tbuckley/cabot-search huggingface dataset:
Abstract SY21-04: Wnt signaling, stem cells, and cancer.
Authors: Roel Nusse
Journal: Cancer Research (2013)

Abstract We are interested in the regulation of growth, development and integrity of animal tissues. We study multiple different organs, trying to identify common principles, and extend these investigations to cancer and injury repair. In most organs, different cell types are generated by stem cells; cells that also make copies of themselves and thereby maintain the tissue. A right balance between the number of stem and differentiated cells is essential for the proper function of the organs. Locally acting signals are important to maintain this balance in a spatially organized manner and these signals are key to understanding the regulation of growth. A common theme linking the work together is the Wnt family of signals. Work from many laboratories has shown that Wnt proteins are essential for the control over stem cells. How this is achieved is far from clear and is the subject of studies in the lab, both in vivo and in cell culture. In vivo, a particular question we address is how physiological changes, such as those occurring during hormonal stimuli, injury or programmed tissue degeneration have an impact on the self-renewal signals and on stem cell biology. Current research includes: 1) Identifying and tracing Wnt-responsive stem cells in tissues; 2) mapping cis-acting transcriptional control elements (enhancers) that control Wnt gene expression in normal and injured tissues; 3) the use of active Wnt proteins to maintain stem cells (including embryonic stem cells) in cell culture; 4) presenting Wnt protein in a vectorial manner to stem cells to direct asymmetric cell division. Citation Format: Roel Nusse. Wnt signaling, stem cells, and cancer. [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 SY21-04. doi:10.1158/1538-7445.AM2013-SY21-04
Abstract 3093: Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness
Authors: Yixiang Xu, Qiang Chen, Wengang Li, Xinhui Su, Tenghui Chen, Yonghong Liu, Yang Zhao, Bert W. O'Malley, Chundong Yu
Journal: Cancer Research (2010)

Abstract Amplified in breast cancer 1 (AIB1; SRC-3) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has been identified to play an important role in malignancy of several cancers such as breast and prostate cancers; however, its involvement in the progression of hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the expression and possible role of AIB1 in HCC. Western blot analysis revealed that AIB1 was significantly increased in 15 of 22 HCC samples (68%), whereas only trace amounts of AIB1 were detected in the most matched nontumorous liver tissues. Functional studies on HCC cells demonstrated that AIB1 specific small interfering RNA mediated down-regulation of AIB1 resulted in decreased cell proliferation rate, cell migration/invasion ability, colony formation ability, and tumorigenic potential in nude mice. Marked increase of cell cycle inhibitor p21Cip1/Waf1 expression and dramatic decrease of the expression of phosphorylated Akt, proliferating cell nuclear antigen (PCNA), and matrix metallopeptidase MMP-9 in AIB1 knockdown cells contributed to these phenotypic changes. Consistent with these results, clinical AIB1-positive HCC exhibited higher levels of PCNA protein expression compared with AIB1-negative HCC. Further statistical calculation revealed a positive and tight correlation between the levels of AIB1 protein and PCNA protein in HCC, indicating that AIB1 contributes significantly to HCC cell proliferation. Conclusion: our results demonstrate that AIB1 promotes the progression of human HCC by enhancing cell proliferation and invasiveness, and could be a potential therapeutic target molecule for HCC treatment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3093.
Ga-67 Scintigraphy in a Case of Mitochondrial Myopathy
Authors: HITOYA OHTA, MASAYUKI SHINTAKU, CHIYO KURIMOTO, DAITA KANEDA
Journal: Clinical Nuclear Medicine (2001)

OHTA, HITOYA M.D.; SHINTAKU, MASAYUKI M.D.; KURIMOTO, CHIYO M.D.; KANEDA, DAITA M.D. Author Information
Evaluation d'une nouvelle aiguille de ponction sous écho-endoscopie dans le diagnostic de tumeurs: résultats pour 29 biopsies
Authors: E Piera, F Poizat, M Giovannini, E Bories, C Pesenti, F Caillol, M Bendahou, B Chetaille, L Xerri, G Monges
Journal: Endoscopy (2011)

Introduction: Au cours des dix dernières années, la ponction sous écho-endoscopie (PSEE) a démontré son efficacité dans le diagnostic des masses péri-digestives. Cette technique, peu invasive, est souvent contributive au diagnostic grâce à la complémentarité des informations apportées par le matériel micro biopsique et le matériel cytologique. Il existe plusieurs aiguilles de calibres différents, dont le choix est dicté par la localisation et la taille de la tumeur. Il s'agit ici d'évaluer une nouvelle aiguille de 19 gauges (G) „Core„ dans le cadre de 29 biopsies.
FRI0506 The diagnostic utility of musculoskeletal ultrasound in early arthritis – a probabilistic (bayesian) approach
Authors: H. Rezaei, E. af Klint, R. F. Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> While musculoskeletal ultrasound examination (MSUS) is used increasingly in the work-up of patients with inflammatory joint disease, the exact diagnostic utility has not been established. <h3>Objectives</h3> To quantify the diagnostic utility of MSUS using a prospective, probabilistic (Bayesian) approach. <h3>Methods</h3> All patients referred to our clinic for evaluation of arthritis were eligible, unless a prior diagnosis was indicated or a certain diagnosis could be made based on the information in the referral letter. Patients were assessed by history and physical examination including joint examination, laboratory testing including acute-phase reactants, RF, and ACPA, and plain x-ray of hands, wrists and feet if clinically indicated. A diagnostic assessment was then performed by the responsible physician where the probability of a) any inflammatory joint disease and b) rheumatoid arthritis was given on a 5-point scale ranging from unlikely (0-20% probability) to very likely (80-100% probability). Subsequently, an ultrasound examination of the wrist, MCP, PIP 2-5 in both hands, MTP 2-5 in both feet and also symptomatic joints was performed by HR and the results of the examination presented to the responsible physician. The latter then assessed the diagnostic probabilities again, using the same scale. The proportions of patients with maximal and minimal diagnostic certainty pre-test and post-test were compared by Fisher exact test. <h3>Results</h3> 67 patients were included, 52 were female, average (SD) age 47.9 (16.5) years. Symptom duration 8.9 (4.0) months, 15 patients were positive for RF and 12 for ACPA. The pre-test and post-test probability distributions for (any) inflammatory joint disease and for RA are given in the table. The final diagnoses in these patients were RA (15), other inflammatory joint diseases (21), non-inflammatory joint disease (31). With regard to a diagnosis of (any) inflammatory joint disease, the proportion of patient for whom diagnostic certainty was maximal (&lt;20% OR &gt;80% likelihood) was 20/67 (29.9%) before MSUS and 42/67 (62.7%) after MSUS (p=0.0002). With regard to a diagnosis of RA, the proportions were 21/67 (31.3%) pre-test and 39/67 (58.2%) post-test (p=0.003). Parallel reductions were seen in the proportions of patients with greatest diagnostic uncertainty (40-60% likelihood), from 24/67 (35.8%) to 10/67 (14.9%) (p=0.0093) and from 17/67 (25.3%) to 4/67 (6.0%) (p=0.0035), respectively. <h3>Conclusions</h3> In this probabilistic (Bayesian) analysis, musculoskeletal ultrasound when added to routine physical and laboratory examination greatly increased the diagnostic certainty in patients referred for the evaluation of arthritis. <h3>Disclosure of Interest</h3> H. Rezaei: None Declared, E. af Klint: None Declared, R. Van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB
A phase III multicenter trial comparing two different sequences of second/third line therapy (irinotecan/cetuximab followed by FOLFOX-4 vs. FOLFOX-4 followed by irinotecan/cetuximab in K-RAS wt metastatic colorectal cancer (mCC) patients refractory to FOLFIRI/Bevacizumab.
Authors: Stefano Cascinu, Gerardo Rosati, Guglielmo Nasti, Sara Lonardi, Alberto Zaniboni, Paolo Marchetti, Massimo Aglietta, Domenico Bilancia, Rosario Vincenz Iaffaioli, Vittorina Zagonel, Monica Giordano, Domenico C. Corsi, Francesco Ferraú, Roberto Labianca, Monica Ronzoni, Irene Claudia Floriani
Journal: Journal of Clinical Oncology (2015)

3582 Background: Improvements in survival have been reported in mCC with the addition of bevacizumab or cetuximab to chemotherapy. However, their efficacy in different therapy lines and the optimal sequence are still controversial. While bevacizumab seems to lose its efficacy along the course of treatment lines, cetuximab is active even in 2° and 3° line therapy. We designed a randomised, phase III study to compare efficacy and safety of two different sequences of Cetuximab or FOLFOX to optimize the treatment of mCC pts refractory to FOLFIRI/bevacizumab. Methods: Pts were randomised in a 1:1 ratio to receive as 2° or 3° line cetuximab/irinotecan followed by FOLFOX-4 (Arm A) or FOLFOX-4 followed by cetuximab/irinotecan (Arm B). Primary end point was progression free survival (PFS); secondary end points were overall survival and toxicity. Results: 109 mCC pts were enrolled and 108 were evaluable for analysis. 63 patients were males and 45 females, with a median age of 61 years. Efficacy results are reported in the table. Treatments were well tolerated with a low number of serious adverse reactions in both arms (8 and 4, respectively), even if grade 3-4 toxicity was overall higher in cetuximab treatment. Conclusions: While the primary end point was not met (PFS was not statistically different), FOLFOX seems to be more effective than cetuximab (overall survival: 18.6 months vs 12.4 months) as 2° line treatment in patients receiving bevacizumab/FOLFIRI. This seems to confirm preclinical and clinical (FIRE-3) data suggesting that a prior anti-VEGF therapy may determine a lower sensitivity to a subsequent anti-EGFR treatment. Clinical trial information: NCT01030042. Evaluable patients Arm A (54 patients) Arm B (54 patients) Hazard Ratio (Arm B vs. Arm A) (95% confidence interval) ORR II line 15/52 (29%) 21/52 (40%) III line 7/30 (23%) 8/38 (21%) PFS (median) (months) 9.9 11.3 HR = 0.85 (0.56-1.28); p = 0.42 OS (median) (months) 12.4 18.6 HR = 0.79 (0.52-1.22); p = 0.28 Treatment compliance Completed II line 66.7% 70.3% III line 80% 71% Arm A: CETUXIMAB followed by FOLFOX; Arm B: FOLFOX followed by CETUXIMAB
P4-02-04: Androgen Receptor (AR) Expression in a Cohort of Patients (pts) with Triple Negative Breast Cancer (TNBC).
Authors: A Gucalp, G Gupta, S Patil, YH Wen, M Akram, E Brogi, SN Powell, AY Ho, CA Hudis, TA Traina
Journal: Cancer Research (2011)

Abstract Background TNBC, defined by the absence of ER, PR, and HER2, is associated with higher risk of recurrence and BC-related mortality, earlier age at diagnosis, menarche, and 1st pregnancy, increased parity, higher BMI, and African-American/Hispanic race. TNBC is a heterogeneous group. Using gene expression analysis, our group described a subset of AR+ ER/PR- BC that exhibits androgen-dependent growth. In vitro studies confirmed the functional role of AR and showed that growth could be abrogated by antiandrogens.(Doane et al 2006) We translated this work into a phase II trial of bicalutamide in pts with AR+ ER/PR- metastatic BC (MBC). (NCT00468715) We now describe the prevalence and clinicopathological characteristics of AR+TNBC in primary disease in a single-institution retrospective cohort. Methods: We identified 1,032 pts with resectable, TNBC (ER/PR&amp;lt;1%; HER2&amp;lt;2+/FISH&amp;lt;2.2) who had surgery at MSKCC from 1998–2006. Exclusion criteria: neoadjuvant chemotherapy, prior radiation, inflammatory/MBC. IRB approval was obtained. We constructed tissue microarrays (TMA) from 210 primary tumors (&amp;gt; 1 cm) with each tumor represented by three 0.6mm cores. AR was tested with DAKO antibody (Clone AR441; dilution 1:500). TMAs were digitized with a Mirax scanner. MetaMorph image analysis software was used to quantify the ratio of DAB staining to hematoxylin signal. A ratio &amp;gt;1 SD above mean was defined as AR+. AR+ cores were manually reviewed; false positives due to core artifact were excluded. To evaluate clinicopathological variables and differences in recurrence-free survival (RFS) and overall survival (OS) by AR status we used chi-square/t-tests and Kaplan-Meier methods/log-rank test, respectively. Results: 169 pts had adequate cores for image analysis/quantification of AR. 10% of pts tested AR+ (17/169). Median (med) followup: AR+=6 years (yr), AR-=5.6yr. Demographic/clinicopathological variables: Table 1 (ages in med yr). Overall med age=54yr (29-84). Adjuvant chemotherapy received: AR+ 82%, AR- 87%, p =0.40; 77% received anthracycline/taxane-based therapy. Med time to distant metastasis (DM)=2.1yr (0.2−6.2yr). We were unable to demonstrate a difference in 5yr RFS (69% vs. 77%; p=0.37) or OS (68% vs. 84%; p=0.25) between AR+ and AR- TNBC. Conclusions: Consistent with our prospective study, AR is expressed in ∼10% of TNBC tumors in this retrospective cohort. The pts in our dataset may be older, postmenopausal, more likely to self-report white race and have T1-2/N0-1 BC. No statistically significant differences were observed in demographic/clinicopathological variables or survival outcomes between AR+ and AR- TNBC. Additional TMA data from our database will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-04.
OUTCOMES IN PATIENTS WITH A FAMILY HISTORY OF ATRIAL FIBRILLATION: FINDINGS FROM THE OUTCOMES REGISTRY FOR BETTER INFORMED TREATMENT OF ATRIAL FIBRILLATION
Authors: Anna Gundlund, Emil Loldrup Fosboel, Sunghee Kim, Gregg Fonarow, Bernard Gersh, Alan S. Go, Peter Kowey, Elaine Hylek, Kenneth Mahaffey, Paul Chang, Laine Thomas, Eric Peterson, Jonathan Piccini
Journal: Journal of the American College of Cardiology (2015)
Abstract 4959: Osteoprotegerin mediates resistance to TRAIL-induced apoptosis in pancreatic ductal adenocarcinoma
Authors: Hirotaka Kanzaki, Akashi Otaki, Mark I. Greene, Ramachandran Murali
Journal: Cancer Research (2012)

Abstract [Purpose] Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) has been shown to have great potential for the treatment of most human tumor cells without harming normal cells. However, some cancers show resistance to TRAIL induced apoptosis. The poor prognosis of both pancreatic ductal adenocarcinoma (PDAC) is likely due to the absence of valid approaches for early detection, the frequency of its metastases at the time of diagnosis, frequent recurrence after surgery, and poor responsiveness to chemotherapy. PDAC is also known as the most common resistant cells to TRAIL. Since osteoprotegerin (OPG) is known as a decoy receptor that binds to TRAIL and inhibits TRAIL-induced apoptosis, we hypothesized that OPG might play a role in mediating resistance to apoptosis in PDAC cells. [Methods and Results] To investigate the expression of OPG in PDAC cells, RT-PCR, Western blot and ELISA were performed. From the results, we found significant expression of OPG in both cell and cell culture medium. To investigate the apoptotic activity of TRAIL, we performed cell viability assay and apoptosis assay with or without siRNA against OPG. We found that PDAC cells showed significantly resistance to TRAIL induced apoptosis and knocking down of OPG sensitized TRAIL induced apoptosis in PDAC cells. [Conclusion] This study demonstrated that OPG played a role in resistance to TRAIL-induced apoptosis in PDAC cells. Expression of OPG might provide PDAC cells with an essential growth advantage through resistance to TRAIL-induced apoptosis. Inhibition of OPG expression and blocking OPG function might be a new therapeutic approach for the treatment of pancreatic cancer patients. 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 4959. doi:1538-7445.AM2012-4959
The Enteric Nervous System
Authors: Raj K. Goyal, Ikuo Hirano
Journal: New England Journal of Medicine (1996)

The enteric nervous system is a collection of neurons in the gastrointestinal tract1 that constitutes the "brain of the gut" and can function independently of the central nervous system.2 This system controls the motility,3,4 exocrine and endocrine secretions,5 and microcirculation6 of the gastrointestinal tract; it is also involved in regulating immune and inflammatory processes.7 In the past decade, major advances in the understanding of the enteric nervous system have led to a greater appreciation of its importance in clinical medicine. In this review we highlight some of these advances.Development of the Enteric Nervous SystemThe enteric nervous system . . .
Abstract B49: Smad4 suppresses Wnt signaling through downregulation of β-catenin
Authors: J. Joshua Smith, Tanner J. Freeman, Natasha G. Deane, Jinghuan Zi, Sabrina Poon, Steven Chen, Christian Kis, Ethan Lee, Punita Dhawan, Mary Kay Washington, Yu Shyr, R. Daniel Beauchamp
Journal: Cancer Research (2009)

Abstract Introduction: Transforming Growth Factorβ (TGFβ) and Wnt signaling pathways modulate differential responses during embryonic development, and later in intestinal epithelial cell differentiation, proliferation and colorectal tumor promotion. β-catenin, the central mediator of canonical Wnt signaling, has been shown to pathologically promote intestinal epithelial cell de-differentiation and induce sustained proliferation in the absence of functional APC. Smad proteins are key developmental proteins involved in TGFβ/Bone Morphogenetic Protein (BMP) signaling involved in epithelial cell growth inhibition. Smad4, in particular, functions as a tumor suppressor and mutation of the Smad4 gene is a frequent and potentially late event in colon cancer. We recently found that expression of wild type Smad4 in Smad4-mutant colon cancer cells results in profound inhibition of β-catenin/TCF-driven transcriptional activation. Purpose: In the current study, we set out to determine the mechanism of Smad4 inhibition of canonical Wnt signaling. Experimental Procedures: We examined steady-state levels of β-catenin mRNA and protein in cells and human tissues, followed by analysis of components of β-catenin transcriptional and degradation machinery in the presence and absence of Smad4, and with and without inhibition of GSK3-β, a critical regulator of cytoplasmic β-catenin. Results: We observed that wild type Smad4 expression resulted in significant repression of Wnt-specific transcriptional activity that could be restored with GSK-3β inhibition and overexpression of wild-type and mutant β-catenin in S W480 cells that have inactivating mutations in both APC and Smad4 genes. Transient overexpression of Smad4 also inhibited β-catenin-dependent transcriptional activity in HEK 293 cells that have wild-type APC and Smad4 genes. β-catenin phosphorylation is intact and unchanged in comparison of controls and Smad4-expressing S W480 cells, but the total level of β-catenin mRNA and protein is decreased in the Smad4-expressing cells. Assessment of human colorectal cancers using tissue microarray analysis revealed an inverse relationship between nuclear Smad4 and tumor cell β-catenin immunostaining. Furthermore, we observed that high Smad4 expression is associated with better disease-free survival and that high β-catenin expression is associated with worse disease-specific survival in analysis of outcomes from 250 patients. Conclusions: Our data suggest that the tumor suppressor role of Smad4 involves reduction of β-catenin levels with resultant reduction of β-catenin/TCF-mediated transcriptional activity, and this regulatory mechanism has an important impact on clinical outcomes in colorectal cancer. Citation Information: Cancer Res 2009;69(23 Suppl):B49.
PWE-212 Genotype-phenotype correlations in cystic fibrosis patients with pancreatitis highlights an increased likelihood of pancreatic insufficiency and identifies unique mutation pairs that potentially predispose to and protect from pancreatitis
Authors: J Westaby, MA Butt, S Shahid, A Sangwaiya, J Burgess, I Gooding, A Steel, C Wadsworth, P Vlavianos, N Simmonds, D Westaby
Journal: Gut (2015)

<h3>Introduction</h3> 1–2% of cystic fibrosis (CF) patients develop symptomatic pancreatitis. Studies have shown these patients present later in life, are pancreatic sufficient (PS) and have a less severe CF phenotype. This study aimed to evaluate the genotype:phenotype relationship of CF patients with pancreatitis in a tertiary referral centre for CF. <h3>Method</h3> CF patients with a history of pancreatitis were identified from 1216 patients in The Royal Brompton Hospital CF database. Each case was age and sex matched with controls. Clinical information on age, sex, PS status, age when CF diagnosed, CF genotype and mortality were collected. To compare pancreatitis patients with controls, a two tailed t-test (age of CF diagnosis, R117H mutation rate) and Kaplan-Meir survival curves (rate of PI and mortality rates) were utilised. <h3>Results</h3> 37 patients (51% females) with pancreatitis were matched to 135 controls (3:1/4:1). Mean age of CF diagnosis was significantly higher in the pancreatitis group (19yrs) than controls (10.6yrs; p = 0.046). Median time between CF diagnosis and pancreatitis was 17 yrs (range 8–36 yrs). 65% (n = 24) of pancreatitis sufferers were PS at presentation to adult services; of these 63% (n = 15) remained PS until their most recent review or death. Furthermore, 67% (n = 16) suffered with recurrent or chronic pancreatitis. Using Log-rank (Mantal-Cox), there was no difference in survival between pancreatitis patients and controls (p = 0.97). However, pancreatitis patients were significantly more likely to develop PI (p = 0.012). The ^F508:R117H mutation pair was noted more frequently in pancreatitis patients (18.9%;n = 7) than controls (3.8%;n = 5) but not significancantly so (p = 0.56). Interestingly in 43% (n = 16) of the remaining pancreatitis patients, 15 mutation pairs unique to this group were identified. Similarly in controls, 50% (n = 65) had mutation pairs unique to this group. <h3>Conclusion</h3> CF patients who suffer with pancreatitis are significantly more likely to develop PI than those who do not. They present with CF at an older age but this does not affect their survival. The R117H mutation is seen more frequently in the pancreatitis group but not significantly so for this phenotype. We have identified a number of mutation pairs that seem to either predispose or protect CF patients from pancreatitis. <h3>Disclosure of interest</h3> None Declared.