tbuckley/cabot-search huggingface dataset:
Abstract P6-05-03: Analysis of College of American Pathologists Recommendations for Reporting HER2 Intra-Tumoral heterogeneity (ITH) on 1329 Breast Cancers
Authors: KH Allison, SM Dintzis, RA. Schmidt
Journal: Cancer Research (2010)

Abstract Background: The College of American Pathologists (CAP) recently published recommendations for reporting intratumoral heterogeneity for HER2 gene amplification in breast cancers. These guidelines recommend reporting cases with between 5-50% of cells with HER2:CEP17 ratios &amp;gt; 2.2 (or &amp;gt; 6 HER2 signals/cell) as “heterogeneous for HER2 gene amplification.” Because these recommendations lack biological and clinical foundation, we applied them to a large number of historical breast cancers and compared the ITH classification to routine FISH Her2 results. Materials and Methods: We collected Her2 and CEP17 counts in 32,116 tumor cells from 1329 consecutive breast cancer cases analyzed by FISH. Data from Excel counting sheets were imported to a SQL Server database for analysis and statistics; histograms and analyses were also performed in Excel. We specifically computed concordances between guidelines for traditional and intra-tumoral heterogeneity (ITH) reporting. Results: 309 of 1,329 cases (23%) met the criteria for heterogeneous HER2 gene amplification by HER2:CEP17 ratio, but &amp;gt; 79% of these were non-amplified by standard FISH reporting criteria. Using Her2 signals per cell, ITH was found in 87 (6.5%) of cases and most of these were not amplified or equivocal by standard criteria. Discussion: A significant proportion of breast cancers contain ITC heterogeneity based on CAP/ASCO reporting recommendations. The majority of these cases are non-amplified without consideration of ITH. Because it is not known whether these patients (who would not currently be treated) would benefit from HER2 targeted therapies, it may be premature to use the ITH reporting recommendations for clinical decision-making. More validation of ITH criteria and biological significance are needed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-03.
P107 Implications of Adverse Drug Reactions to Antibiotics in the Management of Bronchiectasis
Authors: KV Singh, A Sahal, A Sullivan
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Antibiotic adverse reactions present a challenge when choosing appropriate treatment for patients with Bronchiectasis. We explored our data for antibiotic allergy and microbiological resistance in Bronchiectasis patients in a specialist clinic at the Queen Elizabeth Hospital Birmingham. <h3>Methods</h3> We collected retrospective and prospective data on 243 patients from our Bronchiectasis clinic. We limited our microbiological data to colonised or most recent sputum culture. <h3>Results</h3> We have 243 patients on our register. There were 84 (34.6%) males and 159 (65.6%) females. Bronchiectasis was confirmed in 234 patients with CT (Computerised Tomography) scan. The most common aetiology was post-infective. 80 (32.9%) patients had had an adverse drug reaction to at least one antibiotic. 24(9.8%) were allergic to penicillin and 50(20.5%) were allergic to at least one antibiotic. 29 (11.9%) were intolerant of one or more oral antibiotics whereas 18 (7.4%) were intolerant of one or more nebulized antibiotics in this group. Patients with resistant bacteria in their sputum showed a trend towards a greater likelihood of adverse reactions to antibiotics compared to patients with sensitive bacteria (31.5% v 17.8% p Value - 0.05). On subgroup analysis we found that the difference became statistically significant between people infected with resistant versus sensitive Pseudomonas Aeruginosa (46.7% v 42.1% p value–0.031). <h3>Conclusions</h3> This is an interesting observation that patients whose sputum contained resistant organisms were more likely to have had adverse drug reactions to antibiotics. There is likely to be a causal relationship, and further study is required to identify whether the limited range of treatment options for patients with adverse drug reactions leads to a greater chance of antibiotic resistance in colonising organisms in sputum. Antibiotic allergies may have a detrimental effect on the management of patients with Bronchiectasis and therefore a resource implication in the subgroup of patients with adverse drug reactions. Potentially there may be a cost-saving in investigating patient-reported allergies aggressively. <h3>Reference</h3> Antimicrobial therapy for bronchiectasis. O9Donnell AE. <i>Clin Chest Med.</i><i> 2012 Jun;33(2):381–6. doi: 10.1016/j.ccm.2012.03.005. Epub 2012 Apr 24</i> Clinical challenges in managing bronchiectasis<b>. </b>Tsang KW, Bilton D. <i>Respirology. 2009 Jul;14(5):637–50. doi: 10.1111/j.1440–1843.2009.01569.x</i>
Abstract P1-01-21: Sentinel Lymph Node detection after previous breast tumour surgical resection: identification rate and false negative rate through a prospective multi institutional study.
Authors: J-M Classe, N Andrieux, C de Lara Tunon, H Charitansky, F Lecuru, J-L Houpeau, C Faure, P De Blaye, G Houvenaeghel, D Kere, F Marchal, P Raro, C Lefebvre, P-F Dupré, J-F Rodier
Journal: Cancer Research (2012)

Abstract Background: Large multi institutional studies have pointed that previous surgical resection of breast tumours before axillary sentinel node detection (ASLND) was the main criteria of failure of this technique. Screening campaigns provide small tumours and despite efforts to obtain a diagnosis of early breast cancer, this is not always obtained, due to small tumours or false negative results of micro biopsies. The aim of our series was to assess identification rates and false negative rates of ASLND after previous surgical resection of breast tumours. Material and Methods: In a prospective multi institutional setting (14 multidisciplinary teams), we have included patients with a previous breast tumour surgical resection for the diagnosis of infiltrative breast adenocarcinoma. Patients with only a core biopsy and no surgical removal of the tumor before axillary surgery were not included. Each patient underwent a secondary surgical procedure for ASLND and axillary lymphadenectomy, and sometimes a breast secondary surgical procedure for margins. ASLND was performed with the combined method, with blue dye and technetium. Pathology was performed with serial sectioning, eosin safron and immune histo chemistry (IHC). Results: From July 2006 to November 2011, 138 patients where included. The median tumor size was 9mm. Identification rate was 86% (118/138). A macrometastasis was found in 11 cases, in a sentinel node (9), or in a non sentinel node(2). False negative rate was 9% (1 false negative sentinel node with macrometastasis in non sentinel node from lymphadenectomy/11 cases with a macrometastasis in either a sentinel node or a non sentinel node). In 1 case a micrometastasis was found in a sentinel node through IHC, with a macrometastasis in a non sentinel node from lymphadenectomy. Without IHC or without the decision of performing a complementary lymphadenectomy in the case of micrometastasis, the false negative rate would have been 18%. Conclusions: After previous surgical resection of early breast cancer, ASLND remains feasible with a low identification rate of 86%, despite the use of the combined method. The False negative rate is acceptable with the use of IHC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-21.
Abstract 3486: CXCR1 and CXCR2 silencing alters endothelial cell proliferation, migration and capillary tube formation
Authors: Seema Singh, Michelle L. Varney, Rakesh K. Singh
Journal: Cancer Research (2011)

Abstract CXCR1 and CXCR2 are receptors for CXCL-8 and are differentially expressed on endothelial cells, however, their functional significance in angiogenesis remains unclear. In this study, we determined the functional role of these receptors in modulating endothelial cells phenotype by knocking-down the expression of CXCR1 and/or CXCR2 in human microvascular endothelial cells (HMEC-1) using short-hairpin RNA (shRNA). Cell proliferation, migration, invasion and capillary tube formation were carried out in in vitro. Our data demonstrate that knock-down of CXCR1 and/or CXCR2 expression, inhibited endothelial cell proliferation, survival, migration, invasion and capillary tube formation in vitro. Additionally, we examined the mechanism of CXCL-8-dependent CXCR1 and/or CXCR2 mediated phenotypic changes by evaluating ERK phosphorlyation and cytoskeletal rearrangements. We observed inhibition of ERK phosphorylation and cytoskeltal rearrangement in HMEC-1-shCXCR1, HMEC-1-shCXCR2 and HMEC-1-shCXCR1/2 cells. The number of apoptotic cells acquiesced with decreased survival-associated gene expression. Together, these data demonstrate that CXCR1 and CXCR2 expression play a critical role in regulating multiple biological activities in human microvascular endothelial cells. 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 3486. doi:10.1158/1538-7445.AM2011-3486
Abstract 4063: Estrogen receptor alpha functions as an RNA binding protein to regulate GATA3 protein levels: a novel role for ER
Authors: Karen Joyce, Christine Hostetter, George Chamoun, Judith C. Keen
Journal: Cancer Research (2010)

Abstract The role of estrogen receptor alpha (ER) as a transcription factor has been well established. ER transcriptionally activates genes by binding to DNA directly within the gene promoter region or by binding to DNA indirectly through protein-protein dependent mechanisms. Many ER-responsive genes that are activated through ER-mediated transcriptional activation have been identified, including GATA3. While the role of GATA3 in breast cancer still remains largely unknown, numerous reports have shown that ER and GATA3 are coordinately expressed in breast cancer and that ER may play a role in regulating GATA3 expression. A recent report by Eeckhoute et al (2007) has shown that ER transcriptionally activated GATA3 expression in T47D breast cancer cells. Using MCF7 cells, we have recently identified a novel role for ER as an RNA binding protein that binds to GATA3 mRNA. Interestingly, silencing of ER using siRNA probes slightly increased GATA3 mRNA levels, however GATA3 protein levels decreased significantly. This decrease in protein was not due to improper export of GATA3 mRNA from the nucleus to the cytoplasm where protein translation occurs, as GATA3 mRNA expression was equivalent in both the nuclear and cytoplasmic compartments. This suggested that the decrease in protein expression was not due to impaired GATA3 mRNA transport but could be due to impaired protein translation. Since silencing of ER had dramatically different effects on RNA and protein levels, this data suggested that ER protein may function as an RNA binding protein that binds to the GATA3 mRNA to regulate its protein translation. Using biotin pulldown techniques, we found that ER does function as an RNA binding protein by binding directly to a site within a 125 nucleotide region of the GATA3 3‘UTR. This role of ER as an RNA binding protein is consistent with the data of Lanz et al (1999, 2000) that demonstrated that ER protein can bind to an RNA transcript, the steroid receptor co-activator, SRA. When bound to SRA, however, ER did not alter the RNA levels or protein expression of SRA but did result in increased activation of ER. Therefore, our data is the first to identify a novel role for ER as a RNA binding protein that can regulate the protein expression of the RNA transcript to which it is bound. Altering such ER-RNA interactions could potentially provide a new therapeutic avenue for the treatment of breast cancer. 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 4063.
REGIONAL MULTI-LAYER STRAIN MEASUREMENTS USING TRANSTHORACIC ECHOCARDIOGRAM WITH EXERCISE STRESS CAN DETECT CLINICALLY STABLE MYOCARDIAL ISCHEMIC SEGMENTS
Authors: Takeshi Nishi, Nobusada Funabashi, Koya Ozawa, Hiroyuki Takaoka, Masayuki Takahara, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2016)
Visualization of a Supradiaphragmatic Stomach in a Patient with Esophagogastrectomy Who Practiced Urine Therapy During Bone Scan
Authors: K T Yang, T S Lin
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine* and the Division of General Thoracic Surgery,† Changhua Christian Hospital, Changhua, Taiwan Received for publication January 25, 2001. Revision accepted May 16, 2001. Reprint requests: Kuang-Tao A. Yang, Department of Nuclear Medicine, Changhua Christian Hospital, 135 Nan-Shiao Street, Changhua, Taiwan 500, Taiwan. E-mail: [email protected]
Usefulness of Chromosome Examination in the Diagnosis of Malignant Pleural Effusions
Authors: Gordon Dewald, David E. Dines, Louis H. Weiland, Hymie Gordon
Journal: New England Journal of Medicine (1976)

To determine whether chromosome analysis could facilitate the diagnosis of malignant pleural effusions, we examined chromosomes in effusions from 104 unselected patients. An effusion was regarded as malignant if at least three of 30 metaphase cells were hyperdiploid or contained a marker chromosome. Results were compared with standard cytologic diagnoses. All 22 benign effusions were diagnosed correctly by cytologic examination, but one nosed correctly by cytologic examination, but one (acute rheumatoid lung disease) was misclassified as positive by chromosome criteria. Of the 82 malignant effusions, 53 (65 per cent) were diagnosed correctly by cytologic tests, as compared with 58 (71 per cent) by chromosome analysis (P greater than 0.2). Among patients with malignant neoplasms, 13 had leukemia or lymphoma; only four of these (31 per cent) were diagnosed by cytologic tests as compared with 11 (85 per cent) by chromosome analysis (P less than 0.01). The combination of standard cytologic and chromosome analyses correctly identified 83 per cent of the neoplasms, a result significantly better than that with either technic alone (P less than 0.01).
Preliminary Results of “Bonadiuv” Trial: A Single-Blind, Randomized, Placebo-Controlled Study Designed to Evaluate the Impact of Bisphosphonate Treatment on Bone Mineral Density in Osteopenic Women Taking Aromatase Inhibitors
Authors: S. Cecchini, V. Scotti, I. Meattini, M.L. De Feo, C. De Luca, L. Livi, G. Biti
Journal: Annals of Oncology (2013)
AB0110 Iguratimod inhibits rankl-induced osteoclastogenesis in raw264.7 cells
Authors: W. Tan, K. Gan, M. Zhang, X. Feng, F. Wang
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Iguratimod, also named as T- 614, is a member of the family of methanesulfonanilide. We previously reported that Iguratimod is effective and well tolerated for treatment of patients with active RA in a multicenter, randomized, double-blind, controlled trial, which make it develop as a novel disease-modifying antirheumatic drug for RA in China and Japan. Many efforts have been made recently to explore the mechanism of Iguratimod for treatment RA. Growing evidences indicated that Iguratimod could reduce the production of various inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, IL-17, tumor necrosis factor α, and interferon-γ and stimulate osteoblastic differentiation in vitro and in vivo. However, whether iguratimod could affect osteoclastogenesis remain unknown. <h3>Objectives</h3> To study the effect of iguratimod on osteoclastogenesis in osteoclast precursors RAW264.7 cell line. <h3>Methods</h3> Osteoclast differentiation was induced by the receptor activator for nuclear factor κB ligand (RANKL) in RAW264.7 cells in the presence or absence of Iguratimod. Osteoclast formation was evaluated tartrate-resistant acid phosphatase (TRAP) staining. Gene expressions of osteoclastic marker was analyzed by Real time quantitative PCR. The expressions of NFATc1, c-Jun and c-Fos protein and phosphorylation of NF- κ B p50 and JNK signaling pathway in RAW264.7 cells were examined by western-blot. Bone resorption activity of mature osteoclast was tested by pit formation assay. <h3>Results</h3> Iguratimod strongly inhibited osteoclast differentiation in a dose-dependent manner. RANKL-induced expression of NFATc1, c-Jun, c-Fos, metalloproteinase-9 and cathepsin K were suppressed by Iguratimod in the RAW264.7 cells. Furthermore, Iguratimod could downregulate phosphorylation of the NF- κB p50 and JNK signaling pathway and inhibited the bone-resorbing activity of mature osteoclasts measured by osteologic discs. <h3>Conclusions</h3> These results indicate that iguratimod is a potent inhibitor of osteoclastogenesis, supporting its therapeutic benefit for preventing bone erosion in RA. <h3>References</h3> Lu LJ, Bao CD, Dai M, Teng JL, et al. Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate. Arthritis Rheum. 2009 Jul 15;61(7):979-87. <h3>Disclosure of Interest</h3> None Declared
Primary lymphoma of the common bile duct presenting with acute pancreatitis and cholangitis
Authors: C. Luigiano, F. Ferrara, C. Fabbri, S. Ghersi, M. Bassi, A. Polifemo, P. Billi, A. Fornelli, F. Cinquantini, N. D’Imperio
Journal: Endoscopy (2010)

Malignant lymphoma primarily originating from the extrahepatic bile duct is extremely rare, and preoperative diagnosis is difficult because symptoms and imaging are nonspecific [1] [2]. The most common symptoms of primary biliary lymphoma are abdominal pain, weight loss, fever, and obstructive jaundice [1] [2]. A total of 23 cases have been reported in literature [1] [2] [3] [4] [5], and, to the best of our knowledge, this is the fourth case of diagnosis made preoperatively and the first report of primary biliary lymphoma with acute pancreatitis and cholangitis as the first clinical manifestations.
Increased Growth after Long-Term Oral 1α,25-Vitamin D<sub>3</sub>in Childhood Renal Osteodystrophy
Authors: Russell W. Chesney, A. Vishnu Moorthy, John A. Eisman, Diane K. Jax, Richard B. Mazess, Hector F. DeLuca
Journal: New England Journal of Medicine (1978)

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15±5 pg per milliliter (mean ± S.E.M.) and after treatment rose to 54±13. Serum calcium rose from 7.5±1.6 mg per deciliter (mean ± S.D.) to 9.8±0.6 after one month (P<0.02). Alkaline phosphatase activity fell from 536±298 to 208±91 IU per liter after 12 months (P<0.05). Serum immunoreactive parathyroid levels fell from 900±562 μl eq per milliliter to 411±377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6±0.8 to 8.0±3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children. (N Engl J Med 298:238–242, 1978)
Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia
Authors: T Padró, R Bieker, S Ruiz, M Steins, S Retzlaff, H Bürger, T Büchner, T Kessler, F Herrera, J Kienast, C Müller-Tidow, H Serve, WE Berdel, RM Mesters
Journal: Leukemia (2002)
Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR
Authors: G Mitterbauer, C Zimmer, C Fonatsch, OA Haas, R Thalhammer-Scherrer, I Schwarzinger, P Kalhs, U Jaeger, K Lechner, C Mannhalter
Journal: Leukemia (1999)
153 TELAPREVIR BLOOD LEVELS ARE UNALTERED IN PATIENTS WITH CICLOSPORIN AND TACROLIMUS BASED IMMUNOSUPPRESSION AFTER ORTHOTOPIC LIVER TRANSPLANTATION
Authors: H. Farnik, T. Zimmermann, P. Galle, W.O. Bechstein, B. Kronenberger, E. Herrmann, G. Geisslinger, C. Sarrazin, S. Zeuzem, M.W. Welker
Journal: Journal of Hepatology (2013)
Abstract 3392: New findings of kinase switch in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis.
Authors: Maiko Ako, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Yasuaki Miyazaki, Kazuki Shimada, Takayuki Ikezoe, Takahiro Taguchi, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichirou Doki, Tetsuji Naka, Toshirou Nishida
Journal: Cancer Research (2013)

Abstract Despite the initial effectiveness of imatinib for gastrointestinal stromal tumors (GISTs), patients must continue lifelong imatinib therapy, and may eventually relapse owing to acquired drug resistance. Pathology reveals the persistence of viable cells during imatinib therapy, even in the disappearance region upon radiological examination. These cells are thought to cause acquired drug resistance and relapse. To uncover the mechanisms underlying these clinical issues, we used GIST-T1 cells to investigate the phosphoproteomic alterations induced by imatinib treatment. Because some tyrosine kinases might be activated after imatinib exposure, it is important to reveal the increased phosphorylation of proteins on a proteomic scale, and elucidate drug-resistant proteins. Proteins extracted from imatinib-treated or untreated GIST-T1 cells were digested with trypsin. The resulting tyrosine-phosphorylated peptides were purified using an immunoaffinity-enriched and iTRAQ-labeled reagent, and analyzed using mass spectroscopy. Using this phosphoproteomic approach, we identified 171 tyrosine phosphorylation sites spanning 134 proteins. We also detected increased tyrosine phosphorylation of Fyn (Y420) and focal adhesion kinase (FAK) (Y576). Increased phosphorylation was also confirmed by Western blot analysis, and knockdown of Fyn or FAK increased cells’ sensitivity to imatinib. Furthermore, the anti-proliferative effect of imatinib significantly enhanced imatinib-resistant GIST-T1 cells, which exhibited constitutive phosphorylation of FAK when treated with a FAK-selective kinase inhibitor. Moreover, FYN was proved to be a signal of FAK of upper reaches. These results indicate that an iTRAQ-based quantitative phospho-tyrosine-focused phosphoproteomic approach is a powerful method for screening phosphoproteins associated with drug resistance. Fyn or FAK might be potential therapeutic targets to overcome acquired resistance to imatinib in GISTs. Citation Format: Maiko Ako, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Yasuaki Miyazaki, Kazuki Shimada, Takayuki Ikezoe, Takahiro Taguchi, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichirou Doki, Tetsuji Naka, Toshirou Nishida. New findings of kinase switch in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis. [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 3392. doi:10.1158/1538-7445.AM2013-3392