tbuckley/cabot-search huggingface dataset:
Abstract 61: A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A
Authors: Yuanzhong Wu, Tiebang Kang
Journal: Cancer Research (2016)

Abstract The regulation of stability is particularly crucial for unstable proteins in cells. However, a convenient and unbiased method of identifying regulators of protein stability remains to be generated. Recently, genome-scale CRISPR-Cas9 library has been established as a genetic tool to mediate loss of function screening. Here, we developed a method named Protein Stability Regulators Screening Assay (Pro-SRSA) by combining the whole genome CRISPR-Cas9 library with a dual-fluorescence-based protein stability reporter and high-throughput sequencing to screen regulators of protein stability. Using Cdc25A as an example, Cul4B-DDB1-DCAF8 was determined to be a new E3 ligase for Cdc25A. Moreover, the acetylation of Cdc25A at lysine 150, which was mediated by p300/CBP and deacetylated by HDAC3, was revealed to prevent its ubiquitin-mediated degradation by proteasome. This is the first report that the acetylation as a novel posttranslational modification modulates the Cdc25A stability, and we believe that this efficient and unbiased screening method at the genome-scale will be widely used to globally identify regulators of protein stability. Citation Format: Yuanzhong Wu, Tiebang Kang. A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 61.
Abstract 4236: SUPR-PET: Nuclear imaging of Her2-positieve breast cancer with SUPR peptides
Authors: Lindsay E. Kelderhouse, Amanda Hardy, Federica Pisaneschi, Joshua P. Gray, Seth Gammon, Richard W. Roberts, Terry T. Takahashi, Steve Fiacco, Steven W. Millward
Journal: Cancer Research (2016)

Abstract In recent years, patients with Her2-positive breast cancer have benefitted greatly from targeted therapies such as Trastuzumab and Pertuzumab. However, there are currently no FDA-approved Her2-targeted imaging agents to diagnose and monitor Her2-positive breast cancer leaving physicians to rely on biopsies to determine Her2 status. Whole-body visualization of Her2 would allow the noninvasive identification of all Her2 primary and metastatic lesions as well as serve as a powerful tool to monitor the effectiveness of Her2-targeted therapeutics. We recently described the generation of Her2-targeted SUPR (Scanning Unnatural Protease Resistant) peptides that selectively bind the Her2 receptor in vitro with low nanomolar affinity. Cy5-labeled SUPR peptides showed rapid and Her2-specific tumor uptake and minimal retention in non-tumor tissues after 24 hours of washout. In this study, we describe 18F radiolabeling of Her2-targeted SUPR peptides and their evaluation as PET radiotracers to visualize Her2 expression in vivo. The lead compound, SUPR4, was labeled with 18F-fluoroethylazide in high radiochemical yield and specific activity on an automated radiochemical synthesis platform. The resulting radiotracer (SUPR-18F) showed rapid and Her2-selective tumor uptake between 30-60 minutes post-injection with minimal liver uptake. The majority of the tracer was cleared by the kidneys at 2 hours post-injection although some activity was observed in the GI tract suggesting hepatobiliary excretion. No significant uptake was observed in the brain. 90 minute dynamic PET scans were performed to estimate the rate of tumor uptake and clearance in major organ systems and the biodistribution quantified by autoradiography post-mortem. Pre-injection of unlabeled SUPR peptide, Trastuzumab, and Pertuzumab followed by PET imaging with SUPR-18F was used to confirm tumor uptake as a function of specific binding to the Her2 receptor. Having established the utility of SUPR-18F in pre-clinical mouse models, we anticipate that this class of PET tracers could be employed in same-day imaging procedures throughout the administration of Her2-targeted therapy. Citation Format: Lindsay E. Kelderhouse, Amanda Hardy, Federica Pisaneschi, Joshua P. Gray, Seth Gammon, Richard W. Roberts, Terry T. Takahashi, Steve Fiacco, Steven W. Millward. SUPR-PET: Nuclear imaging of Her2-positieve breast cancer with SUPR peptides. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4236.
Abstract 1296: Vascular shutdown anti-tumor effect of tetra-arsenic oxide on cervical cancer cells
Authors: Yong-Wan Kim.
Journal: Cancer Research (2016)

Abstract Background: Tetra arsenic oxide (As4O6) is a novel arsenic compound that exhibits potent anti-vascular activity and significantly suppresses solid tumor growth. The present study was conducted to investigate the vascular shutdown effects in HPV E6/E7-expressing tumors bearing mice. Methods: After tumors reached 300-350 mm3 in volume, mice were randomly divided into four groups and treated intraperitoneally with three different dose of As4O6 at 1-week interval. Tumor blood perfusion and vascularity were visualized using Hoechst 33342, CD31 staining respectively from 1 hour to 1 week after As4O6 treatment. Histopathological features were observed following hematoxylin and eosin staining. Apoptosis, TNF-a, caspase activity and tumor regression were used to determine the mechanisms for vascular shutdown effects. Results: As4O6 significantly suppressed tumor growth compared with control group. This tumor growth inhibition led to massive necrosis and vascular shutdown in tumor tissue, and also tumor tissue necrosis and apoptosis. Mice treated with As4O6 had a reduction in tumor vessel dimensions compared with the control animals, with CD31 stained microvessels still being apparent at the outer edge of the tumor. Additionally, in the control group, vessel area and diameter increased over time, whereas in the tumors from the As4O6-treated group, vessel area and diameter remained stable or decreased. Apoptotic cell populations induced by As4O6 were increased by double staining the TC-1 cells with annexin V and propidium iodide. Conclusions: The results suggest that As4O6 has potential anticancer activity that is exerted by vascular shutdown in C57BL/6 mice transplanted with TC-1 cells. The study is novel in the observation of recovery of disturbed vascular function. Citation Format: Yong-Wan Kim. Vascular shutdown anti-tumor effect of tetra-arsenic oxide on cervical cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1296.
The Worth of Surveillance for Vancomycin-Resistant Enterococci in the Hematology-Oncology Unit
Authors: Marcelo Bellesso, Edson Abdala, Juliana Pereira, Rodrigo Santucci, Karim Yaqub Ibrahim, Maristela Pinheiro Freire, Lumena Vaz Carvalho Fratelli, Patricia Andréa Crippa Marques
Journal: Blood (2014)
Abstract 4124: Sub-cytotoxic concentrations of a novel polyphenol fatty acid ester derivative arrest breast cancer cell proliferation and metastasis
Authors: Wasundara Fernando, Melanie R. Power Coombs, David W. Hoskin, H. P. Vasantha Rupasinghe
Journal: Cancer Research (2016)

Abstract In this study, the antiproliferative and antimetastatic properties of phloridzin docosahexaenoate (PZ-DHA), a novel polyphenol fatty acid ester derivative, were explored using in vitro and in vivo models of mammary carcinoma. PZ-DHA combines phloridzin (PZ, a dihydrochalcone found in apple peels) with docosahexaenoic acid (DHA, an omega-3 fatty acid). The regioselective acylation reaction was catalyzed by lipase B enzyme from Candida antarctica. PZ-DHA-induced selective cytotoxicity towards breast cancer cells (triple-negative mammary carcinoma cells, MDA-MB-231, MDA-MB-468, and 4T1; estrogen receptor-positive mammary carcinoma cells, MCF-7 and T-47D) was observed compared to human mammary epithelial cells (HMECs and MCF 10A) using the MTS assay. Significantly less (p&amp;lt;0.05) cytotoxicity of PZ-DHA for normal cells was also confirmed using flow cytometric analysis of annexin-V-FLUOS/propidium iodide-stained MCF 10A and human dermal fibroblasts compared to MDA-MB-231 cells. Flow cytometric analysis of Oregon Green 488-stained MDA-MB-231 cells showed an antiproliferative effect of PZ-DHA at sub-cytotoxic concentrations (10 to 30 μM). Cell cycle analysis showed that MDA-MB-231 replication was arrested at the G2/M phase of the cell cycle following treatment with PZ-DHA at sub-cytotoxic concentrations. PZ-DHA suppressed the migration of MDA-MB-231 and 4T1 cells in vitro in wound healing and cell migration assays. Reduced expression of proteins (β-catenin, slug, Zinc finger E-box-binding homeobox 1, vimentin and matrix metalloproteinase-2) involved in the epithelial-to-mesenchymal transition was demonstrated by western blot analysis of PZ-DHA-treated MDA-MB-231 cell lysates. Finally, 4T1 tumor bearing-female BALB/c mice that received intra-peritoneal injections of PZ-DHA showed a significant reduction (p&amp;lt;0.05, n = 9) in primary tumor volume at the mammary fat pad and fewer metastatic lesions in the lungs compared to the saline-treated control mice, suggesting an in vivo antimetastatic effect of PZ-DHA. In conclusion, findings of this study reveal that PZ-DHA suppresses mammary carcinoma cell proliferation and metastasis, suggesting a potential clinical application to prevent breast cancer progression in patients. Citation Format: Wasundara Fernando, Melanie R. Power Coombs, David W. Hoskin, H. P. Vasantha Rupasinghe. Sub-cytotoxic concentrations of a novel polyphenol fatty acid ester derivative arrest breast cancer cell proliferation and metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4124.
Abstract 785: The prepubertal mammary gland transcriptome suggests a role for the immune system in hormone-independent breast cancer
Authors: Hillary Stires, Catina Crismale-Gann, William J. Belden, Wendie S. Cohick
Journal: Cancer Research (2016)

Abstract Identifying signaling pathways involved in mammary gland development has contributed to our understanding of breast cancer. While growth of the gland is isometric between birth and puberty, ductal expansion is significant and morphological changes such as terminal end bud formation occur during this developmental window. While estrogen receptor alpha (ERá) and progesterone receptor (PR) expression are evident during this time, pre-pubertal levels of free estradiol are low and growth is independent of ovarian hormones. Basal-like breast cancers represent a subset of breast cancers (10-15% of all women with breast cancer) that often lack ERá, PR and HER2 (i.e. triple negative), are ovarian hormone independent, and have a worse prognosis than other tumor subtypes. Animal models for basal-like breast cancer are limited. Therefore identifying gene changes during prepubertal mammary gland development may give insight into the mechanisms that drive these breast cancers. Offspring from individual Sprague Dawley dams were sacrificed on postnatal days (PND) 2, 10 and 20 (n = 5 to 6 for each PND) and the fourth inguinal glands were removed. RNA was isolated and sequenced by RNASeq using 25 million paired end reads. Bioinformatics analysis utilizing TopHat, Bowtie2, and CummeRbund revealed &amp;gt;7000 genes that changed during this time (alpha = 0.05). Analysis by DAVID/KEGG and Ingenuity Pathway Analysis demonstrated differences in immune pathways over time whereby immune genes increased from PND 2 to 10 to 20. Specifically, T Cell Receptor Signaling and B Cell Development were two of the most affected pathways. These results are interesting as recent studies have indicated that the immune system may influence basal-like breast cancers. Molecular signatures defining subtypes of basal-like breast cancer have been described and include basal-like immunosuppressed (BLIS) and basal-like immune activated (BLIA). A better understanding of the role of the immune system in prepubertal mammary gland development may help guide treatment strategies for hormone independent breast cancers. Citation Format: Hillary Stires, Catina Crismale-Gann, William J. Belden, Wendie S. Cohick. The prepubertal mammary gland transcriptome suggests a role for the immune system in hormone-independent breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 785.
Abstract 1888: Protein kinase C beta II suppresses colorectal cancer by regulating IGF1 mediated cell survival
Authors: Catriona M. Dowling, James Phelan, Julia A. Callender, Mary Clare Cathcart, Brian Mehigan, Paul McCormick, Tara Dalton, John C. Coffey, Alexandra C. Newton, Jacintha O’Sullivan, Patrick A. Kiely
Journal: Cancer Research (2016)

Abstract Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (60%) survival in patients with relatively high levels of the protein. Consistent with PKC Beta II levels protecting against colon cancer, overexpression of PKC Beta II in colon cancer cell lines reveals that PKC Beta II reverses transformation in cell based assays. Further to this, activation of PKC Beta II in an IGF-1 dependent manor showed a downregulation of AKT, indicating a role for PKCs in regulating IGF-1 mediated cell survival. Thus, PKC Beta II is a tumour suppressor in colon cancer and low levels serve as a predictor for poor survival outcome. Citation Format: Catriona M. Dowling, James Phelan, Julia A. Callender, Mary Clare Cathcart, Brian Mehigan, Paul McCormick, Tara Dalton, John C. Coffey, Alexandra C. Newton, Jacintha O’Sullivan, Patrick A. Kiely. Protein kinase C beta II suppresses colorectal cancer by regulating IGF1 mediated cell survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1888.
Donor-Type Aplasia After Bone Marrow Transplantation in Children with Aplastic Anemia: A Nationwide Retrospective Study
Authors: Nao Yoshida, Hiroshi Yagasaki, Hiromasa Yabe, Akira Kikuchi, Ryoji Kobayashi, Yoshiyuki Takahashi, Jiro Inagaki, Masami Inoue, Keisei Kawa, Ritsuro Suzuki, Koji Kato, Seiji Kojima
Journal: Blood (2012)
Abstract 1398: RNA DIRECT: A novel strategy for targeted RNA enrichment of transcripts associated with solid tumors
Authors: Kruti M. Patel, Sarah K. Bowman, Theodore B. Davis, Salvatore Russello, Daniel C. Kraushaar, Amy B. Emerman, Noa Henig, Cynthia L. Hendrickson
Journal: Cancer Research (2016)

Abstract RNA sequencing (RNA-seq) has become a powerful platform for profiling transcriptomes that enables gene expression analysis and identification of nucleotide or structural variations. RNA-seq, however, can be cost prohibitive due to the size and complexity of most transcriptomes, which require deep sequencing coverage to achieve the necessary sensitivity for a reliable analysis. By combining targeted enrichment strategies with next-generation sequencing (NGS), a subset of transcript regions or sequences can be enriched for and analyzed with the resolution required for both research and clinical applications. The RNA DIRECT targeted enrichment method utilizes probe-based hybridization to capture only relevant cDNA sequences. Targeted sequences are then ligated to NGS platform specific adaptors and amplified by PCR. The RNA DIRECT strategy provides a robust and cost effective method for the enrichment of transcript sequences for the purpose of identification and detection of known or novel variants and gene fusions. To demonstrate the high specificity, sensitivity and uniformity of this method, we have applied it to the capture of targets commonly associated with solid tumors. Citation Format: Kruti M. Patel, Sarah K. Bowman, Theodore B. Davis, Salvatore Russello, Daniel C. Kraushaar, Amy B. Emerman, Noa Henig, Cynthia L. Hendrickson. RNA DIRECT: A novel strategy for targeted RNA enrichment of transcripts associated with solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1398.
Abstract 3405: The analysis of TRPV6 expression in lymphoid tumours
Authors: Ashley M. DiPasquale, Tarek Rahmeh, Lauren Andrew, Jane Agar, Kim Miller, Matthew Finniss, Alli Murugesan, Anthony Reiman
Journal: Cancer Research (2016)

Abstract Introduction: TRPV6 is a calcium channel that is found overexpressed in various malignancies and is correlated with the prognosis of patients with prostate cancer. TRPV6 targeted anticancer therapies are in development. We are interested in the potential of TRPV6 as a potential biomarker and therapeutic target in lymphoma. This retrospective study examines the expression levels of TRPV6 in various lymphoid tumour types, and correlates expression levels with grade, prognostic scores, and survival rates. Methods: A clinical-pathological database was constructed using the health records and lymphoid tumor samples of patients diagnosed with diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma (FL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and Hodgkin's lymphoma (HL). Immunohistochemical studies were performed on lymphoid tumor samples to analyze the level of TRPV6 expression. Tumor samples were graded on a 3-point scale. A score of +3 indicated dense staining with high expression levels, and a score of +1 indicated minimal staining with low expression levels. TRPV6 expression levels were correlated with prognostic scores (IPI, FLIPI) and survival rates using Chi-squared, Mantel-Cox, and Kaplan-Meier survival curves. Descriptive statistics were used to describe patient demographics. Results: We found high TRPV6 expression levels in DLBCL and HL tumor samples with &amp;gt; 40% of samples scoring +3. We found low TRPV6 expression levels in FL and SLL/CLL with &amp;gt; 40% of samples scoring +1. We found no significant correlation between the level of TRPV6 expression and prognostic scores or survival rates in any of the lymphoma subtypes studied. In follicular lymphoma tumor samples, it was noted on observation that the large tumor cells generally stained +3 while the small tumor cells generally stained +1. Conclusion: This retrospective study showed DLBCL and HL tumors have high levels of TRPV6 expression. It also showed that TRPV6 is found highly expressed in the large transformed cells (centroblasts) in follicular lymphoma. These results demonstrate a need to further assess the role of TRPV6 in the aggressiveness of follicular lymphoma, as well as the prognosis and survival in DLBCL and HL with a larger sample size. Further studies of the potential of TRPV6 as a therapeutic target in lymphoma will focus on DLBCL, high grade/transformed FL, and HL. Citation Format: Ashley M. DiPasquale, Tarek Rahmeh, Lauren Andrew, Jane Agar, Kim Miller, Matthew Finniss, Alli Murugesan, Anthony Reiman. The analysis of TRPV6 expression in lymphoid tumours. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3405.
Abstract 2857: The yeast homolog of the mammalian oncogene, Bax Inhibitor-1, regulates the unfolded protein response by altering the ER microenvironment
Authors: Savannah Benko, Melissa Brown, Morgan McCarthy, Matthew Sanborn, William Cavedon, Lukas Ritzer, B. Michael Berry, Nicanor Austriaco
Journal: Cancer Research (2016)

Abstract Bax inhibitor-1 (BI-1) is an anti-apoptotic gene whose expression is upregulated in a wide range of human cancers. The yeast homolog of BI-1, yeast Bax inhibitor-1 (BXI1), encodes a protein that belongs to the Bax Inhibitor (TMBIM) family of proteins. The crystal structure of a prokaryotic member of the family, BsYetJ, has revealed that the Bax inhibitor proteins are pH sensitive calcium leaks. Our studies have shown that yeast Bxi1p is localized to the ER and is involved in the unfolded protein response (UPR) that is triggered by ER stress. We have recently found that Bxi1p regulates the UPR downstream of endonuclease Ire1p clustering but upstream of HAC1 mRNA splicing. Studies with an ER localized calcium reporter and an ER redox reporter suggest that Bxi1p accomplishes this by altering the ER microenvironment. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.] Citation Format: Savannah Benko, Melissa Brown, Morgan McCarthy, Matthew Sanborn, William Cavedon, Lukas Ritzer, B. Michael Berry, Nicanor Austriaco. The yeast homolog of the mammalian oncogene, Bax Inhibitor-1, regulates the unfolded protein response by altering the ER microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2857.
Les plans pandémiques antigrippaux en Europe : historique et principes
Authors: C Hannoun
Journal: Eurosurveillance (1998)

La grippe espagnole de 1918-1919 a touche pratiquement toutes les familles. Au soulagement apporte par la fin d'une guerre mondiale atroce venaient se substituer les epreuves engendrees par un fleau foudroyant qui fit plus de 20 millions de victimes. La grippe dont les formes epidemiques ont des consequences tres differentes (tableau 1) peut en effet devenir un fleau redoutable.