tbuckley/cabot-search huggingface dataset:
Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis
Authors: Mary C. Playdon, Michael B. Bracken, Tara B. Sanft, Jennifer A. Ligibel, Maura Harrigan, Melinda L. Irwin
Journal: JNCI Journal of the National Cancer Institute (2015)

Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer–specific, all-cause mortality and recurrence outcomes. Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer–specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided. Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I2 = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25kg/m2 (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25kg/m2 or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer–specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05). Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher.
The potential efficacy of noninvasive ventilation with administration of a neutrophil elastase inhibitor for acute respiratory distress syndrome
Authors: Takuma Matsumura, Kenji Tsushima, Jiro Terada, Seiichiro Sakao, Yuji Tada, Yasunori Kasahara, Nobuhiro Tanabe, Koichiro Tatsumi, Keishi Kubo
Journal: European Respiratory Journal (2014)

Purpose : Noninvasive ventilation (NIV) can reduce the need for invasive mechanical ventilation. The aim of this investigation was to determine whether the combination of NIV with administration of a neutrophil elastase inhibitor could improve outcome and respiratory conditions in acute respiratory distress syndrome (ARDS)-patients, according to the Berlin definition.   Methods : ARDS-patients were treated with NIV and a neutrophil elastase inhibitor. We investigated clinical data and outcome among patients classified as having mild, moderate and severe ARDS. ARDS-patients were divided into survivors and nonsurvivors on day 28 after the induction of NIV.   Results : A total of 47 ARDS-patients received NIV, and 37 of these patients did not require endotracheal intubation. Eight of 10 mild, 17 of 22 moderate, and 10 of 15 severe ARDS-patients were alive on day 28 after the induction of NIV. When ARDS-patients were divided into groups based upon an initial PaO 2 /FIO 2  greater or less than 150 torr, the serial changes of both the PaO 2 /FIO 2  and the lung injury score improved dramatically in those patients with a PaO 2 /FIO 2  g150. The survival ratio showed statistically significant differences in mild and moderate ARDS-patients treated with the neutrophil elastase inhibitor.   Conclusions : Administration of neutrophil elastase inhibitor with NIV may be associated with successful outcome in mild-to-moderate ARDS-patients with initial PaO 2 /FIO 2  g150.
Adenocarcinoma of the Vagina and Stilbestrol as a "Morning-after" Pill
Authors: R A Hatcher, C C Conrad
Journal: New England Journal of Medicine (1971)

It is contended that the use of stillbestrol in high doses as a morning-after pill taken immediately after an unprotected intercourse should be discouraged because of numerous unknowns about the effect of such treatment on the womans  subsequent pregnancies.  Reports have been filed of the development of adenocarcinoma of the vagina in young women whose mothers used stilbestrol in pregnancy.  It is not known whether stilbestrol as a morning- after pill (50 mg per day for 5 days) could similarly affect subsequent pregnancies whether the effect is related to a certain timing dosage or duration of therapy and whether other  estrogens used in the same manner would have the same effect.  Patients should be administered stilbestrol in these doses only in rare cases of semiemergency and they should be warned of the potential hazard to the fetus.
Comprehensive analysis of EGFR signaling pathways in non-small cell lung cancer.
Authors: Yoshiro Fujiwara, Shinobu Hosokawa, Shinichi Toyooka, Nagio Takigawa, Katsuyuki Hotta, Masaki Tokumo, Tadashi Yoshino, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4100 

Recent advances in our understanding of tumor biology have led to a major shift in the treatment strategy of non-small cell lung cancer (NSCLC) towards targeting aberrant signaling pathways caused by genetic alterations. Epidermal growth factor receptor ( EGFR ) gene mutations are found in a certain subset of patients with NSCLC, and are known to confer the sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKI), including gefitinib. Preclinical studies have shown that activating EGFR mutations constitutively enhance the signaling of intracellular cascades such as PI3K/Akt and Ras/Raf/MAPK pathways. However, the correlation between EGFR mutations and phosphorylation of EGFR and the activation of its downstream molecules has not been fully evaluated in clinical setting. To better understand these relationship, we studied the EGFR mutation status by direct sequence method as well as by immunohistochemical staining to investigate the protein expression level of EGFR, phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), and phosphorylated MAPK (p-MAPK) in 93 surgically resected NSCLC patients. Clinical information was also obtained from these individuals to determine the impact of molecular changes on clinical characteristics and survival in patients with NSCLC. The results revealed that there were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, 14 in exon 21). Protein expression of EGFR, p-EGFR, p-Akt, and p-MAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. As expected, EGFR mutations were significantly associated with female gender, never-smoking history, and adenocarcinoma histology (P<0.05, each). Of note, p-Akt expression was also associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (P<0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (P<0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but p-MAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (P<0.05), suggesting the strong linkage between p-MAPK expression and survival benefit from gefitinib. These results could provide new insights into the rational application of inhibitors of Akt and MAPK as single agent or in combination with EGFR-TKI for the treatment of NSCLC.
Improved Surgical Outcome for Chronic Severe Aortic Regurgitation With Severely Depressed Left Ventricular Systolic Function⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Paul A. Grayburn
Journal: Journal of the American College of Cardiology (2007)
CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GN
Authors: Hans-Joachim Paust, Jan-Hendrik Riedel, Christian F. Krebs, Jan-Eric Turner, Silke R. Brix, Sonja Krohn, Joachim Velden, Thorsten Wiech, Anna Kaffke, Anett Peters, Sabrina B. Bennstein, Sonja Kapffer, Catherine Meyer-Schwesinger, Claudia Wegscheid, Gisa Tiegs, Friedrich Thaiss, Hans-Willi Mittrücker, Oliver M. Steinmetz, Rolf A.K. Stahl, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2015)

Chemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the T H 1–associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA–associated crescentic GN and colocalize with CXCR3 + effector T cells. To investigate the functional role of CXCR3 + Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3 eGFP-Cre × Cxcr3 fl/fl ) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming T H 1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFN γ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3 + T H 1 cells, allowing Treg localization and control of excessive T H 1 responses at sites of inflammation.
Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis
Authors: Yanli Yan, Li Ma, Xiaoxu Zhou, Murugavel Ponnusamy, Jinhua Tang, Michelle A. Zhuang, Evelyn Tolbert, Georgia Bayliss, Jianwen Bai, Shougang Zhuang
Journal: Kidney International (2015)
Assessment of infection in chronic wounds based on the activities of elastase, lysozyme and myeloperoxidase
Authors: D. Schiffer, M. Blokhuis-Arkes, J. van der Palen, E. Sigl, A. Heinzle, G.M. Guebitz
Journal: British Journal of Dermatology (2015)

Assessment of infection in chronic wounds based on the activities of elastase, lysozyme and myeloperoxidase
Level of PD-1 expression on CD8+ T cells influence prognosis and respond to PD-1 therapy in a murine model
Authors: Benjamin A Kansy, Raghvendra M Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jing Li, William Gooding, Sven Brandau, Stephan Lang, Nicole Schmitt, Gordon J Freeman, David A Clump, Robert L Ferris
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Prognosis varies dramatically in head and neck squamous cell carcinoma (HNSCC) based on HPV status. In HPV+ patients, programmed death (PD)-1 expression has been linked to a better clinical outcome. We hypothesized that extent of PD-1 expression may differentially impact T cell
Impaired Ferritin mRNA Translation in Primary Erythroid Progenitors: Shift to Iron-Dependent Regulation by the v-ErbA Oncoprotein
Authors: Wolfgang Mikulits, Matthias Schranzhofer, Anton Bauer, Helmut Dolznig, Lioba Lobmayr, Anthony A. Infante, Hartmut Beug, Ernst W. Müllner
Journal: Blood (1999)
Diversity of Lesion Morphology in CTEPH Analyzed by OCT, Pressure Wire, and Angiography
Authors: Haruhisa Ishiguro, Masaharu Kataoka, Takumi Inami, Nobuhiko Shimura, Ryoji Yanagisawa, Takashi Kawakami, Keiichi Fukuda, Hideaki Yoshino, Toru Satoh
Journal: JACC. Cardiovascular imaging (2015)
High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series.
Authors: J Y Blay, T Conroy, C Chevreau, A Thyss, N Quesnel, H Eghbali, R Bouabdallah, B Coiffier, J P Wagner, A Le Mevel, D Dramais-Marcel, E Baumelou, F Chauvin, P Biron
Journal: Journal of Clinical Oncology (1998)

The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression.Prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL.With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX-containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007).Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series.
Abstract P198: Does Cetp Mass Contribute to the Response of LDL Particle Size to a 1-yr Lifestyle Modification Program in Viscerally Obese Dyslipidemic Men?
Authors: Emilie Pelletier Beaumont, Jean Bergeron, Natalie Alméras, Angelo Tremblay, Paul Porier, Jean-Pierre Després
Journal: Circulation (2012)

Numerous studies have demonstrated improvements in lipid and lipoprotein levels with endurance exercise training and weight loss. However, less is known about the contribution of the enzyme cholesteryl ester transfer protein (CETP) to the response of lipoprotein levels to a physical activity/healthy eating lifestyle modification program. Objective: To examine the effect of a 1-year lifestyle modification program inducing loss of visceral adipose tissue on plasma CETP mass in abdominally obese dyslipidemic men. Methods: Plasma CETP mass concentration was measured by ELISA at baseline and after a 1-year lifestyle modification program in 116 abdominally obese men aged 30 to 65 years without diabetes. Visceral adiposity was assessed by computed tomography and a complete fasting plasma lipoprotein-lipid profile was also obtained at baseline and after the intervention. Results: After 1 year, no significant changes were observed in CETP mass (1.91±0.45 vs.1.93±0.49 mg/l, ns). However, both HDL (81.7±2.1 vs. 83.8±3.1 Å, p&lt;0.0001) and LDL (252.1±3.9 vs. 253.6±3.7 Å, p&lt;0.0001) particle sizes assessed by gradient gel electrophoresis were increased. Whereas no significant correlation between change in HDL size and CETP mass was observed, change in LDL size was significantly correlated with change in CETP mass (r=−0.30, p=0.001). We also divided men into two groups: men who showed no change or an increase in their CETP mass (ΔCETP≥0) and men who decreased their CETP mass (ΔCETP&lt;0). Men who reduced their CETP mass after one year showed a greater increase in LDL size (Δ 2.37±3.18 vs.0.32±3.04 Å, p=0.0006) and a greater decrease in triglyceride levels (Δ-0.70±0.86 vs. −0.34±0.80 mmol/l, p=0.03) than men who showed no change or an increase in CETP mass. A Multivariate analysis revealed that 19% of the variance in the response of LDL size could be attributed to changes in triglyceride levels (15%) and in CETP mass (4%) (p=0.02). Conclusion: Whereas no significant change in CETP mass was observed, our results showed that individual variation in the response of CETP mass contributed to the response of LDL particle size to a 1-yr lifestyle modification program in viscerally obese dyslipidemic men.
Comment on “Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity” and “Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination”
Authors: Scott B. Halstead
Journal: Science Translational Medicine (2015)

New insights into toxicity of dengue virus protein NS1 provide context to previous work and prompt further questions.
Challenges of harmonising data from UK national health surveys: a case study of attempts to estimate the UK prevalence of asthma
Authors: Bright I Nwaru, Mome Mukherjee, Ramyani P Gupta, Angela Farr, Martin Heaven, Andrew Stoddart, Amrita Bandyopadhyay, Deborah Fitzsimmons, Michael Shields, Ceri Phillips, George Chamberlain, Colin Fischbacher, Christopher Dibben, Chantelle Aftab, Colin R Simpson, Ronan Lyons, David Strachan, Gwyneth A Davies, Brian McKinstry, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2015)
Can Natriuretic Peptides Help Identify Heart Failure Patients for Whom Statins Are Beneficial?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Lori B. Daniels, Elizabeth Barrett-Connor
Journal: Journal of the American College of Cardiology (2009)
The lipokine, or palmitoleic acid (16:1), is a biomarker of lung function in chronic obstructive pulmonary disease (COPD)
Authors: Hiroo Wada, Shin-ichi Hagiwara, Yorihiro Yamamoto, Hajime Goto, Ian Adcock, Hajime Takizawa
Journal: European Respiratory Journal (2014)

Introduction: Palmitoleic acid, 16:1, is amajor free fatty acid found in bloodsynthesized from palmitic acid (16:0) by stearoyl-CoA desaturase-1 (SCD-1), and a bio-marker for oxidative stress. 16:1 was recently identified as lipokine, a lipid hormone, regulating cell proliferation, inflammatory response and glucose metabolism. We examined the association between 16:1 and lung function in healthy control subjects and patients with chronic obstructive pulmonary disease (COPD).

Methods: 103 subjects with normal lung function and 18 COPD patients were enrolled. Plasma was collected and free fatty acid componentsmeasured. Univariate regression analysis wasperformed prior to the mutivariate analyses to elucidate characteristics that were associated with FEV1 and 16:1. 16:1 association with FEV1 with age was investigated by regression analysis and ANCOVA in healthy subjects and COPD patients.

Results: 16:1 levels and FEV1 were significantly associated (p<0.05) although multivariate analyses revealed that FEV1 was significantly associated with age (p<0.0001) and body height (p<0.001), rather than 16:1 directly. There was a significant positive association between 16:1/16:0 ratio and age in healthy subjects (p<0.01). The association between 16:1/16:0 ratio with ageing was significantly different between healthy subjects and COPD patients (p<0.01).

Conclusion: The association between 16:1 and FEV1 is due to an age-dependent increase in 16:1/16:0, or SCD-1 activity, in health subjects. The down regulation of this age-dependency may play a pathogenic role in COPD.
Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.
Authors: Sung Rok Kim, Sung-En Park, Young Jin Yuh, Byeong Seok Sohn, Hye Ran Lee, Hong-Suk Song, Kyung-Hee Lee
Journal: Journal of Clinical Oncology (2015)

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m 2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m 2 /day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m 2 and 100mg/m 2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m 2 and 100mg/m 2 , respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.
Development and implementation of communities of practice at Cancer Care Ontario (CCO).
Authors: Marissa Mendelsohn, Stephen Breen, David D'Souza, Sophie Foxcroft, Anthony W. Fyles, Eric Gutierrez, Joon-Hyung J. Kim, Elizabeth Lockhart, Elizabeth Murray, Ananth Ravi, Raxa Sankreacha, Dani Scott, Khaled Zaza, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2013)

58 Background: A “Community of Practice” (CoP) has been defined as a group of people who share a passion for something they do and learn to improve as they translate knowledge and interact together. Methods: The primary goal of the Radiation Treatment Program (RTP) at CCO is to improve the quality of care delivered to Ontario patients receiving radiation treatment. We identified variations in practice in the 14 Regional Cancer Centers (RCC) in Ontario and facilitated the development of 3 CoPs to share best practices and standardize care where appropriate. Through this initiative, two multidisciplinary [Radiation Oncologists, Physicists and Radiation Therapists (MRT(T)s)] CoPs have been established in Head and Neck (H&amp;N) and Gynecological (GYN) Cancers and one discipline-specific CoP has been started in Radiation Treatment External Beam Delivery involving MRT(T)s alone . During initial meetings of each CoP key variations in practice affecting quality of care were identified. Results: Each CoP has developed recommendation documents for improving care: H&amp;N Cancer – Nomenclature for anatomic structures in treatment volumes and Evaluation of Intensity Modulated treatment Plans; GYN Cancer – Imaging strategies for Intracavitary Brachytherapy of Cervical Cancer; Treatment Delivery – Protocol Development Toolkit and Image Guided Radiation Therapy Education Checklist. These recommendation documents are currently being piloted in each RCC with a view to standardizing care across the province. Conclusions: These CoP initiatives have enabled the development of recommendation reports by front-line staff to ensure evidence-based, high-quality radiation treatment to improve the safety and quality of care for all cancer patients across a jurisdiction of 13M people.