tbuckley/cabot-search huggingface dataset:
Abstract LB-112: The human papillomavirus type 16 E5 protein represses X-box binding protein 1 and cyclooxygenase-2 stress signaling in keratinocytes
Authors: Sawali R. Sudarshan, Xuefeng Liu, Richard Schlegel
Journal: Cancer Research (2010)

Abstract Human papillomavirus (HPV) is the causative agent of 99% of cervical cancers, around 60% of which are caused by the high-risk type 16. While two of its three oncoproteins, E6 and E7, have been well characterized, the biological functions of the E5 protein remain elusive. Recent studies have suggested that E5 enhances HPV-induced oncogenesis, although in isolation it is not tumorigenic. In this study, we analyzed the gene expression changes induced by the endoplasmic reticulum (ER) resident HPV-16 E5 protein in primary human keratinocytes. Using real-time RT-PCR, we identified the downregulation of spliced X-box binding protein 1 (XBP-1), a key player in the ER-stress response, as a biochemical marker of E5 expression. The transmembrane kinase receptor responsible for the cleavage of XBP-1, ER-to-nucleus signaling 1 protein (IRE1α/ERN1), was also downregulated in E5-transduced cells. Furthermore, a microarray analysis of E5-transduced keratinocytes revealed the downregulation of another member of the ER-stress response pathway, prostaglandin G/H synthase and cyclooxygenase (COX-2/PTGS2). In addition, levels of COX-2 and XBP-1 were measured in keratinocytes expressing either low-risk HPV-6b E5 or a C-terminal 16E5 mutant containing a two amino acid mutation. The latter mutant had the histidine and alanine residues (conserved in the high-risk HPVs) replaced with tyrosine and isoleucine (conserved in the low-risk HPVs). Importantly, neither 6bE5 nor the H77YA78I 16E5 mutant was able to affect levels of these ER-stress response genes, suggesting that the ability to induce such changes in gene expression is specific to high-risk 16E5. Since preliminary data showed that expression of the E6 and E7 proteins in keratinocytes greatly induced XBP-1 splicing, we hypothesized that 16E5 might play a protective role against the host response to viral infection. In agreement with this postulate, we found that cells co-expressing E6, E7 and E5 had lower levels of COX-2 expression than cells expressing E6 and E7 alone. Interestingly, the levels of COX-2 in E6/E7-transduced cells were also supressed when compared to vector alone, suggesting that multiple pathways of COX-2 repression may exist. The mechanism by which E5 downregulates COX-2 is currently unknown, but it can be overcome by treatment with thapsigargin or tunicamycin, which initiate ER stress via calcium fluxes and abnormal protein glycosylation respectively. It is therefore unlikely that E5 is specifically tempering these pathways. Our data suggest a potential role for E5 in repressing the cellular ER-stress response following HPV infection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-112.
Fatal Hantavirus Pulmonary Syndrome in Indiana
Authors: Thomas G. Slama, Robin Zon
Journal: New England Journal of Medicine (1994)

To the Editor: On January 8, 1994, a 48-year-old diabetic male teacher from a small town in rural Indiana presented to the hospital with a three-day history of myalgia, weakness, fever, chills, a nonproductive cough, and progressive shortness of breath. He had not traveled to the southwestern United States and had no known exposure to rodent excreta1–3. He had a temperature of 39 °C (102 °F), tachycardia, tachypnea, diaphoresis, and a moderate amount of respiratory distress. Moist rales and decreased breath sounds were noted in all lung fields, but he had no petechiae, ecchymoses, or other signs of . . .
Association of Mutations in the Apolipoprotein B Gene with Hypercholesterolemia and the Risk of Ischemic Heart Disease
Authors: Anne Tybjærg-Hansen, Rolf Steffensen, Hans Meinertz, Peter Schnohr, Børge G. Nordestgaard
Journal: New England Journal of Medicine (1998)

Familial hypercholesterolemia leads to premature ischemic heart disease and is often caused by mutations in the gene for the low-density lipoprotein receptor. Mutations in the apolipoprotein B gene, which encodes a ligand for this receptor, may also result in this phenotype.
MEASUREMENT OF GLOMERULAR FILTRATION RATE BY THE SINGLE INJECTION METHOD WITHOUT URINE COLLECTION: A COMPARISON OF SINGLE SAMPLE, DOUBLE SAMPLE, AND MULTIPLE SAMPLE METHODS USING YTTERBIUM-DTPA.
Authors: C. D. Russell, P. G. Bischoff, F. Kontzen, K. L. Rowell, M. V. Yester, L. K. Lloyd, W. N. Tauxe, E. V. Dubovsky
Journal: Clinical Nuclear Medicine (1984)

Russell, C. D.; Bischoff, P. G.; Kontzen, F.; Rowell, K. L.; Yester, M. V.; Lloyd, L. K.; Tauxe, W. N.; Dubovsky, E. V. Author Information
Abstract LB-268: Loss of HPV16 E2 protein expression and transcriptional modulation of cellular and viral genes correlate with progression to cervical carcinoma
Authors: Francoise Thierry
Journal: Cancer Research (2012)

Abstract Integration of the viral DNA in the cellular genome has been suggested to be critical in carcinogenic progression of HPV-associated cervical neoplasia. This event can be accompanied by disruption of the open reading frame (ORF) encoding the E2 repressor, thus leading to transcriptional up-regulation of the E6 and E7 viral oncogenes. At this stage, it is unclear whether disruption of the E2 ORF is mandatory for carcinogenic progression. We measured E2 RNA and protein expression in clinical samples of various grades of HPV16-associated cervical neoplasia and compared it with the status of the viral genome. RNA extracted from paraffin embedded tissues was hybridized to specific probes and quantified by the NanoString technology. Protein expression was appreciated by immunohistochemistry and the status of viral DNA was determined by in situ hybridization, all performed on serial sections of the same samples. E2 protein was found highly expressed in CIN2 lesions where the HPV DNA was highly replicating, while it was decreased in more advanced grade lesions where replication is decreased or lost (CIN3 and SCC). Our data demonstrate that integration of the viral DNA in the cellular genome is always accompanied by drastic reduction of expression of the E2 protein, even when the E2 ORF is not disrupted by integration. The viral genes appear differentially expressed during progression as transcription of the HPV16 E6/E7 oncogenes, only when compared to E2-E4, is significantly higher in high grade lesions than in CIN2. In addition, transcription of 400 cellular genes of the cell cycle and immune-response were also studied in 20 clinical samples that show modulation during progression. We will discuss the establishment of a transcriptional signature for progression in cervical cancer and the role of local immune response in the fate of cervical lesions associated with HPV16. 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 LB-268. doi:1538-7445.AM2012-LB-268
Abstract 5404: Inhibition of AKT sensitizes HeLa-S3 cells to arsenite-induced mitotic cell apoptosis
Authors: Ling-Huei Yih, Nai-Chi Hsu, Yi-Chen Wu, Wen-Yen Yen, Yu-Hsuan Tang
Journal: Cancer Research (2010)

Abstract Arsenic trioxide (ATO) was proved effective in the treatment of promyelocytic leukemia by inducing apoptosis. However, the use of ATO as a single agent in clinical trials against solid tumors was found to be mostly not effective or too toxic. Induction of mitotic arrest was recently shown to be one of the major mechanisms for arsenite-induced apoptosis in cancer cells. Reagents that could effectively enhance ATO-induced mitotic arrest might help improve the therapeutic potential ATO. Cotreatement of HeLa-S3 cells with ATO and LY294002 or a specific AKT inhibitor significantly enhanced mitotic cell accumulation and suppressed the viability of cells at concentrations at which ATO alone was relatively ineffective. The suppression of cell viability was associated with enhanced induction of ATO-induced mitotic abnormalities and was due to induction of mitotic cell apoptosis. Ectopic expression of the constitutively active AKT1 had no effect on ATO-induced mitotic abnormalities, but accelerated mitosis exit, prevented mitotic cell apoptosis, and enhanced the formation of micro- or multi-nuclei after cell division. In addition, AKT1 activation upregulated the expression of aurora kinase B (AURKB) and survivin, and depletion of AURKB and survivin reversed the resistance of AKT1-activated cells to arsenite-induced apoptosis. These results indicate that AKT1 activation suppresses arsenite-induced mitotic cell apoptosis, despite the presence of numerous spindle abnormalities, by upregulation of AURKB and survivin and that inhibition of AKT effectively sensitizes cancer cells to ATO by enhancing mitotic cell apoptosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5404.
Estrogen Receptor Variants in Normal Human Mammary Tissue
Authors: E. R. Leygue, P. H. Watson, L. C. Murphy
Journal: JNCI Journal of the National Cancer Institute (1996)

BackgroundSeveral estrogen receptor (ER) variant messenger RNAs (mRNAs) have been identified previously in human breast cancer biopsy samples and cell lines. The relative levels of certain ER variant mRNAs have been observed to increase with breast tumor progression. In vitro assays of the function of polypeptides encoded by some of these variant mRNAs have led to speculation that ER variants may be involved in the progression from hormone dependence to independence in breast cancer.
P117 HOLISTIC APPROACH TO UNRAVEL FUNCTIONS AND REGULATION OF HGF IN LIVER REGENERATION
Authors: L.A. D'Alessandro, C. Meyer, J.G. Hengstler, U. Klingmüller, S. Höhme, S. el Kariem, K. Safferling, A. Raue, J. Timmer, D. Drasdo, N. Grabe, S. Dooley
Journal: Journal of Hepatology (2014)
Abstract 4144: Improvement of tumor cell transduction with lentiviral vectors using chemical and cell targeting approaches.
Authors: Ines Höfig, Michael J. Atkinson, Christian Thirion, Natasa Anastasov
Journal: Cancer Research (2013)

Abstract Although lentiviral transduction methods are widely used in cancer research their application is frequently hindered by the low transduction efficiency seen for a number of different cell types, in particular primary cells. We have previously reported that a mixture of poloxamer synperonic F108 and polybrene combines reduced toxicity and increased lentiviral gene delivery into a range of different primary cell cultures (1). We now report further improvement in efficiency through a novel combination of the poloxamer-based adjuvant with a modified lentiviral envelope. The envelope was rendered cell specific by fusing monoclonal antibody fragments directed against specific cell-surface epitopes with the viral attachment glycoprotein VSV-G. For specific cellular targeting we inserted chimeric antiCD30 or antiEGFR antibody-VSV-G fusion proteins into the lentiviral genome. The combination of VSV-G-fused antibody fragments against specific tumor cell antigens and the improved adjuvant resulted in a 3-fold higher transduction rate using a GFP reporter containing lentivirus in CD30-positive lymphoma and EGFR-positive epithelial breast cancer cells. The combination of optimized transduction enhancer molecules and retargeted lentiviral vectors enabled quantitative transduction of previously hard-to-transduce cell types. When mixtures of antigen-negative and antigen-positive tumor cells were selected the modified lentivirus particles showed a preference for infecting antigen-positive cells by a factor 4. These results demonstrate that improvements in both chemical charge protecting adjuvants and membrane targeting can lead to increased transduction efficiency without a loss of specificity. The combination of chemical adjuvant and envelope design can lead to the optimization of lentiviral transductions in large-scale systems. *1. Höfig I, Atkinson MJ, Mall S, Krackhardt AM, Thirion C, Anastasov N. Poloxamer synperonic F108 improves cellular transduction with lentiviral vectors. J Gene Med. 2012 Aug;14(8):549-60. Citation Format: Ines Höfig, Michael J. Atkinson, Christian Thirion, Natasa Anastasov. Improvement of tumor cell transduction with lentiviral vectors using chemical and cell targeting approaches. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4144. doi:10.1158/1538-7445.AM2013-4144
Randomized Phase III Trial of Aprepitant Compared with Dexamethasone for Emesis Induced by Carboplatin
Authors: H. Daga, S. Kinbara, U. Katsushima, H. Okada, A. Tsuya, K. Taira, S. Tokunaga, M. Nakao, T. Yoshida, K. Takeda
Journal: Annals of Oncology (2013)
Mucinous carcinoma of the eyelid with colonic mass: a rare partnership
Authors: Alisha Hinds, Dina Ahmad, Kristi Lopez, Jason Holly, Michelle Matteson-Kome, Matthew Bechtold
Journal: Endoscopy (2014)

Mucinous carcinoma of the eyelid is a rare cancer. In medicine, rarely will the diagnosis of one cancer lead to the diagnosis of a second unrelated cancer. However, mucinous carcinoma of the eyelid has been rarely associated with colon cancer [1]. This case demonstrates a very rare occurrence of mucinous carcinoma of the eyelid leading to the diagnosis of sporadic colon cancer.
Abstract 2327: Anti-angiogenic activity of a CovX bi-functional antibody conjugate targeting both activin-receptor like kinase type 1 (ALK-1) and vascular endothelial growth factor (VEGF)
Authors: Alice Lee, Joseph Stock, Janet Do, Marla Matin, Joselyn Del Rosario, Lijin feng, Sachiko Yamamoto, Jennifer Souratha, Lioudmila Tchistiakov, Michael Gallo, Yijie Gao, Steven Pirie-Shepherd, Reid Bissonnette, Rodney Lappe, Gary Woodnutt, Vincent Blot
Journal: Cancer Research (2012)

Abstract Angiogenesis is essential for tumor growth and metastasis, and controlling tumor-associated angiogenesis is a proven therapeutic intervention to limit tumor progression. Several pathways have been involved in tumor-associated angiogenesis and the predominant target of current interventions is the vascular endothelial growth factor (VEGF) pathway. Recently, Activin-receptor like kinase type 1 (ALK-1) has been proven to be a novel and potent target of tumor angiogenesis. Our results indicate that inhibiting VEGF and ALK1 have different effects on tumor vasculature, suggesting that targeting both pathways could have a more potent effect than targeting either pathway alone. We have created a bi-functional antibody conjugate targeting both ALK-1 and VEGF by conjugating VEGF-trap peptides to an anti-ALK1 monoclonal antibody. We demonstrate that our bi-functional molecule binds both ALK-1 and VEGF with high affinity in vitro, blocks both ALK-1 and VEGF pathways in HUVEC primary human endothelial cells and has good pharmacokinetics properties in mice. Finally, in a MDA-MB-231 xenograft model in SCID mice, the ALK-1/VEGF bi-functional antibody conjugate slowed tumor growth and prolonged survival with greater efficacy than anti-VEGF therapy alone. 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 2327. doi:1538-7445.AM2012-2327
The role of the cerebellum in motor learning is limited
Authors: Mark Hallett
Journal: Behavioral and Brain Sciences (1996)

Motor learning can be divided into adaptation and skill learning. The cerebellum plays the major role in adaptation learning, which can be described as context-response linkage. Motor skill learning is development of a new ability such as a sequence of motor actions. Skill learning can occur in patients with cerebellar lesions. Cortical mechanisms play a major role in development of skills, [THACH]
AB0852 Imaging of Infectious Spondylo Discitis in Tunisia
Authors: M. Slouma, K. Ben Abdelghani, L. Souabni, S. Kassab, S. Chekili, A. Laatar, L. Zakraoui
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Infectious spondylodiscitis remains an important cause of morbidity and mortality in Tunisia. Clinical presentation may be insidious with unremarkable initial radiographs providing false reassurance. MR imaging is considered as the imaging technique of choice in infectious spondylodiscitis. <h3>Objectives</h3> The aim of this study was to provide an overview of the radiological features of infectious spondylodiscitis. <h3>Methods</h3> A retrospective study effectuated in the department of Rheumatology in Tunisia between 1995 and 2013. We included all patients with infectious spondylodiscitis. <h3>Results</h3> Forty one patients were included. There were 21 males and 20 females. The mean age was 61.66 years, ranged from 25 to 89 years. Duration of symptoms varied from 20 to 90 days. All patients presented with back pain. Fever was noted in 38 cases. A neurological deficit was noted in 7 patients. Inflammation tests were disturbed in 87% of cases (n=36). Spondylodiscites was suspected according to X-ray findings in 39 cases, showing disc space narrowing and irregularity of the end-plates. It was normal in 2 cases in which the duration of symptoms was 20 days in the first case and one month in the second case. The diagnosis was then confirmed by Disco-vertebral biopsy showing a pyogenic infection. MR imaging was performed in only 27 patients and had showed epiduritis in 12 patients and paravertebral abscess in 8 patients. CT- guided disco vertebral biopsy was performed in 36 patients leading to the diagnosis in 22 cases. The Lumbar region was the most common affected (58%) followed by dorsal spine (32%) and cervical spine (10%). A multi-stage spondylodiscitis was found in 4 cases. Pyogenic Spondylodiscitis was associated with a septic arthritis in one case. Spinal Tuberculosis was complicated by hepatic tuberculoma in one case. All patients underwent initially adapted antibiotics and immobilization leading to recovery in 73% of cases (n=30). Seven patients were lost during follow up. Neurological complication occurred in 3 cases and sepsis in 1 case. <h3>Conclusions</h3> MR imaging had greatly contributed to prompt diagnosis, thus allowing implementation of timely appropriate treatment, indeed in patient with normal spine X-ray. In our study, MR imaging revealed epiduritis and paravertebral abscesses which still frequent in our country. The importance of whole spine imaging should be also underlined especially in case of multifocal infectious spondylodiscitis. <h3>References</h3> Leone A, Dell9Atti C, Magarelli N, Colelli P, Balanika A, Casale R, Bonomo L. Imaging of spondylodiscitis. Eur Rev Med Pharmacol Sci 2012;16:8-19. An HS, Seldomridge JA. Spinal infections: diagnostic tests and imaging studies. Clin Orthop Relat Res 2006;444:27-33. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5561
P725Anti-inflammatory effect of tanshinone IIA on oxidative-injured vascular endothelial cells is mediated by estrogen receptor activation and through ERK signaling pathway
Authors: LX Liu, YHJ Yin, GCY Guo, MXJ Ma, ZY Zhang, SMY Sun, PYT Pan
Journal: Cardiovascular Research (2014)

Purpose: To investigate the estrogenic protective effect and mechanism of Tanshinone IIA on oxidative-injured vascular endothelial cells.
Bilateral temporomandibular joint dislocation after upper gastrointestinal endoscopy in an intensive care unit patient: a rare complication
Authors: Diane Lorenzo, Florence Boissier, Alexandra Prost, Claire Gallois, Christophe Faisy
Journal: Endoscopy (2014)

A 60-year-old man, without dental articulation disorders or a history of dislocation of the temporomandibular joint, was admitted to our intensive care unit after surgery for aortic dissection. He had been intubated without complication 4 days earlier. On the day of surgery, he was sedated with midazolam and sufentanyl, and received a neuromuscular blocker. Using a flexible endoscope, upper gastrointestinal endoscopy to rule out gastrointestinal bleeding was performed without technical difficulty. Immediately afterwards, examination demonstrated an inability to close the mouth and emptiness of the mandibular fossa. Bilateral temporomandibular joint dislocation (TMJD) was diagnosed and was corrected temporarily using the Nélaton maneuver. A subsequent computed tomography (CT) scan ruled out a fracture of the mandibular arch ([Fig. 1]).
Abstract 270: Modulation of EGFR localization and transcriptional activity
Authors: Benjamin G. Bitler, Aarthi Goverdhan, Joyce Schroeder
Journal: Cancer Research (2010)

Abstract The triple negative (ER-, PR-, Her2-) or basal-like breast cancers are the most difficult forms of breast cancer to treat, because the cancer is often chemoresistant and highly metastatic. As these cancers progress from early to late stage the 5-year survival rate drops dramatically. Many proteins are responsible for this progression, including MUC1 and the Epidermal Growth Factor Receptor (EGFR). MUC1 is a heavily O-glycosylated transmembrane protein that is over expressed in 90% of all breast and ovarian cancers. In normal cells, MUC1 is only found on the apical surface of epithelium, but in cancer, MUC1 is found to be mislocalized. As a result, MUC1 plays a role in promoting tumorigenesis and metastases, by interacting with other oncogenes such as EGFR. EGFR is overexpressed in about 60% of the most aggressive form of breast cancer (triple negative). In an EGFR-dependent mouse model of breast cancer, the loss of Muc1 directly correlates to the loss of cyclin D1. Additionally, blocking MUC1 and EGFR interactions significantly inhibited tumor progression in a xenograft and s spontaneous mouse model of breast cancer. Recently, a novel trafficking pathway of EGFR has been discovered, which was described as EGFR trafficking to the nuclear compartment. Following entry into the nucleus EGFR can act in an oncogenic manner by aberrantly activating transcription of genes such as, cyclin D1 and v-myb. In this study we discovered a novel regulator function of MUC1 in EGFR trafficking and transcriptional activity. We found that MUC1 expression in basal-like breast cancer promotes the accumulation of nuclear EGFR and mediates EGFR's interaction with chromatin. Additionally, we determined that EGFR's interaction with the cyclin D1 promoter and upregulation of the cyclin D1 protein was MUC1-dependent. The main focus of anti-EGFR therapeutics have been its tyrosine kinase activity, however this study reveals that EGFR's subcellular localization should also be considered in the development of future cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 270.