tbuckley/cabot-search huggingface dataset:
Abstract 4618: Response post first autologous stem cell transplantation (ASCT) for multiple myeloma identify patients who may benefit from tandem transplants: A single center prospective phase II study
Authors: Jan S. Moreb, Donya Salmasinia, Helen Leather, Amy Davis, Jack Hsu, Laura Wiggins, Christopher R. Cogle, Myron N. Chang, John R. Wingard
Journal: Cancer Research (2012)

Abstract The role of tandem transplants as well as a later salvage second transplant has been in the center of interest for many myeloma investigators. Also, the need for tandem ASCT in patients (pts) achieving very good partial remission (VGPR) or complete remission has not been studied prospectively. We conducted a prospective phase II clinical trial in which enrolled myeloma pts are assessed after the first ASCT and offered either 2nd tandem ASCT if they achieve ≤ PR or maintenance if they achieve ≤ VGPR. These latter pts received 2nd salvage transplant after relapse. The conditioning regimens used were different for the two ASCT: Busulfan 0.75 mg/kg PO q 6 hr days –8 through –5, Cyclophosphamide (CP) 60 mg/kg IV days –3 and –2, and Etoposide 10 mg/kg IV days –4 to –2 for the first ASCT, and 96 hr (days –6 to –3) continuous IV CP 6 gr/m2 and total body irradiation (TBI) 600 cGy (days –2 and –1) for the second ASCT. Etoposide was omitted if pts were ≤ 65 year old, and TBI was substituted by melphalan 140 mg/m2 if prior radiation did not allow TBI. Between the years 2001-2009, 76 pts were enrolled. Of the 31 pts planned to have tandem ASCT, 20 received tandem ASCT, 2 additional pts had tandem auto-allo transplants and one patient had progressive disease. The primary reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources and physical co-morbidities. Maintenance treatment was offered to both groups of pts. There were no treatment related mortalities in the ASCT pts. We compared the progression-free (PFS) and overall (OS) survival following the first ASCT between pts who received tandem ASCT (n=20) and pts who received single ASCT (n=54). The median PFS for tandem pts was 27 mo (range, 10-93) versus 28 mo for single ASCT (range, 4-99) (P=0.889); the OS was 38 mo (range, 11-120) versus 72 mo (range, 5-136), respectively (P=0.293). At the present time, a total of 7 (35%) and 30 (55%) pts are still alive in the tandem and single ASCT groups, respectively. Among the tandem pts, 2 underwent salvage ASCT and one non-myeloablative allogeneic transplant (allo-SCT); while in the single ASCT group 6 had salvage ASCT and 6 had allo-SCT. All salvage transplants were done at a median of 37 mo (range, 8-91) from 1st ASCT. In conclusion, pts who achieve ≤ VGPR after 1st ASCT have similar PFS and may be better OS than pts who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk pts that will do well without the upfront tandem ASCT. 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 4618. doi:1538-7445.AM2012-4618
RESECCIÓN DE LESIONES SUBEPITELIALES ASISTIDA MEDIANTE INYECCIÓN SUBMUCOSA GUIADA POR ECOENDOSCOPIA.
Authors: A Repiso, M Pérez-Carreras, C Arribas, J Díaz-Tasende, R Gómez, JM Carrobles, G Castellano-Tortajada
Journal: Endoscopy (2012)

Introducción: En el tratamiento de las lesiones subepiteliales podría plantearse la resección endoscópica en casos seleccionados. Una de las técnicas endoscópicas que ha demostrado ser útil y evitar la perforación de la pared gástrica consiste en la inyección intramural de suero fisiológico y posterior resección con asa de polipectomía. Sin embargo, si la inyección es superficial y no se realiza en la base del tumor la resección puede ser técnicamente muy compleja y finalmente incompleta. Nuestro objetivo ha sido evaluar la utilidad de la ecoendoscopia en la inyección submucosa previa a la resección endoscópica de lesiones subepiteliales. Material y método: Se incluyeron pacientes remitidos a la Unidad de Endoscopias de nuestros hospitales (junio de 2008– diciembre de 2011) para valorar la resección de lesiones submucosas y en los que decidió realizar resección asistida por ecoendoscopia. Se procedió a la punción con aguja de 22G colocando la punta entre el borde inferior de la lesión y la muscular propia. Se inyectó suero fisiológico y se comprobó ecográficamente como la muscular propia se separaba de las capas superficiales. Posteriormente con visión endoscópica se procedió a resección con asa de polipectomía. Resultados. Se trataba de seis pacientes que presentaban tres lesiones gástricas (dos tumores carcinoides y un pólipo inflamatorio fibroide), dos rectales (dos tumores carcinoides) y una duodenal (páncreas heterotópico). El tamaño medio de las lesiones fue de 9,8mm (rango 7–13mm), localizadas en cuatro casos en la submucosa y en dos en la mucosa profunda. Se consiguió resección completa en una sola sesión endoscópica en cinco de ellas y en un caso fue preciso un segundo procedimiento para conseguir una resección completa. No existieron recidivas en un periodo medio de seguimiento de 24 meses (rango: 8–36 meses). En dos casos se produjo sangrado tras la resección que se controló con tratamiento endoscópico. No existieron perforaciones ni otras complicaciones. Conclusión. La ecoendoscopia aumenta la seguridad de la resección de lesiones subepiteliales al permitir la inyección de suero fisiológico bajo la lesión y comprobar en tiempo real una adecuada separación entre lesión y muscular propia.
Abstract P3-02-05: Evaluation of Gene Transcripts in Primary Tumors at Time of Diagnosis and Circulating Tumor Cells (CTCs) at Time of Metastatic Disease
Authors: AM Sieuwerts, B Mostert, J Bolt-de Vries, J Kraan, LY Dirix, PA van Dam, A van Galen, P van der Spoel, R Ramírez-Moreno, JX Yu, Y Wang, JW Gratama, S Sleijfer, JA Foekens, JWM. Martens
Journal: Cancer Research (2010)

Abstract Introduction: The enumeration of CTCs has already shown to bear clinical relevance as a prognostic and predictive factor in metastatic breast cancer. In addition to enumeration, isolation of CTCs enables their molecular characterization and thus holds great promise to establish association of their genetic profile with patient outcome and to identify potential drugable targets. In this study we established epithelial-specific mRNA and microRNA profiles in CTCs of patients with metastatic breast cancer, compared these profiles to the profiles measured in corresponding primary tumors, and determined their association with clinical parameters. Study design: For this study we included 50 breast cancer patients, of which 32 presented themselves with over 5 CTCs at the time of metastatic disease. From 14 of these patients with more than 5 CTCs at the time of metastatic disease also the primary tumor at time of breast cancer diagnosis was evaluated. Total RNA was extracted 1) from blood of the 50 patients with metastatic disease after EpCAM-based enrichment of 7.5 mL whole blood with the CellSearch™ Profile Kit [Veridex LCC], 2) from 14 unprocessed whole blood preparations from healthy blood donors, and 3) from 14 primary tumors. Gene transcript levels of CTC-specific and potentially clinically relevant mRNAs and microRNAs were compared in CTCs isolated at time of metastatic disease and the corresponding primary tumors. In addition, the association of these transcript levels with clinical data was assessed. Results: We identified 24 mRNA and 14 microRNAs more abundantly expressed in CellSearch-enriched fractions from patients with at least 5 CTCs compared with those without CTCs and/or compared with unprocessed whole blood prior to CellSearch enrichment (Mann-Whitney U-test P&amp;lt;0.05). In addition, when comparing transcript levels present in CTCs during metastatic disease and those measured in the corresponding primary tumor, potentially clinically relevant discrepancies were observed. Findings of interest included changes in transcript levels of genes such as ESR1, ERBB2, TOP2A and MGB1, and in genes associated with proliferation and EMT. Finally, associations were observed between transcript levels measured in CTC preparations and clinical data like nodal status and size of the primary tumor. Conclusion: Our results show that molecular characterization of CTCs is feasible and has potential for a more tailored clinical approach above CTC enumeration in the treatment of metastatic breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-05.
FUNCTIONAL PRESENCE OF M2 MACROPHAGE MARKERS IN GBM TUMOR CELLS
Authors: W. Debinski, A. Rodriguez, D. Gibo, S. B. Tatter, R. Mott, M. Lively, L. Miller, D. F. Seals
Journal: Neuro-Oncology (2014)

BACKGROUND: Tumor associated macrophages (TAMS) have been suggested to be key players in the tumor microenvironment. The M2 activation phenotype is believed to be the predominant TAM phenotype in solid tumors. To further define the role of M2 TAMs and analyze the cross-talk between tumor cells and TAMs, we examined the presence of macrophage markers in glioblastoma (GBM) tumors, their responses to various treatments, the genetic profile of M2 macrophages and also potential mediators of tumor cells communication with TAMs. METHODS: GBM tumor specimens were assayed for macrophage/microglia and M2 activation markers via immunohistochemistry and immunofluorescence. GBM tumor lysates and glioma tumor cell lines were assayed for M2 macrophage activation markers, CD163, CD204 and CD206 via immunoblotting. Gene expression analysis in a THP-1 model of macrophages was performed using Affymetrix Human Gene 1.0 ST Array. Proteins released by GBM cells were analyzed by mass spectrometry (LC-MS). Cells were cultured under various conditions of hypoxia or stem-like cells promoting or they were exposed to irradiation. RESULTS: Pan-macrophage CD68, microglia CD11b, and monocyte marker CD14 were all readily detected in GBM. CD163 + , CD204 + , and CD206+ cells were found to be richly present throughout GBM tumors. To confirm the M2 activation phenotype marker expression pattern, THP-1 monocytic cells model polarized by IL-4/IL-13 expressed CD163, CD204 and CD206. We also isolated the CD163+ cells from the resected specimens that, interestingly, expressed also an astrocytic cell marker, GFAP. Unexpectedly, GBM cells in culture were also found to express macrophage markers. Macrophage markers expression was differential in response to hypoxia, stem-like cells conditions and irradiation. In situ staining of GBM tumor specimens showed the co-localization of M2 macrophage markers and GFAP. We also found two groups of gene expression patterns in THP-1 M2 macrophages that differ from M1 and M0 types, with potential individual candidates for new M2 and also M1 markers. Among the proteins specifically picked by LC-MS, several are known to be associated with activated astrocytes (CTGF), immune cells (CCL2) or other stromal cells (periostin), and to some extent with tumor cells. CONCLUSIONS: GBM cells express macrophage activation markers CD163, CD204 and CD206, which is a novel observation. This finding implies the existence of a subset of GBM cells with a potential important functional role in the tumor microenvironment. Also, more specific markers for M2 macrophages are needed. Moreover, GBM cells release an abundance of factors enabling communication with TAMs. SECONDARY CATEGORY: Immunobiology & Immunotherapy.
Abstract 1156: Cell-surface marker discovery for colorectal cancer
Authors: Kamini Sewda, Jonathan W. Wojtkowiak, Steven Enkemann, Alexis S. Lopez, Domenico Coppola, David Shibata, Timothy J. Yeatman, Robert J. Gillies, David L. Morse
Journal: Cancer Research (2012)

Abstract In the United States and Europe, colorectal cancer (CRC) has the second highest mortality rate of all cancers. Early diagnosis allows for treatment and improved survival. Currently, colonoscopy is the standard of care for detection of early-stage CRC, which is an invasive procedure that requires a cathartic bowel preparation and general anesthesia. Consequently, less invasive screening methods are highly desirable. The objective of this study is to develop a targeted molecular imaging technique termed “molecular colonography,” that can non-invasively detect dysplastic and neoplastic colonic lesions with high sensitivity and conspicuity by oral administration of ligand-targeted probes containing image contrast agents followed by clearance and non-invasive colonography with MRI, CT or Fluorescence imaging. The first step in the development of molecular colonography is identification of cell-surface markers for CRC. To accomplish this goal, gene expression profiling of DNA microarray data from 432 adenocarcinomas, 39 adenomas and 16 inflammatory bowel disease; and unaffected patient tissue samples (178 colon, 6 small intestine, 4 stomach, 4 esophagus, 4 trachea, 3 oral mucosa and 3 tonsil) was performed. Data were filtered using a previously compiled list of 3,800 cell surface genes from the NCBI Gene Expression Omnibus database. Of these, 1085 genes were broadly expressed in CRC and were ranked by differential expression in adenomas and adenocarcinomas vs. normal tissues. Six cell-surface markers were identified that are highly and broadly expressed as mRNA in adenomas and adenocarcinomas relative to unaffected tissues: TLR4, GPR56, GRM8, LY6G6D, CLDN1 and SLC01B3. TLR4 and/or GRM8 were shown to be expressed in 100% of the colon adenomas and adenocarcinomas in this dataset. To confirm protein expression, immunohistochemistry of normal (n=15) and CRC (16 adenoma and 60 adenocarcinoma) patient tissue samples and 26 CRC cell lines was performed. All six markers were highly and broadly expressed in adenomas and adenocarcinomas compared to normal colon. Further validations by mRNA (qRT-PCR) and protein expression (Western blot and immunocytochemistry) of these markers were also performed in nine colon tumor cell lines (COLO-205, DIFI, HCT15, HCT116, HT-29, KM12C, Km12SM, SW480 and SW620). Development of specific binding ligands for selected targets is underway. 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 1156. doi:1538-7445.AM2012-1156
Abstract 2953: Involvement of HDAC11 in cell division cycle
Authors: Tapan K. Bagui, Savitha Sharma, W. J. Pledger
Journal: Cancer Research (2011)

Abstract Histone deacetylases (HDACs) are a group of enzymes that catalyze removal of acetyl groups from a ε-N-acetyl lysine amino acid on histones. A number of non-histone proteins are also known to be deacetylated by these enzymes. Hence, these proteins are now also being referred to as lysine deacetylases (KDAC). Based on function and DNA sequence similarity, HDAC proteins are classified in four groups; Class I, Class II, Class III and Class IV HDACs. HDAC11, the only member of Class IV HDAC, shows a DNA sequence similarity with both Class I and Class II HDACs. In general, HDAC proteins are known as transcriptional inhibitors and are involved in cellular growth, development and apoptosis. Unlike other HDACs, function of HDAC11 is not widely studied. Although this enzyme is reported as a transcriptional inhibitor, little is known about its role in connection to cell division cycle or cell density. Analysis of our microarray data shows that Balb/C 3T3 cells, stimulated with PDGF and plasma, contain considerably reduced level of HDAC11 transcript compared to that in the quiescent Balb/C 3T3 cells. The protein level under similar conditions mimics the pattern of transcript level. These results indicate that as cells leave quiescence state HDAC11 expression is down-regulated or may be reduction of HDAC11 expression causes quiescent cells to enter cell cycle. It may also be possible that cell-cell contact inhibition positively regulates HDAC11 expression and as the cell grows in presence of PDGF and plasma, the contact inhibitory property is lost which in turn causes the reduction of the protein expression. Further work is in progress to elucidate the role of HDAC11 with respect to cell cycle regulation or cell density. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2953. doi:10.1158/1538-7445.AM2011-2953
MOVING TOWARD A NATIONAL CONSENSUS ON PEDIATRIC HEART FAILURE QUALITY MEASURES: THE ACC QUALITY METRICS WORKING GROUP INITIATIVE
Authors: Christopher S.D. Almond, Angela Lorts, Kevin Daly, Esther Liu, David Rosenthal, Anica Bulic, Michelle Gurvitz, Andrew Shin, Joseph Rossano, Jack Price
Journal: Journal of the American College of Cardiology (2016)
Abstract 265: c-Myc and NFκB are reciprocal and contextual transcriptional regulators of glioma cell proliferation or invasion
Authors: Harshil D. Dhruv, Wendy S. McDonough, Nhan Tran, Brock Armstrong, Serdar Tuncali, Jenny Eschbacher, Kerri Kislin, Michael E. Berens
Journal: Cancer Research (2011)

Abstract Classic histological features of glioblastoma include dense proliferative areas rich in angiogenesis as well as centripetal dissemination of neoplastic cells into adjacent brain tissue (most frequently white matter). The infiltrative dispersion patterns of malignant glioma preclude complete tumor resection; growth of satellite lesions causes significant neurological morbidity and mortality, and accounts for much of the post-treatment, recurrent (fatal) disease. Distinct transcriptomes are discernable between GBM cells at the tumor core and invasive rim, and many of the differentially-expressed genes are co-associated with migration and the collateral phenotype of cell survival; reciprocal downregulation of genes in invasive glioma cells are ontologically associated with proliferation. Our studies of glioma cells from paired core and rim human biopsy specimens reveal a higher proliferative index (Ki67 Mib-1 IHC score) at the core as compared to the rim (19 out of 35 specimens) p &amp;lt; 0.002. Analysis of activation states of transcription factors (Luminex multiplex assay) revealed that nuclear c-myc activity is up in the tumor core while nuclear NFκB activity is up at the invasive rim of the tumor. Depletion of c-myc (siRNA oligonucleotides) resulted in an increase in the migration rate of glioma cells in vitro, whereas inhibition of NFκB by SN50 resulted in a decrease in migration rate both in vitro and ex vivo (rat brain slice). Immunohistochemical validation using a glioma tissue microarray containing paired core and rim biopsy specimens showed that phosphorylated c-myc staining was higher in the core than in the rim for 23 out of 39 biopsy specimens scored, and that phosphorylated NFκB was higher in the rim than the core for 30 out of 43 biopsy specimens scored. The Go vs Grow hypothesis suggests cell proliferation and cell migration are temporally exclusive behaviors and tumor cells postpone cell division for migration. Our findings argue that differential suppression/activation of c-myc and NFκB underlie the shift of glioma cells from growing to going. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 265. doi:10.1158/1538-7445.AM2011-265
DNAM-1 ligand expression on Ag-stimulated T lymphocytes is mediated by ROS-dependent activation of DNA-damage response: relevance for NK–T cell interaction
Authors: Michele Ardolino, Alessandra Zingoni, Cristina Cerboni, Francesca Cecere, Alessandra Soriani, Maria Luisa Iannitto, Angela Santoni
Journal: Blood (2011)
Abstract 4949: A dynamic TGFBR3-JUND expression circuit in single basal-like breast epithelial cells
Authors: Chun-Chao Wang, Leen Jamal, Sameer S. Bajikar, Kristen A. Atkins, Kevin A. Janes
Journal: Cancer Research (2012)

Abstract Basal-like carcinoma is a subtype of breast cancer that is characterized by poor prognosis and high intratumor heterogeneity. In basal-like breast epithelia, we have identified two anticorrelated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first program contains multiple TGFβ-related genes including TGFBR3, and its heterogeneous induction is critical to suppress ductal branching. The second program contains JUND together with the basal-like marker, KRT5. Homogenizing JUND expression in single cells leads to 3D acini with bridged lumina that are similar to cribiform ductal carcinoma in situ. TGFBR3 and JUND together comprise a circuit that is interconnected via four negative-feedback loops. Computational modeling of the circuit predicts damped, antiphase oscillations upon stimulation with endogenous impulses of TGFβ-like ligand, and we directly observe these spontaneous responses in 3D culture by live-cell imaging. The TGFBR3-JUND circuit and its ECM-dependent regulation are remarkably conserved in early basal-like tumors that heterogeneously express KRT5, suggesting that asynchronous circuit dynamics are active in this patient subset. Preliminary studies suggested this intrinsic single-cell expression circuit might be regulated by a transcription factor, Nrf2, and a tumor suppressor, menin. Together, breast tumor heterogeneity need not stem from partial basal-like differentiation and could instead reflect dynamic toggling of individual cells between expression states. 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 4949. doi:1538-7445.AM2012-4949