tbuckley/cabot-search huggingface dataset:
Abstract LB-234: Bcl-2, a novel target of Bmi-1 (the stem cell associated factor), induced Wnt signaling: Implications on prostate cancer
Authors: Mohammad Saleem, Hifzur R. Siddiqui, Rohinton S. Tarapore, Amanda M. Kohl
Journal: Cancer Research (2010)

Abstract In the current report we provide a novel finding about the regulation of Bcl-2 expression in prostate cancer (CaP) cells. Bcl-2 is known to be regulated by Sonic Hedgehog (SHH) signaling. Here, we provide evidence that human CaP cells exhibit SHH-independent Bcl-2 activation which is regulated by Bmi-1-induced Wnt signaling. Bmi-1 is a member of polycomb group gene family and is reported to be involved in stemness and self-renewal capability of cancer stem cells. We investigated the role of Bmi-1 in human CaP development and delineate its mechanism of action. On the basis of immunohistochemical analysis of prostatic specimens of 125 human CaP patients, we show that Bmi-1 protein levels are highly elevated in patients with advanced disease. To understand the mechanism of action of Bmi-1, we employed two-prong strategy. Firstly, Bmi-1 was knocked down in CaP cells (LNCaP, DU145 and PC-3) by employing siRNA technique. Bmi-1-silenced CaP cells exhibited decreased proliferative and clonogenic potential. Secondly, Bmi-1 was over-expressed in CaP cells by transfecting Bmi-1 overexpressing plasmid (pbabe-Bmi-1) in CaP cells. Bmi-1-overexpressing cells exhibited increased clonogenicity and rate of proliferation. We performed a micro-array analysis of Bmi-1-silenced cells and found that silencing of Bmi-1 caused a decrease in the Cyclin D1 (Wnt signaling target) and Bcl-2 (SHH signaling target), however an increase in p16 was observed. These studies were validated by performing immunoblot analysis. We generated a hypothesis that the Bmi-1 regulates the expression of Cyclin D1 and Bcl-2 by interacting with Wnt /SHH signaling in CaP cells. We show that despite blocking SHH signaling (by treating CaP cells with cyclopamine, a SHH signaling inhibitor), Bmi-1 induces the Bcl-2 expression in CaP cells suggesting the involvement of SHH-independent pathway in the regulation of Bcl-2 activation. We identified Wnt signaling as the pathway that regulates Bcl-2 independent of SHH signaling in CaP cells. We provide evidence that Bcl-2 promoter region of Bcl-2 gene has binding sites for Tcf transcriptional factor (Wnt signaling component). We found that Bmi-1 induces Wnt signaling in CaP cells. Taken together, these studies provide deep-insight into the mechanism of CaP cell proliferation (even after chemotherapy such as cyclopamine treatment). We suggest that Bmi-1 could be developed as a novel molecular and therapeutic target for human CaP treatment. 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-234.
Abstract 1484: Aldose reductase inhibition prevents breast cancer cell growth and restores breast cancer cell hormone dependency
Authors: Aramati Bindu M. Reddy, Hareesh B. Nair, Kota V. Ramana, Naseem H. Ansari, Rajeswar R. Tekmal, Satish K. Srivastava
Journal: Cancer Research (2010)

Abstract Breast Cancer (BC) is the second leading cause of cancer deaths in the U.S. women. Hormone ablation therapy reduces the risk of cancer recurrence and improves the survival rate of most BC patients. Although BC initially responds to estrogen ablation therapy, as the cancer progresses, the cancer cells become hormone-independent and prone to metastasis, a major cause of mortality in BC patients. The few currently available drugs that restore hormone dependence are only partially effective and prohibitively costly. Hence there is an urgent need for novel therapeutic modalities. We have recently shown that aldose reductase (AR)-catalyzed GSH-lipid aldehyde conjugates such as GS-DHN induces growth factors-, cytokines- and chemokines-mediated signals that activate PKC, PLC and PI3K, which regulate transcription of NF-κB- and AP1-dependent inflammatory markers. Further, AR has been shown to be overexpressed in human breast cancers. We have investigated the efficacy of AR inhibition in preventing BC cells growth and reversing hormone dependency of BC cells. Our results indicate that pharmacological inhibition of AR or siRNA ablation of AR prevents growth factor -induced proliferation of BC cells (MCF-7) in culture. Similar results were observed when MDA-MB-231 and MDA-MB-468 BC cells were used. To further investigate how AR inhibitor prevents BC cell growth, we have examined the role of AR in resensitization of BC cells to letrozole. We found that combination of fidarestat with letrozole was very effective in inducing maximum cell death in LTLT-Ca cells when compared to fidarestat alone. The combination treatment not only restored estrogen receptor-α (ER-α) levels but also down-regulated HER2/MAPK-signaling proteins. Further, AR-siRNA - transfected MCF-7/Aro and MCF-7 cells upregulated ER-α in western blot and ER-functionality assays whereas in LTLT-Ca cells, ER-α levels were down-regulated as in fidarestat treated cells. Targeting the LTLT-Ca cells with PLG-based fidarestat nanoparticles having polyethylene glycol (PEG)-5000 as stabilizer and conjugated with FITC significantly prevented the aromatase activity in BC cells. Thus we have identified a novel role of AR in BC cell growth and estrogen-dependence of hormone insensitive BC cells and suggest the use of AR inhibitors either alone or in combination with letrozole to prevent as well as treat BC. 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 1484.
MIP-1alfa Level in Nasopharyngeal Aspirates at First Wheezing Episode Is a Predictor of Recurrent Wheezing
Authors: Kazuko Sugai, Hirokazu Kimura, Yumiko Miyaji, Masakazu Yoshizumi, Hiroyuki Tsukagoshi, Yumi Yamada, Masanori Ikeda, Masahiro Noda, Kunihisa Kozawa, Shigemi Yoshihara, Akihide Ryo, Hiromitsu Ogata, Yoshimichi Okayama
Journal: Journal of Allergy and Clinical Immunology (2016)
Uncertainties Abound in Radon Research: Lung Cancer Risk Hard to Quantify
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Uncertainties Abound in Radon Research: Lung Cancer Risk Hard to Quantify Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 10, 22 May 1989, Pages 728–731, https://doi.org/10.1093/jnci/81.10.728 Published: 22 May 1989
The Privileged Access Model of 1,3-Butadiene Disposition
Authors: M C Kohn, R L Melnick
Journal: Environmental Health Perspectives (2000)

In previous attempts to model disposition of 1,3-butadiene in mice and rats, parameter values for 1,2-epoxybut-3-ene metabolism were optimized to reproduce elimination of this gas from closed chambers. However, each of these models predicted much higher concentrations of circulating epoxybutene than were subsequently measured in animals exposed to butadiene. To account for this discrepancy, a previous physiologically based pharmacokinetic model of butadiene disposition was modified to describe a transient complex between cytochrome P450 and epoxide hydrolase on the endoplasmic reticulum membrane. In this model the epoxide products are directly transferred from the P450 to the epoxide hydrolase in competition with release of products into the cytosol. The model includes flow-restricted delivery of butadiene and epoxides to gastrointestinal tract, liver, lung, kidney, fat, other rapidly perfused tissues, and other slowly perfused tissues. Blood was distributed among compartments for arterial, venous, and capillary spaces. Oxidation of butadiene and epoxybutene and hydrolysis and glutathione conjugation of epoxides were included in liver, lung, and kidney. The model reproduces observed uptake of butadiene and epoxybutene from closed chambers by mice and rats and steady-state concentrations of butadiene, epoxybutene, and 1,2;3,4-diepoxybutane concentrations in blood of mice and rats exposed by nose only. Successful replication of these observations indicates that the proposed privileged access of epoxides formed in situ to epoxide hydrolase is a plausible mechanistic representation for the metabolic clearance of epoxide-forming chemicals.
A Comparison of Two Antimicrobial-Impregnated Central Venous Catheters
Authors: Rabih O. Darouiche, Issam I. Raad, Stephen O. Heard, John I. Thornby, Olivier C. Wenker, Andrea Gabrielli, Johannes Berg, Nancy Khardori, Hend Hanna, Ray Hachem, Richard L. Harris, Glen Mayhall
Journal: New England Journal of Medicine (1999)

The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters.
Abstract 527: Pyrrole-Imidazole polyamide inhibits MMP-9 transcription and induces suppression of tumor metastasis
Authors: Xiaofei Wang, Hiroki Nagase
Journal: Cancer Research (2010)

Abstract Pyrrole-Imidazole (PI) polyamide that targets the AP-1-binding site of the MMP-9 promoter was designed and synthesized as a gene-silencing agent for tumor metastases. MMP-9, the 92-kDa type IV collagenase, contributes to tumor invasion and metastases, and strategies to down-regulate its expression could ultimately be of clinical utility. The synthesized MMP-9 PI polyamide showed selective DNA binding ability and significantly inhibited MMP-9 mRNA and protein expression and enzymatic activity in both MDA-MB-231 and Hela cells. Furthermore, the MMP-9 PI polyamide inhibited migration and invasion by in vitro wound-healing and matrigel-invasion assay. The FITC-labeled PI polyamide was localized in nuclei in 45 minutes of incubation with an MDA-MB-231 cell and remained in the nuclei up to 96 hours after incubation in vitro. It was also quickly localized in the mouse cellular nuclei of many tissues, including liver, kidney and spleen, after intravenous injection without using any drug-delivery system. Moreover, the polyamide treatment significantly decreased metastasis of xenografted tumor cells and host angiogenesis in tumors in a mouse model of liver metastasis. Our results suggest that this PI polyamide that targets the MMP-9 gene promoter can be a novel MMP-9 down-regulating molecule for anti-metastasis. 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 527.
THU0184 TNF Production is Regulated by Adalimumab Treatment in Rheumatoid Arthritis Patients
Authors: C. Diaz-Torne, C. Zamora, C. Geli, C. Diaz-Lopez, M. A. Ortiz, P. Moya, J. C. Nieto, I. Castellvi, E. Cantó, J. Casademont, C. Juarez, J. M. Llobet, S. Vidal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adalimumab is a neutralizing anti-TNFα monoclonal antibody that blocks specifically TNFα action. It has been shown to be effective in clinical and quality of life improvement in rheumatoid arthritis (RA) patients. However, the influence of adalimumab on TNFα production and secretion remains unknown. <h3>Methods</h3> Twelve rheumatoid arthritis patients with no previous biological therapy were treated with adalimumab according to clinical practice. We collected demographic (age and gender) clinical (disease duration and DAS28) and laboratory data (RF, a-CCP, ESR and CRP) before and 4, 12 and 24 weeks after the initiation of adalimumab. In whole blood stimulated with LPS, we evaluated: a) free secreted TNFα levels in supernatant (not neutralized by adalimumab) by ELISA; b) TNFα expression on monocyte surface (not neutralized by adalimumab) by flow cytometry; c) Intracellular TNFα production by flow cytometry. <h3>Results</h3> Ten RA patients completed all time of treatment; two RA patients withdraw treatment due to adverse effects. Baseline characteristics of RA patients were: mean age 56.6 ± 12.6 years, 90 % were female, mean duration of disease was 13.7 ± 11.2 years, 70 % of RA patients were RF or anti-CCP positive, mean DAS28 5.05 ± 0.5, mean CRP was 15.6 ± 17.8 mg/L and mean ESR 40.1 ± 23.6 mm/h. Intracellular TNFa production was different in RA patients compared to controls (healthy donors) (33.15 ± 16.71 vs 71.28 ± 1.04% of CD14+TNFα+ cells respectively, p&lt;0.05). After treatment with adalimumab, intracellular TNFα levels increased. Twenty-four weeks after initiating treatment, the intracellular TNFa levels in patients were comparable to controls. Levels of TNFα on monocyte surface were significantly reduced at four weeks and these levels remained low thereafter (see table). Significant changes in intracellular TNFα, surface TNFα and TNFα secretion were detected in RA patients with a good/moderate EULAR response to adalimumab. However, none of these changes were observed in RA patients with bad EULAR response. <h3>Conclusions</h3> Active RA patients showed a defective regulation of TNFα production. Blocking TNFα with adalimumab corrected this defect. After receiving adalimumab, intracellular TNFa levels in RA patients and controls were comparable. <h3>Disclosure of Interest</h3> None Declared
Prevention Studies Under Way
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Prevention Studies Under Way Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 18, 15 September 1993, Pages 1449–1450, https://doi.org/10.1093/jnci/85.18.1449 Published: 15 September 1993
SAT0391 Cumulative Incidence and Clinical Meaning of Severe Infection in a Large Spanish Cohort of Systemic Lupus Erythematosus
Authors: I. Rúa-Figueroa, J. Pego-Reigosa, F. Lόpez-Longo, M. Galindo, J. Calvo-Alén, V. Del Campo, A. Fernández-Nebro, A. Olivé, C. Erausquin, L. Horcada, E. Uriarte, E. Tomero, A. Sánchez-Atrio, M. Freire, A. Zea, J. Andreu, V. Martínez-Taboada
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There are scanty data about infection in Systemic Lupus Erythematosus (SLE) patients from large multicenter cohorts. <h3>Objectives</h3> To describe the prevalence of severe infection (SInf), investigate associated factors and clinical meaning in a large SLE cohort from Spanish Rheumatology Society Lupus Registry (RELESSER). <h3>Methods</h3> Patients with Sinf were compared with patients without SInf in terms of severity, damage, comorbidities and demographic characteristics (bivariate analysis and Cox regression to survival until the first infection). <h3>Results</h3> A total of 3.658 SLE patients included, 90% female, median age 32.9 years (DQ 9.7), 93% Caucasian and 5% Hispanic (Amerindian,mestizo). Mean follow-up (months) was 120.2 (SD: ±87.6). A total of 705 (19.3%) of the patients suffered ≥1 SInf, with an overall of 1.227 SInf. The density of incidence was 29.2 (95%CI: 27.6 - 30.9) infections/ 1000 patients-year. The survival until second infection was lower than survival until first infection (log rank p&lt;0.000). There was predominance of bacterial cause (51.9%), with a 30.4% of unknown cause, and the respiratory tract was the most frequent localization 35.5%. A total of 208 (5.7%) patients died during the follow-up period, 24.5% of them by infection. The predominant localization for the fatal infection was the circulatory stream (bacteraemia/sepsis) (42.0%). In the Cox proportional-hazards regression model age at diagnosis (HR 1.016; 95%CI: 1.009-1.023, p=0.0000) Hispanic ethnic (HR 2.151; 95%CI: 1.539-3.005 p=0.0000) corticosteroids (≥10 mg/day) (HR 1.271; 95%CI: 1.034-1.561, p=0.0224) immunosuppressors (HR 1.348; 95%CI: 1.079-1.684 p=0.0085), hospitalization by SLE (HR 2.567; 95%CI: 1.905-3.459, p=0.0000) renal involvement (HR 1.370; 95%CI: 1.130-1.660, p=0.0013), severity Katz index (SKI) (HR 1.160; 95%CI: 1.105-1.217, p=0.0000), damage index (SDI) (HR 1.069; 95%CI: 1.031-1.108, p=0.0003) and tobacco (HR: 1.332; 95%CI: 1.121-1.583, p=0.0011) were all associated with SInf. Time on antimalarials (months) proved to be protective (HR: 0.998; 95%CI: 0.997-0.999, p=0.0022) <h3>Conclusions</h3> SInf remains a frequent and potentially fatal complication of SLE and/or immunosuppressive therapies, and it9s a marker of more severe disease. Respiratory bacterial infections are the most common SInf in SLE, but bloodstream infections are the most common mortal ones. A previous infectious event seems to increment the risk of a subsequent infection in SLE. SInf are more common in male and Hispanics and is associated age, tobacco use and other co-morbidities. Antimalarials use exerts a time-dependent protective effect <h3>Disclosure of Interest</h3> None declared
WHO recommends further delay in journals publishing research on bird flu
Authors: N. Hawkes
Journal: BMJ (2012)

Controversial research into a more deadly, laboratory created version of the H5N1 bird flu virus should be published—but not yet, says the World Health Organization.

An expert meeting convened by WHO concluded that the importance of the research to public health outweighed the risk that the deadly form might be used as a biological weapon. Research should continue, and papers that have been held back by Science and Nature because of security concerns should be published ( BMJ 2012;344:e1268, 20 Feb, doi:10.1136/bmj.e1268), but public concerns should first be dealt with, said Keiji Fukuda, WHO’s assistant director general for health security and environment, summarising the conclusion of the two day meeting last week.

Last year two teams, one led by Ron Fouchier at Erasmus Medical Centre in Rotterdam and the other by Yoshihiro Kawaoka at …
P116 Serum PARC (CCL18) and exacerbation frequency in COPD
Authors: C. G. George, J. K. Quint, R. J. Sapsford, G. C. Donaldson, J. A. Wedzicha, J. R. Hurst
Journal: Thorax (2010)

<h3>Introduction</h3> Patients with Chronic Obstructive Pulmonary Disease (COPD) experience intermittent exacerbations. The frequency of exacerbations varies amongst patients but the ‘Frequent Exacerbator’ appears to be an independent disease phenotype. As frequent exacerbations are associated with more rapid lung function decline, a validated biomarker is needed to identify those susceptible, prompting rigorous medical treatment and aiding selective recruitment to clinical trials. Pulmonary and Activation-Regulated Chemokine (PARC/CCL18) is a plausible biomarker based on previous reports in other respiratory diseases, making it worthy of study in COPD. <h3>Methods</h3> PARC was measured using ELISA in serum samples from 115 patients enrolled in The London COPD cohort, including 44 paired samples taken at baseline and exacerbation (pre-treatment). PARC was assessed with relation to exacerbation frequency and other inflammatory markers. <h3>Results</h3> The study cohort comprised of 77 males, 34 current smokers, mean age 69.6 years (SD 9.1), FEV<sub>1</sub> 1.13 (0.47) l (45.3 (18.0)% predicted), baseline PARC concentration 124 ng/ml (40.4), median (IQR) exacerbation frequency 1.8/year (0.6–3.0). Higher PARC concentration was associated with more frequent exacerbations (r=0.22, p=0.035). PARC was not related to age, sex, BMI, disease severity (FEV<sub>1</sub>), or smoking pack years (all p&gt;0.05). Significantly lower PARC concentrations were found in current smokers compared to ex-smokers, 112 ng/ml vs 130 ng/ml respectively (p=0.036). PARC did not change from baseline to exacerbation (131 ng/ml vs 125 ng/ml, p=0.256), and the correlation between PARC in the two states was highly significant (r=0.53, p&lt;0.0001). PARC was related to baseline CRP (r=0.28, p=0.013) and blood eosinophil count (r=0.39, p=0.001), with no significant associations at exacerbation, and no relationship with neutrophils or total white blood cell count. <h3>Conclusion</h3> A relationship has been demonstrated between serum PARC concentration and exacerbation frequency in patients with COPD. Correlations between PARC, eosinophils and CRP indicate that this biomarker may identify a subset of patients with a particular inflammatory profile, suggesting specific treatment options. Further work should be carried out to explore the relevance of PARC as a biomarker in the COPD population.
Microsatellite instability is not a defining genetic feature of acute myeloid leukemogenesis in adults: results of a retrospective study of 132 patients and review of the literature
Authors: LM Rimsza, KJ Kopecky, J Ruschulte, I-M Chen, ML Slovak, C Karanes, J Godwin, A List, CL Willman
Journal: Leukemia (2000)
Scintigraphic Detection of Peritoneal Leakage
Authors: Paul W L Thimister, Willibrorous H M Van Kuijk, Sreve G E A Halders, Guido A K Heidendal
Journal: Clinical Nuclear Medicine (2002)

THIMISTER, PAUL W.L. M.D., Ph.D.*; VAN KUIJK, WILLIBROROUS H.M. M.D., Ph.D.†; HALDERS, SERVÉ G.E. A.*; HEIDENDAL, GUIDO A.K. M.D.* Author Information
Diagnosis of Inferior Vena Cava Obstruction on Tc-99m Arcitumomab (CEA Scan) Scintigraphy
Authors: ROBERT J. ENTEL, BARRY R. WEISS
Journal: Clinical Nuclear Medicine (1998)

Tc-99m Arcitumomab (CEA scan) is a radioimmunoscintigraphic agent used in the diagnosis and staging of recurrent colorectal carcinoma. Multiple small collateral veins mostly involving the abdominal wall were identified in the study. Inferior vena cava obstruction was confirmed on contrast venography.
Sclerotherapy for the Treatment of Nodular Intraoral Kaposi's Sarcoma in Patients with AIDS
Authors: Brian C. Muzyka, Michael Glick
Journal: New England Journal of Medicine (1993)

To the Editor: Kaposi's sarcoma is a tumor of endothelial or spindle-cell origin classically described as a multicentric, pigmented angiosarcoma appearing on the lower extremities of older men of Jewish or Mediterranean ancestry1. Since the first report of Kaposi's sarcoma in homosexual and bisexual men in 1981, it has been recognized as the most common tumor among patients with disease due to the human immunodeficiency virus2 and is considered a diagnostic symptom of AIDS3. Kaposi's sarcoma commonly presents as a cutaneous lesion, but intraoral lesions are the initial manifestation in 20 percent of patients4. These oral lesions . . .
207 PERIPORTAL SINUSOIDAL FIBROSIS IS AN EARLY MARKER OF PORTAL HYPERTENSION AND SIGNIFICANT FIBROSIS IN HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: Z. Marino, L. Mensa, G. Crespo, S. Lens, R. Miquel, J.A. Carrion, S. Perez del Pulgar, J. Bosch, X. Forns, M. Navasa
Journal: Journal of Hepatology (2012)