tbuckley/cabot-search huggingface dataset:
BAL protein profiles specific of different interstitial lung diseases
Authors: Elena Bargagli, Claudia Landi, David Bennett, Pasquale Di Sipio, Luca Bini, Paola Rottoli
Journal: European Respiratory Journal (2012)

Interstitial lung diseases (ILD) are an heterogeneous group of lung disorders with different etiopathogenesis, clinical courses and prognosis. In the last ten years our group of research is focusing on the proteomic analysis of BAL in different interstitial lung diseases.  Aims of this proteomic study were to compare protein profiles of Sarcoidosis (S), Idiopathic Pulmonary Fibrosis (IPF), Langerhans cell Histiocytosis (PLCH), pulmonary fibrosis associated with Systemic sclerosis (SSc) patients in order to identify proteins of interest involved in specific pathogenetic networks or potential biomarkers with clinical value.  Methods: Population of patients was composed by 9 S, 7 IPF, 9 PLCH, 7 SSc. Proteomic analysis was performed by 2D-electrophoresis. Image analysis was done by Image Master Platinum 7.0 software. Protein identification was performed by mass spectrometry.  Results: Image analysis revealed distinct expression profiles for each ILD. Among the proteins differently expressed in our ILD samples there were Complement C3, complement factor B, complement factor I, antithrombin III, angiotensinogen, vitamin D binding protein, Leucin-rich alpha-2-glycoprotein, 14-3-3 protein epsilon, calcyphosin, kininogen N-term, alpha-2-HS-glycoprotein.  Conclusion: The proteomic analysis of BAL confirmed the possibility to use 2D-electrophoresis to highlight different protein profiles among specific ILDs.
Interaction of Retinoic Acid and 3-Methylcholanthrene on the Fine Structure of Mouse Prostate Epithelium in Vitro
Authors: L Müller-Salamin, A Matter, I Lasnitzki
Journal: JNCI Journal of the National Cancer Institute (1979)

The effects of 3-methylcholanthrene (MCA) and retinoic acid (RA) on the fine structure of AKR mouse prostate epithelium in organ culture were correlated with changes in cell proliferation. In intact glands before explantation, the epithelial cytoplasm showed concentric flat or globular cisternae of endoplasmic reticulum in both supranuclear and basal areas, a well-developed Golgi complex, secretory vesicles, and numerous microvilli at the luminal surface. After explantation, the cytoplasmic organelles, particularly the endoplasmic reticulum, regressed and tonofilaments appeared. The regression was largely prevented by RA. MCA induced considerable epithelial hyperplasia and squamous metaplasia. The fine structure of the newly formed cells revealed a complete loss of endoplasmic reticulum, Golgi apparatus, secretory vesicles, and microvilli, with the appearance of bundles of tonofilaments and a striking increase in the number of desmosomes. Administration of RA to explants pretreated with the carcinogen partially reversed the hyperplasia and squamous metaplasia. The tonofilaments disappeared and the number of desmosomes greatly decreased, whereas endoplasmic reticulum, Golgi complex, secretory vesicles, and microvilli were largely reestablished. Planimetric measurements of the alveolar epithelium showed that the squamous transformation and its partial reversal by RA coincide with the rise and decline of epithelial hyperplasia. The data suggest that the restoration of secretory differentiation by RA was responsible for the initial breakdown of the hyperplastic epithelium, whereas the lowering of DNA synthesis by RA prevented further hyperplasia and kept cell replication within normal limits.
Enhanced binding of Aspergillus fumigatus spores to A549 epithelial cells and extracellular matrix proteins by a component from the spore surface and inhibition by rat lung lavage fluid
Authors: Z. Yang
Journal: Thorax (2000)

BACKGROUND Aspergillus fumigatus is a pathogenic fungus which causes a range of diseases, particularly in the human lung. The pathological mechanism is unknown but may involve a complex mixture of biomolecules which can diffuse from the spore surface. This material is known as A fumigatus diffusate (AfD) and has previously been shown to have a range of immunosuppressive functions. It is hypothesised that AfD may influence the binding of spores to extracellular matrix (ECM) proteins and lung epithelial cells, thereby affecting the ability of the fungus to cause infection. METHODS The binding of spores to ECM proteins and to epithelial cells was carried out using a direct binding assay in microtitre plates and spores were counted by phase contrast microscopy. Rat bronchoalveolar lavage (BAL) fluid was enriched for surfactant protein D (SP-D) using maltose agarose affinity chromatography. The effects of AfD and the SP-D enriched BAL fluid were assessed by pre-incubation with ECM proteins or epithelial cells in the direct binding assay. RESULTS AfD enhanced the binding of spores to laminin by 137% and to A549 epithelial cells by 250%. SP-D enriched BAL fluid inhibited spore binding to ECM proteins and epithelial cells. Pre-incubation of ECM proteins and epithelial cells with SP-D enriched BAL fluid prevented the enhancement of spore binding by AfD, and pre-incubation of ECM proteins and epithelial cells with AfD prevented the inhibition of spore binding by SP-D enriched BAL fluid. This pretreatment did not prevent the enhancement of spore binding, giving an increase of 95% for collagen I, 80% for fibronectin, 75% for laminin, and 150% for A549 cells. CONCLUSIONS The hypothesis that AfD would affect spore binding to ECM proteins and epithelial cells was confirmed. Rat BAL fluid, with SP-D as the possible bioactive agent, prevented this enhancement. The in vivo significance is unclear but the enhanced binding of spores may increase the chance of fungal infection in the lung which could be prevented by the protective effects of lung surfactant components (possibly SP-D). The results suggest that there may be competition between AfD and a BAL fluid component (possibly SP-D) for the same or similar binding sites on ECM proteins and epithelial cells. Whether this competition occurs in vivo requires further investigation.
Prenatal exposure to environmental contaminants and asthma and eczema in school-age children
Authors: Lidwien A.M. Smit, Virissa Lenters, Birgit Bjerre Høyer, Christian H. Lindh, Henning S. Pedersen, Iuliia Lermontova, Bo A.G. Jönsson, Aldert H. Piersma, Jens Peter Bonde, Gunnar Toft, Roel Vermeulen, Dick Heederik
Journal: European Respiratory Journal (2014)

Background  Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children.   Aim  We explored associations of prenatal exposures to a large set of environmental contaminants with asthma and eczema symptoms in school-age children from a birth cohort in Greenland (n=572) and Ukraine (n=607).   Methods  Data were collected by means of an interview-based questionnaire when the children were 6-9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153 and p,p´-DDE. Scores of five components (PCs) explaining 70% of the variance were included in multiple logistic regression models.   Results  The PC3 score (reflective of DEHP metabolites) was positively associated with wheeze in Ukrainian children (current wheeze: OR 1.57, 95%CI 1.04-2.38; ever wheeze: OR 1.32, 0.97-1.78). The PC5 score (dominated by perfluorooctanoic acid, PFOA) was inversely associated with current wheeze (OR 0.63, 0.40-0.99). In children from Greenland, negative associations of PC2 (DiNP metabolites) with current eczema (OR 0.63, 0.40-1.00) and PC4 (organochlorines) with ever eczema (OR 0.76, 0.60-0.95) were found.   Conclusion  We found limited evidence to support a link between prenatal exposure to measured contaminants and an increased risk of asthma and eczema symptoms in school-age children.
Body composition analysis using computed tomography image in patients with advanced lung cancer
Authors: Valerie Coats, Jean-Simon Lalancette, Fernanda Ribeiro, Yves Lacasse, Lise Tremblay, François Maltais, Didier Saey
Journal: European Respiratory Journal (2013)

Background: Despite the importance of muscle wasting in lung cancer, body composition in this disease has been mostly assessed using methods that do not allow differentiation between muscle and other tissues.  Aim: To compare body composition of patients with lung cancer (1-year survivors versus 1-year non-survivors) using computed tomography (CT scan) image analysis at diagnosis and at the end of follow-up (at 1 year or at death).  Method: 39 patients newly diagnosed with advanced lung cancer who had a thoraco-abdominal CT-scan were recruited and separated in two groups according to whether they were alive at one year or not. Following the collection of clinical data, we quantified muscle, visceral fat and subcutaneous fat areas from a single abdominal cross-sectional image at the level of the third lumbar vertebra. Sarcopenia was assessed using CT-based criteria and defined as having a muscle area ≤ 55 cm²/m² for men and ≤ 39 cm²/m² for women.  Results: CT scans from 17 males/22 females with advanced lung cancer and a mean age of 64 ±9 years and a body mass index of 26 ±4 Kg/m² were analysed. The one-year survival rate was 51%. At diagnosis, average muscle, visceral fat and subcutaneous fat areas were 141 ±67 cm², 134 ±96 cm² and 141 ±67 cm² respectively. Overall, 28% of patients were sarcopenic at diagnosis but the prevalence tend to be higher in the non-survivors compared to survivors, 37% vs 20% respectively. During the one-year follow-up, the rate of sarcopenia rised in both groups but stayed higher in the non-survivors, 58% vs 40% respectively.  Conclusion: Sarcopenia was prevalent in patients with advanced lung cancer and tend to be higher in those who did not survive at one year.
Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma.
Authors: A L Yu, M M Uttenreuther-Fischer, C S Huang, C C Tsui, S D Gillies, R A Reisfeld, F H Kung
Journal: Journal of Clinical Oncology (1998)

To evaluate the toxicity, immunogenicity, and pharmacokinetics of a human-mouse chimeric monoclonal antibody (mAb) ch 14.18 directed against disialoganglioside (GD2) and to obtain preliminary information on its clinical efficacy, we conducted a phase I trial in 10 patients with refractory neuroblastoma and one patient with osteosarcoma.Eleven patients were entered onto this phase I trial. They received 20 courses of mAb ch 14.18 at dose levels of 10, 20, 50, 100, and 200 mg/m2. Dose escalation was performed in cohorts of three patients; intrapatient dose escalation was also permitted.The most prevalent toxicities were pain, tachycardia, hypertension, fever, and urticaria. Most of these toxicities were dose-dependent and rarely noted at dosages of 20 mg/m2 and less. Although the maximum-tolerated dose was not reached in this study, clinical responses were observed. These included one partial (PR) and four mixed responses (MRs) and one stable disease (SD) among 10 assessable patients. Biologic activity of ch 14.18 in vivo was shown by binding of ch 14.18 to tumor cells and complement-dependent cytotoxicity of posttreatment sera against tumor target cells. An anti-ch 14.18 immune response was detectable in seven of 10 patients studied.In summary, with the dose schedule used, ch 14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxicities. Further clinical trials of mAb ch 14.18 in patients with neuroblastoma are warranted.
Amelioration of B16F10 melanoma lung metastasis in mice by a combination therapy with indomethacin and interleukin 2.
Authors: R S Parhar, P K Lala
Journal: The Journal of Experimental Medicine (1987)

Our earlier work revealed that PGE-mediated inactivation of NK cells in tumor-bearing mice by host macrophages promoted spontaneous lung metastasis that could be prevented or ameliorated by chronic indomethacin therapy. Since PGE was found to suppress the in vitro development and/or activation of a family of tumoricidal lymphocytes such as CTL, NK, and LAK cells by one or both of two mechanisms, that is to say, a down regulation of IL-2-R and an inhibition of IL-2 production, the present study tested whether a combined therapy with indomethacin and IL-2 was more effective than one with indomethacin or IL-2 alone in ameliorating established experimental lung metastasis. B6 mice injected intravenously with 10(6) highly metastatic B16F10 melanoma cells showed profuse micrometastases in the lungs by day 5, and macrometastases by day 10 which were confluent on day 21. Chronic indomethacin therapy by the oral route (14 micrograms/ml in drinking water) starting on day 0 or day 5, or a single round of IL-2 therapy (25,000 U rIL-2, every 8 h for 5 d on days 10-14) reduced the number of metastatic nodules by two-thirds (from a median of 473 in control mice receiving vehicles alone) by day 21. A single round of IL-2 as above, combined with either protocol of indomethacin therapy, completely or nearly completely irradicated the lung metastases, corroborated by a histological examination. An evaluation of splenic killer cell activity measured with a 4-h 51Cr-release assay against NK-sensitive YAC-1 lymphoma and B16F10 melanoma or NK-resistant thymic lymphoma 9705 targets revealed negligible activity in control tumor-bearing mice, and a good restoration of activity against NK-sensitive targets with either protocols of indomethacin therapy. IL-2 alone or a combination of IL-2 and indomethacin given by either protocol generated strong killer activity against all these targets, most marked with the combination therapy. Splenic killer cell phenotype in normal as well as all treated animals was ASGM1+, Thy-1-, and Lyt-2-. The combination therapy resulted in the strongest mononuclear cell infiltration in the lungs, with areas of young granulation tissue suggestive of repair sites of original metastases.
Patient Characteristics and Management of Primary Cardiac Angiosarcoma: National Cancer Center Hospital Experience
Authors: Yosuke Tanaka, Jun Hashimoto, Akihiko Yoshida, Makoto Kodaira, Harukaze Yamamoto, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura
Journal: Annals of Oncology (2014)
Use of an RNA interference screen-derived mitotic and ceramide pathway metagene to predict response to paclitaxel combination chemotherapy in primary breast cancer.
Authors: C. Swanton, N. Juul, J. M. Larkin, A. Eklund, Q. Li, C. Desmedt, C. Sotiriou, L. Pusztai, Z. Szallasi
Journal: Journal of Clinical Oncology (2010)

569 Background: Addition of taxanes to preoperative chemotherapy in breast cancer increases the rate of pathological complete response (pCR). Despite this improvement, a significant proportion of patients do not respond and the prognosis for patients with ER-/PR-/ERBB2- disease failing to achieve a pCR remains particularly poor. Identification of such patients in a reliable manner is the first step towards determining who might benefit from alternative treatment regimens within clinical trials. We previously reported an RNA interference screen in 3 cancer cell lines, including an ER-/PR- /ERBB2- breast cancer cell line, identifying genes involved in mitosis or ceramide metabolism that influenced sensitivity to paclitaxel. Our goal was to evaluate these genes as a predictor of pCR to paclitaxel combination chemotherapy in ER-/PR-/ERBB2- breast cancer. Methods: We derived a paclitaxel response metagene based on mitotic and ceramide genes identified by functional genomics studies. We used AUC and multivariate logistic regression to evaluate the metagene in five ER-/PR-/ERBB2- neoadjuvant chemotherapy breast cancer clinical trial cohorts; two treated with paclitaxel and four treated without paclitaxel. Results: The paclitaxel response metagene was predictive of pCR in ER-/PR-/ERBB2- patients in paclitaxel-treated cohorts (AUC = 0.79, 0.72) in contrast to non-paclitaxel-treated cohorts (AUC = 0.53, 0.36, 0.53, 0.59). Following multivariate logistic regression analysis, the paclitaxel response metagene was associated with pCR (p = 0.02) and a test for interaction of the metagene with paclitaxel regimen was significant (p = 0.009). Conclusions: The paclitaxel response metagene shows promise as a paclitaxel-specific predictor of pCR in ER-/PR-/ERBB2- breast cancer patients. In contrast to predictive microarray signatures developed through associative learning strategies, these results highlight the potential for RNA interference screens to identify genes required for drug response in vivo and accelerate predictive biomarker development without the need for training clinical trial cohorts. No significant financial relationships to disclose.
Computed digital absorptiometry of the hand: screening method of bone loss in postmenopausal women with RA
Authors: J M NOLLA
Journal: Annals of the Rheumatic Diseases (2000)

How should we manage fibromyalgia?We read with interest your leader, "How should we manage fibromyalgia?". 1 We were puzzled by Paul Reilly's statement that a comprehensive pain management programme...has the best chances of success, although even rheumatologists can practise amateur cognitive behavioural therapy in the clinic".Is Dr Reilly really suggesting that a rheumatologist's amateur eVorts oVer the best outcome for people with fibromyalgia?Dr Reilly oVers no evidence to support this statement.He does, however, find evidence to raise questions as to the value of patient self help groups.Dr Reilly cites a 1992 paper that reports an association between membership of such a group and worse prognosis in chronic fatigue syndrome. 2As the authors emphasised the caution with which the results should be interpreted, it is surprising that Dr Reilly has used this evidence to inform his clinical practice.Firstly, this is ancient research.Things have moved on.Although we would agree that some so called self help groups can end up as a circular review of symptoms, self management courses, which we at Arthritis Care espouse, are a very diVerent matter.Challenging Arthritis is a self management programme-and that title was chosen very deliberately.It is run by people with arthritis for people with arthritis.It gives people the skills to take control of their lives and their arthritis.It is practical and positive, and it works.The eVectiveness of similar programmes in the USA is well recorded. 3 Experience in the United Kingdom shows similar results, including better understanding of symptoms, improved communication with medical staV, and increased use of exercise and relaxation techniques.Probably most importantly of all, self management programmes significantly decrease pain, fatigue, and anxiety. 4 So it is extremely important to diVerentiate between navel gazing self help systems and courses such as ours, which encourage people to take control for themselves-and which work.Similar courses run on the Challenging Arthritis model are now available to people with other chronic conditions.Given Dr Reilly's desire to disabuse patients of the notion that their fibromyalgia is his problem alone, shouldn't eVective courses which encourage people to take control for themselves be a welcome adjunct to his treatment, even if it is run by a patient self management group?ROBINA
Bradyarrhythmias Associated with Sofosbuvir Treatment
Authors: Hélène Fontaine, Arnaud Lazarus, Stanislas Pol, Caroline Pecriaux, François Bagate, Philippe Sultanik, Estelle Boueyre, Marion Corouge, Vincent Mallet, Anaïs Vallet-Pichard, Philippe Sogni, Denis Duboc
Journal: New England Journal of Medicine (2015)
Abstract 779: Osteopontin gene expression is associated with 5-fluorouracil drug resistance in colon cancer
Authors: Go Nakajima, Hidekazu Kuramochi, Masakazu Yamamoto, Kazuhiko Hayashi
Journal: Cancer Research (2014)

Abstract Background: Resistance to chemotherapeutic drugs complicates the treatment of cancer patients. The extracellular matrix protein osteopontin (OPN) plays multiple roles in the proliferation and metastasis of cancer cells. We therefore attempted to determine whether OPN expression correlated with drug resistance. Methods: OPN expression in the HCT 116 colon cancer cell line was inhibited by an OPN-short interfering RNA (siRNA). We determined the cytotoxic effect (IC50) of 5-fluorouracil (5FU) on these cells. Patients with recurrence or colorectal cancer or harbored residual tumor cells were treated with S-1-based chemotherapy. The levels of OPN mRNA expression in the tumors were determined and compared with the patients’ responses to chemotherapy. Results: The IC50 of 5FU for HCT 116 cells transfected with the OPN-siRNA was 32.9 μM. In contrast, the IC50 values for cells transfected with a negative control siRNA, mock-transfected cells, or untreated cells were 6.58 μM, 7.08 μM, and 6.76 μM, respectively (P&amp;lt;0.001). The level of OPN mRNA expression in the S-1 non-responder group was significantly lower than that of the responder group (P = 0.0387). Survival analysis revealed no significant difference between the responder and non-responder groups (P = 0.8737). Conclusions: The level of OPN expression plays a role in the resistance of colorectal tumor cells to 5FU. Citation Format: Go Nakajima, Hidekazu Kuramochi, Masakazu Yamamoto, Kazuhiko Hayashi. Osteopontin gene expression is associated with 5-fluorouracil drug resistance in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 779. doi:10.1158/1538-7445.AM2014-779