tbuckley/cabot-search huggingface dataset:
A Systematic Review and Meta-Analysis of the Pharmacological Treatment of Cancer-Related Fatigue
Authors: O. Minton, A. Richardson, M. Sharpe, M. Hotopf, P. Stone
Journal: JNCI Journal of the National Cancer Institute (2008)

Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.
Functional analysis of human hematopoietic repopulating cells mobilized with granulocyte colony-stimulating factor alone versus granulocyte colony-stimulating factor in combination with stem cell factor
Authors: David A. Hess, Krysta D. Levac, Francis N. Karanu, Michael Rosu-Myles, Martin J. White, Lisa Gallacher, Barbara Murdoch, Michael Keeney, Pamela Ottowski, Ronan Foley, Ian Chin-Yee, Mickie Bhatia
Journal: Blood (2002)
Key observations from the NHLBI Asthma Clinical Research Network
Authors: Stanley J Szefler, Vernon M Chinchilli, Elliot Israel, Loren Clark Denlinger, Robert F Lemanske, William Calhoun, Stephen P Peters
Journal: Thorax (2012)

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate its findings to the medical community. The ACRN conducted 15 major clinical trials. In addition, clinical data, manual of operations, protocols and template informed consents from all ACRN trials are available via NHLBI BioLINCC (https://biolincc.nhlbi.nih.gov/studies/). This network contributed major insights into the use of inhaled corticosteroids, short-acting and long-acting ß-adrenergic agonists, leukotriene receptor antagonists, and novel agents (tiotropium, colchicine and macrolide antibiotics). They also pioneered studies of the variability in drug response, predictors of treatment response and pharmacogenetics. This review highlights the major research observations from the ACRN that have impacted the current management of asthma.
Incidence of sports injuries in elite competitive and recreational windsurfers
Authors: R Dyson, M Buchanan, T Hale
Journal: British Journal of Sports Medicine (2006)

To investigate the incidence of injury in windsurfing and to consider methods of prevention.A total of 107 raceboard (RB) and wave/slalom (WS) national/international competitors and recreational (REC) windsurfers completed a questionnaire on injury incidence over two years. Recurrent injury, ability level, and any preventive measures taken were noted.Overall the injury incidence was 1.5/person/year. The WS group suffered more injuries (2.0/person/year) than the RB (1.0) or REC (1.2) group. The most common injury was muscle strain at 35% of new injuries, much higher than in earlier studies. Overall 45% of new injuries were muscle/tendon strains (RB 55%, WS 42%, and REC 43%) and 8% were ligament sprains. In the WS group cuts and abrasions were common. The WS and REC groups reported five and one case of concussion respectively. Nearly a quarter (22%) of new lower body injuries were lower back muscular strain, with 34% of recurrent injuries. Approximately 60% of the remaining lower body soft tissue injuries involved the knee or lower leg, with the ankle/foot most often involved. The shoulder, upper arm, and elbow were the sites of 41% of new upper body soft tissue injuries. The WS group reported 250% more recurrent muscular strains than the RB group. Recurrent ligament injuries (particularly knee) were most common in the WS group. The RB group reported recurrent serious bruising to the lower leg.The injury incidence was 1.5/person/year with a high incidence of new and recurrent muscular strain. Lower back muscular strain was prevalent, indicating the need for preventive measures. Wave/slalom was associated with more new and recurrent injuries and the need for head protection.
Acute Lung Injury Is Reduced in <i>fat-1</i> Mice Endogenously Synthesizing n-3 Fatty Acids
Authors: Konstantin Mayer, Almuth Kiessling, Juliane Ott, Martina Barbara Schaefer, Matthias Hecker, Ingrid Henneke, Richard Schulz, Andreas Günther, Jingdong Wang, Lijun Wu, Joachim Roth, Werner Seeger, Jing X. Kang
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency.To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI.We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice--markers of sickness behavior--were also recorded.In ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B(2) levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster.fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI.
Embryonic Inductive Tissues That Cause Histologic Differentiation of Murine Mammary Carcinoma In Vitro&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J J DeCosse, C Gossens, J F Kuzma, B R Unsworth
Journal: JNCI Journal of the National Cancer Institute (1975)

A murine mammary tumor was cultured in vitro for 14 days, either in direct combination with various embryonic murine inductive tissues or separated by a Millipore filter from these tissues. From 456 test cultures and 269 control cultures of tumor alone, morphologic, histochemical, and autoradiographic evidence for cytodifferentiation was obtained in the tumor after exposure to inductive tissues directly or through the filter. There appeared to be a gradient in potency of the inductive tissues; embryonic mammary mesenchyme was the most active of the tissues tested. Tumor growth was not different from that of controls, however, when the cultured, inductive tissue-exposed neoplasm was returned to the murine host.
CD8+ T Cells Specific for Tumor Antigens Can Be Rendered Dysfunctional by the Tumor Microenvironment through Upregulation of the Inhibitory Receptors BTLA and PD-1
Authors: Julien Fourcade, Zhaojun Sun, Ornella Pagliano, Philippe Guillaume, Immanuel F. Luescher, Cindy Sander, John M. Kirkwood, Daniel Olive, Vijay Kuchroo, Hassane M. Zarour
Journal: Cancer Research (2011)

Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally impotent in eliciting tumor rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies for immune therapy. The inhibitory receptors PD-1 and Tim-3 are known to negatively regulate CD8(+) T-cell responses directed against the well-characterized tumor antigen NY-ESO-1. Here, we report that the upregulation of the inhibitory molecule BTLA also plays a critical role in restricting NY-ESO-1-specific CD8(+) T-cell expansion and function in melanoma. BTLA-expressing PD-1(+)Tim-3(-) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in patients with melanoma. These cells were partially dysfunctional, producing less IFN-γ than BTLA(-) T cells but more IFN-γ, TNF, and interleukin-2 than the highly dysfunctional subset expressing all three receptors. Expression of BTLA did not increase with higher T-cell dysfunction or upon cognate antigen stimulation, as it does with PD-1, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. Collectively, our findings indicate that targeting BTLA along with the PD-1 and Tim-3 pathways is critical to reverse an important mechanism of immune escape in patients with advanced melanoma.
Influenza A/H1N1 in patients with cystic fibrosis in Italy: a multicentre cohort study
Authors: C. Colombo, P. M. Battezzati, V. Lucidi, G. Magazzu, V. Motta, G. Alicandro, G. Taccetti, T. Repetto
Journal: Thorax (2011)

Focetria (Novartis) monovalent inactivated pandemic influenza vaccine corresponding to 7.5 mg of haemagglutinin (HA) antigen strain A/California/7/2009 (H1N1)v like strain (X-179A) MF59-adjuvanted between November 2009 and February 2010.The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm on day 0. Blood samples were collected on day 0 and on day 21 to assess immunogenicity according to the Committee for Proprietary Medicinal Products (CPMP) criteria 5 ; CD4 T cell counts were also assessed on day 0 to exclude immunodeficiency.Patients or their parents recorded in a diary card the onset and severity of solicited local and systemic reactions within 7 days after the vaccine administration.We enrolled 48 CF patients with an average good pulmonary function and nutritional status.They showed normal CD4 T cell counts.All patients were assessed for safety and 33 of them for immunogenicity.There were no dropouts because of adverse reactions.The vaccine was well tolerated and no serious adverse events have been reported.All recorded symptoms were mild and shortlasting.The most frequent reported symptoms were local reactions.Seroconversion rate was satisfactory and met all the CPMP criteria.Demographics, immunogenicity and safety data are shown in table 1.In conclusion, a single 7.5 mg dose of the monovalent A/H1N1 MF59-adjuvanted vaccine results in a high rate of seroconver-sion in CF patients.These data support the current influenza vaccination strategy.The vaccine is well tolerated and the frequency of adverse events is comparable with literature data regarding other influenza vaccines.However, we studied a small cohort of young patients with an overall good nutritional and lung status.In severe malnourished CF patients, supposed to have a decreased immune response, the vaccine may not have the same efficacy.Future prospectical studies are needed to evaluate the benefits of influenza vaccines on defined clinical outcomes.
Optical Imaging of the Heart
Authors: Igor R. Efimov, Vladimir P. Nikolski, Guy Salama
Journal: Circulation Research (2004)

Optical techniques have revolutionized the investigation of cardiac cellular physiology and advanced our understanding of basic mechanisms of electrical activity, calcium homeostasis, and metabolism. Although optical methods are widely accepted and have been at the forefront of scientific discoveries, they have been primarily applied at cellular and subcellular levels and considerably less to whole heart organ physiology. Numerous technical difficulties had to be overcome to dynamically map physiological processes in intact hearts by optical methods. Problems of contraction artifacts, cellular heterogeneities, spatial and temporal resolution, limitations of surface images, depth-of-field, and need for large fields of view (ranging from 2x2 mm2 to 3x3 cm2) have all led to the development of new devices and optical probes to monitor physiological parameters in intact hearts. This review aims to provide a critical overview of current approaches, their contributions to the field of cardiac electrophysiology, and future directions of various optical imaging modalities as applied to cardiac physiology at organ and tissue levels.
Secondary Colorectal Carcinoma After Childhood Cancer
Authors: Kerri Nottage, Joshua McFarlane, Matthew J. Krasin, Chenghong Li, Deokumar Srivastava, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2012)

Colorectal carcinoma (CRC) has been described as a subsequent malignant neoplasm (SMN), although little is known about associated risk factors. We aimed to quantify the long-term risk of secondary CRC and identify treatment-related risk factors.In this nested case-control study, 19 cases of adenocarcinoma of the colon or rectum were identified from 13,048 oncology patients treated for childhood cancer at St Jude Children's Research Hospital. Group 1 controls (n = 148) were matched for age at primary malignancy and follow-up interval. Group 2 controls (n = 72) were matched on primary diagnosis in addition to group 1 criteria. Exact conditional logistic regression was performed to calculate odds ratios (ORs) for chemotherapy and radiation exposure.Forty-year cumulative incidence of secondary CRC was 1.4%. Standardized incidence ratio was 10.9 (95% CI, 6.6 to 17.0) compared with that in the general US population. Secondary CRC was more likely in an irradiated segment of the colon (group 1 OR, 7.7; P = .001; group 2 OR, 15.4; P = .002). Risk increased by 70% with each 10-Gy increase in radiation dose. Increasing radiation volume increased risk (group 1 OR, 1.5; P < .001; group 2 OR, 1.8; P < .001). Alkylating agent exposure was associated with an 8.8-fold increased risk of secondary CRC (P = .03).In matched analyses, radiation and alkylator exposure are associated with secondary CRC. This risk is proportional to dose and volume of radiation. Surveillance should be initiated at a young age among survivors receiving high-risk exposures.
PTP1B regulates lymphocytes responses androgen deprivation
Authors: Simo Arredouani, Haydn Kissick, Laura Dunn, Martin Sanda
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Androgen deprivation therapy (ADT) synergizes with prostate cancer (PCa) immunotherapy through androgen receptor- (AR) mediated immunoregulation. We show that surgical castration of male mice induces dramatic alterations in CD4+ T cell transcriptome. Pathway analysis identified T
RABBIT MACROPHAGE INTERFERONS
Authors: Thomas J. Smith, Robert R. Wagner
Journal: The Journal of Experimental Medicine (1967)

Interferon is produced in cultures of rabbit leukocytes in response to infection with Newcastle disease virus or in the absence of known viral infection. The macrophage appears to be the responsible producing cell. Cultures prepared from sterile peritoneal exudates, which contained about 90% macrophages, are at least as efficient as cultures of rabbit kidney (RK) cells in their capacity to synthesize NDV-induced interferon. Interferon can be detected in the medium by 2 hr after viral infection and the titers usually reach a peak of 10,000 PDD(50)/ml by 4-6 hr. Exposure to actinomycin prior to or shortly after viral induction effectively blocks interferon synthesis by cells of both types. However, macrophages become refractory to actinomycin by 30-60 min compared with 607-120 min for RK cells, a finding which suggests earlier and more rapid transcription of interferon-specific messenger RNA in macrophages. Macrophages harvested from the peritioneal cavity of rabbits injected intravenously with NDV 48 hr previously also exhibit slightly reduced capacity to synthesize interferon, but this tolerant state is less marked than is tolerance to production of circulating interferon in intact rabbits. Interferon is also synthesized by rabbit macrophages not infected with virus but simply incubated at 37 degrees C in medium with or without added bacterial endotoxin. Uninfected polymorphonuclear leukocytes, rabbit kidney and spleen cells produced no detectable interferon under similar conditions of cultivation. No interferon was released by intact macrophages incubated at 4 degrees C or by ultrasonically disrupted macrophages incubated at 37 degrees C. Although interferon titers were found to be higher when uninfected cultures were exposed to 10-100 microg/ml of E. coli lipopolysaccharide, unavailability of suitable pyrogen-free maintenance media precluded answering the question whether macrophages can continually synthesize and release interferon spontaneously. Interferon yields from uninfected macrophages were only 1% or less of the yields from NDV-infected macrophages, but the rates of synthesis were similar under both conditions. Studies with actinomycin and puromycin revealed that sequential transcriptive and translational events are required for de novo interferon synthesis by uninfected cells in a manner similar to virus-induced interferon synthesis. The physical properties and molecular weights of these rabbit interferons are discussed in the following report (12).
mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of <i>PTEN</i> Loss
Authors: Susmita Ghosh, Lidenys Varela, Akshay Sood, Ben Ho Park, Tamara L. Lotan
Journal: Cancer Research (2013)

Abstract Oncogenic signaling pathways are tightly regulated by negative feedback circuits and relief of these circuits represents a common mechanism of tumor drug resistance. Although the significance of these feedback pathways for signal transduction is evident, their relevance for cellular differentiation and morphogenesis in a genetically defined context is unclear. In this study, we used isogenic benign mammary organotypic cultures to interrogate the role of mTOR-mediated negative feedback in the specific setting of PTEN inactivation. We found that mTOR signaling promoted basal-like differentiation and repressed nuclear hormone receptor expression after short-term PTEN loss in murine cell cultures analyzed ex vivo. Unexpectedly, we found that PTEN inactivation inhibited growth factor-induced epithelial invasion and that downstream mTOR-mediated signaling feedback was both necessary and sufficient for this effect. Mechanistically, using isogenic MCF10A cells with and without somatic PTEN deletion, we showed that mTOR inhibition promoted EGF-mediated epithelial invasion by derepressing upstream EGF receptor, SRC tyrosine kinase, and phosphoinositide 3-kinase signaling. In addition to offering new signal transduction insights, these results bring to light a number of important and potentially clinically relevant cellular consequences of mTOR inhibition in the specific context of PTEN loss, including modulation of hormone and growth factor responsiveness and promotion of epithelial invasion. Our findings prompt future investigations of the possibility that mTOR inhibitor therapy may not only be ineffective but even deleterious in tumors with PTEN loss. Cancer Res; 73(16); 5218–31. ©2013 AACR.
WNK1 Activates Large-Conductance Ca2+-Activated K+ Channels through Modulation of ERK1/2 Signaling
Authors: Yingli Liu, Xiang Song, Yanling Shi, Zhen Shi, Weihui Niu, Xiuyan Feng, Dingying Gu, Hui-Fang Bao, He-Ping Ma, Douglas C. Eaton, Jieqiu Zhuang, Hui Cai
Journal: Journal of the American Society of Nephrology (2014)

With no lysine (WNK) kinases are members of the serine/threonine kinase family. We previously showed that WNK4 inhibits renal large-conductance Ca2+-activated K+ (BK) channel activity by enhancing its degradation through a lysosomal pathway. In this study, we investigated the effect of WNK1 on BK channel activity. In HEK293 cells stably expressing the α subunit of BK (HEK-BKα cells), siRNA-mediated knockdown of WNK1 expression significantly inhibited both BKα channel activity and open probability. Knockdown of WNK1 expression also significantly inhibited BKα protein expression and increased ERK1/2 phosphorylation, whereas overexpression of WNK1 significantly enhanced BKα expression and decreased ERK1/2 phosphorylation in a dose-dependent manner in HEK293 cells. Knockdown of ERK1/2 prevented WNK1 siRNA-mediated inhibition of BKα expression. Similarly, pretreatment of HEK-BKα cells with the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of WNK1 siRNA on BKα expression in a dose-dependent manner. Knockdown of WNK1 expression also increased the ubiquitination of BKα channels. Notably, mice fed a high-K+ diet for 10 days had significantly higher renal protein expression levels of BKα and WNK1 and lower levels of ERK1/2 phosphorylation compared with mice fed a normal-K+ diet. These data suggest that WNK1 enhances BK channel function by reducing ERK1/2 signaling-mediated lysosomal degradation of the channel.