tbuckley/cabot-search huggingface dataset:
Abstract 766: Downregulation of MUC4 in pancreatic cancer cells by thymoquinone: A promise for pancreatic cancer therapies
Authors: Maria P. Torres, Moorthy P. Ponnusamy, Subhankar Chakraborty, Hwyda A. Arafat, Surinder K. Batra
Journal: Cancer Research (2010)

Abstract Pancreatic cancer remains one of the most lethal cancers in the world. Currently, the existing therapies have not been optimized and the survival of pancreatic cancer patients remains under 5% after being diagnosed. The high molecular weight glycoprotein Mucin-4 (MUC4) contributes to the regulation of differentiation, proliferation, and metastasis of pancreatic tumor cells. As it is not expressed in normal pancreatic epithelial cells, MUC4 is a promising target for novel cancer therapeutics. Among the natural derived drugs that are being investigated, the extracts from the seeds of the plant Nigella sativa, particularly thymoquinone (TQ), possess multiple benefits, including anti-tumorigenic properties. The main objective of this study was to evaluate the effect of TQ on pancreatic cancer cells and determine the role of the drug on MUC4 expression by analyzing the cytotoxicity, protein and gene expression, and metastatic properties on the MUC4-expressing pancreatic cancer cell line FG/COLO357. Experimental techniques used included western blot, polymerase chain reaction (PCR), transient gene silencing, confocal, and flow cytometry analyses, among other functional assays. The results indicated a decrease in cell viability at increasing concentrations of TQ that correlated with MUC4 downregulation, which occurred thru the proteasomal degradation pathway. The genes that were regulated in FG/COLO357 cells after treatment with TQ were determined by microarray analysis and the results were confirmed by functional assays. It was found that TQ activated the Jun N-terminal Kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) pathways. As the activation of these pathways is directly related to a decrease in proliferation, survival, and invasion of cancer cells, these results indicate the direct involvement of TQ on the induction of apoptosis of pancreatic cancer cells. The results present evidence that TQ induces the apoptosis of pancreatic cancer cells and the downregulation of MUC4 is related to the apoptotic effect of the drug. In conclusion, TQ, which has a role in downregulation of MUC4 among other anti-tumorigenic properties, represents promise for the development of novel therapies against pancreatic cancer. 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 766.
Resolvin D1 Inhibits IL-1beta Induced Alveolar Epithelial Cell Activation
Authors: Ruan R. Cox, Oluwakemi Phillips, Jutaro Fukumoto, Itsuko Fukumoto, Prasanna Tamarapu, Tran Luong, Richard F. Lockey, Narasaiah Kolliputi
Journal: Journal of Allergy and Clinical Immunology (2013)
Abstract 4317: Stim1 and Orai1 are critical regulators of melanoma invasion and anoikis
Authors: Shengyu Yang, Jianwei Sun, Huifang He
Journal: Cancer Research (2012)

Abstract Store-operated calcium (SOC) influx is the major calcium entry mechanism in non-excitable cells regulating a plethora of physiological and pathological processes. The internal store calcium sensor and plasma membrane pore-forming unit are recently identified to be Stim1 and Orai1, respectively. We were the first to demonstrate the critical roles of Stim1 and Orai1 in breast tumor cell migration and metastasis (Cancer Cell, 2009, 15:124). There are still a few important questions remained to be answer: Whether Stim1 and Orai1 play a role in the dissemination of other tumors? How do Stim1 and Orai1 dysregulate and reorganize actin cytoskeleton to promote tumor cell invasion and metastasis? Do Stim1 and Orai1 contribute to tumor progression in cancer patients? Our recent data suggested that Stim1 and Orai1 were important regulators of tumor cell migration and invasion in multiple tumors. SOC inhibitors block cell migration and invasion in all the tumors tested. Stim1 and Orai1 promote tumor cell invasion and degradation of extracellular matrix by promoting the formation of invadopodia. Stim1 and Orai1 regulate invadopodia formation through facilitating SOC calcium influx and activation of non-receptor tyrosine kinase Src. The activation of Src by SOC influx also contributes to anoikis resistance in tumor cells. We were able to further demonstrate that the expression levels of Stim1 correlate with tumor progression and metastasis in multiple solid tumors. Therefore, our data suggested that Stim1 overexpression in tumors may promote tumor metastasis through calcium influx and Src activation, which facilitate extracellular matrix degradation and promote anchorage-independent growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4317. doi:1538-7445.AM2012-4317
Lymph Node Transplantation in Breast Reconstruction Using Perforator Flaps.
Authors: M. LoTempio, R. Studinger, J. Vaisille, C. Chen, J. Levine, R. Allen
Journal: Cancer Research (2009)

Abstract Introduction: For many women undergoing breast reconstruction, the negative impact of upper extremity lymphedema outweighs the benefits of breast reconstruction.Patients with lymphedema present a challenging problem, and typically is not addressed during the reconstruction process. Lymph node dissections have decreased secondary due to the advent of the sentinel node biopsy. However, 7% of patients undergoing sentinel lymph node biopsy develop lymphedema. Previous treatments options have not proved to be highly successful, and include lymphatic massage and lymphaovenous anastomosis. We introduce a combined treatment for breast reconstruction using deep inferior epigastric perforator flap (DIEP) along with lymph node transplantation for lymphedema.Methods: Beginning in 2007, 23 patients have undergone bilateral breast reconstruction using the DIEP along with simultaneous lymph node transplantation. Each patient had demonstrated upper extremity lymphedema by measurements and subjective findings. Of the 23 patients 18 had radiation therapy and five had sentinel node dissection. The lymph node flap was harvested surrounding the superficial circumflex vessels in conjunction with the DIEP. The combined DIEP and lymph nodes were anastomosed to the internal mammary artery. Preparation of the axilla included removal of scar tissue, and fixation of the lymph nodes into the axilla.Results: Each patient had an uncomplicated postoperative course. These patients started to experience resolutions of lymphedema as early as ten days after surgery and continued up to six months. Currently, 15 patients no longer need lymphatic massage nor wear compression garment. One patient had a recurrence of breast cancer. Each patient reported their arm circumference had improved and decreased morbidity associated with lymphedema.Conclusion: Lymph node transplantation is a relatively new and exciting option for the management of lymphedema. Women who undergo breast reconstruction using perforator flaps can have simultaneous lymph node transplantation with minimal morbidity. These patients experienced an overall 89% improvement of symptoms. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3112.
COLOCACION DE GASTROSTOMIA ENDOSCOPICA PERCUTANEA (“PEG”) MEDIANTE GASTROPEXIA E INTRODUCCIÓN TRANSABDOMINAL
Authors: A López-Serrano, RA Villagrasa Manzano, I Ferrer Bradley, JM Santiago Sánchez, N Maroto Arce, C Montón Rodríguez, I Conde Amiel, A Campos Catalá, A Díaz Fernández, JE Hinojosa del Val
Journal: Endoscopy (2011)

Introduccion: La PEG es una técnica rutinaria para la colocación abdominal de tubos de alimentación enteral. Suele realizarse mediante la tracción desde la pared abdominal de una sonda introucida a través de la cavidad oral. En los pacientes con tumores de cabeza y cuello y de esófago, su colocación puede ser imposible por estenosis de la vía digestiva y puede estar asociada a un mayor riesgo de complicaciones (infecciones, implantes tumorales). La gastropexia y posterior PEG transabdominal a estómago puede permitir la colocación segura de un tubo de alimentación.
Abstract LB-165: Low TCR diversity (divpenia) is a new prognosis factor of overall survival in metastatic breast cancer
Authors: Manuarii Manuel, Olivier Tredan, Thomas Bachelot, Tioka Rabeony, Sylvie Chabaud, Jean-François Mouret, Audrey Grives, Solène Perez, Alain Puisieux, Jean-Yves Blay, Christophe Caux, Nicolas Pasqual, Christine Menetrier Caux
Journal: Cancer Research (2011)

Abstract Rationale Lymphopenia (&amp;lt;1000 Lymphocytes/μl) or CD4+ T cell lymphopenia (&amp;lt;450/μl), detected before initiation of chemotherapy are predictive factors for toxicity and death in metastatic solid tumors (Borg et al 2004; Ray Coquard et al 2009). The goal of the present study was to further identify the characteristics of the T cells in these lymphopenic patients. TCR diversity was investigated and tested as predictive factor for overall survival (OS). Patients and methods The ImmunTraCkeR® assay (ImmunID, Grenoble France), which analyzes, through semi quantitative multiplex PCR, the V-D-J combinatorial diversity of TCR-beta chain (TRB), was used to investigate diversity of T cell repertoire on cryopreserved blood samples from a prospective cohort of untreated metastatic breast cancer patients (SEMTOF study)(n=66). Univariate and multivariate analysis of prognostic factors for OS were investigated in this series as well as in a validation series. Results A severe T cell Divpenia (T cell diversity below 33%) (average diversity for healthy people is 70%) was associated with median survival of 9 months vs 24 months for the remaining patients (logrank p.value=0.0047). In a multivariate analysis, including haemoglobin level, polynuclear neutrophil count and liver metastasis, divpenia (defined at 30% threshold defined by ROC curve analysis) was identified as an independent prognostic factor. The NDL® score (Numeration Diversity Lymphocytes representation) that combines lymphocytes numeration with TRB diversity, demonstrated that lympho-divpenia (T cell diversity below 33% and lymphopenia at 1Giga/L threshold) was associated with a poor prognosis in term of patients survival compared to patients with either a good numeration or good diversity or both good numeration and diversity (p.value=0.0202). Prognostic value of NDL® score was then evaluated on a prospective validation cohort of 33 patients (logrank p.value=0.002). Conclusion: Divpenia, and a combined parameter NDL are predictive factors for survival in metastatic breast cancer patients. An open clinical study (LYMPHOS1) will investigate divpenia and NDL® score in a larger prospective cohort of metastatic breast patients. Acknowledgments M.MANUEL is a CIFRE recipient. This work (Proof of Concept “LYMPHOS1”) was financially supported by CLARA (LYON, France) 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 LB-165. doi:10.1158/1538-7445.AM2011-LB-165
Abstract LB-241: Silencing of microRNA-31 prevents esophageal neoplasia in zinc deficient rats.
Authors: Cristian Taccioli, Hongping Chen, Michela Garofalo, Yubao Jiang, Gianpiero Di Leva, Hansjuerg Alder, Justin Middleton, Karl J. Smalley, Arianna Bottoni, Stefan Costinean, John L. Farber, Carlo M. Croce, Louise Y Y Fong
Journal: Cancer Research (2013)

Abstract Dietary zinc deficiency (ZD) is implicated in the pathogenesis of human esophageal squamous cell carcinoma (ESCC). microRNA-31 (miR-31) is overexpressed in human ESCC. In the rat a ZD diet promotes esophageal carcinogenesis by inducing cellular proliferation and changes in the expression of microRNA and mRNA, including overexpression of miR-31 and cancer-related proinflammation genes. Here we report that treatment of ZD rats with locked nucleic acid (LNA)-modified inhibitor of miR-31 (LNA-antimiR) prevents the development of a precancerous esophageal phenotype. Weanling rats were fed ZD or zinc-sufficient (ZS) diet for 5 weeks. Simultaneously, ZD rats were administered intravenously (twice a week) LNA-antimiR, LNA-scramble miR-31 or the vehicle saline. ZS rats received saline. Compared to ZS rats, LNA-scramble miR-31-treated or saline-treated ZD rats overexpressed miR-31 and displayed a highly proliferative and inflammatory esophageal phenotype. Treatment of ZD rats with LNA-antimiR reduced miR-31 expression in esophageal epithelia and circulating blood by ~60% and reversed the ZD-induced esophageal pathology, as evidenced by a thinned esophageal epithelium with reduced cell proliferation by PCNA immunohistochemistry and increased apoptosis by caspase-3/7 activity. Transcriptome analyses of esophageal epithelia demonstrated derepression of target mRNAs with miR-31 seed sites. In particular, Stk40 (a negative regulator of NF-κ? signaling) was demonstrated to be a bona fide miR-31 target. Using in situ hybridization and immunohistochemistry, miR-31 overexpression in ZD esophageal sections correlated with downregulation of STK40 protein, as well as with upregulation of an NF-κ? p65 - RAGE-S100A9 inflammatory pathway that in turn, was normalized by miR-31 silencing. Thus, silencing miR-31 prevents esophageal neoplasia. Overexpression of miR-31 promotes ESCC initiation by enhancing inflammation via STK40 - NF-κ? signaling. The data indicate that miR-31 may be a promising therapeutic target for improved ESCC diagnosis and prevention. Funding: National Institutes of Health grants U01 CA152758 to CMC and R01CA118560 &amp; R21CA152505 to LYYF. Citation Format: Cristian Taccioli, Hongping Chen, Michela Garofalo, Yubao Jiang, Gianpiero Di Leva, Hansjuerg Alder, Justin Middleton, Karl J. Smalley, Arianna Bottoni, Stefan Costinean, John L. Farber, Carlo M. Croce, Louise Y Y Fong. Silencing of microRNA-31 prevents esophageal neoplasia in zinc deficient rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-241. doi:10.1158/1538-7445.AM2013-LB-241
PWE-228 An assessment of the impact 5ASA dose, dose interval, preparation and delivery have on maintaining remission in ulcerative colitis
Authors: J R O'Kelly, I D Arnott
Journal: Gut (2012)

<h3>Introduction</h3> 5-Aminosalicylic Acid (5ASA) plays a key role in both induction and maintenance of remission in ulcerative colitis (UC). A number of questions remain poorly assessed by clinical trials including the role of dose, dose interval, preparation and delivery method in maintaining remission. We aimed to assess the value of preparation, dose, delivery method and dosing interval on the duration of first remission in patients with newly diagnosed UC. <h3>Methods</h3> We retrospectively assessed an inception cohort of 100 newly diagnosed UC patients diagnosed between 2004 and 2008 and followed-up for 3 years. 69 patients took oral Pentasa and 11 took oral Asacol. The diagnosis adhered to the criteria of Lennard-Jones and clinical details were categorised according to the Montréal classification. Data were also collected on 5ASA maintenance drug (Asacol or Pentasa), dose (high dose or low dose), and delivery (oral or oral and rectal). Relapse was defined as an increase in symptoms needing an increase in anti-inflammatory therapy. Risk of relapse was evaluated using HR, and by using Cox regression to control for potential confounders. <h3>Results</h3> From induction of remission to the end of our 3 yr follow-up, 76% of patients relapsed, with a mean time to relapse of 16 months. Mean daily dose taken of Asacol was 2.3 g/day (IQR 0 g/day) and Pentasa 2.4 g/day (IQR 2–3 g/day). We found no significant difference in the relapse rates between Asacol and Pentasa. (Relapse rate 7/11 Asacol vs 53/69 Pentesa, c<sup>2</sup>=0.574, HR 1.78 (p=0.19)). We also found no significant difference between: relapse rates for patients taking high dose 5ASA vs low dose. (Relapse rate 9/10 high dose vs 42/58 low dose, c<sup>2</sup>=0.114 HR 0.505 (p=0.223)); Oral and rectal vs oral alone (Relapse rate 10/12oral + rectal vs 59/77 oral, c<sup>2</sup>=0.374, HR 0.49 (p=0.09)); Twice daily and once daily (Relapse rate 44/60 TD vs 5/6 OD, c<sup>2</sup>=0.306, HR 2.12 (p=0.43)), and three times daily compared with twice daily (Relapse rate 20/23 TD vs 44/60 BD, c<sup>2</sup>=0.107, HR 0.82 (p=0.6)). <h3>Conclusion</h3> The duration of first remission in UC is variable and although 5ASA are effective the majority of patients will relapse within 3 years. These data demonstrate that relapse is influenced relatively little by high dose or bi-directional therapies and there were no differences in the preparations studied. This would indicate that concordance with therapy is a vital aspect of 5ASA efficacy and clinicians should reinforce this point when discussing therapy. <h3>Competing interests</h3> None declared.
A5.06 Ultrasound-defined tenosynovitis predicts ra in patients with recent-onset inflammatory arthritis
Authors: I Sahbudin, L Pickup, P Nightingale, G Allen, Z Cader, P de Pablo, CD Buckley, K Raza, A Filer
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objective</h3> Tenosynovitis is common in early arthritis and the OMERACT Ultrasound Task Force recommended that US is a reproducible tool for evaluating tenosynovitis (TS) in RA. However, the value of US-defined tenosynovitis (TS) in the prediction of RA development is unclear. We assessed the ability of US-defined TS to predict the development of persistent RA in a prospective cohort of patients with early arthritis. <h3>Methods</h3> 107 patients with clinically apparent synovitis of at least one joint and symptom duration ≤3 months underwent baseline clinical, laboratory and tendon US assessments and the presence of grey scale and Power Doppler TS at 16 bilateral tendon compartments was determined [bilateral fingers (flexor compartments), wrists (extensor and flexor compartments), shoulders (biceps tendon), ankles (anterior extensors, peroneals, posterior tibialis)]. Outcome was determined after 18 months, applying the 2010 ACR/EULAR classification criteria for RA. The predictive values of US-defined TS for persistent RA were compared with clinical and serological variables. <h3>Results</h3> A total of 3424 tendon compartments were included in the analysis. 43 patients developed persistent RA (RA), 20 patients developed non-RA persistent disease (NRAP) and 44 patients had resolving disease at follow-up. All groups had evidence of TS in at least one tendon compartment at baseline (RA 85%, NRAP 71%, and Resolving 71%). In multivariate logistic regression, extensor carpi ulnaris (ECU) and digit flexor tendon involvement were predictive of persistent RA and provided additional predictive data over and above the presence of high levels of autoantibodies and clinical involvement of more than 10 joints [ECU or digit flexor TS (OR&nbsp;=&nbsp;5.25, p = 0.001), &gt;10 clinically tender or swollen joints (OR&nbsp;= 7.96, p &lt; 0.001), RF or ACPA high-positivity (OR&nbsp;=&nbsp;7.31, p = 0.001); AUC&nbsp;=&nbsp;0.86, Nagelkerke's R<sup>2 </sup>=&nbsp;0.499]. <h3>Conclusion</h3> This is the first study to illustrate that US-detected TS is predictive of persistent RA in patients with early arthritis. ECU and digit flexor tendon scanning provides optimal predictive data over and above clinical and serological variables.
Diffuse Bone Marrow Infiltration of a Neuroblastoma Mimicking the Findings of a Bone Marrow Scan on I-123 MIBG Scintigraphy
Authors: Thomas Grüning, Joachim Kropp, Wolg-Gunter Franke
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Carl Gustav Carus Medical School, University of Technology, Dresden, Germany Received for publication February 22, 2001. Accepted June 20, 2001. Reprint requests: Thomas Grüning, Department of Nuclear Medicine, Carl Gustav Carus Medical School, University of Technology, Fetscherstrasse 74, D-01307 Dresden, Germany. E-mail: [email protected]
A Case of Paranasal Sinuses Osteoma Detected on Bone SPECT/CT
Authors: Yan Xing, Jinhua Zhao, Taisong Wang
Journal: Clinical Nuclear Medicine (2011)

We present a 51-year-old woman with a history of colectomy for colon cancer who was referred to our department for bone assessment. Planar image revealed a focus of increased uptake of Tc-99m methylene diphosphonate in the nose root. According to the images of SPECT combined with low-dose CT, the abnormal radiotracer uptake at the site of left frontal sinus was considered to be osteoma. We conclude that SPECT/CT provides an accurate evaluation of the localization of the lesions and supplies anatomic information that can be valuable for diagnosis of nonmalignant bone diseases.
OC-161 Investigation of the action of histone deacetylase inhibitors in ex vivo and in vitro models of inflammatory bowel disease
Authors: A J P Edwards, M Gwiggner, A G Claridge, R J Morgan-Walsh, A L Hayden, A Bateman, J R F Cummings, G K Packham, S L F Pender
Journal: Gut (2012)

<h3>Introduction</h3> The management of inflammatory bowel disease (IBD) has evolved rapidly with anti-TNFα agents and the more appropriate use of immunomodulators. Despite this, a large therapeutic gap remains to be filled. Histone deacetylase (HDAC) inhibitors (HDI) preserve acetylation of core histones which prevents chromatin from condensing thus facilitating gene transcription. HDI have been approved for the treatment of sub-cutaneous T-cell lymphoma and recent work has shown that HDI may have a protective anti-inflammatory effect in murine models of UC (Tao <i>et al</i> 2007). We hypothesise that HDI have anti-inflammatory effects in human IBD and aim to investigate this using a human ex vivo model of IBD. <h3>Methods</h3> Carefully phenotyped patients with active UC (n=7) and CD (n=10) undergoing lower GI endoscopy had 8 pinch biopsies (≈3 mm<sup>2</sup>) taken for these experiments. Biopsies were cultured ex vivo at an air liquid interface for 8 h±FK228 or SAHA. Additionally, gut fibroblasts isolated from resection tissue were used to model mucosal plasticity in vitro±TNF-α and FK228 and a monocytic cell line (U937) was differentiated in vitro with GMCSF±FK228. Supernatants, RNA and tissue were collected for analysis by qRT-PCR, mesoscale assay, western blotting and histology. <h3>Results</h3> Nanomolar levels of FK228 significantly reduce mRNA expression and protein secretion of Th1 and Th2 cytokines and pro-inflammatory mediators (IL-8, MMP-1, -3, -9 and -12) in the ex vivo UC and CD biopsy models. Data suggest that FK228 can decrease mRNA expression of Th1 and Th17 signalling molecules in the ex vivo models. FK228 significantly decreases IL-8, MMP-3 and MMP-12 mRNA expression as well as IL-8 and MMP-3 protein secretion by gut fibroblasts and decreases GMCSF induced MMP-12 protein production by U937 cells. <h3>Conclusion</h3> This human ex vivo biopsy culture model is relevant for pre-clinical study of drug action in IBD as it utilises small amounts of tissue in a human system. FK228 produces significant anti-inflammatory effects at low doses by reducing cytokines and MMPs in this model. FK228 is able to act upon specific cells found in the gut such as lymphocytes, fibroblasts and monocytes to elicit anti-inflammatory effects. Based upon our initial findings, further investigation of the role of FK228 in IBD is warranted. <h3>Competing interests</h3> None declared.