tbuckley/cabot-search huggingface dataset:
Abstract 1590: CD133-expressing circulating tumor cells might predict poor prognosis in patients with head and neck cancer
Authors: Jason Chia-Hsun Hsieh, Harber Hung-Bo Shiao, Bill Yuan-Jhih Chao, Ming-Jung Lin, John Wen-Cheng Chang, Hung-Ming Wang, Tyler Min-Hsien Wu
Journal: Cancer Research (2015)

Abstract PURPOSE: The prognostic value of circulating tumor cells (CTCs) number in patients with head and neck carcinoma (HNSCC) has been reported to be positive. The hypothesis of the additional markers on CTCs might predict clinical outcomes have been proposed. This study aimed to elucidate the prognostic/predictive value of CD133-expressing CTCs in HNSCC patients. PATIENTS AND METHODS: In a prospective single-center study, CTCs were enumerated in the peripheral blood of 24 subjects, including 14 patients with HNSCC and 10 healthy donors, at baseline and 2 weeks after starting first dose of chemotherapy. CTCs were measured using an immunomagnetic separation technique by combined negative and positive selection strategies. Immunofluorescence staining methods were applied for surface marker identification. Tumor response at 12 weeks after chemotherapy of the whole cohort was performed by computed tomograpgy or magnetic resonance imaging scans following RECIST criteria 1.1. RESULTS: In the first step of efficacy evaluation phase, an average recovery rate of 85.5% and a R2 value of 0.9932 were found when compared between spiked and recovered blood samples. A CTCs detection rate of 100.0% (14/14) was found by this protocol and the number could successfully differ HNSCC patients from healthy donors (P = 0.001). The mean and median (range) of baseline CTC number were 105.0 and 87.2 (34.5-358.1) cells/mL of blood. The higher baseline CTCs number was associated with higher tumor stage (AJCC 7th edition, P = 0.003). The higher absolute number (&amp;gt;5cells/mL of blood) of baseline CD133-expressing CTCs could predict poor survivals (Kaplan-Meier survival curves, P = 0.013). In all assessable patients, a high correlation rate of 92.9% was found between changes of CTCs (decline or elevation) and CT responses (progressive disease [PD] and partial response [PR]/Stable disease [SD]) with a P value of 0.005 (Fisher exact test). CONCLUSION: The number of CD133-expressing CTCs might be a useful prognostic for survivals and predictors for imaging response evaluation at 12 weeks in patients with HNSCC. Further investigation in large-scale prospective trials is warranted on the basis of the findings in this study. Citation Format: Jason Chia-Hsun Hsieh, Harber Hung-Bo Shiao, Bill Yuan-Jhih Chao, Ming-Jung Lin, John Wen-Cheng Chang, Hung-Ming Wang, Tyler Min-Hsien Wu. CD133-expressing circulating tumor cells might predict poor prognosis in patients with head and neck 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 1590. doi:10.1158/1538-7445.AM2015-1590
Abstract 5205: Docosahexaenoic acid (DHA) alters breast cancer exosome-mediated microRNA signaling
Authors: Bethany N. Hannafon, Karla Carpenter, William Berry, Ralf Janknecht, William Dooley, Wei-Qun Ding
Journal: Cancer Research (2015)

Abstract DHA is a long-chain omega-3 polyunsaturated fatty acid that has anticancer properties, including the ability to suppress tumor angiogenesis. However, the precise mechanism of DHAs anti-angiogenic activity is not well defined. It is recognized that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are nanometer-sized extracellular vesicles that are important mediators of intercellular communication and in recent years, the role of tumor-derived exosomes in cancer progression has been realized. However, ways to limit or alter their influence on cancer progression has not been demonstrated. At this time, very little is known about the role of breast cancer derived exosomes in contributing to breast cancer progression and whether these exosomes mediate DHAs anticancer activity. To investigate, breast cancer exosomes were collected from the conditioned media of MCF7 and MDA-MB-231 breast cancer cells engineered to express GFP-tagged CD63 after treatment with DHA. We observed an increase in exosome secretion from the DHA-treated cells. Total RNA was extracted from the DHA-treated and control MCF7-derived exosomes and analyzed by small RNA sequencing. The expression of 83 exosome microRNAs was altered by DHA (&amp;gt;2-fold) and several of the most abundant exosomal microRNAs (miR-23b, miR-27a/b, miR-21, and miR-320b) are known to have anti-angiogenic activity. When DHA-treated MCF7 cells were co-cultured with or the collected exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, an effect that could be reversed by inhibition of exosome secretion via Rab27A knockdown. These results suggest that the microRNAs transferred by exosomes mediate DHAs anti-angiogenic action. Our data demonstrates that DHA alters breast cancer exosome secretion and microRNA contents that leads to the inhibition of endothelial tube formation. These results provide insight into the future possibility of developing new cancer therapeutic strategies targeting exosome secretion and content transmission. Citation Format: Bethany N. Hannafon, Karla Carpenter, William Berry, Ralf Janknecht, William Dooley, Wei-Qun Ding. Docosahexaenoic acid (DHA) alters breast cancer exosome-mediated microRNA signaling. [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 5205. doi:10.1158/1538-7445.AM2015-5205
Can High Dose Therapy Change the Course of Low Grade Lymphoma? A Study Considering Patients as Their Own Control.
Authors: Stephane Vignot, Nicolas Mounier, Guillaume Sergent, Pauline Brice, Jean-Pierre Marolleau, Nathalie Parquet, Josette Briere, Eric DeKerviller, Isabelle Madeleine, Christian Gisselbrecht
Journal: Blood (2004)
P1227 : Intra-hepatic Cholestasis of Pregnancy (ICP): Prevention of recurrence of ICP and intra uterine fetal death by pre-pruritus administration of ursodeoxycholic acid
Authors: J.R. Bernuau, P. Millot, D.C. Valla, A.-M. Bernard, E. Sauvanet, D. Luton, D. Dhumeaux
Journal: Journal of Hepatology (2015)
702. Detection and Isolation of Immune Cells After Intramuscular AAV Injection in Mouse and Human
Authors: Gwladys Gernoux, Alisha Gruntman, Terence R. Flotte, Christian Mueller
Journal: Molecular Therapy (2016)

Recombinant adeno-associated viral (rAAV) vectors are promising tools for gene transfer to the skeletal muscle. However, studies on mouse and large animal models as well as humans demonstrate that intramuscular (IM) rAAV delivery can trigger immune responses to AAV capsid and/or transgene. Recently, IM delivery of rAAV1 in humans induced a tolerogenic response to rAAV characterized by the presence of capsid-specific regulatory T cells (Tregs) in the periphery. The aim of our study was to develop an assay to allow detection and characterization of immune cells in situ after AAV gene transfer. Mice were injected intramuscularly with an AAV vector. Seven days after injection, muscles were collected and enzymatic dissociation was performed. Our results show that we are able to detect immune cells (monocytes/macrophages, lymphocytes) in mouse muscle by flow cytometry. This assay was also used on a human muscle biopsy collected 5 years after AAV1-AAT gene transfer and revealed the presence of infiltrated Tregs and CD8+ T-cells at the site of injection. This method appears as a new tool in understanding immune responses in the muscle after AAV gene transfer.
Abstract 3013: RNF126 promotes homologous recombination via regulating E2F1-mediated BRCA1 expression
Authors: Ying Wang, Ou Deng, Zhihui Feng, Zhanwen Du, Xiahui Xiong, Ceshi Chen, Zhefu Ma, Junran Zhang
Journal: Cancer Research (2015)

Abstract Abstract: Homologous recombination (HR)-mediated DNA double-strand break repair is important for cell proliferation, cancer prevention and cancer therapy resistance. HR protein BRCA1 is one of the most important breast/ovarian cancer suppressor genes. Lower expression of BRCA1 has been frequently observed in a broad spectrum of human cancers, particularly sporadic breast/ovarian cancers. However, the mechanisms governing BRCA1 expression is elusive. RNF126 is an E3 ubiquitin ligase and is mapped to chromosome 19 p13.3 which is a commonly deleted region in ovarian cancers. In addition, high-resolution 19p13.2-13.3 allelotyping of breast carcinomas demonstrates frequent loss of heterozygosity. The Cancer Genome Atlas (TCGA) data suggested that RNF126 depletion present in a broad spectrum of human tumors, particularly ovarian cancers. Although a recent study suggested that RNF126 promote cell growth, the function of RNF126 remains largely unknown. Here, we demonstrate that RNF126 facilitates HR by promoting the expression of BRCA1, in a manner independent of its E3 ligase activity but depending on E2F1, a well-known transcription factor of BRCA1 promoter. In support of this result, RNF126 promotes transactivation of BRCA1 promoter by directly binding to E2F1. Most importantly, an RNF126 mutant lacking 10 amino acids that is responsible for the interaction with E2F1 has a dominant-negative effect on BRCA1 expression by suppressing E2F1-mediated transactivation of BRCA1 promoter and blocking the enrichment of E2F1 on BRCA1 promoter. Last, RNF126 depletion leads to the increased sensitivity to ionizing radiation (IR) and poly (ADP-ribose) polymerase (PARP) inhibitor. Collectively, our results suggest a novel role of RNF126 in promoting HR-mediated repair through the positive regulation on BRCA1 expression by binding to E2F1. This study not only offers novel insights into our current understanding of the biological functions of RNF126 but also provides a potential therapeutic target for the cancer treatment. Key words: Homologous recombination, RNF126, E2F1, BRCA1 Citation Format: Ying Wang, Ou Deng, Zhihui Feng, Zhanwen Du, Xiahui Xiong, Ceshi Chen, Zhefu Ma, Junran Zhang. RNF126 promotes homologous recombination via regulating E2F1-mediated BRCA1 expression. [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 3013. doi:10.1158/1538-7445.AM2015-3013
Prospective Evaluation of Azacitidine Maintenance Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Harinder Gill, Albert Kwok Wai Lie, Yok Lam Kwong, Anskar Y.H. Leung
Journal: Blood (2015)
Abstract 3608: Prostaglandin E-2 promotes resistance to oxaliplatin in colorectal cancer cells
Authors: Huakang Huang, Daniel W. Rosenberg
Journal: Cancer Research (2015)

Abstract Oxaliplatin, a platinum-based DNA crosslinking agent, has been used successfully as a first-line chemotherapeutic agent for the treatment of metastatic colorectal cancer (CRC). However, long-term treatment with oxaliplatin results in resistance in nearly all patients, limiting its therapeutic efficacy. Previous studies have shown that treatment of CRC cells with selective inhibitors of the enzyme Cyclooxygenase-2 (COX-2) leads to the development of drug resistance. One of the terminal products of the COX-2 pathway, prostaglandin E-2 (PGE2), is a pro-inflammatory lipid that has been implicated in colorectal tumorigenesis; however, it is unknown whether PGE2 plays a role in the development of drug resistance. In this study, we have begun to investigate the relationship between PGE2 and oxaliplatin resistance using the human CRC cell lines, HT29 and HCT116. Oxaliplatin-resistant HT29 cells (HT29-OXR) were generated by continuous exposure of parental HT29 cells to increasing concentrations of oxaliplatin over a period of 3 months. We have found that HT29-OXR cells produce significantly higher levels of PGE2 (3-fold increase, p&amp;lt;0.05) compared to the parental HT29 cell line. In addition, we have observed concomitantly elevated levels of the terminal PGE2 synthase, microsomal prostaglandin E synthase-1 (mPGES-1). Furthermore, we have demonstrated that the addition of exogenous PGE2 to both parental HT29 and HCT116 cells significantly (p&amp;lt;0.0001) decreased their sensitivity (IC50) to oxaliplatin, measured by the MTT cell viability assay. These findings suggest that PGE2 promotes resistance to oxaliplatin in CRC cells. FACS analysis showed that co-treatment of HT29 cells with exogenous PGE2 for 24 hours leaded to 27% reduction in oxaliplatin-induced Annexin V staining for early apoptosis, while exogenous PGE2 maintained G2/M arrest and simultaneously reduced the proportion of dead sub-G1 cells by approximately 80.4% in parental HCT116 cells. Our findings reveal a role for PGE2 in oxaliplatin resistance, possibly via regulation of apoptosis, and provide new data suggesting that targeting mPGES-1 may be a useful strategy for overcoming oxaliplatin resistance. Citation Format: Huakang Huang, Daniel W. Rosenberg. Prostaglandin E-2 promotes resistance to oxaliplatin in colorectal cancer cells. [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 3608. doi:10.1158/1538-7445.AM2015-3608
Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation In Autologous Hematopoietic Stem Cell Transplantation (HSCT) for Severe Multiple Sclerosis (MS).
Authors: Riccardo Saccardi, Filippo Fani, Annamaria Repice, Pietro Maggi, Massimo Di Gioia, Elisabetta Andreoli, Alberto Bosi, Stefano Guidi, Antonella Gozzini, Luca Massacesi, Maria Pia Amato, Chiara Nozzoli
Journal: Blood (2010)
Assessment of Hematologic and Non-Hematologic Toxicity in Older Cancer Patients Receiving Systemic Chemotherapy: Results from a Prospective Nationwide Registry.
Authors: Naeem Tahir, Jerome H. Goldschmidt, Eva Culakova, Marek S. Poniewierski, Debra A. Wolff, David C. Dale, Jeffrey Crawford, Gary H. Lyman
Journal: Blood (2004)
345. A Novel Toolbox for RNA-Editing Based on Massively Parallel Screening Using Barcoded Viral Vectors
Authors: Marcus Davidsson, Patrick Aldrin-Kirk, Paula Díaz-Fernández, Luis Quintino, Cecilia Lundberg, Tomas Björklund
Journal: Molecular Therapy (2015)

Recent technical advances have opened up new avenues in molecular science with great impact on both in vitro and in vivo applications. Next generation sequencing has become available to a greater extent and advanced molecular techniques and methods within RNA/DNA-editing, barcoding and generation of high diversity DNA libraries are constantly evolving, giving rise to novel applications and discoveries. The aim of this study was to establish an unbiased, totally randomized screening assay for RNA-editing that can be universally utilized. By creating high resolution DNA-libraries from genomic sequences where each fragment is uniquely labelled with a DNA-barcode, we were able to map the biological function of each complete sequence. Here, we have utilized this approach to identify the most promising intronic sequences for RNA-editing. The screening assay was performed by deep sequencing of a lentiviral library, where each fragment was linked to a corresponding barcode. mRNA from transduced cells in vitro and in vivo was sequenced to identify and count the expressed barcodes, thus we could identify specific fragments suitable for RNA-editing. RNA-editing was achieved via trans-splicing, where two different pre-mRNAs (one endogenous and one virally derived) hybridize through complementary sequences and form one mRNA. In trans-splicing, only the downstream segment of the mRNA is replaced, thus the gene is still under the control of its native promoter and other endogenous regulatory elements remain unaltered. Trans-splicing is inherently specific since the part of the mRNA that is delivered requires endogenous expression to exert an effect. By combining advanced cloning methods, DNA-barcoding and Next generation sequencing, we could screen extensive DNA libraries and select fragments highly efficient in RNA-editing. Our method can be used for correction of mutations, protein tracing and cell type identification.
Shear forces induce the synthesis of urokinase-type plasminogen activator in human iliac vein endothelial cells in vitro;
Authors: E.D. Ponfoort, J.H. van Bockel, V.W.M. van Hinsbergh
Journal: Circulation (1995)

Abstracts From the 68th Scientific Sessions, Anaheim Convention Center Anaheim, California November 13-16, 1995
Abstract 3860: USP7 deubiquitinase promotes ubiquitin-dependent DNA damage signaling by stabilizing RNF168
Authors: Qianzheng Zhu, Nidhi Sharma, Jingshan He, Gulzar Wani, Altaf A. Wani
Journal: Cancer Research (2015)

Abstract In DNA damage response (DDR), histone ubiquitination by RNF168 is a critical event, which orchestrates the recruitment of downstream DDR factors, e.g. BRCA1 and 53BP1. Here, we report USP7 deubiquitinase regulates the stability of RNF168. We showed that USP7 disruption impairs the monoubiquitination of H2A (uH2A) and ultraviolet radiation (UVR)-induced monoubiquitination of γH2AX, and decreases the levels of pBmi1, Bmi1, RNF168, pChk1 and BRCA1. USP7 silencing by siRNA reduces uH2A and UVR-induced monoubiquititination of γH2AX, as well as the levels of Ring1B, Bmi1, RNF168 and BRCA1, recapitulating the chronic USP7 deficiency. USP7 disruption also compromises the formation of UVR-induced foci (UVRIF) and ionizing radiation-induced foci (IRIF) of uH2A, poly-K63-ubiquititination and BRCA1, but does not affect UVRIF and IRIF of 53BP1. USP7 was shown to physically bind RNF168 in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytic-inactive or interaction-defective mutants, prevents UVR-induced RNF168 degradation. Both USP7 mutants are unable to cleave Ub-conjugates of RNF168 in vivo. Furthermore, ectopic expression of RNF168, or both RNF8 and RNF168 together, rescue the formation of UVRIF and IRIF of poly-K63-ubiquititination and BRCA1. Taken together, these findings reveal an important role of USP7 in regulating ubiquitin-dependent signaling via stabilization of RNF168. Note: This abstract was not presented at the meeting. Citation Format: Qianzheng Zhu, Nidhi Sharma, Jingshan He, Gulzar Wani, Altaf A. Wani. USP7 deubiquitinase promotes ubiquitin-dependent DNA damage signaling by stabilizing RNF168. [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 3860. doi:10.1158/1538-7445.AM2015-3860
Concurrent CBDCA plus radiotherapy for locally advanced head and neck cancer patients inappropriate for use of CDDP
Authors: Satoshi Hamauchi, Tomoya Yokota, Yusuke Onozawa, Hirofumi Ogawa, Tsuyoshi Onoe, Tetsuo Nishimura, Tomoyuki Kamijo, Yoshiyuki Iida, Tetsuro Onitsuka, Hirofumi Yasui
Journal: Annals of Oncology (2015)
Abstract 3055: Regulation of mitochondria-nuclear crosstalk in triple negative breast cancer
Authors: Jun H. Park, Sajna A. Vithayathil, Nagireddy Putluri, Efrosini Tsouko, Taraka R. Donti, Daniel E. Frigo, Chad J. Creighton, Michael T. Lewis, Arun Sreekumar, Lee-Jun Wong, Benny A. Kaipparettu
Journal: Cancer Research (2015)

Abstract Driver pathways of triple negative breast cancer (TN BCa) is still poorly understood. Thus, it is important to identify the underlying mechanisms of TN BCa progression. Importantly, African American and Hispanic patients are more likely to be diagnosed of BCa at a younger age, have a higher probability of developing TN BCa. They also diagnosed with a more advanced stage of the disease compared to Caucasian women. Src oncognenic pathway is one of the major tumor driving mechanisms in TN BCa. Src pathway is frequently over-expressed in TN BCa and Src inhibitors are one of their current treatments of choices. However, recent single drug therapy Phase-II trials with Src inhibitors failed to control unselected metastatic TN BCa. This raises some important questions on the underlying mechanism in the regulation of Src in TN BCa especially in aggressive metastatic BCa. Mitochondria, a semiautonomous organelle in cells, play an important role in cellular energy metabolism, free radical generation, and apoptosis. Mitochondria-nuclear crosstalk is a bidirectional pathway of communication between mitochondria and nucleus that influences many cellular and organismal activities. This crosstalk can regulate several oncogenic pathways involved in tumorigenesis. Using transmitochondrial cybrid (cybrid) technology, we generated different cybrid models under common nuclear background of TN BCa. Mitochondria from cells of different cancer potential including benign breast epithelium, moderately and highly metastatic breast cancer cell lines were used to understand cancer mitochondria regulated tumor pathways. Extensive analysis of cybrid models as well as confirmation in parental cell lines and other tumor models suggested that autophosphorylation of c-Src is regulated by mitochondrial tumor characteristics. Ongoing studies using knock-down and over expression approaches focus on the role of specific mitochondrial proteins that are responsible for mitochondria-nuclear crosstalk and the regulation oncopathways in TN BCa. Citation Format: Jun H. Park, Sajna A. Vithayathil, Nagireddy Putluri, Efrosini Tsouko, Taraka R. Donti, Daniel E. Frigo, Chad J. Creighton, Michael T. Lewis, Arun Sreekumar, Lee-Jun Wong, Benny A. Kaipparettu. Regulation of mitochondria-nuclear crosstalk in 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 3055. doi:10.1158/1538-7445.AM2015-3055
A new alphabet for COPD care: where “E” stands for España
Authors: Robert P. Young, Raewyn J. Hopkins
Journal: European Respiratory Journal (2017)

We read with interest the editorial by Kerwin [1] on the management of chronic obstructive pulmonary disease (COPD). This editorial follows the publication of the AFFIRM trial showing the superior bronchodilating effects of a long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combination over an inhaled corticosteroid (ICS)/LABA combination in a head-to-head trial, although symptom-based outcomes were not different [2]. These findings replicate those of the FLAME trial showing non-inferiority between a LAMA/LABA over an ICS/LABA combination, although reductions in exacerbations were greater in the former [3]. We would like to endorse the view of Kerwin [1] and Vogelmeier et al. [4] that it is a good time to "refine the paradigmatic GOLD classification". An alternative schema to the 2011 GOLD A-to-D strategy, where the "E" category represents patients with ACOS only <http://ow.ly/BGiN3069GKD>
Decreased NO Bioavailability Leading to Endothelial Dysfunction in Children with ALL Results From Increased eNOS Inhibiting by Asymmetrical Dimethylarginine and May Be Associated with Increased Mortality
Authors: Julita Porwolik, Ewa Niedzielska, Adrian Doroszko, Alicja Piasecka-Grzeszek, Urszula Solska, Alicja Chybicka, Andrzej Szuba
Journal: Blood (2011)
Methylation Profiling of Three Homogenous Cancers: Chronic Myelogenous Leukemia (CML), Acute Promyelocytic Leukemia (APL) and Gastrointestinal Stromal Tumors (GIST).
Authors: Hyang-Min Byun, Shahrooz Eshaghian, Jia Yi Jiang, Si Ho Choi, Laleh Ramezani, Dan Douer, Guillermo Garcia-Manero, Jean-Pierre Issa, Dan Yang, Jonathen Trent, Allen S. Yang
Journal: Blood (2006)