tbuckley/cabot-search huggingface dataset:
Various Methods of Analysis of mdr-1/P-Glycoprotein in Human Colon Cancer Cell Lines
Authors: C. E. Herzog, J. B. Trepel, L. A. Mickley, S. E. Bates, A. T. Fojo
Journal: JNCI Journal of the National Cancer Institute (1992)

Multidrug resistance (MDR) mediated by high levels of mdr-1 (also known as PGY1)/P-glycoprotein (Pgp) has been studied in tissue culture systems; however, most tumor samples which express mdr-1/Pgp have much lower levels.We wanted to determine if levels seen clinically could be detected by commonly used methods and to determine if these levels conferred MDR reversible by Pgp antagonists.We studied multi-drug-resistant cell lines and sublines with levels of mdr-1/Pgp expression comparable to those seen clinically. We evaluated the expression of mdr-1 RNA by Northern blot analysis, slot blot analysis, polymerase chain reaction (PCR) analysis, and in situ hybridization. We evaluated protein expression by immunofluorescence, immunohistochemistry, fluorescence-activated cell sorting, and immunoblotting analyses. Drug resistance and reversibility were determined by cell growth during continuous drug exposure.In most cases, the low level of mdr-1/Pgp present in these cell lines could be detected by each method, but the assays were at the limit of sensitivity for all methods except the PCR method. These low levels of mdr-1/Pgp are capable of conferring MDR, which can be antagonized by verapamil.Levels of mdr-1/Pgp similar to those found in clinical samples can be detected by each of these methods, but the PCR method was the most sensitive and most reliably quantitative.In vitro sensitization by the addition of verapamil in cell lines with these low levels of mdr-1/Pgp suggests that clinically detected levels may confer drug resistance in vivo.
F-18 FDG PET Images for Subcutaneous Panniculitis-like T-Cell Lymphoma
Authors: Shan-Ying Wang, Yen-Wen Wu, Cheng-Hsiang Hsiao, Meng-Fang Li, Pei-Ying Hsu, Ruoh-Fang Yen
Journal: Clinical Nuclear Medicine (2010)

A 14-year-old girl, who had been suffering from intermittent fevers for 2 months, developed painful erythematous plaques on the lower extremities. Laboratory data revealed elevated C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase/alanine aminotransferase (AST/ALT). Blood and urine cultures were negative. CT showed hepatosplenomegaly. F-18 FDG PET revealed multiple patchy uptakes on the subcutaneous surfaces residing mainly at the lower trunk and extremities. The PET images and clinical manifestations appeared indistinguishable from those due to panniculitis while the pathology from skin biopsy demonstrated panniculitis-like T-cell lymphoma. She received chemotherapy and the follow-up PET showed significant resolution of previous abnormal uptakes from the subcutaneous lesions.
Abstract 3805: Furanodienone downregulates EGFR and Her-2 signaling in BT-474 breast cancer cells
Authors: Yingwei Li, Guoyuan Zhu, Suisui Dong, Xiaoling Shen, Zhiling Yu, Wang-fun David Fong
Journal: Cancer Research (2010)

Abstract Epidermal growth factor receptor (EGFR) and Her-2 are members of the ErbB receptor family of type 1 tyrosine kinases. Also, ligand-induced EGFR /Her-2 heterodimerization triggers potent proliferative and survival signals. EGFR and Her2 frequently overexpress in breast cancer and their overexpression is correlated with a poor prognosis. Therefore dual EGFR/ Her-2 inhibition is an attractive therapeutic strategy for breast cancer treatment. Furanodienone is a compound isolated from Rhizoma Curcumae, which is commonly used in cancer treatment in China. In this study, we used the breast cancer cell BT-474 as the model to investigate the mechanism of furanodienone in breast cancer treatment. We found that furanodienone induced G1 arrest and effectively blocked EGF-stimulated cell cycle progression in BT-474 cells. Moreover, furanodienone decreased protein levels of EGFR, phosphorylation of EGFR and Her-2, so that it prevented the activation of downstream molecules like Akt, Gsk3β and c-Raf, which resulted in inhibiting cell cycle progression. These findings suggested that furanodienone induced growth inhibition in BT-474 human breast cancer cells through inhibiting EGFR /Her-2 signaling pathway. Furthermore, furanodienone and its related compounds provided insights into novel approaches for the prevention and treatment of human breast cancers, especially for those with EGFR /Her-2 overexpression. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3805.
Differentiation of Newly Diagnosed Glioblastoma Multiforme and Intracranial Diffuse Large B-cell Lymphoma Using 11C-Methionine and 18F-FDG PET
Authors: Yumiko Okada, Takashi Nihashi, Masazumi Fujii, Katsuhiko Kato, Yoshiyuki Okochi, Yoshio Ando, Masato Yamashita, Satoshi Maesawa, Shigenori Takebayashi, Toshihiko Wakabayashi, Shinji Naganawa
Journal: Clinical Nuclear Medicine (2012)

Purpose The aim of our study was to examine the usefulness of PET with 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) in the differentiation of glioblastoma multiforme (GBM) and intracranial diffuse large B-cell lymphoma (DLBCL). Materials and Methods We evaluated 22 patients retrospectively with an enhancing brain tumor on MRI, including 15 GBM and 7 DLBCL, which was confirmed by histopathology. Dynamic PET scans with MET and FDG were performed for preoperative differential diagnosis. We assessed the images qualitatively and quantitatively. In quantitative assessment, the SUVmax was used on FDG PET and both late and early phases on MET PET. In addition, the ratio of SUVmax in the late and early phases on MET-PET was evaluated (ΔSUVmax). Results SUVmax on FDG PET of DLBCL was significantly higher than that of GBM. Setting an SUVmax of 12.0 as the cutoff for differentiating DLBCL from GBM, 1 GBM and 1 DLBCL were found to be false-positive and false-negative, respectively. SUVmax in the late and early phases of MET-PET was not significantly different between DLBCL and GBM; however, we also found significant differences in ΔSUVmax on MET-PET. Using ΔSUVmax 1.17 as the cutoff, we could differentiate DLBCL from GBM completely. In the present study, ΔSUVmax on MET-PET was slightly superior to SUVmax on FDG PET. Conclusions Both SUVmax on FDG PET and ΔSUVmax on MET-PET were considered to be good diagnostic tests when encountering difficulties in this differential diagnosis.
Angiogenesis in breast cancer: comparison between three vascular endothelial markers.
Authors: BB da Silva, PV Lopes-Costa, AR dos Santos, EC Sousa-Júnior, G Facina, AC Nazário
Journal: Cancer Research (2009)

Abstract Abstract #1037 Background: Controversial results have been reported on the three vascular endothelial markers most commonly evaluated in breast carcinomas. The objective of this study was to evaluate the quantification of angiogenesis by comparing the performance of anti-Factor VIII related antigen, anti-CD31 and anti-CD34 monoclonal antibodies to assess microvessel density in breast cancer. Methods: Twenty-three postmenopausal women diagnosed with stage II breast cancer and submitted to mastectomy or segmentectomy were evaluated. The monoclonal antibodies used were anti-Factor VIII, anti-CD31 and anti-CD34. Microvessels were counted in the areas of highest microvessel density using a magnification of 200x in 10 random fields. Microvessel density was defined as the mean number of microvessels counted in 10 fields. The data were analyzed using the Kruskal-Wallis nonparametric test (p&amp;lt;0.05). Results: Mean microvessel densities with anti-Factor VIII, anti-CD31 and anti-CD34 were 4.16, 4.09 and 6.59, respectively. Microvessel density as detected by anti-CD34 was significantly greater than that detected by anti-CD31 or anti-factor VIII (p&amp;lt;0.0001). There was no statistically significant difference between microvessel density detected by anti-CD31 and anti-Factor VIII (p=0.4889) (see Table 1 and Figure 1).&amp;#x2028; &amp;#x2028; [figure1]Discussion: In the present study, despite the current controversies, a higher density of microvessels and a greater intensity of staining were found when anti-CD34 was used in comparison with anti-CD31 and anti-Factor VIII related antigen in paraffin-fixed samples of infiltrating ductal breast carcinoma from postmenopausal women. These findings justify the increasing use of this monoclonal antibody in the study of angiogenesis, not only in breast cancer but also in other neoplasias. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1037.
Treatment of Chronic Pulmonary Histoplasmosis
Authors: J. D. Parker, G. A. Sarosi, I. L. Doto, R. E. Bailey, F. E. Tosh
Journal: New England Journal of Medicine (1970)

Of 408 patients with chronic pulmonary histoplasmosis alone, 238 were treated initially with amphotericin B only, 43 with pulmonary surgery combined with amphotericin B, and 27 with pulmonary surgery alone, and 100 were not treated. Among those who received amphotericin B alone and those who were not treated, death was directly related to the age of the patient at the time of diagnosis and, in the treated group, to the stage of disease before therapy. In the treated group death was inversely related to the total initial dose of amphotericin B. There were significantly fewer deaths among patients who received a total dose of over 35 mg of drug per kilogram of body weight than among those who received less. In comparison with the untreated group, there were significantly fewer deaths in the group treated with amphotericin B alone.
Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis
Authors: Ren-Yuan Bai, Verena Staedtke, Charles M. Rudin, Fred Bunz, Gregory J. Riggins
Journal: Neuro-Oncology (2014)

Medulloblastoma is the most common malignant brain tumor in children. Current standard treatments cure 40%–60% of patients, while the majority of survivors suffer long-term neurological sequelae. The identification of 4 molecular groups of medulloblastoma improved the clinical management with the development of targeted therapies; however, the tumor acquires resistance quickly. Mebendazole (MBZ) has a long safety record as antiparasitic in children and has been recently implicated in inhibition of various tyrosine kinases in vitro. Here, we investigated the efficacy of MBZ in various medulloblastoma subtypes and MBZ's impact on vascular endothelial growth factor receptor 2 (VEGFR2) and tumor angiogenesis. The inhibition of MBZ on VEGFR2 kinase was investigated in an autophosphorylation assay and a cell-free kinase assay. Mice bearing orthotopic PTCH1-mutant medulloblastoma allografts, a group 3 medulloblastoma xenograft, and a PTCH1-mutant medulloblastoma with acquired resistance to the smoothened inhibitor vismodegib were treated with MBZ. The survival benefit and the impact on tumor angiogenesis and VEGFR2 kinase function were analyzed. We determined that MBZ interferes with VEGFR2 kinase by competing with ATP. MBZ selectively inhibited tumor angiogenesis but not the normal brain vasculatures in orthotopic medulloblastoma models and suppressed VEGFR2 kinase in vivo. MBZ significantly extended the survival of medulloblastoma models derived from different molecular backgrounds. Our findings support testing of MBZ as a possible low-toxicity therapy for medulloblastomas of various molecular subtypes, including tumors with acquired vismodegib resistance. Its antitumor mechanism may be partially explained by inhibition of tumor angiogenesis.
Fatal Transfusion Reactions from Massive Bacterial Contamination of Blood
Authors: Craig W. Borden, Wendell H. Hall
Journal: New England Journal of Medicine (1951)

THE sterility of stored whole blood depends on three factors: aseptic technic, a sterile system for collection and storage and immediate, continuous refrigeration. These measures are highly effective for preserving blood in a relatively sterile state. Nevertheless, under certain circumstances, gross bacterial contamination of stored blood can occur. Although the essential features of accidents resulting from the administration of contaminated Wood are mentioned by Whitby,1 detailed descriptions are not available.The administration of contaminated blood produces a characteristic clinical syndrome that may be incorrectly interpreted. There is reason to believe that transfusion reactions due to bacterial contamination have occurred more . . .
Longer GP opening hours would require 2bn shift of funding into primary care, says GP leader
Authors: G. Iacobucci
Journal: BMJ (2013)

The government’s plans for patients in England to have access to a general practitioner any day of the week and in the evenings would require an investment of £35 (€41; $56) per head of population, a senior GP has claimed.

Ministers last week set out plans to trial a new scheme that would make it possible for patients to see their GP from 8 am to 8 pm, seven days a week, funded by £50m to be shared among nine pilot sites covering half a million people.1

James Kingsland, a Department of Health …
Abstract 636: Role of Prostaglandin E2 in breast-cancer associated lymphangiogenesis in an in vitro system
Authors: Gannareddy V. Girish, Lida Radan, Elena Tutunea-Fatan, Mousumi Majumder, Rabindra Bhattacharjee, Xiping Xin, Neena Lala, Peeyush K. Lala
Journal: Cancer Research (2010)

Abstract Lymphatic metastasis is a common occurence in breast cancer. Molecular mechanisms in breast cancer-associated lymphangiogenesis and lymphatic metastasis are poorly defined. We had earlier shown that elevated cyclo-oxygenase (COX)-2 expression by human as well as murine breast cancer cells promotes tumor progression and metastasis by multiple mechanisms: inactivation of host anti-tumor immune cells, stimulation of tumor cell migration and tumor-associated angiogenesis. Furthermore, COX-2 was causally associated with increased VEGF-C expression/secretion in human and murine breast cancer cell lines, thus promoting tumor-associated lymphangiogenesis. VEGF-C production was partially dependent on endogenous PGE-2 mediated activation of EP4 receptors on breast cancer cells thus making EP4 a good therapeutic target. It was unclear whether tumor or host derived PGE-2 had any direct effect on lymphangiogenesis, and if so, whether EP4 receptors on lymphatic endothelial cells played any role. To address these questions, we devised an in vitro lymphangiogenesis assay using a LYVE-1 expressing rat mesenteric lymphatic endothelial cell line (RMLEC) plated on growth factor- reduced Matrigel. Endothelial tube formation by RMLEC was rapidly induced in 12-18 hours after plating on Matrigel even under serum-free conditions, whereas plating them on collagen gel even in the presence of serum did not induce any tube formation. This suggested the presence of some inducing factor(s) in the Matrigel, possibly also present in the ECM in vivo. Matrigel-induced tube formation was completely abrogated in the presence of COX 1/2 inhibitor indomethacin (10mM), COX-2 inhibitor NS-398 (15mM), and a selective EP4 antagonist CJ-042794 (2.5 mM). In each case, an additional presence of PGE2 (1 µM) or an EP4 agonist PGE-1 alcohol (1µM) completely restored the tube formation on matrigel. A similar restoration was also achieved in the presence of serum-free conditioned media (24 h culture) of a COX-2 expressing murine breast cancer cell line C3L5 that induces lymphangiogenesis in vivo. These results indicate the roles of tumor as well as host-derived PGE2 in inducing lymphangiogenesis possibly by activating COX-2/EP4 receptors on lymphatic endothelial cells. Further studies are in progress to identify the tube-inducing component(s) in the Matrigel and C3L5 cell conditioned medium. (Supported by grants from the Canadian Breast Cancer Foundation, Ontario chapter and the Ontario Institute of Cancer Research to PKL. The gift of the RMLEC from Dr Sophia Ran, Southern Illinois Univ School of Medicine is gratefully acknowledged). 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 636.
Comparison of Diagnostic Accuracy of 111In-Pentetreotide Spect and 68Ga-Dotatoc Pet: a Lesion-By-Lesion Analysis in Prrt-Patients
Authors: S. Van Binnebeek, B. Vanbilloen, K. Baete, C. Terwinghe, M. Koole, F.M. Mottaghy, P.M. Clement, L. Mortelmans, K. Bogaerts, K. Haustermans, E. Van Cutsem, C. Verslype, A. Verbruggen, C.M. Deroose
Journal: Annals of Oncology (2013)
Is stiffness a byproduct or a target?
Authors: Hiroaki Gomi
Journal: Behavioral and Brain Sciences (1996)

To examine the model of the biological motor control proposed by A. Smith, this commentary briefly introduces some result of stiffness measurements during multi-joint arm movements, and, in the light of these results, discusses how likely it is that stiffness is a control parameter and that the cerebellum solely codes the stiffness, [SMITH]
357 DIPEPTIDYL PEPTIDASE 4-DEFICIENT RATS ARE PROTECTED FROM HIGH FAT DIET-INDUCED CHOLESTATIC INJURY
Authors: I. Zvibel, S. Ben Shlomo, L. Rabinowich, I. Goldiner, E.M. Santo, Z. Halpern, R. Oren, S. Fishman
Journal: Journal of Hepatology (2012)
AB0626 Multicenter Registry in Inflammatory Myopathies: Preliminary Descriptive Study
Authors: L. Nuño, F.J. Lόpez Longo, I. Llorente, P. García De la Peña, T. Cobo, R. Almodόvar, L. Lojo, J. Díez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Clinical manifestations, course and prognosis of idiopathic inflammatory myopathies (IIM) are extremely heterogeneous which, combined with its low prevalence, makes difficult the study of the disease in the absence of multicenter studies. <h3>Objectives</h3> To analyze the clinical characteristics and mortality in a cohort of patients diagnosed with IIM in rheumatology units from several hospitals in Madrid. <h3>Methods</h3> A multicenter retrospective longitudinal descriptive study of a cohort of patients diagnosed with IIM and in follow-up sometime between January 1980 and February 2013 in rheumatology from several hospitals in Madrid. All patients who met at least 2 criteria of Bohan and Peter<sup>1</sup> for polymyositis (3 criteria if dermatomyositis) were included. We performed a descriptive study ot the initial cases recruited during the first months of the stuydy. All patients in current follow-up signed informed consent. Statistical analysis was performed using SPSS 11.5 for Windows, with a significance level of p&lt;0.05. <h3>Results</h3> 127 cases were included in this study, with a 15% of patients lost to follow-up. There is a predominance of polymyositis over dermatomyositis (59.8% vs. 40.2% respectively). 74% of the cases were women, and patients had a medium age at diagnosis of 42.5±22.7 years, with a mean follow-up time of 76.8±70.8 months. Most of the cases were Caucasian (90.6% Caucasian, 7.9% Hispanic, 1.6% other). 97.6% met at least 3 criteria of Bohan and Peter. The most frequent form of classification were primary myopathies (47.6% primary myopathies, 26.2% myopathies associated with other connective tissue disease, 17.5% juvenile myopathies, 6.3% paraneoplastic myopathies, 1.6% inclusion body myopathies, and 0.8% necrotizing myopathies). Clinical manifestations associated with the disease included systemic manifestations (38.1%), joint manifestations (65.1%), skin manifestations (56.3%, the most frequent being Gottron sign) and interstitial lung disease (18.9%). EMG and muscle biopsy were performed in 96.1% and 66.9% and compatible with IIM in 92.6% and 77.6% of the cases respectively. 26 patients died (20.5%), mainly due to infections (26.9%), followed by cancer (19.2%), cardiovascular events (15.4%), interstitial lung disease (7.7%) and other causes. <h3>Conclusions</h3> In this retrospective, longitudinal study on idiopathic inflammatory myopathies followed-up in several hospitals inMadrid, 127 have been recruited for the moment. The most common subtype were primary myopathies (47.6%). 20.5% of patientsdied, mainly due to infections, followed by cancer, cardiovascular events, interstitial lung disease and other causes. More cases willbe included. <h3>References</h3> Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975 Feb 13;292(7):344-7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3732
Notch-1 activates ErbB-2 through a PEA3-dependent mechansim.
Authors: AG Clementz, C Osipo
Journal: Cancer Research (2009)

Abstract Abstract #6015 Over-expression or gene amplification of ErbB-2 occurs in 25% of breast cancer which is associated with malignancy, poor overall survival, and resistance to some anti-hormonal therapies. Although trastuzumab has had a tremondous impact on survival, resistance results within the first year of treatment in 15% of cases and remains a major problem in the metastatic setting. We have recently published (Osipo et al., 2008. Oncogene) that the expression and activity of Notch-1, a potent breast oncogene and cell fate determinant is increased in ErbB-2 positive breast cancer cells in response to trastuzumab. Furthermore, we have shown that Notch-1 might contribute to trastuzumab resistance. In the current study, we asked whether Notch-1 could activate ErbB-2. Results demonstrated that a Notch inhibitor, γ-secretase inhibitor (GSI) or a Notch-1 siRNA decreased tyrosine phosphorylated and total ErbB-2 expression in SKBR3, MCF-7, and MDA-MB-231 cells. Furthermore, overexpression of constitutively active Notch-1 increased tyrosine phosphorylated ErbB-2 and reversed the inhibition by a GSI. ErbB-2 promoter activity using a luciferase reporter construct was decreased by Notch-1 siRNA only when the PEA3 Ets binding site was mutated. These results suggest that Notch-1 is an activator of ErbB-2 in breast cancer cells that express low or inactive PEA3. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6015.
ASSOCIATION OF ORTHOSTATIC HYPERTENSION WITH MORTALITY IN THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM
Authors: William J. Kostis, Abel Moreyra, Davit Sargsyan, Javier Cabrera, Nora Cosgrove, John Kostis, William Cushman, John Pantazopoulos, Sara Pressel, Barry Davis
Journal: Journal of the American College of Cardiology (2016)
Anterior arytenoid cartilage dislocation, a rare complication of esophagogastroduodenoscopy
Authors: N. Kakushima, K. Hotta, M. Tanaka, N. Kawata, H. Sawai, K. Imai, T. Takao, M. Takao, K. Takizawa, H. Matsubayashi, Y. Yamaguchi, H. Ono, T. Onitsuka
Journal: Endoscopy (2012)

Arytenoid cartilage dislocation is a rare complication after tracheal intubation, occurring in less than 0.1 % of cases [1] [2]. Here we present a case of arytenoid cartilage dislocation following esophagogastroduodenoscopy (EGD). A man in his sixties underwent EGD as a follow-up examination after endoscopic treatment for early gastric cancer. The examination was carried out with a standard endoscope (GIFH260, Olympus, Tokyo, Japan), under conscious sedation with midazolam (3 mg) and pethidine chloride (35 mg), and was completed uneventfully. After a 1-hour rest in the recovery unit, the patient developed aphonia without any throat pain. Following treatment with dequalinium chloride troches, the patient still had persisting hoarseness and difficulty swallowing 4 days later. Laryngoscopy showed anterior dislocation of the left arytenoid cartilage, with a flaccid and fixed left vocal cord ([Fig. 1]). Fiberscopic reduction was carried out as an ambulatory procedure, under local anesthesia, and reposition was confirmed on the following day ([Fig. 2]). The dysphonia and vocal cord movement improved gradually over the next 2 weeks ([Fig. 3]).