tbuckley/cabot-search huggingface dataset:
Lung cancer * 8: Management of malignant mesothelioma
Authors: C Parker
Journal: Thorax (2003)

<h3>Background</h3> Promising therapeutic approaches have emerged in chronic periaortitis, whereas peripheral blood biomarkers are lacking. CCL18 is known as a marker of fibrotic activity and prognosis in pulmonary fibrosis<sup>1</sup>. <h3>Objectives</h3> In this study we investigated whether CCL18 levels are increased in patients with chronic periaortitis and associated with clinical, laboratory, and imaging findings. <h3>Methods</h3> In this retrospective study, serum concentrations of CCL18 were assessed in 30 patients with chronic periaortitis and related to clinical data, laboratory parameters and imaging studies. Serum levels were compared to 15 apparently healthy volunteers and 15 controls with aortic sclerosis. <h3>Results</h3> CCL18 serum concentrations were increased in patients with chronic periaortitis (197.6 (262.2; 163.8) ng/ml) compared to healthy volunteers (34.6 (53.6; 27.7) ng/ml; p&lt;0.0001) and controls with aortic sclerosis (50.4 (24.5-141.2) ng/ml; p&lt;0.0001). CCL18 levels correlated (n=30; r=0.461; p=0.01) and increased with the transversal diameter of the periaortic mantle &lt;5, 5-10 and ≥10 mm (p=0.008). Contrast enhancement (p=0.044), treatment naivety (p=0.042), and the occurrence of systemic symptoms (p=0.007) were associated with higher CCL18 levels. During follow-up changes of CCL18 correlated with changes of the transverse diameter of the periaortic mantle (n=17; r=0.512; p=0.033) <h3>Conclusions</h3> CCL18 serum concentration reflects fibro-inflammatory activity and disease extent in patients with chronic periaortitis. <h3>References</h3> Prasse A, Probst C, Bargagli E, Zissel G, Toews GB, Flaherty KR, et al. Serum CCchemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2009;179:717-723. <h3>Disclosure of Interest</h3> None Declared
Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers
Authors: C. Neurohr, A-G. Lenz, I. Ding, H. Leuchte, T. Kolbe, J. Behr
Journal: European Respiratory Journal (2003)

The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as gamma-glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit. To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra- and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed. GSHt was increased in ELF from smokers (1,090.1 +/- 163.0 microM versus 559.2 +/- 48.2 microM). GSHt content of BAL cells (nmol x mg protein(-1)) was decreased in smokers without differences reaching statistical significance (8.0 +/- 1.4 versus 12.4 +/- 2.6). GCLM expression was also reduced in smokers (0.6 +/- 0.1 versus 2.8 +/- 0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid. The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamate-cysteine ligase subunit rather than the catalytic subunit.
Enhanced Nitric Oxide-Mediated Vascular Relaxation in Radial Artery Compared With Internal Mammary Artery or Saphenous Vein
Authors: O. M. Shapira, A. Xu, G. S. Aldea, J. A. Vita, R. J. Shemin, J. F. Keaney
Journal: Circulation (1999)

The superior long-term patency of internal mammary artery coronary bypass grafts compared with venous grafts has been attributed in part to increased endothelium-derived nitric oxide (. NO) production. Interest in the radial artery as an alternative bypass conduit has recently been revived; however, its biological characteristics remain incompletely defined. The purpose of this study was to compare the.NO-mediated vasomotor properties of the radial artery to those of the internal mammary artery and saphenous vein.Matched segments of radial artery, internal mammary artery, and saphenous vein (n=24 patients) were examined by use of organ-chamber methodology. Endothelium-dependent and -independent vasomotor responses were assessed by dose-response curves to acetylcholine, N(G)-nitro-L-arginine methyl ester (L-NAME), 8-bromo-cyclic 3',5'-guanosine monophosphate (8-bromo-cGMP), and nitroglycerin. Maximum.NO-mediated radial artery relaxation in response to acetylcholine (86+/-10%) was significantly greater than internal mammary artery (56+/-9%) or saphenous vein (11+/-5%, both P<0.0001). Similarly, acetylcholine-stimulated cGMP accumulation in radial artery (9.1+/-1.7 pmol/mg protein) was also greater than internal mammary artery (6.2+/-0.3 pmol/mg protein) or saphenous vein (1.4+/-0.2 pmol/mg protein, both P<0.05). Estimated basal endothelial.NO production, assayed as the percent maximum contraction in response to L-NAME, was greater in radial artery (39+/-5%) than internal mammary artery (23+/-6%) or saphenous vein (5+/-2%, both P<0.05). Maximum relaxation of all vessels to nitroglycerin was similar, although the sensitivity of radial artery to nitroglycerin was greater (EC(50)=33+/-7 nmol/L) than the internal mammary artery (203+/-32 nmol/L) or saphenous vein (97+/-12 nmol/L, both P<0.05). Vascular cGMP in response to 0.1 micromol/L nitroglycerin was significantly higher in the radial artery (8.3+/-1. 4 pmol/mg protein) compared with the internal mammary artery (3. 5+/-1.3 pmol/mg protein) or saphenous vein (1.4+/-0.3 pmol/mg protein, both P<0.0001). Relaxation to 8-bromo-cGMP was identical for all 3 conduits.These data indicate that. NO-dependent relaxation of radial artery is greater than that of internal mammary artery or saphenous vein. This difference is related to endothelial production of.NO and/or vessel sensitivity to. NO. Such favorable physiological characteristics of radial artery could conceivably contribute to improved long-term patency of this conduit compared with saphenous vein.
Bad medicine: atrial fibrillation
Authors: Des Spence
Journal: BMJ (2013)

General practitioners are the canaries of epidemiology, monitoring large cohorts of patients over many decades and observing changes in illness trends long before research does. Consider atrial fibrillation (AF), with a reported lifetime risk of 25% for men and 17% for women, the Framingham study found.1 And this is an underestimate for paroxysmal AF, which apparently carries the same risk of stroke but is often missed.⇑

The annual risk of stroke in people with AF is 3-4%.2 As AF is so prevalent, it follows that a large proportion of the population will have a stroke. …
Impact of drug injection using on TB-AIDS treatment outcomes
Authors: Evelina Lesnic, Vasile Zlepca
Journal: European Respiratory Journal (2013)

Drug injection users (DIUs) are the most vulnerable group for TB/HIV co-infection. Estimated 5.2% TB cases were HIVpositive (2010). No data available about the prevalence of TB at DIUs. Aim Assessment of drug injection using impact on TB-AIDS treatment outcomes. Design: Case-control study was performed, including study group (SG)-38 DIUs with pulmonaryTB-AIDS and control group (CG)-49 never-DIUs with TB-AIDS. Results Men 57%vs37%(p
The Evolution of Seminal Ribonuclease: Pseudogene Reactivation or Multiple Gene Inactivation Events?
Authors: Slim O. Sassi, Edward L. Braun, Steven A. Benner
Journal: Molecular Biology and Evolution (2007)

Two approaches, one novel, are applied to analyze the divergent evolution of ruminant seminal ribonucleases (RNases), paralogs of the well-known pancreatic RNases of mammals. Here, the goal was to identify periods of divergence of seminal RNase under functional constraints, periods of divergence as a pseudogene, and periods of divergence driven by positive selection pressures. The classical approach involves the analysis of nonsynonymous to synonymous replacements ratios (ω) for the branches of the seminal RNase evolutionary tree. The novel approach coupled these analyses with the mapping of substitutions on the folded structure of the protein. These analyses suggest that seminal RNase diverged during much of its history after divergence from pancreatic RNase as a functioning protein, followed by homoplastic inactivations to create pseudogenes in multiple ruminant lineages. Further, they are consistent with adaptive evolution only in the most recent episode leading to the gene in modern oxen. These conclusions contrast sharply with the view, cited widely in the literature, that seminal RNase decayed after its formation by gene duplication into an inactive pseudogene, whose lesions were repaired in a reactivation event. Further, the 2 approaches, ω estimation and mapping of replacements on the protein structure, were compared by examining their utility for establishing the functional status of the seminal RNase genes in 2 deer species. Hog and roe deer share common lesions, which strongly suggests that the gene was inactive in their last common ancestor. In this specific example, the crystallographic approach made the correct implication more strongly than the ω approach. Studies of this type should contribute to an integrated framework of tools to assign functional and nonfunctional episodes to recently created gene duplicates and to understand more broadly how gene duplication leads to the emergence of proteins with novel functions.
Cisplatin-induced epigenetic activation of miR-34a sensitizes bladder cancer cells to chemotherapy
Authors: Heng Li, Gan Yu, Runlin Shi, Bin Lang, Xianguo Chen, Ding Xia, Haibing Xiao, Xiaolin Guo, Wei Guan, Zhangqun Ye, Wei Xiao, Hua Xu
Journal: Molecular Cancer (2014)

Abstract Background Accumulating evidence suggests a tumor suppressive role for miR-34a in human carcinogenesis. However, its precise biological role remains largely elusive. This study aimed to reveal the association of the miR-34a expression and its modulation of sensitivity to cisplatin in muscle-invasive bladder cancer (MIBC). Methods miR-34a expression in MIBC cell lines and patient tissues was investigated using qPCR. The methylation analysis of miR-34a promoter region was performed by MassARRAY. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vector were used to regulate miR-34a expression in MIBC cells to investigate its function in vitro and in vivo . Results miR-34a expression was frequently decreased in MIBC tissues and cell lines through promoter hypermethylation while it was epigenetically increased in MIBC cells following cisplatin treatment. Increased miR-34a expression significantly sensitized MIBC cells to cisplatin and inhibited the tumorigenicity and proliferation of cancer cells in vitro and in vivo. Furthermore, we identified CD44 as being targeted by miR-34a in MIBC cells following cisplatin treatment, and increased CD44 expression could efficiently reverse the effect of miR-34a on MIBC cell proliferation, colongenic potential and chemosensitivity. Conclusions Cisplatin-based chemotherapy induced demethylation of miR-34a promoter and increased miR-34a expression, which in turn sensitized MIBC cells to cisplatin and decreased the tumorigenicity and proliferation of cancer cells that by reducing the production of CD44.
Prognostic factors for patients with advanced stage serous borderline tumours of the ovary
Authors: P. Morice, S. Camatte, A. Rey, D. Atallah, C. Lhommé, P. Pautier, C. Pomel, J.-F. Coté, C. Haie-Meder, P. Duvillard, D. Castaigne
Journal: Annals of Oncology (2003)
Sulfasalazine Suppresses Drug Resistance and Invasiveness of Lung Adenocarcinoma Cells Expressing AXL
Authors: Jong-Ding Lay, Chih-Chen Hong, Jhy-Shrian Huang, Ya-Yu Yang, Chung-Yi Pao, Ching-Hang Liu, Yi-Pin Lai, Gi-Ming Lai, Ann-Lii Cheng, Ih-Jen Su, Shuang-En Chuang
Journal: Cancer Research (2007)

Abstract Metastasis and drug resistance are the major causes of mortality in patients with non–small cell lung cancer (NSCLC). Several receptor tyrosine kinases (RTKs), including AXL, are involved in the progression of NSCLC. The AXL/MER/SKY subfamily is involved in cell adhesion, motility, angiogenesis, and signal transduction and may play a significant role in the invasiveness of cancer cells. Notably, no specific inhibitors of AXL have been described. A series of CL1 sublines with progressive invasiveness established from a patient with NSCLC has been identified that positively correlates with AXL expression and resistance to chemotherapeutic drugs. The ectopic overexpression of AXL results in elevated cell invasiveness and drug resistance. Nuclear factor-κB (NF-κB) signaling activity is associated with AXL expression and may play an important role in the enhancement of invasiveness and doxorubicin resistance, as shown by using the NF-κB inhibitor, sulfasalazine, and IκB dominant-negative transfectants. In the current study, sulfasalazine exerted a synergistic anticancer effect with doxorubicin and suppressed cancer cell invasiveness in parallel in CL1 sublines and various AXL-expressing cancer cell lines. Phosphorylation of AXL and other RTKs (ErbB2 and epidermal growth factor receptor) was abolished by sulfasalazine within 15 min, suggesting that the inhibition of NF-κB and the kinase activity of RTKs are involved in the pharmacologic effects of sulfasalazine. Our study suggests that AXL is involved in NSCLC metastasis and drug resistance and may therefore provide a molecular basis for RTK-targeted therapy using sulfasalazine to enhance the efficacy of chemotherapy in NSCLC. [Cancer Res 2007;67(8):3878–87]
Selective downregulation of rat cardiac beta1-adrenoceptors by cyclosporine a: Prevention by diltiazem or angiotensin-converting enzyme inhibitors
Authors: Otto-Erich Brodde, Melanie Adamczyk, Frauke Busch, Claus Bossaller, Ellen Duske, Eckart Fleck, Stephan Götze, Wolfgang Auch-Schwelk
Journal: Journal of the American College of Cardiology (1995)
Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress
Authors: Lan-Feng Dong, Emma Swettenham, Johanna Eliasson, Xiu-Fang Wang, Mikhal Gold, Yasmine Medunic, Marina Stantic, Pauline Low, Lubomir Prochazka, Paul K. Witting, Jaroslav Turanek, Emmanuel T. Akporiaye, Stephen J. Ralph, Jiri Neuzil
Journal: Cancer Research (2007)

Abstract “Mitocans” from the vitamin E group of selective anticancer drugs, α-tocopheryl succinate (α-TOS) and its ether analogue α-TEA, triggered apoptosis in proliferating but not arrested endothelial cells. Angiogenic endothelial cells exposed to the vitamin E analogues, unlike their arrested counterparts, readily accumulated reactive oxygen species (ROS) by interfering with the mitochondrial redox chain and activating the intrinsic apoptotic pathway. The vitamin E analogues inhibited angiogenesis in vitro as assessed using the “wound-healing” and “tube-forming” models. Endothelial cells deficient in mitochondrial DNA (mtDNA) were resistant to the vitamin E analogues, both in ROS accumulation and apoptosis induction, maintaining their angiogenic potential. α-TOS inhibited angiogenesis in a mouse cancer model, as documented by ultrasound imaging. We conclude that vitamin E analogues selectively kill angiogenic endothelial cells, suppressing tumor growth, which has intriguing clinical implications. [Cancer Res 2007;67(24):11906–13]
Migration and Function of Antigen-Primed Nonpolarized T Lymphocytes in Vivo
Authors: Giandomenica Iezzi, Doris Scheidegger, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (2001)

Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as the capacity to migrate to inflamed tissues. However, the antigen-primed T cells that receive a short T cell receptor (TCR) stimulation do not acquire effector function and remain in a nonpolarized state. Using TCR transgenic CD4+ T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes. In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes, nonpolarized T cells proliferated and acquired effector function in response to antigenic stimulation, displaying lower activation threshold and faster kinetics compared with naive T cells. These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.
Increased 2-Hydroxylation of Estradiol as a Possible Mechanism for the Anti-Estrogenic Effect of Cigarette Smoking
Authors: Jon J. Michnovicz, Richard J. Hershcopf, Hiroshi Naganuma, H. Leon Bradlow, Jack Fishman
Journal: New England Journal of Medicine (1986)

Epidemiologic data indicate that cigarette smoking is associated with an important anti-estrogenic effect, and increased hepatic metabolism has been suggested as a possible mechanism. We examined the hypothesis that cigarette smoking in women induces an increase in estradiol 2-hydroxylation. This irreversible metabolic pathway yields 2-hydroxyestrogens, which possess minimal peripheral estrogenic activity and are cleared rapidly from the circulation. We found a significant increase in estradiol 2-hydroxylation in premenopausal women who smoked at least 15 cigarettes per day. The extent of the reaction (mean ±SEM) was 53.6±2.2 percent among 14 smokers and 35.1±1.8 percent among 13 nonsmoking controls — an increase of approximately 50 percent (P<0.001). The extent of 2-hydroxylation among five smokers did not vary during the follicular and luteal phases of their menstrual cycles. In addition, urinary excretion of estriol relative to estrone was significantly decreased among smokers (P<0.01), providing evidence that the smoking-induced increase in 2-hydroxylation diminishes the competing metabolic pathway involving 16α-hydroxylation. This study demonstrates that smoking exerts a powerful inducing effect on the 2-hydroxylation pathway of estradiol metabolism, which is likely to lead to decreased bio-availability at estrogen target tissues. Elucidation of the mechanism responsible for smoking-induced changes in 2-hydroxylation may be useful in the development of strategies to reduce the risk of hormone-dependent tumors. (N Engl J Med 1986; 315:1305–9.)
Significant improvement in survival of patients presenting with metastatic colon cancer in the south of The Netherlands from 1990 to 2004
Authors: H.J. Meulenbeld, L.N. van Steenbergen, M.L.G. Janssen-Heijnen, V.E.P.P. Lemmens, G.J. Creemers
Journal: Annals of Oncology (2008)
Clinical features and results of management of superior vena cava syndrome secondary to lymphoma.
Authors: R Perez-Soler, P McLaughlin, W S Velasquez, F B Hagemeister, J Zornoza, J T Manning, L M Fuller, F Cabanillas
Journal: Journal of Clinical Oncology (1984)

Thirty-six of 915 patients with non-Hodgkin's lymphoma presented with superior vena cava syndrome (SVCS). The histologic types associated with SVCS were diffuse large cell in 23 patients, lymphoblastic in 12, and follicular large cell in one patient. Radiotherapy alone appeared equal to chemotherapy alone or in combination with radiotherapy in achieving relief of SVCS symptoms. Chemotherapy alone or in combination with radiotherapy was superior to radiotherapy alone in prolonging relapse-free survival and overall survival. No differences in relapse-free survival and survival were found between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy, but the addition of radiotherapy appeared to prevent local relapses in the group with large-cell lymphoma. The presence of symptoms of involvement of other mediastinal structures such as dysphagia, hoarseness, or stridor (DHS), a higher grade of intensity, and a shorter duration of symptoms (less than or equal to 2 weeks) appeared to adversely influence relapse-free survival and survival. The following conclusions were made: (1) a histologic diagnosis before the onset of treatment is desirable and feasible in patients presenting with SVCS except in those with severe respiratory distress, (2) both chemotherapy and radiotherapy are equally effective in alleviating the symptoms of SVCS, and (3) combined modality treatment with chemotherapy and radiotherapy results in a lower frequency of local relapses compared to chemotherapy alone but survival was similar in both groups.
Degree of Damage to the Small Bowel and Serum Antibody Titers Correlate With Clinical Presentation of Patients With Celiac Disease
Authors: Juha Taavela, Kalle Kurppa, Pekka Collin, Marja–Leena Lähdeaho, Teea Salmi, Päivi Saavalainen, Katri Haimila, Heini Huhtala, Kaija Laurila, Harri Sievänen, Markku Mäki, Katri Kaukinen
Journal: Clinical Gastroenterology and Hepatology (2012)
An Attempt to Demonstrate Arterial Pressure-Volume Relationships in the Intact Dog by an Ultra-Rapid Bleeding Technic
Authors: DAVID F. OPDYKE, MARY E. ZANETTI, GORDOX B. THOMAS
Journal: Circulation Research (1955)

The response of arterial pressure to very rapid central venous bleeding has been utilized in an attempt to establish an arterial pressure-volume relation in the intact dog. When dogs were bled for a brief period at rates between 200 and 500 cc. per minute the arterial pressure declined as a rectilinear function of the bleeding volume. The compensatory mechanisms of cardiac acceleration and vasoconstriction do not influence this relationship. Abolition of the vasomotor pathways does, however, increase the slope of the blood pressure decline curve. This is explained on the basis of a decrease in the initial volume of the arterial reservoir.
Rescue of early-stage myelodysplastic syndrome-deriving erythroid precursors by the ectopic expression of a dominant-negative form of FADD
Authors: Yann-Erick Claessens, Sophie Park, Anne Dubart-Kupperschmitt, Virginie Mariot, Carmen Garrido, Stany Chrétien, François Dreyfus, Catherine Lacombe, Patrick Mayeux, Michaëla Fontenay
Journal: Blood (2005)