tbuckley/cabot-search huggingface dataset:
PMO-127 Biological effects of oral nanoporous carbon in bile duct ligated rats
Authors: J Macnaughtan, J Soeda, A Mouralidarane, S Sandeman, C Howell, O Kozynchenko, S Tennison, S Mikhalovsky, N Davies, J Oben, R Mookerjee, R Jalan
Journal: Gut (2012)

<h3>Introduction</h3> Gut-derived bacterial products and associated dysregulated inflammatory response play a central role in the pathogenesis of cirrhosis. Therapeutic options to target these factors are currently limited to long-term antibiotics. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules such as cytokines and endotoxin. We sought to determine their biological effects in bile-duct ligated rats as a model of cirrhosis. <h3>Methods</h3> 131 male Sprague-Dawley rats underwent bile duct-ligation or sham biliary surgery. Animals were pair fed with or without oral carbon therapy 2 weeks from surgery until completion of the experiment at 4–5 weeks. Intra-peritoneal lipopolysaccharide (LPS) was administered to four subgroups 3.5 h prior to completion of the study. The following groups were studied: Sham (n=16), Sham + carbon (n=15), Sham + LPS (n=11), Sham+LPS+carbon (n=10), BDL (n=27), BDL + carbon (n=26), BDL+LPS (n=10), BDL+LPS+carbon (n=16). Portal haemodynamics were performed on 93 rats and Kupffer cell (KC) numbers and Reactive oxygen species (ROS) production assessed by flow cytometry in a sub-group of animals. Liver biochemistry and portal venous cytokines were performed. <h3>Results</h3> A significant reduction in portal pressure was observed in BDL+LPS (mean 18.05±0.88 mm Hg untreated, 10.17±1.07 mm Hg with carbon, p&lt;0.05) and BDL (mean 12.57±0.43 mm Hg untreated, 11.02±0.28 mm Hg with carbon, p&lt;0.05) groups following carbon treatment. A significant reduction in ALT was observed in the carbon treated BDL+LPS (p&lt;0.05) and BDL groups (p&lt;0.05). Carbon treatment in BDL rats was associated with a significant reduction in LPS-induced ROS production. A trend towards reduction in portal venous IL-4 and IL-10 was observed in carbon-treated BDL rats. No significant difference in portal venous TNF-α was observed. Finally, a significant increase in body mass was observed in the BDL carbon-treated group (p&lt;0.05). <h3>Conclusion</h3> Oral nanoporous carbon therapy results in a significant reduction in portal pressure and liver biochemistry associated with a reduction in endotoxin-induced KC ROS production. We postulate therefore, that the effect of nanoporous carbon is possibly via a reduction in endotoxin induced KC stimulation. <h3>Competing interests</h3> None declared.
Abstract 5691: Significance of combination treatment of antiprogestin and aromatase inhibitors in aromatase overexpressing T47D breast cancer cells
Authors: Akash Gupta, Xinjian Peng, Genoveva Murillo, Rajeshwari R. Mehta, Ronald Wiehle, Rajendra G. Mehta
Journal: Cancer Research (2010)

Abstract Treatment with aromatase inhibitors (AI) is considered as the first line of treatment for ER+PR+ cancers. However, many patients acquire resistance to aromatase inhibitors. Therefore, there is a need for new approaches to overcome resistance to AI in these patients. In the present study we determined the effects of third generation AI in genetically engineered high aromatase overexpressing T47Darom cells. Treatment of T47Darom cells with Leterozole (L), Anastrazole(A) and Exemestane(E) at 5μM concentration exhibited inhibition of 32% 19% and 18% respectively, however, in combination with proellex overall inhibition increased to 50% suggesting additive effect of proellex along with aromatase inhibitor. Interestingly, Proellex showed dose-dependent inhibition of T47Darom cells incubated with testosterone (1nM and 10nM) suggesting that Proellex also has aromatase inhibitory property. Furthermore, Proellex inhibited cell proliferation of both ER/PR positive (T47D and T47Darom) and ER/PR negative (MDA-MB231cells). These results suggested that the mechanism of action may not be entirely dependent to PR status. Since both T47Darom and MDA-MB231 cells exhibit increased COX2 expression and increased COX2 expression has been associated with enhanced cell proliferation and malignancy in breast cancer, we determined the effects of Proellex on COX2 expression. Results showed that in both these cell lines COX2 expression was decreased as determined by real-time PCR when the cells were treated with Proellex at 10−6M. These studies suggest that Proellex either alone or in combination with aromatase inhibitors may provide a new treatment strategy for breast cancer patients.(This work is supported by Repros Therapeutics) 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 5691.
Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid)
Authors: Raymond P. Warrell, Stanley R. Frankel, Wilson H. Miller, David A. Scheinberg, Loretta M. Itri, Walter N. Hittelman, Rohini Vyas, Michael Andreeff, Agostino Tafuri, Ann Jakubowski, Janice Gabrilove, Michael S. Gordon, Ethan Dmitrovsky
Journal: New England Journal of Medicine (1991)

Patients with acute promyelocytic leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor—alpha (RAR-α). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with acute promyelocytic leukemia, we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent.
A2.21 The increase of circulating CD4<sup>+</sup>T-cells with effector phenotype in patients with systemic lupus erythematosus may be reverted after belimumab therapy
Authors: S Piantoni, M Scarsi, L Andreoli, F Dall’Ara, A Zanola, A Tincani, P Airò
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and highly experienced memory T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28-T-cells, a subpopulation with peculiar effector activities. Recent studies showed that memory CD4<sup>+</sup> T-cells are increased in the peripheral blood of SLE patients, whereas contradictory data are reported on CD28-T-cells. Belimumab is an anti-Blys therapy approved for SLE. The aims of this study were the characterisation of T-cell phenotype in a cohort of patients with SLE, according with disease activity, and the analysis of T-cell phenotype modifications after 6 months of therapy with belimumab. <h3>Materials and methods</h3> Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry. First, a cross-sectional study on 41 consecutive SLE patients was performed. Second, 7 patients treated with belimumab were longitudinally followed. Disease activity was evaluated by SLEDAI-2K score. <h3>Results</h3> SLE patients were divided in two groups according disease activity: patients with SLEDAI-2K ≥6 (n.6) had a higher percentage of circulating CD4<sup>+</sup>T-cells with CD28- phenotype (11 vs 2.5%, p = 0.01), as well as of those with an effector memory (34 vs 18%, p = 0.03), or highly experienced memory (8 vs 1%, p = 0.01) phenotype, in comparison with patients with low disease activity (n.35). After 6 months of treatment with belimumab, a trend toward a reduction of the CD4<sup>+</sup>CD28- T-cells was observed (from 10.5% to 4.6%; p:0.12). In particular, a reduction of CD4<sup>+</sup>CD28- T-cells showing an effector memory phenotype (from 31.6 to 26% of CD4<sup>+</sup>CD28- cells, p = 0.01) was found. <h3>Conclusions</h3> CD4<sup>+</sup> T-cells subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE, but some of these abnormalities seems to be reverted by anti-BlyS therapy. Since the presence of BlyS receptor 3 on T cells and of a BLyS-dependent T-cell activation pathway have been well demonstrated, further studies are warranted to understand the possible effects of anti-BlyS therapy on T cells from SLE patients.
Bcl-2 family members in childhood acute lymphoblastic leukemia: relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome
Authors: GS Salomons, LA Smets, M Verwijs-Janssen, AAM Hart, EG Haarman, GJL Kaspers, ER Van Wering, A Van Der Does-Van Den Berg, WA Kamps
Journal: Leukemia (1999)
Abstract 5076: Multi-protein tissue and blood plasma protein marker patterns of endometrioid endometrial and squamous cervical cancers
Authors: Marta Lomnytska, Susanne Becker, Ulf Hellman, Ulla Engström, Ann-Cathrin Hellström, Kristina Hellman, Caroline Lundgren, Sonia Andersson, Miriam Mints, Gert Auer
Journal: Cancer Research (2011)

Abstract Endometrial cancer is the second spread cancer of women in Western Europe and Nothern America. There is no screening developed for early detection of endometrial cancer, its major types and precursor lesions. We used proteomics-based methods including two-dimensional gel electrophoresis of tissue and blood plasma proteins, analyses of gels by SameSpot (Nonlinear) software and MALDI-TOF MS-assisted identification of proteins. Measurement of DNA ploidy was used for the selection of genomic subtypes of endometrial cancer. Expression of identified proteins was evaluated in endometrial cancers, atypical and simple hyperplasia and normal endometrium using immunohistochemistry. Tumor tissue biopsies of endometrial cancer, normal endometrium, squamous cervical cancer, and squamous cervical epithelium as well as low-abundant blood plasma proteins of the same patients were used for two-dimensional gel electrophoresis. We also analyzed published data on chromosomal changes in early and prognostically unfavorable endometrial cancer and corresponded proteins identified by us to the corresponding coding genes. One hundred and thirty differentially expressed tissue proteins were identified as being related to malignant transformation towards endometrial and cervical cancers. Among them is a group of proteins that specifically differentiate genomically stable and unstable endometrial cancers. Many similarities between the protein expression were found for genomically unstable endometrial cancer and squamous cervical cancer which in most cases are genomically unstable. Moreover, inclusion of squamous cervical cancer cases made it possible to select proteins that are specific for endometrial cancer and proteins which characterize non-malignant tissues. Using available data on chromosomal changes in endometrial cancer we have selected proteins that are markers of prognostically unfavourable endometrial cancer and that change their expression already in atypical hyperplasia of the endometrium. By analysis of low-abundant blood plasma proteins we have identified 18 marker proteins that differentiate endometrial cancer from cervical cancer. In conclusion, proteins differentially expressed in tissue of endometrial cancer include patterns that are typical for genomically stable and unstable subtypes and changes in their expression are detectable already in atypical hyperplasia of the endometrium. Endometrial and cervical cancers are characterized by differential blood plasma protein expression patterns. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5076. doi:10.1158/1538-7445.AM2011-5076
PIOGLITAZONE INCREASED CIRCULATING MICRORNA-24 WITH DECREASES IN CORONARY NEOINTIMAL HYPERPLASIA IN TYPE 2 DIABETIC PATIENTS: OPTICAL COHERENCE TOMOGRAPHY ANALYSIS
Authors: Soon Jun Hong, Jong-Ho Kim, Seung-Cheol Choi, Hyung Joon Joo, Jae Hyoung Park, CheolWoong Yu, Do-Sun Lim
Journal: Journal of the American College of Cardiology (2015)
Discovery May Improve Transplant Success
Authors: Judith Randal
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Discovery May Improve Transplant Success Get access Judith Randal Judith Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 404–406, https://doi.org/10.1093/jnci/87.6.404 Published: 15 March 1995
SOX2 IDENTIFIES THE TREATMENT-REFRACTORY STEM CELL POPULATION IN GROUP 2 MEDULLOBLASTOMA
Authors: S. K. Singh, B. Manoranjan, C. Venugopal, P. Vora, N. McFarlane, N. Garg, M. Singh, A. Mann, D. Bakhshinyan, S. Mahendran, S. Dunn
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain tumors represent the leading cause of childhood cancer mortality, of which medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Recent studies have demonstrated the presence of several MB molecular subgroups, each distinct in terms of prognosis and predicted therapeutic response. Although, group 2 MBs characterized by activation of the sonic hedgehog (Shh) signaling pathway have been of particular therapeutic interest, treatment-resistance has posed a significant challenge. Given the identification of brain tumor-initiating cells (BTICs), which have the ability to initiate and maintain tumor growth while promoting resistance to radio- and chemotherapy, we investigated the mechanistic profile of treatment-resistant Shh-dependent MB BTICs. METHODS: Through investigating a differential stem cell gene expression profile of 325 primary human MBs, followed by a subsequent series of step-wise knockdown, overexpression, chromatin immunoprecipitation (ChIP), and in vitro self-renewal analyses we assessed the mechanistic role of Sox2 as a novel downstream target of Shh effector proteins, Gli1 and Gli2. We further determined the clinical utility of this mechanism by treating our MB BTICs with conventional radio- and chemotherapy as per the Children's Oncology Group (COG) protocol for MB patients in order to assess the validity of Sox2 as a marker of Shh-dependent treatment-refractory MB BTICs. RESULTS: Activation and inhibition of the Shh pathway and Sox2 expression using small molecule Shh agonists and antagonists, respectively, were observed only in distinct subsets of tumor cells (CD15+ MB BTICs). ChIP experiments further demonstrated the presence of a differential Shh signaling mechanism within distinct cell populations of the bulk tumor mass as Gli proteins showed Sox2 promoter binding only in CD15+ MB BTICs. The functional relevance of this cell-specific signaling mechanism was assessed through an in vitro and in vivo increase in treatment-resistant Sox2+ MB BTICs following conventional and combinatorial radio- and chemotherapy with Shh pathway inhibitors. CONCLUSIONS: Our work demonstrates for the first time that Sox2 expression in MB is regulated by the Shh signaling pathway and Sox2+ MB BTICs represent the treatment-resistant clone in Group 2 MBs, suggesting a need for combinatorial therapy as tumors evolve over the course of treatment. Aside from implicating developmental genes and pathways in oncogenesis, we have also demonstrated the importance of studying cancer at a cellular level, as distinct differences in rare subsets of tumor cells may not otherwise be appreciated with genomic profiling of the bulk tumor mass. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.
AB0418 The carotid artery atherosclerosis burden and its associated cardiovascular risk factors in african black and caucasian patients with established rheumatoid arthritis
Authors: P.H. Dessein, A.J. Woodiwiss, A.T. Abdool-Carrim, B.A. Stevens, G.R. Norton, A. Solomon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Compared to persons from developed populations, those that belong to developing populations are at an earlier epidemiological health transition stage [1-3]. Accordingly, black Africans still experience a distinctly low prevalence of atherosclerotic cardiovascular disease [2-3]. It is unknown whether this protection is present in patients with established rheumatoid arthritis (RA) from developing populations [4]. <h3>Objectives</h3> To compare the carotid atherosclerosis burden and its relationships with cardiovascular risk and predisposing factors between Africans with RA from a developing black and developed Caucasian population. <h3>Methods</h3> We assessed cardiovascular risk factors and the carotid intima-media thickness (cIMT) and plaque by high resolution B-mode ultrasound in 243 patients with established RA of whom 121 were black and 122 Caucasian. Data were analyzed in multivariable regression models. <h3>Results</h3> The mean (SD) cIMT was 0.694 (0.097) and 0.712 (0.136) mm in black and Caucasian patients (adjusted p=0.8), respectively. Plaque prevalence was also similar in black compared to Caucasian cases (35.5 and 44.3%, respectively; adjusted OR [95% CI]=0.83 [0.32-2.20], p=0.7). Compared to their Caucasian counterparts, black patients with RA had more prevalent hypertension, a smaller pack-year history of smoking, higher body mass index, less years of education and less frequent extraarticular manifestations (p&lt;0.02), serum total cholesterol$÷ $HDL cholesterol ratio (p=0.004), C-reactive protein concentrations (p=0.01) and the presence of extraarticular manifestations (p=0.01) in Caucasians but, contrastingly, the Arthritis Impact Measurement Scales tension score (p≤0.04) and use of non-steroidal anti-inflammatory agents (p=0.03) in black patients. The Framingham score was significantly associated with atherosclerosis in Caucasians (p <h3>Conclusions</h3> In keeping with existing disparate epidemiological transition stages, cardiovascular risk factor profiles and their relationships with atherosclerosis vary substantially amongst Africans with RA. However, the carotid atherosclerosis burden is similar in black compared to Caucasian Africans with RA. Conventional cardiovascular risk factors and systemic inflammation may be insufficient in atherosclerosis risk assessment in patients with RA from developing groups of black African descent. <h3>References</h3> Yusuf S et al. Circulation 2001;104:3554-61. Steyn K et al. Circulation 2005;112:3554-61. Mayosi BM et al. Lancet 2009;374:934-47. Solomon A et al. J Rheumatol 2010;37:953-60. <h3>Disclosure of Interest</h3> P. Dessein Grant/Research support from: Medical Research Council, A. Woodiwiss: None Declared, A. Abdool-Carrim: None Declared, B. Stevens: None Declared, G. Norton: None Declared, A. Solomon: None Declared
Abstract P5-10-16: miRNAs as novel therapeutic adjuvants for the prognosis and treatment of triple negative breast cancers
Authors: B Zoghi, Y-F Chang, P Subbarayalu, JR Plyler, M Rao
Journal: Cancer Research (2012)

Abstract Approximately 15–20% of all breast cancers account for triple negative breast cancers (TNBCs) that exhibit an aggressive, distinct metastatic pattern and poor prognosis resulting in a disproportionate number of breast cancer deaths. More than 50% of patients with TNBC develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. In spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that regulate this phenomenon. Recently, we have discovered that small non-coding RNAs-miRNAs play critical roles in mediating drug sensitivity/resistance in TNBCs. We have identified miRNAs that are differentially expressed between chemo-resistant and sensitive breast cancer cells. In particular, through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant TNBC cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Interestingly, our studies revealed that specific miRNAs including miR-185 (patent pending) that sensitize resistant TNBCs to paclitaxel are expressed at significantly lower levels in relapsed metastatic TNBC patient sera compared to sera from their healthy siblings. Furthermore, using liposome- or biocompatible PLGA nanoparticle-based approaches, we show that systemic delivery of one of the sensitizer miRNAs suppresses breast cancer lung metastasis without any hepatotoxicity in preclinical mouse tumor models. Importantly, we show that one of the mechanisms by which sensitizer miRNAs regulate paclitaxel sensitivity is by targeting Stathmin, a microtubule destabilizer protein that can bind to tubulin dimers and stimulate microtubule destabilization. These findings suggest that tumor-specific miRNAs render selective cell cytotoxicity in a drug-specific manner, that these miRNAs may serve as detection markers for identifying patients who might benefit most from specific drug treatment, and that these miRNAs may represent novel therapeutic tools for the treatment of the TNBCs. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product targeted by conventional cancer treatments that are typically prone to drug resistance. Since paclitaxel is used for the treatment of many cancers, the long-term implications of this study are likely not limited to breast cancer alone but may apply to other tumor types. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-16.