tbuckley/cabot-search huggingface dataset:
Abstract 558: MEDI3379, a human monoclonal antibody against HER3, suppresses HER3 activity and cell proliferation in both ligand-dependent and independent cancers.
Authors: Carrasco A. Rosa, Leslie Wetzel, Krista Kinner, Hong Chen, Raymond Rothstein, David Tice, Robert Hollingsworth, Philipp Steiner, Zhan Xiao
Journal: Cancer Research (2013)

Abstract HER3 (ErbB3) is a member of the EGFR/HER family of receptor tyrosine kinases (RTK), consisting of EGFR, HER2, HER3 and HER4. Due to its unique kinase-deficient nature, HER3 needs to form heterodimers with EGFR, HER2 or other RTKs to be functionally active. Dimerization is induced by either HER3 ligand (Heregulin, HRG) binding, or overexpression of partner RTKs in a ligand-independent (LI) manner. In both settings, HER3 acts as a critical scaffold coupling the upstream RTKs to efficient PI3K/AKT pathway induction to drive tumor growth and survival. We have developed a potent antagonistic human monoclonal antibody against HER3, termed MEDI3379, and tested it in multiple cancer models with either ligand-dependent or ligand-independent HER3 activities. For ligand-dependent models, we have chosen MDA-MB-175VII, a breast cancer cell-line with known γ-HRG expression, and HMCB, a melanoma cell-line with β-HRG expression. Efficient suppression of cell proliferation by MEDI3379 or 2C2, a precursor of MEDI3379, was observed in both models. This anti-tumor effect is directly due to the abrogation of HER3 activation (as determined by pHER3 formation) and its downstream effector pAKT. Her2-amplified breast cancer models such as BT474 are known to display high ligand-independent HER3 activity that is due to constitutive dimerization of HER2 and HER3. Treatment of BT474 with MEDI3379 led to effective suppression of pHER3, pAKT, and cell-proliferation in vitro. We extended this observation in vivo by exploring the antitumor activity of MEDI3379 in several orthotopic HER2-amplified breast cancer xenografts in nude mice. Consistent with in vitro observations, the BT474 xenograft model responded to MEDI3379 treatment with 65% tumor growth inhibition. In contrast, two published HER3 mAbs (Ab #6 and U1-15) failed to display activity in this ligand-independent model. In conclusion, our findings demonstrated that MEDI3379 is a HER3 antagonist that is effective in models of human cancers driven by both ligand-dependent as well as ligand-independent HER3 activities. Citation Format: Carrasco A. Rosa, Leslie Wetzel, Krista Kinner, Hong Chen, Raymond Rothstein, David Tice, Robert Hollingsworth, Philipp Steiner, Zhan Xiao. MEDI3379, a human monoclonal antibody against HER3, suppresses HER3 activity and cell proliferation in both ligand-dependent and independent cancers. [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 558. doi:10.1158/1538-7445.AM2013-558
885 INTRAHEPATIC MRNA LEVELS OF THE SUPPRESSORS OF CYTOKINE SIGNALLING 1 AND 3 ARE ASSOCIATED WITH CIRRHOSIS BUT NOT WITH TREATMENT RESPONSE IN CHRONIC HEPATITIS C
Authors: S. Clement, S. Pascarella, M.T. Dill, S. Conzelmann, M. Lagging, G. Missale, A.U. Neumann, J.-M. Pawlotsky, S. Zeuzem, P.-Y. Bochud, F. Negro
Journal: Journal of Hepatology (2012)
Noninvasive Diagnosis of Emphysema
Authors: MARTIN KOHLHÄUFL, PETER BRAND, CLEMENS ROCK, THORSTEN RADONS, GERHARD SCHEUCH, THOMAS MEYER, HOLGER SCHULZ, KLAUS J. PFEIFER, KARL HÄUSSINGER, JOACHIM HEYDER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0. 001). Among all lung function parameters under consideration ADAM showed the highest sensitivity and specificity for separating patients with emphysema from those without emphysema (area under the operating characteristics curve: p(ROC), 0.92), followed by ABD (p(ROC), 0.90), a marker for ventilation inhomogeneities. In patients with HRCT-confirmed macroscopic emphysema, peripheral air-space dimensions (EAD) at a relative volumetric lung depth V(pr) of 0.20 measured by ADAM were 155% larger, and bolus dispersion (ABD) at a lung depth of V(p) 600 ml was 53% larger than those observed in patients with other lung diseases (EAD = 0.84 +/- 0.53 mm versus 0.33 +/- 0.10 mm, p < 0.0001; ABD = 706 +/- 154 cm(3) versus 462 +/- 109 cm(3); p < 0.0001). EAD showed a significant correlation with the HRCT visual score (r = 0.78, p = 0.01). ABD showed weak significant correlations with all HRCT parameters under consideration (visual score, pixel density, mean lung density) (r = 0.45 to 0.66; p < 0.05). ADAM and ABD are powerful tools for the noninvasive diagnosis of macroscopic emphysema.
PMO-060 Restoring intestinal continuity after a small bowel infarction reduces the volume and frequency of parenteral nutrition: Abstract PMO-060 Table 1
Authors: A Rajendran, Y K Cheung, J M D Nightingale
Journal: Gut (2012)

<h3>Introduction</h3> A small bowel resection for ischaemia is one of the most common reasons for an admission to an intestinal failure unit (IFU) and for a patient needing home parenteral nutrition (HPN). The aim was to determine the changes in parenteral fluid, sodium and energy given to patients who have had a massive small bowel resection for ischaemia and in whom intestinal continuity is subsequently re-established by anastomosing the duodenum/jejunum to the remaining colon. <h3>Methods</h3> Patients were identified using the IFU database. Case notes were retrospectively reviewed for the fluid, sodium and energy requirements before and after intestinal continuity was restored. Median values of the weekly requirements were calculated for 2 years after the continuity surgery had been performed. <h3>Results</h3> 12 (5M) patients, mean age 51 years (range 30–77). 2 patients died at 12 months (one sepsis, one brainstem stroke) and one patient had not reached 24 months follow-up. The resection was for arterial infarction in eight patients, venous infarction in one patient, volvulus in one patient, incarcerated hernia in one patient and iatrogenic following surgery in one patient. Six patients had a small bowel length of &lt;50 cm, nine patients had colon beyond hepatic flexure (five with ileocaecal valve) and three patients anastomosis to transverse colon. Two patients stopped PN completely at 1 month. These two patients had final small bowel lengths of 90 cm and 260 cm. There was a significant reduction in volume of feed and sodium given t1, 3–6, 12 and 24 months (p&lt;0.05, Wilcoxon matched pairs test). <h3>Conclusion</h3> Restoration of intestinal continuity to bring the colon into circuit results in less parenteral fluid (at least a litre/day) and sodium being needed but not necessarily the amount of energy. The number of nights where PN is required may be reduced in the 2 years after continuity has been restored. <h3>Competing interests</h3> None declared.
Abstract 4813: Modeling interactions between endothelial cells and metastatic breast cancer cells in a three-dimensional culture
Authors: Yamicia Connor, Rania Harfouche, Cassie Liu, Michael Oh, Shiladitya Sengupta
Journal: Cancer Research (2010)

Abstract Standard two-dimensional model systems are limited in their ability to accurately capture the molecular mediators underlying breast cancer, and cannot be used to study interactions between multiple cell types. Previous studies have shown that three-dimensional systems provide a more physiologically relevant platform to study cancer progression in a structurally appropriate context 1. However, these systems do not capture the interactions between tumor cells and the angiogenic component, an essential step in tumor progression2. Here we describe, a novel three-dimensional co-culture system combining angiogenic endothelial cells and breast epithelial cells in a three-dimensional tumor matrix. Endothelial cells underwent angiogenic tubulogenesis on a matrigel matrix. Addition of metastatic green fluorescent protein+ve MDA-MB-231 resulted in a unique phenotype characterized by the alignment of the tumor cells on the endothelial tubes. We demonstrate FAK and B1 integrin signaling are important mediators of the observed phenotypes. Inhibiting FAK-B1 signaling disrupted the architecture, reducing the ability of the MDA-MB-231 cells to migrate and adhere to cultured vessels. Furthermore, treatment with small molecule inhibitors of phosphatidylinositol 3 kinase, LY294002 1.6uM, and mitogen activated protein kinase (MAPK), PD98059 20uM, also perturbed this architecture, indicating that these signaling pathways play a key role in controlling the observed phenotype. Furthermore, the inhibition of the PI3K and MAPK pathways, destroyed the tumor vasculature and inhibited progression and invasion of the MDA-MB-231 by 86% (p&amp;lt;0.001) while enhancing the cells’ susceptibility to the cytotoxic agent doxorubicin. Our study shows that a three-dimensional co-culture system provides a powerful in vitro model system to study the mechanisms underlying tumor metastasis and is a powerful tool to screen combination therapies. Supported by DoD BCRP. 1 Lee GY, et al. Nat Methods. 2007 Apr;4(4):359-65. 2Sengupta S, et al. FASEB J. 2004 Oct;18(13):1565-7. 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 4813.
Abstract 1918: Type 2 diabetes mellitus and colorectal neoplasia risk in Puerto Rican Hispanics: A case-control study
Authors: Yaritza Diaz-Algorri, Dilka Gonzalez, Maria E. Lozada, Jessica Hernandez, Carmen Pedrosa, Doris H. Toro, Marcia Cruz-Correa
Journal: Cancer Research (2011)

Abstract Background: Epidemiological studies have provided inconclusive evidence regarding the potential link between type 2 diabetes mellitus (DM) and colorectal cancer (CRC).The association between type 2 DM and colorectal neoplasia (colorectal cancer and/or adenomas) has not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. Objective: To evaluate the association between type 2 DM and colorectal neoplasia (CRN) in Puerto Rican Hispanic adults enrolled in the studies Epidemiology of Loss of Imprinting in Colorectal Cancer, Familial Colorectal Cancer Registry and the Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: A case-control study at the VA Caribbean Healthcare System. Methods: The case-control study included patients with incident CRN and controls with negative colonoscopy and without previous history of CRC or adenomas evaluated from January 1, 2005 to December 31, 2009. Diagnosis of type 2 DM was established by previous medical diagnosis and/or anti-diabetic medications use. Unconditional logistic regression was employed to estimate the odds ratio (OR) between type 2 DM and CRN using STATA 10.0. Results: A total of 422 participants (mean age 60.8 ± 12.1 yrs., 61.1% males), prevalence of type 2 DM was 26.3%. 276 patients with CRN and 146 controls were evaluated. In the cases, the prevalence of colorectal adenomas was 25.4% (70/276) and the prevalence of colorectal cancer was 74.6% (206/276). Colorectal neoplasia were mostly adenocarcinomas (60.4%), located in the distal colon (37.3%), and with TNM stage III (21.4%). Cases were mostly men (p=0.01), had lower education (p&amp;lt;0.001) and reported lower use of aspirin (p=0.02) compared to the controls. Cases and controls did not differ by median age (p=0.52), first degree of family history of CRC (p=0.27), first degree of family history of DM (p=0.33) or obesity (p=0.73). There were no statistical significant associations between DM and CRN (OR=1.41; 95% CI: 0.74-2.68), DM and CRC (OR=1.70; 95% CI: 0.74-3.87) or DM and colorectal adenomas (OR=1.04; 95% CI: 0.45-2.42) after adjusting for gender, age, education, aspirin use, obesity and study center. Conclusion: We did not observe a statistical significant association between type 2 DM and CRN. Nonetheless, a tendency towards an increase risk of colorectal neoplasia was observed among type 2 DM patients on adjusted analysis. Possible explanation for our lack of association may be related to high prevalence of type 2 DM in cases and controls and/or the high prevalence of obesity in the study sample. 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 1918. doi:10.1158/1538-7445.AM2011-1918
FRI0095 Incidence of Malignancy in Adult Patients with Rheumatoid Arthritis: an Updated Analysis of the Literature
Authors: T. Simon, A. Thompson, K. Gandhi, M. Hochberg, S. Suissa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with RA have been shown to have an increased risk for malignancies compared with the general population.<sup>1</sup> This has raised concerns, particularly with widespread use of immune modulating therapies, including biologic DMARDs. <h3>Objectives</h3> To update the previously published meta-analysis<sup>1</sup> quantifying the incidence of malignancies in patients with RA compared with the general population. <h3>Methods</h3> An updated literature search consistent with and similar to the previous study<sup>1</sup> was conducted. MEDLINE, BIOSIS Previews, Embase, Derwent Drug File and SciSearch databases were searched using specified search terms and predefined inclusion criteria for identification of relevant observational studies from 2007 through 2013 that provide estimates of relative risk of malignancy in patients with RA compared with the general population. Data on overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal and breast) were extracted. Study-specific estimates of relative risk, as measured by standardized incidence ratios (SIRs) relative to the general population were compared with previously published rates. <h3>Results</h3> A total of 7 new publications met the inclusion criteria; 4 reported SIRs for overall malignancy, 3 for lymphoma, 7 for lung, 7 for colorectal and 7 for breast cancer. Compared with the general population, the SIR estimates in patients with RA suggest a modest increased risk in overall malignancy compared with those observed previously (Figure). For the cancer sub-types, patients with RA continue to have an increased risk of lymphoma and lung cancer compared with the general population. This was observed in the previous evaluation of the literature.<sup>1</sup> Most of the SIR estimates represented as data points in the figure for both colon and rectal, and breast cancer continue to show no increase in risk for patients with RA when compared with the general population. <h3>Conclusions</h3> Patients with RA are at an increased risk for lung and lymphoma malignancies. The additional data shown here are consistent with previously reported data. It is important to quantify differences in malignancy rates between non-biologic and biologic DMARD-treated patients with RA to understand the malignancies that may be related to treatment versus underlying disease. <h3>References</h3> Smitten AL, et al. Arthritis Res Ther 2008;10:R45. <h3>Disclosure of Interest</h3> T. Simon Employee of: BMS, A. Thompson Employee of: BMS, K. Gandhi Employee of: BMS, M. Hochberg Grant/research support: NIH, Consultant for: BMS, Eli Lilly Co., EMD Serono Inc., Genentech/Roche, Novartis Pharma AG, Pfizer Inc, UCB Inc, S. Suissa Consultant for: BMS, Genentech, Roche <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1732
Endoscopic resection for diagnosis and endosonographic follow-up of gastric GI stromal tumors larger than 2cm
Authors: Lin Chun-Jung
Journal: Endoscopy (2011)

Background: Gastric subepithelial tumors originated from the muscularis propria (MP) layer are difficult on differenzial diagnosis before surgical resection, even with EUS or EUS-FNA. Although the small gastric GIST (<Q2cm) carried very low malignant progression (Miettinen and Lasota 2006), it is uncertain for the potential malignancy and prognosis in GIST between 2cm and 5cm, without confirmed mitotic rate.
1169 GENERATION OF PERMISSIVE BCLC5 CELL LINES FOR THE STUDY OF HCV REPLICATION: ROLE OF miR122 IN REPLICATION ENHANCEMENT
Authors: M. Coto-Llerena, G. Koutsoudakis, L. Boix, J.M. López-Oliva, C. Fernández-Carrillo, P. Gonzalez, J. Bruix, X. Forns, S. Perez-del-Pulgar
Journal: Journal of Hepatology (2013)
AB0771 Tocilizumab in patients with recent onset polymyalgia rheumatica (PMR) and contraindications to steroid use:
Authors: L. Boiardi, P. Macchioni, M. Catanoso, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Corticosteroids (CS) are the drug of choice in treating polymyalgia rheumatica (PMR). However CS-related adverse events are frequently observed during treatment course. A previous report showed that tocilizumab (TCZ) is able to control signs and symptoms of PMR patients who are resistant to CS therapy (1). <h3>Objectives</h3> To evaluate the safety and efficacy of TCZ in the treatment of recent onset (PMR) in patient with contraindications to the use of CS. <h3>Methods</h3> Two patients entered the study. According to treatment protocol TCZ was administered at a dose of 8 mg/kg ev every four weeks for 6 months without use of CS. Pts were evaluated at baseline and then every month for the following measures of disease activity: pain (10 cm VAS), patient and physician global assessment, HAQ, duration of morning stiffness, ESR and CRP. Disease activity score (DAS) according to Leeb were calculated at every visit (2). Serum IL-6 and serum IL-6 receptor was evaluated at each visit. Patient were permitted to initiate CS in the case of absent or incomplete response to TCZ. The presence of adverse events were considered at every visit. <h3>Results</h3> Table 1 shows demographic characteristics of the two female patients and the main outcome measures at 6 months as percentage variation (Δ) 6 month study visit vs baseline. The first patient had disease recurrence 6 months after the end of the TCZ treatment course. The second one was treated with CS (prednisone 4 mg/day) after two infusion of TCZ because of a partial response (Leeb's DAS 37.01). No adverse event was observed during TCZ therapy. TCZ treatment induced a marked increase of serum IL-6 and serum IL-6 receptor concentration. <h3>Conclusions</h3> In patients with recent onset PMR, TCZ treatment seems to be able to partially control PMR symptoms without use of CS. In our two patients TCZ was well tolerated. As observed in other diseases TCZ treatment induced a marked increase of serum IL-6 and serum IL-6 receptor concentration. <h3>References</h3> Hagihara K, Kawase I, Tanaka T, Kishimoto T. Tocilizumab ameliorates clinical symptoms in polymyalgia rheumatica. J Rheumatol. 2010;37:1075-6. Leeb BF, Bird HA. A disease activity score for polymyalgia rheumatica. Ann Rheum Dis. 2004;63:1279-83. <h3>Disclosure of Interest</h3> None Declared
PREDICTION OF MODE OF DEATH IN PATIENTS WITH CHRONIC HEART FAILURE BY CARDIAC I-123 METAIODOBENZYLGUANIDINE IMAGING: A PROSPECTIVE COMPARATIVE STUDY WITH FRAGMENTED QRS COMPLEXES
Authors: Masahiro Seo, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Satou, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2015)
Researchers Look For Ways To Overcome Multidrug Resistance
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Researchers Look For Ways To Overcome Multidrug Resistance Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 9, 1 May 1991, Pages 599–601, https://doi.org/10.1093/jnci/83.9.599 Published: 01 May 1991
Proximal duodenal obstruction - Bouveret's syndrome revisited
Authors: C. Werner, F. Graepler, J. Glatzle, D. Stüker, T. Kratt, J. Schmehl, M. Bitzer, A. Königsrainer, N. Malek, M. Goetz
Journal: Endoscopy (2013)

A 62-year-old man presented to our emergency department with acute epigastric pain and vomiting. He was found to have elevated markers of inflammation with a white cell count of 16.1 × 109/L and C-reactive protein (CRP) of 30 mg/L (normal < 5 mg/L), impaired renal function with a creatinine of 1.8 mg/dL, and evidence of mild cholestasis with a bilirubin of 1.3 mg/dL and γ-glutamyltransferase (GGT) of 78 IU/L.
A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016
Authors: Su Jong Yu
Journal: Clinical and Molecular Hepatology (2016)

Many guidelines for hepatocellular carcinoma (HCC) have been published and updated globally. In contrast to other cancers, there is a range of treatment options for HCC involving several multidisciplinary care of the patient. Consequently, enormous heterogeneity in management trends has been observed. To support standard care for HCC, we systematically appraised 8 current guidelines for HCC around the world, including 3 guidelines from Asia, 2 from Europe, and 3 from the United States according to the selection criteria of credibility influence and multi-faceted. After a systematic appraisal, we found that these guidelines have both similarities and dissimilarities in terms of surveillance and treatment allocation recommendations due to regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a solid, high level of evidence. In contrast to other tumors, the geographic differences in tumor biology (i.e., areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, medical technology, accessibility to treatment, health systems, and health resources) make it impractical to have an internationally universal guideline for all patients with HCC. Although Barcelona-Clinic Liver Cancer (BCLC) has long been dominant system for treatment-guiding staging of HCC, many Asia-pacific experts do not fully agree with its principle. The concepts of BCLC, for surgical resection or other locoregional therapy, are considered too conservative. Asian guidelines represent consensus about surgical resection and TACE indication for more advanced tumor.
Use of the Megathrombocyte as an Index of Megakaryocyte Number
Authors: Sudershan K. Garg, Edward L. Amorosi, Simon Karpatkin
Journal: New England Journal of Medicine (1971)

Abstract An excellent correlation was obtained between the percentage of large platelets, or megathrombocytes, and the number of bone-marrow megakaryocytes in 115 patients with both thrombocytopeni...
Case 24-1999
Authors: Lawrence D. Recht, James M. Primavera
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 65-year-old man was admitted to the hospital because of impaired cognition and a gait disorder.The patient had been well until 10 months earlier, when he began to have a diffuse, mild, nonprogressive headache that was continuous. Six months before admission, hematochezia led to the discovery of carcinoma of the sigmoid colon. One month later, the tumor was resected at another hospital; there was no evidence of hepatic metastasis. Microscopical examination of the specimen revealed adenocarcinoma, grade 2 of 4, that had penetrated the serosa and metastasized to 1 of 12 pericolonic lymph nodes. An induction . . .