tbuckley/cabot-search huggingface dataset:
Abstract LB-413: A multi-stage association study in breast cancer identifies a protective allele at NCOA7
Authors: Kathryn S. Poland, Joan P. Breyer, Kevin M. Bradley, Peggy A. Schuyler, W. Dale Plummer, Marcia G. Freudenthal, Amy Trentham-Dietz, Polly A. Newcomb, Linda T. Titus-Ernstoff, Montserrat Garcia-Closas, Melinda E. Sanders, David L. Page, Kathleen M. Egan, William D. Dupont, Jeffrey R. Smith
Journal: Cancer Research (2010)

Abstract Estrogen metabolism and growth factor signaling pathway genes play a potential role in breast cancer predisposition. We evaluated pathway genes in a nested case-control investigation of women within the Nashville Breast Cohort, using germline DNA obtained from archival benign breast biopsies (formalin-fixed paraffin embedded). We applied methods enabling large-scale candidate gene investigation in the archival DNA (2 to 6 decades old). The study included 447 women who progressed to breast cancer (cases), and 838 women who did not (controls, matched on age and year of biopsy to cases in a ∼ 2:1 ratio). Single allele- and haplotype-based tests of association were explored among 115 tagged pathway genes, and results were compared to those of the CGEMS GWAS (1,145 cases, 1,142 controls). Findings across the two study populations were concordant in 8 genes. Further replication of results was sought in the Collaborative Breast Cancer Study (1,552 cases, 1,185 controls). FGFR2 and NCOA7 associations were concordant across all three studies. FGFR2 carries known susceptibility variants confirmed in prior GWAS, whereas the association at NCOA7 on 6q22.32 is novel. NCOA7 encodes a nuclear receptor co-activator that directly interacts with estrogen receptor to modulate its activity. A haplotype of NCOA7 had a significant inverse association with breast cancer in each of the three studies (odds ratios of 0.67, 0.77, and 0.78 (respectively) for haplotype carriers relative to non-carriers), with a combined odds ratio of 0.77 (95% CI 0.65-0.89), P = 5.1 × 10-4. These observations provide credible evidence that this NCOA7 variant has a protective effect on breast cancer risk. 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 LB-413.
Radionuclide Three-Phase Whole-Body Bone Imaging
Authors: DAVID C. YANG, RITA S. RATANI, PARDEEP K. MITTAL, RUFO S. CHUA, SUREKHA M. PATEL
Journal: Clinical Nuclear Medicine (2002)

To describe the radionuclide three-phase whole-body bone imaging (TPWBBI) technique and discuss the usefulness of its application.TPWBBI was performed after a single intravenous injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m MDP. Whole-body arterial flow (phase one) followed by blood-pool and tissue perfusion (phase two) images were obtained with the moving detector head speed set at 150 cm/minute and 40 cm/minute, respectively. Conventional whole-body static bone images (phase three) were obtained 3 hours later.When 542 consecutive TPWBBI results were reviewed, 394 (166 extraskeletal and 228 skeletal) abnormalities were detected during phases one and two. The 166 extraosseous lesions included vascular diseases: abdominal aortic aneurysms and peripheral vascular diseases and renal abnormalities, liver abnormalities, ascites, and pleural effusions. Many of these were incidentally detected clinically significant findings and would not have been identified on conventional static bone images. It helps to differentiate among acute and chronic fractures, active and inactive inflammatory diseases such as arthritis or osteomyelitis, and Paget's disease.With a single injection of Tc-99m MDP, whole-body images obtained in the arterial phase, the blood-pool and tissue perfusion phase, and the static bone phase can identify many clinically significant skeletal and soft tissue abnormalities. TPWBBI can differentiate between active and inactive phases of different disease processes and thereby provide a diagnosis that is more specific than a conventional single-phase bone scan. It may be applicable as a tool for nuclear physical examination.
SAT0072 Frequency of interferon-gamma-positive TH17 (TH17-1) cells is up-regulated in synovial fluids in patients with rheumatoid arthritis
Authors: N. Sakurai, I. Hidekazu, K. Kayakabe, T. Sakairi, Y. Kaneko, A. Maeshima, K. Hiromura, Y. Nojima
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Th17 cells are a recently identified CD4<sup>+</sup> CD45RO<sup>+</sup>helper T cell subset that produce IL-17 with proinflammatory actions and are thought to play a critical role in the pathogenesis of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA) (1). Recently, Nistala et al. showed that Th17 cells obtained from the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients co-expressed IFN-γ (2). Moreover, they found that Th17-1 cells (Th17 cells co-expressing IFN-γ) were enriched in SF compared to peripheral blood mononuclear cells (PBMC) in patients with JIA. However Th17-1 has not been investigated in patients with RA. <h3>Objectives</h3> To explore the significance of Th17-1 in human RA, we examined the frequency of Th1, Th17, and Th17-1 cells in PBMC and SF derived from RA patients by flow cytometry and compared them with those in PBMC from healthy donors. <h3>Methods</h3> PBMC from 14 healthy donors (Control-PBMC) and 33 RA patients (RA-PBMC), and SF from 17 RA patients (RA-SF) were obtained and used in this experiment. Isolated mononuclear cells were stimulated with PMA and ionomycin for 5 hours, and then the expression of intracellular cytokines and cell surface markers were analyzed by flow cytometry. Among double positive cells for CD4 and CD45RO, single positive cells for IFN-γ or IL-17, and double positive cells for both IFN-γ and IL-17 were defined as Th1, Th17, and Th17-1 cells, respectively. <h3>Results</h3> The frequency of Th17 and Th17-1 cells in PBMC from RA patients were significantly lower than those from controls, whereas the frequency of Th1 cells were similar between them (Th17, 2.2±1.1% vs. 3.0±1.1%, P=0.006; Th17-1, 0.4±0.3% vs. 1.0±0.5%, P=0.0002; Th1, 24±11% vs. 28±5.6%, P=0.0624; RA-PBMC vs. Control-PBMC). Among RA patients, the frequency of Th17 cells in SF was significantly lower than that of PBMC, whereas Th1 and Th17-1 cells in SF were significantly higher than those in PBMC (Th17, 2.2±1.1% vs. 1.8±1.4%, P=0.0381; Th1, 24±11% vs. 38±14%, P=0.0004; Th17-1, 0.4±0.3% vs. 1.1±0.9%, P=0.0006; RA-PBMC vs. RA-SF). <h3>Conclusions</h3> In patients with RA, the frequency of both Th1 and Th17-1 cells but not of Th17 in SF were significantly up-regulated, suggesting that a local inflammation in RA joints is dominantly mediated by IFN-γ. <h3>References</h3> Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009. 27:485–517. Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, Evans JG, Cimaz R, Bajaj-Elliott M, Wedderburn LR. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A. 2010. Aug 17;107(33):14751-6. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-304: Sp1 expression regulates lung tumor progression
Authors: Tsung-I Hsu, Jan-Jong Hung
Journal: Cancer Research (2012)

Abstract The role of Sp1 in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upregulated in lung adenocarcinoma cells with low invasiveness and in patients with stage I lung cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma cells with high invasiveness and in patients with stage IV lung adenocarcinoma. Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein. Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells increased expression of E-cadherin, a suppressor of metastasis, and attenuated the translocation of β-catenin into the cellular nucleus which leads to tumor malignancy. Taken together, Sp1 level accumulated strongly in early stage and then declined in late stage, which is important for lung cancer cell proliferation and metastasis during 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 LB-304. doi:1538-7445.AM2012-LB-304
Measures of Clinical Efficacy
Authors: Barbara J. McNeil, S. James Adelstein
Journal: New England Journal of Medicine (1975)

An attempt was made to discover the difference in outcomes between treating all patients with essential and renovascular hypertension by drug therapy independent and ignorant of etiologic classification and identifying the patients with renovascular disease and operating on them. Outcomes were categorized as well without complications of hypertension, alive but suffering from a related morbid illness such as coronary or cerebral arterial disease, and dead from the complications of diagnosis, surgery or high blood pressure. The identification and surgical treatment of hypertensive renovascular disease resulted in an incremental benefit in morbidity over blind antihypertensive medical therapy only when the compliance with medical treatment was about 50 per cent or less (the rate suggested for most patient populations). The study underscores the extent to which the quantitative efficacy of diagnositc and therapeutic procedures depends not only on the inherent risks and benefits but also on related social and medical factors.
Abstract 4712: Characterization of estrogen quinone-derived protein adducts and their identification in human serum albumin
Authors: Po-Hsiung Lin, Tzu-Wen Wang, Tzu-Han Wei, Tsung-Chou Yang, Dar-Ren Chen
Journal: Cancer Research (2010)

Abstract Both estrogen-2,3-quinone (E2-2,3-Q) and estrogen-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen that are thought to be responsible for the estrogen-induced genotoxicity. The aim of this study was to establish a methodology to analyze estrogen quinone-derived protein adducts and to measure the background levels of these adducts in human serum albumin (Alb) derived from female blood donors in Taiwan. The methodology, which employs trifluoroacetic acid anhydride and methanesulfonic acid to selectively cleave cysteinyl adducts, had previously been applied to measure naphthalene adducts in blood proteins. Results from in vitro experiments confirmed that the production of estrogen quinone-derived adducts on serum albumin increased with increased concentration of estrogen quinones (0-100 nM). The average formation of estrogen quinone-derived cysteinyl adducts per unit concentration of estrogen quinones was estimated to be 13.0, 48.2, and 36.1 (pmol/g Alb)/(nM) for E2-2,3-Q-1-S-Alb, E2-2,3-Q-4-S-Alb, and E2-3,4-Q-2-S-Alb, respectively. Time-course experiments indicated that both E2-2,3-Q- and E2-3,4-Q-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter. Additionally, with 2,3,7,8-tetrachlorodibenzo-p-dioxin pretreatment (10 nM for 72 h), production of estrogen quinone-derived protein adducts was also detected in human MCF-7 breast cancer cells exposed to estrogen (1 μM for 9 h). Co-treatment of Ro 41-0960, a catechol-o-methyl transferase inhibitor, further enhanced the production of estrogen quinone-derived adducts in all cases. When we investigated the levels of estrogen quinone-derived adducts in human serum Alb derived from female blood donors in Taiwan, cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb were detected in all subjects (n=10). The median levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in human subjects were estimated to be 398 (range 240-807) and 39.0 (range 0.3-101) (pmol/g), respectively. We noticed that levels of E2-2,3-Q-4-S-Alb were significantly correlated with those of E2-3,4-Q-2-S-Alb (correlation coefficient r = 0.684, p&amp;lt;0.05). (This work was supported by the National Science Council, Taiwan, through grants NSC95-2314-B-005-001, and NSC97-2314-B-005-001). 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 4712.
AB0538 TNFAIP3 RS675520 variant may predict response to rituximab treatment in rheumatoid arthritis
Authors: I. Guseva, N. Soroka, A. Devyataykina, G. Lukina, E. Aleksandrova, A. Novikov, S. Glukhova, D. Trofimov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Individual response to biological treatment is highly variable and potentially subject to genetics influence. There is a need for biomarkers that are able to predict clinical response to rituximab (RTX) treatment. <h3>Objectives</h3> To examine whether there are genetic polymorphisms associated with response to RTX therapy. <h3>Methods</h3> 53 RA patients receiving RTX therapy were included in this pharmacogenetic prospective study (mean age 51±15 years and mean disease duration 8.2±6.2 years). Response to RTX therapy was evaluated using the EULAR criteria (DAS28-ESR) at 6 months after the first RTX course (two intravenous infusions at weeks 0 and 2). The following gene polymorphisms (SNPs) were genotyped: IL-6 (rs1800795), IL-6RA (rs8192284), TNFA (rs1800629), TNFAIP3 (rs675520, rs6920220, rs10499194), MCP-1/CCL2 (rs1024611), CTLA4 (rs3087243), PTPN22 (rs2476601). Comparison of responses for the following groups (good responders vs moderate/non responders, and good responders vs moderate responders) was evaluated using logistic regression, and the results were expressed as ORs with 95% CI. <h3>Results</h3> After the 1st RTX course a good response was achieved in 18 (40,0%) patients. 29 (54,7%) patients were defined as moderate responders and 6 (11,3%) patients as non-responders. A SNP at TNFAIP3 locus (rs675520) tended to be associated with the response to RTX treatment in both groups of responders vs moderate/non responders (OR 4,6, 95% CI 0,9-23,6, p=0,06) and responders vs moderate responders (OR 4,8, 95% CI 0,9-25,5, p=0,062). The patients with homozygous genotype CC had the worse results than patients with CT and TT genotypes in the swollen joint count (p=0,036), tender joint count (p=0,034), DAS28 (p=0,01) and HAQ (p=0,01) at 6 months after the first course of treatment. No evidence for association was detected at the other SNPs tested <h3>Conclusions</h3> Our preliminary results suggest the TNFAIP3 SNP (rs675520) may possibly influence the response to RTX therapy. This finding requires replication in additional patients groups. <h3>Disclosure of Interest</h3> None Declared
COMPARISON OF IVABRADINE AND METOPROLOL IN PATIENTS WITH ACUTE INFERIOR WALL MYOCARDIAL INFARCTION: EXPANDING ARENA FOR IVABRADINE
Authors: Rajendra Kumar Gokhroo, Kumari Priti, Bhanwar Lal Ranwa, Avinash Anantharaj, Kamal Kishor, Shashikant Pandey, Ramsagar Roy
Journal: Journal of the American College of Cardiology (2016)
Duodenal Obstruction from a Gastric Feeding Tube
Authors: G. Michael Tibbitts, R. James Sorrell
Journal: New England Journal of Medicine (1999)

To the Editor: A 43-year-old man in a persistent vegetative state was admitted to the hospital with recurrent bouts of vomiting — bilious emesis without coffee-ground material. He received gastric-tube feedings through a 20-French Foley catheter. During the previous six months he had had several episodes of emesis; they were usually single, nocturnal events. There was no diarrhea, abdominal pain, or obstipation associated with the vomiting. The patient was afebrile. The abdominal examination was unremarkable. A flat-plate x-ray film of the abdomen showed a normal bowel-gas pattern with the gastric tube over the upper abdomen. The results of computed tomography . . .
Abstract 387: Development of a model of acquired resistance to a multi targeted VEGFR TKI and strategies to target resistance mechanisms through combination
Authors: Scott J. Garza, Kenneth E. Hook, Maruja E. Lira, Keith Ching, Jing Yuan, Julie Kan, Dana Hu-Lowe, James G. Christensen
Journal: Cancer Research (2010)

Abstract Anti angiogenic agents that target the VEGF pathway (bevacizumab, sorafenib and sunitinib (SU)) have demonstrated improved clinical benefit as single agents or in combination with chemotherapy in a variety of solid tumor types. Although this class of agents has provided an improved treatment option to certain tumor types, it is evident that some patients do not respond to therapy or will relapse despite an initial response to treatment due to an acquired resistance. To better understand this mode of acquired resistance to this class of agents, a model of Renal Cell Carcinoma (RCC) which has shown regression, eventually developed evasive resistance during long term administration of the single agent sunitinib (a small-molecule inhibitor of the VEGF-1, 2, 3, PDGF-α,β, KIT, CSF-1R and FLT-3 receptor tyrosine kinases). Despite the observation that resistant tumors under continuous treatment with sunitinib (60 mg/kg PO, QD) demonstrated a gross phenotypic reduction of micro-vascular density (MVD), they continued to show a progressive increase in size. Because the observed low MVD phenotype was suggestive of an ability of resistant tumor cells to survive in an increasingly hypoxic environment with a reduced functional vasculature, emphasis was placed on identifying tumor cell derived resistance factors. Gene expression and/or proteomic profiling studies accompanied by confirmatory immunoblotting indicated a subset of differentially expressed genes and/or proteins in resistant vs. sensitive treated tumors. Although profiling studies did not clearly elucidate definitive resistance mechanisms, the dysregulation of EGFR, FGFR1, &amp; TGFB1 pathways and downstream signaling through PI3K and MEK were potentially implicated. Comparative genomic hybridization studies did not identify any resistance mechanisms at the cytogenetic level. Sunitinib combination studies designed to target pathways potentially involved in resistance (SU + a PI3K/mTOR inhibitor; SU + a MEK inhibitor) demonstrated the ability to restore sensitivity in the sunitinib resistance model. The ability to identify and characterize resistance mechanisms and circumvent resistance through combination approaches may have utility in developing future combination regimens for anti angiogenic therapies. 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 387.
275P Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma for general condition patients: a single institution experience from Thailand
Authors: E. Tharavichitkul, S. Chakrabandhu, P. Klunklin, W. Onchan, B. Supawongwattana, N. Pukanhaphan, R.M. Galalae, I. Chitapanarux
Journal: Annals of Oncology (2015)
Double Uterus with Horn Menstruating into the Abdomen
Authors: John B. Vernaglia
Journal: New England Journal of Medicine (1948)

A review of the literature has disclosed no case similar to the one reported below, which is that of a completely separated double uterus, both halves well developed, in which one uterus did not communicate with the vagina and menstruated into the abdomen. The situation was recognized at operation at the time of the patient's third menstrual period, and a hemi-hysterectomy was done. Later, the patient became pregnant and was delivered of a living child by cesarean section.Congenital anomalies of the uterus are interesting but potentially serious conditions that warrant the careful consideration of every surgeon, gynecologist and obstetrician. . . .
Outcomes of Hepatic Resection in Intrahepatic Cholangiocarcinoma Patients with Diabetes, Hypertension, and Dyslipidemia: Significance of Routine Follow-Up
Authors: Takayoshi Nishioka, Shoji Kubo, Shogo Tanaka, Kenichi Wakasa, Shigekazu Takemura, Masahiko Kinoshita, Genya Hamano, Yuko Kuwae, Toshihiko Shibata, Shigefumi Suehiro
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt;&lt;b&gt; &lt;/b&gt;The outcomes of hepatic resection in intrahepatic cholangiocarcinoma (ICC) patients with diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DL) (metabolic components) remain unclear. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt;&lt;b&gt; &lt;/b&gt;The outcomes of 43 ICC patients without known risk factors for ICC who underwent hepatic resection were retrospectively reviewed. These patients were divided into three groups: those followed-up for metabolic components at least every 6 months (follow-up group, n=16), those not followed-up for metabolic components (no follow-up group, n=14), and those without metabolic components (control group, n=13). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt;&lt;b&gt; &lt;/b&gt;In the follow-up group, 13 (81%) patients were further examined for ICC during follow-up because of abnormal screening results, such as elevated serum gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 (CA19-9) concentrations or detection of hepatic tumor on ultrasonography and/or computed tomography, whereas most patients in the other two groups exhibited ICC-related symptoms. No patient in the follow-up group exhibited lymph node metastasis, whereas 43% of those in the no follow-up group and 46% in the control group had lymph node metastasis (p=0.005 and 0.004 vs. the follow-up group, respectively). All 16 patients in the follow-up group were diagnosed as International Union Against Cancer pathologic stage I or II (early stage). There were no significant differences in the incidence of postoperative recurrence between the three groups; however, the incidence of extrahepatic recurrence was lower in the follow-up group than in the no follow-up group and the control group (13% vs. 78% vs. 63%, p=0.0232). The 1-, 3-, and 5-year overall survivalrates in the follow-up group were better than those in the no follow-up and control groups (93/93/66% vs. 77/34/34% and 85/24/0%, p=0.034 and 0.001, respectively). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt;&lt;b&gt; &lt;/b&gt;Routine measurement of serum gamma-glutamyl transpeptidase and/or CA19-9 levels and imaging examinations every 12 months (or 6 months, if possible) are recommended during follow-up for DM, HT, and DL to detect ICC at an early stage.