tbuckley/cabot-search huggingface dataset:
PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy
Authors: Yue Wang, Yiying Wang, Jie Li, Zeng Yuan, Bingbing Yuan, Tingguo Zhang, Janiel M Cragun, Beihua Kong, Wenxin Zheng
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy. Methods Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n = 96), metastatic cancers (n = 22), and benign controls (n = 50). Results Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n = 4) and the metastasis from gastrointestinal tract (n = 17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n = 4) and endometriosis (n = 1), 25 PAX8-/Calretinin + cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia. Conclusions PAX8 identifies all Müllerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.
Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials
Authors: J. Bergh, K. Pritchard, K. Albain, S. Anderson, R. Arriagada, W. Barlow, W. Bergsten-Nordström, J. Bliss, F. Boccardo, R. Bradley, M. Buyse, D. Cameron, M. Clarke, M. Coates, R. Coleman, C. Correa, J. Costantino, J. Cuzick, N. Davidson, C. Davies, A. Di Leo, M. Dowsett, M. Ewertz, J. Forbes, R. Gelber, R. Geyer, R. Gianni, M. Gnant, A. Goldhirsch, R. Gray, D. Hayes, C. Hill, J. Ingle, W. Janni, E. MacKinnon, M. Martín, P. McGale, L. Norton, Y. Ohashi, S. Paik, H. Pan, E. Perez, R. Peto, R. Piccart, L. Pierce, V. Raina, P. Ravdin, J. Robertson, E. Rutgers, J. Sparano, S. Swain, C. Taylor, G. Viale, G. Von Minckwitz, X. Wang, T. Whelan, N. Wilcken, E. Winer, N. Wolmark, W. Wood
Journal: The Lancet (2015)

Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer.
A Multicenter, Randomized, Controlled Trial of Dexamethasone for Bronchiolitis
Authors: Howard M. Corneli, Joseph J. Zorc, Prashant Mahajan, Kathy N. Shaw, Richard Holubkov, Scott D. Reeves, Richard M. Ruddy, Baqir Malik, Kyle A. Nelson, Joan S. Bregstein, Kathleen M. Brown, Matthew N. Denenberg, Kathleen A. Lillis, Lynn Babcock Cimpello, James W. Tsung, Dominic A. Borgialli, Marc N. Baskin, Getachew Teshome, Mitchell A. Goldstein, David Monroe, J. Michael Dean, Nathan Kuppermann
Journal: New England Journal of Medicine (2007)

Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limited.We conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). We enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). We also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events.Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes.In infants with acute moderate-to-severe bronchiolitis who were treated in the emergency department, a single dose of 1 mg of oral dexamethasone per kilogram did not significantly alter the rate of hospital admission, the respiratory status after 4 hours of observation, or later outcomes. (ClinicalTrials.gov number, NCT00119002 [ClinicalTrials.gov].).
Regulation of angiotensin type 1 receptor and its gene expression
Authors: D H Wang, Y Du, H Zhao, J P Granger, R C Speth, D J Dipette
Journal: Journal of the American Society of Nephrology (1997)

Low sodium intake has been demonstrated to upregulate the gene expression of the predominant renal type 1 angiotensin II (Ang II) receptor (AT1), the AT1A subtype. The study presented here tests the hypothesis that the upregulation of renal AT1 mRNA induced by sodium depletion occurs conjointly with an elevation of the AT1 receptor that modulates renal growth. Seven-week-old male Wistar rats were divided into four groups and treated for 2 wk with normal sodium diet, normal sodium diet plus 3 mg/kg/day losartan, low sodium diet, or low sodium diet plus losartan. Body weight and MAP were not significantly different among the four groups. Plasma renin activity was significantly elevated by losartan treatment, low salt intake, or a combination of the two, compared with the plasma renin activity of the controls. Northern blot analysis indicated that renal AT1 mRNA levels were significantly increased-183% by losartan, 212% by low salt intake, and 227% by the combination of the two-compared with their levels in controls. Radioligand binding assays revealed that AT1 receptors were significantly increased by low salt intake but were significantly decreased by losartan treatment. Renal AT1 receptor binding in the rats subjected to sodium depletion plus losartan did not differ from that in control rats. Kidney weight, kidney weight/body weight ratio, and renal DNA and protein content were not altered by sodium depletion but were significantly lowered by losartan treatment with both normal and low sodium intake, compared with those of controls. The protein/DNA ratio was not significantly different among the four groups. Blockade of renal AT1 receptors with losartan was found to retard normal renal growth, indicating that Ang II is required for normal renal development. Low sodium intake was found to increase mRNA and expression of the renal AT1 receptor but to have no effect on renal growth, suggesting that an increase in renal mass above a normal level requires the activation of multiple factors. Blockade of the AT1 receptor by losartan was found to upregulate AT1 mRNA but to down-regulate the AT1 receptor, suggesting that AT1 receptor-mediated intracellular events are necessary to sustain functional AT1 receptor expression in the kidney.
The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers
Authors: D. Lawrence, K. J. Hancock, S. Kisely
Journal: BMJ (2013)

<b>Objective</b> To examine the mortality experience of psychiatric patients in Western Australia compared with the general population. <b>Design</b> Population based study. <b>Setting</b> Western Australia, 1985-2005. <b>Participants</b> Psychiatric patients (292 585) registered with mental health services in Western Australia. <b>Main outcome measures</b> Trends in life expectancy for psychiatric patients compared with the Western Australian population and causes of excess mortality, including physical health conditions and unnatural causes of death. <b>Results</b> When using active prevalence of disorder (contact with services in previous five years), the life expectancy gap increased from 13.5 to 15.9 years for males and from 10.4 to 12.0 years for females between 1985 and 2005. Additionally, 77.7% of excess deaths were attributed to physical health conditions, including cardiovascular disease (29.9%) and cancer (13.5%). Suicide was the cause of 13.9% of excess deaths. <b>Conclusions</b> Despite knowledge about excess mortality in people with mental illness, the gap in their life expectancy compared with the general population has widened since 1985. With most excess deaths being due to physical health conditions, public efforts should be directed towards improving physical health to reduce mortality in people with mental illness, in addition to ongoing efforts to prevent suicide.
Trastuzumab in CSF
Authors: Bernhard C. Pestalozzi, Sue Brignoli
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.11.2349 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10829059 Trastuzumab in CSF Bernhard C. PestalozzixBernhard C. PestalozziSearch for articles by this author , Sue BrignolixSue BrignoliSearch for articles by this author Show More University Hospital ZurichSwitzerlandGenentech Inc. San FranciscoCA https://doi.org/10.1200/JCO.2000.18.11.2349 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells
Authors: H M Roche, A M Terres, I B Black, M J Gibney, D Kelleher
Journal: Gut (2001)

Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects. Tight junctions of epithelial cells determine epithelial membrane integrity and selective paracellular permeability to ions and macromolecules. Occludin and ZO-1 are integral structural components of the tight junction, which are involved in the biogenesis and functional integrity of the epithelial monolayer. This study investigated the effects of two isomers of CLA (cis-9 and trans-10 isomers) on Caco-2 cell transepithelial resistance (TER) development, paracellular epithelial permeability, and occludin and ZO-1 expression. Caco-2 cells were grown in media supplemented with 0.05 mM linoleic acid, cis-9 CLA, or trans-10 CLA for 21 days. The trans-10 CLA isomer delayed Caco-2 cell TER development, which is an in vitro measure of epithelial cell integrity, and increased paracellular epithelial permeability. Immunofluorescent staining of Caco-2 cell epithelial monolayers grown in media supplemented trans-10 CLA showed that the trans-10 CLA isomer altered distribution of occludin and ZO-1. The trans-10 CLA isomer delayed the acquisition of transepithelial resistance and altered the cellular distribution of occludin, which have important implications in relation to epithelial permeability.
Adverse effects of oral corticosteroids in relation to dose in patients with lung disease
Authors: L J Walsh, C A Wong, J Oborne, S Cooper, S A Lewis, M Pringle, R Hubbard, A E Tattersfield
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group. <h3>METHODS</h3> Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression. <h3>RESULTS</h3> A total of 367 patients (⩾50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising. <h3>CONCLUSIONS</h3> By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.
Matrix Metalloproteinase-14 Mediates a Phenotypic Shift in the Airways to Increase Mucin Production
Authors: Hitesh S. Deshmukh, Anne McLachlan, Jeffrey J. Atkinson, William D. Hardie, Thomas R. Korfhagen, Maggie Dietsch, Yang Liu, Peter Y. P. Di, Scott C. Wesselkamper, Michael T. Borchers, George D. Leikauf
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Induced mainly by cigarette smoking, chronic obstructive pulmonary disease (COPD) is a global public health problem characterized by progressive difficulty in breathing and increased mucin production. Previously, we reported that acrolein levels found in COPD sputum could activate matrix metalloproteinase-9 (MMP9).To determine whether acrolein increases expression and activity of MMP14, a critical membrane-bound endopeptidase that can initial a MMP-activation cascade.MMP14 activity and adduct formation were measured following direct acrolein treatment. MMP14 expression and activity was measured in human airway epithelial cells. MMP14 immunohistochemistry was performed with COPD tissue, and in acrolein- or tobacco-exposed mice.In a cell-free system, acrolein, in concentrations equal to those found in COPD sputum, directly adducted cysteine 319 in the MMP14 hemopexin-like domain and activated MMP14. In cells, acrolein increased MMP14 activity, which was inhibited by a proprotein convertase inhibitor, hexa-d-arginine. In the airway epithelium of COPD subjects, immunoreactive MMP14 protein increased. In mouse lung, acrolein or tobacco smoke increased lung MMP14 activity and protein. In cells, acrolein-induced MMP14 transcripts were inhibited by an epidermal growth factor receptor (EGFR) neutralizing antibody, EGFR kinase inhibitor, metalloproteinase inhibitor, or mitogen-activated protein kinase (MAPK) 3/2 or MAPK8 inhibitors, but not a MAPK14 inhibitor. Decreasing the MMP14 protein and activity in vitro by small interfering (si)RNA to MMP14 diminished the acrolein-induced MUC5AC transcripts. In acrolein-exposed mice or transgenic mice with lung-specific transforming growth factor-alpha (an EGFR ligand) expression, lung MMP14 and MUC5AC levels increased and these effects were inhibited by a EGFR inhibitor, erlotinib.Taken together, these findings implicate acrolein-induced MMP14 expression and activity in mucin production in COPD.
HIV Infection, Inflammation, Immunosenescence, and Aging
Authors: Steven G. Deeks
Journal: Annual Review of Medicine (2010)

Although antiretroviral therapy for HIV infection prevents AIDS-related complications and prolongs life, it does not fully restore health. Long-term treated patients remain at higher than expected risk for a number of complications typically associated with aging, including cardiovascular disease, cancer, osteoporosis, and other end-organ diseases. The potential effect of HIV on health is perhaps most clearly exhibited by a number of immunologic abnormalities that persist despite effective suppression of HIV replication. These changes are consistent with some of the changes to the adaptive immune system that are seen in the very old ("immunosenescence") and that are likely related in part to persistent inflammation. HIV-associated inflammation and immunosenescence have been implicated as causally related to the premature onset of other end-organ diseases. Novel therapeutic strategies aimed at preventing or reversing these immunologic defects may be necessary if HIV-infected patients are to achieve normal life span.
Temperature‐Sensitive Magnetic Drug Carriers for Concurrent Gemcitabine Chemohyperthermia
Authors: Dong‐Hyun Kim, Yang Guo, Zhuoli Zhang, Daniel Procissi, Jodi Nicolai, Reed A. Omary, Andrew C. Larson
Journal: Advanced Healthcare Materials (2013)

To improve the efficacy of gemcitabine (GEM) for the treatment of advanced pancreatic cancer via local hyperthermia potentiated via a multi-functional nanoplatform permitting both in vivo heating and drug delivery is the goal of this study. Here, a chemohyperthermia approach to synergistically achieve high intra-tumoral drug concentrations, while permitting concurrent hyperthermia for more effective tumor cell kill and growth inhibition, is proposed. Drug delivery and hyperthermia are achieved using a hydroxypropyl cellulose (HPC)-grafted porous magnetic drug carrier that is MRI visible to permit in vivo visualization of the biodistribution. These synthesized magnetic drug carriers produce strong T2 -weighted image contrast and permit efficient heating using low-magnetic-field intensities. The thermomechanical response of HPC permits triggered GEM release confirmed during in vitro drug release studies. During in vitro studies, pancreatic cancer cell growth is significantly inhibited (≈82% reduction) with chemohyperthermia compared to chemotherapy or hyperthermia alone. Using PANC-1 xenografts in nude mice, the delivery of injected GEM-loaded magnetic carriers (GEM-magnetic carriers) is visualized with both MRI and fluorescent imaging techniques. Chemohyperthermia with intra-tumoral injections of GEM-magnetic carriers (followed by heating) results in significant increases in apoptotic cell death compared to tumors treated with GEM-magnetic carriers injections alone. Chemohyperthermia with GEM-magnetic carriers offers the potential to significantly improve the therapeutic efficacy of GEM for the treatment of pancreatic cancer. In vivo delivery confirmation with non-invasive imaging techniques could permit patient-specific adjustments therapeutic regimens for improve longitudinal outcomes.
Randomized Controlled Trial of the Effects of Print Materials and Step Pedometers on Physical Activity and Quality of Life in Breast Cancer Survivors
Authors: Jeffrey K.H. Vallance, Kerry S. Courneya, Ronald C. Plotnikoff, Yutaka Yasui, John R. Mackey
Journal: Journal of Clinical Oncology (2007)

To determine the effects of breast cancer-specific print materials and step pedometers on physical activity (PA) and quality of life (QoL) in breast cancer survivors.Breast cancer survivors (N = 377) were randomly assigned to receive one of the following: a standard public health recommendation for PA, previously developed breast cancer-specific PA print materials, a step pedometer, or a combination of breast cancer-specific print materials and step pedometers. The primary outcome was self-reported moderate/vigorous PA minutes per week. Secondary outcomes were QoL (Functional Assessment of Cancer Therapy-Breast), fatigue, self-reported brisk walking, and objective step counts. Assessments were conducted at baseline and postintervention (12 weeks).Attrition was 10.3% (39 of 377). On the basis of linear mixed-model analyses, PA increased by 30 minutes/week in the standard recommendation group compared with 70 minutes/week in the print material group (mean difference, 39 minutes/week; 95% CI = -10 to 89; d = 0.25; P = .117), 89 minutes/week in the pedometer group (mean difference, 59 minutes/week; 95% CI, 11 to 108; d = 0.38; P = .017), and 87 minutes/week in the combined group (mean difference, 57 minutes/week; 95% CI, 8 to 106; d = 0.37; P = .022). For brisk walking minutes/week, all three intervention groups reported significantly greater increases than the standard recommendation group. The combined group also reported significantly improved QoL (mean difference, 5.8; 95% CI, 2.0 to 9.6; d = 0.33; P = .003) and reduced fatigue (mean difference, 2.3; 95% CI, 0.0 to 4.7; d = 0.25; P = .052) compared with the standard recommendation group.Breast cancer-specific PA print materials and pedometers may be effective strategies for increasing PA and QoL in breast cancer survivors. A combined approach appears to be optimal.ClinicalTrials.gov Identifier NCT00221221
TRPV4 Channels Mediate Cyclic Strain–Induced Endothelial Cell Reorientation Through Integrin-to-Integrin Signaling
Authors: Charles K. Thodeti, Benjamin Matthews, Arvind Ravi, Akiko Mammoto, Kaustabh Ghosh, Abigail L. Bracha, Donald E. Ingber
Journal: Circulation Research (2009)

Cyclic mechanical strain produced by pulsatile blood flow regulates the orientation of endothelial cells lining blood vessels and influences critical processes such as angiogenesis. Mechanical stimulation of stretch-activated calcium channels is known to mediate this reorientation response; however, the molecular basis remains unknown. Here, we show that cyclically stretching capillary endothelial cells adherent to flexible extracellular matrix substrates activates mechanosensitive TRPV4 (transient receptor potential vanilloid 4) ion channels that, in turn, stimulate phosphatidylinositol 3-kinase–dependent activation and binding of additional β1 integrin receptors, which promotes cytoskeletal remodeling and cell reorientation. Inhibition of integrin activation using blocking antibodies and knock down of TRPV4 channels using specific small interfering RNA suppress strain-induced capillary cell reorientation. Thus, mechanical forces that physically deform extracellular matrix may guide capillary cell reorientation through a strain-dependent “integrin-to-integrin” signaling mechanism mediated by force-induced activation of mechanically gated TRPV4 ion channels on the cell surface.