tbuckley/cabot-search huggingface dataset:
Abstract 3542: Upregulation of microRNA-372 &amp; 373 associates with cervical lymph node metastasis and poor prognosis of oral carcinomas
Authors: Chung J. Liu, Hsi-Feng Tu, Hui-Wen Cheng, Kuo-Wei Chang
Journal: Cancer Research (2014)

Abstract Purpose: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. MicroRNAs (miRNAs) have an important regulatory role in human cancer including oral carcinogenesis. MicroRNA 372 and microRNA 373 play as oncogenic and tumour-suppressive functions of between different human maligngncy. This study investigated the microRNA-372 and microRNA 373 expression and their clinical implication in OSCC. Experimental Design: Fifty patients with primary OSCC were included in the study. Primary cancer cells and matched normal oral epithelium were purified by laser capture microdissection. RNA were extracted from these samples. The expression levels of miR-372 and miR-373 in the tissue of OSCC patients were measured by quantitative RT-PCR. Results: both miR-372 and miR-373 was up-regulated in OSCC tissue relative to control mucosa. Among different clinical variables, over-expression of miR-372 and miR-373 were associated with nodal metastasis, lymphovascular invasion and poor survival. Multivariate analysis showed that both high miR-372 and miR-373 expression were independent predictors for poor survival in OSCC. Conclusion: Over expression of miR-372 and miR-373indicate worse survival in OSCC. Citation Format: Chung Ji Liu, Hsi-Feng Tu, Hui-Wen Cheng, Kuo-Wei Chang. Upregulation of microRNA-372 &amp; 373 associates with cervical lymph node metastasis and poor prognosis of oral carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3542. doi:10.1158/1538-7445.AM2014-3542
181. Human CBS (Cystathionine β-Synthase) Gene Transfer Mediated by Recombinant Adeno-Associated Virus Vector
Authors: Hyun-Jeong Oh, Eun-Sook Park, Warren Kruger, Sung-Chul Jung, Jin-Sung Lee
Journal: Molecular Therapy (2004)

Cystathionine β-synthase (CBS) deficiency in human is the most common cause of Homocystinuria, a rare autosomal recessive disease. Patients with this disorder have premature arteriosclerosis and thrombosis, mental retardation, ectopia lentis, osteoporosis, skeletal abnormalities, which are resulted by elevated plasma homocysteine levels. About 50% of patients with CBS deficiency respond to pyridoxine therapy with a marked reduction in plasma total homocysteine, whereas the remaining subjects respond poorly. At least 60 different mutations of the gene have been described, with I278T and G307S as the most common. Interestingly, a number of patient-derived mutations in the CBS catalytic region can be functionally suppressed by either deletion of the c-terminal regulatory region or specific point mutation in this region. For the gene therapy of Homocystinuria, we constructed human CBS cDNA containing recombinant AAV vector (rAAV-hCBS). We used three kinds of hCBS cDNA, one was normal CBS cDNA, two were mutated hCBS cDNA which were deleted or mutated in the region of catalytic domain. We used adenovirus-free production system for the production of rAAV-hCBS vectors. Three kinds of rAAV-hCBS vectors were transduced into NIH3T3 for in vitro evaluation. Western blot analysis using anti-hCBS antibody demonstrated that all rAAV-hCBS vectors expressed high levels of Cytathionine β-synthase enzyme. CBS enzyme activities were checked using TLC. There were no much differences among those three vectors. Following the in vitro experiment, we evaluated the transgene expression in homocystinuria mice. We administered an recombinant adeno-associated virus vector encoding hCBS to homocystinuria mice on day 6 of life by IP. The life span of mice was prolonged about 2 times than untreated disease mice. Studies are currently underway to further evaluate our vector in homocystinuria mice.
Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial
Authors: Ruben Veldkamp, Esther Kuhry, Wim C J Hop, J Jeekel, G Kazemier, H Jaap Bonjer, Eva Haglind, Lars Påhlman, Miguel A Cuesta, Simon Msika, Mario Morino, Antonio M Lacy
Journal: The Lancet Oncology (2005)
Abstract 3425: Whole-transcriptome analyses of EBV-associated nasopharyngeal carcinoma using next-generation transcriptome sequencing
Authors: Cathy Ka-Yan Mak, Grace Tin-Yan Chung, Kevin Yuk-Lap Yip, Ken Kai-Yuen Tso, Sau-Dan Lee, Siu-Tim Cheung, Sai-Wah Tsao, Pierre Busson, Ka-Fai To, Kwok-Wai Lo
Journal: Cancer Research (2014)

Abstract Nasopharyngeal carcinoma (NPC) is unique among epithelial cancers arising from the head and neck regions. This specific cancer type is consistently associated with EBV infection. Using RNA-seq, we have conducted a comprehensive assessment of EBV and cellular gene expression in six NPC cell line and patient-derived xenografts (PDXs). In these tumor lines, expression of EBV latent genes including EBNA1, LMP1, LMP2A and BamH1 A transcripts was quantitated. Among the viral genes, the BamH1 A transcripts were detected as the major transcripts with various splicing variants. Expression of these transcripts in NPC was further validated by qRT-PCR analysis. Active lytic gene expression and lytic viral replication was not observed in these tumor lines. Analysis of the RNA-seq data has identified multiple fusion transcripts. A total of 18 candidate fusions were validated in these tumor lines. A novel fusion transcript, UBR5-ZNF423 was detected in C666-1 cells and 8.3% of primary tumors. The transcript produces a chimeric fusion protein which might alter the function of EBF transcription factor. A significant growth inhibitory effect was observed in UBR5-ZNF423 knockdown C666-1 cells. Constitutive expression of UBR5-ZNF423 fusion in NIH3T3 cells induced in vivo tumor formation in nude mice model. The findings strongly suggest that the fusion gene play a causative role in NPC tumorigenesis. Using the expression profile of immortalized nasopharyngeal epithelial cells as control, our study also revealed the differential expression of cellular genes and specific alternative spliced transcripts in NPC. Significant upregulation of genes involved in cytokine-cytokine receptor interaction (e.g. CCL5, CCL20, CXCL10, CXCR4, IL2RG) was consistently detected in the tumor lines. Most of them were targets of the NF-kappaB signaling pathways, which are constitutively activated in EBV-associated NPC. In addition, the analyses also discovered several potential druggable targets (e.g. CD74) and oncogenic non-coding RNAs (e.g. AFAP1-AS1) in NPC, which may contribute to the development of new therapeutic strategies for this cancer. The whole-transcriptome analyses greatly enhance our understanding of the molecular basis of EBV-infected NPC. Citation Format: Cathy Ka-Yan Mak, Grace Tin-Yan Chung, Kevin Yuk-Lap Yip, Ken Kai-Yuen Tso, Sau-Dan Lee, Siu-Tim Cheung, Sai-Wah Tsao, Pierre Busson, Ka-Fai To, Kwok-Wai Lo. Whole-transcriptome analyses of EBV-associated nasopharyngeal carcinoma using next-generation transcriptome sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2014-3425
Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance
Authors: Zhen Zhao, Abhay P Sagare, Qingyi Ma, Matthew R Halliday, Pan Kong, Kassandra Kisler, Ethan A Winkler, Anita Ramanathan, Takahisa Kanekiyo, Guojun Bu, Nelly Chuqui Owens, Sanket V Rege, Gabriel Si, Ashim Ahuja, Donghui Zhu, Carol A Miller, Julie A Schneider, Manami Maeda, Takahiro Maeda, Tohru Sugawara, Justin K Ichida, Berislav V Zlokovic
Journal: Nature Neuroscience (2015)
The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy
Authors: P. Devillier, M. Le Gall, F. Horak
Journal: Allergy (2010)

To cite this article: Devillier P, Le Gall M, Horak F. The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy. Allergy 2011; 66: 163–169. The clinical development of allergen immunotherapy for allergic rhinoconjunctivitis because of pollen is complicated by seasonal, geographical and subject-related variability in allergen exposure. Using an allergen challenge chamber (ACC), a room that enables reproducible challenges with controlled levels of inhalant allergens for several hours, these factors can be controlled. The ACC has often been used to evaluate symptomatic medications but is underexploited in the field of allergen immunotherapy. When used in conjunction with a programme of natural-exposure trials, the ACC enables researchers to (i) facilitate the allergen immunotherapy dose-finding process, (ii) accelerate the transition from Phase I/II to Phase III trials, (iii) characterize the onset and maintenance of action, (iv) avoid the confounding effects of rescue medication, (v) better characterize the baseline or pretreatment characteristics of trial subjects, (vi) perform better-standardized physical and laboratory measurements during an acute challenge, (vii) simplify trial logistics and use smaller numbers of subjects than would be required in equivalent natural-exposure studies and (viii) support (but not replace) Phase III natural-exposure trials for the investigation into long-term and disease-modifying effects. ACC studies can further increase levels of evidence for allergen immunotherapy – the only current therapy potentially capable of modifying the underlying allergic disease.
Extracts from "Clinical Evidence": Acute ischaemic stroke
Authors: G. Gubitz
Journal: BMJ (2000)

Definition Stroke is characterised by rapidly developing clinical symptoms and signs of focal, and at times global, loss of cerebral function lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin.1 Ischaemic stroke is defined as stroke due to vascular insufficiency (such as cerebrovascular thromboembolism) rather than haemorrhage.

#### Interventions

Acute ischaemic stroke 

##### Beneficial:

Stroke units

Aspirin

##### Trade-off between benefits and harms:

Thrombolytic treatment

##### Likely to be ineffective or harmful:

Immediate systemic anticoagulation

Acute reduction of blood pressure

Intracerebral haematomas 

##### Unknown effectiveness:

Evacuation

Incidence/prevalence Stroke is the third most common cause of death in most developed countries.2 It is a worldwide problem: about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people over 70 years old.3

Aetiology About 80% of all acute strokes are caused by cerebral infarction, usually resulting from thrombotic or embolic occlusion of a cerebral artery4; the remainder are caused either by intracerebral or subarachnoid haemorrhage.

Prognosis About 10% of all people with acute ischaemic strokes will die within 30 days of stroke onset.5 Of those who survive the acute event, about 50% will experience some level of disability after six months.6

Aims To achieve rapid restoration and maintenance of blood supply to the ischaemic area in the brain, and to minimise brain damage and hence impairment, disability, and secondary complications.

Outcomes Risk of death or dependency (generally assessed as the proportion of people dead or requiring physical assistance for transfers, mobility, dressing, feeding, or toileting three to six months after stroke onset7); quality of life.

Clinical Evidence researchers searched the Cochrane Library and the Cochrane Stroke Review Group database in 1998 and performed an update search and appraisal for systematic reviews and subsequent randomised controlled trials (RCTs) in June 1999.

Question: What …
Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study
Authors: Jean‐Marie Michot, Danielle Canioni, Henda Driss, Laurent Alric, Patrice Cacoub, Felipe Suarez, David Sibon, Catherine Thieblemont, Jehan Dupuis, Benjamin Terrier, Cyrille Feray, Hervé Tilly, Stanislas Pol, Véronique Leblond, Catherine Settegrana, Pascaline Rabiega, Yoann Barthe, Houria Hendel‐Chavez, Florence Nguyen‐Khac, Hélène Merle‐Béral, Françoise Berger, Thierry Molina, Frédéric Charlotte, Fabrice Carrat, Frédéric Davi, Olivier Hermine, Caroline Besson
Journal: American Journal of Hematology (2014)

Hepatitis C virus (HCV) infection increases the risk of B‐cell non‐Hodgkin lymphomas (B‐NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC‐13 Lympho‐C study aimed at a better understanding of the impact of AT on HCV associated B‐NHL. This multicentric study enrolled 116 HCV‐positive patients with B‐NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B‐cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three‐year overall survival (OS) and progression‐free survival were 78% 95%CI [63–88] and 64% [48–76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV‐associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [ clinicalTrials.gov Identification number NCT01545544] Am. J. Hematol. 90:197–203, 2015. © 2014 Wiley Periodicals, Inc.
Endothelial dysfunction in patients with obstructive sleep apnea
Authors: Mostafa Elshazly, Azah Farag, Abeir Zakaria
Journal: European Respiratory Journal (2011)

Background: Obstructive sleep apnea (OSA) influences endothelial function and causes cardiovascular diseases.

Objectives: To assess the prevalence of endothelial dysfunction in patients with OSA.

Methods: Twenty-seven obese patients with OSA and 26 healthy obese subjects were investigated. The presence or absence of OSA was evaluated with a sleep study. Endothelial function was investigated with brachial artery ultrasound examination.

Results: Baseline characteristics were equivalent between the two groups.Minimal SaO2 and AHI in the OSA and control groups were [72.1±11.6 versus 86.5±4.5% (P=0.000), and 27.9±23.1 versus 2.0±1.5 (P=0.000). There was no statistically significant difference in percentage change 2 of BADSLnitrate between patients and control groups (P=0.05) i.e. endothelial independent dilatation. Flow-mediated dilatation (FMD) percentage change 1 was highly significant lower in OSA patients in comparison to control group [Mean ± SD: 3.1±2.8 vs 10.6±6.9, (P=0.000) respectively. i.e. endothelial dysfunction. There was positive significant statistical correlation between BMI and BAD (basal, FMD and SL nitrate).Regarding the correlations, there was positive significant statistical correlation between ESS and AHI, the time in which O2 saturation <90%, BADFMD and BADbasal among the patients with OSA, but there was negative significant correlation between ESS and minimal nocturnal O2 saturation among the patients with OSA.

Conclusions: We detected a prominent deterioration in endothelial function in obese OSA patients compared with healthy obese subjects. This deterioration may occur due to ongoing hypoxemia and it may be a possible cause of cardiovascular diseases in patients with OSA.
Molecular pharmacodynamics of emixustat in protection against retinal degeneration
Authors: Jianye Zhang, Philip D. Kiser, Mohsen Badiee, Grazyna Palczewska, Zhiqian Dong, Marcin Golczak, Gregory P. Tochtrop, Krzysztof Palczewski
Journal: Journal of Clinical Investigation (2015)

Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators.
Molecular pharmacology and antitumor activity of palmarumycin based inhibitors of thioredoxin reductase
Authors: Garth Powis, Peter Wipf, Robert M. Halter, D. Lynn Kirkpatrick
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4858 

The cytosolic thioredoxin (Trx) redox system comprising Trx-1 and Trx-1 reductase (TR) which catalyses the NADPH dependent reduction of Trx-1, regulates cell growth and survival. Trx-1, together with peroxiredoxin-1, is an antioxidant that scavenges H2O2. Trx-1 also reduces protein oxidized cysteine residues to regulates the activity of transcription factors including p53, HIF-1α, Sp1 and Nrf2, and to inhibit the activity of the apoptosis inducing proteins Ask-1 and PTEN. Trx-1 is overexpressed in many human tumors where it is associated with increased cell proliferation, decreased apoptosis and poor patient survival. TR provides an ideal target to regulate the activity of overexpressed Trx-1. We have identified the naphthoquinone spiroketal fungal metabolite palmarumycin CP1 as a potent inhibitor of TR in cells but attempts to exploit the activity of CP1 analogs as antitumor agents in vivo have been hampered by their insolubilityA. We have recently developed a series of water soluble CP1 analog prodrugsB the most active being PX-916 with a water solubility of 10 mg/ml and an IC50 for TR of 0.28 μM, which is similar to that of CP1 and the CP1-analog PX-960 to which PX-916 is converted at pH 7.0 (t1/2 = 1 hr) and in plasma (t1/2  100 fold selectivity for TR compared to NADPH dependent human glutathione reductase and cytochrome P-450 reductase. The IC50 for inhibition of MCF-7 breast cancer cell TR by PX-916 was 0.25 μM and the IC50 for growth inhibition 3.1 μM. PX-916 was stable (t1/2 = 37 hr) at pH 4.0 which was used for iv administration to mice. A single iv dose of PX-916 of 25 mg/kg inhibited MCF-7 tumor xenograft TR up to 60% at 24 hr and the inhibition was maintained for at least 48 hr. The growth of MCF-7 tumor xenografts was decreased from 140 mm3/day in the vehicle control to 15 mm3/day 5 days after the end of dosing by PX-916 at 27.5 mg/kg iv daily for 5 doses (89 % decrease, p < 0.05) and to 10 mm3/day by PX-916 at 27.5 mg/kg iv every other day for 5 doses (93 % decrease, p < 0.05). A-673 rhabdomyosarcoma and SHP-77 small cell lung cancer xenografts also showed marked growth inhibition with PX-916 given at 25 to 30 mg/kg iv or ip daily for 5 days. The major toxicities observed 24 hr after the last off 5 daily doses of PX-916 of 25 mg/kg were neutropenia and thrombocytopenia, with no increase in plasma liver enzymes and no significant weight loss. Thus, the studies demonstrate that TR offers a good target for cancer drug discovery and that water soluble palmarumycin analogs inhibit tumor TR and can give excellent tumor growth control. A Wipf et al. Org. Biomol. Chem. 2004, 2 , 1651-1658. B Wipf et al. Org. Biomol. Chem. 2005 , 3 , 3880-3882.
Brain activity during transient sadness and happiness in healthy women
Authors: M S George, T A Ketter, P I Parekh, B Horwitz, P Herscovitch, R M Post
Journal: American Journal of Psychiatry (1995)

The specific brain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if H2(15)O positron emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women.Eleven healthy and never mentally ill adult women were scanned, by using PET and H2(15)O, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces.Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of significantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right prefrontal and bilateral temporal-parietal regions.Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion.