tbuckley/cabot-search huggingface dataset:
Abstract 3138: FOXC1 represses estrogen receptor-α expression via increasing NF-κB activity in breast cancer: A novel mechanism to explain antiestrogen resistance
Authors: Jinhua Wang, Guifa Li, Partha Ray, Myung-Shin Sim, Michael A. Walter, Armando E. Giuliano, Xiaojiang Cui
Journal: Cancer Research (2011)

Abstract The Forkhead-box transcription factor FOXC1 has recently been identified as a critical marker for human basal-like breast cancer, which lacks or under-expresses estrogen receptor-α (ERα). Here we show a consistent inverse correlation between FOXC1 expression and ERα expression in multiple cDNA microarray data sets of human breast cancer. Overexpression of FOXC1 in ERα-positive breast cancer cells induces cell growth, migration, and invasion, but downregulates ERα mRNA and protein levels and consequently reduces cellular responses to estradiol and tamoxifen. This could explain why tamoxifen-refractory breast cancer cells exhibit higher FOXC1 levels as compared with tamoxifen-sensitive parental cells. We also found that FOXC1 induces NF-κB activation, which is known to be associated with ER-negative breast cancer, by increasing Pin1-mediated p65 protein stability and thus p65 protein levels. NF-κB mediates, at least in part, the regulation of ERα by FOXC1, because inhibition of NF-κB by an IκBα super-repressor and small-molecule inhibitors attenuated the suppression of ERα expression by FOXC1. Furthermore, the importance of the NF-κB pathway in FOXC1-stimulated cell growth was demonstrated by increased cell sensitivity to pharmacologic inhibition of NF-κB. Taken together, these results reveal a novel ERα-regulating mechanism that may explain the loss or low expression of ERα in basal-like breast cancer and also may provide new insight into mechanisms for antiestrogen resistance in breast cancer. 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 3138. doi:10.1158/1538-7445.AM2011-3138
Endoscopic retrograde cholangiopancreatography (ERCP)-related esophageal perforation in osteogenesis imperfecta
Authors: R. Kochar, R. Pandey, W. Mileski, S. Lick, M. Schreiber, S. Parupudi
Journal: Endoscopy (2012)

A 77-year-old woman with osteogenesis imperfecta was admitted with symptomatic choledocholithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) was carried out and mild resistance was encountered in the distal esophagus with "red out" during intubation. The duodenoscope was withdrawn and gastroscopy revealed a tear in the distal esophagus ([Fig. 1]). As a perforation was suspected, a nasogastric tube was deployed, intravenous antibiotics were started, and surgery was consulted. An esophagogram confirmed the esophageal leak ([Fig. 2]) and thoraco-abdominal computed tomography (CT) showed a 0.7-cm esophageal perforation and air–fluid collection (3 cm × 10 cm) in the posterior mediastinum ([Fig. 3]). Conservative management was decided on due to clinical stability and poor operative candidacy. Within 48 hours the liver function tests normalized and parenteral nutrition was started. The day 7 esophagogram showed partial healing. Enteral feeding was started with a nasojejunal tube placed fluoroscopically. An esophagogram on day 27 showed complete healing ([Fig. 4]). The patient started an oral diet and was discharged with plan for elective cholecystectomy.
AB0812 Spine-Hip Diagnostic Discordance among Osteoporotic Patients
Authors: L. Sanchez Riera, N. Wilson, I. Hussein, S. Nuhaily, N. Qahtani, N. Ibrahim, R. Aneja, T. Khan, S. Gonuguntla, H. Maashari, S. Waheeduddin, M. Al Maini
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Abstract</h3> Collagen deposition and stromal stiffening accompany malignancy, compromise treatment, and promote tumor aggression. Clarifying the molecular nature of and the factors that regulate extracellular matrix stiffening in tumors should identify biomarkers to stratify patients for therapy and therapeutic interventions to improve outcome. We profiled lysyl hydroxylase- and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in more aggressive human breast cancer subtypes with the stiffest stroma. These tissues also harbored the highest number of tumor-associated macrophages (TAM), whose therapeutic ablation not only reduced metastasis, but also concomitantly decreased accumulation of collagen crosslinks and stromal stiffening. Epithelial-targeted expression of the crosslinking enzyme lysyl oxidase had no impact on collagen crosslinking in PyMT mammary tumors, whereas stromal cell targeting did. Consistently, stromal cells in microdissected human tumors expressed the highest level of collagen crosslinking enzymes. Immunohistochemical analysis of a cohort of breast cancer patient biopsies revealed that stromal expression of lysyl hydroxylase two, an enzyme that induces hydroxylysine aldehyde-derived collagen crosslinks and stromal stiffening correlated significantly disease specific mortality. The findings link tissue inflammation, stromal cell-mediated collagen crosslinking and stiffening to tumor aggression and identify lysyl hydroxylase two as a novel stromal biomarker. <h3>Significance</h3> We show infiltrating macrophages induce stromal fibroblast, and not epithelial, expression of collagen crosslinking enzymes that drive tumor stiffening. Stromal enzyme LH2 is significantly upregulated in breast cancer patients with the stiffest stroma, the most trivalent HLCCs and the worst prognosis, underscoring its potential as a biomarker and therapeutic target.
RAC Unanimously Approves Cancer Vaccine Trial
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article RAC Unanimously Approves Cancer Vaccine Trial Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Page 1000, https://doi.org/10.1093/jnci/84.13.1000 Published: 01 July 1992
DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China
Authors: Xin Li, Yingying Cui, Zhenchang Sun, Lei Zhang, Ling Li, Xinhua Wang, Jingjing Wu, Xiaorui Fu, Wang Ma, Xudong Zhang, Yu Chang, Feifei Nan, Wencai Li, Liping Su, Jinghua Wang, Hongwei Xue, Mingzhi Zhang
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Optimal treatment strategies for advanced natural killer/T (NK/T)-cell lymphoma have not been fully defined. We compared the safety and efficacy of DDGP and SMILE regimens for advanced NK/T-cell lymphoma in a randomized controlled, multicenter, and open-label clinical trial. Experimental Design: Patients were newly diagnosed in stages III–IV and had performance scores in 0 to 2. Six cycles of DDGP (dexamethasone, cisplatin, gemcitabline, and pegaspargase) or SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy were randomly assigned to them. The primary end point was progression-free survival (PFS). Secondary end points included response rate and overall survival (OS). The trial is ongoing and is registered with ClinicalTrials.gov (No. NCT01501149). Results: Of 42 patients enrolled, 21 were treated with DDGP therapy, and 21 patients were treated with SMILE therapy. The 1-year PFS and 2-year OS rates were better in the DDGP group than that in the SMILE group (86% vs. 38% for 1-year PFS, P = 0.006; 74% vs. 45% for 2-year OS, P = 0.027). Complete remission (CR) rate and overall response rate (ORR) of the DDGP group were higher than that in the SMILE group (71% vs. 29%, P = 0.005 for CR rate; 95% vs. 67%, P = 0.018 for ORR). The SMILE group showed more serious leucopenia (P = 0.030) and severe allergic reaction (P = 0.015) than the DDGP group. In addition, two cases in the SMILE group underwent grade 4 mucosal reaction. Conclusions: DDGP chemotherapy resulted in significant improvement in PFS, OS, and better tolerability compared with SMILE chemotherapy for newly diagnosed advanced NK/T-cell lymphoma patients. Clin Cancer Res; 22(21); 5223–8. ©2016 AACR.
AB0329 Clinical effectiveness and infection rate in rheumatoid arthritis patients switched from anti-tnf agents to abatacept
Authors: M. Pietrosanti, R. Di Rosa, S. Salemi, M. Markovic, V. Carusi, M. I. Biondo, M. Catoni, B. Laganà, M. L. Sorgi, R. D’Amelio
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increased risk of infection is an important safety concern in Rheumatoid Arthritis (RA) patients receiving biological therapies. Previous reports suggest a more favourable safety profile for Abatacept (ABT) respect to anti TNF. <h3>Objectives</h3> The aim of our study is to compare the incidence of mild/moderate and serious infections in a group of RA patients switched from anti-TNF agents, to ABT. <h3>Methods</h3> From 2008 to 2012 19 patients previously treated with anti-TNF agents, switched to ABT for inefficacy or adverse events. 6/19 patients (31%) were previously treated with more than one anti-TNF agent. We used the Chi-Square test to evaluate incidence of infections during prior therapy with anti-TNF compared with incidence of infections occurred with ABT. T test was used to test effectiveness of ABT at T0 and T6 analyzing DAS 28 and HAQ. <h3>Results</h3> Incidence of infections during previous treatment with anti-TNF agents was not statistically different from what observed during ABT treatment (p&lt; 0,2). We observed significant improvement in the disease activity between T0 and T6 according to DAS 28 (p&lt; 0,002). Moreover the difference between HAQ T0 and T6 supported improvement of disease activity, although statistically non significant (p&lt; 0,06). <h3>Conclusions</h3> RA patients under both ABT and anti-TNF agents treatment are susceptible to infections, nevertheless the incidence of infections results unchanged. ABT effectiveness was improved from T0 to T6, demonstrating the favourable effect of switching to ABT in patients with RA previously failing anti-TNF agents. <h3>Disclosure of Interest</h3> None Declared
Massive pneumoperitoneum during endoscopic ultrasound-guided drainage of a pancreatic cyst lesion, treated with an enteral self-expanding metal stent and paracentesis
Authors: Claudia Consiglieri, Joan Gornals, Carlos Huertas, Zoilo Madrazo, Carme Loras
Journal: Endoscopy (2014)

A 54-year-old patient with a supposed 9-cm pseudocyst located in the pancreatic tail was referred to our unit for endoscopic ultrasound (EUS)-guided transmural drainage ([Fig. 1]). The fluoroscopic image showed the immediate creation of a pneumoperitoneum when the cystotome was used, because the cystic lesion was not adherent to the gastric wall ([Fig. 2 a]). First, we attempted to seal the ostomy (or iatrogenic perforation), with the purpose of preventing leakage of fluids to the peritoneal cavity, by using a 'diabolo'-shaped self-expanding metal stent (SEMS) (AXIOS 10 mm × 10 mm; Xlumena, Mountain View, California, USA), without success ([Fig. 2 b]). Finally, a successful rescue maneuver was done in which a fully covered SEMS (60 mm × 16 mm, Hanaro; MI-Tech, Seoul, Korea) was delivered coaxially with the first and migrated stent ([Fig. 3 a, b]). Computed tomography (CT) showed a sealed perforation without leakage of fluid, and a massive pneumoperitoneum ([Fig. 4], [Video 1]).
Pituitary Prolactinoma Imaged by 99mTc-Sestamibi SPECT/CT in a Multiple Endocrine Neoplasia Type 1 Patient
Authors: Yu Pan, Jing Lv, Rui Guo, Mengyi Pan, Yifan Zhang
Journal: Clinical Nuclear Medicine (2016)

A 35-year-old woman who had undergone bilateral inferior parathyroidectomy for primary hyperparathyroidism was referred to our hospital to evaluate the cause of irregular menses, galactorrhea, and paroxysmal headache. Multiple endocrine neoplasia type 1 was then suspected for the high levels of plasma prolactin, parathyroid hormone, serum calcium, insulin, and related symptoms. A 99mTc-sestamibi SPECT/CT acquired to evaluate parathyroid glands unexpectedly revealed an increased accumulation in the pituitary gland, which was further confirmed by enhanced magnetic resonance imaging as a pituitary microadenoma. Bromocriptine treatment gradually reduced the prolactin level.
Abstract 2122: The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells.
Authors: Chintda Santiskulvong, Shivani Sharma, Laurent Bentolila, Jian Y. Rao, James Gimzewski, Oliver Dorigo
Journal: Cancer Research (2013)

Abstract Introduction: Cell stiffness (Young's E modulus), as measured via Atomic Force Microscopy (AFM) is a newly recognized characteristic of cancer cells. We previously demonstrated that cisplatin-resistant ovarian cancer cells have a stiffer cell membrane as compared to their syngeneic cisplatin-sensitive counterpart, and that cisplatin increases cell stiffness in cisplatin-sensitive cells. Here we examine the role of Rho GTPase in cell stiffness and cisplatin resistance. Experimental Procedures: Prior to AFM analysis, cells were stained with Annexin V-FLUOS and only non-apoptotic cells were chosen for measurements. Cell stiffness was measured via AFM on live cells in physiological buffer. The actin cytoskeleton was visualized using phalliodin-ATTO 647N. Cells were imaged with a Leica TCS SP5 STED confocal system or a Nikon Eclispe 90i. Cisplatin sensitivity was determined via the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt] cell viability assay. A nonlinear regression curve fit (one phase exponential decay) was used to analyze cisplatin dose response experiments and determine the IC50 (GraphPad Prism). Rho inhibition and activation were accomplished using Rho Inhibitor I and Rho Activator II, respectively (Cytoskeleton, Inc.). Results: The cisplatin IC50 of cisplatin-sensitive (A2780, OVCAR5, SKOV3) and cisplatin-resistant (CP70, OVCAR5-CisR, SKOV3-CisR, RMG-1) cells correlated with Young's E modulus, with increasing IC50 corresponding to a stiffer cell phenotype. Cells that are resistant to cisplatin displayed an actin cytoskeleton that consisted of long stress fibers that spanned the width of the cell. Rho inhibition in CP70 and OVCAR5-CisR cells abolished this network of actin stress fibers, decreased cell stiffness, and increased cisplatin sensitivity. In contrast, Rho activation in A2780 and OVCAR5 cells induced the reorganization of the actin cytoskeleton into long stress fibers, increased cell stiffness, and decreased cisplatin sensitivity. We demonstrated previously that cisplatin increases cell stiffness in cisplatin-sensitive OVCAR5 cells, and here we show that cisplatin induces actin stress fiber formation in these cells. Conclusions: Rho-mediated actin stress fiber formation increases cell stiffness and mediates cisplatin resistance in ovarian cancer cells. Citation Format: Chintda Santiskulvong, Shivani Sharma, Laurent Bentolila, Jian Y. Rao, James Gimzewski, Oliver Dorigo. The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells. [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 2122. doi:10.1158/1538-7445.AM2013-2122
FRI0581-HPR Falls Associated with Muscle Strength and Pain in Knee Osteoarthritis Patients with Self-Reported Knee Instability
Authors: M. Van Der Esch, A. de Zwart, M. Pijnappels, M. Hoozemans, M. van der Leeden, L. Roorda, W. Lems, J. Dekker, J. van Dieen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Subjects with knee osteoarthritis (OA) and self-reported knee instability have a higher fall incidence than healthy older adults<sup>1</sup>. Increased risk of falls might be associated with knee instability related factors: muscle weakness, impaired proprioception, high varus-valgus joint laxity and knee pain<sup>2</sup>. <h3>Objectives</h3> To establish the associations between knee muscle strength, knee joint proprioception, varus-valgus knee joint laxity, knee pain and falls in patient reporting knee instability and with established knee OA. <h3>Methods</h3> Data of 301 subjects (203 females, 98 males, 35-82 year) with diagnosed knee OA and self-reported knee instability were analysed. The experience of at least one fall in the previous 3 months was assessed by questionnaire. Knee muscle strength, knee proprioception, and varus-valgus knee joint laxity were assessed using specifically designed measurement devices and pain was assessed with a numeric rating scale (NRS). Differences in biomechanical factors between fallers and non-fallers were calculated. To assess the associations between biomechanical factors and falls, logistic regression analyses were performed. <h3>Results</h3> Over 10% (31 out of 301) of subjects reported a fall in the previous 3 months. Between fallers and non-fallers, significant differences were found for knee extension muscle strength (p=0.017), knee flexion muscle strength (p=0.041) and knee pain (p&lt;0.001). Knee extension muscle strength (OR 0.3, 95% CI 0.1-0.8, p=0.022), knee flexion muscle strength (OR 0.2, 95% CI 0.0-1.0, p=0.048) and knee pain (OR 1.4, 95% CI 1.2-1.6, p&lt;0.001) were associated with falls. No significant associations were found for knee proprioception and varus-valgus knee joint laxity. The association between knee muscle strength (extension and flexion) and falls was not affected by knee proprioception or varus- valgus knee joint laxity. Knee pain was independently associated with falls. In multivariate regression analyses, both knee extension and flexion strength were not associated with falls when pain was included in analyses. <h3>Conclusions</h3> Low knee extension and flexion muscle strength, and high knee pain are associated with an increased risk of falls in patients with knee OA and self-reported knee instability <h3>References</h3> Hoops ML, Rosenblatt NJ, Hurt CP, Crenshaw J, Grabiner MD. Does lower extremity osteoarthritis exacerbate risk factors for falls in older adults? Women9s Health. 2012;8(6):685-98. Sturnieks DL, Tiedemann A, Chapman K, Munro B, Murray SM, Lord SR. Physiological risk factors for falls in older people with lower limb arthritis. The Journal of Rheumatology. 2004;31(11):2272-9. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5145
Increased incidence of invasive group A streptococcal disease in Ireland, 2012 to 2013
Authors: M Meehan, S Murchan, S Bergin, D O’Flanagan, R Cunney
Journal: Eurosurveillance (2013)

Invasive group A streptococcal (iGAS) infections have been notifiable in Ireland since 2004. Incidence rates (2004-2011) have ranged from 0.8 to 1.65 per 100,000. In 2012, the iGAS rate rose to 2.66 per 100,000 and was associated with a high proportion of emm1 isolates. A further increase in January to June 2013 has been associated with increased prevalence of emm3. Public health departments and clinicians have been alerted to this increase.
Abstract 2458: MicroRNA miR-34 as a natural regulator and potential therapeutic for pancreatic cancer stem cells
Authors: Xiaojie Meng, Qing Ji, Xinbao Hao, Wenhua Tang, Liang Xu
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) have been implicated in cancer initiation and progression and are involved in cancer stem cell dysregulation. We show that miR-34 directly regulates Notch and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines and the potential link to cancer stem cells. Restoration of miR-34 expression in the cancer cells downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cancer cells to chemotherapy and radiation. We identified that CD44+/CD133+ cancer cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to significant reduction of the tumor-initiating cell population, accompanied by inhibition of tumorsphere growth in vitro and tumor-initiation in vivo. Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer. Our data support that miR-34 may be involved in cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in cancer stem cell self-renewal and/or cell fate determination. Currently, we are exploring the nanoparticle-targeted delivery of miR-34 to cancer stem cells as a novel molecular therapy for human pancreatic cancer, based on our patented nanobiotechnology which has been approved by FDA for clinical trials. Taken together, our results demonstrate that restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting cancer stem cells. Molecularly targeted miRNA therapy could be a powerful tool to correct the cancer stem cell dysregulation. Supported in part by NIH grants CA121830(S1) and CA134655. 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 2458. doi:10.1158/1538-7445.AM2011-2458