tbuckley/cabot-search huggingface dataset:
Abstract P5-14-02: Immediate Breast Reconstruction: The Effect of Radiation
Authors: ESS Hwang, T Sasaki, K Itakura, R Foster, B Fowble, J Tanaka, CA Ewing, MD Alvarado, LJ. Esserman
Journal: Cancer Research (2010)

Abstract Background: Prior history of breast irradiation or anticipated need for postmastectomy radiation have been considered relative contraindications for immediate breast reconstruction. We evaluated the surgical outcomes between three groups of patients: patients without radiation exposure, those with radiation prior to immediate reconstruction, and those with radiation following immediate reconstruction to determine the differences in risk of post-surgical complications among groups. Methods: All patients undergoing mastectomy and immediate reconstruction with either a tissue expander or implant between January 1, 2005 and June 30, 2009 were entered into an IRB-approved prospective database. Routine institutional protocol consisted of immediate reconstruction with tissue expander, expansion during the1-2 months following surgery, radiation if indicated, followed by implant exchange at 3-6 months after completion of radiation. All complications were collected and recorded within a week of the event, and all patients had a minimum follow-up period of 6 months after implant exchange to allow for sufficient monitoring of complications. Major complications included infection requiring IV antibiotics, unplanned return to surgery, and tissue expander/implant loss. Results: A total of 446 mastectomies were identified. Of these, 341 had no radiation history, 33 had prior ipsilateral breast radiation, and 72 had post-mastectomy radiation. Overall, there were 160 major complications (36%), including 50 (11%) expander/implant losses. Patient age, BMI, diabetes, and history of tobacco use were not associated with increased risk of major complications in this cohort. However, both prior and postoperative radiation was associated with higher risk of both major complications and implant loss. Conclusion: Immediate reconstruction with implant or tissue expander is associated with a 36% risk of major postoperative complications, with the greatest number seen in those patients with history of previous chest wall irradiation. However, most implants were salvaged even in the setting of complications, and the overall implant loss rate was only 8% in unirradiated patients and 22% in those patients with postoperative RT. Although radiation history is not a contraindication to immediate breast reconstruction, patients undergoing this procedure must be well informed of their substantial risk of postoperative complications. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-02.
The Alteration of 18F-FDG Uptake in Bone Marrow After Treatment With Interleukin 11
Authors: Chang Yi, Xinchong Shi, Xiaoyan Wang, Zhifeng Chen, Bing Zhang, Xiangsong Zhang
Journal: Clinical Nuclear Medicine (2014)

Diffuse increased 18F-FDG in the bone marrow can be seen with colony-stimulating factors. Here, we reported a case of idiopathic cytopenia of undetermined significance treated with interleukin 11. After administration of interleukin 11, both diffuse and focally increased FDG activity in the bone marrow were noted. The focal activity was histologically proven as hyperplastic bone marrow.
PWE-080 Beware The Interaction Between Thiopurines And Warfarin
Authors: M Dadgar, G Pickford, P MacCallum, D Rampton, L Langmead
Journal: Gut (2014)

<h3>Introduction</h3> It is not uncommon for patients to require both immunosuppression and anticoagulation and for warfarin and thiopurines to be prescribed concurrently. There is limited evidence that thiopurines can inhibit the actions of warfarin. This potential interaction needs to be addressed when monitoring patients established on warfarin as they commence thiopurines or change dose. IBD patients are increasingly changed to combination low dose thiopurine and allopurinol for high methylmercaptopurine: thioguanine nucleotide (MeMP:TGN) ratio to optimise thiopurine efficacy. However, allopurinol also may potentiate warfarin and this could further exacerbate the effect of Azathioprine/mercaptopurine dose lowering on warfarin activity. <h3>Aim</h3> To raise awareness of risk of harm from a clinically important interaction between thiopurines and warfarin +/- allopurinol. <h3>Methods</h3> We studied 8 patients, identified from our anticoagulation database, who had been previously established on warfarin, and then commenced azathioprine or mercaptopurine for inflammatory bowel disease (2), systemic lupus erythematosus (1), nephritic syndrome (1), Wegener’s granulomatosis (1), polyarteritis nodosa (1), dermatomyositis (1) and renal transplant (1). The effect of thiopurine on international normalised ratio (INR), and warfarin dose prior to and following commencement of thiopurine was recorded. <h3>Results</h3> In 6/8 patients, following introduction of azathioprine or mercaptopurine, the warfarin dose had to be significantly increased (100% [18–500], Median [range]) in order to maintain a therapeutic INR. Any subsequent reductions in thiopurine dose were mirrored by a rise in INR and lower requirement for warfarin. In 2 IBD patients, each with a high warfarin requirement, thiopurine metabolites were measured. In both patients MeMP:TGN ratio was &gt;11. Thiopurine dose was reduced to 25% and allopurinol 100 mg added. INR was carefully monitored. In both cases INR increased within a week (to 6.9 and 11.2) and warfarin doses were subsequently reduced by ½ and 2/3 respectively to regain therapeutic INR. <h3>Conclusion</h3> It is important for clinicians to be aware of the potential inhibitory action of thiopurines on warfarin’s anticoagulant effect. Close INR monitoring is essential when initiating thiopurines and especially when reducing their dose and/or adding allopurinol. Failure to recognise the latter could result in bleeding due to over-anticoagulation. The high MeMP:TGN ratio in 2 of our patients also raises the possibility that thiopurine metabolites may play a role in the interaction between thiopurines and warfarin. <h3>Disclosure of Interest</h3> None Declared.
Abstract 2132: Cigarette smoking increases copy number alterations in non-small cell lung cancer
Authors: Yen-Tsung Huang, Xihong Lin, Lucian R. Chirieac, Ray McGovern, John C. Wain, Rebecca S. Heist, Vidar Skaug, Shanbeh Zienolddiny, Aage Haugen, Li Su, David C. Christiani
Journal: Cancer Research (2010)

Abstract BACKGROUND: Cigarette smoking is a well-established risk factor of lung cancer. How smoking induces oncogenesis in lung remains not fully understood. We conducted a genome-wide study of copy number and smoking pack-years in a large collection of non-small cell lung cancer (NSCLC) tumors on three different scales: whole genome, chromosome and focal region. METHODS: Genome-wide analyses of copy number and pack-years of cigarette smoking were performed on NSCLC tumors (n=264), which was randomly divided into a discovery set (n=134) and a validation set (n=130). Copy numbers were inferred from the dense single nucleotide polymorphisms array by dChip. On the scales of whole genome and chromosome, four indices were proposed to test large-scale copy number alterations (CNAs) patterns between heavy and light smokers: total CNAs events, continuous CNAs pattern, discrete CNAs pattern, and selecting effect with respect to gene locations. On the scale of focal region, genome-wide association (GWA) analyses of focal copy number and smoking pack-years were performed on 256,554 loci. RESULTS: On the whole genome scale, heavy cigarette smokers (&amp;gt;60 pack-years) have significantly more copy number gains than non-/light smokers (≤60 pack-years) (p=2.46×10−4). Copy number losses tend to occur away from genes in non-/light smokers (p=5.15×10−5) but not in heavy smokers (p=0.52). Smoking-associated copy number gains are most significant on chromosomes 8 (p=1.19×10−5), 10 (p=4.81×10−4) and 12 (p=3.31×10−3). For the focal region, GWA analyses show six loci with strong association of copy number and cigarette smoking pack-years, including four neighboring loci at 12q23.2 (p=1.79×10−8 to 6.17×10−7) where IGF1 (insulin-like growth factor 1) is located. All above analyses were tested in the discovery set and confirmed in the validation set. CONCLUSIONS: Heavy smokers have more copy number gains and less selection of gene locations in copy number losses. Copy number increases in 12q23.2 where IGF1 is located are positively associated with cigarette smoking pack-years. Supported by US National Institutes of Health Grants No. CA092824, CA074386, CA090578; and the Norwegian Cancer Society 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 2132.
Abstract LB-467: miR-135b and miR-210 induce invasion and distant metastasis by targeting SIAH1 and SETD2 in colorectal cancer
Authors: Giridhar Mudduluru, Taral R. Lunavat, Maike Scharp, Santoshi Muppala, Nitin Patil, Jörg H. Leupold, Mohammed Abba, Heike Allgayer
Journal: Cancer Research (2012)

Abstract The metastatic spread of tumor cells is ultimately responsible for the vast majority of cancer related mortality. In the attainment of a metastatic phenotype, several intricately interwoven processes are involved that lead to uncontrolled proliferation, loss of intracellular adhesions, extracellular matrix degradation, intravasation and dissemination into distant organs. Therefore, an improved understanding of molecular mechanisms which regulate metastatic transformation and progression of the cancer cells is of paramount importance. In this present study we performed miRNA-microarray analysis of six patient samples comprising normal, primary tumor and distant metastasis tissues, where we found miR-135b, miR-210, miR-378, miR-19a to be significantly up-regulated in both tumor and metastasized tissues as compared to the respective normal equivalents. We validated miR-135b and -210 in a series of 30 colorectal patients, in which we were able to demonstrate an increased expression in tumor as compared to normal tissues (p=0.008 and p=0.03, respectively). Forced in vitro expression of these miRNAs resulted in increased migration and invasion of Rko, SW480 and SW620 colorectal cancer (CRC) cell lines. Additionally, these cells manifested a gain of mesenchymal marker (N-cadherin) and a loss of epithelial marker (E-cadherin) expression at the protein level. Furthermore, of the several predicted targets identified, through luciferase, RT-PCR and Western blot analysis we found SIAH1 and SETD2 to be regulated by miR-135b and -210, respectively. Furthermore, in vivo, chorioallantoic membrane (CAM) metastasis assays revealed that miR-135b and miR-210 significantly induce distant metastasis to the lungs and liver (p=0.05). Our preliminary findings suggest that miR-135b and 210 play important roles in inducing tumor progression and may be useful as potential targets for mitigating metastatic spread Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-467. doi:1538-7445.AM2012-LB-467
EFFECT OF SURGICAL UNROOFING OF A MYOCARDIAL BRIDGE ON EXERCISE INDUCED QT INTERVAL DISPERSION AND ANGINAL SYMPTOMS IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Vedant Pargaonkar, Makiko Nishikii, Jack Boyd, Ian Rogers, Ingela Schnittger, Jennifer Tremmel
Journal: Journal of the American College of Cardiology (2016)
Abstract SY10-04: Delineating cellular targets of transformation in breast cancer
Authors: Nai Yang Fu, François Vaillant, Geoffrey J. Lindeman, Jane E. Visvader
Journal: Cancer Research (2012)

Abstract To understand relationships between the mammary epithelia, ‘cells of origin’ and cancer stem cells in breast tumors, it is necessary to dissect the normal mammary epithelial hierarchy. We have isolated discrete populations of mouse and human mammary epithelial cells on the basis of cell-surface markers and identified cell subsets that are highly enriched for mammary stem (MaSC), luminal progenitor and mature luminal cells. Analysis of different mouse models of mammary tumorigenesis using syngeneic transplantation assays and interrogation of molecular profiles has revealed potential ‘cells of origin’ in preneoplastic tissue and the presence of a definitive cancer stem cell subset in different mouse mammary tumors. Cell lineage tracing studies in the mouse provide the current gold standard for identifying cells of origin. Towards this end, we have constructed a series of transgenic mice harboring lineage-specific gene regulatory regions (180 kB) that can be used to direct the expression of specific mammary oncogenes to discrete epithelial cell types. This will allow us to address the contribution of ‘cells of origin’ and the nature of the oncogene itself to mouse mammary tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY10-04. doi:1538-7445.AM2012-SY10-04
P150 The Development of a Cough Hypersensitivity Questionnaire (CHQ)
Authors: J La-Crette, KK Lee, S Chamberlain, J Saito, J Hull, KF Chung, SS Birring
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> Cough reflex hypersensitivity (CRH) is a key feature of most patients with a refractory chronic cough and has distinct clinical features of hypertussia, allotussia (cough due to nontussive stimuli e.g. talking) and laryngeal paraesthesia (throat tickle). Cough challenge tests, the gold standard used to identify CRH, are limited for clinical use because of the wide overlap between healthy subjects and chronic cough. We aimed to develop a patient reported cough hypersensitivity questionnaire (CHQ) to identify abnormal CRH symptoms and evaluated it in subjects with and without cough. <h3>Methods</h3> The CHQ was developed following literature review, MDM and patient interviews. It assessed the presence and severity of cough triggers and laryngeal sensations on a Likert scale. It contained 35 items, score range 0–150. 38 Subjects (16 healthy, 10 refractory chronic cough (RCC: rhinitis, gastro-oesophageal reflux disease, asthma/eosinophilic bronchitis) and 12 respiratory disease (RD: bronchiectasis, sarcoidosis, interstitial lung disease and emphysema) with cough) completed the CHQ, LCQ (health status), capsaicin cough reflex sensitivity (C5) and urge to cough VAS during capsaicin test. <h3>Results</h3> Capsaicin cough reflex sensitivity, compared to healthy subjects, was increased in both RCC (geometric mean(logSD) C5 for RCC 18.1 (1.1) vs Normal 134.3 (0.8) p=0.0084) and RD (p=0.0126); figure 1. CHQ scores were raised in RCC compared to healthy subjects (p=0.0001) and RD (p=0.0068), figure 1. The upper limit of normal for CHQ score was 46. CHQ identified subjects with RCC better than C5. There was no significant relationship between CHQ and age or gender. CHQ was associated with logC5 (all subjects) r= –0.33, p=0.045 and health status (LCQ in RCC and RD) r= –0.58, p=0.006. There were no significant differences in mean(SD) urge to cough VAS during capsaicin test between subjects; healthy 52(25), RCC 39(24) and RD 54(29); p= 0.2317. <h3>Conclusion</h3> In conclusion, this preliminary study suggests that laryngeal sensations and cough triggers assessed with the CHQ may identify patients with CRH. Further work is needed to repeat the study in a larger number of subjects, investigate whether the number of CHQ items could be reduced and to develop better objective tests of CRH.
Cytotoxic doses of curcuminoids provoke a down-regulation of phospholipid biosynthesis – a focused metabolomic profiling.
Authors: M Bayet-Robert, D Morvan, P Chollet, C Barthomeuf
Journal: Cancer Research (2009)

Abstract Abstract #6029 Background: Curcuminoids of which curcumin have proved efficacy in breast cancer prevention [Aggarwal et al, Anticancer Res (2003);23(1A):363]. In addition, there is growing evidence that these compounds may treat cancer [Karunagaran et al, Curr Cancer Drug Targets (2005);5(2):117]. However, the mechanisms of cytotoxicity of curcuminoids remain partially unknown. Functional genomics include several tools increasingly applied in pharmacology, like DNA and RNA microarrays, and proteomics. It was recently shown that a novel post-genomics technology, NMR spectroscopy-based metabolomics, was able to unravel metabolic pathways of the response to anticancer drugs [Morvan et al, Cancer Res. (2007);67(5):2150 ; Bayet-Robert et al, AACR Proceedings (2008);abstract 3938]. We applied this technique to investigate the metabolic features of the response of MCF7 human breast carcinoma cells to curcuminoids. We here report the analysis of the phospholipid metabolism subset of our data.&amp;#x2028; Material and Methods: MCF7 cells were exposed to 10 µg/mL curcuminoids and followed at 12, 36 and 72 h intervals of time. Cytotoxicity assay was performed using Hoescht 33342. A novel high resolution magic angle spinning 1H-NMR spectroscopy-based metabolomics technique was used to obtain a quantitative metabolite profiling of about thirty metabolites, among which 8 phospholipid metabolism derivatives, in intact treated and untreated MCF7 cells.&amp;#x2028; Results: A 72 h-exposure to 10 µg/mL curcuminoids decreased MCF7 cell survival to 4% (p=0.0039). Polyunsaturated fatty acids increased by +120% at 36 h and +62% at 72 h (both p=NS, Mann-Whitney test), phosphoethanolamine by +24% at 36 h (p=NS) and +120% at 72 h (p=0.0062), cytidinediphosphocholine (CDP-Cho) by +22% at 12 h, +132% at 36 h (both p=NS), and +547% at 72 h (p=0.0062). There was a decrease of phosphatidylcholine (PtdCho) by -30% at 36 h (p=NS), and -42% at 72 h (p=NS). Glycerophosphoethanolamine decreased by -28% at 12 h (p=0.0446) and glycerophosphocholine by -53% (p=0.0106). The PtdCho/CDP-Cho ratio decreased from +93% to +8% between 12 and 72 h, which indicates a blockade of PtdCho biosynthesis.&amp;#x2028; Discussion and Conclusion: Our results are consistent with a rapidly progressive down-regulation of cholinephosphotransferase activity in response to curcuminoids, a biochemical mechanism closely linked to apoptosis [Miquel et al, J Biol Chem. (1998);273(40):26179 ; Cui et al, Biochim Biophys Acta. (2002);1585(2-3):87]. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6029.
Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin
Authors: Donghyun Kim, Yun-Gi Kim, Sang-Uk Seo, Dong-Jae Kim, Nobuhiko Kamada, Dave Prescott, Mathias Chamaillard, Dana J Philpott, Philip Rosenstiel, Naohiro Inohara, Gabriel Núñez
Journal: Nature Medicine (2016)
Management of the contralateral breast in women with breast cancer.
Authors: T Tuttle
Journal: Cancer Research (2009)

Abstract Abstract #MS1-2 Patients with unilateral breast cancer are at increased risk for developing a second cancer in the contralateral breast. The annual risk of clinically detected metachronous contralateral breast cancer is about 0.7% Some women choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. A recently published study found that the use of CPM increased by 150% from 1998 to 2003 in the United States. Several studies have demonstrated that CPM significantly decreases the occurrence of contralateral breast cancer; the risk reduction is about 97%. Since the risk of systemic metastases often exceeds the risk of contralateral breast cancer, most patients will not experience any survival benefit from CPM. Moreover, CPM is not risk free, and patients may need to undergo additional surgical procedures, especially if reconstruction is performed. Nevertheless, most patients are satisfied with their decision to undergo CPM. Alternatives to CPM include close surveillance with clinical breast examination, mammography, and possibly breast magnetic resonance imaging. Endocrine therapy with tamoxifen or aromatase inhibitors significantly reduces the risk of contralateral breast cancer and may be more acceptable than CPM for some patients. Ovarian ablation and cytotoxic chemotherapy also reduce the risk of contralateral breast cancer. For women with unilateral breast cancer, management of the normal contralateral breast is complex. Future prospective studies are critically needed to evaluate the decision-making processes leading to CPM. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr MS1-2.
Atypical Parkinsonian Syndromes With Very Poor Striatal Uptake on 123I-Ioflupane SPECT Imaging
Authors: Elizabeth H Dibble, Don C Yoo, Richard B Noto, Joseph H Friedman
Journal: Clinical Nuclear Medicine (2014)

We report a case series of unusual I-ioflupane SPECT imaging findings. Three patients with atypical parkinsonian symptoms underwent I-ioflupane imaging to assist in diagnosis. The patients had complete or near-complete absence of striatal activity. The imaging deficit severity did not consistently correlate with the clinical deficit severity. These cases suggest that markedly abnormal uptake patterns may be seen with atypical parkinsonian syndromes. Further research is warranted to evaluate differences in I-ioflupane uptake patterns among the various parkinsonian syndromes.
High-Dose Intramuscular Triamcinolone in Severe, Chronic, Life-Threatening Asthma
Authors: Raja G. Ogirala, Thomas K. Aldrich, David J. Prezant, Mark J. Sinnett, Jay B. Enden, M. Henry Williams
Journal: New England Journal of Medicine (1991)

Despite oral corticosteroid therapy, some patients with asthma have frequent exacerbations requiring emergency room visits, hospitalization, and occasionally, mechanical ventilation. We compared the effects of high-dose intramuscular triamcinolone with oral prednisone in patients with severe chronic asthma.