tbuckley/cabot-search huggingface dataset:
Changes in the Dynamic Relationship between ER and HER2 in Paired Breast Cancer (BC) Biopsies from Patients (Pts) with Recurrent Tamoxifen-Resistant Breast Cancer.
Authors: A. Leary, S. Drury, S. Drury, S. Detre, L. Martin, M. Dowsett, M. Dowsett, S. Johnston
Journal: Cancer Research (2009)

Abstract Background: Paired biopsies at diagnosis and relapse on tamoxifen (TAM) provide information regarding adaptive changes associated with endocrine resistance. We previously reported that conversion to a HER2+ phenotype occurs infrequently1, however modest increases in HER2 may be relevant in the context of TAM resistance. Also while TAM resistance in general is associated with a fall in mean ER and PgR levels, this masks changes in individual pts.Aim: To determine whether a subset of HER2 negative BC demonstrated modest increases in HER2 by IHC and FISH, and if so whether this correlated with changes in ER and PgR expression in individual pts.Methods: Triplicate TMAs were constructed of paired primary and recurrent tumor samples from pts relapsing after adjuvant TAM. TMAs were stained for ER and HER2, whole sections for PgR. HER2 amplification was assessed by FISH.Results: Paired samples from primary and TAM-resistant recurrences were available on 53 ER+ and/or PgR+ pts. 10% had a HER2+ primary (IHC3+ and FISH+). 19% (10/53) showed increasing HER2 in the relapsed tumor (0 to 1+ in 5 pts, 1+ to 2+ in 2 pts and 0/1+ to 3+ in 3 pts). The 3 pts converting to 3+ also became FISH+. 71% (38/53) had stable or decreasing HER2. DFI was 50.3 months in the subset with stable or decreasing HER2, 40.2 in the subset with increasing HER2, and 35.2 in the HER2+ subset (p=NS). We next compared changes in ER and PgR in the 3 subsets. Among pts with stable or decreasing HER2 (N=38), there was a significant decrease in mean H-scores for both ER (p=0.001) and PgR (p=0.002) at relapse (Fig 1); the majority recurred with reduced ER (76%) or PgR levels (84%). In contrast, among pts with increasing HER2, there was no change in mean ER or PgR levels (Fig 2A); however when considering changes in individual pts, there was a balanced split between tumors relapsing with up- vs. down-regulation in ER/PgR (Fig 2B,C). In the HER2 positive subset, 100% of the pts relapsed with suppressed ER and PgR.Conclusion: In an updated series of TAM-resistant pts, we show that while conversions to HER2 3+/FISH+ remain rare (5%), modest increases in HER2 are more frequent (19%). TAM resistance in general is associated with decreasing ER and PgR. However, among pts with adaptive increases in HER2, TAM resistance is associated with either down- or up-regulation in ER expression and function. This is consistent with data from acquired endocrine resistance models we previously reported2,3.1Gutierrez et al, JCO 20052Pancholi et al, ERC 2008,3 Martin et al, JBC 2003 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 704.
LeukoScan for Imaging Infection in Different Clinical Settings
Authors: S Gratz, M L Schipper, J Dorner, H Höffken, W Becker, J W Kaiser, M Béhé, T M Behr
Journal: Clinical Nuclear Medicine (2003)

Purpose The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation. Patients and Methods 138 patients (63 men, 75 women; mean age, 58.29 ± 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan). Results True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively. Conclusions Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.
Computed Tomographic Screening for Lung Cancer Trends at Leading Academic Medical Centers From 2013 to 2015
Authors: Phillip M. Boiselle, Caroline Chiles, James G. Ravenel, Charles S. White
Journal: JAMA Oncology (2016)

Leading US academic medical centers were resurveyed to reassess their practices and determine whether there would be greater conformity of practice patterns and increased patient volumes in response to changes in policy and payment decisions and nodule guidelines.
Damage to pharynx and esophagus due to bone soup
Authors: Xiao-jun Zhao, Xin Wang, Ai-qin Li, Jian-qiu Sheng
Journal: Endoscopy (2014)

A 61-year-old woman sought medical attention after experiencing throat irritation, chest pain, and difficulty swallowing for 1 week. Chest computed tomography (CT) showed diffuse wall thickening in the upper and middle esophagus, as well as an esophageal stricture ([Fig. 1]), suggestive of esophageal carcinoma. An esophagogastroduodenoscopy (EGD) was performed. Before the endoscopy, a slightly tender swelling was observed on the right side of the neck. The endoscopy revealed swelling in the left side of the pharynx ([Fig. 2 a]) and at the entrance to the esophagus ([Fig. 2 b]), and a stenosis was also apparent; however, the lumen and mucosa exhibited normal elasticity and the lumen distended normally after air inflation. Some regions of the esophageal mucosa appeared purplish-blue ([Fig. 2 c]), although the mucosal surface was smooth with no abnormalities.
Effect of Strict Glycemic Control on Renal Hemodynamic Response to Amino Acids and Renal Enlargement in Insulin-Dependent Diabetes Mellitus
Authors: Katherine R. Tuttle, J. Lewis Bruton, Marie C. Perusek, Jack L. Lancaster, David T. Kopp, Ralph A. DeFronzo
Journal: New England Journal of Medicine (1991)

Many patients with insulin-dependent diabetes mellitus have an increase in the glomerular filtration rate and renal enlargement early in the course of their disease. Both these changes may be risk factors for the later development of diabetic nephropathy. Their cause is not known, but they could be due to augmented renal responses to the increase in plasma amino acid concentrations that occurs when dietary protein intake is high, a factor known to increase glomerular filtration and renal blood flow in normal subjects.
Abstract 2922: Androgen receptor driven transcription in a subtype of estrogen receptor negative breast cancer is controlled by FoxA1
Authors: Jessica L. Robinson, Gordon D. Brown, David E. Neal, Wayne D. Tilley, Jason S. Carroll
Journal: Cancer Research (2012)

Abstract Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumors were recently identified as an additional subgroup, characterised as ERα- AR+, but with an expression profile that resembles ERα+ luminal breast cancer. Previously, we mapped global AR binding events in a cell line model of molecular apocrine breast cancer (termed MDA-MB-453 cells) using ChIP-seq. Our results suggested that these tumours are driven by AR through its interaction with critical ER cis-regulatory elements, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers. Additionally, we found that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a Nuclear Receptor. By silencing FoxA1 using specific siRNA, we observe dramatic changes in the gene expression profile of the cells (730 genes are differentially expressed) including many of the signature molecular apocrine genes. Furthermore, silencing of FoxA1 in these breast cancer cells results in altered AR binding to the chromatin (lost, conserved and de novo binding events are found) as has been previously seen in the prostate cancer cell line, LNCaP. We are investigating this phenomenon further using proteomics to discover new AR interacting proteins and histone mark ChIP-seq to understand the proteins and epigenetic events that may mediate the reprogrammed AR binding in the absence of FoxA1. 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 2922. doi:1538-7445.AM2012-2922
Declining Rates of Lung Cancer in the United States in Young Men and Women
Authors: ANDREW GLASS
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Declining Rates of Lung Cancer in the United States in Young Men and Women Get access ANDREW GLASS ANDREW GLASS Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 368–370, https://doi.org/10.1093/jnci/83.5.368-a Published: 06 March 1991
Platelet Aggregation in Patients with Laennec's Cirrhosis of the Liver
Authors: Duncan P. Thomas, V. Jane Ream, R. Kenneth Stuart
Journal: New England Journal of Medicine (1967)

HEMORRHAGIC disorders are common in patients with Laennec's cirrhosis of the liver, and constitute one of the main causes of death in this condition.1 However, the nature of the hemostatic defect in cirrhosis is complex, and thrombocytopenia,2 low procoagulant levels,3 abnormal plasminogen-plasmin system activity4 and defective fibrin polymerization5 have all been implicated. Current concepts of hemostasis emphasize the central role of platelets in the formation of a hemostatic plug.6 Interference with normal platelet function, therefore, is particularly apt to endanger hemostasis.Proteolytic degradation products of fibrinogen, produced as a result of excessive fibrinolysis, have been demonstrated in the blood of . . .
FRI0521 A framework and process to develop core outcome measurement sets for clinical trials in rheumatology: omeract filter 2.0
Authors: M. Boers, J. R. Kirwan, G. Wells, D. Beaton, L. Gossec, M.-A. d’Agostino, P. G. Conaghan, C. O. Bingham, P. M. Brooks, R. B. M. Landewé, L. March, L. S. Simon, J. A. Singh, V. Strand, P. Tugwell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to advance clinical practice and improve health. Agreement on a core set of outcome measures to be reported in all trials could address this problem. Over the past two decades the Outcome Measures in Rheumatology (OMERACT) international consensus initiative has successfully developed core sets for many rheumatologic conditions but its expanding scope called for clarification and update of its underlying conceptual framework and working process. <h3>Objectives</h3> To formulate a conceptual framework for outcome measurement across health conditions in rheumatology and to establish an explicit process to develop core sets. <h3>Methods</h3> Literature searches, iterative consensus process (internet-based surveys, small and large group processes) of stakeholders including patients, health professionals and methodologists within and outside rheumatology. <h3>Results</h3> The framework comprises three core "Areas": Death, Life Impact and Pathophysiologic Manifestations; with a fourth strongly recommended: Resource Use. The process of core set development for a health condition starts by selecting core Domains within the Areas ('core domain set'). This requires literature searches, involvement of all relevant stakeholders — especially patients — and one or more consensus process. Next, developers select at least one applicable measurement instrument for each core Domain. Applicability means that the instrument must be Truthful (face, content and construct validity), Discriminative (between situations of interest) and Feasible (understandable, acceptable (time and monetary) costs). Depending on the quality of the instruments stakeholders formulate either a preliminary or a final 'core outcome measurement set'. In the OMERACT 11 consensus conference in May 2012, 96% of voting participants (n=125) endorsed the model and process. <h3>Conclusions</h3> OMERACT has established a strongly endorsed, generic framework including a process to develop core outcome measurement sets for rheumatology, that is likely to be useful in other areas of health care as well. <h3>Acknowledgements</h3> Caroline Terwee, Leanne Idzerda, Reuben Escorpizo, Annelies Boonen, Susan Magasi, Ian Sinha, Paula Williamson, Jane Blazeby, Gerold Stucki who gave valuable advice on this abstract; all survey participants. <h3>Disclosure of Interest</h3> None Declared
MS-30 * MENINGEAL MELANOCYTOMA WITH MULTIFOCALITY, RAPID CNS SEEDING, AND SYSTEMIC METASTASES
Authors: R. Young, W. F. Mourad, J. Graber, S. Patel, J. Glanzman, R. Kabaritti, T. Santiago, S. Kalnicki, M. Garg
Journal: Neuro-Oncology (2014)

OBJECTIVE: Meningeal melanocytomas are rare entities that range from benign and well-differentiated lesions with a favorable prognosis to higher-grade lesions that may undergo malignant transformation with subsequent CNS dissemination. Transition from a meningeal melanocytoma to primary CNS melanoma is particularly rare with only a handful of cases reported. Systemic spread of a transformed meningeal melanocytoma, an exquisitely rare occurrence, is, to the best of our knowledge, reported in only three cases. Here we report the case of a woman who initially presented with multifocal meningeal melanocytomas with subsequent rapid transformation, diffuse CNS seeding, and systemic metastases. CLINICAL PRESENTATION AND MANAGEMENT: A 43 year-old woman presented with headaches, nausea, and vomiting for two months with negative GI work-up. She experienced a syncopal episode with CT and MRI brain scans showing 3 dural-based lesions involving the foramen magnum, fourth ventricle, and right CPA. The patient underwent STR of the lesions; the anterior lesion was inaccessible. Pathology reported a melanocytoma with malignant features. A negative dermatology and ophthalmology work-up were performed. The patient received post-operative radiotherapy (50.4 Gy) to the posterior fossa. Six months following surgery she presented with new neurological symptoms, and MRI of the neuroaxis showed new leptomeningeal enhancement within the cerebellum, thoracic spine, and supratentorially. With neuro-oncology input, she was started on Temodar and underwent palliative spinal RT. Unfortunately she continued to experience pain, and follow-up MRI showed new intrathecal C-spine nodules. Abdominal imaging revealed multiple lung and liver metastases, with biopsy of a 7-cm liver lesion revealing malignant melanoma. The patient unfortunately continued to deteriorate and succumbed to her disease approximately 9 months following diagnosis. CONCLUSION: Meningeal melanocytomas are rare tumors that are not only challenging to diagnose, but challenging to clinically predict and manage. This case illustrates these challenges and the multidisciplinary response needed to optimize outcomes.
OP0109 Evaluation of potential risk factors of amyloidosis in familial mediterranean fever
Authors: T. Kasifoglu, S. Bilge, E. Gonullu, F. Bekdemir, C. Korkmaz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is a genetic disease which is frequently seen in Middle East Region. The most common reason of morbidity and mortality is the end stage renal failure due to amyloidosis. <h3>Objectives</h3> The potential risk factors of amyloidosis are known as ethnic origin (Jewish, Armenian, Turkish, and North African origin), non-usage of colchicines, and family history. Various investigators suggest that M694V mutation, especially homozygote pattern, is a risk factor for amyloidosis. In literatures reported from Turkey, it is stated that there is only a limited association. In this study, we aimed to investigate the affects of MEFV mutations and other potential risk factors on amyloidosis. <h3>Methods</h3> The findings of 396 FMF patients of our clinic was retrospectively evaluated such as amyloidosis, MEFV mutations, gender, clinical features, family history, ages at initial symptoms, ages at diagnosis, the duration of colchicin usage. Amyloidosis was diagnosed by rectal or renal biopsies of patients with proteinuria over than 500 mg/day. <h3>Results</h3> Renal amyloidosis was diagnosed at 8.3% (33) patients. There was no difference between patients with amyloidosis and without amyloidosis in terms of clinical features, family history, ages at initial symptoms, ages at diagnosis, the duration of colchicin usage. MEFV mutation was studied in 159 of 363 patients without amyloidosis and in 27 of 33 patients with amyloidosis. The mutations detected in patients with amyloidosis were M694V homozygote, M694V heterozygote, and compound heterozygote of M694V/V726A, M694V/M680I, V726A/M680I or V726A/R761H. The most common mutation was M694V homozygote of patients with and without amyloidosis (59.3% versus 32%). The frequency of M694V homozygote of patients with amyloidosis was statistically high from the frequency of patients without amyloidosis (p&lt;0.001). But there was no difference in terms of other mutations. <h3>Conclusions</h3> It is shown that, the only most common risk factor of Turkish patients is the M694V homozygote gene mutation in our study. But amyloidosis is not seen in all patients with M694V homozygote mutation. Therefore, large series are needed to evaluate the other potential risk factors. Close monitoring could be necessary for patients with M694V homozygote mutation. <h3>Disclosure of Interest</h3> None Declared
NI-39 * INITIAL EVALUATION OF AN ADENOSINE RECEPTOR AGONIST'S ABILITY TO TRANSIENTLY DISRUPT THE BLOOD BRAIN BARRIER (BBB) IN PATIENTS WITH IN NORMAL BRAINS
Authors: S. Jackson, M. Lodge, A. Piotrowski, R. Wahl, S. Grossman
Journal: Neuro-Oncology (2014)

BACKGROUND: Regadenoson is an FDA approved adenosine receptor agonist which transiently disrupts the BBB in rodents allowing systemically administered high molecular weight dextran (MW 70kD) to enter brain parenchyma. This agent is used clinically for cardiac stress tests in patients unable to exercise in conjunction with 99mTc-sestamibi and cardiac SPECT imaging. 99mTc-sestamibi (MW 600) has been studied as an imaging agent in patients with brain tumors and demonstrates permeability only where there is BBB disruption. METHODS: Patients undergoing clinically indicated and standard pharmacologic cardiac stress tests (10mCi of 99mTc-sestamibi with cardiac imaging followed by 30mCi of 99mTc-sestamibi with regadenoson and cardiac imaging) were eligible. This IRB approved study only added brain SPECT imaging to the pre- and post-regadenoson imaging to determine if more isotope entered the brain following regadenoson administration. RESULTS: Six patients were accrued and pre- and post-regadenoson isotope quantitation in brain parenchyma and overlying scalp were compared to correct for the different 99mTc-sestamibi doses routinely administered in cardiac stress tests. The results were strikingly consistent between patients. Mean isotope counts in the brain were 3.1 times higher (range 2.6-3.4) and in the scalp were 4.2 times higher (range 3.4 to 4.5) post-regadenoson. CONCLUSION: Significantly higher isotope counts were seen in each of these patients with presumably normal brains in the post-regadenoson setting. However, brain imaging with this standard cardiac imaging protocol, which includes different doses of isotope in the pre and post-regadenoson settings, does not allow a definitive statement regarding the ability of this agent to temporarily disrupt the BBB and allow entry of previously impermeable systemically administered compounds into the brain. Further studies are underway to answer this question definitively as transient disruption of the BBB would be of major importance to the field of neuro-oncology.
Time of Truth for Cancer Vaccines
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Time of Truth for Cancer Vaccines Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 5, 2 March 1994, Pages 330–331, https://doi.org/10.1093/jnci/86.5.330 Published: 02 March 1994
An Ectopic Mediastinal Parathyroid Adenoma Accurately Located by a Single-Day Imaging Protocol of Tc-99m Pertechnetate–MIBI Subtraction Scintigraphy and MIBI-SPECT–Computed Tomographic Image Fusion
Authors: Domenico Rubello, Dario Casara, Davide Fiore, Piercarlo Muzzio, Giancarlo Zonzin, Brahm Shapiro
Journal: Clinical Nuclear Medicine (2002)

Purpose Because ectopic parathyroid adenoma (PA) is a frequent cause of failed initial surgery, an imaging approach with accurate preoperative localization is recommended by some authors in patients with primary hyperparathyroidism (HPT). Methods The authors describe a 52-year-old woman in whom primary HPT was diagnosed incidentally during a screening program for osteoporosis. The peculiarity of this case is that the patient was examined before operation in a single-day multimodal imaging protocol based on the combination of high-resolution cervical ultrasound, planar Tc-99m pertechnetate–MIBI scans, and an MIBI-SPECT–computed tomographic (CT) image fusion study. An ectopic PA was accurately located in the upper middle mediastinum, close to the lower margin of the sternal notch. Results Guided by the MIBI-SPECT–CT fusion images, the surgeon performed a limited median sternotomy and easily removed the PA that was revealed before operation. To confirm the completeness of resection, a bilateral neck exploration was performed through the same incision, with identification of three normally sized parathyroid glands. Conclusions Our experience suggests the utility of multimodality imaging procedures for the accurate preoperative localization of PAs, particularly when they are present in ectopic mediastinal locations. Such procedures, including the MIBI-SPECT–CT image fusion study, can be performed in a single day.
299 DOSE-DEPENDENT MODULATION OF NF-κB AND miR-21 BY DEOXYCHOLIC ACID DURING APOPTOSIS OF PRIMARY RAT HEPATOCYTES
Authors: P.M. Rodrigues, M.B. Afonso, A.L. Simao, D.M.S. Ferreira, P.M. Borralho, C.M.P. Rodrigues, R.E. Castro
Journal: Journal of Hepatology (2013)