tbuckley/cabot-search huggingface dataset:
Abstract 4924: Connective tissue growth factor (CTGF) mediates metastases of breast cancer stem cells.
Authors: Jing Zhong, Xiaoping Zhu, Hong Zhao, Stephen Tc Wong, Stephen Tc Wong
Journal: Cancer Research (2013)

Abstract Background: Recent studies on various cancer types suggest that the mere acquisition of cancer stem-like cells (CSCs) phenotype is not sufficient to confer metastatic potential. Epithelial-Mesenchymal transition (EMT) has been implicated in enhancing cancer metastatic dissemination, and generating CSCs, which may be a key determinant in imparting metastatic potential to CSCs. Our goal is to determine the metastasis potential of the CSCs generated from EMT and to explore critical molecules involved in the metastatic cascade process. Experimental design and methods: The metastatic ability of the EMT-generated-CSCs (HMLE-Ras-Snail) and the control cell line (HMLE-Ras-vector) were compared by the migration, invasion and chemotaxis assays in vitro, as well as experimental and spontaneous metastases mice models in vivo. A microarray gene profiling analysis was performed to explore signaling molecules involved in the EMT-CSCs-metastasis. Functional assays were used to verify the identified molecule in vitro and in vivo. Results: HMLE-Ras-Snail cells showed significant high migration, invasive behaviors, especially under the different organ protein as chemo-attractants (lung, brain and liver). Experimental lung and brain metastasis mice study showed a significant enhancement of tumor extravasation and outgrowth of HMLE-Ras-Snail cells compared with the control cells. Spontaneous metastases mice studies showed that 7 out of 9 mice developed lung metastasis, and 2 out of 9 with brain metastasis for the HMLE-Ras-Snail model, while none of the HMLE-Ras-vector cell-injected mice were detected with metastases. Two-photon live animal imaging also showed enhanced single cell adhesion and movement in the lung or brain micro-vessels in the HMLE-Ras-Snail cell-injected mice. The differential gene expression analyses and western blot indicated that the CTGF is up-regulated in the EMT-generated-CSCs. Knockdown of CTGF in the HMLE-Ras-Snail cells not only enhanced the expression of epithelial marker and decreased the mesenchymal marker, but also decreased the in vitro proliferation, migration, invasion, mammosphere formation and in vivo lung metastases. Conclusions: CTGF may play an important role in breast cancer metastasis, with enhancing cell motility, invasiveness and also give cell self-renewal stem cell-like characteristic to facilitate EMT-CSCs-Metastasis. Citation Format: Jing Zhong, Xiaoping Zhu, Hong Zhao, Stephen Tc Wong, Stephen Tc Wong. Connective tissue growth factor (CTGF) mediates metastases of breast cancer stem 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 4924. doi:10.1158/1538-7445.AM2013-4924 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4169: Systematic in vivo analysis of PI3K pathway aberrations in a mouse model of invasive lobular carcinoma
Authors: Martine Van Miltenburg
Journal: Cancer Research (2016)

Abstract Invasive lobular carcinoma (ILC) is the second most prevalent breast cancer subtype, which develops in the milk-producing glands (lobules) and metastasizes to distant organs. A key feature of ILC is loss of the CDH1 gene, encoding the E-cadherin cell-cell adhesion receptor. Though E-cadherin is thought to be a tumour suppressor, it is interesting to note that mammary-gland specific deletion of E-cadherin does not lead to tumour development indicating that other factors are necessary for the induction of ILC. Recent data from the cancer genome atlas reveals that besides E-cadherin loss, mutations in PIK3CA, and to a lesser extent PTEN, TBX3, and FOXA1 were found as ILC enriched features. These data implicate PI3K signaling as a driving force in ILC development. Using our in-house established GEMM-ESC strategy, we have developed innovative mouse models for ILC to study novel aspects of the functional interplay between E-cadherin and PI3K in ILC development. We have discovered an intriguing new interplay between these components in which E-cadherin loss suppresses growth of normal mammary epithelium, which appears to involve senescence, whereas it effectively accelerates tumor growth in a PIK3CAmutant background. Therapeutically, PIK3CAE545K and AKTE17K ILCs were sensitive to AZD8055, an mTOR inhibitor, and BKM120, a PI3K 110α inhibitor in vivo, indicating that PI3K signaling is required for their tumor maintenance. Currently, we are dissecting the sensitivity of ILCs displaying PIK3CAE545K or AKTE17K mutations, and PTEN loss, to a large panel of inhibitors, which will likely provide new clinical options. Citation Format: Martine Van Miltenburg. Systematic in vivo analysis of PI3K pathway aberrations in a mouse model of invasive lobular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4169.
OP0275 Development of A Composite Outcome Measure for Systemic Sclerosis-Related Interstitial Lung Disease
Authors: E. Volkmann, N. Li, D. Tashkin, D. Furst, R. Elashoff
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> While clinical trials in systemic sclerosis-related interstitial lung disease (SSc-ILD) have traditionally used FVC% predicted as the primary outcome, combining individual outcomes may lead to a more comprehensive measure of treatment response and minimize the risk of type 1 error from multiple testing of secondary outcomes. <h3>Objectives</h3> To develop a composite outcome measure to assess treatment response in patients with SSc-ILD. <h3>Methods</h3> Using data from the SLS-I study comparing cyclophosphamide treatment versus placebo in 158 patients with SSc-ILD, we entered the following outcome variables into an univariate analysis to determine which variables had a significant treatment effect at 12 months: FVC% predicted, TLC% predicted, computer-based quantitative lung fibrosis in the zone of maximum fibrosis (QLF-ZM) score from thoracic high-resolution computed tomography scans, transitional dyspnea index (TDI), visual analogue scale for breathing (VAS-B). We subsequently combined the variables with significant treatment effects in a principal component analysis to assess the difference between treatment groups. <h3>Results</h3> Of the 158 patients, 83 had complete outcome data and were included in this analysis. The univariate analysis demonstrated significant treatment effects for the following individual outcome variables (estimate [SE]; p-value): QLF-ZM (-10.5 [3.6]; p=0.005), TDI (3.7 [0.8]; p&lt;0.0001). There was a trend for a significant treatment effect using FVC% predicted as the outcome in the univariate analysis (estimate 3.6 [SE 1.8]; p=0.05). The regression model with the first principal component for TDI and QLF-ZM as the composite outcome demonstrated a significant treatment effect favoring cyclophosphamide (Estimate 0.7 [SE 0.2]; p=0.001). Adding FVC% predicted to the composite outcome model did not change the overall treatment effect. <h3>Conclusions</h3> The composite outcome comprised of QLF-ZM and TDI demonstrated a significant treatment effect favoring cyclophosphamide for the treatment of SSc-ILD. The treatment effect observed from using the composite outcome was more significant than the effect observed using FVC %predicted. These findings suggest that combining a patient-reported outcome with a structural outcome into a single measure may serve as a more robust measure of treatment response compared with FVC alone. This model requires validation using another dataset. <h3>Acknowledgements</h3> The Specialty Training and Advanced Research (STAR) Program at the David Geffen School of Medicine at UCLA supports the first author. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2068
High Titers of Cytopathic Virus in Plasma of Patients with Symptomatic Primary HIV-1 Infection
Authors: Stephen J. Clark, Michael S. Saag, W. Don Decker, Sherri Campbell-Hill, Joseph L. Roberson, Peter J. Veldkamp, John C. Kappes, Beatrice H. Hahn, George M. Shaw
Journal: New England Journal of Medicine (1991)

Primary infection with the human immunodeficiency virus (HIV-1) frequently causes an acute, self-limited viral syndrome. To examine the relations among viral replication, the immune response of the host, and clinical illness during this initial phase of infection, we undertook a quantitative, molecular, and biologic analysis of infectious HIV-1 in the blood and plasma of three patients with symptomatic primary infection and of a sexual partner of one of them.
Factors influencing the miss rate of polyps in a back-to-back colonoscopy study
Authors: A. Leufkens, M. van Oijen, F. Vleggaar, P. Siersema
Journal: Endoscopy (2012)

<b>Background and study aims: </b>In patients undergoing colonoscopy, 22 % – 28 % of polyps and 20 % – 24 % of adenomas are missed. It is unclear which factors contribute to polyp miss rates, but colorectal cancer detected within 3 years after colonoscopy may originate from missed lesions. The aim of the current study was to determine patient- and polyp-related factors that influence the miss rates of polyps and adenomas during colonoscopy. <b>Patients and methods: </b>Data from 406 patients were obtained from a multicenter, randomized back-to-back colonoscopy study investigating the Third Eye Retroscope (TER) in improving polyp detection rate by visualizing hidden areas such as folds and curves. Patients were randomized to undergo standard colonoscopy followed by colonoscopy with TER, or vice versa. Miss rates were calculated for all polyps and adenomas. All lesions were categorized for size and location within the colon/rectum. Odds ratios (ORs) were computed using adjusted logistic regression models to identify factors independently associated with missed lesions. <b>Results: </b>The miss rate was 25 % (150 /611) for all polyps and 26 % (90 /350) for adenomas. Miss rates were significantly lower (21 % vs. 29 %) in patients randomized to TER as the first procedure (<i>P</i> < 0.03). Taking all groups together, > 2 polyps compared with ≤ 2 polyps detected during the first colonoscopy increased the risk of missing additional polyps (adjusted OR = 2.83; 95 % confidence interval [CI] 1.22 – 6.70). Adenomas in the left colon compared with adenomas in the right colon were also more frequently missed (adjusted OR = 1.65; 95 %CI 1.06 – 2.58). <b>Conclusions: </b>A quarter of polyps were missed during colonoscopy. Physicians should be aware that the risk of missing a polyp is related to patient factors (presence of > 2 polyps) and polyp factors (left colon location).
The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference
Authors: Claire M Nolan, Louise Longworth, Joanne Lord, Jane L Canavan, Sarah E Jones, Samantha S C Kon, William D-C Man
Journal: Thorax (2016)

<h3>Background</h3> The EQ-5D, a generic health status questionnaire that is widely used in health economic evaluation, was recently expanded to the EQ-5D-5L to address criticisms of unresponsiveness and ceiling effect. <h3>Aims</h3> To describe the validity, responsiveness and minimum important difference of the EQ-5D-5L in COPD. <h3>Methods</h3> Study 1: The validity of the EQ-5D-5L utility index and visual analogue scale (EQ-VAS) was compared with four established disease-specific health status questionnaires and other measures of disease severity in 616 stable outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were measured in 324 patients with COPD before and after 8 weeks of pulmonary rehabilitation. Distribution and anchor-based approaches were used to estimate the minimum important difference. <h3>Results</h3> There were moderate-to-strong correlations between utility index and EQ-VAS with disease-specific questionnaires (Pearson9s r=0.47–0.72). A ceiling effect was seen in 7% and 2.6% of utility index and EQ-VAS. Utility index decreased (worsening health status) with indices of worsening disease severity. With rehabilitation, mean (95% CI) changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to 10.7), respectively, with standardised response means of 0.39 and 0.44. The mean (range) anchor estimates of the minimum important difference for utility index and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively. <h3>Conclusions</h3> The EQ-5D-5L is a valid and responsive measure of health status in COPD and may provide useful additional cost-effectiveness data in clinical trials.
Tc-99m Tetrofosmin Accumulation in Lung Cancer and Its Metastases
Authors: ORAZIO SCHILLACI, ROBERTA DANIELI, ROSANNA TAVOLARO, FRANCESCO SCOPINARO
Journal: Clinical Nuclear Medicine (1997)

Tc-99m tetrofosmin is a new myocardial-perfusion imaging agent that also has been used in the detection of various tumors. In this case, Tc-99m tetrofosmin imaging was performed in a patient with adenocarcinoma of the left lung. Increased uptake was observed in the primary tumor site and in its metastatic lesions (right mediastinal lymph nodes and brain). The primary tumor and its brain metastasis had been previously detected by chest x-ray and CT. Mediastinal lymph node involvement was later confirmed by mediastinoscopy. These findings suggest a possible role for Tc-99m tetrofosmin as a noninvasive method to evaluate patients with lung cancer.
Abstract 3602: Effect of alcohol on DB[a,l]P, an environmental pollutant and a tobacco smoke constituent, on DNA adduct formation in mouse oral tissues.
Authors: Shang-Min Zhang, Kun-Ming Chen, John R. Richie, Ana Calcagnotto, Cesar Aliaga, Arthur Berg, Yuan-Wan Sun, Arun K. Sharma, Shantu Amin, Karam El-Bayoumy
Journal: Cancer Research (2013)

Abstract Alcohol acts synergistically with tobacco smoke to greatly increase the risk of oral squamous cell carcinoma (OSCC) up to 20-fold; the mechanisms of this synergism remain unknown. Research in this area has been hampered by the lack of appropriate animal models that would mimic chronic simultaneous human exposure to alcohol and representative carcinogens in tobacco or tobacco smoke as a whole. Recently, we developed a more relevant animal model (Int. J. Cancer, 2012, 2783-90) and showed that dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke component, induces SCC in oral tissues of mice. We also showed that its diol epoxide metabolite, (±)-anti-DB[a,l]PDE, is a potent and specific carcinogen in tongue and other oral tissues in mice. We hypothesize that chronic alcohol consumption will increase the carcinogenic potency of DB[a,l]P in the mouse oral cavity by multiple mechanisms including the depletion of glutathione (GSH) and increasing levels of covalent DB[a,l]PDE-DNA adducts. As an initial study to test our hypothesis, mice were fed Isocaloric Lieber-DeCarli-type liquid diets formulated by BioServ (Frenchtown, N.J.) with or without ethanol (35% of total calories, increased gradually from 0, 11, 22 to 35%). After 3 weeks, mice were treated with 2 daily doses of DB[a,l]P (240 nmol each) and/or tobacco smoke particulates (TSP, 2R4F, 2.5 mg/mouse). Mice were sacrificed 24 hrs later and DB[a,l]PDE-DNA adduct levels were quantified by our recently developed LC-MS/MS method (Chem. Res. Toxicol. 2011, 1297-303). We showed that alcohol consumption significantly increased the levels of (-)-anti-trans-DB[a,l]P-dA in the absence of TSP (25%) or in the presence of TSP (75%). We also demonstrated that GSH levels in buccal mucosa were decreased (38%) in mice fed with liquid diet (35% calories from ethanol) compared with mice fed with control diet (0.89±0.13 μmol/g vs 1.23±0.17 μmol/g). Collectively, our preliminary results support our hypothesis that alcohol consumption will increase the carcinogenic potency of DB[a,l]P by altering the metabolic detoxification via depleting GSH and increasing DNA damage in oral tissues of mice. Citation Format: Shang-Min Zhang, Kun-Ming Chen, John R. Richie, Ana Calcagnotto, Cesar Aliaga, Arthur Berg, Yuan-Wan Sun, Arun K. Sharma, Shantu Amin, Karam El-Bayoumy. Effect of alcohol on DB[a,l]P, an environmental pollutant and a tobacco smoke constituent, on DNA adduct formation in mouse oral tissues. [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 3602. doi:10.1158/1538-7445.AM2013-3602
Ash-Leaf Spots in Tuberous Sclerosis
Authors: G Kurlemann, G Schuierer
Journal: New England Journal of Medicine (1998)

Figure 1. The skin of a two-year-old boy with mental retardation appears unspotted in a photograph taken in normal daylight (left-hand panel). A photograph taken under Wood's light shows a hypopigmented spot in the shape of a leaf from the mountain ash tree (right-hand panel). Wood's light is a blue light with an emission peak of 360 nm. The blue end of visible light is absorbed by epidermal pigmentation. If there is no epidermal pigmentation in a site, the area will appear nonpigmented as compared with the surrounding skin. Minimally visible hypopigmented spots are more easily visualized with the Wood's . . .
Feasibility of endoscopic ultrasound-guided hepaticogastrostomy in a patient with previous gastric banding
Authors: D. Galasso, E. Bories, F. Caillol, E. Forero Pineros, C. Pesenti, M. Giovannini
Journal: Endoscopy (2013)

Endoscopic ultrasound-guided hepaticogastrostomy (EUS–HGS) was first reported in 2003 [1] [2]. However, reported experience with EUS–HGS is still limited, and therefore we describe an interesting case of EUS–HGS in a 53-year-old male with severe obesity and previous gastric banding who presented with advanced Klatskin tumor.
FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA. A POETIC CONSORTIUM TRIAL
Authors: M. W. Kieran, X. Yao, M. Macy, S. Leary, K. Cohen, T. MacDonald, J. Allen, J. Boklan, A. Smith, K. Nazemi, L. Gore, T. Trippett, J. DiRenzo, A. Narendran, J. Perentesis, S. Prabhu, N. Pinches, N. Robison, P. Manley, S. Chi
Journal: Neuro-Oncology (2014)

BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant ras/raf signaling is involved in tumorigenesis through promotion of cell proliferation, survival, and differentiation in sporadic LGG. Everolimus (RAD001) is a potent and selective inhibitor of mTOR, a downstream element of the ras/raf pathway. The activity, safety and pharmacokinetics of everolimus in pediatric patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric patients with radiographic progressive or recurrent LGGs without neurofibromatosis type I were treated with oral everolimus 5mg/m2/dose once daily. Therapy was provided for 28 days (one cycle) and could be repeated for a total of 12 cycles. Response, as determined by standard 2-D MRI criteria, was assessed for all patients. Pharmacokinetics, pharmacogenetics, pharmacodynamic parameters including inhibition of p70s6 kinase activity, 4E-BP1 phosphorylation inhibition and suppression of cMyc expression, as well as the toxicity profile of everolimus were evaluated. RESULTS: Twenty-three patients with a median age of 9 years (range, 3–17 years) were enrolled, all of whom had received prior chemotherapy (average # regimens = 2.7) including progression after a carboplatin-containing regimen. Median number of cycles of therapy was 10 (range, 1-12). Responses were determined by blinded central review and included 4 patients with PR (>50% decrease) and 13 with stable disease. Six patients had progressive disease by one year. Overall therapy was well tolerated; two patients discontinued therapy due to mouth sores (n = 1) and withdrawal of consent (n = 1). Everolimus PK parameters were similar to those previously reported in both adult and pediatric patients and drug trough levels were maintained above 5ng/ml. Pharmacodynamic analysis demonstrated inhibition of downstream targets of mTOR including phospho-S6 kinase, 4E-BP1 phosphorylation and cMyc expression within 14 days of initiation of everolimus therapy and this inhibition was maintained throughout the treatment period. CONCLUSIONS: Everolimus was well tolerated in pediatric patients with progressive or recurrent LGGs and demonstrated activity in this multiply recurrent/progressive patient population. Incorporation of everolimus into frontline LGG therapy is being proposed. SECONDARY CATEGORY: Clinical Neuro-Oncology.
AB0373 Treatment of primary sjogren’s syndrome-associated lung disease: a prospective study
Authors: H. Gao, J. He, X.-W. Zhang, M. Feng, W. Zhao, Y. Ding, Z.-G. Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary involvement is common in primary Sjögren’s syndrome (pSS), which seriously affects the prognosis and survival rate. However, the treatment of those patients has hardly been explored before. Most studies were specifically designed to evaluate sicca features. <h3>Objectives</h3> To analyze efficacy and safety of corticosteroid therapy combined with hydroxychloroquine (HCQ) or intravenous cyclophosphamide (CTX) in pSS-associated lung disease. <h3>Methods</h3> A total of 15 patients were recruited in the prospective study. Among them, 7 patients took oral prednisone combined with HCQ and 8 patients received oral prednisone combined with intravenous CTX. Prednisone was prescribed initially at a dosage of 30-40mg/day, and was tapered to 7.5mg/d within 4 months. This dosage of prednisone was maintained or tapered for the rest of the follow up as appropriate. HCQ was administered at a dosage of 200mg, twice a day. CTX was administered intravenously at an initial dosage of 400mg, every 2 weeks for 6 months, and then tapered to 400mg every 4 weeks. <h3>Results</h3> Fourteen patients receiving oral prednisone combined with HCQ or intravenous CTX were followed up for 11.57±4.91 months. One patient from CTX group withdrew from the study for stopping DMARDs to have surgery. Six of 7 patients (85.71%) were female of both groups. The mean age was 55.57±14.52 and 55.43±14.33 years old for HCQ group and CTX group, with median disease duration 120 and 180months, respectively. During the follow up, there was evidence of improvement in HRCT for most of the patients, and no obvious deterioration of PFT was observed. One patient in HCQ group presented hypoleukemia, which was ameliorated after reducing to 100mg, twice a day. Two patients had pneumonia and one had herpes zoster virus (HZV) infection in CTX group. No life-threatening side effect was observed in both groups. <h3>Conclusions</h3> Corticosteroid therapy combined with hydroxychloroquine or intravenous cyclophosphamide is administered with a favorable response seen in the majority of patients. This should be further confirmed in a large cohort. <h3>References</h3> Ramos-Casals M, Tzioufas AG, Stone JH, Siso A, Bosch X. Treatment of primary Sjogren syndrome: a systematic review. <i>JAMA</i>. 2010; 304: 452-60. Shi JH, Liu HR, Xu WB, et al. Pulmonary Manifestations of Sjogren’s Syndrome. <i>Respiration</i>. 2009; 78: 377-86. <h3>Disclosure of Interest</h3> None Declared