tbuckley/cabot-search huggingface dataset:
Infiltration of M2‐polarized macrophages in infected lymphatic malformations: possible role in disease progression
Authors: W. Zhang, K.‐F. He, J.‐G. Yang, J.‐G. Ren, Y.‐F. Sun, J.‐H. Zhao, Y.‐F. Zhao
Journal: British Journal of Dermatology (2016)

Lymphatic malformations (LMs), slow-flow vascular anomalies resulting from abnormal development of lymphatic channels, often progress rapidly after trauma or infection.To explore the possible mechanism by which local infection promotes the progression of LMs.Immunohistochemistry in serial sections and immunofluorescence were performed to label polarized macrophages. Tertiary lymphoid organs (TLOs) in LMs were identified using antibodies against CD3 (a T-cell marker), CD20 (a B-cell marker) and PNAd (a high endothelial venule marker). Pearson's correlation and cluster analysis were carried out to delineate the relationship between macrophage infiltration and TLO formation. Rat models of LM were established to examine the role of lipopolysaccharide in LM development.Compared with normal skin tissues, both M1- and M2-polarized macrophages were prevalent in LMs. Moreover, M2-polarized macrophages were significantly increased in infected LMs with an elevated density of TLOs. M2-polarized macrophages were observed in the centre of TLOs accompanied by intensive staining of macrophage colony-stimulating factor, a strong chemotactic factor for monocytes/macrophages, suggesting that macrophages might be recruited through TLOs. Cluster analysis and Pearson's correlation suggested a close relationship between macrophage infiltration and TLO formation. Furthermore, the expression of CD68 was also correlated with that of vascular endothelial growth factor (VEGF)-C and Ki67. Importantly, in an established LM rat model, lipopolysaccharide promoted the progression of the malformations with increased macrophage infiltration and TLO formation.M2-polarized macrophages that may be recruited through TLOs in infected LMs may contribute to the progression of the disease by secreting VEGF-C, and therefore accelerating the proliferation of lymphatic endothelial cells.
The plastic cellular states of liver cells: Are EpCAM and Lgr5 fit for purpose?
Authors: Meritxell Huch, Laurent Dollé
Journal: Hepatology (2016)

Adult liver cells have been considered restricted regarding their fate and lineage potential. That is, hepatocytes have been thought able only to generate hepatocytes and duct cells, only duct cells. While this may be the case for the majority of scenarios in a state of quiescence or homeostasis, evidence suggests that liver cells are capable of interconverting between cellular states of distinct phenotypic traits. This interconversion or plasticity had been suggested by classical studies using cellular markers, but recently lineage tracing approaches have proven that cells are highly plastic and retain an extraordinary ability to respond differently to normal tissue homeostasis, to tissue repair, or when challenged to expand ex vivo or to differentiate upon transplantation. Stemness, as “self‐renewal and multipotency,” seems not to be limited to a particular cell type but rather to a cellular state in which cells exhibit a high degree of plasticity and can move back and forth in different phenotypic states. For instance, upon damage cells can dedifferentiate to acquire stem cell potential that allows them to self‐renew, repopulate a damaged tissue, and then undergo differentiation. In this review, we will discuss the evidence on cellular plasticity in the liver, focusing our attention on two markers, epithelial cell adhesion molecule and leucine‐rich repeat‐containing G protein‐coupled receptor 5, which identify cells with stem cell potential. (H epatology 2016;64:652‐662)
Pathogenesis of Experimental Feline Leukemia Virus Infection2
Authors: Jennifer L. Rojko, Edward A. Hoover, Lawrence E. Mathes, Richard G. Olsen, Joseph P. Schaller
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Pathogenesis of Experimental Feline Leukemia Virus Infection Get access Jennifer L. Rojko, Jennifer L. Rojko 3Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward A. Hoover, Edward A. Hoover 3Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence E. Mathes, Lawrence E. Mathes 3Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard G. Olsen, Richard G. Olsen 3Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210.4The Ohio State University Comprehensive Cancer Center, 357 McCampbell Hall, 1580 Cannon Drive, Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph P. Schaller Joseph P. Schaller 3Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210. 5We acknowledge the excellent assistance provided by Mr. Kenneth Milliser, Ms. Pamela Wilson, Mr. Patrick Adams, and Ms. Nancy Mesoloras. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 759–768, https://doi.org/10.1093/jnci/63.3.759 Published: 01 September 1979 Article history Received: 27 October 1978 Accepted: 11 March 1979 Published: 01 September 1979
Pemetrexed alone or in combination with cisplatin in the treatment of patients with peritoneal mesothelioma (PM): Outcomes of an expanded access program (EAP) in patients with malignant mesothelioma (MM)
Authors: J. Bloss, A. Wozniak, P. Janne, C. Belani, M. Keohan, H. Ross, J. Polikoff, D. Mintzer, L. Bloss, C. Obasaju
Journal: Journal of Clinical Oncology (2004)

7198 Background: The improved efficacy of pemetrexed (ALIMTA, Eli Lilly and Co) in combination with cisplatin versus cisplatin alone, in a phase 3 trial of patients with malignant pleural mesothelioma, has led to a demand for patient access to pemetrexed prior to regulatory approval. An Eli Lilly and Co EAP was opened to allow access to all eligible patients with MM. This non-randomized study was designed to gather additional efficacy and safety data on pemetrexed alone and in combination with cisplatin. The experience of those patients with PM is reported here. Methods: From 6/12/2002 to the present, > 650 patients with mesothelioma were enrolled at 462 sites in the US. Of these patients, 43 (6.65%) had PM. Patients received pemetrexed 500mg/m2 alone or in combination with cisplatin 75mg/m2, both of which were administered once every 21 days for a maximum of 6 cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results: Demographic information is currently available for 43 patients (26 M, 17 F). Median age was 61.1 (range: 25 - 81) years. To date, 14 patients have been evaluated with a current objective response rate of 21.5%: 1 CR (7.2%), 2 PRs (14.3%), 4 SDs (28.5%), and 7 PDs (50%). Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database. This database included all patients from the EAP with either pleural or peritoneal mesothelioma. SAEs, irrespective of causality, were reported by number of events: nausea (44), vomiting (41), diarrhea (21), renal insufficiency (21), asthenia (13), atrial fibrillation (13), cellulitis (9), constipation (8), dysphagia (4), rash (2), neuropathy (2), stomatitis (2), anemia (12), thrombocytopenia (7), neutropenia (7), and neutropenic fever (4). Conclusions: Pemetrexed with or without cisplatin has a favorable safety profile and the clinical benefit rate of 50% indicates activity in this subset of patients with peritoneal mesothelioma. This trial will conclude early in 2004, and all response and safety data will be forthcoming. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.
Systematic review of research trends in cancer cachexia: Insights from the literature and funding agencies
Authors: F. S. Braiteh, G. Pratt, R. Kurzrock, E. Bruera
Journal: Journal of Clinical Oncology (2009)

e17540 Background: Cancer cachexia affects about 250,000 patients in the US worsening treatment outcome and quality of life. To evaluate the scholar contribution to cancer cachexia, we analyzed the cachexia literature and funding support. Methods: In May 2008, we conducted a search of the major databases Medline, Web of Sciences, and Scopus of all publications with MeSH heading “cachexia” or keywords “cachexia, cachectic, cachexic” since 1982, distinguishing “original research” from “review” articles. To examine the trend over time, we compared the publication rate in the field of cachexia to that of published manuscripts in reference fields (cancer, AIDS, Alzheimer's disease, and CHF). To study the federal funding for cachexia research, we examined the Computer Retrieval of Information on Scientific Projects database. Only descriptive statistical analysis was adopted because of the heterogeneity of methods. Results: We identified 1990 published manuscripts, 677 (34%) of which are “reviews”. Out of the 2,890 country of origin affiliations, the US is the lead contributor (N = 1,105; 38%). In the last 5 years, the ratio of “review” articles in cachexia increased significantly (49%), compared to cancer (17%), and science publications (8%). Unlike the of publications in reference fields, the increase in cachexia has been mostly due to the dominance of “review” articles (ratio of original/review of 0.928 in cachexia, versus 0.417 in CHF, 0.337 in Alzheimer and 0.206 in AIDS). Nevertheless, published cachexia articles in journals with high impact factors (IF ≥ 4.0) remains similar (8.49%) to that of science research (8.63%) with a predominance of “review’ articles. Only one in four published manuscripts (24%) acknowledged federal support. Cachexia research support by US federal agencies declined significantly in the last decade (with a peak of 161 awards in 1999 down to 40 in 2006), the NCI remains the leading funding agency (17%). Only 275 out of the total of 121,997 NCI- awards over 25 years (0.22%) were awarded to cachexia research, with a clear decline in the latest decade by 50% (0.14% vs. 0.29%). Conclusions: Advances in the field of original cancer cachexia research have been very limited, perhaps related to the lack of federal research funding support, which is on the decline. No significant financial relationships to disclose.
Serum Parathyroid Hormone Levels in the Hypercalcaemia of Urological Malignant Disease
Authors: J W A Ramsay, W F Hendry
Journal: Journal of the Royal Society of Medicine (1986)

Serum parathyroid hormone (PTH) levels have been measured in 8 patients with hypercalcaemia associated with urological malignancy: 3 renal cell carcinomas, 2 adenocarcinomas of prostate, 2 transitional cell carcinomas of bladder and one transitional cell carcinoma of kidney. Five (63%) of these 8 patients had bone metastases. PTH was detectable in the serum of all 8 hypercalcaemic patients, but in only 2 cases was the PTH level above the normal range, and in one of these a coincidental parathyroid adenoma was found to be responsible for the hypercalcaemia. It appears that these tumours can produce a hormone-like substance with biological effects similar to PTH.
Controlling nausea in patients receiving chemotherapy: Can nausea be used as a reliable primary endpoint in randomized clinical trials?
Authors: K. Cheng, R. J. Gralla
Journal: Journal of Clinical Oncology (2008)

20528 Background: Marked progress has been made in controlling chemotherapy-related emesis (E) and nausea (N), with control rates of acute emesis exceeding 80% even in highly emetic settings. Emesis control exceeds that of nausea, and that patients generally express greater impact from nausea than from emesis (Warr, JCO 2005). Trials have shown that physicians and nurses underestimate N rates experienced by patients, especially in delayed settings (Grunberg, Cancer 2004). This poorer N control has led to the suggestion that N be considered as the primary endpoint for future trials, rather than E or aggregate endpoints. While improved control of N is a desired goal, can this subjective symptom be reliably measured in large randomized clinical trials [RCTs] using visual analog scales (VAS)? Methods: To approach this question, we analyzed similar large double-blind RCTs testing antiemetic regimens in previously untreated patients receiving highly emetic chemotherapy (cisplatin) or moderately (mod) emetic regimens (cyclophosphamide, anthracyclines, carboplatin [CTX, Anth, CRB]) and compared the reproducibility of N control rates with the control of E (considered the most accurate endpoint). 4 RCTs with cisplatin included 489 to 1054 patients each; the 2 studies with moderate agents included 866 and 1085 patients. All trials shared a control arm of ondansetron IV plus dexamethasone; the findings from these arms are analyzed in the table. Results: Analysis was complicated by differing evaluation criteria in several trials. Results in the table below use as comparable methodology as possible. Conclusions: Using validated assessment tools (VAS), the range of nausea scores in these large RCTs was similar among the trials in highly emetic settings, and in moderate risk trials; this range compared favorably with that reported for emesis. We conclude that if established methods are followed, trials designed with nausea as the primary endpoint can expect accurate and reproducible results. Ranges of Emesis and Nausea Control Highly Emetic Risk (Patients=2642/RCTs=4) Acute E Delayed E Acute N Delayed N Control rate-Range 69% - 81% 48% - 64% 62%-69%* 40%-48%* 87%-90%** 65%-72%** Mod Emetic Risk (Patients=1951/RCTs=2) Acute E Acute & Delayed E Acute N Acute & Delayed N Control rate- Range 60% - 77% 45% - 59% —– 33% - 45%* * Nausea= none or <5mm on VAS; ** Nausea= no significant nausea or < 25mm on VAS No significant financial relationships to disclose.
Autophagy is involved in survival of hepatocellular carcinoma by downregulating Bnip3
Authors: Chang Wook Park, Eung-Sam Kim, Kwan Yong Choi
Journal: Clinical Cancer Research (2007)

C33   Autophagy is an evolutionarily conserved homeostatic process that removes cellular proteins and cytoplasmic organelles in response to stress or starvation. Recently, there have been several reports that autophagy has an important role in cancer. That is why series of therapeutic trial are focused on autophagy. But, there are conflicting results from those trials, because it is still unclear whether autophagy inhibits tumorigenesis or rescues cancer cells under stress conditions. Here, we show that Bnip3, essential molecul for hypoxia-induced autophagy, is overexpressed in liver cancer cells from a patient. Interestingly, Bnip3 is downregulated by autophagy under conditions of nutrient deprivation and upregulated by Vinblastine, an anti-mitotic drug used to treat certain kinds of cancer. Our results suggest that autophagy has a protective role in a certain type of liver cancer and the protection process can be mediated by removing the pro-death molecule, Bnip3. To our knowledge, it is the first report that autophagy contributes to survival of cancer cells by sequestering another autophagic signaling molecule.
Abstract 11215: Exercise Influences Penetrance and Outcomes in Family Members of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients Carrying a Pathogenic Desmosomal Mutation
Authors: Abhishek C Sawant, Brittney Murray, Crystal Tichnell, Aditya Bhonsale, Anneline S te Riele, Harikrishna Tandri, Ryan J Tedford, Daniel P Judge, Hugh Calkins, Cynthia A James
Journal: Circulation (2014)

Background: Endurance exercise is associated with adverse arrhythmic outcomes and development of heart failure in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated desmosomal mutation carriers. However studies comparing exercise participation in family members with desmosomal mutations are lacking. Methods: Structured exercise interviews were performed focusing on duration, intensity and timing among ten families with 37 patients (9 probands, 28 family members) carrying a pathogenic plakophilin ( PKP2 ) mutation. Exercise was classified based on 36 th Bethesda Conference into endurance/dynamic sports and static sports. Baseline characteristics, non-invasive and invasive clinical data, family history data and occurrence of ventricular tachycardia/appropriate defibrillator intervention (VT/VF) were collected. Results: Exercise duration (hours/year) at last follow up was highest among probands. Family members meeting 2010 Task Force Criteria [TFC] had significantly higher exercise duration (Figure 1-A), were more likely to be endurance athletes (77% vs. 33%, p=0.03), and had significantly higher participation in sports with high dynamic component (Median 416[IQR:123-864] vs. 214[IQR:48-408] hours/year; p=0.046) than family members not meeting TFC. Family members who were endurance athletes had worse arrhythmic course (Figure 1-B), were more likely to meet a major or minor 2010 TFC for depolarization/repolarization abnormalities (p=0.05), 2010 TFC for structural abnormalities (p=0.024) and had significantly lower right ventricular ejection fraction (48% vs. 57%; p=0.007). Conclusion: Mutation carrier family members of probands who are endurance athletes have increased penetrance, worse arrhythmic outcomes and greater structural changes compared with family members who are not endurance athletes and should be advised to restrict participation in exercise, especially with a high dynamic component.
Pulmonary gas exchange during mechanical non invasive ventilation in acute hypercapnic patients with obesity hypoventilation syndrome (OHS)
Authors: Virginia Serrano, J.E. Gavela, Pilar Gavari, B. Carton, F. Muñiz, E. G. Santalla, E. Bollo, F. Diez
Journal: European Respiratory Journal (2011)

Introduction: It is well known that non invasive ventilation in chronic respiratory diseases improves arterial blood gases by enhancing alveolar ventilation without relevant changes in ventilation-perfusion (VA/Q) relationships. ( O.Diaz et al., Am J Res Crit Care 1997;156:1-6). The adequate patient-ventilator synchronism throughout the breathing cycle should be a priority to ensure appropriate alveolar ventilation.

Hypothesis: We hypothesize that Pressure Support Ventilation (PSV) may be a useful modality of non invasive ventilation in hypercapnic patients with a restrictive ventilatory defect due to Obesity Hypoventilation Syndrome (OHS).

Aims: To this end, the effects of PSV versus VSV (volume support ventilation) on pulmonary gas exchange were analyzed in twenty hospitalized patients with hypercapnic respiratory failure due to OHS (BMI: 39±3 kg/m2). Blood Gases at the time of the study (FIO2 0.21): pH (7.34±0.05), PaO2 55±10 mmHg, PaCO2 62±5 mmHg, (A-a)O2 21±7mmHg.

Methods: Pulmonary gas exchange were measured at 30' in each of the conditions: a) baseline; b)PSV (BiPAP Vision System, Respironics) or VSV (BREAS, PV) in random order; keeping FIO2 and PEEP (4cm H2O) unchanged. The ventilatory settings were established according to patient's confortability.

Results: Compared with baseline, PSV increased PaO2 (64±10 mmHg, p<0.02) and decreased PaCO2 (50±8 mmHg, p<0.01) similar to VSV (PaO2 62±12 mmHg, ns, PaCO2 52±10 mmHg, p<0.01).

Conclusions:
MICL controls inflammation in rheumatoid arthritis
Authors: Pierre Redelinghuys, Lauren Whitehead, Andrea Augello, Rebecca A Drummond, Jean-Michel Levesque, Simon Vautier, Delyth M Reid, Bernhard Kerscher, Julie A Taylor, Peter A Nigrovic, John Wright, Graeme I Murray, Janet A Willment, Lynne J Hocking, Maria J G Fernandes, Cosimo De Bari, Iain B Mcinnes, Gordon D Brown
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C-type lectin receptor (CLR) expressed predominantly by myeloid cells. Previous studies have suggested that MICL is involved in controlling inflammation. <h3>Objective</h3> To determine the role of this CLR in inflammatory pathology using Clec12A<sup>−/−</sup> mice. <h3>Methods</h3> Clec12A<sup>−/−</sup> mice were generated commercially and primarily characterised using the collagen antibody-induced arthritis (CAIA) model. Mechanisms and progress of disease were characterised by clinical scoring, histology, flow cytometry, irradiation bone-marrow chimera generation, administration of blocking antibodies and in vivo imaging. Characterisation of MICL in patients with rheumatoid arthritis (RA) was determined by immunohistochemistry and single nucleotide polymorphism analysis. Anti-MICL antibodies were detected in patient serum by ELISA and dot-blot analysis. <h3>Results</h3> MICL-deficient animals did not present with pan-immune dysfunction, but exhibited markedly exacerbated inflammation during CAIA, owing to the inappropriate activation of myeloid cells. Polymorphisms of MICL were not associated with disease in patients with RA, but this CLR was the target of autoantibodies in a subset of patients with RA. In wild-type mice the administration of such antibodies recapitulated the Clec12A<sup>−/−</sup> phenotype. <h3>Conclusions</h3> MICL plays an essential role in regulating inflammation during arthritis and is an autoantigen in a subset of patients with RA. These data suggest an entirely new mechanism underlying RA pathogenesis, whereby the threshold of myeloid cell activation can be modulated by autoantibodies that bind to cell membrane-expressed inhibitory receptors.
P-237 K-RAS exon 2 mutations in advanced colorectal cancer: are they really so bad prognostic indicators? A phase II mono-institutional retrospective study
Authors: V. Dadduzio, M. Basso, S. Rossi, T. Cenci, E. Cerchiaro, S. Capodimonti, A. Strippoli, M. Larocca, P. Lombardi, M. Bensi, A. Cassano, M. Martini, C. Barone
Journal: Annals of Oncology (2015)
Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy
Authors: Rowida Almomani, Judith M.A. Verhagen, Johanna C. Herkert, Erwin Brosens, Karin Y. van Spaendonck-Zwarts, Angeliki Asimaki, Paul A. van der Zwaag, Ingrid M.E. Frohn-Mulder, Aida M. Bertoli-Avella, Ludolf G. Boven, Marjon A. van Slegtenhorst, Jasper J. van der Smagt, Wilfred F.J. van IJcken, Bert Timmer, Margriet van Stuijvenberg, Rob M. Verdijk, Jeffrey E. Saffitz, Frederik A. du Plessis, Michelle Michels, Robert M.W. Hofstra, Richard J. Sinke, J. Peter van Tintelen, Marja W. Wessels, Jan D.H. Jongbloed, Ingrid M.B.H. van de Laar
Journal: Journal of the American College of Cardiology (2016)
MA/My Strain of the Marsh Albino Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: William S. Murray
Journal: JNCI Journal of the National Cancer Institute (1963)

Data on 424 treated and 920 untreated females of the MA/My derivative of the Marsh albino mouse indicate that the MA/My strain is highly susceptible to the virus-like mammary tumor inciter or milk agent, yet apparently carries none of it, a characteristic acquired without experimental manipulation.