tbuckley/cabot-search huggingface dataset:
Abstract 2098: The receptor tyrosine kinase AXL is a target for the human miR-34a microRNA
Authors: Mark Mackiewicz, Konrad Huppi, Robert Cornelison, Natasha J. Caplen
Journal: Cancer Research (2010)

Abstract Determining the protein targets of microRNAs (miRNAs) will be critical to understanding the role these non-coding RNAs play in regulating gene function and what impact they have in cancer biology. In this study, we show by a combination of microarray, Northern, and PCR-based analyses that the human miR-34a miRNA is significantly under-expressed in basal-like breast cancer cell lines exhibiting triple receptor negative characteristics, as compared to a non-tumorigenic mammary epithelial cell line control. Introduction of a synthetic mimic of hsa-miR-34a into MDA-MB-231 cells resulted in a substantial alteration in both the mRNA and protein levels of the receptor tyrosine kinase AXL, 48 hours post-transfection. Furthermore, the transfection of the hsa-miR-34a mimic decreased the migratory potential of these cells in a manner consistent with the function of AXL as a promoter of cell proliferation, invasion, and metastasis in a number of cancer cell types including breast cancer. This observed phenotypic effect supports the hypothesis that miR-34a functions as a tumor suppressor, with the direct translational repression of AXL representing just one of many possible targets that this miRNA regulates. 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 2098.
Passage of a Sialolith
Authors: Makoto Adachi, Masayuki Motohashi
Journal: New England Journal of Medicine (2015)

An otherwise healthy 77-year-old woman presented with a 6-month history of dull pain on the right side of the tongue. Intraoral examination revealed a visible sialolith emerging from Wharton's duct, with marked redness and swelling of the right sublingual caruncle.
Abstract 3954: A role for the cholecystokinin 2 receptor (CCK-2R) in promoting cancer progression
Authors: Cerys M. Mayne, Anna M. Grabowska, Susan A. Watson
Journal: Cancer Research (2010)

Abstract Background and aims: The gastrointestinal (GI) hormone, gastrin, promotes cancer progression and its down-regulation has been linked to reduced cancer stem cell numbers. Gastrin acts through the cholecystokinin 2 receptor (CCK-2R) and its biological effects are blocked by CCK-2R inhibitors. We investigated a potential role for CCK-2R in promoting survival of cancer stem cells using RNAi combined with a sensitive method to detect CCK-2R mRNA. Materials and methods: A panel of cancer cell-lines was used, including GI, glioblastoma and small cell lung cancer (SCLC), with CCK-2R-transfected cells as a positive control. Linear-after-the-Exponential (LATE)-PCR was used to quantify CCK-2R gene expression and its sensitivity compared with a Taqman-based assay. Flow cytometry was used to investigate receptor protein expression. The activity of CCK-2R promoter reporters constructed in pGL4, using between 250 and 2000bp of DNA upstream of the CCK-2R start codon, was quantified using luciferase assays. Results: LATE-PCR for CCK-2R gene expression is 1000-fold more sensitive than the Taqman-based assay. Cell-lines from the panel, including HCT116 (colorectal) and H209 (SCLC), in which CCK-2R mRNA was not detectable by the Taqman assay, were positive using the LATE-PCR. CCK-2R siRNAs resulted in up to 86% knockdown of the receptor in CCK-2R-transfected AGS cells, confirming the specificity of the LATE-PCR. FACS analysis for the CCK-2R protein suggests the presence of a small population of cells within HCT116 (colorectal) and AGS (gastric) cell-lines that express CCK-2R very highly. CCK-2R expression was enriched when cells were grown as colospheres and RNAi demonstrated a role for the CCK2R in promoting cell survival. The CCK-2R promoter constructs were active in cancer cell-lines, indicating that the 250bp proximal to the CCK-2R start codon are most crucial for transcription. However, transcriptional activity did not always correlate with gene expression. Conclusions: LATE-PCR provides a highly sensitive method for detection of genes such as CCK-2R which have important biological functions but low expression. An element just upstream of the CCK-2R transcriptional start site appears to be controlling transcription in cell-lines showing low levels of endogenous expression of the CCK-2R genes, but lack of correlation between the RNA levels and transcriptional activity suggests possible post-transcriptional regulation of this gene. CCK-2R protein expression is elevated in a subset of cells, and may play a role in promoting survival of cancer stem cells. 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 3954.
Abstract 3033: Identification of the MUC16/CA125 interaction network: Results of a high-throughput yeast two-hybrid screening
Authors: Stephan Polterauer, Dharmarao Thapi, Nikolaus Schultz, Ouathek Ouerfelli, Nancy Chen, Nestor Rosales, Xiu Yan, David R. Spriggs
Journal: Cancer Research (2012)

Abstract Background: MUC16 is a well-known serum marker for the diagnosis of ovarian cancer. MUC16 is involved in oncogenic transformation and is associated with migration, invasion, and tumor growth. Due to the large size of this mucin, the interacting partners involved in signaling and transformation have not been investigated. Materials and Methods: We performed a high-throughput yeast two-hybrid screening to investigate putative protein interactions with MUC16. A construct of the MUC16 carboxyterminus, lacking the transmembrane domain (≥mC89), was cloned into the activation domain of the yeast vector pGBKT7. Three different ovarian cancer cDNA prey libraries were tested against the bait μmC89. Of all blue yeast colonies cDNA prey-inserts were analysed with PCR and plasmids were recovered from yeast cultures. Basic Local Alignment Search Tool was used to identify corresponding genes in the GenBank Database. Gene expression- and correlation analyses of human ovarian cancer data of The Cancer Genome Atlas (TCGA) were performed. Immunoprecipitation analyses and magnetic immonoassays were performed to confirm potential interaction partners in human ovarian cancer cell lines. Results: Screening of approximately 30,000,000 colony-forming units identified 238 yeast colonies that maintained promoter activation when cultivated in selective media. PCR and sequencing of cDNA inserts of cultivated yeast colonies nominated 84 candidates as putative binding partners for MUC16. Analysis of TCGA data did not identify direct linkage between mRNA expression of MUC16 and the nominated partners in human ovarian cancers. Based on this analysis and on their biological function, six partners were chosen for further confirmatory analyses: AMHR2, eEF1α, EGF, GAL1, PPP2CB, and SEPT2. Results of the confirmation analyses are pending. Our findings suggest a role of these proteins in regulating MUC16 signaling and transformation mechanisms. Conclusions: We nominate six novel potential partners for interaction with the MUC16 carboxyterminus (≥mC89). These proteins might be involved in ovarian cancer signaling and transformation and might be useful novel targets for vaccines, antibodies and drug inhibitors for the treatment of ovarian cancer. 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 3033. doi:1538-7445.AM2012-3033
FRI0110 Trends in serious infections in rheumatoid arthritis:
Authors: E.L. Matteson, P.D. Fitz-Gibbon, C.S. Crowson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have increased susceptibility for infections, which contributes to increased mortality. <h3>Objectives</h3> To compare the rates of serious infections among patients diagnosed with RA in 1995-2007 to rates previously reported among patients with RA from the same geographical area who were diagnosed in 1955-1994. <h3>Methods</h3> A population-based inception cohort of patients with RA who fulfilled 1987 ACR criteria for RA in 1995-2007 was assembled and followed through their complete medical records until death, migration, or 12/31/2008. The outcome measures included all serious infections (requiring hospitalization or IV antibiotics), which were categorized into the following types: bacteremia/septicemia, septic arthritis, osteomyelitis, pneumonia, lower respiratory tract, urosepsis/ pyelonephritis, skin/soft tissue, gastrointestinal, intra-abdominal and other. Urinary tract infections were excluded. Person-year methods were used to compare rate of infection by type for patients diagnosed in 1955-1994 vs. 1995-2007. <h3>Results</h3> Among the 464 patients with RA diagnosed in 1995-2007 (mean age 56 years; 69% female; mean followup 5.9 years; 2,715 total person-years [py]), 54 had ≥1 serious infection (178 total serious infections). They were compared to 609 patients with RA diagnosed in 1955-1994 (mean age 58 years; 73% female; mean followup 12.7 years; 7,730 total py), of which 290 experienced ≥1 serious infection (740 total serious infections). The rate of serious infections in patients in the 1995-2007 time period (6.6 per 100 py) was less than in the 1955-1994 time period (9.6 per 100 py). The rates of each type of serious infections declined in the 1995-2007 time period compared to the 1955-1994 time period with one exception: the rate of serious gastrointestinal infections (including diverticulitis, gastroenteritis and infective colitis) increased from 0.5 per 100 py in the 1955-1994 cohort to 1.25 per 100 py in the 1995-2007 time period. Despite the decline in rates of serious infections over time, the rate of subsequent infection following the first serious infection increased from 16.5 per 1000 py in the 1955-1994 cohort to 37.4 per 100 py in the 1995-2007 cohort. <h3>Conclusions</h3> With the exception of gastrointestinal infections, the rate of serious infections in patients with RA has declined in recent years. However, subsequent infections are more common in recent years than previously. <h3>Disclosure of Interest</h3> E. Matteson Grant/Research support from: Genentech Pharmaceuticals, P. Fitz-Gibbon Grant/Research support from: Genentech Pharmaceuticals, C. Crowson Grant/Research support from: Genentech Pharmaceuticals
Abstract 1221: Microscopy based high throughput screen for the mechanistic analyses of ErbB2 degradation in response to Hsp90-targeted therapeutics
Authors: Tameka A. Bailey, Haitao Luan, Amy L. Wells, David L. Kelly, Mayumi Naramura, Srikumar Raja, Vimla Band, Hamid Band
Journal: Cancer Research (2012)

Abstract ErbB2 expression is observed in 25 - 30 % of invasive breast cancers and is associated with reduced response to chemotherapy, and shorter time to relapse and reduced overall survival of breast cancer patients. Malignant mammary epithelial cells that overexpress ErbB2 exhibit enhanced proliferation, invasion of mammary tissue and metastasis. The stability of overexpressed mature ErbB2 at the plasma membrane of mammary epithelial cells is critically dependent on its interaction with the chaperone protein, heat shock protein 90 (Hsp90). Thus, Hsp90 promotes the proliferation and survival of malignant mammary epithelial cells and interruption of this interaction is expected to inhibit the growth of ErbB2-overexpressing tumors. 17-AminoAllyl-Geldanamycin (17-AAG), an Hsp90 inhibitor, is a semi-synthetic ansamycin antibiotic currently in phase II clinical trials for breast cancer treatment (www.clinicaltrials.gov). Because it preferentially binds to Hsp90 of the chaperone complex in malignant mammary epithelial cells, treatment of ErbB2-overexpressing breast cancer with 17-AAG is expected to destabilize ErbB2 and inhibit tumor growth. While a number of Hsp90 client proteins have been identified, ErbB2 is amongst the most sensitive to Hsp90 inhibition. These facts provide strong rationale for using 17-AAG as a part of the targeted therapy against ErbB2-overexpressing breast cancer. However the cellular machinery responsible for 17-AAG induced degradation of ErbB2 is not completely understood. At present it is unclear whether internalization of ErbB2 occurs via Clathrin-dependent or -independent endocytosis. Furthermore it is unresolved if the degradation of ErbB2 is dependent upon proteasomal or lysosomal proteolysis. And although C-terminus of Hsp70 Interacting Protein (CHIP) and Cullin 5 were identified as E3 ligases responsible for the ubiquitination of ErbB2, it is unknown if these ligases are the sole E3s responsible for the ubiquitnation of ErbB2. Also vague is if the rerouting of ErbB2 from the recycling pathway to the degradative pathway in response to 17-AAG is exclusively dependent upon ubiquitnation. In this current work we attempt to bridge these critical gaps in our knowledge of the mechanisms of 17-AAG induced degradation of ErbB2 using an automated microscopy-based analysis to identify genes whose siRNA-dependent suppression reduces 17AAG-induced ErbB2 degradation. We expect that this work will identify additional targets for therapeutic intervention and potential biomarkers of response to breast cancer drug therapy with Hsp90 inhibitors. 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 1221. doi:1538-7445.AM2012-1221
IMPACT OF BODY MASS INDEX ON THE ACCURACY OF NT-PROBNP AND BNP FOR PREDICTING OUTCOMES IN PATIENTS WITH CHRONIC HEART FAILURE AND REDUCED EJECTION FRACTION: INSIGHTS FROM THE PARADIGM-HF STUDY
Authors: Wilson Nadruz Junior, Brian Claggett, John McMurray, Milton Packer, Michael Zile, Jean Rouleau, Akshay Desai, Karl Swedberg, Martin Lefkowitz, Victor Shi, Margaret Prescott, Scott Solomon
Journal: Journal of the American College of Cardiology (2016)
Association of Maternal Systemic Lupus Erythematosus with Congenital Complete Heart Block
Authors: Leon Chameides, Raymond C. Truex, Victoria Vetter, William J. Rashkind, Frank M. Galioto, Jacqueline A. Noonan
Journal: New England Journal of Medicine (1977)

Infants born to mothers with disseminated lupus erythematosus occasionally have transient manifestations of the maternal disease. In six infants with congenital heart block born to mothers with systemic lupus erythematosus we postulated a causative relation. In one of the infants a post-mortem study of the conduction system suggested faulty embryonic development of the atrioventricular node with an abnormally thick annulus fibrosus and the effects of early inflammatory changes. Two of the infants had a cardiomyopathy and three, associated congenital heart disease.
FRI0070 Ultrasound doppler activity correlates with systemic autoimmunity and swollen joints in a healthy population at risk for rheumatoid arthritis
Authors: L. Brulhart, E. Ciubotariu, M. J. Nissen, D. Gascon, S. Bas, C. Gabay, A. Finckh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Diagnosing rheumatoid arthritis (RA) early and identifying pre-clinical RA has become a high-stakes undertaking. In RA patients, musculoskeletal ultrasound (US) is more sensitive than clinical assessment for synovitis detection. Whether US is associated with joint involvement in healthy individuals at increased risk for RA is unknown. <h3>Objectives</h3> To assess the value of US to detect specific phases leading to the development of RA in a healthy population at increased risk of RA. <h3>Methods</h3> This study is nested within an ongoing prospective cohort study of healthy first-degree relatives of RA patients (FDRs), who had no established rheumatic disease at inclusion. Data collection included health questionnaires, physical examination and blood tests, including inflammatory markers, HLA-DR genotyping, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP2) levels by ELISA. A standardized US examination was performed according to the OMERACT criteria: synovitis was scored in B-mode and Doppler by a semi-quantitative scale ranging from 0 to 3 on MCPs and PIPs 2 to 5, wrists, olecranon fossa and knees. A composite endpoint of either presence of auto-antibodies (RF-IgM, RF-IgA or anti-CCP2) or at least one swollen joint on physical examination was chosen (group 1<b>)</b>. To test if US was independently associated with the primary end point, we used logistic regression, adjusting for potential confounders such as age, sex, body mass index, Caucasian race and smoking. <h3>Results</h3> One hundred consecutive healthy FDRs were included in this analysis. Baseline characteristics were similar between the two groups except for swollen joints and RF by definition (table 1). Doppler activity was detected significantly more often in group 1 (60%) than in the control group (34%) (p=0.05, adjusted OR: 3.02 (95%CI: 0.82 – 11.1). The mean Doppler score was also significantly higher in group 1: 1.46 compared to 0.62 (p=0.02, adjusted OR: 1.64 (95%CI: 1.01 – 2.66)). However, neither the presence of synovitis grade 2 or 3 on B-mode (47% versus 42%, p=0.76) nor the median B-mode score (6 (IQR: 4 – 9) versus 6 (IQR: 4 – 10), p=0.75) allowed to discriminate the two groups. <h3>Conclusions</h3> Doppler signal on US was associated with the presence of auto-antibodies or clinical signs of synovitis, thus identifying early signs of arthritis in a population at risk to develop RA. <h3>Disclosure of Interest</h3> None Declared
Abstract 4115: Prediction of drug sensitivity based on correlation of molecular and genetic signatures between lung tumor cell lines and tumor tissue samples from NSCLC cancer patients
Authors: Hua C. Gong, David Beer, Sharat Singh, Edvelyn Webster, Gary Meyer
Journal: Cancer Research (2011)

Abstract To establish transition of preclinical response profiles to the subsequent clinical treatment, we profiled pathway activation and genomic signature in tumor cell lines and human tumor tissues. This profiling has allowed us to define molecular pathways and these models may serve as an excellent platform to evaluate the efficacy of targeted therapies. We profiled pathway activation, mutation status, and clinical histology of a panel of representative lung tumor cell lines and 50 human lung adenocarcinoma samples. We cluster patients samples with corresponding tumor cell lines based on such signature and predicted treatment options for the patients based on response to selected candidate treatment of the cell lines. Subsets of patients were identified as candidates to treatment with inhibitors of EGFR, cMET, IGFR, MEK, and PI3K/mTOR. EGF pathways in EGFR mutant cell lines NCI-H1975, HCC827 and NCI-H1650 are highly activated, and those cells were sensitive to inhibitors blocking EGFR signaling. A group of patients were identified to share the similar profiles, and we predict those are candidates for EGFRi therapies. While H1973 is a cMET amplified line with cMET and EGFR activated, patients sharing this genotype may respond to cMET inhibitor treatment. IGF1R expressing A549 and NCI-H358 cells were sensitive to IGF1R inhibition, the patients sharing the similar profile may be candidates to this class of therapies. PI3K/mTOR inhibitor, BEZ 235, effectively inhibited tumor cell growth in most of the cell lines except NCI-H1993 and NCI-H358 cells; while MEK inhibitor PD-325901 was less active in blocking growth of k-RAS mutant cell lines NCI-H460, NCI-H1734, NCI-H358 and A549. Patients with a similar signature may benefit from those treatments. By combining pathway biomarker, mutation status, and clinical features, we were able to cluster clinical patient samples to the lung tumor cell lines and propose treatment options for the patients based on their signature overlap. 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 4115. doi:10.1158/1538-7445.AM2011-4115
FRI0496 Does long distance running cause joint effusion of the knees and ankles? the munich marathon experience
Authors: F. Proft, M. Schramm, F. Mueller, M. Kriegmaier, H. Schulze-Koops, M. Grunke, C. S. Reindl
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The effect of extreme physical exercise on joint effusions is unclear. Previous data are controversial concerning the impact of physical exercise on joint structures. <h3>Objectives</h3> An ultrasound (US) evaluation was performed to investigate if long distance running causes effusion of knees and ankles and enthesitis or tendovaginitis of the patellar tendon or of the tendons around the ankles. <h3>Methods</h3> 119 participants of the Munich Marathon, performing a full distance or half distance marathon in October 2012 were included in the study. Ultrasound examination of both knees and ankles was performed with a gray scale grading from 0-3 between 48 and 16 h before the event (baseline (BL)). In addition, the medial and lateral tendons of the ankles were examined for tendovaginitis and both patellar tendons were examined for enthesitis with power-doppler. The participants were asked to fill out a questionnaire about age, bodyweight, workout and arthralgia or joint swelling. Immediately after the longdistance run a second ultrasound examination of the same structures was performed (follow-up (FU)) and the participants were asked to fill out a second questionnaire about their complaints during the run. <h3>Results</h3> 105 runners completed both ultrasound examinations and questionnaires (61 marathon and 44 half marathon runners). 210 knees were examined, 98 joints (47%) showed an effusion at BL. At follow-up 98 joint effusions were found (p &gt; 0.05). No changes were seen in 135 knees (64%) between BL and FU. In 75 knees (36%), an alteration was detected at FU with 39 knees showed a new or progressive (3 knees) joint effusion, and 36 knees with effusion at BL showed regressive (2 knees) or no effusion any more. Enthesitis of the patellar tendon was detected by power-doppler in one knee at BL and persisted at FU, while new enthesitides at this location were found in 20 examinations (p &lt; 0.001). Of 210 examined ankles, 38 showed an effusion at BL. At FU, 32 ankles with effusion were counted (p &gt; 0.05). 173 (82%) ankles showed a stable finding at BL and FU, while in 37 an alteration was detected. 15 joints showed a new or progressive (1 ankle) effusion, 22 ankles with effusion at BL showed regressive (3 ankles) or dissolved effusion at FU. Only one medial tendovaginitis was detected at FU. <h3>Conclusions</h3> Long distance running does not cause joint effusion in knees or ankles or tendovaginitis of the ankles´ tendons, but a significant increase of enthesitides of the patellar tendons. <h3>Disclosure of Interest</h3> None Declared