tbuckley/cabot-search huggingface dataset:
Abstract LB-299: Prognostic impact of EMT (epithelial-mesenchymal-transition) related protein expression in endometrial cancer
Authors: Yoshimichi Tanaka
Journal: Cancer Research (2012)

Abstract Objectives: Epithelial-mesenchymal-transition (EMT) is recently identified as a important step in the invasion and metastasis of cancer. In this process, a critical molecular feature is the down regulation of E-cadherin and which is controled mainly by the Snail-related zinc-finger transcription factors (Snail and Slug). The aim of this study is to evaluate the prognostic impact of EMT related protein (E-cadherin, Snail and Slug) expression in endometrial cancer. Methods: We perfomed immunohistochemical annalysis using tissue microarray samples of 354 primary tumors and 30 metastases of endometrial carcinomas, and investigated the relationship between protein expression, clinicopathologic features and outcomes. Results: Reduced E-cadherin was seen in 39.8% in primary tumors. In endometrioid adenocarcinoma, reduced E-cadherin was seen in 19.5%, 40.8% and 72.7% in G1, G2 and G3 tumors, respectively. Nuclere expression of Snail was positive in 16.9% in primary tumors. Both redeced E-cadherin and nuclear expression of Snail were significantly associated with histological type, FIGO stage, myometrial invasion, ascites positive, lymph node metastasis and patient survival (P&amp;lt;0.01). Nuclear expression of Slug was seen in only 3.7% in primary tumors. Allmost all cases of Slug positive were carcinosarcomas, therefore, it was also associated with patient survival (P&amp;lt;0.01). We couldn't find any differencies in the rates of reduced E-cadherin and nuclear expression of Snail/Slug between in the primary tumors and metastases. In multivariate analysis, nuclear expression of Snail or Slug was found to be a significant predictor for both the progression free survival and overall survival (P&amp;lt;0.01). Conclusions: These data indicate that reduced E-cadherin and nuclear expression of Snail and Slug have a prognositic impact in endometrial cancer. Therefor, to clarify and control of EMT signaling is a promising molecular targeting therapy in endometrial cancer. 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-299. doi:1538-7445.AM2012-LB-299
THE TRANSPULMONARY RATIO OF ENDOTHELIN-1 IS INCREASED IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE AND SUPERIMPOSED PRECAPILLARY PULMONARY HYPERTENSION
Authors: David Meoli, Yan Ru Su, Evan Brittain, Ivan Robbins, Anna Hemnes, Ken Monahan
Journal: Journal of the American College of Cardiology (2016)
SAT0583 The CASE of “Case Reports” in Rheumatology Literature
Authors: S. Yilmaz, S. Kendirlioglu, K. Kaba, U. Ozdemir, M. Ozturk, I. Simsek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> With the increased encouragement of evidence-based medicine, case reports (CRs) are gradually sidelined and assumed to have minimal impact on the management of patients. In the field of rheumatology (R) CRs are generally published in several journals of the specialty while most major journals restrict or do not accept CRs because they may lower journal9s impact factor. There are no studies to date assessing the magnitude and the focus of the CRs published in R literature. <h3>Objectives</h3> The aims of this study were to investigate the proportion and the topic of the CRs published in major R journals. <h3>Methods</h3> All CRs published in 6 major English language R journals (Rheumatology – Rheum, Journal of Rheumatology – JR, Clinical Experimental Rheumatology – CER, Rheumatology International – RI, Arthritis and Rheumatism – AR, Journal of Clinical Rheumatology - JCR) from January 2007 to December 2011 were searched manually by the authors. The number, percentage (according to the total number of articles published in each issue of the journal), and the main category of the CRs as well as their relation to the individual journal and publication year were analyzed. <h3>Results</h3> Total 1357 CRs were analyzed. Twelve percent of all articles published in R journals between 2007–2011 were CRs. The highest percentage of CRs was published in JCR (56.4%), while AR had the lowest percentage (0.05%) of CRs. There was no statistically significant change in the proportion of CRs published within 5-year period (Fig. 1). Case reports reporting rare condition, new and unique treatment, and unusual presentation of a common disease were more likely to be published (Table 1). <h3>Conclusions</h3> While the data is limited, the proportion of CRs published in R journals was comparable to the publication rates found in other specialties<sup>1,2</sup>. Despite the common belief regarding the decreased space for CRs in R journals, there seems to be no decreasing trend, at least within the study period. Case reports regarding rare conditions and new treatments find more space in the journals. <h3>References</h3> Kljakovic M. Single cases in general practice and general medical journals. Aust Fam Physician. 2002 Jul;31(7):669-73. Review. S. Nabil, N. Samman. The impact of case reports in oral and maxillofacial surgery. Int. J. Oral Maxillofac. Surg. 2012; 41: 789–796 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1962
Erythremia after Renal Transplantation
Authors: Boyd A. Nies, Roy Cohn, Stanley L. Schrier
Journal: New England Journal of Medicine (1965)

IN the various reports of experiences with human renal allografts,1 2 3 4 5 6 7 8 there have been only brief notes regarding the appearance of nucleated red cells in the peripheral blood after renal transplantation.7 , 9 To our knowledge, however, there has been no report of erythremia in such patients. In the following case an outpouring of nucleated red cells occurred six weeks after renal transplantation and was associated with the appearance of erythremia.Case ReportR.B., a 22-year-old secretary, was first seen at the Stanford Medical Center on March 9, 1964, for treatment of uremia. She had had scarlet fever at the age of 4 . . .
Will TAVR Become the Predominant Method for Treating Severe Aortic Stenosis?
Authors: Neil E. Moat
Journal: New England Journal of Medicine (2016)

The results of the Placement of Aortic Transcatheter Valves (PARTNER) 2 trial that have now been published in the Journal represent another important piece of evidence by which to guide the contemporary management of symptomatic severe aortic stenosis.1 Who were the patients in this trial, and what does it teach us about their treatment?The Oxford English Dictionary defines the word "intermediate" as "holding the middle place . . . between two extremes." The reader may assume that the patients in this trial form the middle ground in the risk spectrum between patients at low and high risk. The authors . . .
Abstract 3892: Discovery and analysis of COMMD1 in the DNA damage response network
Authors: Nicholas T. Woods, Huey Nguyen, Marcelo Carvalho, Xueli Li, Virna Dapic, Alvaro Monteiro
Journal: Cancer Research (2011)

Abstract Spatially distinct domains impart functionality to the proteins and are often under evolutionary pressure to maintain sequence and/or structure. The BRCA1 C-terminal (BRCT) domain has an established role in cancer susceptibility and in the DNA damage response (DDR), as mutations in cases of familial breast cancer often result in a truncated protein lacking the two BRCT domains which are required for interactions with proteins such as p53, ABRAXAS, BACH1, and CtIP. BRCT domains can occur as singletons or as tandem domains (tBRCT) that function as a single cohesive structural unit involved in binding phosphorylated peptides targeted by PI3K-like proteins such as ATM in response to DNA damage. Using the Yeast Two-Hybrid system (Y2H) as well as Tandem Affinity Purification coupled to mass spectrometry (TAP-MS), we have built a domain centric protein-protein interaction network for a subset of tBRCT domains from BRCA1, TP53BP1, LIG4, PAXIP1, ECT2, BARD1, and MDC1. Evaluation of this network has revealed a number of interesting interactions and highlighted the interconnectivity potential found in these domains. Analysis of this network has revealed several interesting proteins that are highly interconnected with tBRCT domains, such as COMMD1 (an important regulator of copper homeostasis, sodium transport, NF-κB, and HIF-1), which has not yet been characterized to participate in the DDR, but was found to interact with the tBRCT domains of BARD1, BRCA1, and LIG4. Furthermore, an earlier Y2H screen conducted by our laboratory found COMMD1 as an interaction partner of CHK2. Therefore, we sought to determine the role of COMMD1 in response DNA damaging agents. Convincingly, the levels of COMMD1 are inversely related to apoptotic induction caused by cisplatin and doxorubicin. Furthermore, CHK2 signaling appears to control the ability of COMMD1 to enhance cisplatin induced apoptosis as wild type but not CHK2-/- HCT116 cells exhibited a repression in cisplatin induced apoptosis when COMMD1 was over expressed. These results indicate the importance of COMMD1 for cellular susceptibility to traditional chemotherapeutics. Currently, we are exploring the mechanisms by which COMMD1 in coordination with tBRCT domain containing proteins and CHK2 sensitizes cells to DNA damaging agents. 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 3892. doi:10.1158/1538-7445.AM2011-3892
The Cost of a Successful Delivery with in Vitro Fertilization
Authors: Peter J. Neumann, Soheyla D. Gharib, Milton C. Weinstein
Journal: New England Journal of Medicine (1994)

The use of in vitro fertilization has engendered considerable debate about who should have the procedure, whether health insurance should cover the cost, and if so, to what extent. We investigated the cost of a successful delivery with in vitro fertilization.
Kidney Function during 12 Months of Strict Metabolic Control in Insulin-Dependent Diabetic Patients with Incipient Nephropathy
Authors: Bo Feldt-Rasmussen, Elisabeth R. Mathiesen, Laszlo Hegedüs, Torsten Deckert
Journal: New England Journal of Medicine (1986)

Thirty-six patients with insulin-dependent diabetes mellitus who had Albustix-negative urine but elevated urinary albumin excretion (30 to 300 mg per 24 hours) were matched in pairs according to their urinary albumin level, blood glycosylated hemoglobin level, and sex and assigned randomly to either unchanged conventional treatment or continuous insulin infusion. During the next 12 months a significant improvement in glycemic control was observed in the insulin-infusion group, with a reduction in the mean glycosylated hemoglobin level from 9.5 to 7.3 percent. There was no change in the control group (9.3 to 9.2 percent). No significant change in albumin excretion was observed in either group. The mean blood pressure increased slightly in both groups (from 98 to 101 mm Hg in the insulin-infusion group and from 98 to 103 mm Hg in the control group). Kidney size was significantly reduced in all patients during insulin infusion, but no consistent change was observed in the control group. No significant change was observed in the glomerular filtration rate. Our data suggest that the pathologic processes causing microalbuminuria in early renal disease are not reversed during 12 months of strict metabolic control.
Abstract 1220: Role of human sLZIP in PMA-induced apoptosis in LNCaP prostate cancer cells
Authors: Yoonseo Kim, Jesang Ko
Journal: Cancer Research (2010)

Abstract Androgen and the androgen receptor (AR) play important roles in prostate cancer development, and androgen ablation has been the main therapeutic option for the treatment of locally advanced or metastatic prostate cancer. It has been reported that androgen-dependent LNCaP prostate cancer cells undergo apoptosis upon phorbol ester 12-myristate 13-acetate (PMA) treatment. In this study, we investigated whether transcription factor sLZIP is able to protect LNCaP cells from PMA-induced apoptosis. Results from cell morphology, cell cycle and apoptosis assay showed that PMA-induced apoptosis of LNCaP cells was inhibited in cells transfected with sLZIP. We also examined the effect of sLZIP on PARP cleavage and caspase 3 activation. PMA induced PARP cleavage and capase 3 activation, however, cells transfected with sLZIP exhibited reduced cleavage of PARP and caspase 3 in a dose dependent manner. sLZIP induced phosphorylation of ERK and increased cyclin D3expression. OverexpressionofsLZIPattenuatedPMA-mediatedTNF-α induction in LNCaP cells. These results indicate that human sLZIP negatively regulates PMA-induced apoptosis of prostate cancer cells. 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 1220.
Hereditary Fructose Intolerance
Authors: Marvin Cornblath, Ira M. Rosenthal, Solomon H. Reisner, Susan H. Wybregt, Robert K. Crane
Journal: New England Journal of Medicine (1963)

HEREDITARY fructose intolerance is an uncommon metabolic disorder, characterized by symptoms of nausea, vomiting, malaise, substernal pain, excessive sweating, tremor, confusion, coma and convulsions, that follows the ingestion of foods containing fructose.1 With continued ingestion of fructose cirrhosis2 3 4 and mental retardation4 , 5 may develop. To date, 23 cases in 14 families1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 have been reported from European clinics. The first description of hereditary fructose intolerance was presented by Chambers and Pratt6 in 1956. In the following year, Froesch et al.5 presented several cases in 1 family, fully described the symptoms of this condition and found that in the patients affected, low levels . . .
Regulation of Vascular Endothelial Growth Factor Expression by Estrogens and Progestins
Authors: S M Hyder, J C Huang, Z Nawaz, H Boettger-Tong, S Mäkelä, C Chiappetta, G M Stancel
Journal: Environmental Health Perspectives (2000)

Estrogens increase the expression of vascular endothelial growth factor (VEGF) mRNA in the rodent uterus. This regulatory effect is rapid, beginning within 1 hr after hormone treatment, dose dependent, and blocked by the pure antiestrogen ICI 182,780. The induction of the transcript is blocked by inhibitors of RNA but not of protein synthesis, and we have recently identified estrogen response elements in the VEGF gene. Collectively, these findings indicate that estrogens regulate uterine VEGF expression at the transcriptional level via the classical nuclear estrogen receptor pathway. Estrogen induction of VEGF occurs in the stromal layer of the rodent uterus, and estradiol induces expression of VEGF transcript levels in cultured human uterine stromal cells. Progestins also induce VEGF expression in the rodent uterus, although the effect is less marked and slower in onset than estrogenic effects. The effect of progestins is blocked by the antiprogestin mifepristone (RU-486), suggesting that it is also mediated by a classical nuclear receptor pathway. In addition, progestins regulate expression of VEGF mRNA and protein in cultured human T47-D breast cancer cells. The development of uterine leiomyomas is associated with exposure to ovarian sex steroids, abnormal uterine bleeding is commonly seen in patients with leiomyomas, and fibroids require an increased vascular supply for their growth. These observations suggest that VEGF and other angiogenic factors may represent potential targets for the treatment and prevention of uterine fibroids.
Abstract 2180: Development of novel targeted therapies for non-small cell carcinoma by novel Midkine inhibitors.
Authors: Takuya Fukazawa, Yutaka Maeda, Huifang Hao, Tomoki Yamatsuji, Munenori Takaoka, Nagio Takigawa, Yoshio Naomoto
Journal: Cancer Research (2013)

Abstract In the past few years a subset of driver mutations has been identified in non-small cell lung carcinoma (NSCLC), the most common type of lung adenocarcinoma. These driver mutations have differential sensitivities to various targeted therapies. The number of identified mutations in lung adenocarcinomas is limited, therefore identification of more molecular targets is needed in order to develop new treatments for NSCLCs. Efforts to find target mutations in lung adenocarcinoma with KRAS mutations are especially important because such adenocarcinomas account for 20% of lung adenocarcinoma, the most frequent type of lung adenocarcinomas. Midkine is a heparin-binding cytokine that is induced by retinoic acid in embryonal carcinoma cells. It is involved in the development of cancer because of its mitogenic effect, promotion of angiogenesis, anti-apoptotic activity and transforming activity. Midkine expression is increased in various malignant tumors, including lung, esophageal, stomach, colon, hepatocellular, breast and pancreatic carcinomas, when compared with the level of expression in normal tissues. In a proof-of-principle effort to identify novel compounds that inhibit Midkine expression, we recently conducted cell-based high-throughput screening (HTS) of 44,000 compounds in the compound library using the Midkine promoter. We identified sixteen small molecules that inhibit Midkine promoter activity. Significantly, many of these inhibitors, which reduced Midkine protein, also inhibited proliferation in non-small cell lung cancer cells which express high levels of endogenous Midkine. We assigned the name iMDK1 to one of these compounds and assessed its ability to target non-small cell lung cancer cells. 48 hours after treatment, iMDK1 dose-dependently inhibited cell growth of Midkine expressing H441 pulmonary adenocarcinoma cells but did not impair the viability of normal proliferating human lung fibroblast cells. Hoechst 33342 staining and cell cycle analysis performed by flow cytometry demonstrated that the iMDK1 compound induced apoptosis in H441 cells. Furthermore, immunoblot analysis showed that iMDK1 inhibits the PI3 kinase pathway in H441 cells. These results indicate that iMDK1 might be a promising new therapeutic tool for the treatment of Midkine -expressing lung adenocarcinoma with KRAS mutations. Here we show a novel strategy to treat non-small cell lung cancer with Midkine inhibitors. Citation Format: Takuya Fukazawa, Yutaka Maeda, Huifang Hao, Tomoki Yamatsuji, Munenori Takaoka, Nagio Takigawa, Yoshio Naomoto. Development of novel targeted therapies for non-small cell carcinoma by novel Midkine inhibitors. [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 2180. doi:10.1158/1538-7445.AM2013-2180
Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study
Authors: Maria Frantzi, Kim E. van Kessel, Ellen C. Zwarthoff, Mirari Marquez, Marta Rava, Núria Malats, Axel S. Merseburger, Ioannis Katafigiotis, Konstantinos Stravodimos, William Mullen, Jerome Zoidakis, Manousos Makridakis, Martin Pejchinovski, Elena Critselis, Ralph Lichtinghagen, Korbinian Brand, Mohammed Dakna, Maria G. Roubelakis, Dan Theodorescu, Antonia Vlahou, Harald Mischak, Nicholas P. Anagnou
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted. Experimental Design: Two studies (total n = 1,357) were performed for detecting primary (n = 721) and relapsed urothelial bladder cancer (n = 636). Cystoscopy was applied for detecting urothelial bladder cancer, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine–based peptide biomarker panels were derived from nested cross-sectional studies in primary (n = 451) and recurrent (n = 425) urothelial bladder cancer. Results: Two biomarker panels were developed on the basis of 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n = 270) and recurrent urothelial bladder cancer (n = 211), respectively. At the optimal threshold, the classifier for detecting primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC = 0.87). Conclusions: The developed urine-based peptide biomarker panel for detecting primary urothelial bladder cancer exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence. Clin Cancer Res; 22(16); 4077–86. ©2016 AACR.