (5mCT = 3.15±0.49% vs.5mCNT = 3.80±0.12% (p&amp;lt;0.0001) and 5hmC (5hmCT = 0.11±0.04% vs. 5hmCNT = 0.23±0.07%, p&amp;lt;0.0001) in tumor tissues were statistically significantly lower than in non-tumor tissues. Older age was associated with lower 5mC content (5mC&amp;lt;60y = 3.32±0.43% vs. 5mC≥60y = 3.00±0.50%, p = 0.001), while tumor DNA of transplant (LT) patients had higher 5hmC levels compared to surgical resection (LR) patients (5hmCLR = 0.10±0.04% vs. 5hmCLT = 30.13±0.04%, p = 0.0053). However, survival was predicted by whether transplant or resection were performed (Hazard ratio LT vs. LR, 3.54 (95% confidence interval:1.34-9.29), p = 0.01). Our study had a limited sample size, but suggests that future studies of 5hmC might be informative concerning HCC prognosis. Citation Format: Lissette Delgado-Cruzata, Hui Chen Wu, Tiffany Thomas, Abby B. Siegel, Jing Shen, Yu-Jing Zhang, Abhishek Goyal, Christine C. Hsu, Helen Remotti, Regina M. Santella. Levels of 5-methyl-cytosine and 5-hydroxymethyl-cytosine in hepatocellular carcinoma prognosis. [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 4770. doi:10.1158/1538-7445.AM2015-4770