tbuckley/cabot-search huggingface dataset:
Loss of RUNX3 Expression Significantly Affects the Clinical Outcome of Gastric Cancer Patients and Its Restoration Causes Drastic Suppression of Tumor Growth and Metastasis
Authors: Daoyan Wei, Weida Gong, Sang C. Oh, Qiang Li, Won Dong Kim, Liwei Wang, Xiangdong Le, James Yao, Tsung T. Wu, Suyun Huang, Keping Xie
Journal: Cancer Research (2005)

Abstract Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P &amp;lt; 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin D1 but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer.
Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication
Authors: Nada Chaoul, Catherine Fayolle, Belinda Desrues, Marine Oberkampf, Alexandre Tang, Daniel Ladant, Claude Leclerc
Journal: Cancer Research (2015)

Abstract The metabolic sensor mTOR broadly regulates cell growth and division in cancer cells, leading to a significant focus on studies of rapamycin and its analogues as candidate anticancer drugs. However, mTOR inhibitors have failed to produce useful clinical efficacy, potentially because mTOR is also critical in T cells implicated in immunosurveillance. Indeed, recent studies using rapamycin have demonstrated the important role of mTOR in differentiation and induction of the CD8+ memory in T-cell responses associated with antitumor properties. In this study, we demonstrate that rapamycin harms antitumor immune responses mediated by T cells in the setting of cancer vaccine therapy. Specifically, we analyzed how rapamycin affects the antitumor efficacy of a human papilloma virus E7 peptide vaccine (CyaA-E7) capable of eradicating tumors in the TC-1 mouse model of cervical cancer. In animals vaccinated with CyaA-E7, rapamycin administration completely abolished recruitment of CD8+ T cells into TC-1 tumors along with the ability of the vaccine to reduce infiltration of T regulatory cells and myeloid-derived suppressor cells. Moreover, rapamycin completely abolished vaccine-induced cytotoxic T-cell responses and therapeutic activity. Taken together, our results demonstrate the powerful effects of mTOR inhibition in abolishing T-cell–mediated antitumor immune responses essential for the therapeutic efficacy of cancer vaccines. Cancer Res; 75(16); 3279–91. ©2015 AACR.
Systematic Review: Randomized, Controlled Trials of Nonsurgical Treatments for Urinary Incontinence in Women
Authors: Tatyana A. Shamliyan, Robert L Kane, Jean F Wyman, Timothy J Wilt
Journal: Annals of Internal Medicine (2008)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: Urinary incontinence in women is a common problem that adversely affects quality of life. Purpose: To synthesize evidence of management of urinary incontinence in women. Data Sources: MEDLINE, CINAHL, and the Cochrane Library. Study Selection: 96 randomized, controlled trials (RCTs) and 3 systematic reviews published in English from 1990 through May 2007. Data Extraction: Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference. Data Synthesis: Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Different injectable bulking agents and medical devices were associated with similar continence and improvement rates. Electrical stimulation failed to resolve urinary incontinence. Oral hormone administration increased rates of urinary incontinence compared with placebo in most RCTs (1243 women). Transdermal or vaginal estrogen resulted in inconsistent improvement of urinary incontinence. Adrenergic drugs did not resolve or improve urinary incontinence. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose–response association. Limitations: Inconsistent measurements of outcomes limited the findings. Predictors of better effect have not been identified in RCTs. Conclusion: Moderate levels of evidence suggest that pelvic floor muscle training and bladder training resolved urinary incontinence in women. Anticholinergic drugs resolved urinary incontinence, with similar effects from oxybutynin or tolterodine. Duloxetine improved but did not resolve urinary incontinence. The effects of electrostimulation, medical devices, injectable bulking agents, and local estrogen therapy were inconsistent.
Immune responses in lungs of patients with tuberculous pleural effusion without pulmonary tuberculosis
Authors: Mjid Meriem, Jouda Cherif, Sonia Toujani, Leila Bouhaja, Yassine Ouahchi, Nozha Ben Salah, Hafedh Zakhama, Jalloul Daghfous, Béchir Louzir, Samir Boubaker, Abdemajid Ben Hmida, Nadia Mehiri, Majed Béji
Journal: European Respiratory Journal (2013)

Background: Because most studies of tuberculous pleural effusion (TPE) focused on the pleural space, little information regarding lung parenchyma is available. We hypothesized that TPE patients without pulmonary tuberculosis (TB) would have pulmonary immunological changes.  Aim: Investigate the composition of cells in the bronchoalveolar lavage (BAL) in TPE patients without pulmonary TB and to compare BAL composition of the same and contra lateral side of the TPE.  Methods: Newly diagnosed untreated patients with TPE were enrolled in this study. TPE was confirmed in all cases by pleural biopsy. Patients with any evidence of pulmonary TB were excluded. BAL was performed at the same (Group 1:G1) and the contra lateral side (Group 2:G2) of TPE. All patients were consenting for participation in the study.  Results: During the study period, 19 patients were enrolled (10 female and 9 male). Mean age was 40 ± 19 years. Clinical manifestations were dominated by chest pain and fever. Pleural effusion was unilateral in all cases (right-side: 14 cases, left-side: 5 cases). Tuberculin skin tests were positive in 8 patients and peripheral blood lymphopenia was found in 10 cases. BAL fluid formula was abnormal in 17 cases (G1) versus 10 cases G2 (p 0.05). There were significant immune responses in the same side of TPE patients without pulmonary tuberculosis.  Conclusion: These results suggest that TPE may induce a significant immune response in lung parenchyma especially in adjacent tissue.
GREY HAIR AND DISEASE LIMITED TO THE NASO-LABIAL AREA
Authors: G. L. Cheatle
Journal: BMJ (1915)

After opening the abdn(loinu lhaemilorirhagc froml tlle pani- creas must be stopped by deep-sutures or by the use of tlhe tamponi, tlle iuujtired area being packed off witlh gauze and drained.A break in.tlle continuity of the orgacn nmay permiit of a closure witlh deep sutures.A careful searcll for woundls of otlher viscera is necessarv in all cases.Tllc peritonieal cavity slhould be washed out witl normal salt solutioln, for in tlle majority of cases pan- creatic secretion will lhave escaped into it.The pancreatic juice, even when aseptic, is said to be hlighlly toxic and to lower thle resistance of tlle peritoneuni to micro- organisms.Von Mikulicz collected 45 cases of pancreatic injury; 21 were penetratinig wounds, and 24 subcutaneous wounds from blunt force.Of the penetrating varietv, 12 were gunshot and 9 stab wounlds.Five of the gunshot wounds were operated on, with 2 deaths.Tlle 7 that were niot operated on died.The 9 stab wouinds were all operated on, with only 1 fatalityr.These favourable resuilts were due to the fact tllat the panicreatic injury was really a prolapse in 7 cases; and in some of these oinly a miinor lesion of thle prolapsed portion was present.Of the 24 subcutaneous injutries, 13 were niot operated upon, and all died.Eleven were suibnmitted to operationi, ancd 7 1c- covered.The operations conisisted in exposing the iinjured pancreas and in drainage..~~~~~~~~~~~~~~r.F .s
Celecoxib and NS-398 Enhance Photodynamic Therapy by Increasing <i>In vitro</i> Apoptosis and Decreasing <i>In vivo</i> Inflammatory and Angiogenic Factors
Authors: Angela Ferrario, Anita M. Fisher, Natalie Rucker, Charles J. Gomer
Journal: Cancer Research (2005)

Abstract Photodynamic therapy (PDT) elicits both apoptotic and necrotic responses within treated tumors and produces microvascular injury leading to inflammation and hypoxia. PDT also induces expression of angiogenic and survival molecules including vascular endothelial growth factor, cyclooxygenase-2 (COX-2), and matrix metalloproteinases. Adjunctive administration of inhibitors to these molecules improves PDT responsiveness. In the current study, we examined how the combination of PDT and COX-2 inhibitors improve treatment responsiveness. Photofrin-mediated PDT combined with either celecoxib or NS-398 increased cytotoxicity and apoptosis in mouse BA mammary carcinoma cells. Immunoblot analysis of protein extracts from PDT-treated cells also showed poly(ADP-ribose) polymerase cleavage and Bcl-2 degradation, which were further enhanced following combined therapy. Tumor-bearing mice treated with PDT and either celecoxib or NS-398 exhibited significant improvement in long-term tumor-free survival when compared with PDT or COX-2 inhibitor treatments alone. The combined procedures did not increase in vivo tumor-associated apoptosis. Administration of celecoxib or NS-398 attenuated tissue levels of prostaglandin E2 and vascular endothelial growth factor induced by PDT in treated tumors and also decreased the expression of proinflammatory mediators interleukin-1β and tumor necrosis factor-α. Increased tumor levels of the antiinflammatory cytokine, interleukin 10, were also observed following combined treatment. This study documents for the first time that adjunctive use of celecoxib enhances PDT-mediated tumoricidal action in an in vivo tumor model. Our results also show that administration of COX-2 inhibitors enhance in vitro photosensitization by increasing apoptosis and improve in vivo PDT responsiveness by decreasing expression of angiogenic and inflammatory molecules.
PWE-170 Proton pump inhibitors and clopidogrel combination: is there any risk?
Authors: I Haq, P Priyadharshan, S Lindsay, J Kurian, S Bulugahapitiya
Journal: Gut (2012)

<h3>Introduction</h3> Dual anti-platelet therapy (DAT) with aspirin and clopidogrel is prescribed up to 1 year following Acute Coronary Syndrome (ACS). Proton Pump Inhibitors (PPIs) are often used in selective patients to reduce the risk of gastrointestinal (GI) bleeding. Some studies have suggested that there is a possible interaction between PPIs and clopidogrel resulting in an adverse cardiac event rate. Main objective of this study was to determine if prescription of PPIs in ACS patients on dual anti-platelet therapy results in increased cardiac events compared to patients not receiving PPIs. <h3>Methods</h3> A retrospective observational, comparative study of 200 admissions with ST elevation myocardial infarctions (STEMIs) and non-ST elevation myocardial infarction (nSTEMIs) over a period of 1 year. Patients were divided in two groups: PPI group (Patients on DAT and PPIs) and Non-PPI group (Patients on DAT only). End points were readmissions with ACS or death. <h3>Results</h3> Mean age was 67 (24–96), 65% male and 35% female, 75% Caucasian and 25% Asians. 27 patients were excluded (24 patients not receiving DAT, 3 patients on H2 antagonist). For PPI group (54% on lansoprazole, 35% on pantoprazole and 11% on omeprazole), baseline characteristics were (Patient number—89, 27-STEMIs, 62-nSTEMIs; mean age—69) whereas the corresponding values for non-PPI group were (Patient number—84, 38-STEMIs, 46-nSTEMIs, mean age—63). Mean GRACE score at admission (predictor of death or MI in 6 months) was 29% for PPI group whereas the corresponding value for the non-PPI group was 27% (p=0.075). 26 patients were re-admitted with ACS, 20 in PPI group and six in non-PPI group (OR 3.76, 95% CI 1.43 to 9.92, z statistic 2.68, p=0.007). Five deaths due to ACS were observed, four in PPI group and one in non-PPI group (RR 3.77, 95% CI 0.43 to 33.09, p=0.23). <h3>Conclusion</h3> This study suggests that there is an association between PPIs and clopidogrel resulting in increased readmission with acute coronary syndromes but not in increased mortality. Larger scale studies are required to confirm or refute these observations. <h3>Competing interests</h3> None declared.
IRF-1 Promotes Inflammation Early after Ischemic Acute Kidney Injury
Authors: Yanxia Wang, Reji John, Jianlin Chen, James A. Richardson, John M. Shelton, Michael Bennett, Xin J. Zhou, Glenn T. Nagami, Ying Zhang, Qing Qing Wu, Christopher Y. Lu
Journal: Journal of the American Society of Nephrology (2009)

Acute renal ischemia elicits an inflammatory response that may exacerbate acute kidney injury, but the regulation of the initial signals that recruit leukocytes is not well understood. Here, we found that IFN regulatory factor 1 (IRF-1) was a critical, early proinflammatory signal released during ischemic injury in vitro and in vivo. Within 15 min of reperfusion, proximal tubular cells of the S3 segment produced IRF-1, which is a transcription factor that activates proinflammatory genes. Transgenic knockout of IRF-1 ameliorated the impairment of renal function, morphologic injury, and inflammation after acute ischemia. Bone marrow chimera experiments determined that maximal ischemic injury required IRF-1 expression by both leukocytes and radioresistant renal cells, the latter identified as S3 proximal tubule cells in the outer medulla by in situ hybridization and immunohistochemistry. In vitro, reactive oxygen species, generated during ischemia/reperfusion injury, stimulated expression of IRF-1 in an S3 proximal tubular cell line. Taken together, these data suggest that IRF-1 gene activation by reactive oxygen species is an early signal that promotes inflammation after ischemic renal injury.
Phase I/Ib Study of Olaparib and Carboplatin in BRCA1 or BRCA2 Mutation-Associated Breast or Ovarian Cancer With Biomarker Analyses
Authors: Jung-Min Lee, John L. Hays, Christina M. Annunziata, Anne M. Noonan, Lori Minasian, Jo Anne Zujewski, Minshu Yu, Nicolas Gordon, Jiuping Ji, Tristan M. Sissung, William D. Figg, Nilofer Azad, Bradford J. Wood, James Doroshow, Elise C. Kohn
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundOlaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
Multiple organ-reactive IgG antibody induced by an antiidiotypic antibody to a human monoclonal IgM autoantibody.
Authors: K Essani, J Srinivasappa, P R McClintock, B S Prabhakar, A L Notkins
Journal: The Journal of Experimental Medicine (1986)

MOR-h1 is a human multiple organ-reactive (MOR) monoclonal autoantibody (Ab1) that reacts with human growth hormone (hGH) and a 35 kD protein found in the anterior pituitary, thyroid, stomach, and pancreas. 4E6 is a mouse monoclonal anti-idiotypic antibody (Ab2) that reacts with the paratope of MOR-h1 and is ligand inhibitable. In the present study, we immunized a rabbit with 4E6 and purified an IgG fraction (anti-4E6) from the sera. Competitive inhibition experiments showed that anti-4E6 (Ab3) binds to the same epitope on 4E6 and to the same antigens (i.e., hGH and 35 kD protein) as does MOR-h1. By immunofluorescence, anti-4E6, an IgG antibody, shows the same multiple organ reactivity with tissues as does MOR-h1, an IgM antibody. From these and other studies, we conclude that the 4E6 paratope (Ab2) has a conformational resemblance to an epitope on hGH and the 35 kD protein. This raises the possibility that antibodies made in response to certain anti-idiotypic antibodies may be one of the mechanisms for triggering an autoimmune response.
Insulin and glucagon infusion in acute alcoholic hepatitis: A prospective randomized controlled trial
Authors: George Bird, Johnson Y. N. Lau, John Koskinas, Claire Wicks, Roger Williams
Journal: Hepatology (1991)

In a randomized, controlled trial to investigate the possible benefit of insulin and glucagon therapy in severe acute alcoholic hepatitis, 86 patients were randomized to receive 30 U insulin and 3 mg glucagon in 250 ml 5% dextrose over 12 hr each day for 3 wk or a similar regime of identical placebo. No significant differences were seen in patients’ clinical characteristics and disease severity in the treated and placebo groups. Of the 43 patients receiving insulin and glucagon, 15 (35%) died within 4 wk of randomization, compared with 14 deaths (33%) in the control patients (p = not significant). When the patients surviving the first 4 wk were examined there were five more deaths in the treatment group, compared with one death in the control group at 6-mo follow-up (p = not significant). No significant differences in the frequency of short-term or long-term complications of alcoholic liver disease or relapse to alcohol were seen when the two groups were compared, although hypoglycemia was seen in six patients during infusion of insulin and glucagon. Similarly, no significant differences were seen in the improvement in clinical or biochemical features at 4 wk and at 6 mo in survivors when the insulin and glucagon-treated patients were compared with patients in the placebo group. This study does not confirm previous reports that insulin and glucagon infusion improves the outcome of severe acute alcoholic hepatitis. (Hepatology 1991;14:1097-1101.)
ANCCA/ATAD2 Overexpression Identifies Breast Cancer Patients with Poor Prognosis, Acting to Drive Proliferation and Survival of Triple-Negative Cells through Control of B-Myb and EZH2
Authors: Ekaterina V. Kalashnikova, Alexey S. Revenko, Abigael T. Gemo, Nicolas P. Andrews, Clifford G. Tepper, June X. Zou, Robert D. Cardiff, Alexander D. Borowsky, Hong-Wu Chen
Journal: Cancer Research (2010)

Abstract Chromatin coregulators are important factors in tumorigenesis and cancer progression. ANCCA is an AAA+ ATPase and a bromodomain-containing nuclear coactivator for the estrogen and androgen receptors that is crucial for assembly of chromatin-modifying complexes and proliferation of hormone-responsive cancer cells. In this study, we show that ANCCA is overexpressed in &amp;gt;70% of breast tumors and that its high protein level correlates well with tumor histologic grades (P &amp;lt; 0.0001), highlighting ANCCA as a prognostic factor for poor overall survival and disease recurrence. Strikingly, high-level ANCCA correlated with triple-negative tumors that represent highly aggressive disease. Analysis of ANCCA transcript levels in multiple expression profiles of breast cancer identified ANCCA as a common signature gene, indicating that elevated transcripts also strongly correlate with tumor metastasis and poor survival. Biological and mechanistic investigations revealed that ANCCA is crucial for proliferation and survival of triple-negative/basal-like cancer cells and that it controls the expression of B-Myb, histone methyltransferase EZH2, and an Rb-E2F core program for proliferation, along with a subset of key mitotic kinesins and cell survival genes (IRS2, VEGF, and Akt1). In particular, ANCCA overexpression correlated strongly with EZH2 in tumors. Our results suggest that ANCCA may integrate multiple oncogenic programs in breast cancer, serving in particular as a prognostic marker and a therapeutic target for triple-negative cancers. Cancer Res; 70(22); 9402–12. ©2010 AACR.
Measurement of the Walking Duration With Therapeutic Shoes in Neuropathic Diabetic Patients by a Novel Device (Show-me)
Authors: Thomas Kästenbauer, Johann Wassermann, Elisabeth Krippl, Rudolf Prager, Karl Irsigler
Journal: Diabetes Care (2006)

Therapeutic shoes and other prophylactic interventions are used to prevent diabetic foot ulceration (1,2), but patient’s compliance to use prescribed footwear has never been investigated in primary care. Therapeutic footwear might be effective in secondary ulcer prevention, as demonstrated in two noncontrolled trials, but was only effective when worn >60% of the daytime (3) or >8 h a day (4). In a controlled clinical trial, no benefit was observed between control patients wearing their own footwear and intervention patients wearing specialized footwear (5).

The aim was to measure the duration of walking with therapeutic shoes by a novel device, “Show-me” (shoe-wearing measuring equipment), in neuropathic patients without a history of …
Study of proprioceptive function in professional volleyball athletes with atrophy of the infraspinatus
Authors: J I Salles, H Alves, M V Amaral, M Cagy, V Cunha-Cruz, R Piedade, P Ribeiro
Journal: British Journal of Sports Medicine (2011)

Background The isolated atrophy of the infraspinatus muscle is an uncommon clinical alteration, generally secondary to the selective lesion of the suprascapular nerve related to sport activities, especially in professional volleyball players. The lesion of the suprascapular nerve can cause kinesthetic deficits. The assessment of kinesthesia is determined by the ability to detect joint movement and has been traditionally conducted by measuring the Threshold of Perception of Passive Motion (TPPM). Objective The goal of the present study was to compare the TPPM among a group of healthy individuals (control group), a group of World League volleyball players with atrophy of the infraspinatus muscle on the dominant side, and group of athletes with no shoulder pathologies. Design, setting and participants Observational study at a controlled research laboratory at the Brazilian Volleyball Training Center (CDV – Saquarema). 12 healthy non-athlete controls, 12 athletes with atrophy of the infraspinatus muscle, and 12 athletes without the atrophy. Interventions A proprioception-testing device passively moved the shoulder and participants were instructed to respond as soon as movement was detected (TPPM) by pressing a button-switch. EEG and electromyographic (EMG) activities were recorded simultaneously. Response latency was established as the delay between the stimulus (movement) and the response (button press). The time-frequency dynamics of the EEG was analyzed. Results An analysis of variance indicated a significant latency reduction (p&lt;0.000) in the group of athletes without the atrophy when compared both to the group of athletes with the atrophy and to the control group. Furthermore, distinct patterns of cortical activity were observed in the three experimental groups. Conclusions The results suggest that systematically trained motor abilities, as well as the atrophy of the infraspinatus muscle, change the cortical representation of the different stages of proprioceptive information processing and, ultimately, the cortical representation of the TPPM.