tbuckley/cabot-search huggingface dataset:
The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors
Authors: JingWei Lu, Terra-Dawn Plank, Fang Su, XiuJuan Shi, Chen Liu, Yuan Ji, ShuaiJun Li, Andrew Huynh, Chao Shi, Bo Zhu, Guang Yang, YanMing Wu, Miles F. Wilkinson, YanJun Lu
Journal: Journal of Clinical Investigation (2016)

Inflammatory myofibroblastic tumors (IMTs) are characterized by myofibroblast proliferation and an inflammatory cell infiltrate. Little is known about the molecular pathways that precipitate IMT formation. Here, we report the identification of somatic mutations in UPF1, a gene that encodes an essential component of the nonsense-mediated RNA decay (NMD) pathway, in 13 of 15 pulmonary IMT samples. The majority of mutations occurred in a specific region of UPF1 and triggered UPF1 alternative splicing. Several mRNA targets of the NMD pathway were upregulated in IMT samples, indicating that the UPF1 mutations led to reduced NMD magnitude. These upregulated NMD targets included NIK mRNA, which encodes a potent activator of NF-κB. In human lung cells, UPF1 depletion increased expression of chemokine-encoding genes in a NIK-dependent manner. Elevated chemokines and IgE class switching events were observed in IMT samples, consistent with NIK upregulation in these tumors. Together, these results support a model in which UPF1 mutations downregulate NMD, leading to NIK-dependent NF-κB induction, which contributes to the immune infiltration that is characteristic of IMTs. The molecular link between the NMD pathway and IMTs has implications for the diagnosis and treatment of these tumors.
Correlation of cancer-associated macrophage-like cells with systemic therapy and pathological stage in numerous malignancies.
Authors: Daniel L Adams, Raymond C. Bergan, Stuart S Martin, Saranya Chumsri, Monica Charpentier, Rena G. Lapidus, R. Katherine Alpaugh, Massimo Cristofanilli, Susan Tsai, Cha-Mei Tang, Martin J. Edelman
Journal: Journal of Clinical Oncology (2015)

11095 Background: Recently we published preliminary data on the presence of Cancer Associated Macrophage-Like cells (CAMLs) in a variety of malignancies and their clinical use in tracking cancer progression (Adams et al., PNAS 2014). This report is a follow-up in identifying and tracking CAMLs, with an emphasis on correlating clinical and pathological stage from baseline samples. Methods: This multi-institutional prospective pilot study consisted of 105 patient (pt) samples: Stage I-IV; breast (n = 34), prostate (n = 25), pancreatic (n = 39) and lung (n = 7). Evaluators were blinded to the source and stage of the pts. Additionally, 30 non-blinded healthy controls with no known malignant disease were analyzed. 7.5 mL of whole blood was collected; filtered by the CellSieve microfiltration assay; and stained with DAPI, CK 8/18/19, EpCAM and CD45. CAMLs were enumerated and identified as large multinucleated circulating myeloid cells (e.g. CD14+). We report CAML number at clinical stage in relation to healthy controls and compare with patient’s pathological stage. Results: CAMLs were identified in 98/105 samples (93%), ranging from 0-105 CAMLs per peripheral blood sample at baseline, while 0 were found in 30 healthy controls; Sensitivity = 93.3% (CI95% 87-97%) and Specificity = 100% (CI95% 88-100%). Pts with breast, prostate and pancreatic cancer underwent surgical procedures and pathologically staged (n = 98). The number of CAMLs at baseline had a weak association with clinical stage; stage I (8.7 per sample), Stage II (6.8), Stage III (16), Stage IV (26.1); R2= 0.82. However, the number of CAMLs at baseline highly correlated with final pathological staging; stage I (4.3), Stage II (6.3), Stage III (14), Stage IV (24.6); R2= 0.94. Conclusions: Our data suggests that 1) CAMLs are circulating immune cells specific to malignant disease and 2) the number of CAMLs is weakly associated with clinical stage but highly correlative with pathological stage in a variety of malignancies. These findings indicate that CAMLS may be a valuable supplement to current screening and staging procedures.
Calcium channel blockers are not associated with increased risk of breast cancer, study finds
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Calcium channel blockers were found not to be associated with an increased risk of breast cancer in a study of women who had a higher risk of the disease because they had a sister with the diagnosis.1

Whether taking calcium channel blockers would increase a woman’s risk of breast cancer has been much debated. A case control study published in 2013 found that women who used calcium channel blockers to treat …
Predictive value of exhaled nitric oxide in healthy infants for asthma at school age
Authors: Jakob Usemann, Oliver Fuchs, Pinelopi Anagnostopoulou, Insa Korten, Olga Gorlanova, Martin Röösli, Philipp Latzin, Urs Frey
Journal: European Respiratory Journal (2016)

Exhaled nitric oxide fraction ( F eNO) is a noninvasive biomarker that is elevated in subjects with asthma and allergic diseases [1]. Nitric oxide (NO) is produced by three NO synthase (NOS) enzymes: neuronal, endothelial and inducible (iNOS), all present in the human lung [2]. The increase of F eNO in asthmatic patients has mainly been attributed to an activation of iNOS, mediated through proinflammatory cytokines in the airways [3]. F eNO in newborns before exposure to environmental factors is not associated with school-age asthma development <http://ow.ly/ShQQ300xiN2> The authors would like to thank all study participants for participating in the study, along with our lung function technicians Gisela Wirz and Sharon Schmid, and our study nurses Christine Becher, Monika Graf, Barbara Hofer, Sandra Lüscher and Linda Beul-Béguin (all Division of Respiratory Medicine, Dept of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland) for their support. We thank Karine Landgren Hugentobler (UKBB, Basel, Switzerland) for helping with English style.
Essential Roles for Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and G-CSF in the Sustained Hematopoietic Response ofListeria monocytogenes–Infected Mice
Authors: Yifan Zhan, Graham J. Lieschke, Dianne Grail, Ashley R. Dunn, Christina Cheers
Journal: Blood (1998)
An outbreak of mumps in the Province of León Spain 1995-1996
Authors: L. E. Visser, K. C. González Perez, J Ramos Tejera, A C Berjón Barrientos, Y Vergara Guerrero, J. F. Martinez Navarro
Journal: Eurosurveillance (1998)

In Spain mumps vaccine is given at the age of 15 months together with measles and rubella vaccines since 1982. Increased numbers of cases and outbreaks of mumps appeared in several autonomous communities in 1995. An outbreak of mumps in the province of -
Rate of hemoglobin (Hb) decline from less than 10 g/dl to less than 9 g/dl in placebo-treated patients (pts) receiving chemotherapy: A pooled analysis of data from six randomized darbepoetin alfa trials.
Authors: R. Pirker, H. Collins, J. C. Legg, J. F. Vansteenkiste
Journal: Journal of Clinical Oncology (2011)

e19637 Background: Cancer pts often develop chemotherapy-induced anemia (CIA), which can be treated with erythropoiesis-stimulating agents (ESAs). Controlled trials have shown that ESAs reduce transfusion needs in CIA pts. Recent changes to the ESA product labels restricted ESA use in CIA (i.e., ESAs are now initiated in the US at Hb < 10 g/dL and in the EU at Hb ≤ 10 g/dL). Some evidence suggests pts with low Hb (< 9 g/dL) at ESA initiation are at higher risk for transfusion. Understanding how quickly CIA pts transition from Hb < 10 g/dL to < 9 g/dL may therefore help optimize ESA use. Methods: An exploratory, pooled analysis was performed in a subset of placebo-treated pts from 6 randomized darbepoetin alfa CIA trials. Pts had baseline Hb ≥ 10 g/dL and Hb < 10 g/dL at least once during the study-treatment period. Kaplan-Meier (K-M) estimates were calculated for the incidence of pts with transfusions, Hb < 9 g/dL, and Hb < 8 g/dL (or transfusion) by week 0, 3, 6, and 9 after Hb < 10 g/dL was reached. Results: Of 411 pts analyzed, 59% were men, 97% were white, 72.3% had lung cancer, 87.8% had known ≥ stage III cancer, and 79.3% had an ECOG status ≤ 1. The mean (Q1, Q3) age was 62.5 (56, 70) years, and mean (Q1, Q3) baseline Hb was 11.26 (10.47, 12.00) g/dL. Median time (95% CI) to Hb < 9 g/dL was 5 weeks (4, 7). Time-to-event analyses indicated that over half (54%) of pts transitioned from Hb < 10 g/dL to < 9 g/dL by 6 weeks (Table). Incidence of transfusion from Hb < 10 g/dL and incidence of Hb < 8 g/dL (or transfusion) from Hb < 10 g/dL are shown (Table). Conclusions: This exploratory analysis suggests pts receiving chemotherapy transition quickly from Hb < 10 g/dL to Hb < 9 g/dL. As evaluating the suitability of ESAs for CIA pts may take time, doing so early could mitigate some risk of pts requiring transfusions or reaching low Hb levels. Incidence of events from Hb < 10 g/dL for 411 placebo-treated pts receiving chemotherapy. Transfusion Hb < 9 g/dL Hb < 8 g/dL or transfusion Events, n (%) 178 (43%) 244 (59%) 196 (48%) K-M% of events (95% CI) By week 0 3% (2, 6) 13% (10, 16) 4% (3, 7) By week 3 20% (16, 24) 40% (35, 45) 23% (20, 28) By week 6 32% (27, 36) 54% (49, 59) 37% (33, 42) By week 9 39% (35, 44) 58% (53, 63) 45% (40, 50)
Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer (ACTS-HNC).
Authors: Takahide Taguchi, Akira Kubota, Kunitoshi Yoshino, Kichinobu Tomita, Naoyuki Kohno, Kazuyoshi Kawabata, Masaori Fukushima, Kiyoaki Tsukahara, Hideki Takemura, Yasuhisa Hasegawa, Tomonori Terada, Kunihiko Nagahara, Hiroaki Nakatani, Yuichiro Higaki, Shigemichi Iwae, Takeshi Beppu, Yutaka Hanamure, Satoshi Teramukai, Masato Fujii
Journal: Journal of Clinical Oncology (2013)

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.
Adenoma risk score for surveillance of colorectal neoplasm – a step forward?
Authors: Sri Misra, Ravi Kant, Manisha Dwivedi
Journal: Endoscopy (2016)

Colorectal cancer (CRC) is the third most common cancer worldwide, and accounts for 10 % of all malignancies and 8 % of cancer mortality [1]. Most colonic cancers arise from premalignant adenomatous polyps, and it has been assumed that the time taken for an adenoma to transform into carcinoma is about a decade. It seems logical, therefore, that the detection and removal of adenoma(s) is an opportunity for colonic cancer prevention. It is also well known that people who have undergone screening colonoscopy, and had adenomas removed during the screening process, also have an increased risk of developing adenoma(s) and CRC in the long term. To reduce the burden of CRC, various guidelines for surveillance have been published, and all guidelines recommend colonoscopy as the method of choice for surveillance of CRC.
The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat
Authors: L COLLETTI
Journal: Hepatology (1996)

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and have shown that this injury induces the production and release of hepatic-derived tumor necrosis factor α (TNF-α), which mediates, in part, local liver injury following hepatic reperfusion. In the present study, we have extended these previous observations to assess whether an interrelationship exists between TNF-α and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein, that may account for some of the pathology of neutrophil-mediated ischemia/reperfusion-induced liver injury. We observed that hepatic ischemia/reperfusion injury leads to: (1) a coincident increase in hepatic neutrophil sequestration, elevated serum alanine aminotransferase (ALT) levels, and hepatic production of epithelial neutrophil activating protein; (2) passive immunization with neutralizing antibodies to TNF-α resulted in significant suppression of hepatic-derived epithelial neutrophil activating protein; and (3) neutralization of epithelial neutrophil activating protein by passive immunization significantly attenuated neutrophil sequestration in the liver and serum ALT levels. These findings support the notion that local expression of hepatic epithelial neutrophil activating protein produced in response to TNF-α is an important mediator of the local neutrophil-dependent hepatic injury associated with hepatic ischemia/reperfusion.
Tumor progression locus 2 reduces severe allergic airway inflammation by inhibiting Ccl24 production in dendritic cells
Authors: Yashaswini Kannan, Yanda Li, Stephanie M. Coomes, Isobel S. Okoye, Victoria S. Pelly, Srividya Sriskantharajah, Eva Gückel, Lauren Webb, Stephanie Czieso, Nikolay Nikolov, Andrew S. MacDonald, Steven C. Ley, Mark S. Wilson
Journal: Journal of Allergy and Clinical Immunology (2016)

BackgroundThe molecular and cellular pathways driving the pathogenesis of severe asthma are poorly defined. Tumor progression locus 2 (TPL-2) (COT, MAP3K8) kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kinase signaling pathway following Toll-like receptor, TNFR1, and IL-1R stimulation.ObjectiveTPL-2 has been widely described as a critical regulator of inflammation, and we sought to investigate the role of TPL-2 in house dust mite (HDM)-mediated allergic airway inflammation.MethodsA comparative analysis of wild-type and Map3k8−/− mice was conducted. Mixed bone marrow chimeras, conditional knockout mice, and adoptive transfer models were also used. Differential cell counts were performed on the bronchoalveolar lavage fluid, followed by histological analysis of lung sections. Flow cytometry and quantitative PCR was used to measure type 2 cytokines. ELISA was used to assess the production of IgE, type 2 cytokines, and Ccl24. RNA sequencing was used to characterize dendritic cell (DC) transcripts.ResultsTPL-2 deficiency led to exacerbated HDM-induced airway allergy, with increased airway and tissue eosinophilia, lung inflammation, and IL-4, IL-5, IL-13, and IgE production. Increased airway allergic responses in Map3k8−/− mice were not due to a cell-intrinsic role for TPL-2 in T cells, B cells, or LysM+ cells but due to a regulatory role for TPL-2 in DCs. TPL-2 inhibited Ccl24 expression in lung DCs, and blockade of Ccl24 prevented the exaggerated airway eosinophilia and lung inflammation in mice given HDM-pulsed Map3k8−/− DCs.ConclusionsTPL-2 regulates DC-derived Ccl24 production to prevent severe type 2 airway allergy in mice.
Abstract 4716: Correlation Between Plaque Color Classification by Coronary Angioscopy and Fibrous Cap Thickness by Optical Coherence Tomography
Authors: Hiroki Ikenaga, Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Yasuharu Nakama, Tatsuya Maruhashi, Eisuke Kagawa, Kazuoki Dai
Journal: Circulation (2009)
High-Dose Gemcitabine Combined With Busulfan and Melphalan (Gem/Bu/Mel) With Autologous Stem-Cell Transplant (ASCT) In Refractory and Relapsed Myeloma
Authors: Yago Nieto, Nina Shah, Uday R Popat, Roy B Jones, Qaiser Bashir, Rolland Bassett, Benigno C. Valdez, Borje S Andersson, Simrit Parmar, Robert Z. Orlowski, Jatin J. Shah, Sheeba K. Thomas, Michael Wang, Richard E Champlin, Muzaffar Qazilbash
Journal: Blood (2013)
C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis
Authors: Tie Wang, Yuzhe Wei, Lining Tian, Hongjiang Song, Yan Ma, Qian Yao, Meiyan Feng, Yanying Wang, Meizhuo Gao, Yingwei Xue
Journal: International Journal of Surgery (2016)
Abstract 17051: Relationship Between Neurohormonal Blockade Dose and Clinical Outcome in Patients With Heart Failure With Recovered Ejection Fraction
Authors: Min-Seok Kim, Hyo-In Choi, Jin-Oh Park, Ju Hyeon Kim, Yeong jin Jeong, Jae-Joong Kim
Journal: Circulation (2015)

Introduction: Heart failure (HF) patients who recover left ventricular function (HF-Recovered) have reported to have a different prognosis compared to HF with reduced or preserved ejection fraction (EF). However, no study has analyzed the dosage of neurohormonal blockade in these patients. Hypothesis: Higher dose of neurohormonal blockade might be important for better outcomes in HF-Recovered patients. Methods: HF-Recovered patients were defined with left ventricular EF ≥40% at time of study entry and retrospectively checked EF &lt;40%. 256 patients were enrolled between Mars 2009 and September 2014. Results: Of the study population, 48.8% received &lt;50% of the target dose of angiotensin-converting enzymes inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs), whereas 51.2% received ≥50% of the target dose at time of EF ≥40%. 55.5% received &lt;50% of the target dose of β-blockers (BBs), whereas 44.5% received ≥50% of the target dose. 31.3% increased the dose of ACEIs/ARBs or BBs at time of EF ≥40% (uptitration group), and 68.8% maintained the doses (maintenance group). During an average of 29.8 months of follow-up, 35 patients (13.7%) were died. In multivariable Cox proportional hazard analysis, ≥50% of the target dose of BBs was associated with lower all-cause mortality (HR=0.38, 95% CI 0.16-0.88, p=0.024). This dose-survival relationship was not the case for ACEIs/ARBs. Figure shows survival curves according to the uptitration or dose of BBs at time of EF ≥40%. Dose of BBs at time of EF ≥40% was lower among uptitration group than maintenance group. However, last follow-up doses of BBs between two groups were the same. Moreover, higher dose of BBs at time of EF recovery was associated with higher last follow-up dose. Conclusions: The dose of BBs was associated with mortality in HF-Recovered patients. High dose of neurohormonal blockade, especially BBs may prevent future adverse events, even if EF was recovered to ≥40% suggesting the importance of dose-uptitrating effort.
NTCT-05EFFICACY AND SAFETY ASSESSMENT OF THE USE OF BEVACIZUMAB AND TEMOZOLOMIDE PLUS RADIOTHERAPY IN PATIENTS WITH RECENTLY DIAGNOSED GLIOBLASTOMA, A SINGLE INSTITUTION EXPERIENCE
Authors: Karina Murillo-Medina, Amancio Guerrero-Maldonado, Victor Garcia-Navarro, Alejandro Juarez-Ramiro, Aura Argentina Erazo-Valle-solis, Guadalupe Cervantes-Sanchez
Journal: Neuro-Oncology (2015)

In the present study, we report on the safety and efficacy of bevacizumab and temozolomide plus radiotherapy for recently diagnosed GBM patients after surgical resection (either partial or near total). METHODS: Five consecutive patients diagnosed with GBM who presented to our institution after primary surgical resection, underwent a first line of therapeutics protocol, a combination of bevacizumab (10 mgs/kg) and temozolamide (75mgs/ m2) for 6 weeks, until progression, toxicity or death. Assessments were performed every two weeks and the primary end points were therapeutic safety and efficacy, tolerance as evaluated by clinico-radiological response as well the Common Terminology Criteria Adverse Events (CTCAE v5.0) and WHO Performance Status. RESULTS: From the five patients included on the study 3 women and 2 men, median age 55, 2 patients present grade I proteinuria, 2 patients present with hypertension grade I and II the last one requiring treatment and follow up by cardiology None of them required discontinuation of the treatment, all of them showed remission during the follow up. CONCLUSIONS: The results of the current study shows that bevacizumab and temozolamide plus radiotherapy as a front line therapy is safe and effective in treating patients with recently diagnosed GBM.
Neurological Complications of Infective Endocarditis
Journal: BMJ (1970)

Nasal Cancer in the Shoe Industry SIR,-In our article on "Nasal Cancer in the Northamptonshire Boot and Shoe Industry" (14 February, p. 385) we were unable to give estimates of incidence within the industry because we lacked comprehensive information on the numbers of men employed in the different departments.We have since received from the British Foot- wear Manufacturers' Federation national figures relating to 1949-61 inclusive giving the numbers of operatives in each sex employed in the various departments.The figures include the numbers of men and women employed in clicking, closing, pressing, lasting, finishing, and shoe room departments.In making the calculations in the Table the figures for 1949-61 have been averaged and the proportions applied to the Northamptonshire industry.If the cases of Adenocarcinoma Other Carcinomas All Carcinomas
U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes
Authors: Zhilei Shan, Sijing Chen, Taoping Sun, Cheng Luo, Yanjun Guo, Xuefeng Yu, Wei Yang, Frank B. Hu, Liegang Liu
Journal: Environmental Health Perspectives (2016)

Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare.