tbuckley/cabot-search huggingface dataset:
The Absence of Human Equilibrative Nucleoside Transporter 1 Is Associated with Reduced Survival in Patients With Gemcitabine-Treated Pancreas Adenocarcinoma
Authors: Jennifer Spratlin, Randeep Sangha, Darryl Glubrecht, Laith Dabbagh, James D. Young, Charles Dumontet, Carol Cass, Raymond Lai, John R. Mackey
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Gemcitabine monotherapy is the standard palliative chemotherapy for pancreatic adenocarcinoma. Gemcitabine requires plasma membrane nucleoside transporter proteins to efficiently enter cells and exert it cytotoxicity. In vitro studies have demonstrated that deficiency of human equilibrative nucleoside transporter 1 (hENT1), the most widely abundant and distributed nucleoside transporter in human cells, confers resistance to gemcitabine toxicity, but the distribution and abundance of nucleoside transporters in normal and malignant pancreatic tissue is unknown. Experimental Design: We studied tumor blocks from normal pancreas and 21 Alberta patients with gemcitabine-treated pancreatic cancer. Immunohistochemistry on the formalin-fixed, paraffin-embedded tissues was performed with specific hENT1 and human Concentrative Nucleoside Transporter 3 monoclonal antibodies and scored by a pathologist blinded to clinical outcomes. Results: hENT1 was detected in normal Langerhan cells and lymphocytes but not in normal glandular elements. Patients in whom all adenocarcinoma cells had detectable hENT1 had significantly longer median survivals from gemcitabine initiation than those for whom hENT1 was absent in a proportion (10 to 100%) of adenocarcinoma cells (median survival, 13 versus 4 months, P = 0.01). Immunohistochemistry for human Concentrative Nucleoside Transporter 3 revealed moderate to high-intensity staining in all adenocarcinoma tissue samples. Conclusions: Patients with pancreatic adenocarcinoma with uniformly detectable hENT1 immunostaining have a significantly longer survival after gemcitabine chemotherapy than tumors without detectable hENT1. Immunohistochemistry for hENT1 shows promise as a molecular predictive assay to appropriately select patients for palliative gemcitabine chemotherapy but requires formal validation in prospective, randomized trials.
Molecular Beacons of Xeno-Nucleic Acid for Detecting Nucleic Acid
Authors: Qi Wang, Lei Chen, Yitao Long, He Tian, Junchen Wu
Journal: Theranostics (2013)

Molecular beacons (MBs) of DNA and RNA have aroused increasing interest because they allow a continuous readout, excellent spatial and temporal resolution to observe in real time.This kind of dual-labeled oligonucleotide probes can differentiate between bound and unbound DNA/RNA in homogenous hybridization with a high signal-to-background ratio in living cells.This review briefly summarizes the different unnatural sugar backbones of oligonucleotides combined with fluorophores that have been employed to sense DNA/RNA.With different probes, we epitomize the fundamental understanding of driving forces and these recognition processes.Moreover, we will introduce a few novel and attractive emerging applications and discuss their advantages and disadvantages.We also highlight several perspective probes in the application of cancer therapeutics.
PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model
Authors: R. Datta, A. S. Naura, M. Zerfaoui, Y. Errami, M. Oumouna, H. Kim, J. Ju, V. P. Ronchi, A. L. Haas, A. H. Boulares
Journal: Allergy (2011)

To cite this article: Datta R, Naura AS, Zerfaoui M, Errami Y, Oumouna M, Kim H, Ju J, Ronchi VP, Haas AL, Boulares AH. PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model. Allergy 2011; 66: 853–861. Background: We recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1−/− mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5. Objective: To explore the mechanism by which PARP-1 regulates IL-5 production and to determine how PARP-1 inhibition blocks allergen-induced eosinophilia. Methods: This study was conducted using a murine model of allergic airway inflammation and primary splenocytes. Results: PARP-1 knockout-associated reduction in IL-5 upon allergen exposure occurs at the mRNA level. Such an effect appears to take place after IL-4 receptor activation as PARP-1 inhibition exerted no effect on JAK1/JAK3 activation. Signal transducer and activator of transcription-6 (STAT-6) protein was severely downregulated in spleens of PARP-1−/− mice without any effect on mRNA levels, suggesting an effect on protein integrity rather than gene transcription. Interestingly, the degradation of STAT-6 in PARP-1−/− mice required allergen stimulation. Additionally, PARP-1 enzymatic activity appears to be required for STAT-6 integrity. The downregulation of STAT-6 coincided with mRNA and protein reduction of GATA-binding protein-3 and occupancy of its binding site on the IL-5 gene promoter. IL-4 was sufficient to induce STAT-6 downregulation in both PARP-1−/− mice and isolated splenocytes. Such degradation may be mediated by calpain, but not by proteasomes. Conclusion: These results demonstrate a novel function of PARP-1 in regulating IL-5 expression during allergen-induced inflammation and explain the underlying mechanism by which PARP-1 inhibition results in IL-5 reduction.
Identifying patients with axial spondyloarthritis in primary care: how useful are items indicative of inflammatory back pain?
Authors: A Braun, E Saracbasi, J Grifka, J Schnitker, J Braun
Journal: Annals of the Rheumatic Diseases (2011)

Background The value of clinical items defining inflammatory back pain to identify patients with axial spondyloarthritis (SpA) in primary care is unclear. Objective To identify predictive clinical parameters for a diagnosis of axial SpA in patients with chronic back pain presenting in primary care. Methods Consecutive patients aged &lt;45 years (n=950) with back pain for &gt;2 months who presented to orthopaedic surgeons (n=143) were randomised based on four key questions for referral to rheumatologists (n=36) for diagnosis. Results The rheumatologists saw 322 representative patients (mean age 36 years, 50% female, median duration of back pain 30 months). 113 patients (35%) were diagnosed as axial SpA (62% HLA B27+), 47 (15%) as ankylosing spondylitis (AS) and 66 (21%) as axial non-radiographic SpA (nrSpA). Age at onset ≤35 years, improvement by exercise, improvement with non-steroidal anti-inflammatory drugs, waking up in the second half of the night and alternating buttock pain were identified as most relevant for diagnosing axial SpA by multiple regression analysis. Differences between AS and nrSpA were detected. No single item was predictive, but ≥3 items proved useful for good sensitivity and specificity by receiver operating characteristic modelling. Conclusion This study shows that a preselection in primary care of patients with back pain based on a combination of clinical items is useful to facilitate the diagnosis of axial SpA.
Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis
Authors: T Yli-Kerttula
Journal: Annals of the Rheumatic Diseases (2000)

<h3>BACKGROUND</h3> Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. <h3>OBJECTIVE</h3> To evaluate the effect of a three month course of ciprofloxacin on ReA. <h3>METHODS</h3> In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. <h3>RESULTS</h3> Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. <h3>CONCLUSION</h3> Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.
Allogeneic Tumor-Syngeneic Muscle Sandwich Grafts: A Method for Promoting Nonspecific Growth 2
Authors: Richard C. Parks
Journal: JNCI Journal of the National Cancer Institute (1976)

In H-2-incompatible mice, four strain-specific transplantable murine tumors grew when sandwiched between layers of muscle syngeneic to the intended recipient. The allogeneic tumor-syngeneic muscle sandwich (TMS) graft did not grow in recipients presensitized to the allogeneic tumor and in recipients immunized concurrently with tumor or skin allografts from the same strain as the sandwiched tumor. Third-party muscle, allogeneic to both tumor and host, also was effective in promoting nonspecific growth. The escape of the allogeneic tumor from immunologic destruction when it was implanted as a TMS graft may have been due to an afferent blockade.
Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.
Authors: D H Patil, D Westaby, Y R Mahida, K R Palmer, R Rees, M L Clark, A M Dawson, D B Silk
Journal: Gut (1987)

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.
Aortic Stiffness of Kidney Transplant Recipients Correlates with Donor Age
Authors: Michel Delahousse, Michel Chaignon, Laurent Mesnard, Pierre Boutouyrie, Michel E. Safar, Thierry Lebret, Myriam Pastural-Thaunat, Leila Tricot, Anne Kolko-Labadens, Alexandre Karras, Jean-Philippe Haymann
Journal: Journal of the American Society of Nephrology (2008)

Increased aortic stiffness is a major factor responsible for the high cardiovascular mortality in patients with end-stage renal disease, but the impact of kidney transplantation on recipient aortic stiffness remains poorly defined. The use of expanded-criteria kidney donors is associated with decreased recipient survival compared with the use of standard-criteria donors, although the underlying mechanisms are incompletely understood. It was hypothesized that donor characteristics may affect recipient aortic stiffness, which may contribute to cardiovascular mortality in these patients. Aortic stiffness was evaluated by measurement of carotid-femoral pulse wave velocity in 74 cadaveric kidney recipients at 3 and 12 mo after transplantation. At 3 mo, aortic stiffness was associated exclusively with recipient-related factors: Age, gender, and mean BP. At 12 mo, age of the donor kidney emerged as an additional determinant. The change in aortic stiffness between 3 and 12 mo strongly correlated with donor age; stiffness improved in recipients of young kidneys (first tertile of donor age) and worsened in recipients of older kidneys (upper tertile of donor age). At 12 mo, the carotid-femoral pulse wave velocity was >1 m/s higher in recipients of the oldest kidneys than in the recipients of younger kidneys. The association between donor age and aortic stiffness was independent of recipient age, gender, mean BP, pretransplantation dialysis duration, conventional cardiovascular risk factors, medication, posttransplantation events, and GFR. These results demonstrate that the impact of kidney transplantation on recipient aortic stiffness is dependent on donor age and suggest that ongoing damage to large arteries might contribute to the mechanism underlying the association of old-donor kidneys and increased cardiovascular mortality.
Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis
Authors: L. Eriksson, M. Ahluwalia, J. Spiewak, G. Lee, D. S. R. Sarma, M. J. Roomi, E. Farber
Journal: Environmental Health Perspectives (1983)

Hepatocyte (“hyperplastic”) nodules induced in the liver by initiation with diethylnitrosamine and selected by dietary 2-acetylaminofluorene plus partial hepatectomy (“resistant hepatocyte model”) have a special pattern of biochemical behavior and metabolic activity different than that seen acutely with many xenobiotics including many promoting agents and carcinogens. The nodule cells show a very low uptake of 2-acetylaminofluorene, relative to surrounding and normal liver, low levels of activity in the cytochromes P-450 and aryl hydrocarbon hydroxylase, high levels of activity in γ-glutamyltransferase, microsomal epoxide hydrolase, soluble glutathione-S-transferase and soluble UDP-glucuronyltransferase (UDP-GT1) and elevated levels of glutathione. This metabolic pattern appears to maximize the resistance of the nodules to xenobiotics generally, such as 2-acetylaminofluorene, and thereby may account for the resistant behavior of nodule hepatocytes to the inhibition of cell proliferation and the cytotoxicity by 2-acetylaminofluorene and other carcinogens. The possible importance of this seemingly new metabolic program in carcinogenesis is discussed briefly.
Plague as a Biological Weapon
Authors: Thomas V. Inglesby, David T. Dennis, Donald A. Henderson, John G. Bartlett, Michael S. Ascher, Edward Eitzen, Anne D. Fine, Arthur M. Friedlander, Jerome Hauer, John F. Koerner, Marcelle Layton, Joseph McDade, Michael T. Osterholm, Tara O'Toole, Gerald Parker, Trish M. Perl, Philip K. Russell, Monica Schoch-Spana, Kevin Tonat, None for the Working Group on Civilian Biodefense
Journal: JAMA (2000)

The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population.The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies.MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000.The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members.An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.
Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages
Authors: K. Kamiya, Y. Aoyama, O. Yamasaki, A. Kamata, J. Yamagami, K. Iwatsuki, Y. Tokura
Journal: British Journal of Dermatology (2015)

Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)‐treated Dsg3 enzyme‐linked immunosorbent assay (ELISA) we have shown that the proportion of anti‐Dsg3 antibodies against calcium‐dependent epitopes decreased upon shifting to the inactive phase in patients with PV. To analyse the epitope profiles of anti‐Dsg1 antibodies across the different activity stages of PF. We evaluated five patients with PF who retained high serum levels of anti‐Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA‐treated and exfoliative toxin‐treated ELISAs. To map the epitopes of anti‐Dsg1 antibodies, immunoprecipitation–immunoblotting was performed using a set of Dsg1/Dsg2 domain‐swapped molecules. Anti‐Dsg1 antibodies against the calcium‐dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti‐Dsg1 antibodies against the calcium‐dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation–immunoblotting showed that most of the anti‐Dsg1 antibodies bound to the extracellular domains (EC)1–2 of Dsg1. In patients with PF, the calcium‐dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.
Gemtuzumab ozogamicin in pediatric CD33-positive acute lymphoblastic leukemia: first clinical experiences and relation with cellular sensitivity to single agent calicheamicin
Authors: ChM Zwaan, D Reinhardt, H Jürgens, D R Huismans, K Hählen, O P Smith, A Biondi, E R van Wering, J Feingold, G J L Kaspers
Journal: Leukemia (2003)
Chromosome translocation and c-MY Cactivation by Epstein-Barr virus and Euphorbia tirucalli in B lymphocytes
Authors: T. Aya, T. Kinoshita, S. Imai, S. Koizumi, F. Mizuno, T. Osato, C. Satoh, T. Oikawa, N. Kuzumaki, H. Ohigashi, K. Koshimizu
Journal: The Lancet (1991)
Letter to the editor: Seafarers: a new risk group for meticillin-resistant Staphylococcus aureus (MRSA)
Authors: W S Lekkerkerk, P J van Genderen, J A Severin, J P Peper, E F Storm, M C Vos
Journal: Eurosurveillance (2013)

Preview this article: Letter to the editor: Seafarers: a new risk group for meticillin-resistant Staphylococcus aureus (MRSA), Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/18/43/art20618-en-1.gif
Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma
Authors: Sun Joo Lee, Sukhen C. Ghosh, Hee Dong Han, Rebecca L. Stone, Justin Bottsford-Miller, De Yue Shen, Edmond J. Auzenne, Alejandro Lopez-Araujo, Chunhua Lu, Masato Nishimura, Chad V. Pecot, Behrouz Zand, Duangmani Thanapprapasr, Nicholas B Jennings, Yu Kang, Jie Huang, Wei Hu, Jim Klostergaard, Anil K. Sood
Journal: Clinical Cancer Research (2012)

Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown to result in reduced normal tissue toxicity and to minimize "off-treatment" exposure resulting in an improved therapeutic ratio.We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1 or HeyA8 ovarian cancer cells were treated intraperitoneally (i.p.) with MET HA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects.All MET HA-TXL-treated mice and the MTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values < 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL-treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistant HeyA8-MDR model, significant reduction in tumor weight and nodule counts was noted in the metronomic groups whereas the response of the MTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis.This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism.
E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation
Authors: Xu Zhi, Dong Zhao, Zehua Wang, Zhongmei Zhou, Chunyan Wang, Wenlin Chen, Rong Liu, Ceshi Chen
Journal: Cancer Research (2012)

Abstract To identify novel oncogenic E3 ubiquitin ligases as anticancer targets, we screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the sulphorhodamine B assay in the MDA-MB-231 breast cancer cell line and the PC3 prostate cancer cell line. RNF126 was identified and validated as a candidate from this screening. Knockdown of RNF126 dramatically decreased cell viability in these cancer cell lines. Consistently, RNF126 knockdown delayed cell-cycle G1–S progression and decreased cell proliferation. Using protein array analysis we found that RNF126 silencing increased cell-cycle dependent kinase inhibitor p21cip protein levels in both MDA-MB-231 and PC3. Knockdown of RNF126 stabilized the p21 protein rather than increased p21 mRNA levels. We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. RNF126 knockdown induced loss of cell viability in MDA-MB-231 and PC-3 can be partially rescued by depletion of p21. RNF126 stable knockdown in PC3 inhibited tumor growth in SCID mice. Finally, we found that RNF126 is highly expressed in a subset of breast cancer cell lines and negatively correlated with p21 expression levels. These findings suggest that RNF126 promotes cancer cell proliferation by targeting p21 for ubiquitin-mediated degradation. RNF126 could be a novel therapeutic target in breast and prostate cancers. Cancer Res; 73(1); 385–94. ©2012 AACR.