tbuckley/cabot-search huggingface dataset:
Abstract 2702: Renal cell carcinomas lack arginosuccinate synthetase expression and respond to pegylated arginine deiminase treatment
Authors: Wei He, Jianhe Chen, Yuhui Zheng, Zaoming Dai, Yan He, Bor-Wen Wu, John Bomalaski
Journal: Cancer Research (2010)

Abstract Biomarkers may be predictive of benefit from therapy. As a result, there is increasing interest in determining new biomarkers and new agents that may target specific pathways that are abnormal in a certain cancer. Normal cells produce arginine internally via the urea cycle. However, certain cancer cells lack one of the urea cycle enzymes, argininosuccinate synthetase (ASS) and become dependent upon an exogenous supply of arginine for growth and survival. For these ASS-deficient cancers, preferential killing of tumor cells induced by arginine deprivation may be effective and safe. ADI-PEG20 is a microbial enzyme, arginine deiminase conjugated with polyethylene gycol. The primary mechanism of action of ADI-PEG20 is arginine deprivation. Thus cancers that are deficient in ASS expression and require arginine could benefit from ADI-PEG20. ADI-PEG20 has been in phase 2 clinical trials for the treatment of hepatocellular carcinoma and metastatic melanoma. Patients whose cancers were deficient in ASS expression have demonstrated medical benefit from ADI-PEG20. Thus at least in these cancers, lack of ASS expression could serve as a biomarker to predict clinical benefit from ADI-PEG20. Other investigators have noted that human renal cell carcinoma (RCC) tissue specimens lack expression of ASS. To confirm these observations and investigate the extent of ASS deficiency in RCC, we analyzed biopsy samples obtained from 31 patients for ASS expression by immunohistochemistry and found all to be ASS negative. We also established three primary RCC cell lines and tested them for response to ADI-PEG20 treatment. Dose dependent growth inhibition was observed after 48 hours for all three cell lines using the MTS proliferation assay. We further tested three ATCC RCC cell lines, 786-O, ACHN and Caki-1 using the MTS assay and observed similar growth inhibition after 48 hours. Cell cycle analysis using the three primary RCC lines revealed that G1 arrest was apparent in samples treated with ADI-PEG20. After 48 hours of ADI-PEG20 treatment, the percentage of cells in G1 increased from 33% to 62%. These results suggest that ADI-PEG20 can potentially be an effective therapeutic agent for the treatment of RCC. They also suggest the potential utility of ASS expression as a biomarker in identifying patients that are most likely to benefit from the ADI-PEG20 treatment. 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 2702.
SP0027 How to use the eular brussels declaration in support of national campaigning
Authors: D. Chichikj
Journal: Annals of the Rheumatic Diseases (2013)

The Brussels Declaration can provide an enormous leverage for taking action on national level in any EU country. The European Union is probably one of the greatest achievements in human history. Thus, any collaborative efforts, declarations or laws that represent all the people in this union, in general the unified efforts by people can have much bigger and profound impact in every aspect. Though R. Macedonia at the time politically is not part of the EU, it is represented in EULAR. This is a great achievement by the people and organizations that form and represent EULAR. There is no doubt; this gave NGO NORA and Macedonia an enormous leverage while working side by side with EULAR and its members. Familiarizing the general public and health institutions with the Brussels Declaration in R. Macedonia, initiated a very positive chain of developments. NGO NORA chose to focus on just three out of the six issues targeted in the Brussels Declaration however the activities around these key issues give a much needed focus. Thus, the Brussels Declaration can give sharp and very precise form to act upon, on whose almost any national organization can build on. This also proves that almost all nations face similar or closely related problems. <h3>Disclosure of Interest</h3> None Declared
Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis
Authors: Sijia Huang, Nicole Chong, Nathan E. Lewis, Wei Jia, Guoxiang Xie, Lana X. Garmire
Journal: Genome Medicine (2016)

More accurate diagnostic methods are pressingly needed to diagnose breast cancer, the most common malignant cancer in women worldwide. Blood-based metabolomics is a promising diagnostic method for breast cancer. However, many metabolic biomarkers are difficult to replicate among studies.We propose that higher-order functional representation of metabolomics data, such as pathway-based metabolomic features, can be used as robust biomarkers for breast cancer. Towards this, we have developed a new computational method that uses personalized pathway dysregulation scores for disease diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods.The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under the Curve, a receiver operating characteristic curve) of 0.968 and 0.934, sensitivities of 0.946 and 0.954, and specificities of 0.934 and 0.918. These two metabolomics-based pathway models are further validated by RNA-Seq-based TCGA (The Cancer Genome Atlas) breast cancer data, with AUCs of 0.995 and 0.993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer.We have successfully developed a new type of pathway-based model to study metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease diagnosis.
Abstract 709: Mitosis interference of cancer cells by NovoTTF-100A causes decreased cellular viability.
Authors: Sze Xian Lee, Eric T. Wong, Kenneth D. Swanson
Journal: Cancer Research (2013)

Abstract Cancer cell death from traditional cytotoxic chemotherapy and radiation is a result of triggering cell cycle checkpoint with p53 playing a prominent role in orchestrating this effect. Unlike these traditional approaches, the NovoTTF-100A device, which has been approved for the treatment of recurrent glioblastomas, kills tumor cells by a novel mechanism that interferes with the proper progression through mitosis. As is the case with earlier therapeutic interventions, only a subset of patients shows significant response to TTFields treatment. Our research reveals that the tumor-treating fields (TTFields) affects processes proximal to the metaphase-to-anaphase transition, leading to cell cycle arrest in anaphase and eventual cell death. Tissue culture cells exposed to the TTFields during mitosis exhibit a variety of outcomes, including cell arrest in anaphase, cytokinesis with cytokinetic furrow regression, and slippage out of mitosis without division. Time-lapse movies of cells stained with the DNA stain DRAQ5 and exposed to the TTFields revealed membrane blebbing and oscillation, as well as failed segregation of sister chromatids from the metaphase plate, both of which were initiated near the time of metaphase-to-anaphase transition. Immunoflourescence of cells after short-term treatment with TTFields during mitosis showed disordered separation of chromosomes from metaphase plates accompanied by lagging chromosomes, dispersion of chromosomes from the metaphase plate, chromosomes de-condensation in the absence of cytokinesis, and daughter cells with asymmetric chromosomal segregation. Flow cytometry also revealed the presence of cells with abnormal DNA content in cultures treated with TTFields. In contrast to the p53 mutant cell lines, MDA-MB-231 and HCT 116, U87 cells with wild-type p53 exhibit increased Annexin V binding, Caspase activation and increased markers of endoplasmic reticulum (ER) stress after brief exposure during mitosis. This suggests the TTFields induced cellular damage is able to trigger p53-dependent cell death in cells that escape killing during M-phase. These data show that the effects of TTFields on cellular damage during M-phase and provide evidence for the notion that the differential responses to treatment seen in patients may be rooted in the underlying genetic alterations in their tumors. Citation Format: Sze Xian Lee, Eric T. Wong, Kenneth D. Swanson. Mitosis interference of cancer cells by NovoTTF-100A causes decreased cellular viability. [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 709. doi:10.1158/1538-7445.AM2013-709
From the Orange Country
Authors: B. Armstrong
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Your esteemed correspondent from the little Republic on the south of us—Dr. Ellis Quay of Dublin (<b>199</b>:768, 1967)—complains that Dr. Gode's discussion of the penis lacks rigor (<b>199</b>:256, 1967). And then the man lets out with a flurry of fancy words from the French and the Latin! Well, Sir, if it's rigor he wants, and if he's got any deep regard for the language, let him take a journey north across the border—that is, if he isn't afraid. Then I and some other Ulster boys can meet him for an hour or so of talk, and a drink or two. He'll have a grand time, and we'll remind him of some old words and sayings that his dad, and his dad's dad, used when discussing these matters. We'll recall for him things he can say and write that will match his subject, and ours, far
Correlation between pN0(mol+) and standard clinico-pathological prognostic factors in SLN of breast cancer patients.
Authors: M Varela, A Moreno, C Falo, E Villalba, E Benito, J Serra, A Fernández, AP Escobedo
Journal: Cancer Research (2009)

Abstract Abstract #1025 Objective: To establish the significance of disease detected by reverse transcription polymerase reaction (RT-PCR) in sentinel lymph nodes (SLN) of breast cancer patients.&amp;#x2028; Background: In breast cancer patients, the axillary status is the most important prognostic factor. The RT-PCR appeared to be a sensitive method, but the relevance of pN0(mol+) has not yet been established.&amp;#x2028; Methods: 674 patients with T1-T3 primary invasive breast cancer were included in a prospective study. SLN were analysed by routine pathology analysis (staging with hematoxylin-eosin – H&amp;E– and immunohistochemistry – IHQ–) and RT-PCR. Correlations between molecular diagnostics and standard clinicopathological prognostic factors, including St. Gallen risk categories were analyzed.&amp;#x2028; Results:&amp;#x2028; Of the 674 patients, 131 (19.4%) had one or more pathology-positive SLN detected by routine pathological, 137 (20.3%) were exclusive molecular positive - pN0 (mol+) - and 406 (60.2%) were without evidence of disease.&amp;#x2028; We evaluated correlation between nodal staging with pathological and molecular analysis and clinicopathological factors in the whole patient cohort. Positive cases were significantly associated with tumor size (p&amp;lt;0.010), histological grade (I-II vs. III) (p&amp;lt;0.048), vascular invasion (p&amp;lt;0.000) and St. Gallen risk category (p&amp;lt;0.003).&amp;#x2028; Conclusions: molecular staging of SLN using RT-PCR could serve as a useful complement to standard clinico-pathological risk factors. Correlation between pN0(mol+) patient group with survival rates will define the clinical relevance of lymph node molecular detected micrometastases in this patient population. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1025.
Morphologic and Functional Evidence for Release of Mast-Cell Products in Bullous Pemphigoid
Authors: Bruce U. Wintroub, Martin C. Mihm, Edward J. Goetzl, Nicholas A. Soter, K. Frank Austen
Journal: New England Journal of Medicine (1978)

We studied nine patients with bullous pemphigoid, a generalized cutaneous eruption- for evidence of mast-cell involvement during development of lesions. As in other reports, six of nine patients demonstrated a serum antibody directed against the epidermal basement-membrane zone. Direct immunofluorescence studies of lesions revealed depostion of immunoglobulin and complement proteins at the basement-membrane zone in six of nine and nine of nine patients, respectively. Participation of mast cells was suggested by a sequence of pathologic alterations in which there was progressive mast-cell degranulation and late eosinophil infiltration. In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid. The data indicate that, in addition to activation of the complement system, involvement of mast cells is an early and continuing event in the development of the cutanenous lesions of bullous pemphigoid.
Absence of Thirst in Association with Hydrocephalus
Authors: Richard M. Hays, Paul R. McHugh, Hibbard E. Williams
Journal: New England Journal of Medicine (1963)

DEHYDRATION is commonly seen in patients with impaired consciousness whose thirst mechanism is undamaged, but who are unable to ask for water.1 A few cases have been described, however, in conscious patients who, for a variety of reasons, have lost the ability to experience thirst. Avioli and his associates,2 for example, have recently reported absence of thirst in a twelve-year-old girl with extensive hypothalamic damage caused by Schüller–Christian disease. In the case presented below, the patient, although fully alert and carrying on normal activities, required hospitalization twice in a five-year period for severe dehydration and hypernatremia. Investigation revealed an inability . . .
Abstract 4861: Identification of premalignant bladder markers using DNA microarray analysis of the UPII-SV40Tag model for invasive bladder UCC
Authors: Randolph Stone, Anita Sabichi, Jennifer Gill, I-Ling Lee, Urska Cvek, Marjan Trutschl, Patrick Adegboyega, Michael Dai, Rasiah Loganantharaj, John Clifford
Journal: Cancer Research (2011)

Abstract Urothelial cell carcinoma of the bladder (UCC) ranks 5th in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. A few urine-based tests for screening and surveillance are commercially available for bladder cancer, but there are no reliable non-invasive methods for detecting premalignant UCC. In order to determine molecular mechanisms involved in early UCC development and to identify new biomarkers for detection, diagnosis and prognosis of UCC, a transgenic mouse model for invasive bladder cancer (UPII-SV40Tag mice) was analyzed by DNA microarray technology. Genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild type (WT) littermates at 3, 6, 20 and 30 weeks of age were identified. The ages selected correspond to premalignant, carcinoma in-situ, and early and later stage papillary UCC, respectively. Approximately 1,900 unique genes were differentially expressed (≥ 3-fold difference at one or more time points) between WT and UPII-SV40Tag urothelium during the time course of tumor development. A high proportion of cell cycle regulatory genes and proliferation signaling genes were more strongly expressed in the UPII-SV40Tag bladder urothelium. Several of the genes upregulated and downregulated in UPII-SV40Tag urothelium were tested as biomarkers for premalignancy, including autocrine motility factor (AMFR), hyaluronan-mediated motility receptor (Hmmr), proliferating cell nuclear antigen (PCNA), Rac GTPase activating protein 1 (RacGAP1), superoxide dismutase 3 (SOD3), collagen 1a2 (Col1a2), and others. These tests were performed by analyzing urine samples from a recently completed Phase II, randomized, placebo controlled chemoprevention trial (N01 CN85186, PI: A. Sabichi) that was designed to test whether celecoxib can prevent recurrence in patients successfully treated by transurethral resection (TUR) for non-muscle invasive bladder cancer. Positive markers, Hmmr and RacGAP1, and a negative marker, Col1a2, have been identified in patient urine samples that show promise for detecting UCC recurrence. We are currently attempting to determine the biological function of Hmmr, and RacGAP1 in bladder premalignancy. 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 4861. doi:10.1158/1538-7445.AM2011-4861
Chronomodulated Administration of Oxaliplatin plus Capecitabine (XELOX) as First Line Chemotherapy in Metastatic Colorectal Cancer Patients: Phase II Brunch Regimen Study.
Authors: Kezban Nur Pilanci, Sezer Saglam, Alper Okyar, Serap Yucel, Zeliha Pala Kara, Cetin Ordu, Esat Namal, Rumeysa Ciftci, Ulkuhan Koksal, Esra Kaytan Saglam
Journal: Journal of Clinical Oncology (2015)

e14646 Background: The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered morning and noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first line XELOX chemotherapy in patients with metastatic colorectal cancer. Methods: Measurable disease in at least one site (a lesion that can be accurately measured in size) identified by instrumental examinations and chemotherapy-naive patients with 30 advanced CRC were considered eligible for the study accrual. Oxaliplatin 130 mg/m2 on day 1 plus chronomodulated oral capecitabine 2000 mg/m2 per day; (50% dose at 8:00 AM and 50% dose at 12:00 noon), days 1-14 every 21 days. Tumour lesions were evaluated every third cycle and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST). After completion of treatment, computed tomography scan was carried out every third month until progression was documented. Results: Median age was 57.1 years (range 32–77 years). Median follow-up was 15.9 months (range 3.0–33.0 months). Response was calculated according to RECIST. In an intent-to-treat efficacy analysis; 3 patients(10%) had complete response, 13 patients(43.3%) had partial response and 7 patients(23.3%) had no change. Ten patients had progressive disease at their first evaluation(33.3%). The median progression free survival(PFS) was 9.5 months(3-21months). There were no grade IV toxicities. One patient(3.3%) had grade III neutropenia. Hand-foot syndrome developed in two patients ( 6.6%, grade 1) and one patient (3.3%, grade 2). Conclusions: By using this chronomodulated treatment schedule in metastatic colorectal carcinoma patients neither doses of drugs were modified nor causing a delay in treatment were adressed because of the adverse affects. Avoiding from toxicity with this regiment may be related to the high remission rates in our study.
Extramedullary Gastric Relapse of Acute Lymphoblastic Leukemia Following Allogeneic Stem Cell Transplant
Authors: Anthony Ciarallo, William Makis, Javier-A. Novales-Diaz, René P. Michel
Journal: Clinical Nuclear Medicine (2011)

A 26-year-old man with a prior history of acute leukemia that was treated with a stem cell transplant (SCT) was referred for an F-18 FDG PET/CT to assess suspicious new gastric mucosal lesions. The lesions were FDG-avid and were histologically proven to be acute lymphoblastic leukemia (ALL). Extramedullary relapse of ALL after SCT is very rare, with only 60 cases reported in the literature, and the role of F-18 FDG PET/CT in monitoring for ALL relapse following SCT has not been previously investigated. This rare case report highlights the use of F-18 FDG PET/CT in staging gastric relapse of ALL following SCT.
Case 38-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, J.R. Levinson, J.F. Southern
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 33-year-old man was admitted to the hospital because of aortic regurgitation and aneurysmal dilatation of the ascending aorta.The patient was in good health until six months earlier, when severe substernal pain developed. He was seen in the emergency ward of another hospital, where no abnormality was found. An x-ray film of the chest was reported to show that the heart and mediastinum were normal. Thereafter he experienced occasional mild exertional dyspnea, fatigue, and extensive loss of scalp hair. Four months before entry a dental procedure was performed without incident.Twelve days before admission the patient . . .
RADIOFREQUENCY ABLATION OF THE INTERVENTRICULAR SEPTUM TO TREAT OUTFLOW TRACT GRADIENTS IN HOCM: NOVEL USE OF CARTOSOUND TECHNOLOGY TO GUIDE ABLATION
Authors: Robert Cooper, Suneel Simon Modi, Adeel Shahzad, Jonathan Hasleton, Joseph DeGiovanni, Mark Hall, Derick Todd, Rod Stables
Journal: Journal of the American College of Cardiology (2015)
Frequent Exacerbations of Chronic Obstructive Pulmonary Disease — A Distinct Phenotype?
Authors: Donald P. Tashkin
Journal: New England Journal of Medicine (2010)

Chronic obstructive pulmonary disease (COPD) is a partially reversible disorder characterized by progressive airflow obstruction, the course of which is punctuated by episodes of acute symptomatic worsening (exacerbations) of variable severity and frequency. Exacerbations have an important effect on both the patient and society, including worsening health status and increased risks of hospitalization — with its attendant costs — and death.1 Because of these negative consequences, prevention of exacerbations is recommended as a key goal of COPD management.1 Given its symptomatic nature, however, and the absence of a readily available and validated biomarker, there is no complete consensus regarding the . . .
Abstract 3408: Gene expression profiling of MCF10A series of Ha-Ras transformed human breast epithelial cells: Gene expression involved in EMT pathway
Authors: Sihyung Yang, April E. Cho, Eunhye Lee, Soojeong Lim, Raymond F. Novak, So Hee Kim
Journal: Cancer Research (2012)

Abstract MCF10A series (10A, 10AT, 10ATG3B, 10CA1h and 10CA1a) of breast epithelial cells were examined for gene expression involved in epithelial-mesenchymal transition (EMT) process. This model represents a unique system for examining early and progressive alterations that occur in cells. Microarray analysis showed more than 720 genes are highly expressed (&amp;gt;2 fold, P&amp;lt;0.05) but over 870 genes significantly decreased (&amp;lt;0.5 fold, P&amp;lt;0.05) compared to control 10A. Ontology analysis of 759 highly expressed genes in malignant 10CA1a showed genes involved in metabolism were the greatest. 72 genes progressively increased and 392 genes gradually decreased with the tumorigenicity. 12 genes in EMT were significantly reduced (&amp;lt;0.5 fold, P&amp;lt;0.05) and 24 genes significantly increased (&amp;gt;2 fold, P&amp;lt;0.05) from microarray and 12 genes significantly decreased (P&amp;lt;0.01) and 18 genes were highly expressed (P&amp;lt;0.01) from PCR array. Based on two analyses, BMP7, COL5A2, DSC2, GSK3B, RGS2, TSPAN13 and VIM were highly expressed but MAP1B, TIMP1 and WNT5A significantly decreased. Collectively, altered gene levels in EMT process may correlate with increasing risk of tumorigenicity and these genes may serve as an early prognostic indicator of tumorigenic potential. Supported by grant from NRF (R-2009-006-6765). 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 3408. doi:1538-7445.AM2012-3408