tbuckley/cabot-search huggingface dataset:
Prognostic factors and survival in malignant pleural mesothelioma at a large tertiary referral center in Turkey
Authors: Berna Komurcuoglu, Kadri A. Cirak, Nur Yucel, Gulru Polat, Ozan Usluer
Journal: European Respiratory Journal (2012)

Malignant pleural mesothelioma is a rare tumor but increasing incidance and poor prognosis despite new therapy modalities.  In this study we aimed to investigate the effects of various pretreatment clinical and laboratory characteristics on survival of patients with malignant pleural mesothelioma (MPM).  During last five years, 125 histological proven MPM cases were evaluated at large tertiary refferal center in eastern part of Turkey.  Patients age, gender, performance score, histology, asbestos exposure, smoking history, sympyoms, plasma platelet count, haemoglobin, white blood cell (WBC), plasma LDH level, stages were evaluted in both multivariate and univariate analysis. Univariate analysis showed that patients with extensive stage, N2 nodal invasion and M1 metastasis have a worse prognosis. Multivariate Cox regression analysis showed that sarcomatous histology has found to be indicators of worse prognosis (HR 1, % 95 CI 1.015- 2.19, p= 0.017).  As a result; The patients with extensive stage, n2 nodal inavsion and M1 metastasis were found to related with shorter survival. Sarcomatous histology were found as an indipendent worse prognostic factor in MPM.
Differentially expressed genes in the lungs of fetuses mice exposed to ambient air pollution
Authors: Thaís Mendes-Lopes, Mariana Veras, Natália Costa, Tatiane Mazzotti, Glauber Brito, Roger Chammas, Paulo Saldiva, Thais Mauad
Journal: European Respiratory Journal (2014)

Introduction -  Epidemiologic studies indicate that air pollution affects lung health in prenatal and early childhood. However, the mechanisms involved remain unknown. Aims -  Investigate the influence of gestational exposure to concentrated ambient particles (CAPs) derived from vehicular emissions on the expression of genes involved in lung development. Methods -  Dams were continuously exposed to either filtered air (control group) or CAP (600µg/m 3 /day) from gestational day 5 (intrauterine exposure) until 14 days post conception (dpc), using a Harvard Ambient Particle Concentrator. At the end of the exposures, the total RNA was isolated from the lungs of fetuses at 14 dpc (n=5/group), using the RNeasy Mini kit (Qiagen). Gene expression profiles were investigated with  AffymetrixGeneChip® Mouse 2.0 ST Arrays . Enrichment analysis was performed by Funcassociate 2.0. Results- Microarray data analysis revealed that 86 genes, related to embryogenic development, were differentially expressed in the fetal lung tissue of exposed group when compared to the control group. Fifty-two upregulated (e.g. Shh) and 34 downregulated (e.g. Hoxa5) genes. Notably, upregulated genes were involved in  G-protein coupled receptor activity  (GO:0004930, corrected p-value l0.001). Furthermore, downregulated genes were enriched in genes regulated by the polycomb repressor complex, which contains both EZH2 and Suz12 transcription factors. Conclusions -  Exposure to particulate air pollution during intrauterine life affects the regulation of important genes involved in lung development. We speculate that these alterations in gene regulation could be related to abnormal lung development and function observed in previous studies.
Antitumor Activity of Interferon Against Murine Osteogenic Sarcoma Cells In Vitro 2 3
Authors: Lowell A. Glasgow, John L. Crane, Earl R. Kern
Journal: JNCI Journal of the National Cancer Institute (1978)

Murine interferon inhibited the growth of a continuous line of osteogenic sarcoma (OGS) cells in tissue culture. Inhibition of tumor cell growth by interferon was demonstrated by: a) decreased colony formation In soft agar. b) suppression of clone formation in liquid medium, and c) reduction of tumor cell counts in monolayer cultures. This inhibition of cell growth was further documented by suppression of [3H]thymidine uptake by OGS cells exposed to interferon, which suggested inhibition of DNA synthesis of tumor cells. Exposure of tumor cells for 4 hours, 24 hours, and 2, 3, 4, 6, and 8 days demonstrated greater activity with prolonged exposure to interferon. Inhibition of cell growth was significantly greater for OGS cells than for normal mouse embryo fibroblasts. Finally, the antitumor activity of the interferon preparation could be reversed by anti-interferon antibody.
Abstract 667: Angiotensin II-induced Osteopontin Expression in Vascular Smooth Muscle Cells involves G <sub>q/11</sub> , Ras, ERK, Src and Ets-1.
Authors: Keiko Abe, Mari Ishida, Mariko Sawano, Hidekatsu Nakashima, Nwe Nwe Soe, Lisa Hokama, Narimasa Miho, Hiroshi Sugino, Kazuaki Chayama, Masao Yoshizumi, Takafumi Ishida
Journal: Circulation (2007)

Background : Osteopontin (OPN), an extracellular matrix component produced by vascular smooth muscle cells (VSMC) and monocytes in response to biological stressors, is a regulator of cellular proliferation and migration. Recent studies revealed that OPN also plays a critical role in the progression of atherosclerotic plaques and that angiotensin II (AngII) is a potent upregulator of OPN expression. Therefore, the goal of the present study was to characterize the signaling mechanisms whereby AngII increases OPN expression. Methods and Results : YM254890, a specific inhibitor of G q/11 , potently suppressed AngII-induced OPN expression and ERK1/2 activation. Among DN mutants of small G proteins (Ras, Rac, Rho), only DN-Ras completely suppressed AngII-induced OPN promoter activity. Dominant negative (DN)-MEK1 inhibited AngII-induced OPN promoter activity by 54%, while DN-c-Jun N-terminal kinase (JNK) or DN-p38MAP kinase had no effect. DN-Src and Csk suppressed AngII-induced OPN promoter activity by 49% and 71%, respectively. In addition, small interfering RNA against Ets-1 (a transcriptional factor downstream of ERK1/2) suppressed AngII-induced OPN expression by 54 ± 4.3%. In a separate experiment, rats were treated with the AngII type I receptor blocker, valsartan (1 mg/kg/day), or vehicle for 2 weeks after carotid artery balloon injury. The intima/media ratio and OPN expression were significantly lower in valsartan-treated rats than in vehicle-treated rats. Conclusion : These data suggest that AngII-induced OPN expression in VSMC is mediated by signaling cascades involving G q/11 , the Ras-ERK axis, and c-Src, and by the transcription factor, Ets-1. Further, OPN may play a role in AngII-induced neointimal formation. These signaling molecules may represent therapeutic targets for the prevention of pathological vascular remodeling in patients with hypertension and atherosclerosis.
Tamoxifen for the Prevention of Breast Cancer: Psychosocial Impact on Women Participating in Two Randomized Controlled Trials
Authors: Lesley Fallowfield, Anne Fleissig, Rob Edwards, Andrea West, Trevor J. Powles, Anthony Howell, Jack Cuzick
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. PATIENTS AND METHODS: The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. RESULTS: Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report cheklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. CONCLUSION: In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women’s psychosocial and sexual functioning.
Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy.
Authors: D W Northfelt, B J Dezube, J A Thommes, R Levine, J H Von Roenn, G M Dosik, A Rios, S E Krown, C DuMond, R D Mamelok
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the efficacy and safety of pegylated-liposomal doxorubicin in patients with AIDS and Kaposi's sarcoma (AIDS-KS) who experienced failure of standard chemotherapy. METHODS Fifty-three patients with advanced AIDS-KS who experienced disease progression or intolerable toxicities while receiving standard doxorubicin/bleomycin/vincristine (ABV) or bleomycin/vincristine (BV) chemotherapy were identified from a cohort of patients who were then treated with pegylated-liposomal doxorubicin. Patients received 20 mg/m2 pegylated-liposomal doxorubicin (Doxil; Sequus Pharmaceuticals, Inc, Menlo Park, CA) every 3 weeks. RESULTS Nineteen patients (36%) had a partial response (PR) and one patient had a clinical complete response (CCR). The median duration of response and time (from study entry) to treatment failure were 128 and 134 days, respectively. Of 28 patients who experienced disease progression while receiving combination regimens that contained standard doxorubicin, the PR rate was 32%, which suggests that the pegylated-liposomal encapsulation increases the therapeutic effect of doxorubicin. Patients obtained clinical benefits such as flattening of lesions (48%), improved lesion color (56%), relief of pain (45%), and loss of edema (83%). Forty-nine percent of patients had more than one clinical benefit. The most common adverse effect was leukopenia, which occurred in 40% of patients. Only 15% of patients had nausea and/or vomiting, none of which was severe; 9% experienced alopecia, also generally mild. CONCLUSION Pegylated-liposomal doxorubicin offers a new alternative for treatment of patients who have experienced failure of standard chemotherapy for AIDS-KS.
Detection of neuroblastoma cells in bone marrow using GD2 specific monoclonal antibodies.
Authors: N K Cheung, D D Von Hoff, S E Strandjord, P F Coccia
Journal: Journal of Clinical Oncology (1986)

Three murine monoclonal antibodies (Mab) against a cell surface antigen, the disialoganglioside GD2, were investigated for detecting bone marrow metastasis in patients with neuroblastoma (NB) by indirect immunofluorescence (IF). As few as 0.01% NB cells could be detected. No Mab reactivity was found in 60 non-NB marrows. Thirty-five marrows from patients with stage III and stage IV NB at diagnosis were examined during the course of their disease. Tumor involvement was found in 74% by Mab, 55% by the two-layer soft agar clonogenic assay (CA), and 27% by conventional histochemical stains. All marrows containing NB histologically were positive for tumor by Mab; 71% were also positive by CA. Of histologically negative marrows, 63% were Mab positive, the majority (78%) of which were also positive by CA. All Mab nonreactive samples were negative histologically and by CA. We conclude that these antibodies are highly sensitive and specific in detecting NB metastasis in bone marrow.
Bowel dysfunction after sphincter-preserving surgery.
Authors: L. K. Temple, S. Patil, P. Paty, M. R. Weiser, G. Nash, J. G. Guillem, K. A. Goodman, W. D. Wong, D. Schrag
Journal: Journal of Clinical Oncology (2010)

3657 Background: Alterations in bowel function following sphincter-preserving surgery (SPS) for rectal cancer have not been well studied, limiting our ability to effectively counsel patients regarding appropriate surgery. Methods: A prospective single-institution longitudinal study of stage I-III rectal cancer patients undergoing SPS was performed from 1/07-7/09. Patients completed the validated MSKCC Bowel Function Instrument (BFI) and EORTC-QOL30/38. Comparisons between preoperative and 6 month responses were made using paired t test; predictors of 6 month bowel function were assessed with t test. Results: 91 of 117 (78%) rectal cancer patients completed surveys preoperatively and 6 months post restoration of bowel continuity (Table). Significant dysfunction at 6 months was reported; >57% reported >4 bowel movements/day. 15 of 18 BFI items were reported in >75% of patients, many severe. 80% reported altering their activities to compensate for bowel dysfunction. Compared to preoperative scores, 6 month scores were worse on all BFI subscales (frequency (p=0.003), urgency (p<0.001), dietary (p<0.001)), EORTC-CRC38 GI subscale (p=0.002) and total BFI score (p<0.001). Predictors of poor function included male gender, radiation, low tumor, hand-sewn anastomosis (Table). Conclusions: Post SPS bowel function is significantly worse 6 months after restoration of bowel continuity, and is associated with patient and treatment factors. Longer follow-up of this cohort will provide better assessment of long-term bowel function after SPS, enabling us to better counsel rectal cancer patients preoperatively. N 6-mo BFI total score (range 14-70) p Gender Male 55 51 (31-66) 0.016 Female 36 47 (28-64) Median age 54 (25-85) <55 47 (28-66) ≥55 48 (34-65) 0.79 Pre-op atage I/II 30 N/A III 61 Median level of tumor from anal verge (cm) 8 (1-16) <8 cm 46 (28-65) ≥8 cm 48 (37-66) 0.022 Pre-op therapy No RT (18 CT only) 39 50 (36-66) 0.006 Combined CT/RT 52 48 (28-64) Surgery LAR 26 48 (37-66) 0.30 LAR/CAA 63 48 (28-65) TAE 2 Too small LAR and LAR/CAA No. pouch vs straight 20 vs. 59 51 (28-65) vs. 48 (31-66) 0.07 No. hand sewn vs. stapled 24 vs. 65 45 (31-64) vs. 50 (28-66) 0.003 Temp stoma vs. no stoma 67 vs. 24 47 (29-65) vs. 51 (37-66) 0.09 No significant financial relationships to disclose.
Effects of Angiotensin II Type 1 Receptor Blockade on β-Cell Function in Humans
Authors: Syed Bokhari, Zarmen Israelian, Jonelle Schmidt, Eliot Brinton, Christian Meyer
Journal: Diabetes Care (2006)

Evidence indicates that activation of the angiotensin II type 1 receptor (AT1R) acutely decreases insulin secretion in animals and humans (1–3), mediated at least partially by reductions in islet blood flow and proinsulin biosynthesis (1,2). In contrast, AT1R blockade increased insulin secretion by 40–60% in Zucker diabetic fatty (ZDF) rats (4) and in obese db/db mice (5), thereby delaying the otherwise premature onset of diabetes in the latter animal model. If this were the case in humans, it would provide an explanation for the finding that AT1R antagonist treatment reduces the incidence of type 2 diabetes by ∼25% in high-risk individuals in clinical trials despite no improvement in insulin sensitivity in most …
Missing data in IPF trials: do not let methodological issues undermine a major therapeutic breakthrough
Authors: Gabriel Thabut, Bruno Crestani, Raphaël Porcher, Luca Richeldi
Journal: European Respiratory Journal (2015)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disorder associated with a poor prognosis. Until recently, there has been limited evidence that any drug could alter the course of the disease [1]. However, thanks to worldwide cooperative efforts, large randomised controlled trials have recently demonstrated the efficacy of pirfenidone and nintedanib in slowing down the course of IPF [2–4]. After decades of disappointing results in a number of clinical trials, these robust, groundbreaking studies now give patients with IPF the choice of safe and effective therapeutic options. Missing data will not disappear in future IPF (and not only IPF) trials <http://ow.ly/PijJo>
Non–Clear Cell Renal Cancer: Features and Medical Management
Authors: Daniel Y. C. Heng, Toni K. Choueiri
Journal: Journal of the National Comprehensive Cancer Network (2009)

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically with the introduction of targeted therapies against vascular endothelial growth factor and the mammalian target of rapamycin. Because patients with clear cell histology account for more than 80% of patients with RCC, little evidence is available on treating patients with non-clear cell histologies. Most clinical trials have excluded them from enrollment, except for a randomized study investigating temsirolimus. Many retrospective studies on the use of sunitinib, sorafenib, and temsirolimus in patients with non-clear cell histology have shown response rates ranging from 3.7% to 16%. Prospective studies in non-clear cell histologies are ongoing. Although response rates may not be as high as those in patients with clear cell histologies, targeted therapy may provide a clinically meaningful response. New investigational therapies are on the horizon for papillary RCC--the most-common non-clear cell RCC histology--targeting pathways specific to this histology, such as the c-MET pathway.
Abstract 15247: Endothelial Overexpression of LOX-1 Protects from in vivo Arterial Thrombosis and Modulates TF Expression
Authors: Alexander Akhmedov, Giovani G Camici, Simona Stivala, Erik W Holy, Alexander Breitenstein, Christine Lohmann, Juerg-Hans Beer, Felix C Tanner, Christian M Matter, Thomas F Luescher
Journal: Circulation (2012)

Background-The hallmark of the initiation of atherosclerotic lesion is foam cell formation, and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process....
Evaluation of human dendritic cell vaccine coexpressing a SOCS1 inhibitor, tumor-associated antigen, and TLR ligand
Authors: Bangxing Hong, Xiaotong Song, Bingya Liu, Lisa Rollins, Si-Yi Chen, Xue F Huang
Journal: Cancer Research (2007)

2723   Dendritic cell (DC)-based tumor vaccine represents a promising therapeutic approach, but has only achieved limited success in the clinic. The major obstacle is that the current DC vaccine immunization only elicits weak CTL responses against self tumor-associated antigens that are insufficient to break self-tolerance at the host level. Recent studies indicate the immunostimulatory potency of DCs is inhibited by negative regulators of proinflammatory signal transduction pathways such as the suppressor of cytokine signaling (SOCS1). SOCS1 is an inducible, negative feedback regulator of JAK/STAT signal transduction pathways and the inhibition of SOCS1 significantly enhances the sensitivity of mouse bone-marrow-derived DCs to stimulation with TLR agonists. In this study, we investigated the immunostimulatory potency of a human PBMC-derived DC vaccine that coexpresses a SOCS1-siRNA, tumor-associated antigen, and TLR agonist. We constructed and produced a recombinant adenovirus (Ad-siSSF) which co-expresses hSOCS1-siRNA, tumor-associated antigen (a transdominant negative survivin mutant), and bacterial flagellin, a ligand for TLR5. We also generated a recombinant adenovirus (Ad-S) expressing the transdominant negative survivin mutant as control. We found that human PBMC-derived DCs transfected with Ad-siSSF showed enhanced expression of co-stimulatory molecules such as CD40, CD80, CD86 and chemokine receptors such as CCR7, in comparison with human DCs transfected with Ad-S or Ad-CMV controls. Increased levels of pro-inflammatory cytokines and chemokines, including IL-6, IL-12, IFN-γ, TNF-α, and Rantes, were produced by human DCs transfected with Ad-siSSF.  In vitro  assays further demonstrated that the transduced human DCs had an enhanced migration function in response to chemokines. Further study is under way to investigate the immunostimulatory potency of the human DC vaccine to activate antigen-specific CTL responses  in vitro  and in SCID-hu mouse models.
Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes
Authors: S. Ladhani, M.P.E. Slack, M.E. Ramsay, P.T. Heath, P.B. McIntyre, J. Diez-Domingo, J. Campos, R. Dagan
Journal: Clinical Microbiology and Infection (2009)
Abstract 15003: The Association of Depression Severity to Future Death and Incident Cardiovascular Disease Overall and Stratified by Age
Authors: Heidi T May, Tami L Bair, Brenda Reiss-Brennan, Stacey Knight, Jeffrey L Anderson, Benjamin D Horne, Kimberly D Brunisholz, Joseph B Muhlestein
Journal: Circulation (2014)

Background: Depression has been reported to be associated with increased risk of death and cardiovascular (CV) disease. Although limited, there is some evidence that this elevated risk may vary by age and symptom severity. Methods: Pts (N=44,331) within an integrated healthcare system who were administered the patient health questionnaire (PHQ-9) within a primary care setting (>85 primary care clinics), ≤40 yrs of age, and without prior CV disease were studied. The first questionnaire completed was used to assess depression and symptom severity. Symptom severity was categorized as: none (score 0-9), mild (score 10-14), moderate (score 15-19), and severe (score ≤20). Cox hazard regression was used to evaluate the association of depression severity overall and by age (40-54 yrs [n=22,987], 55-69 yrs [n=15,435], and ≤70 yrs [n=5909]) to all-cause death, CAD, CVA, and MACE (death, CAD, CVA). Results: Pts were 66% female, 36% had hypertension, 17% smoked, and 15% were diabetic. Symptom severity for none, mild,...
Manufacturer's information insert and subjective theophylline side-effects
Authors: D Vesco, M Toumi, F Faraj, H Razzouk, J Orehek
Journal: European Respiratory Journal (1990)

In Western Europe medicine packages contain an insert prepared by the manufacturer which enumerates the drug side-effects. We investigated the influence of this insert on alleged theophylline side-effects. Forty literate adult asthmatics were randomly allocated into two groups (n = 20 each): theophylline packages contained the manufacturer's insert in group A but not in group B. Theophylline was prescribed (10 mg.kg-1 body weight qd) for one week. During this period the patients filled a diary grading 13 different symptoms from 0 to 3; 5 of these symptoms were listed on the insert as theophylline side-effects. On the eighth day the patients were interviewed and theophylline blood levels measured. Theophylline side-effects were significantly more marked in group A than in group B, whereas the other symptoms were of similar magnitude. Eight patients prematurely stopped their treatment in group A vs 3 in group B, because of alleged intolerance. Theophylline blood levels did not differ significantly in the two groups; neither did they in the subgroup which stopped treatment and in the one which complied to prescription. We conclude that side-effects were suggested to the patients by the insert and/or that the insert increased their awareness of side-effects, with a subsequent detrimental influence upon compliance to therapy.