tbuckley/cabot-search huggingface dataset:
AB0235 Genetic polymorphisms of endothelial nitric oxide synthase (ENOS) and dermic expression of ENOS/INOS in mexican patients with systemic sclerosis. A preliminary report
Authors: M.P. Cruz-Dominguez, M.A. Martinez-Godinez, O. Vera-Lastra, D.H. Montes-Cortes, G. Medina-Garcia, L.J. Jara, A. Miliar-Garcia
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vascular dysfunction usually preceds clinically detectable fibrosis of systemic sclerosis (SSc). Vascular affection occurs more frequently in limited subtype of SSc (lcSSc) than diffuse subtype (dcSSc). The eNOS catalyses the synthesis of nitricoxide (NO), which maintains basal vascular tone andendothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing disease <h3>Objectives</h3> To investigate the prevalence of polymorphisms T-786C and G894T of the <i>eNOS</i> gene and the differential expression of eNOS/iNOS in the skin of SSc patients. <h3>Methods</h3> We included 139 consecutive SSc patients. The genotyping of T-786C and G894T polymorphisms of <i>eNOS</i> gene was performed by <b>Polymerase Chain Reaction Real-Time Assay</b>. The control group comprised 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc). <h3>Results</h3> Revalence of scleroderma was 53.2% lcSSc (74/139) and46.7% (65/139) dsSSc. In control group: the prevalenceof T-786C polymorphismwas TT 68.45%, TC 29.4%, andCC2.22%;for G894T polymorphism was GG 74.1%, GT 23.02%, TT 2.87%.In lcSSc: T-786Cprevalence was TT 65.5%, TC 30.2% and CC 4.3% (OR 1.8, IC 0.4-7.9 associated to SSc); and the G894T prevalencewas GT 74.3%, GT 20.3% and TT 5.4% (OR 1.94, IC 0.54-7.04 associated to SSc).In dcSSc: the T-786Cprevalence was TT 76.6%, TC 20%, and CC 3.3%, and G894Tpolymorphism was GT 82%, GT 18% and TT 0% without association with SSc.The mean relative expression of eNOS was 10.17±15.5 and iNOS of 7.6±13.05 in lcSSc. For dcSSc the mean relative expression of eNOS was 1.74±1.16 and iNOS of 2.1±2.5. 1.08±0.3 y 1.36±0.7 in skin of volunteers of control group. <h3>Conclusions</h3> Genetic polymorphisms of eNOS were not arisk forpresenting systemic sclerosis in this sample.In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. However this increase was more meaningful in the lcSSc subtype of the disease. <h3>References</h3> Kahaleh B. vascular disease in scleroderma: mechanisms of vascular injury. Rheum Dis Clin North Am 2008;34:57-71. A. Dooley, S. Y. Low, A. Holmes, A. G. Kidane, D. J. Abraham, C. M. Black, and K. R. Bruckdorfer Nitric oxide synthase expression and activity in the tight-skin mouse model of fibrosis Rheumatology, 2008; 47: 272 - 280. <h3>Disclosure of Interest</h3> None Declared
Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease
Authors: J. Zidan, I. Dashkovski, A. Hadary, W. Basher, C. Cozacov
Journal: Journal of Clinical Oncology (2004)

655 Background: HER-2 overexpression, a predictive marker of tumor aggressiveness and responsiveness to therapy, occurs in 20–30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 evaluation is done in primary tumor. HER-2 was measured in both primary and metastases to evaluate whether heterogeneity between primary breast cancer and metastatic sites exists in HER-2 overexpression and the effect of HER-2 on treatment decisions. Methods: Biopsies from primary breast cancer and corresponding metastases of 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically (IHC) in all primary and metastatic sites using CB11 monoclonal antibody and DAKO Hercept-Test scoring. Positive results were confirmed by fluorescence in situ hybridization (FISH). Results: Median time from primary tumor to diagnosis of metastases was 4.5 years (range 1–12 years). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (8 of 58 patients). In 1 patient (2%), HER-2 was negative in metastasis but positive in primary. In 7 (12%) patients HER-2 was positive in metastases and negative in primary. Concordance in HER-2 in primary and metastatic sites was found in 50 (86%) of patients (95% CI: 70.6–94.4). Three patients with HER-2 positive in metastatic sites and negative in primary responded to trastuzumab therapy. Conclusions: HER-2 is an important predictive biological marker for treatment of breast cancer. Possible discordance of HER-2 overexpression between primary and metastatic sites should be considered when making treatment decisions of metastatic sites. No significant financial relationships to disclose.
BC2001: A multicenter phase III randomized trial of standard versus reduced volume radiotherapy for muscle invasive bladder cancer (ISCRTN:68324339)
Authors: R. A. Huddart, N. D. James, F. Adab, I. Syndikus, P. Jenkins, C. Rawlings, C. Hendron, R. Lewis, S. Rogers, E. Hall
Journal: Journal of Clinical Oncology (2009)

5022 Background: Radiotherapy (RT) is an alternative to radical cystectomy in the management of muscle invasive bladder cancer. Limitations are probability of attaining and maintaining local tumour control and risk of late bladder toxicity. BC2001 tests whether concomitant chemotherapy (CT) improves loco-regional control and whether RT volume modification reduces late toxicity without detriment to tumour control. Methods: Pts were randomized in a 2x2 factorial design to (i) RT vs RT + concomitant CT (5FU 500mg/m 2 d1–5 wks 1 &amp; 4 + mitomycin C 12mg/m 2 d1) and/or (ii) standard RT to tumour and whole bladder with 1.5cm margin (sRT) vs reduced volume RT (rvRT) where tumour + 1.5cm margin was treated to 100(±5)% target dose and remaining bladder received 80% target dose. RT dose was 55Gy/20F or 64Gy/32F according to local practice. RT volume comparison results (primary endpoint RTOG toxicity at 1 yr) are reported. Target sample size was 480 pts but the RT randomisation closed early due to slow recruitment. Estimated power is 73% (two-sided α = 0.05) to detect a 20% difference in G3/4 toxicity. Results: 219 pts were recruited (108 sRT; 111 rvRT); 49 received neoadjuvant CT; 31 sRT and 33 rvRT were randomised to concomitant CT. Median age was 74 yrs. Median follow up is 36 mths. There was no difference in loco-regional disease-free survival (LRDFS: HR = 1.06, 95% CI: 0.62–1.84) nor overall survival (HR = 0.99, (0.61 - 1.35)) between randomised RT groups. 2yr LRDFS is 71% in both RT groups. 27 (16) sRT vs 32 (15) rvRT pts have had local (invasive) recurrences (p = 0.09); 32 pts have undergone salvage cystectomy. No difference was seen in CTC G3/4 acute toxicity (26% sRT vs 21% rvRT, p = 0.35), RTOG G3/4 toxicity at 12 mths (8% sRT vs 4% rvRT, p = 0.27) nor Lent Som G3/4 toxicity at 12 mths (45% sRT vs 34% rvRT, p = 0.21). Bladder capacity fell significantly in sRT group (mean reduction at 12 mths: 59mls, 95%CI: 47–118mls, p = 0.02) but not in rvRT group. Conclusions: RT in the modern era can attain local control in most patients with T2-T3 bladder cancer. Acute and late toxicity was less than anticipated in both treatment groups. Modifying standard RT volumes had minimal effect on local control and toxicity in this trial. 2 yr toxicity and quality of life data will be presented. No significant financial relationships to disclose.
First report of endoscopic ultrasound-guided cholecystogastrostomy with a Nagi covered metal stent for palliation of jaundice in extrahepatic biliary obstruction
Authors: Praveer Rai, Ankur Singh, Ram Rao, Malay Sharma
Journal: Endoscopy (2014)

Endoscopic ultrasound (EUS)-guided drainage procedures, such as pancreatic pseudocyst drainage, biliary drainage, and gallbladder drainage, are being increasingly performed in specialist centers [1] [2] [3] [4].
Abstract 4117: A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA in lung cancer patients
Authors: Naoko Aragane, Tomomi Nakamura, Kentaro Iwanaga, Akemi Sato, Kazutoshi Komiya, Tomonori Abe, Norio Ureshino, Shinichiro Hayashi, Toshiya Hosomi, Mitsuharu Hirai, Eisaburo Sueoka, Shinya Kimura
Journal: Cancer Research (2011)

Abstract Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) have great response to lung adenocarinoma with EGFR activating mutations, acquired resistance eventually developed. The half of these patients has the gatekeeper T790M mutation of EGFR in lung cancer tissue. A non-invasive mutation detection system is desired considering the difficulty in obtaining tissue specimens during disease progression_the majority of lung cancer recurrences occur in distant sites. We report a novel non-invasive monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect the mutation using plasma DNA. The MBP-QP method is combined with mutated biased PCR and genotyping based on the analysis of a melting curve of probe DNA which is bound to the target mutated site using a fluorescence quenching probe. The detection limit was 2 copies of control plasmid, and 0.2 ng of genomic DNA isolated from a lung caner cell line harboring T790M. 0.3 % mutant plasmid could be detected in the mixture of plasmids inserted with EGFR exon 20 with or without T790M. With this method, T790M mutations were detected in plasma DNA of 50% of patients who acquired resistance, but not in primary EGFR-TKI non-responders, patients responding to treatment, or patients not treated with EGFR-TKI, which is consistent with the clinical course. The non-invasive MBP-QP method enabled us to monitor T790M repeatedly and will be useful for determining appropriate lung cancer treatment strategies in practice. 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 4117. doi:10.1158/1538-7445.AM2011-4117
Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks
Authors: Richard Sherva, Qian Wang, Henry Kranzler, Hongyu Zhao, Ryan Koesterer, Aryeh Herman, Lindsay A. Farrer, Joel Gelernter
Journal: JAMA Psychiatry (2016)

Cannabis dependence (CAD) is a serious problem worldwide and is of growing importance in the United States because cannabis is increasingly available legally. Although genetic factors contribute substantially to CAD risk, at present no well-established specific genetic risk factors for CAD have been elucidated.
P3-03-04: Targeted Modulation of HER Receptor Signaling in Breast Cancer Using miR-21.
Authors: M Aubele, N Ludyga, H Braselmann, MJ Atkinson, G Auer, N Anastasov
Journal: Cancer Research (2011)

Abstract Introduction: MicroRNAs (miRNAs) are multifunctional nucleic acids that regulate the stability and translational efficiency of targeted messenger RNAs. Endogenously altered miRNA levels have been linked in breast cancer to acquired chemoresistance and changed radiosensitivity. Thus the modification of miRNA expression represents an attractive therapeutic strategy. We now show that the targeted inhibition of miR-21 can modify expression of the HER2 receptor in breast cancer. Materials and Methods: Using TaqMan-based technology the expression of five selected miRNAs (miR-7b, miR-10a, miR-17-5p, miR-125a, and miR-21) was investigated in formalin-fixed, paraffin-embedded breast carcinoma tissues expressing different levels of HER2 (n=60). Possible regulation of HER2 was explored in cell lines using lentivirus to stably downregulate or upregulate HER2 and miR-21 expressions. The effects were analyzed using qRT-PCR, Western blots, proliferation and migration assays. Results: In tumor tissues we identified overexpression of miR-10a and miR-21, and underexpression of miR-17-5p and miR-125a in most of the tumor tissue samples. Significant associations (p≤0.05) were found between HER receptor expression and the expression of miR-17-5p and miR-125a, and miR-21 showed correlation with expression of ER and PR. Furthermore, analysis of miR-21 downregulation in breast cancer cell lines showed inhibition of cellular proliferation and HER2 protein synthesis. Additionally, downregulation of HER2 expression decreased miR-21 expression and showed moderate change in cellular proliferation activity. Conclusions: Based on these results we conclude that there is tight interplay between HER2 and miR-21 expression in breast cancer cells. Because miRNAs modulate gene expression we suggest that modulation of miR-21 has the potential to impact tumor therapy by interference with specific signaling pathways. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-04.
Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function
Authors: Jose M. García-Ruiz, Rodrigo Fernández-Jiménez, Ana García-Alvarez, Gonzalo Pizarro, Carlos Galán-Arriola, Leticia Fernández-Friera, Alonso Mateos, Mario Nuno-Ayala, Jaume Aguero, Javier Sánchez-González, Jaime García-Prieto, Beatriz López-Melgar, Pedro Martínez-Tenorio, Gonzalo J. López-Martín, Angel Macías, Braulio Pérez-Asenjo, José A. Cabrera, Antonio Fernández-Ortiz, Valentín Fuster, Borja Ibáñez
Journal: Journal of the American College of Cardiology (2016)

Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (−25 min) or short (−5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.
Identification and validation of seven genes, as potential markers, for the differential diagnosis of small B cell lymphomas (small lymphocytic lymphoma, marginal zone B cell lymphoma and mantle cell lymphoma) by cDNA macroarrays analysis
Authors: C Thieblemont, K Chettab, P Felman, E Callet-Bauchu, A Traverse-Glehen, F Berger, C Dumontet, C Cerutti, L Baseggio, G Salles, C Paultre, B Coiffier, JL McGregor
Journal: Leukemia (2002)
Abstract 1097: <i>Arf</i> induction by Tgf-beta2 is mediated by Smad-2/3 dependent enhancement of <i>Arf</i> transcription
Authors: Yanbin Zheng, Yi D. Zhao, Patricia Chu, Stephen X. Skapek
Journal: Cancer Research (2010)

Abstract The Arf tumor suppressor gene product, p19Arf, is induced in response to certain oncogenic signals to block cancer development and progression. How the oncogenic cues are coupled to Arf promoter activation remains poorly defined, though. We took advantage of the fact that the Arf promoter is strictly controlled during development to investigate the normal regulatory mechanisms. We have recently published that Tgf-beta2 is required for Arf promoter activation at several sites in the developing mouse. To define mechanisms for the regulation, we developed a cell culture-based assay. We now show that Tgf-beta2 (5 ng/ml) induced p19Arf expression in WT mouse embryo fibroblasts (MEFs), enhanced Arf promoter activity in Arf lacZ/lacZ MEFs, and maintained a G1 cell cycle arrest in an Arf-dependent manner. The Arf promoter was also increased by Tgf-beta1, which functionally overlaps with Tgf-beta2, but not by Pdgf-B, a potent mitogen, nor BMP-2, another Tgf-beta superfamily member. To elucidate which pathway mediated the Tgf-beta2 effects, we used a panel of chemical inhibitors of Smad-dependent and -independent pathways. Among them, SB431542, a Tgf-beta type I receptor inhibitor, blocked Smad2 phosphorylation and impeded Tgf-beta2 induction of Arf. Genetic studies confirmed this because RNAi-driven knock-down of Tgf-beta receptor I, Smad2 or Smad3 impaired ArflacZ induction by Tgf-beta2. Further, Tgf-beta2 failed to induce p19Arf in Cre-treated Tgfbr2 flox/flox MEFs, in which Tgf-beta receptor II was deleted. Interestingly, the p38 MAPK inhibitor SB203580 partially impeded Arf induction, showing cross-talk with Smad signals. Chromatin immunoprecipitation revealed that Tgf-beta2 induced the binding of Smad2/3 and RNA Polymerase II to genomic DNA proximal to Arf exon 1 beta. Increased promoter binding preceded the progressively induced Arf mRNA and primary Arf transcripts at 24 and 48 hours, indicating that the induction was due to increased transcription. In summary, our results indicate that Tgf-beta2 induces the Arf promoter via a direct Smad-dependent signaling pathway. This study provides the first evidence that Arf expression is coupled to cell extrinsic signals. We are currently exploring this pathway in other type of cells and testing whether Arf induction by oncogenes also depends on Tgf-beta signaling. 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 1097.
P65 Treating tuberculosis in rural South Africa
Authors: J. N. Periselneris
Journal: Thorax (2011)

<h3>Methods</h3> All the patients admitted to the male and female Tuberculosis wards at a rural hospital in KwaZulu-Natal, South Africa, during a 1-month period were entered into a database. Basic demographic data were collected as well as information about HIV status, medications, complications and 1-month mortality. The area9s tuberculosis (TB) incidence is 1046 per 100 000 and there is an HIV infection rate of 29%. <h3>Results</h3> 70 patients were admitted during the time allocated. 89% were HIV positive. The mean CD4 count of the HIV positive patients was 114, however only 45% of patients were on ARVs at time of admission. 21% of patients had extrapulmonary TB. Only 17% were AFB positive, a further 9% had culture results back, two patients cultured proven multidrug resistant TB. Two patients had a history of completed XDR TB treatment. 10% patients developed drug induced hepatitis, 3% had pneumothoraces, 10% had coexistant renal impairment, 11% had neurological complications. There was a 23% 1-month mortality. No patients who were HIV negative died. 27% died of respiratory failure, 12% had hepatic failure, likely secondary to antituberculous medication. <h3>Discussion</h3> The mortality rate among this population of patients with tuberculosis far exceeds that in the UK. Sadly a lake of resources, HIV coinfection and high rate of drug resistance (10% MDR rate) conspire to make TB a challenging disease to treat in this area of South Africa.
Adductor Insertion Avulsion Syndrome
Authors: A K Singh, C Dickinson, H J Dworkin, P Sagar, S Patel, A Shirkhoda
Journal: Clinical Nuclear Medicine (2001)

SINGH, AJAY K. M.D.,*; DICKINSON, CHRISTINE M.D.,†; DWORKIN, HOWARD J. M.D.†; SAGAR, PALLAVI M.D.‡; PATEL, SNEHA M.D.*; SHIRKHODA, ALI M.D.* Author Information
P1178 TELAPREVIR-BASED TRIPLE THERAPY IN PATIENTS WITH MODERATE FIBROSIS. SPANISH MULTICENTRE STUDY IN CLINICAL PRACTICE
Authors: J. Cabezas Gonzalez, M. Diago, M. Berenguer, T. Broquetas, M.Á. Serra, R. Morillas, J. García-Samaniego, J.L. Calleja, J.J. Sánchez, S. Lens, S. Soto-Fernández, B. Sacristan, I. Fernández, C. López-Nuñez, M. Buti, M. Romero-Gómez, F. Sáez-Royuela, C. Fernández, F. Jorquera, G. Sánchez-Antolín, J.M. Pascasio, A. Cuadrado, M. Hernández-Guerra, J. Crespo
Journal: Journal of Hepatology (2014)
Abstract A2: Differential dependency of human cancer cells on vascular endothelial growth factor-mediated autocrine growth and survival
Authors: Jungwhoi Lee, Jungsul Lee Lee, Hana Yu, Chulhee Choi, Kyungsun Choi
Journal: Cancer Research (2011)

Abstract Analysis using the public microarray database Gene Expression Omnibus indicates significantly higher mRNA expression of VEGF and VEGFRs in colorectal cancer and high-grade astrocytoma but not in hepatocellular carcinoma compared to normal tissue. Human malignant astrocytoma cell lines (U251-MG and U373-MG) and HT-1080 fibrosarcoma cells expressed relatively higher levels of VEGF and VEGFRs compared to hepatocellular and colorectal cancer cell lines. Administration of exogenous VEGF-A induced cell growth in a dose-dependent fashion in astrocytoma and fibrosarcoma cells but not in colorectal and hepatocellular cancer cells. The blockade of VEGF inhibited cell survival only in U251-MG, U373-MG and HT-1080 cells. These results collectively suggest the role of autocrine VEGF signaling in various cancer cells and provide a basis for the variable clinical responses to antiangiogenic therapy observed in different types of malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A2.
The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells
Authors: K Sugita, T Mori, S Yokota, Ma Kuroki, T O-Koyama, T Inukai, K Iijima, K Goi, T Tezuka, S Kojika, K Shiraishi, M Nakamura, N Miyamoto, N Karakida, K Kagami, S Nakazawa
Journal: Leukemia (1999)