tbuckley/cabot-search huggingface dataset:
Pituitary Adenoma Detected on FDG Positron Emission Tomography in a Patient with Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: RICHARD J. CAMPEAU, ODILE DAVID, ADAM M. DOWLING
Journal: Clinical Nuclear Medicine (2003)

A 52-year-old woman with a history of treated non-Hodgkin’s lymphoma, B-cell type, was examined for a right eyelid mass proved on excision to be a mucosa-associated lymphoid tissue lymphoma. She was referred for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging of the whole body, including the brain, to identify the possible presence or recurrence of lymphoma. The FDG-PET images revealed focal marked FDG uptake in the pituitary gland but no evidence of abnormal metabolic sites in the rest of the body, including the orbital regions. Magnetic resonance imaging and computed tomography confirmed a 1.8 × 1.5 cm intrasellar mass. Surgery was performed, and histologic examination revealed a nonfunctional adenoma that was negative for leukocyte common antigen staining, an antigen that is positive in lymphoma but negative in pituitary adenoma. This case provides evidence for avid uptake of FDG on PET imaging of pituitary adenomas.
Rociletinib: has the TIGER lost a few of its stripes?
Authors: K Dhingra
Journal: Annals of Oncology (2016)

In this issue of Annals of Oncology, Yver et al. [1] chronicle the history of the development of osimertinib (AZD9291), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor designed to target T790, a common mutation associated with resistance to first- and second-generation EGFR-targeted small molecule drugs. A commendable time of 32 months from first human dose to first approval was achieved through a combination of thoughtful clinical development strategy, close interaction with regulatory authorities and timely development of companion diagnostics.
AB0182 Increased Expression of Hypoxia Inducible Factor-1 Alpha in Lupus Nephritis
Authors: W. Deng, Y. Ren, X. Feng, L. Sun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Evidence has accumulated that hypoxia played a significant role in the pathogenesis and progression of both acute renal injury and chronic renal disease. <h3>Objectives</h3> In this study, the expression of hypoxia inducible factor-1 alpha (HIF-1α) in lupus nephritis (LN) was explored. <h3>Methods</h3> Renal biopsy samples from 23 LN patients and 20 patients with renal carcinoma were obtained. The expression of HIF-1α was examined using immunohistochemical staining, and their correlations with clinical and pathological features were assessed. To confirm the results in human study, HIF-1α expression in kidney sections from both MRL/lpr and C57BL/6J mice was measured. Dimethyloxaloylglycine (DMOG), inhibitor of HIF-degrading prolylhydroxylases, was applied to detect the effect of HIF-1α on cell proliferation in mouse glomerular mesangial cell line by CCK8 assay. <h3>Results</h3> Tissues from LN patients exhibited higher HIF-1α expression in both glomerular (81.50±1.55% vs 60.52±5.00%, p&lt;0.001) and tubulointerstitial location (80.25±1.94% vs 65.40±4.19%, p&lt;0.01) than the tumor surrounding tissues from patients with renal carcinoma. HIF-1α was significantly elevated in class IV LN compared to other pathological types. There were associations between intraglomerular number of HIF-1α-positive cells and renal pathology activity index as well as several clinical variables in LN patients, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein and serum albumin. Intraglomerular HIF-1α-positive cells in MRL/lpr mice were also significantly increased (70.88±4.91% vs 34.50±5.94%, p&lt;0.001). After DMOG stimulation, the proliferation rate of glomerular mesangial cells was significantly elevated (OD value 1.32±0.03 vs. 1.11±0.0, p&lt;0.001). <h3>Conclusions</h3> HIF-1α is highly expressed in both glomerular and tubulointerstitial tissues in LN, especially in class IV LN. High expression of HIF-1α can promote the proliferation of glomerular mesangial cells, thus may represent a novel target for LN therapy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2418
PWE-204 Does cholangioscopy improve the diagnosis of “indeterminate” biliary strictures?
Authors: S Menon, V Lehkaraju, R Sturgess
Journal: Gut (2012)

<h3>Introduction</h3> The precise assessment of a biliary stricture can be challenging. Multi-modal imaging with CT/MR and EUS can generally determine the nature of a biliary stricture and EUS in particular, can offer histological diagnosis. However, ERCP is often necessary for diagnostic evaluation and management of biliary strictures and biliary cytology performed at ERCP has a diagnostic yield of only 10–40%. Assessment of focal intrahepatic strictures can thus, be even more difficult. Cholangioscopy offers the advantage of tissue sampling under direct vision, thereby enhancing diagnostic precision. The aim of the study was to review our experience of cholangioscopy in the assessment of biliary strictures. <h3>Methods</h3> A review of a prospectively maintained database of all procedures involving per oral single operator cholangioscopy at our institution (June 2008–2011), was performed. “Indeterminate” strictures were defined as biliary strictures referred for diagnostic evaluation with previous negative cytology. Other biliary strictures were referred for evaluation after negative EUS-FNA, or directly based on radiological abnormalities. Follow-up data were acquired through case note review and phone calls to referring hospitals. Summary statistics were applied. <h3>Results</h3> 72 patients underwent cholangioscopy for “indeterminate strictures” during the study period (42 males, mean age 64 years (SD 11)). These patients had a total of 228 investigations performed as part of their evaluation (mean 3 investigations/person). 39 (54%) had a previous ERCP (range 1–6 procedures per person). At cholangioscopy, adequate mucosal visualisation was achieved in 64 (89%) and direct biopsy sampling was carried out in 36 (50%) patients. 35 patients needed prior sphincterotomy. Tissue diagnosis was achieved in 54 (75%) patients (15 cholangiocarcinoma, 5 PSC-related strictures, 12 ischaemic/inflammatory, 1 biliary leiomyoma and 21 normal tissue). 6 (10%) had complications related to the procedure (5 cholangitis, 1 post-sphincterotomy bleed). On follow-up (mean 10 months (range 2–24 months), four patients underwent surgery (2 cholangiocarcinoma, 2 ischaemic/inflammatory strictures), 13 had endoscopic palliation for cholangiocarcinoma, of which seven died (mean 9 months). <h3>Conclusion</h3> Cholangioscopy is valuable tool in the diagnostic evaluation of biliary strictures. <h3>Competing interests</h3> None declared.
Case 35-1997
Authors: L. Jack Faling, Eugene J. Mark
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 65-year-old woman was admitted to the hospital because of a persistent dry cough, diarrhea, and paroxysmal atrial fibrillation with orthostatic hypotension.The patient had had hypertension for 40 years and diabetes mellitus for 6 months. Six years before admission, she was treated for ulcerative proctitis. Thirty-nine months before admission, she had an anterior myocardial infarct, with cardiac arrest and ventricular fibrillation. Amiodarone was administered. Percutaneous transluminal angioplasty of the left anterior descending coronary artery was performed 13 months later. An episode of paroxysmal atrial fibrillation failed to respond to other maneuvers but was treated successfully with . . .
Establishing a Framework — Does Testosterone Supplementation Help Older Men?
Authors: Eric S. Orwoll
Journal: New England Journal of Medicine (2016)

Aging is variably but inevitably accompanied by declines in health; concomitantly, in men, circulating sex-steroid levels fall with age.1 To what extent these two processes are causally linked and whether testosterone therapy can prevent or ameliorate important age-related problems have been major issues in men’s health. In 2003, a committee assembled by the Institute of Medicine (IOM) found a paucity of randomized, placebo-controlled clinical trials involving older men and noted a lack of definite evidence that testosterone therapy conferred benefits.2 The committee recommended that clinical trials be initiated, first to evaluate the efficacy of testosterone supplementation in older men and . . .
Abstract 749: Characterization of p54nrb/NonO promoter in NSCLC.
Authors: Sheng-Yi Lin, Yi-Hua Lai, Hsuan-Yu Chen, Huei-Wen Chen, Sung-Liang Yu, Tse-Ming Hong, Gee-Chen Chang, Jeremy J.W. Chen
Journal: Cancer Research (2013)

Abstract p54nrb/NonO is a multiple function nuclear protein. It has been implicated in numerous processes within the nucleus including transcriptional regulation, DNA unwinding, nuclear RNA processing, DNA double-strand break repair and tumorigenesis. In vivo, p54nrb usually forms a heterodimer with its partner PSF as a RNA splicing factor, but its roles in tumor progress is unknown. In recent years, p54nrb has been report in bladder cancer and prostate cancer that different expression of p54nrb between normal tissue and tumor tissue. p54nrb is upregulated in bladder cancer and prostate cancer. However, the mechanism about transcriptional regulation of p54nrb is still unknown. In this study, we characterize p54nrb function in non-small cell lung cancer cell (NSCLC) line and the transcriptional regulation of p54nrb promoter. First we find p54nrb transcription start site and use PCR technology to clone -1671/+1261 (2952 bp) p54nrb promoter. Then we analyzed p54nrb promoter region by deletion of p54nrb promoter 5’ end and luciferase report assay. The results of luciferase assay demonstrated that there is an important regulation region in p54nrb promoter +311/+414 fragment. And deletion of p54nrb promoter +109/+203 region can cause a part of luciferase activity decreasing. Furthermore, we used programe to predict what kind of transcription factor binding site on these two p54nrb promoter region. And we found three CCAAT box and AP-1, AP2α, Sp1, PEA3, NF-1, YY1 binding site. To investigate which transcription factors involve in transcriptional regulation of p54nrb. We observed the change of p54nrb after overexpressed AP-1, AP2α and Sp1 in CL1-0, CL1-5 and A549 cell line, and the protein level and mRNA level of p54nrb didn't change after overexpressed AP-1, AP2α and Sp1. Citation Format: Sheng-Yi Lin, Yi-Hua Lai, Hsuan-Yu Chen, Huei-Wen Chen, Sung-Liang Yu, Tse-Ming Hong, Gee-Chen Chang, Jeremy J.W. Chen. Characterization of p54nrb/NonO promoter in NSCLC. [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 749. doi:10.1158/1538-7445.AM2013-749 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4716: The antitumor effect of HDAC inhibitor Tenovin-6 for gastric cancer cells
Authors: Takunori Ueno, Sachiko Hirai, Mitsuaki Hirose, Shinji Endo, Hideo Suzuki, Kenji Yamato, Ichinosuke Hyodo
Journal: Cancer Research (2012)

Abstract Aim: Tenovin-6 is one of the small molecule inhibitors of Histone Deacetylase (HDAC), which have been to shown to suppress cancer cell growth and angiogenesis. In Japan, the mortality of gastric cancer is still high and innovative strategies are required for patients with advanced unresectable gastric cancer. We conducted this study to verify anti-tumor effect of Tenovin-6 as a single agent for gastric cancer cells and also in combination with cytotoxic agents including 5-fluorouracil (5-FU) and cisplatin (CDDP) in vitro. Moreover, we validated the effectiveness of Tenovin-6 on animal xenografted model.Methods: 4 gastric cancer cell lines, MKN-45, NUGC-4 (p53 wild), NUGC-3 (p53 mutant) and Kato-III (p53 null), were incubated with Tenovin-6 in dose and time dependent manner. Cell viability was calculated by WST-8 assay after treatment with Tenovin-6 alone or in combination with 5-FU or CDDP. Protein expression of Sirt-1, p53, p21, DR5 and Caspase-3 were monitored by western blotting to reveal mechanism of antitumor effects by Tenovin-6. In vivo xenograft model established with human gastric cancer cell line MKN-45 was treated with intraperitoneal administration of Tenovin-6 at dose of 50 mg/kg/day for 2 weeks. Results: All 4 gastric cancer cells decreased dramatically by addition of Tenovin-6 with 2.3 to 4.3 μM of IC50. The decreasing trend was not different among cell lines. The additive and synergic effects were shown with combination of 5-FU or CDDP. The expression of Caspase-3, p21 and DR5 were increased by Tenovin-6 in time dependent manner. In contrast, the expression of Sirt-1 and p53 was not changed in all periods. Also in vivo, single agent therapy with Tenovin-6 significantly reduced subcutaneous xenograft tumor growth in nude mice. Conclusion: Tenovin-6 showed excellent anti-tumor effects in all gastric cancer cells via induction of apoptosis and cell cycle arrest. It may be promising therapeutic material for gastric cancer patients. 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 4716. doi:1538-7445.AM2012-4716
Effectiveness of First-Line Pemetrexed Plus Platinum for Advanced Nonsquamous Non-Small Cell Lung Cancer
Authors: M.D.R.A. Brandão, M.S. Luis, N.C. Amaral, M. Cassiano Neves, C. Camacho, A.C. Rodrigues, I. Pousa, J. Oliveira, I. Azevedo
Journal: Annals of Oncology (2015)
P248Markers of interstitial fibrosis in hypertensive patients with left ventricle hypertrophy:
Authors: MV Krestjyaninov, VA Razin, RH Gimaev
Journal: Cardiovascular Research (2014)

It′s well known that left ventricle (LV) geometry type is strongly associated with stroke and myocardial infarction in hypertensive patients. The most negative prognosis have persons with concentric hypertrophy of LV and concentric remodelling of LV. Both cardiomyocytes and extracellular matrix are involved in left ventricle remodelling process and their ratio determine disorders of left ventricle function and structure which result in complications. The purpose of the study is to evaluate levels of plasma markers of myocardial fibrosis in hypertensive patients with different types of left ventricle geometry models. Materials and methods: Were examined 324 patients with arterial hypertension (AH) 2-3 grade and ischemic heart disease (stable angina 2-3 functional class) complicated by CHF I-III NYHA functional class. The mean age of patients - 77 (61; 84) years. Patients with arrhythmias, diabetes mellitus were excluded from the study. As control group were enrolled 42 healthy persons (mean age - 70 (17) years). In all patients was performed ECG in 12 standard leads, EchoCG (ASE/EAE recommendations 2005) and were evaluated plasma levels of aldosteron, tissue inhibitor of metalloproteinases-1 (TIMP-1) and Insulin-like growth factor 1 (IGF-1). Statistical significance was defined at the level of methods for p<0,05. Results: As it can be seen from Table 1 The values of aldosteron (which known as interstitial fibrosis trigger) and TIMP-1 (plasma marker of interstitial fibrosis) were significant higher in patients with concentric hypertrophy and eccentric hypertrophy in comparison with hypertensive patients with normal geometry of LV and healthy persons. Conclusion: Thus, the results of the study show that levels of plasma markers of interstitial myocardial fibrosis indicate higher levels of interstitial fibrosis in hypertensive patients with such geometric models of left ventricle as concentric hypertrophy and concentric remodelling. Markers of interstitial fibrosis & LVH Results are shown in M (SD).*- p<0.05 in comparison with healthy persons, †- p<0.05 in comparison with patients with normal geometry of LV Markers of interstitial fibrosis & LVH Results are shown in M (SD).*- p<0.05 in comparison with healthy persons, †- p<0.05 in comparison with patients with normal geometry of LV
The Status of Forensic Pathology in the United States
Authors: William J. Curran
Journal: New England Journal of Medicine (1970)

THE condition of forensic pathology has never been strong in the United States. It has been a specialty of virtually handfuls of dedicated people over the nearly 200 years of the American republic. By contrast, the field of legal medicine (a broader field than forensic pathology, but including this subspecialty) has been strong and vigorous in Continental Europe for over 400 years. In 1876 Chaillé reviewed the field of legal medicine in the United States and could not name a single leading practitioner of forensic pathology and legal medicine in the United States.1 In the late 1920's and early 1930's, . . .
AB1087 Tuberculosis infections and chronic inflammatory rheumatisms:
Authors: S. Esseghir, L. Souabni, K. Ben Abdelghani, K. Salma, C. Salma, S. Belhadj, L. Ahmed, Z. Leith
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The incidence of tuberculosis among patients with systemic rheumatic diseases is much higher than in the general population. Reactivation of a latent tuberculosis is frequent, and is related to immunosuppression induced by the underlying disease, and of immunosuppressive therapy. <h3>Objectives</h3> To evaluate the risk of TB infection among Tunisian patients suffering from systemic disease and to determine the characteristics of. <h3>Methods</h3> A retrospective study of records of patients who developed TB infection during the evolution of a systemic disease. <h3>Results</h3> Among 742 patients suffering from rheumatoid arthritis, 68 patients from systemic lupus, and 365 from ankylosing spondylitis, four patients were selected. <h3>Conclusions</h3> The screening strategies for tuberculosis should be extended in all patients with systemic rheumatic diseases receiving glucocorticoids and/or immunosuppressive therapy. In tunisa, tuberculosis remains frequent despite the efforts of TB control. <h3>Disclosure of Interest</h3> None Declared
Investigation of the Mechanism of Tamoxifen-Stimulated Breast Tumor Growth With Nonisomerizable Analogues of Tamoxifen and Metabolites
Authors: D. M. Wolf, S. M. Langan-Fahey, C. J. Parker, R. McCague, V. C. Jordan
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The nonsteroidal antiestrogen tamoxifen (TAM) is the front-line endocrine treatment for breast cancer, but disease recurrence is common. Treatment failure may occur because tumors become insensitive to TAM. Alternatively, resistance may occur because tumors become stimulated rather than inhibited by TAM. TAM-stimulated growth of MCF-7 human breast tumors has been observed in athymic mice after prolonged treatment with TAM. Purpose : Our purpose was to examine the mechanism of treatment failure by determining whether TAM-stimulated tumors acquire the ability to excrete TAM and its antiestrogenic metabolites or to convert them to estrogenic compounds with weakened antiestrogenic activity. Methods : We used high-pressure liquid chromatography to quantitate TAM and its metabolites in serum and tumors from ovariectomized athymic mice and in MCF-7 cells grown in vitro. We treated tumor-bearing mice with subcutaneous sustained-release preparations of estradiol, TAM, or a nonisomerizable (fixed-ring) analogue and then assessed the activity of these compounds on TAM-inhibited parental MCF-7 tumors and on TAM-stimulated MCF-7 TAM tumors. Results : We found negligible differences in intratumoral TAM levels between TAM-inhibited parental MCF-7 tumors and TAM-stimulated MCF-7 TAM variants. We did not detect metabolite E (Met E), an estrogenic TAM metabolite, in serum or tumors. Using MCF-7 cells in vitro, we determined that the (Z) isomer of Met E, the form directly produced by TAM metabolism, must be present in the cell at a concentration of over 1000 ng/g to overcome growth inhibition by physiological levels of TAM and antiestrogenic metabolites, but the (E) isomer of Met E was effective at 10 ng/g. We reasoned that conversion of Met E from the (Z) (a weak estrogen) to (E) isomer (a potent estrogen) would be required if formation of Met E were responsible for TAM-stimulated growth. However, fixed-ring TAM, which can only form (Z) Met E, was shown to be as capable as TAM of initiating and maintaining antiestrogen-stimulated growth of MCF-7 tumors in athymic mice. Conclusion : Metabolism and isomerization of TAM to estrogenic compounds is not the mechanism of TAM-stimulated growth in our model. Implication : Other potential mechanisms for TAM-stimulated growth, such as estrogen receptor mutation, must be investigated so that effective strategies can be devised to control breast cancer once therapy fails. [J Natl Cancer Inst 85: 806–812, 1993]
P4-07-13: Prognostic Impact of Circulating Tumor Cells Assessed with the Cell Search Assay and Adna Test Breast in Metastatic Breast Cancer Patients – The DETECT Study.
Authors: V Mueller, S Riethdorf, B Rack, J Wolfgang, PA Fasching, E Solomayer, B Aktas, S Kasimir-Bauer, D Mury, K Pantel, T Fehm
Journal: Cancer Research (2011)

Abstract Background Over the last decade circulating tumor cells (CTC) were established as a prognostic factor in breast cancer patients. However, there are very limited studies comparing different test methods, although several are available.The DETECT trial for metastatic breast cancer patients was designed to investiate the prognostic impact of CTC. Here, we report on the prognostic relevance of CTC testing with different detection methods. Material and Methods: Patients with primary metastatic breast cancer or metastatic recurrence were prospectively enrolled in this multicenter trial. CTC were detected using the FDA-approved Cell Search® assay applying immunocytochemistry and the RNA-based Adna Test Breast Cancer™. After a median follow-up of 11 months the first survival data are now presented. Results: Both methods could be performed in 221 patients. Using the CellSearch™ assay 116 of 221 patients were CTC-positive based on the cut-off level of 5 cells. Presence of CTC was associated with the site of metastatic disease. The OS was 15.4 months in CTC positive pts. (95%-CI: 13.5−17.1 mths) compared to 20.4 mths. in CTC negative pts. (19.1−21.9 mths.; p&amp;lt;0.001). In the multivariate analysis presence of CTC was the only independent predictor for overall survival (HR: 3.4, 95%-CI: 1.7−6.3) including tumorbiological factors, menopausal status, number and sites of metastatic disease. The progression-free survival was not correlated with CTC status in our cohort receiving different types of systemic treatment (p=0.197). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC positive. Except for HER2 status, no correlation could be observed between CTC positivity and any of the clinicopathological factors. CTC positivity assessed by the AdnaTest Breast has no impact on PFS and OS. A multivariate analysis was therefore not performed. Conclusions: Currently, several different tests are available for CTC detection. Only a few tests have been approved by the FDA and been validated in large clinical trials. Therfore, it will be important to compare new techniques with the Cell Search assay. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-13.