tbuckley/cabot-search huggingface dataset:
Targeted eicosanoid lipidomics of induced sputum as compared to exhaled breath condensate in asthmatics
Authors: Marek Sanak, Lucyna Mastalerz, Anna Gielicz, Barbara Sokolowska, Natalia Celejewska-Wόjcik, Andrzej Szczeklik
Journal: European Respiratory Journal (2011)

Eicosanoids are mediators of arachidonic acid pathway. Induced sputum (IS) is a non-invasive material from the lower airways; its sampling is well standardized. Advantage of exhaled breath condensate (EBC) is shorter collection time and low protein content, but this is compromised by extreme dilution and inter-individual variation. Both matrices have been introduced for assessment of inflammatory mediators in asthma.

We compared eicosanoids concentration in IS and EBC samples collected according to the current guidelines and estimated redistribution of eicosanoids and their metabolites as a result of sample processing.

EBC was collected from asthmatics using Jaeger ECO Screen I; IS according to the most recent ERS Task Force recommendations. The same validated quantitative mass spectrometry was used for both matrices ecosanoids' measurements. Random IS samples were split to test enzymatic inhibition during solubilisation.

We quantified 29 eicosanoids, including major prostaglandins, leukotrienes, and their metabolites. Average concentration of eicosanoids was 82 [1-400] times lower in EBC than in IS. IS differed form EBC by higher HETE and undetectable LTC4. Conversion of LTB4 into 5-oxo-LTB4 and increase of tetranor-PGEM was observed during IS solubilisation, non-physiological pH prevented these redistributions only partially.

Although processing of IS shifts eicosanoid profile toward metabolites, significant amounts of mediators are present within detection levels of common immunoassays. A strict adherence to the IS collection protocols is recommended to avoid a pre-analytical bias.

In collaboration with U-BIOPRED within the Innovative Medicine Initiative.
Acidic pH increases airway surface liquid viscosity in cystic fibrosis
Authors: Xiao Xiao Tang, Lynda S. Ostedgaard, Mark J. Hoegger, Thomas O. Moninger, Philip H. Karp, James D. McMenimen, Biswa Choudhury, Ajit Varki, David A. Stoltz, Michael J. Welsh
Journal: Journal of Clinical Investigation (2016)

Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF.
Follow-up of surviving acute respiratory distress syndrome patients using quantitative computed tomography
Authors: Carlos Toufen, Roberta Santiago, Adriana Hirota, Marcelo Amato, Carlos Carvalho
Journal: European Respiratory Journal (2013)

The accumulation of exudates in the air spaces characterizes acute respiratory distress syndrome (ARDS) and accounts for its dramatic clinicoradiographic presentation. Lung aeration assessed by quantitative computed tomography-based (qCT) can help to assess and monitor ARDS survivors. We aimed to evaluate qCT on follow-up of patients with ARDS and the relationship with concomitant pulmonary function test.

METODS: Patients with moderate and severe ARDS were followed-up and evaluated one and two months after ARDS diagnoses with pulmonary function tests (lung volume assessed by body plethysmography) and high-resolution computed tomography (HRCT).

RESULTS: A total of 22 patients with ARDS survived after 2 months. Global lung density one month after ARDS was 280.2 mg/cm3 and decrease to 174.7 mg/cm3 two months after ARDS (p < 0.01). Total lung mass has not changed (p = 0.13). One month after ARDS the lung density adjusted for the volume was significantly correlated with forced vital capacity (FVC) (r = -0.68, p < 0,01), carbon monoxide diffusion capacity (DLCO) (r = -0.54, p = 0.02), and total lung capacity (TLC) (r = -0.76, p < 0.01). After two months of ARDS, the lung density adjusted for the volume was significantly correlated with FVC (r = -0.87, p < 0,01), DLCO (r = -0.84, p < 0.01), and TLC (r = -0.83, p < 0.01). The total lung mass was only correlated with TLC one month of ARDS.

CONCLUSION: The lung density decreased and is correlated with pulmonary function test results two months after ARDS. In surviving ARDS patients, qCT may be used to evaluate pulmonary dysfunction particularly early in the monitoring when some patients may not be able to perform pulmonary lung tests.
CXC chemokine receptor 3 expression on CD34+hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor: chemotaxis and adhesion induced by its ligands, interferon γ–inducible protein 10 and monokine induced by interferon γ
Authors: Tan Jinquan, Sha Quan, Henrik H. Jacobi, Chen Jing, Anders Millner, Bettina Jensen, Hans O. Madsen, Lars P. Ryder, Arne Svejgaard, Hans-Jørgen Malling, Per S. Skov, Lars K. Poulsen
Journal: Blood (2000)
Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis
Authors: Anna A. Marusiak, Natalie L. Stephenson, Hayeon Baik, Eleanor W. Trotter, Yaoyong Li, Karen Blyth, Susan Mason, Phil Chapman, Lorena A. Puto, Jon A. Read, Claire Brassington, Hannah K. Pollard, Chris Phillips, Isabelle Green, Ross Overman, Matthew Collier, Ewelina Testoni, Crispin J. Miller, Tony Hunter, Owen J. Sansom, John Brognard
Journal: Cancer Research (2015)

Abstract MLK4 is a member of the mixed-lineage family of kinases that regulate the JNK, p38, and ERK kinase signaling pathways. MLK4 mutations have been identified in various human cancers, including frequently in colorectal cancer, where their function and pathobiological importance have been uncertain. In this study, we assessed the functional consequences of MLK4 mutations in colon tumorigenesis. Biochemical data indicated that a majority of MLK4 mutations are loss-of-function (LOF) mutations that can exert dominant-negative effects. In seeking to understand the abrogated activity of these mutants, we elucidated a new MLK4 catalytic domain structure. To determine whether MLK4 is required to maintain tumorigenic phenotypes, we reconstituted its signaling axis in colon cancer cells harboring MLK4-inactivating mutations. We found that restoring MLK4 activity reduced cell viability, proliferation, and colony formation in vitro and delayed tumor growth in vivo. Mechanistic investigations established that restoring the function of MLK4 selectively induced the JNK pathway and its downstream targets, cJUN, ATF3, and the cyclin-dependent kinase inhibitors CDKN1A and CDKN2B. Our work indicates that MLK4 is a novel tumor-suppressing kinase harboring frequent LOF mutations that lead to diminished signaling in the JNK pathway and enhanced proliferation in colon cancer. Cancer Res; 76(3); 724–35. ©2015 AACR.
Dynamic oxyhemoglobin saturation changes during Walking and cycling tests in COPD
Authors: Ming-Lung Chuang, I.-Feng Lin
Journal: European Respiratory Journal (2013)

Background: Resaturation of oxyhemoglobin saturation (SpO2) measured with pulse oximetry during exercise has not been addressed. We investigated the patterns and change in SpO2 (ΔSpO2) in six-minute walking test (6MWT) and cycling test in COPD patients.  Methods: Sixty COPD patients with FEV1 54±18%pred estimated the oxygen-cost diagram (OCD) score and performed lung function test and 6MWT. Fifty patients performed cycling test. The patterns of ΔSpO2 were compared within individual tests and between both tests.  Results: In the 6MWT, four patterns of SpO2 changed: mostly, desaturation-resaturation (46%). The ΔSpO2≥3% occurred at 1.23 minute. It resaturated at 3.5±1.4 minutes. The ΔSpO2 between the start and the nadir (ΔSpO2SN) was greater than that between the start and the end (ΔSpO2SE) (p  In the cycling test, three patterns of saturation changed: mostly, desaturation (58%). The ΔSpO2≥3% occurred at 68% of the cycling duration. The non-desaturationers had better body mass index, OCD score, lung function, work of walking, and peak exercise performance (all p  In both tests, the ΔSpO2SN during the 6MWT was greater (p  Conclusions: Taking ΔSpO2SN rather than taking ΔSpO2SE during 6MWT is advocated. Exertional desaturation is related to demographics, lung function, and exercise performance. The OCD scores forecast desaturation in both tests.
Results of a phase II study of picoplatin with docetaxel and prednisone in first-line treatment of castration-resistant prostate cancer (CRPC)
Authors: R. L. De Jager, L. Roman, N. Lopatkin, P. Karlov, H. Breitz, R. Earhart
Journal: Journal of Clinical Oncology (2009)

5140 Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. Previously, a PSA response rate of 25% was observed when Pico monotherapy was infused at 120 mg/m 2 Q3W (N = 20). Recently, a 34-patient Phase I study was performed to investigate the safety and efficacy of Pico in combination with docetaxel (D) + prednisone (pred) as first-line therapy for metastatic CRPC. Picoplatin therapy was well-tolerated at a dose of 120 mg/m 2 and 19 of 32 evaluable pts (59%) achieved a confirmed PSA response. Methods: 32 patients with chemotherapy-naïve CRPC and disease progression received Pico (120 mg/m 2 ) and D (75 mg/m 2 ) Q3W with pred 5 mg po bid for up to 10 cycles. PSA responses were defined as a reduction from baseline of at least 50% maintained for at least 4 weeks. CT and bone scans were also evaluated. Tumor response was measured using RECIST. Results: Patients received a median of 10 cycles (range = 1–10). Median baseline PSA was 340.8 ng/mL (range 5.6–3019). One pt had no baseline PSA data. Of the 24 patients with evaluable post-treatment PSA, 83% (95% CI 64–93%) had PSA decreases &lt;50% of baseline, and in 8 of these (33% of the evaluable population), PSA reached normal levels (&lt; 4 ng/mL). In the intent-to-treat population, the PSA response rate was 63% (95% CI 45–77%). 13 patients evaluated by CT scan had measurable disease; 6 pts had SD by RECIST, 4 had PD, and 3 were not evaluable. The most common adverse events were alopecia (36%), asthenia (32%), neutropenia (29%), increased creatinine (23%), and thrombocytopenia (19%). No neurotoxicity ≥ grade 2 was observed. Conclusions: Picoplatin was safely administered to patients with CRPC as 1 st -line therapy at 120 mg/m 2 Q3W with full doses of docetaxel and prednisone, resulting in a PSA response rate of 83% of evaluable patients. These results support further development of picoplatin as a novel combination with docetaxel for the treatment of CRPC. [Table: see text]
Prognosis and efficacy of fertility spearing treatment for early stage uterine cervical cancer (CxCa)
Authors: H. Fujiwara, T. Urabe
Journal: Journal of Clinical Oncology (2004)

5130 Background: Patients with early stage CxCa and who desire to spare fertility should be offered uterine spearing treatment. Cervical conization therapy has been shown to be good prognosis for early stage CxCa and efficacy for fertility spearing. Methods: Sixty patients with CxCa (stage 0=59, 1a1=1) received carbon dioxide laser conization therapy between 1994 and 2003. Thirty four patients have received cervical conization therapy during or before pregnant. One pregnant was twin. Cases were matched one-to-one with controls for known risk factors for preterm delivery. The pregnant outcome measures were pregnancy duration, rate of preterm delivery, mode of delivery, low birth weight infants, apgar score (APS) and infants abnormalities. Results: None of the patients with early stage CxCa treated with cervical conization have developed recurrent disease (8–107 months, average 45 months). Thirty three women with singletone pregnancies received cervical conization therapy and 33 controls were included in this study. No difference was found in the rate of duration of pregnancy, preterm delivery, mode of delivery, low birth weight infants, apgar score (APS) and infants abnormalities. Especially, infants from patients received cervical conization therapy were all appropriate for dates, high APS and with no abnormalities. Conclusions: Patients with early stage CxCa treated by cervical conization therapy had good prognosis. The risk of prematurity and infants abnormalities did not increase after carbon dioxide laser conization therapy for early stage CxCa. No significant financial relationships to disclose.
Three stakes in hydrazine sulfate's heart, but questionable cancer remedies, like vampires, always rise again.
Authors: V Herbert
Journal: Journal of Clinical Oncology (1994)

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.1994.12.6.1107 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8201370 Three stakes in hydrazine sulfate's heart, but questionable cancer remedies, like vampires, always rise again. V HerbertxV HerbertSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.6.1107 PDF "Three stakes in hydrazine sulfate's heart, but questionable cancer remedies, like vampires, always rise again.." Journal of Clinical Oncology, 12(6), pp. 1107–1108© 1994 by American Society of Clinical Oncology
Bortezomib ± docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): A phase 2 study
Authors: M. P. Fanucchi, F. Fossella, P. Fidias, R. B. Natale, R. J. Belt, D. P. Carbone, R. Govindan, L. Raez, F. Robert, J. Schiller
Journal: Journal of Clinical Oncology (2005)

7034 Background: Bortezomib (VELCADE, Vc, Millennium Pharmaceuticals), a novel proteasome inhibitor, has demonstrated activity against NSCLC as monotherapy in preclinical and phase 1 studies. At the interim analysis of this randomized, multicenter phase 2 study (J Clin Oncol. 2004;22[suppl 14s]:643s), efficacy criteria for continuing the study were met, and toxicity was manageable. Thus, enrollment continued to the full accrual goal, targeted at 155 patients (pts). Methods: Major eligibility criteria: age ≥ 18 y, stage IIIB or IV NSCLC, Karnofsky performance score (KPS) ≥ 70%, and 1 prior chemotherapy regimen. Arm A received Vc 1.5 mg/m2 IV bolus on d 1, 4, 8, and 11 q 21d. Arm B received dexamethasone premedication, docetaxel (TAXOTERE, Tax) 75 mg/m2 IV over 1 hr on d 1 and Vc 1.3 mg/m2 (1 hr after Tax) on d 1, 4, 8, and 11 q 21 d. The primary objective was to assess response to Vc ± Tax. Secondary objectives were safety, tolerability, survival, pharmacokinetics, pharmacodynamics, and pharmacogenomics. Results: 155 pts were enrolled, and data are currently available for the first 62 pts. Arm A had 30 pts, median age 63 y (range, 40–78), 83% prior paclitaxel, 80% KPS ≥ 80%. Arm B had 32 pts, median age 65 y (range, 20–82), 66% prior paclitaxel, 88% KPS ≥ 80%. Arm A demonstrated a partial response (PR) rate by RECIST of 10.0% (3/30). In arm B, the PR rate was 15.6% (5/32), and toxicities were manageable. Median time to progression was 42.5 d in arm A and 86 d in arm B; median duration of response was 299 d (9.8 mo) in arm A and has not yet been reached in arm B, but it is at least 9.8+ mo after a median follow-up of 8.0 mo (n = 5). The median duration of disease stabilization (complete response, PR, or stable disease) was 126 d (4.1 mo) in arm A (n = 8) and 160 d (5.3 mo) in arm B (n = 19). Treatment was well tolerated on both arms. The most common ≥ grade 3 events were dehydration, nausea, and vomiting in arm A, and neutropenia, fatigue, and diarrhea in arm B. Conclusion: Vc demonstrates encouraging activity in pts with NSCLC, both as a single agent and in combination with Tax, and toxicities are manageable. The final analysis is ongoing; updated results for all 158 pts will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, EMD, Genentech, Millennium, Taiho Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Lilly Oncology, Merck, Pfizer, Taiho AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Ligand, Lilly Oncology, Millennium, Pfizer AstraZeneca Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly
Abstract 18406: Gender Influence on the Functional Significance of Intermediate Coronary Artery Stenosis
Authors: Ju-Hee Lee, Bon-Kwon Koo, Kyung-Woo Park, Ben-Dor Itsik, Ron Waksman, Augusto Pichard, Chang-Wook Nam, Joon-Hyung Doh, Naotaka Murata, Nob Tanaka, Chi-Hang Lee, Nieves Gonzalo, Javier Escaned, Marco A Costa, Takashi Kubo, Takashi Akasaka, Xinyang Hu, Jian-An Wang, Hyung-Mo Yang, Myeong-Ho Yoon, Seung-Jae Tahk, Hyo-Soo Kim
Journal: Circulation (2012)

Background Previous studies suggest that there are clinically relevant differences between women and men in patients with ischemic heart disease. However, little is known about the gender influence on the functional significance of coronary artery stenosis. Method A total of 1,032 lesions with available intravascular ultrasound (IVUS) and fractional flow reserve (FFR) were recruited from 11 international centers and 881 de novo lesions with intermediate stenosis located at the non-left main major epicardial coronary arteries (822 patients, male 70.6%) were included in this analysis. All data were analyzed at Seoul National University Data Management Core Laboratory. FFR ≤0.8 was considered functionally significant. Results Angiographic % diameter stenosis and reference diameter were 49.6±12.7 and 3.0±0.5 mm, respectively. Minimum luminal area (MLA) by IVUS was 3.12±1.34mm 2 . Mean FFR was 0.81±0.11 and 353 lesions (40.1%) were functionally significant. There were no differences in angiographic lesion severity and IVUS MLA between male and female patients (Table). However, compared to female patients, FFR was significantly lower in male (male: 0.81±0.11 vs. female: 0.83±0.10, P =0.010) and functionally significant stenosis was more frequent in male patients (FFR ≤0.8; male: 42.8% vs. female: 32.9%, P =0.007). The best cutoff value of angiographic % diameter stenosis to determine the functional significance was 49.4% in male and 53.0% in female patients. The best cutoff value of IVUS MLA was 3.25 mm 2 in male and 3.05 mm 2 in female patients. Conclusion Compared to male patients, female patients may have higher anatomical threshold for the functional significance of coronary artery stenosis.
The use of ErbB/HER activation status as prognostic markers in breast cancer patients treated with trastuzumab
Authors: A. Mukherjee
Journal: Journal of Clinical Oncology (2005)

553 Background: 30 percent of breast cancer patients overexpress the erbB2 (HER 2/neu) tyrosine kinase receptor. Tumors that overexpress this cell-surface receptor exhibit a malignant phenotype and can be treated with Herceptin, an antibody raised against HER2. Since only about 40 percent of those treated with Herceptin respond to this therapy, the levels of other erbB receptors are likely to contribute to disease progression. The development of a quantitative assay for erbB receptors will be invaluable to accurately diagnose and treat breast cancer. Methods: We used multiplexed proximity-based eTag technology to analyze breast tissue biopsies from 32 breast cancer patients treated with Herceptin. We determined total receptor expression, homo/heterodimer formation and phosphorylation states of HER receptors on formalin-fixed, paraffin-embedded tissue sections. The data from these studies was then used to correlate with patient responsiveness to Herceptin. Results: The patients were divided into three groups based on their HER 2 activation level. In the first group, patients exhibited high levels of HER 2/2 dimer expression and were non-responders. In group two, patients showed low levels of HER 2 homodimers and responded to Herceptin treatment. In the last group, all patients expressed moderate levels of HER 2 homodimers. Those in this group that exhibited very high receptor heterodimers presented progressive disease. The other patients in this group had a low heterodimer levels showed stable disease. Conclusions: The eTag assay facilitates analysis of erbB receptor expression and activation in patient biopsies. We have found that heterodimer to homodimer ratio correlates with the outcome of Herceptin treatment in breast cancer patients. A larger study with a hundred Herceptin-treated patients is being undertaken to further assess the clinical utility of eTag assays in the selection of patients for receptor-targeted therapies. No significant financial relationships to disclose.