tbuckley/cabot-search huggingface dataset:
ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma
Authors: M. Dreyling, C. Thieblemont, A. Gallamini, L. Arcaini, E. Campo, O. Hermine, J.C. Kluin-Nelemans, M. Ladetto, S. Le Gouill, E. Iannitto, S. Pileri, J. Rodriguez, N. Schmitz, A. Wotherspoon, P. Zinzani, E. Zucca
Journal: Annals of Oncology (2013)
Prognostic factors in 1038 women with metastatic breast cancer
Authors: R. Largillier, J.-M. Ferrero, J. Doyen, J. Barriere, M. Namer, V. Mari, A. Courdi, J.M. Hannoun-Levi, F. Ettore, I. Birtwisle-Peyrottes, C. Balu-Maestro, P.Y. Marcy, I. Raoust, M. Lallement, E. Chamorey
Journal: Annals of Oncology (2008)
Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial
Authors: Marta Jozwiak, Katrien Oude Rengerink, Marjan Benthem, Erik van Beek, Marja GK Dijksterhuis, Irene M de Graaf, Marloes E van Huizen, Martijn A Oudijk, Dimitri NM Papatsonis, Denise AM Perquin, Martina Porath, Joris AM van der Post, Robbert JP Rijnders, Hubertina CJ Scheepers, Marc EA Spaanderman, Maria G van Pampus, Jan Willem de Leeuw, Ben WJ Mol, Kitty WM Bloemenkamp
Journal: The Lancet (2011)
Immunochemical specificity of the combining site of murine myeloma protein CAL20 TEPC1035 reactive with dextrans.
Authors: S Sugii, E A Kabat, M Shapiro, M Potter
Journal: The Journal of Experimental Medicine (1981)

The immunochemical specificity of the combining sites of murine myeloma protein CAL20 TEPC1035 was studied by quantitative precipitin and precipitin inhibition assays. Myeloma protein CAL20 TEPC1035 precipitated with only three dextrans, B1355S4, B1498S, and B1501S, with high proportions of alpha(1 leads to 3) linkages, but not with any other dextrans, glycogen, and pullulan. Inhibition tests with various sugars show that the combining site of myeloma protein CAL20 TEPC1035 is most complementary to panose, a trisaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc. Panose was 3.3 times more potent than a tetrasaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc alpha(1 leads to 4)DGlc and 8, 23, 42, &amp;gt; 42 times more active than maltose, nigerose, isomaltose, and kojibiose, respectively. These findings were paralleled by their binding properties as determined by affinity electrophoresis. The association constants (Ka) of these three dextrans to myeloma protein CAL20 TEPC1035 ranged from 3.8 X 10(3) ml/g to 5.02 X 10(3) ml/g. The association constant of inhibitor (Kia) of panose was 8.19 X 10(3) M-1. Myeloma protein CAL20 TEPC1035 is an antidextran with specificity different from those of other murine myeloma antidextrans and from human antidextrans reported previously and its combining site size is at least as large as a trisaccharide. The binding constant of methyl alpha-D-glucoside (7.2 X 10(2)) was 73% of that of panose and comparable to that of myeloma protein W3129 (9.4 X 10(2)) with a cavity-type site and 600 times lower (1.6 X 10(0)) for QUPC52 with a groove type site, indicating that the terminal nonreducing residue is held in a cavity. Inhibition data with various alpha(1 leads to 4)-linked oligosaccharides also indicate that the internal portions of these inhibitors may react directly with a portion of the combining site. These findings suggest that myeloma antidextran CAL20 TEPC1035 has a partial cavity-type combining site in which the terminal nonreducing dGlc alpha(1 leads to 6) moiety is held in a cavity with the other two sugars forming a groove. However, oligosaccharides with one or more alternating [leads to 3DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 3)DGlcl leads to] units with and without terminal nonreducing DGlc alpha(1 leads to 6) or DGLc alpha(1 leads to 3) side chains remain to be tested to determine whether structures known to be present in the three dextrans which precipitate CAL20 TEPC1035 may not prove to be more active than panose.
Patient Stratification Based on Prednisolone-Vincristine-Asparaginase Resistance Profiles in Children With Acute Lymphoblastic Leukemia
Authors: M.L. Den Boer, D.O. Harms, R. Pieters, K.M. Kazemier, U. Göbel, D. Körholz, U. Graubner, R.J. Haas, N. Jorch, H.J. Spaar, G.J.L. Kaspers, W.A. Kamps, A. Van der Does-Van den Berg, E.R. Van Wering, A.J.P. Veerman, G.E. Janka-Schaub
Journal: Journal of Clinical Oncology (2003)

To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol.Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol.At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P </=.05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P =.03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P =.07).Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.
Examining the Psychological Pathways to Behavior Change in a Group-Based Lifestyle Program to Prevent Type 2 Diabetes
Authors: Christine R. Critchley, Elizabeth A. Hardie, Susan M. Moore
Journal: Diabetes Care (2012)

To examine the psychological process of lifestyle change among adults at risk for type 2 diabetes.A randomized control trial in which 307 volunteers (intervention, n = 208; wait control, n = 99) diagnosed with prediabetes completed a six-session group-based intervention to promote healthier living. Participants' motivation to change, diet and exercise self-efficacy, mood, knowledge about diabetes, activity levels, healthy eating, waist circumference, and weight were assessed before and after the program.Participation in the program was associated with significant increases in healthy eating and physical activity, reductions in waist and weight, and improvements in motivation, positive mood, self-efficacy, and knowledge. Examination of the pathways to lifestyle change showed that the educational aspect of the program increased activity levels because it increased diabetes knowledge and improved mood. Eating behavior was not mediated by any of the psychological variables. Improvements in diet and physical activity were, in turn, directly associated with changes in weight and waist circumference.Although the program significantly improved motivation, self-efficacy, and mood, its impact on knowledge uniquely explained the increase in physical activity. Group-based programs that are tailored to lifestyle behaviors may provide a cost-effective method of diabetes prevention, but more research is needed to explain why they improve healthy eating.
[<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Is More Sensitive Than Skeletal Scintigraphy for Detecting Bone Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging
Authors: Feng-Yuan Liu, Joseph T. Chang, Hung-Ming Wang, Chun-Ta Liao, Chung-Jan Kang, Shu-Kung Ng, Sheng-Chieh Chan, Tzu-Chen Yen
Journal: Journal of Clinical Oncology (2006)

Purpose Bone metastasis occurs frequently in patients with endemic nasopharyngeal carcinoma (NPC). The main objective of this study is to evaluate positron emission tomography (PET) using fluorine-18–labeled fluorodeoxyglucose ([ 18 F]FDG) and conventional skeletal scintigraphy (SS) for detecting bone metastasis at initial staging. Auxiliary objectives are to identify risk factors for bone metastasis and features associated with poor survival in patients with bone metastasis. Patients and Methods Patients with endemic NPC before initiation of treatment were enrolled. PET and SS were performed at initial staging and compared using McNemar's paired-sample test. Bone metastasis was considered to be present if there was any reliable evidence identified within 1 year after primary diagnosis. Multiple logistic regression and Cox's proportional hazards models were used for auxiliary objectives. Results Thirty (15%) of 202 eligible patients were found to have bone metastasis. [ 18 F]FDG PET was found to be more sensitive than SS in the patient-based analysis (P = .006) and in the region-based analysis at the spine (P = .001). Advanced N stage was the only significant risk factor (P &lt; .0001), and the coexistence of hepatic metastasis was a prognosticator of poor survival (P = .017). The survival was not significantly better for patients with bone metastasis undetected at primary staging than for those with initially detectable bone metastasis (P = .620). Conclusion [ 18 F]FDG PET is more sensitive than SS for detecting bone metastasis in endemic NPC at initial staging, whereas SS can be considered as supplementary in this setting.
The interaction of celecoxib with MDR transporters enhances the activity of mitomycin C in a bladder cancer cell line
Authors: Vincenzo Pagliarulo, Patrizia Ancona, Mauro Niso, Nicola Colabufo, Marialessandra Contino, Luigi Cormio, Amalia Azzariti, Arcangelo Pagliarulo
Journal: Molecular Cancer (2013)

An in vitro model was developed to understand if celecoxib could synergize with Mitomycin C (MMC), commonly used for the prevention of non-muscle invasive bladder cancer recurrence, and eventually elucidate if the mechanism of interaction involves multi drug resistance (MDR) transporters.UMUC-3, a non COX-2 expressing bladder cancer cell line, and UMUC-3-CX, a COX-2 overexpressing transfectant, as well as 5637, a COX-2 overexpressing cell line, and 5637si-CX, a non COX-2 expressing silenced 5637 cell line, were used in the present study. The expression of COX-2 and MDR pumps (P-gp, MDR-1 and BCRP) was explored through western blot. The anti-proliferative effect of celecoxib and MMC was studied with MTT test. Three biological permeability assays (Drug Transport Experiment, Substrate Transporter Inhibition, and ATP cell depletion) were combined to study the interaction between MDR transporters and celecoxib. Finally, the ability of celecoxib to restore MMC cell accumulation was investigated.The anti-proliferative effect of celecoxib and MMC were investigated alone and in co-administration, in UMUC-3, UMUC-3-CX, 5637 and 5637si-CX cells. When administered alone, the effect of MMC was 8-fold greater in UMUC-3. However, co-administration of 1 μM, 5 μM, and 10 μM celecoxib and MMC caused a 2,3-fold cytotoxicity increase in UMUC-3-CX cell only. MMC cytotoxicity was not affected by celecoxib co-administration either in 5637, or in 5637si-CX cells. As a result of all finding from the permeability experiments, celecoxib was classified as P-gp unambiguous substrate: celecoxib is transported by MDR pumps and interferes with the efflux of MMC. Importantly, among all transporters, BCRP was only overexpressed in UMUC-3-CX cells, but not in 5637 and 5637si-CX.The UMUC-3-CX cell line resembles a more aggressive phenotype with a lower response to MMC compared to the wt counterpart. However, the administration of celecoxib in combination to MMC causes a significant and dose dependent gain of the anti-proliferative activity. This finding may be the result of a direct interaction between celecoxib and MDR transporters. Indeed, BCRP is overexpressed in UMUC-3-CX, but not in UMUC-3, 5637, and 5637si-CX, in which celecoxib is ineffective.
Serratia marcescens. A pathogen of increasing clinical importance
Authors: J. T. Davis
Journal: JAMA (1970)

During the 24-month period ending September 1969, a total of 662 isolates of Serratia marcescens were obtained from 314 patients. In 97% of the patients, isolates were from the urinary tract and this seemed to be the most common portal of entry. Blood was the second most common source of isolates, and 12 patients with septicemia had a mortality of 33% (4). In one instance Serratia septicemia was secondary to an infected prosthetic aortic valve.
Short Pigment Epithelial-Derived Factor-Derived Peptide Inhibits Angiogenesis and Tumor Growth
Authors: Yelena Mirochnik, Arin Aurora, Frank T. Schulze-Hoepfner, Ahmed Deabes, Victor Shifrin, Richard Beckmann, Charles Polsky, Olga V. Volpert
Journal: Clinical Cancer Research (2009)

Pigment epithelial-derived factor (PEDF) is a potent angiogenesis inhibitor with multiple other functions, some of which enhance tumor growth. Our previous studies mapped PEDF antiangiogenic and prosurvival activities to distinct epitopes. This study was aimed to determine the minimal fragment of PEDF, which maintains antiangiogenic and antitumor efficacy.We analyzed antigenicity, hydrophilicity, and charge distribution of the angioinhibitory epitope (the 34-mer) and designed three peptides covering its COOH terminus, P14, P18, and P23. We analyzed their ability to block endothelial cell chemotaxis and induce apoptosis in vitro and their antiangiogenic activity in vivo. The selected peptide was tested for the antitumor activity against mildly aggressive xenografted prostate carcinoma and highly aggressive renal cell carcinoma. To verify that P18 acts in the same manner as PEDF, we used immunohistochemistry to measure PEDF targets, vascular endothelial growth factor receptor 2, and CD95 ligand expression in P18-treated vasculature.P14 and P18 blocked endothelial cell chemotaxis; P18 and P23 induced apoptosis. P18 showed the highest IC50 and blocked angiogenesis in vivo: P23 was inactive and P14 was proangiogenic. P18 increased the production of CD95 ligand and reduced the expression of vascular endothelial growth factor receptor 2 by the endothelial cells in vivo. In tumor studies, P18 was more effective in blocking the angiogenesis and growth of the prostate cancer than parental 34-mer; in the renal cell carcinoma, P18 strongly decreased angiogenesis and halted the progression of established tumors.P18 is a novel and potent antiangiogenic biotherapeutic agent that has potential to be developed for the treatment of prostate and renal cancer.
Risk of Subsequent Cancer Following Breast Cancer in Men
Authors: A. Auvinen
Journal: JNCI Journal of the National Cancer Institute (2002)

The etiology of breast cancer in men is not well understood. We assessed the risk of subsequent cancers among all 1788 men diagnosed with a first primary breast cancer from 1973 through 1996 who were registered with the Surveillance, Epidemiology, and End Results (SEER) Program. Although the overall subsequent cancer risk in men was not increased (standardized incidence ratio [SIR] = 0.99, 95% confidence interval [CI] = 0.86 to 1.1), the risk of contralateral second breast cancer was strongly elevated (12 cases; SIR = 30, 95% CI = 15 to 52). The risk was higher for men diagnosed with their first breast cancer before age 50 years than for older men. There were no major differences in the risk of contralateral breast cancer associated with different treatments received for the first breast cancer. The relative risk of second breast cancer was substantially higher among men than among women with breast cancer, but the absolute excess risk was lower. We conclude that men diagnosed with breast cancer are at high risk of contralateral breast cancer.
Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis
Authors: Israel Vlodavsky, Yael Friedmann
Journal: Journal of Clinical Investigation (2001)

Studies of the involvement of ECM molecules in cell attachment, growth, and differentiation have revealed a central role of heparan sulfate (HS) proteoglycans (HSPGs) in early embryogenesis, morphogenesis, angiogenesis, and epithelial-mesenchymal interactions (1–3). HS chains bind a multitude of proteins and ensure that a wide variety of bioactive molecules (e.g., heparin-binding growth factors, chemokines, lipoproteins, and enzymes) cling to the cell surface and ECM. HSPGs can thus influence a variety of normal and pathologic processes, among which are tissue repair, neurite outgrowth, inflammation and autoimmunity, tumor growth and metastasis, vasculogenesis and angiogenesis (1–4). Binding to HS can modulate a tethered molecule’s biological activity or protect it from proteolytic cleavage and inactivation. Transmembrane and phospholipid-anchored HSPGs (syndecans and glypicans, respectively) mediate cell interactions with components of the microenvironment that control cell shape, adhesion, proliferation, survival, and differentiation (2, 3). These species of HSPGs can also serve as coreceptors along with the other cell surface molecules to form functional receptor complexes that transduce signals from various ligands (2, 3).

Because of the important and multifaceted roles of HSPGs in cell physiology, their cleavage is likely to alter the integrity and functional state of tissues and to provide a mechanism by which cells can respond rapidly to changes in the extracellular environment. Enzymatic degradation of HS is, therefore, likely to be involved in fundamental biological phenomena, ranging from pregnancy, morphogenesis, and development to inflammation, angiogenesis, and cancer metastasis. Contrary to some early claims, there is no good evidence for more than one endogenous mammalian HS-degrading endoglycosidases. The recent cloning of a single gene by several groups (5–10), together with biochemical studies (11), suggests that mammalian cells express primarily a single dominant heparanase enzyme (12). This Perspective focuses on the molecular properties, expression pattern, biological functions, and clinical significance of this heparanase in normal and pathological processes, with emphasis on tumor metastasis and angiogenesis.
Inhibition of protein degradation in mouse hearts by agents that cause lysosomal dysfunction.
Authors: K Wildenthal, J R Wakeland, P C Morton, E E Griffin
Journal: Circulation Research (1978)

Although the heart contains lysosomes, it has been uncertain whether these organelles and their proteolytic enzymes can play an important role in cardiac protein degradation. Recent studies have demonstrated that fetal mouse hearts in organ culture sustain selective derangements in lysosomal structure and function during exposure to chloroquine or nonmetabolizable sugars. Accordingly, we tested the effects of these agents on cardiac proteolysis under controlled conditions in vitro using two techniques (measurement of loss of radioactivity from trichoroacetic acid-precipitable protein after prelabeling with tritiated phenylalanine and measurement of loss of cold phenylalanine after blockade of protein synthesis with cycloheximide). Chloroquine (0.1 mM) reduced the average rate of protein breakdown in hearts of matched littermates from 45%/24 hours to 32%/24 hours (P less than 0.01) and decreased the release of cold phenylalanine by 31 +/- 5% (0.108 vs 0.075 nmol/mg per hour, P less than 0.01). Exposure to 100 mM sucrose for 24-48 hours reduced the rate of breakdown from 44%/24 hours to 33%/24 hours (P less than 0.01) and decreased the release of cold phenylalanine by 35 +/- 9% (0.092 vs. 0.060 nmol/mg per hour, P less than 0.01). The results suggest that interference with lysosomal function in cultured fetal mouse hearts causes a significant reduction in the cardiac capacity to degrade proteins.
A Preclinical Xenograft Model Identifies Castration-Tolerant Cancer-Repopulating Cells in Localized Prostate Tumors
Authors: Roxanne Toivanen, Mark Frydenberg, Declan Murphy, John Pedersen, Andrew Ryan, David Pook, David M. Berman, Renea A. Taylor, Gail P. Risbridger
Journal: Science Translational Medicine (2013)

This study uses a preclinical xenograft model to reveal prostate cancer cells that exist in untreated localized disease, survive androgen withdrawal, and are potential therapeutic targets.
X-shaped DNA potentiates therapeutic efficacy in colitis-associated colon cancer through dual activation of TLR9 and inflammasomes
Authors: Jung Eun Koo, Seung Won Shin, Soong Ho Um, Joo Young Lee
Journal: Molecular Cancer (2015)

Immunotherapy has been extensively pursed as a promising strategy for the treatment of cancer. Pattern-recognition receptors (PRRs) play important roles in triggering activation of innate and adaptive immunity. Therefore, agents that stimulate PRRs could be useful for cancer immunotherapy. We developed two kinds of X-shaped double-stranded oligodeoxynucleotides (X-DNA), a single unit of X-DNA (XS-DNA) composed of four strands of DNA and a ligated X-DNA complex (XL-DNA) formed by crosslinking each XS-DNA to the other, and investigated if they had immunostimulatory activity and could be applied to anti-cancer immunotherapy.Activation of MAPKs and NF-κB was determined by immunoblotting in bone marrow-derived primary dendritic cells (BMDCs). Immune cytokines and co-stimulatory molecules were measured by ELISA and flow cytometry analysis. Anti-cancer efficacy was examined in an azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer mouse model. Association of X-DNA and TLR9 was determined by co-immunoprecipitation followed by immunoblotting. The involvement of TLR9 and inflammasomes was determined using TLR9- or caspase-1-deficient BMDCs. Inflammasome activation was examined by degradation of pro-caspase-1 to caspase-1 and cleavage of pro-IL-1β to IL-1β in BMDCs.XL-DNA and XS-DNA induced activation of MAPKs and NF-κB and production of immune cytokines and co-stimulatory molecules in BMDCs. BMDCs stimulated by XL-DNA induced differentiation of naïve CD4(+) T cells to TH1 cells. Intravenous injection of XL-DNA into mice resulted in increased serum IFN-γ and IL-12 levels, showing in vivo efficacy of XL-DNA to activate TH1 cells and dendritic cells. XL-DNA greatly enhanced the therapeutic efficacy of doxorubicin, an anti-cancer drug, in colitis-associated colon cancer. XL-DNA directly associated with TLR9. In addition, immunostimulatory activities of X-DNA were abolished in TLR9-deficient dendritic cells. Furthermore, X-DNA induced caspase-1 degradation and IL-1β secretion in BMDCs, which were abolished in caspase-1-deficient cells.X-DNA induced the activation of dendritic cells as shown by the expression of immune-cytokines and co-stimulatory molecules, resulting in the differentiation of TH1 cells, mediated through dual activation of TLR9 and inflammasomes. X-DNA represents a promising immune adjuvant that can enhance the therapeutic efficacy of anti-cancer drugs by activating PRRs.