tbuckley/cabot-search huggingface dataset:
Mucus production, lung inflammation and functional decay in IPF
Authors: Graziella Turato, Ariel F. Floriani, Simonetta Baraldo, Elisabetta Balestro, Erica Bazzan, Marco Schiavon, Riccardo Cazzuffi, Marco Damin, Nazarena Nannini, Fiorella Calabrese, Federico Rea, Marina Saetta, Manuel G. Cosio
Journal: European Respiratory Journal (2014)

Background. In idiopatic pulmonary fibrosis (IPF) the progression of the disease can be slow or rapid and the rate of progression strongly influences prognosis. Variations in MUC5B promoter, resulting in a variable increase in mucin expression, have been associated with IPF. It is not known if mucus production could be related to the rate of FVC decay.  Aims: 1)To quantify mucus content in severe IPF lungs and to investigate its relation to rate of FVC decline (rapid or slow) and lung inflammation; 2)To compare mucus content in IPF with severe COPD.  Methods. Explanted lungs of 14 IPF patients (age:55±10) classified as slow or rapid progressors based on yearly FVC decline ( 10%predicted) were studied. 7 severe COPD explanted lungs and 7 healthy donors lungs were included for comparison. Mucus content was quantified by point counting in Periodic Schiff stained sections. Inflammation was quantified by immunohistochemistry.  Results. The volume fraction of mucus in IPF (median;range 2.1;0.4-10.6%) was increased compared to donors (0;0-0.2%;p + (p  Conclusions. A prominent mucus production is a distinct finding in the lungs of patients with severe IPF, even surpassing the amount in lungs with COPD. The mucus content paralleled the degree of lung inflammation and FVC decline.
Abstract 12832: Prediction of Pathogenicity of Plakophilin-2 Missense Mutations in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Judith A Groeneweg, Aditya Bhonsale, Cynthia A James, Jeroen F van der Heijden, Brittney Murray, Arthur A Wilde, Crystal Tichnell, Jan D Jongbloed, Harikrishna Tandri, J P van Tintelen, Daniel P Judge, Richard N Hauer, Hugh Calkins, Dennis Dooijes
Journal: Circulation (2012)

Introduction: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is considered a hereditary disease. Genetic screening identifies pathogenic mutations in the majority of ARVD/C pati...
대한간학회지 제8차 춘계학술대회 초록집 : 구연 ; 간이식 후 B형 간염 재발방지를 위한 저용량 헤파빅 근주 및 라미부딘 병용효과
Authors: 배시현 ( Bae Si Hyeon ), 조세현 ( Jo Se Hyeon ), 윤승규 ( Yun Seung Gyu ), 양진모 ( Yang Jin Mo ), 한준열 ( Han Jun Yeol ), 이창돈 ( Lee Chang Don ), 차상복 ( Cha Sang Bog ), 정규원 ( Jeong Gyu Won ), 선희식 ( Seon Hui Sig ), 박두호 ( Park Du Ho ), 김동구 ( Kim Dong Gu ), 최종영
Journal: Clinical and Molecular Hepatology (2002)
Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia
Authors: Andy V. Khamoui, Bong-Sup Park, Do-Houn Kim, Ming-Chia Yeh, Seung-Lyul Oh, Marcus L. Elam, Edward Jo, Bahram H. Arjmandi, Gloria Salazar, Samuel C. Grant, Robert J. Contreras, Won Jun Lee, Jeong-Su Kim
Journal: Metabolism (2016)
Anthracycline cardiotoxicity prevention by dexrazoxane: breakthrough of a barrier--sharpens antitumor profile and therapeutic index.
Authors: K Hellmann
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.2.332 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8636740 Anthracycline cardiotoxicity prevention by dexrazoxane: breakthrough of a barrier--sharpens antitumor profile and therapeutic index. K HellmannxK HellmannSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.2.332 PDF "Anthracycline cardiotoxicity prevention by dexrazoxane: breakthrough of a barrier--sharpens antitumor profile and therapeutic index.." Journal of Clinical Oncology, 14(2), pp. 332–333© 1996 by American Society of Clinical Oncology
Convergent evolution of cysteine residues in sperm protamines of one genus of marsupials, the Planigales.
Authors: J D Retief, J S Rees, M Westerman, G H Dixon
Journal: Molecular Biology and Evolution (1995)

A characteristic feature of the sperm P1 protamines of eutherian mammals is the constant presence of six to nine cysteine residues per molecule. During spermiogenesis these residues become oxidized to form a three-dimensional network of disulfide bridges between, and within, protamine molecules in the sperm chromatin. This covalent cross linking strongly stabilizes eutherian sperm nuclei. In contrast, protamines sequenced from teleost fish, birds, monotremes, and marsupials all lack cysteine residues and their sperm nuclei, without the stabilizing cross links, are easily decondensed in vitro. We have now found that one genus of tiny, shrewlike dasyurid marsupials, the Planigales, possess P1 protamines containing five to six cysteine residues. These residues appear to have evolved since the divergence of Planigales from other members of the family Dasyuridae, such as the marsupial mouse, Sminthopsis crassicaudata. We believe this constitutes a case of convergent evolution in a subfamily of dasyurid marsupials toward the cysteine-rich eutherian form of sperm protamine P1.
Neutropenia and anxiety in advanced non-small cell lung cancer (NSCLC) patients: initial report of a randomized controlled trial using pegfilgrastim to reduce neutropenia complications
Authors: F. Smith, M. Kandahari, D. Tomita, J. Green, R. Dansey, J. Crawford
Journal: Journal of Clinical Oncology (2005)

8173 Background: Maintaining quality of life (QOL) in pts with advanced NSCLC is an important treatment objective. Potential chemotherapy (CT) side effects, including treatment delays, may adversely impact pts’ physical, social, and mental (eg, anxiety) well-being. This pilot study evaluated the association between CT-induced neutropenia and changes in QOL using the Hospital Anxiety and Depression Scale (HADS) and other measures of QOL. Methods: Stage IIIB/IV NSCLC pts receiving carboplatin AUC 5/6 with either paclitaxel 175–225 mg/m2 or docetaxel 75 mg/m2 were enrolled into this open-label study. Pts were randomized to either pegfilgrastim (Neulasta) in first and subsequent cycles, or no pegfilgrastim in cycle 1 with use in subsequent cycles per MD discretion. The CBCs, HADS and FACT instruments were administered at day 1 of cycles 1, 2, and 3, and at expected ANC nadir in cycles 1 and 2. Endpoints included incidence of grade 3/4 neutropenia and change in HADS-anxiety (HADS-A) subscale, which ranges from 0 (not anxious) to 21 (most anxious). Results: 149 pts treated. The mean (SD) age was 65.0 (11.4), 60% male; 52% carboplatin-paclitaxel. The incidence of grade 3/4 neutropenia in cycles 1 and 2 was 5% (95% CL: 2%, 13%) for pts receiving pegfilgrastim from the first cycle and 43% (95% CL: 31%, 55%) for pts receiving pegfilgrastim per MD discretion. Overall, >70% of pts completed all items of the HADS-A at each time point. Exploratory analyses of changes in HADS-A score from baseline to end of cycle 1 and 2 suggest a trend towards statistical significance (p<0.06, p<0.1, respectively). Conclusions: In this study, neutropenia was markedly reduced with the use of pegfilgrastim from the 1st cycle. Initial analysis suggests that anxiety may also have been reduced for patients receiving pegfilgrastim from the 1st cycle. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen
Abstract 307: Phospholipase Cε Is Involved in Gq-Dependent Protein Kinase D Activation in Cardiac Myocytes
Authors: Alan Smrcka, Lianghui Zhang, Sundeep Malik
Journal: Circulation Research (2012)

We previously demonstrated that PLCε is a critical mediator of endothelin-1 (ET-1)- and norepinephrine (NE)-dependent hypertrophy in neonatal rat ventricular myocytes (NRVMs). Both α-adrenergic and ET-1 receptors couple to Gq as well as other G proteins. To determine if PLCε is required for Gαq-dependent hypertrophy NRVMs were infected with adenoviruses expressing wtGαq and PLCε siRNA followed by measurement of hypertrophy. PLCε-siRNA significantly inhibited Gαq-induced increases in myocyte area and atrial natriuretic factor (ANF) mRNA expression. Similarly, disruption of PLCε association with perinuclear mAKAP inhibited Gαq-dependent hypertrophy. These data suggest that ET-1 and PE signal, at least in part, through Gαq and PLCε. To explore the functional role of PLCε in ET-1/Gq dependent hypertrophy, activation of protein kinase D (PKD) in NRVMs was assessed in response to ET-1. PLCε-siRNA significantly inhibited ET-1 induced PKD activation (∼50% inhibition). Disruption of PLCε-mAKAP interactions also significantly inhibited ET-1 induced PKD activation (∼50% inhibition). We propose that PLCε scaffolded to mAKAP at the nuclear envelope responds to Gαq-dependent, as well as other hypertrophic signals, to locally regulate PKD in a process that is critical for hypertrophy development.
Abstract P298: Progression Of Subclinical Atherosclerosis And Its Determinants In Early Postmenopausal Chinese Women - A Five-year Followup Study Of A Population-based Cohort
Authors: Suzanne Ho (Chan), Ruby HY Yu, Stella Ho, Sophie SG Chan, Jean LF Woo, Christopher WK Lam, Nelson Tang
Journal: Circulation (2012)

Introduction: Subclinical atherosclerosis (SA) progresses silently over a period of time before the clinical manifestations of cardiovascular disease. Hypothesis: We hypothesize that early postmenopausal women with adverse cardiovascular risk factors or their progression to abnormal values have a higher risk of SA. This study aimed to investigate the progression of SA and its determinants in early postmenopausal Chinese women. Methods: This is a community-based 5-year followup study on a cohort of 518 women aged 50–64, within 10 years menopause, and recruited through random telephone dialing. Clinical assessments, fasting blood samples, lifestyle and dietary variables based on validated and structured questionnaires, as well as intima-media thickness (IMT) were obtained at baseline and at followup. IMT was measured using a 12.5-MHz linear probe of the HDI 5000 ultrasound scanner at the near and far walls of three 10-mm segments: distal common carotid, bifurcation, proximal internal carotid of both the left and right carotid arteries. Plaque was defined as a focal wall thickening of at least 1.5mm and graded as: grade 0, 1 and 2. Plaque progression was the difference of the plaque index at baseline and followup, and classified into 3 categories. Results: This study of Chinese early postmenopausal women (followup mean age 61.5 years at followup) has revealed a progression of IMT of 2.1% per year (standard deviation = 1.7). 17% were found to have a moderate and 8% severe plaque progression. Stepwise multiple regression analyses showed that baseline IMT, age, low density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure were significant predictors of higher followup IMT, while vegetable and fruit intake were inversely related. Women with values belonging to the “normal” ranges of blood pressure, waist circumference, lipid and fasting blood glucose levels had lower IMT at followup compared to those with abnormal baseline values and those with progression from “normal” to the “abnormal” ranges. Women with high soy-vegetable-fruit intake at both baseline and followup had lower IMT than those with low intakes at both time points. Increasing age, waist circumference ≥80 cm, cholesterol ≥200 mg/L, having diabetes, regular drinking were significant predictors of plaque progression (adjusted odds ratios from 1.10 to 2.81), while higher vegetable and fruit intake lowered the risk. Conclusion: Age, central obesity, diabetes, dislipidaemia, high blood pressure, regular drinking were significant predictors for an increased risk of SA. Maintenance of these CVD factors within normal ranges through early menopausal years with adequate fruit and vegetable intake is important to reduce the progression of SA.
Direct hospital costs of skeletal-related events (SRE) in Portuguese patients (pts) with breast cancer (BC) and bone metastases
Authors: J. Felix, V. Andreozzi, M. Soares, H. Gervásio, A. Moreira, L. Costa, F. Peralta, I. Furtado, C. Albuquerque, J. Passos- Coelho
Journal: Journal of Clinical Oncology (2007)

17084 Background: SRE such as pathological fractures, spinal cord compression, surgery or radiation therapy to bone and tumour- induced hypercalcemia account for substantial health resource utilization (HRU). The objective of this study was to investigate SRE-related direct hospital costs in Portuguese pts with BC and bone metastases. Methods: Pts with BC and at least one SRE within 12 months prior to study entry were eligible for this retrospective medical record review cost analysis study. SRE treatment cost were calculated by multiplying 12 month health resource utilization frequency (hospitalization, clinic visits, diagnostic tests, drugs) by the corresponding unit costs from the Portuguese Ministry of Health costs database. To account for the skewed nature of the data, costs were modelled using generalized linear models with gamma distribution and log link. Results: A total of 121 pts (age at bone metastases, mean 56.8 years, range 21- 89) from six different hospitals in Portugal were included. Median time from BC diagnosis to bone metastases was 38 months [CI95%: 24–57]. ECOG performance status at the time of SRE was 0 in 24.6% of pts, 1 in 45.9%, 2 in 18.0%, 3 in 8.2% and 4 in 3.3%. Total number of SRE over twelve months was 142 (mean 1.2 SRE/pts, SD=0.4) distributed as follows: pathological fractures (12.7%), spinal cord compression (4.9%), surgery to bone (1.4%), radiation therapy to bone (74.7%) and tumour induced hypercalcemia (6.3%) . Mean SRE treatment cost over 12 months was 5,963€ (SD=3,646€): hospitalization 1,312€, clinic visits 36€, diagnostics 103€, radiotherapy 1,481€, drugs 3,031€. According to biphosphonate (Bph) use in the prior 12 months, the mean (SD; pts) unadjusted SRE treatment cost was: no Bph 2,282€ (1,491; n=4), oral Bph 1,579€ (1,123; n=5), zoledronic acid 6,221€ (2,923; n=77), pamidronate 6,766€ (4,476; n=33). When excluding Bph costs, pamidronate pts were 1.8 [95% CI: 1.3–2.7] times more expensive than zoledronic acid when controlling for pts’ clinical characteristics. Conclusions: This study confirms prior data on the high cost of SRE in pts with BC metastatic to bone [Table: see text]
Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.
Authors: Alexander M. Eggermont, Vanna Chiarion-Sileni, Jean Jacques Grob, Reinhard Dummer, Jedd D. Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo Antonio Ascierto, Jon M. Richards, Celeste Lebbe, Virginia Ferraresi, Michael Smylie, Jeffrey S. Weber, Michele Maio, Cyril Konto, Ravichandra Karra Gurunath, Veerle de Pril, Stefan Suciu, Alessandro Testori
Journal: Journal of Clinical Oncology (2014)

LBA9008 Background: Ipilimumab (Ipi), a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses, is an approved treatment for advanced melanoma. Here, we report the results of a phase III trial designed to evaluate Ipi as an adjuvant therapy for resected stage III melanoma at high risk of recurrence. Methods: In this randomized, double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to receive Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) every 3 wks for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival (RFS), analyzed on the intent-to-treat population. 512 RFS events (recurrence or death) were needed to provide 90% power to detect an Ipi vs Pbo hazard ratio (HR) of 0.75 (2-sided α=5%). Results: Overall, 20%/44%/36% of pts had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. At a median follow-up of 2.7 yrs, Ipi significantly improved RFS vs Pbo. RFS benefit was consistent across subgroups (e.g., stage IIIB or IIIC, ulcerated primary). Most common grade 3/4 immune-related adverse events (irAEs) in the Ipi and Pbo arms were gastrointestinal (15.9% vs 0.8%), hepatic (10.6% vs 0.2%), and endocrine (8.5% vs 0%). Most irAEs were managed and resolved using established algorithms. Of 471 pts who started Ipi, 245 (52%) discontinued treatment due to AEs [182 (38.6%) within 12 weeks]; 5 (1.1%) died due to drug-related AEs. Conclusions: In this phase III trial, Ipi as adjuvant therapy provided a clinically and statistically significant improvement in RFS vs Pbo for pts with stage III melanoma at high risk of recurrence. AE profile was generally consistent with that observed in advanced melanoma, although with a higher incidence of endocrinopathies. Clinical trial information: NCT00636168. EudraCT Number: 2007-001974-10. [Table: see text]
Comparative Efficacy of Dronabinol and Megestrol Acetate
Authors: Richard Reynolds, Aminah Jatoi, Charles Loprinzi, Harold Windschitl
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2912 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065574 Comparative Efficacy of Dronabinol and Megestrol Acetate Richard ReynoldsxRichard ReynoldsSearch for articles by this author Aminah JatoixAminah JatoiSearch for articles by this author , Charles LoprinzixCharles LoprinziSearch for articles by this author , Harold WindschitlxHarold WindschitlSearch for articles by this author Show More Bossier City, LAMayo Clinic, Rochester, MNCentraCare Clinic, St Cloud, MN https://doi.org/10.1200/JCO.2002.20.12.2912 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:We are pleased to respond to Mr Reynolds’ concerns. Mr Reynolds notes that our article1 should be “revised to indicate the dosages.” He also notes that our negative findings may have resulted from the dose of dronabinol used in this trial. First, in the Abstract, Patients and Methods, and Discussion sections of our article, we explicitly state the doses of dronabinol and megestrol acetate used in this study. Dosing is obviously an important issue in cancer care, and we have been as unambiguous as possible in informing readers of the doses tested in this trial. Second, we agree that our negative findings with respect to dronabinol as an orexigenic agent may have resulted from the dronabinol dose we tested. However, we have clearly stated the rationale for our choice of the dose 2.5 mg twice a day. If the sole purpose of an agent is appetite stimulation, we think it injudicious to substitute one symptom for a set of others. Because earlier data from Nelson et al2 found an approximately 20% toxicity rate with a higher dose of dronabinol, we opted to test the lower dose of 2.5 mg twice a day. Of note, this decision on dronabinol dosing was made in concert with the manufacturers of dronabinol.Finally, Mr Reynolds states in his letter, “the enthusiasm the study wishes to dampen seems to be the enthusiasm for reclassifying marijuana to a Schedule II substance.” We are not opposed to the rigorous study of marijuana as a palliative or therapeutic agent for cancer patients. However, we did not test marijuana in our trial, nor do we claim to have tested it.1. Jatoi A, Windschitl HE, Loprinzi CL, et al: Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A North Central Cancer Treatment Group Study. J Clin Oncol 20:: 567,2002-573, Link, Google Scholar2. Nelson K, Walsh D, Deeter P, et al: A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care 10:: 14,1994-18, Google Scholar
Design of a phase 0 microdosing trial for correlation of platinum-induced DNA damage to chemotherapy outcomes
Authors: C. Pan, T. Li, M. He, R. de Vere White, D. Gandara, P. Mack, P. N. Lara, K. Turteltaub, P. Henderson
Journal: Journal of Clinical Oncology (2009)

2543 Background: DNA damage is the critical step in cancer cell response to platinum (Pt) chemotherapy. We hypothesize that low levels of Pt-induced DNA damage are predictive of chemoresistance. Accelerator mass spectrometry (AMS), an ultrasensitive method for measuring radiocarbon, can detect [ 14 C]carboplatin bound to the DNA of cancer cells from cell culture, mice bearing tumor xenografts and patients receiving subtoxic microdoses of compound. Methods: Cancer cells and mice bearing tumor xenografts were treated with one microdose (1/100 th of the therapeutic dose) or one therapeutic dose of [ 14 C]carboplatin. Relevant parameters such as drug influx/efflux, intracellular drug inactivation, DNA damage and repair, were measured and correlated with response to chemotherapy. A Phase 0 microdosing trial has been designed to study patients with non-small cell lung or bladder transitional cell cancers who are planning to receive Pt-based chemotherapy. One microdose of [ 14 C]carboplatin is administered to these patients 4 hours before biopsy. Pt-induced DNA damage and repair in tumor biopsy specimens and other relevant parameters will be measured and correlated with the response and toxicity of chemotherapy. Results: Preclinical studies showed that AMS can detect Pt-DNA damage when cancer cells and mice with tumor xenografts are exposed to one microdose of [ 14 C]carboplatin. The levels of microdose-induced DNA damage are directly proportional to the damage caused by a therapeutic drug dose (p&lt;0.001); and these levels of DNA damage correlate with chemoresistance as measured by MTT assay. Measuring drug uptake/efflux and intracellular inactivation allows insights into resistance mechanisms. These data support the conclusion that the levels of DNA damage induced by microdosing can potentially predict chemoresistance in patients. Consequently, a Phase 0 microdosing trial is in progress. Conclusions: These results support a phase 0 microdosing trial employing AMS to identify chemoresistance and determine the underlying chemoresistant mechanisms for personalized therapy before patients receive cytotoxic chemotherapy. [Table: see text]
Inhibition of Leukocyte Adherence by 3-&lt;italic&gt;M&lt;/italic&gt; Potassium Chloride Extracts of Human Colorectal Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Albert T. Ichiki, Yvonne P. Quirin, I. Reid Collmann, Takuo Sonoda, Stephen Krauss
Journal: JNCI Journal of the National Cancer Institute (1980)

Leukocyte adherence inhibition (LAI) assays were performed to test whether peripheral blood leukocytes (PBL) from patients with colorectal cancer could be inhibited from attachment to a glass surface when tumor-associated antigens (TAA) of human colorectal tumors were present. The assays were performed with PBL from 41 patients with adenocarcinoma of the colon or rectum with 3-M KCl extracts of colorectal tumors. The results demonstrated the presence of colorectal TAA in the 3-M KCl extract of colorectal tumor materials. The reactivity of leukocytes from patients with a favorable prognosis showed an increasing LAI trend; the reactivity of leukocytes from patients with an unfavorable prognosis had a decreasing LAI trend. In individual patients, alterations in the sequential LAI results paralleled changes in the clinical status, which thus strongly indicated that the LAI assay could be of value in the assessment of antitumor immunity.