tbuckley/cabot-search huggingface dataset:
P3-05-10: Standardized Quantitative Methods for Investigating the Intratumor Heterogeneity of HER2 in FFPE Breast Cancer Specimens Utilizing the Vectra System, inForm and AQUA Technology.
Authors: CC Hoyt, MD Gustavson, WL Davis, KA Lane, CG Scott, Jr LL Graves,
Journal: Cancer Research (2011)

Abstract Background: While intratumoral heterogeneity of HER2 gene expression is well documented, the HER2 intratumor protein expression heterogeneity and its clinical relevance is largely unknown but generally believed to be worth of investigation to ascertain its impact on HER2 targeted treatment outcome. Methods for investigating intratumor protein expression heterogeneity must preserve tissue architecture yet provide quantitative protein measurement. Immunohistochemistry (IHC) generally lacks standardization and quantitative capabilities and furthermore, current scoring methods do not account for, or report, heterogeneity. Robust and automated methods for characterizing and quantfication of heterogeneity are needed. Material and Methods: Whole tissue samples stained for HER2 expression by fluorescent quantitative IHC methods were analyzed by digital imaging microscopy (Vectra system with inForm software, Caliper, Hopkinton MA) providing automated pattern-recognition-based selection of area of interest and field of view sampling strategies. Quantitative image analysis (AQUA technology, HistoRx, Branford, CT) for quantitative measurement of HER2 protein expression as well as objective, quantitative determination of heterogeneity were performed. Requirements for percent tumor sampling at high-power to capture heterogeneity were assessed, to support optimization of slide scanning. Results: Heatmap representation of HER2 expression levels, and a statistical heterogeneity score developed based on the Simpson's biodiversity index (Simpson 1949) demonstrate visually as well as quantitatively HER2 heterogeneity in breast cancer tissues. Heterogeneity as a function of % area needed for accurate determination of whole section score along with confidence intervals as a function of percentage tumor analyzed inform appropriate sampling strategies. Conclusion: This study demonstrates the suitability of standardized quantitative methods for measuring heterogeneity and the feasibility of its use in investigations exploring the clinical relevance of HER2 intratumor heterogeneity with respect to both measurement strategies as well as treatment outcome. Through characterization of heterogeneous HER2 expression in tumors and optimized measurement strategies, it should be possible to design optimized treatment strategy aimed at treating the whole tumor as a function of objective quantitative assessment of HER2 expression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-10.
Imipramine in Patients with Chest Pain Despite Normal Coronary Angiograms
Authors: Richard O. Cannon, Arshed A. Quyyumi, Rita Mincemoyer, Annette M. Stine, Richard H. Gracely, Wendy B. Smith, Marilla F. Geraci, Bruce C. Black, Thomas W. Uhde, Myron A. Waclawiw, Kathleen Maher, Stanley B. Benjamin
Journal: New England Journal of Medicine (1994)

Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients.
The representation of egocentric space in the posterior parietal cortex
Authors: J. F. Stein
Journal: Behavioral and Brain Sciences (1992)

The posterior parietal cortex (PPC) is the most likely site where egocentric spatial relationships are represented in the brain. PPC cells receive visual, auditory, somaesthetic, and vestibular sensory inputs; oculomotor, head, limb, and body motor signals; and strong motivational projections from the limbic system. Their discharge increases not only when an animal moves towards a sensory target, but also when it directs its attention to it. PPC lesions have the opposite effect: sensory inattention and neglect. The PPC does not seem to contain a "map" of the location of objects in space but a distributed neural network for transforming one set of sensory vectors into other sensory reference frames or into various motor coordinate systems. Which set of transformation rules is used probably depends on attention, which selectively enhances the synapses needed for making a particular sensory comparison or aiming a particular movement.
Abstract C65: Chemopreventive effects of Brazilian traditional medicine <i>Tabebuia avellanedae</i> on in vitro and in vivo carcinogetic systems.
Authors: Harukuni Tokuda, Akira lida, Nobutaka Suzuki
Journal: Cancer Research (2011)

Abstract As part of an ongoing project to investigate the antitumor and antitumor promoting properties of Tabebuia avellanedae, its dry powder essence and its active compound, 5-hydroxy-2- {(1-hydroxymethyl)-naphtho 2,3-b} furan-4,9-dione (NQ-801) were carried out. Tabebuia avellanedae (Bignoniaceae) (TA), which is native in South America from Brazil to northern Argentina, is well known in traditional folk medicine used for the treatment of various disease during five hundred years. The inner bark of this plant produced in Brazil is distributed in Asia as a herb tea and healthy purpose. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enabled rapid and easy detection of naturally occurring substances(anti-tumor promoters, chemopreventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphoblastoid cells. The percentage of the inhibition of TPA-induced EBV-EA activation for these compounds were from 90% to 40%, at experimental concentrations. In addtion, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA initiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. The control animals exhibited a 100 % papilloma incidence at 20 weeks after promotion. However, treatment with the tested compounds(85 nmol) along with initiator and promoter, reduced the percentage of tumor bearing mice by between 13.3-33.3 at 20 weeks. Employing Western blot analysis studies, we found that H-Ras, MEK and p38 levels observed the effects against carcinogenesis. Base on our data, we suggest that one target of these natural source effect in mouse skin is the modulation of the MAPK signal pathway. These results provide a basis for further development of these botanical supplements for human cancer chemoprevention 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 C65.
DIRECT PROCEDURE COST AND 30-DAY OUTCOMES OF DRUG-COATED BALLOON USE IN FEMOROPOPLITEAL INTERVENTION: INSIGHTS FROM THE XLPAD REGISTRY
Authors: Haekyung Jeon-Slaughter, Atif Mohammad, Donald Haagan, Shirling Tsai, Emmanouil Brilakis, Subhash Banerjee
Journal: Journal of the American College of Cardiology (2016)
Abstract 1663: Identification of interleukin 4 receptor alpha (IL-4Rα) as a biomarker of advanced stage human bladder carcinoma
Authors: Bharat H. Joshi, Pamela Leland, Raj K. Puri
Journal: Cancer Research (2011)

Abstract Previously, we have demonstrated that a variety of human and murine cancer cell lines and tumor specimens overexpress Interleukin 4 receptor alpha (IL-4Rα) chain in vitro and in vivo. We have also shown that cancer cell lines and human bladder tumor specimens express high density IL-4Rα at mRNA and protein levels, which sensitized them in vitro and in vivo to a chimeric fusion immunotoxin consisting of circularly permutated IL-4 and a truncated Pseudomonas exotoxin [cpIL-4(38-37)-PE38KDEL]. In the present study, we have examined the expression of two receptor subunits of the IL-4R complex, IL-4Rα and IL-13Rα1, in 60 human bladder carcinoma tissue microarray (TMA) with different pathological grades by IHC and ISH analyses. The TMA consisted of either grade II papillary transitional cell carcinoma or grade I-III transitional cell carcinoma. By IHC analysis for IL-4Rα, we observed that 52/60 (84%) transitional cell carcinoma samples were ≥2+ staining intensity for IL-4Rα. Interestingly, Grade III TCC specimens were most strongly positive (3+) [18/29 (62%)] compared to Grade II specimens [4/26 (15%)]. Grade 1 specimens showed least positivity [5/5 (100%) and showed only 1+ staining intensity]. ISH results corroborated with the IHC findings, which demonstrated that Grade III tumors were more strongly positive (3+) for IL-4Rα mRNA compared to Grade II specimens [19/26 (73%) Grade III versus 4/26 (15%) Grade II, respectively]. 4/5 (80%) Grade I specimens showed 1+ staining and one sample was weakly positive (+/-). All samples expressed IL-13Rα1 at ≤1+ immunostaining intensity by both IHC and ISH analyses. Additional bladder cancer samples and normal or non-cancerous bladder specimens are being studied for IL-4Rα and IL-13Rα1 expression to confirm our observations. Taken together, these results suggest that IL-4Rα may have a role in disease aggressiveness and may serve as a biomarker of advanced stage disease. 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 1663. doi:10.1158/1538-7445.AM2011-1663
Focal Hepatic Hot Spot From Superior Vena Cava Occlusion Visualized on Ventilation/Perfusion Scintigraphy With Contrast-Enhanced CT Correlate
Authors: Michael Lawrence, David M. Schuster
Journal: Clinical Nuclear Medicine (2016)

A 57-year-old woman with superior vena cava stenosis from repeated central line placements underwent ventilation/perfusion scanning after presenting with pleuritic chest pain. The ventilation/perfusion scan was not characteristic for pulmonary embolus, but perfusion images demonstrated abnormal radiotracer activity within hepatic segment 4, along with extensive collateral vessels as seen on SPECT/CT. Two months later, the patient presented with similar complaints and had a chest CT with contrast to evaluate for pulmonary embolus. This showed occlusion of the superior vena cava and arterial enhancement within segment 4 in a similar distribution to the radiotracer in the perfusion scan.
Pronounced Therapeutic Effect of Samarium 153--Ethylenediaminetetramethylene Phosphonate in an Orthotopic Human Osteosarcoma Tibial Tumor Model
Authors: M. Winderen, I. Kjonniksen, O. Fodstad
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Pronounced Therapeutic Effect of Samarium 153—Ethylenediaminetetramethylene Phosphonate in an Orthotopic Human Osteosarcoma Tibial Tumor Model Get access Mette Winderen, Mette Winderen Affiliations of authors: Department of Nuclear Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Inge Kjønniksen, Inge Kjønniksen Department of Tumor Biology. The Norwegian Radium HospitalOslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar Øystein Fodstad Øystein Fodstad * Correspondence to: Øystein Fodstad, M.D., Ph.D., Department of Tumor Biology. The Norwegian Radium Hospital, 0310 Oslo, Norway. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Pages 221–222, https://doi.org/10.1093/jnci/87.3.221 Published: 01 February 1995
Case 12-1995
Authors: R.M. Black, S.M. Meehan
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 59-year-old man was admitted to the hospital because of possible pneumonia and acute renal failure.He had a 17-year history of non-insulin-dependent diabetes mellitus that had been managed in recent years with glyburide, with reportedly good control; he was known to have retinopathy and had undergone laser treatments 5 years before admission. Two months before admission evaluation elsewhere showed that the 24-hour urinary excretion of protein was 3.7 g; the serum creatinine level ranged between 1.0 and 1.5 mg per deciliter (88 and 130 μmol per liter), and the creatinine clearance was 77 ml per minute. . . .
Focal adhesion kinase overexpression in breast cancer molecular subtypes.
Authors: E Melucci, S Buglioni, A Di Benedetto, R Perrone-Donnorso, F Marandino, B Antoniani, P Avetrani, C Nisticò, P Vici, F Cognetti, A Fabi, M Mottolese
Journal: Cancer Research (2009)

Abstract Abstract #1091 Focal adhesion kinase (FAK) is a protein tyrosine kinase which regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis and is a critical mediator of signalling events between cells and their extracellular matrix.&amp;#x2028; FAK is highly expressed in invasive breast cancer (BC) where its upregulation has been implicated in the acquisition of an invasive tumor phenotype. Hierarchical cluster analysis identified subgroups of BC with separate gene expression profiles which detect four main tumor phenotypes, Luminal A (LA), Luminal B (LB), Basal-like (B), and HER2 subtype (HS) characterized by significant differences in prognosis. Up to now, there are no data concerning FAK distribution within the molecular BC subtypes. In this study FAK overexpression was evaluated, by immunohistochemistry (IHC), in a retrospective series of 193 invasive BC surgically treated at our Institution between 2002 and 2005. Associations with conventional pathological factors and with molecular subtypes were analyzed by Multiple Correspondence Analysis (MCA) and chi square test, aimed to determine the impact of FAK high positivity within BC molecular subtypes and to define a biologic profile associated to aggressive bio-pathologic variables such as tumor size (T), nodal status (N), grading (G), p53, Bcl2, Ki-67, p-AKT, p-MAPK . The anti-FAK 4.47 monoclonal antibody was used to detected FAK expression which was scored as high (2 or 3 intensity and ≥ 90% positive cells) or low (0 or 1 intensity and &amp;lt; 90% positive cells).&amp;#x2028; FAK was overexpressed in 41.7% of LA, 70% of LB, in 48.0% of HER2 subtype and 52.2% of Basal-like BC. The relationships among the bio-pathological factors, analysed by MCA, showed that FAK+ is located in the quadrant containing more aggressive tumor phenotypes such as HER2 and Basal like subtypes together with T3-4, N+, G3 and p53+, high Ki67, Bcl2–, p-MAPK+, p-AKT+. Moreover, in LA tumors, FAK overexpression is significantly related to nodal status (p=0.05), grading (p=0.007), p53 nuclear accumulation (p=0.047) and p-AKT overexpression (p=0.001) and it appears to be a useful tool in identifying BC patients at higher risk of progression.&amp;#x2028; The presence of FAK upregulation in LA subtype, may represent a useful tool in identifying those LA patients who would benefit from more aggressive adjuvant therapy. In this context, further investigations are necessary to better assess the prognostic role of FAK overexpression in low risk BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1091.
OP0097 Autoantibodies Precede Interferon Elevation in Pre-Clinical Lupus
Authors: M.E. Munroe, D.A. Fife, J.M. Robertson, Y.D. Zhao, B.F. Bruner, T.B. Niewold, G.C. Tsokos, M.P. Keith, J.B. Harley, J.A. James
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Determining processes that lead to clinical illness in systemic lupus erythematosus (SLE) years before diagnosis would provide insight into the fundamental origins of SLE pathogenesis. <h3>Objectives</h3> This study evaluates the temporal relationship between autoantibody production, interferon (IFN) levels and the onset of SLE. <h3>Methods</h3> Serial sera from 56 pre-clinical SLE cases leading up to SLE classification (average timespan=4.3 years) and matched healthy controls were obtained from the Department of Defense Serum Repository. Sera samples were tested for autoantibodies (BioPlex2200), IFN-α activity, and soluble inflammatory mediators, including IFN associated chemokines and BLyS (B lymphocyte stimulator). Temporal relationships between IFN activity and autoantibody positivity were determined and confirmed using Path analysis. <h3>Results</h3> Serum IFN-α activity scores, as well as IFN-correlated (<i>p&lt;0.001</i>) soluble mediators IFN-γ, IP-10, and BLyS levels increase in patients leading up to SLE disease classification (<i>p≤0.01</i>). IFN activity positive individuals have an increased number of autoantibodies compared to IFN activity negative individuals (<i>p&lt;0.05</i>). Autoantibodies accumulate prior to or concurrent with increases in IFN activity in 84% of IFN positive cases. Of the 3 models of IFN vs. autoantibody positivity determined via Path analysis (autoantibody 1st, IFN activity 1st, or concurrent), autoantibody positivity prior to IFN activity ranked first, irrespective of whether DNA- or RNA-binding autoantibodies were present, as assessed by both Akaike9s information criterion (AIC) and root mean square error of approximation (RMSEA). <h3>Conclusions</h3> That autoantibodies accumulate prior to the increases in IFN activity levels suggests that the elevated IFN activity observed in SLE patients is a consequence of pre-clinical immune system perturbations. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3402
Fighting Cancer with Cigarette Taxes
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Fighting Cancer with Cigarette Taxes Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 10, 22 May 1989, Pages 726–728, https://doi.org/10.1093/jnci/81.10.726 Published: 22 May 1989
Abstract LB-329: Copy number variations associated with hereditary breast and colorectal carcinomas
Authors: Francine B. Abreu, Erika Maria Monteiro Santos, Benedito Mauro Rossi, Maria Isabel Achatz, Ana Cristina, Victorino Krepischi, Luiz Paulo Kowalski, Ricardo Renzo Brentani, Silvia Regina Rogatto
Journal: Cancer Research (2011)

Abstract Breast and colorectal cancer are the most common malignant neoplasia in the world. In Brazil, breast cancer is the first malignant neoplasia and colorectal cancer, the third. It is estimated that among 5–10% of all cancer cases are hereditary. Copy number alterations (CNVs) may affect genes associated to cancer, providing an explanation for high risk cancer families. In this study, 57 individuals with Hereditary Breast and Colorectal Carcinoma were screened for BRCA1, BRCA2, CHEK2, TP53, MLH1 and MSH2 mutations by Sanger's sequencing method. In addition, copy number alterations were evaluated by array comparative genomic hybridization (aCGH) using a platform of 4×180K (Agilent). The data were compared with the Database of Genomic Variations (DGV;http://projects.tcag.ca/variation/) and with a reference dataset obtained from 82 healthy Brazilian individuals. Genomic data were extracted and flagged with Feature Extraction software and analyzed using Genomic Workbench Standard 5.0.14, statistical algorithm ADM2 and sensitivity threshold of 6.7. Alterations identified in more than 5% of the control women were excluded from both groups. The patients were divided into two groups: 28 patients with breast or colorectal cancer (group 1) and 29 women with breast and colorectal carcinoma (group 2). Sixteen relatives from seven patients were also evaluated by aCGH. All patients were negative for BRCA1, BRCA2, CHEK2, TP53, MLH1 and MSH2 pathogenetic mutations. However, the aCGH analysis detected a total of 569 chromosomal alterations in healthy Brazilian dataset (in average 6.8/individual), 170 CNVs (in average 6.1/individual) in group 1, and 232 (in average 8.0/individual) in group 2 patients. Forty-five and 63 chromosomal regions altered were detected in group 1 and 2, respectively. Nineteen chromosomal alterations were common to both groups. Mapped on these regions altered, it was identified 28 microRNAs. Ten specific chromosomal alterations were found in patients and their relatives; seven of them were losses involving genes not previously described in breast and colorectal carcinomas patients. Our results suggest that these chromosomal regions harbor genes associated with Hereditary Breast and Colorectal Carcinomas. Financial Support: FAPESP (2008/57887–9) and CNPq (57589/2008–9) 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 LB-329. doi:10.1158/1538-7445.AM2011-LB-329
Biotech Firms Concerned About Drug Pricing Issues
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Biotech Firms Concerned About Drug Pricing Issues Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 24, December 1993, Pages 1986–1987, https://doi.org/10.1093/jnci/85.24.1986 Published: 01 December 1993
AB0320 Tocilizumab improves left ventricular mass and cardiac output in patients with rheumatoid arthritis
Authors: K. Kume, K. Amano, S. Yamada, T. Kanazawa, H. Ohta, K. Hatta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatologists need to develop primary prevention strategies for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. We reported that tocilizumab (TCZ) improved arterial stiffness as well as etanercept and adalimumab. There is no evidence that TCZ effects on left ventricular (LV) morphology and function. <h3>Objectives</h3> To study the effect of TCZ plus methotrexate (MTX) on LV morphology and function in MTX resistant active RA patients, in a cohort study design. <h3>Methods</h3> RA patients were eligible if they had active disease despite treatment with MTX. All patients have no steroids, and no previous history of CVD. Consecutive 23 patients with moderate to severe active RA patients (DAS28&gt;3.2) despite MTX were received TCZ plus MTX. LV morphology and function was assessed with cardio-MRI at baseline and 24 weeks follow-up. Cardiovascular risk factors and clinical data were collected at regular visits. <h3>Results</h3> 21 patients completed 24 weeks. Left ventricular mass index (LVMI) was attenuated significantly by TCZ (week 0-week24,−18.8±6.9 g/m<sup>2</sup>; p=0.0002). Cardiac output (CO) was attenuated significantly by TCZ (week 0-week24,-0.98± 1.4l/min). DAS28 and CRP improved significantly by TCZ (week 0-week24; DAS28: -2.35±0.85; CRP: 24.3±7.2 mg/l) (<i>p</i>&lt;0.05). Surprisingly, the change of disease activity (DAS 28 and CRP) is no correlation with the change of LVMI or CO in this study. <h3>Conclusions</h3> TCZ improved LVMI and CO in active RA despite. Interleukin (IL) 6 might be an important role of LV hypertrophy. TCZ, anti- Interleukin (IL) 6 receptor antibody, may prevent cardiovascular morbidity and mortality in RA. <h3>References</h3> Kume K, et al. Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimumab monotherapy in rheumatoid arthritis: an open-label randomized controlled trial. J Rheumatol. 2011 Oct;38(10):2169-71. doi: 10.3899/jrheum.110340. Epub 2011 Aug 1.PMID: 21807781 <h3>Disclosure of Interest</h3> None Declared