tbuckley/cabot-search huggingface dataset:
Abstract 3441: Silencing glucosylceramide synthase using MBO-asGCS eliminates tumor metastasis
Authors: Kaustubh N. Bhinge, Vineet Gupta, Yong Yu Liu
Journal: Cancer Research (2012)

Abstract Disseminated metastasis is often observed in cancer patients fail in chemotherapy. Tumor metastasis is known to rely on the interaction of cancer cells and the extracellular matrix components but the molecular mechanism by which drug resistance promotes tumor metastasis is still not clear. Glucosylceramide synthase (GCS) that is a limiting enzyme for ceramide glycosylation and regulates glycosphingolipid (GSL) synthesis can cause drug resistance. Hence we report that GCS is a determinant of metastatic properties of drug-resistant cancer cells, and silencing GCS eliminates tumor metastasis. Our recent study found that the metastatic potency of drug-resistant cancer cells depended on the overexpression of GCS. Compared with drug-sensitive MCF-7 cells, the wound healing, matrigel attachment and MMP-9 activity significantly was 1.5 fold faster, 3 fold more and 2 folds higher respectively in the drug resistant MCF-7/Dox that also had 39-fold higher GCS protein level and 2-fold higher GCS enzyme activity. Introduction of GCS gene enhanced the metastatic potency of MCF-7 cells, because its matrigel attachment and invasion potential significantly increased by 2-fold and 1.5-fold after transfection. In contrast, silencing GCS by using mixed-backbone oligonucleotide against GCS (MBO-asGCS, 100 nM) substantially diminished the metastatic potency of MCF-7/Dox cells, as the wound healing, matrigel attachment and invasion reduced by 2-fold, 1.5-fold and 3-fold respectively. MBO-asGCS treatments eliminated lung metastasis of MCF-7/Dox tumors. Further mechanistic studies disclosed that silencing GCS by MBO-asGCS decreased its expression and enzyme activity and also decreased the levels of globo-series glycosphingolipids (GSLs) in GSL-enriched microdomain located on the plasma membrane. Sequentially, silencing GCS decreased the expression levels of uPA, MMP-9, VEGF and FGF-2 that actively mediated the migration and invasion of cancer cells. This study thus indicates that GCS is determinant for the metastatic potency of drug-resistant cancer cells and silencing GCS by using MBO-asGCS is an effective approach to target the metastasis of tumor with drug resistance. 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 3441. doi:1538-7445.AM2012-3441
Abstract LB-133: Golgin-160 binds to the tumor suppressor Par-4 and attenuates its secretion
Authors: Tripti Shrestha Bhattarai, Jaya Singh, Guofang Qiu, Carolyn E. Machamer, Vivek M. Rangnekar
Journal: Cancer Research (2011)

Abstract Prostate apoptosis response-4 (Par-4) is a pro-apoptotic protein that selectively induces apoptosis in cancer cells but not in normal cells. Previously thought to function exclusively by intracellular mechanisms, Par-4 is now recognized to also utilize an extrinsic pathway that is coupled to intracellular Par-4 to mediate apoptosis. Par-4 is secreted by almost all cell types, and is detected in the conditioned medium of cultured cells or in the serum of animals. Systemic Par-4 inhibits tumor growth progression, yet the precise mechanism(s) involved in the regulation of Par-4 secretion has not been characterized. Par-4 secretion is induced by an increase in endoplasmic reticulum (ER) stress; this observation is paradoxical as protein secretion is generally inhibited by elevated ER stress. Toward the goal of investigating proteins that may directly bind and regulate Par-4 secretion, we performed a yeast two-hybrid analysis, as well as co-immunoprecipitation studies. These studies consistently identified the golgi peripheral membrane protein, Golgin-160, as a binding partner of Par-4. We further noted that Golgin-160 down-modulates the secretion of Par-4 in response to ER stress caused by tunicamycin. Our data suggest that Par-4 secretion is attenuated by binding to Golgin-160. This regulatory process may have important implications in microenvironments (for example, those involving inflammation) that have increased Golgin-160, as depleted Par-4 secretion may show greater propensity for transformation and malignant progression. Since Par-4 selectively induces apoptosis in transformed cells but not in normal/non-transformed cells, strategies to down-modulate Golgin-160 to promote Par-4 secretion may have broad implications in cancer therapeutics. 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 LB-133. doi:10.1158/1538-7445.AM2011-LB-133
Idiopathic CD4+ T-Lymphocytopenia -- An Analysis of Five Patients with Unexplained Opportunistic Infections
Authors: Thomas J. Spira, Bonnie M. Jones, Janet Nicholson, Renu B. Lal, Thomas Rowe, Alison C. Mawle, Carl B. Lauter, Jonas A. Shulman, Roberta A. Monson
Journal: New England Journal of Medicine (1993)

Although patients with idiopathic CD4+ T-lymphocytopenia and serious opportunistic infections have been described previously, the clinical and immunologic features of this condition have not been well defined.
Abstract 2323: Inhibition of in vitro growth of human mesothelioma cells by CSPG4-specific monoclonal antibodies
Authors: Rivera Zeyana, Soldano Ferrone, Haining Yang, Xinhui Wang, Michele Carbone
Journal: Cancer Research (2010)

Abstract The membrane bound chondroitin sulphate protidoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), plays a role in tumor cell proliferation, growth and differentiation, as well as in angiogenesis and extracellular matrix remodeling. Contrary to the early reports which had described CSPG4 expression restricted to melanoma cells, this molecule is expressed by various types of malignant tumors. Because of its high expression on tumor cells, including cancer stem cells, and its restricted distribution in normal tissues, CSPG4 represents an attractive target for immunotherapy. The lack of effective conventional therapy and the paucity of suitable targets for immunotherapy in mesothelioma have prompted us to test whether CSPG4 is expressed by mesothelioma cells and mediates the anti-tumor activity of CSPG4-specific monoclonal antibodies (mAb). Immunohistochemical staining with mAb showed that CSPG4 was expressed on mesothelioma cells in 24 out of 40 MM biopsies with minimal expression on surrounding normal cells. Furthermore FACS analysis and western blots detected CSPG4 in all the 9 human MM cell lines tested and that the expression was induced on MM cells by their interactions with the extracellular matrix (ECM). To test the sensitivity of MM cells to the anti-tumor activity of CSPG4-specific mAb, 3 MM cell lines were incubated with mAb TP41.2 (final concentration 10ug/ml) for up to 72hrs. Cell proliferation was determined by MTT assay. Cells incubated with normal mouse IgG antibodies were used as controls. Addition of mAb TP41.2 to cells already attached to plates had no detectable effect on their proliferation. On the other hand incubation of MM cells with mAb TP41.2 before seeding in plates markedly inhibited their growth. The effect was time-dependent. These results were observed in all 3 cell lines and each cell lines was tested 3 times. The data suggest that CSPG4 promotes MM cell growth by mediating their interactions with ECM. This conclusion is corroborated by the growth of CSPG4-positive MM cells in serum-free medium in plates coated with collagen I, collagen IV or fibronectin. Furthermore CSPG4-specific mAb decreased the expression of the angiogenic growth factors VEGF and HEY1, as determined by RT-PCR, in MM cells. These results suggest that it may be worthwhile to test the hypothesis that CSPG4-specific mAb-based immunotherapy may represent a viable approach for the treatment of MM. 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 2323.
The Journal's Policy on Cost-Effectiveness Analyses
Authors: Jerome P. Kassirer, Marcia Angell
Journal: New England Journal of Medicine (1994)

Concern about cost now dominates many decisions about the use of drugs and other therapeutic interventions. Increasingly, such decisions are being influenced by published economic analyses that relate the effectiveness of treatments and their associated costs (cost-effectiveness analyses). Many of these analyses are supported by grants from the National Institutes of Health (NIH) or other neutral sources. Some, however, are funded by companies that hope these analyses will put their products in a favorable light1. Companies might then even use particularly favorable analyses to justify the prices of new drugs. A cost-effectiveness analysis is usually performed by developing a . . .
AB0382 A single-site, investigator initiated, open-label trial of the adrenocorticotropic hormone (acth) analogue h.p. acthar gel (repository corticotropin injection) among subjects with moderately to severely active systemic lupus erythematosus (sle)
Authors: T. Montroy, J. J. Fiechtner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a serious systemic disease which left untreated or inadequately treated may have a substantial effect on the morbidity and mortality of the individuals who are afflicted. Conventional treatments include immunosuppressive medications and corticosteroids. However, there is a need for alternative therapeutic options, particularly in SLE patients who may not be adequately controlled with or who are intolerant to traditional therapies. Acthar is known to have steroidogenic mechanisms of action through endogenous production of cortisol and is also reported to have immunomodulatory properties facilitated through the interactions with melanocortin receptors found in immune effector cells and other tissues. Self-administered via subcutaneous injection, Acthar may represent a potential treatment option for those patients. <h3>Objectives</h3> This study was designed to evaluate the efficacy of Acthar for reducing the severity of active lupus flares among patients with SLE who inadequately responded to other treatments. <h3>Methods</h3> Seven female patients (mean age=48.3 years, mean duration of disease=7.1 years) who had not, in the clinical judgment of the treating physician, responded adequately to previous treatments were included in the study. Patients received, through self-administration, 1 mL (80 U/mL) of Acthar gel for 7-15 days. Over a period of 28 days, all patients were assessed weekly. Outcome measurements included Medical Doctor Global Assessment (MDGA), Patient Global Assessment (PGA), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Student's t-test was conducted to compare data obtained at Day 28 with those from baseline. <h3>Results</h3> There were statistically significant improvements in both SLEDAI-2K (<i>P</i>=.025) and MDGA (<i>P</i>=.020), as well as a trend toward improvement in PGA (<i>P</i>=.064), indicative of a reduction in the severity of lupus flares. Acthar was well-tolerated; however, bilateral edema was present in the legs/ankles of one patient. No treatment-related serious or unexpected adverse events were observed. <h3>Conclusions</h3> Lupus flares usually require treatment with prednisone in varying doses that depend upon the severity. The results obtained during this trial reveal that, when treated with Acthar, patients who had not responded adequately to other therapeutic agents can have significant improvements in scores that indicate reduction of disease activity. <h3>Disclosure of Interest</h3> T. Montroy Grant/research support from: Questcor Pharmaceuticals, J. Fiechtner Grant/research support from: Questcor Pharmaceuticals
707 SUPERSONIC SHEAR IMAGING ELASTOGRAPHY FOR CHARACTERIZATION OF LIVER TUMOURS - PRELIMINARY FINDINGS
Authors: I. Grgurevic, T. Bokun, M. Kujundzic, M. Milosevic, R. Huzjan-Korunic, J. Curic, M. Vukelic-Markovic
Journal: Journal of Hepatology (2012)
I-131 Orthoiodohippurate Assessment of Renal Function After Heart Transplantation
Authors: RICHARD W. KURTEK, W. NEWLON TAUXE, K. KAY-YIN LAI, JOHN J. FUNG
Journal: Clinical Nuclear Medicine (1999)

Purpose: The authors studied the relation between cardiac output (CO) and effective renal plasma flow (ERPF) and compared values from control patients with various cardiac problems with those in a group of study patients who had undergone heart transplantation. Methods: The experimental group was divided into three subgroups according to the interval between the time of surgery and the time of the CO-ERPF studies. Group 1 consisted of patients studied fewer than 10 days after surgery; group 2 consisted of patients studied 10 to 20 days after operation; and group 3 consisted of patients studied more than 20 days after operation. Effective renal plasma flow was determined by the single-injection, single plasma sample method, where 50 μCi I-131 orthoiodohippurate was injected intravenously in a single dose and plasma concentrations of radioactivity were determined. The quotient of injected dose radioactivity divided by plasma radioactivity is highly predictive of global ERPF. Cardiac output was measured by thermodilution. Results: In the control group, a positive linear correlation was found between CO and ERPF; however, the CO: ERPF ratio was elevated, and after heart transplantation, a lag time was observed for as long as 3 weeks in some patients before CO:ERPF ratios returned to control group levels. The regression equation and standard error for the control group was CO = 1.85 + 0.0065 ERPF (±0.62) l/min versus 1.433 + 0.0068 ERPF (±0.64) l/min for group 3. The correlation coefficients comparing CO with ERPF were r = 0.88, 0.23, 0.51, and 0.85, for the control group and groups 1, 2, and 3, respectively. Conclusion: A localized release of catecholamines from the adrenal gland is proposed to cause ERPF damping after abrupt increases in CO.
Abstract 1977: <i>N</i>-glycosylation level of the type II TGF-β receptor is important for the stability and cell surface localization and affects TGF-β resistance in cancer cells
Authors: Young-Woong Kim, Jinah Park, Hyun-Ju Lee, Seong-Jin Kim
Journal: Cancer Research (2011)

Abstract N-linked glycosylation is a critical determinant of protein structure and function, regulating processes such as protein folding, stability, localization, ligand-receptor binding and intracellular signaling. The type II TGF-β receptor (TβRII) plays a crucial role in the TGF-β signaling pathway. Although N-linked glycosylation of TβRII was first demonstrated over a decade ago, it is unclear how this modification affects TβRII biology. By generating deficient N-linked glycosylation (dNG) mutants, in which each asparagine was converted to glutamine, we show here that N-linked glycosylation occurs on two conserved asparagine residues in the extracellular domain of TβRII. dNG mutant TbRII lines indeed exhibited defective N-linked glycosylation. Notably, non-glycosylated TβRII was more sensitive to proteasome-mediated degradation than fully N-glycosylated TβRII, suggesting that the N-linked glycosylation protects TβRII from proteasome-mediated degradation. Defective N-linked glycosylation also induced TβRII to accumulate in the endoplasmic reticulum (ER), resulting in decreased expression on the cell surface compared to N-glycosylated TβRII. Ultimately, upon TGF-β stimulation, cells expressing dNG mutant TβRII lines were not efficiently able to activate downstream signaling due to the decreased number of cell surface-expressed receptor molecules. These findings demonstrate that N-linked glycosylation is essentially required for the stability and cell surface localization of TβRII. Moreover, by comparing the N-linked glycosylation levels of TβRII in various cancer cell lines, we suggest that the degree of N-linked glycosylation of TβRII might be one of molecular mechanisms involved in the different cellular responses of cancer cell lines upon TGF-β treatment, shedding light on the N-linked glycosylation that fosters TGF-β resistance in many cancers. 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 1977. doi:10.1158/1538-7445.AM2011-1977
SP0174 How to Optimize Health Professional Input in Your Practice
Authors: P. Cornell
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Tricia Cornell will lead the discussion around optimizing the use of health professionals in a rheumatology practice. This should be a lively debate bringing together the aspects of physiotherapy, occupational therapy and nursing in the care of rheumatology patients. <h3>Disclosure of Interest</h3> None Declared
INCREASED LYSYL OXIDASE-LIKE 2 (LOXL2) CORRELATES WITH EJECTION FRACTION (EF) AND BNP IN HUMAN SYSTOLIC HEART FAILURE
Authors: Hongyan Zhong, Amanda Mikels-Vigdal, Emmanuel Moreau, Jacqueline Dupret-Carruel, Preeti Lal, Victoria Smith, Ching-Pin Chang, Lina Yao
Journal: Journal of the American College of Cardiology (2016)
Fluoxetine in the Treatment of Premenstrual Dysphoria
Authors: Meir Steiner, Susanne Steinberg, Donna Stewart, Diana Carter, Charlene Berger, Robert Reid, Douglas Grover, David Streiner
Journal: New England Journal of Medicine (1995)

Premenstrual dysphoria shares certain features with depression and anxiety states, which have been linked to serotonergic dysregulation. We evaluated the efficacy and safety of fluoxetine (which selectively inhibits the reuptake of serotonin) in the treatment of premenstrual dysphoria.The trial consisted of a single-blind, placebo washout period lasting two menstrual cycles, followed by a randomized, double-blind, placebo-controlled trial of fluoxetine at a dose of either 20 mg or 60 mg per day or placebo for six menstrual cycles. Healthy women meeting criteria for what was then called late-luteal-phase dysphoric disorder were recruited at seven university-affiliated women's health clinics in Canada. The primary outcome measure consisted of visual-analogue scales for tension, irritability, and dysphoria during the late luteal phase of each cycle.Of 405 women enrolled in the placebo washout period, 313 subsequently entered the randomized phase of the study, which lasted six menstrual cycles, and 180 completed it. Fluoxetine at a dose of 20 or 60 mg per day was significantly superior to placebo in reducing symptoms of tension, irritability, and dysphoria, as measured by the visual-analogue scales (P < 0.001). The women who received 60 mg of fluoxetine per day reported significantly more side effects than those who received 20 mg per day or placebo (P < 0.001).Fluoxetine is useful in the treatment of premenstrual dysphoria. Treatment with fluoxetine at a dose of 20 mg per day reduces the potential for side effects while maximizing therapeutic efficacy.
Reply to Solís-Muñoz et al.
Authors: E. Kim, S. Jeon
Journal: Endoscopy (2010)

We have read the letter by Solís-Muñoz et al. with great joy. We deeply appreciate their comments and sharing of important opinions on vanishing or unfound gastric cancer cases. In their letter, they report on a very interesting case of a 55-year-old male who was diagnosed with signet ring-cell adenocarcinoma, which was incidentally found in one sample specimen from random endoscopic biopsies for evaluation of gastritis status and antibiogram of Helicobacter pylori. After the meticulous and elaborate evaluation with highly sophisticated methods, including genetic and molecular tests to ensure the specimen belonged to the patient, the patient had been carefully followed up for 4 years and had shown no evidence of disease. We absolutely agree with the authors’ opinion that the focus of tumor cells was eliminated with the forceps biopsy and that a close endoscopic follow-up schedule will be necessary to detect the development of new foci in the future.
EVALUATION OF A NEW QUADRICEPS STRENGTHENING EXERCISE FOR THE PREVENTION OF SECONDARY CARTILAGE INJURY IN PATIENTS WITH PCL INSUFFICIENCY: COMPARISON OF TIBIAL MOVEMENT IN PRONE AND SITTING POSITIONS DURING THE EXERCISE
Authors: T Sakai, M Koyanagi, N Nakae, Y Kimura, Y Sanada, N Nakamura, K Nakata
Journal: British Journal of Sports Medicine (2014)

Background Quadriceps strengthening exercise is recommended for patients with PCL insufficiency (PCLI), but posterior sag may occur under the influence of gravity in general leg extension in the sitting position (LES). We hypothesized that leg extension in the prone position (LEP) would be a safe strengthening exercise because the tibia is repositioned in patients with PCLI. Objective To compare tibial displacement (step off: SO) between LEP and LES, in order to verify the safety of LEP. Design Quasi-experimental study. Setting Controlled laboratory research. Patients 6 patients with PCL insufficiency (SO 2.9±1.6 mm). Interventions: LEP and LES were performed for isometricstrengthening with a flexion angle of the knee of 60 degrees and consistent force of knee extension. SO was measured on lateral X-P images of the knee. Differences in tibial movement between LEP and LES were evaluated using a paired t-test (P&lt;0.05). Main outcome measurement SO measured by digitized XP. Results At the start position of LES, the tibia of all subjects was displaced posteriorly, and the tibia moved anteriorly 7.1±3.1 mm upon contraction of the quadriceps. In contrast, at the start position of LEP, the tibia was not displaced posteriorly in any subjects (SO=− 2.9±2.7 mm). Furthermore, there was significantly less anterior movement of the tibia during LEP (2.8±3.5 mm) than during LES (P&lt;.05). Conclusions Since LES produced excessive anterior movement of the tibia upon contraction of the quadriceps, secondary cartilage injury may occur because of increased compression and shear force. In contrast, the repositioning of the tibia in LEP by gravity indicates it could be a safe quadriceps strengthening exercise for PCL insufficiency.
Primary biliary cirrhosis: Time to replace a misnomer
Authors: Giovanni Battista Levi Sandri
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. We read with interest the recent letter to the editor entitled "Primary Biliary Cirrhosis: Time to Replace a Misnomer" published by Wahl et al. We congratulate the authors for their study based on interviewing new patients and opening again the debate for the name of primary biliary cirrhosis (PBC). The authors concluded that it is time to replace this misnomer with an adequate name for the disease. We agree with the authors' conclusion. PBC is now diagnosed at an early stage1 and the majority of patients will never develop cirrhosis. Although we agree with this, the acronym "PBC" is now used since it was first so called in 1965 by Rubin et al.2 Recently a Monothematic Conference on Primary Biliary Cirrhosis was held in Milan and a beautiful presentation was made by two patient associations. The debate confirmed the results presented by Wahl et al. However, a message has been clearly expressed: "Call it how you want, but please leave the acronym PBC." We would like to draw attention to the importance of the PBC acronym for the scientific community, physician, and patients. Yes, it is time to modify the term "cirrhosis" in PBC.