tbuckley/cabot-search huggingface dataset:
Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer.
Authors: S Wojtowicz-Praga, J Torri, M Johnson, V Steen, J Marshall, E Ness, R Dickson, M Sale, H S Rasmussen, T A Chiodo, M J Hawkins
Journal: Journal of Clinical Oncology (1998)

PURPOSE This phase I study was performed to evaluate the safety and pharmacokinetics of escalating doses of Marimastat (British Biotech, Inc, Oxford, United Kingdom) in patients with advanced malignancies and to determine the phase II recommended dose to be used in subsequent studies. PATIENTS AND METHODS A standard phase I design was used in this study, in which consecutive groups of three patients were treated with escalating doses of the study drug. Marimastat was administered orally at 25, 50, or 100 mg twice daily to consecutive groups of patients with advanced lung cancer. An additional three patients were added at the highest dose studied (100 mg orally twice daily) to assess whether the inflammatory polyarthitis observed at that dose level can be prevented by a concurrent administration of nonsteroidal antiinflammatory drugs (NSAIDS) and/or low-dose corticosteroids. Blood was drawn for safety monitoring, pharmacokinetic analysis, and plasma levels of metalloproteinase (MMP)-2 and MMP-9 (determined by zymography). A total of 12 patients were studied. RESULTS The most significant toxicity at the highest dose studied (100 mg orally twice daily) was a symptomatic inflammatory polyarthritis that persisted for up to 8 weeks after discontinuation of the study drug and was dose-limiting. The estimated plasma elimination half-life of Marimastat was 4 to 5 hours. The mean maximum concentration (Cmax) at a reasonably well-tolerated dose (50 mg orally twice daily) was 196 ng/mL and was reached within 1 to 2 hours (Tmax) after administration. Areas under the curve (AUC) tended to correlate with the dose of Marimastat. Zymographic analysis of peripheral-blood ratios of activated proenzymatic forms of MMP-2 and -9 did not show any consistent patterns of change in MMP levels or in a degree of their activation during the course of treatment. CONCLUSION Marimastat was well absorbed from the gastrointestinal tract, with high levels of the study drug detected in plasma within hours after drug administration. Plasma concentrations of Marimastat achieved at dose levels 2 and 3 (50 mg and 100 mg orally twice daily) were substantially higher than those required for MMP inhibition in vitro. The dose-limiting toxicity (DLT) was severe inflammatory polyarthritis, which seemed to be a cumulative toxicity.
Importance of further follow up in patients with negative histology from CT guided biopsy
Authors: Axel Sylvan, Yin Liu, Tom Houghton, Choong Poon, Ram Sundar, Imran Aziz
Journal: European Respiratory Journal (2012)

Background : Obtaining conclusive histology to diagnose lung cancer is an important part of the management of potential lung cancer patients. Due to recent advancement in the techniques CT guided biopsy is becoming increasingly important in obtaining histology samples. We describe our experience of usefulness of CT guided biopsy samples over 4 years and follow-up of negative histology samples in suspected lung cancer patients.   Results : We collected samples over 4 years (2008-2011) of CT guided biopsy booked in our hospital. 314 procedures were planned in 313 patients. 292 procedures were carried out. The main reason for not carrying out the procedure was shrinkage of the mass seen on the day of the procedure.  234/292 (80.1%) confirmed the diagnosis of lung cancer. 10/292 (3.4%) lead to diagnosis of other cancers (myeloma, metastatic cancer, lymphoma). 42/292 (14.8%) showed non-cancers (mainly inflammation). The biopsy was inconclusive in 6/292 (2%) samples.  The 81 patients who did not have a biopsy or were labelled as non-lung cancers, underwent further investigation or had clinical diagnosis due to ill health. 26/81 (32.1%) had lung cancer, 14/75 (17.3%) had other cancers, 41/81 (50.6%) did not have a cancer diagnosis after follow up.   Conclusions : We have shown that CT guided biopsy provides us with good histology samples and if correct patients are identified the histological diagnosis rate is greater than 90%. At the same time the patients with a high suspicion and negative biopsy have approximately 1 in 3 chance of having a lung cancer. It is therefore recommended that patients with negative histology should have further diagnostic tests.
Multi-Institutional Phase I/II Trial of Paclitaxel, Cisplatin, and Etoposide With Concurrent Radiation for Limited-Stage Small-Cell Lung Carcinoma
Authors: Nathan Levitan, Afshin Dowlati, Donald Shina, Mark Craffey, Wilma Mackay, Russell DeVore, James Jett, Scot C. Remick, Alex Chang, David Johnson
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP) and thoracic radiotherapy. PATIENTS AND METHODS: Thirty-one patients were enrolled onto this study. During the phase I section of this study, the dose of paclitaxel was escalated in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escalation schema at doses of 100, 135, or 170 mg/m 2 intravenously over 3 hours on day 1. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study. For cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m 2 in all patients. On day 2, cisplatin 60 mg/m 2 was administered for all cycles. On days 1, 2, and 3, etoposide 60 mg/m 2 /d (cycles 1 and 2) or 80 mg/m 2 /d (cycles 3 and 4) was administered. Chest radiation was given at 9 Gy/wk in five fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-stimulating factors were used during cycles 3 and 4 only. RESULTS: Twenty-eight patients were assessable. The MTD of paclitaxel was 135 mg/m 2 , with the dose-limiting toxicity being grade 4 neutropenia. Cycles 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fever occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate was 96% (complete responses, 39%; partial responses, 57%). After a median follow-up period of 23 months (range, 9 to 40 months), the median survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 months) CONCLUSION: The MTD of paclitaxel with radiation and EP treatment is 135 mg/m 2 given over 3 hours. In this schedule of administration, a high response rate and acceptable toxicity can be anticipated.
Sarcoidosis and acquired type II-b hyperlipoproteinaemia
Authors: S Umeki, Y Niki, R Soejima
Journal: European Respiratory Journal (1988)

In four of eleven patients with histologically-proven sarcoidosis (stage II or III), type II-b hyperlipoproteinaemia (HLP) with increased levels of total cholesterol, triglycerides and low density lipoprotein, and a decreased level of high density lipoprotein was observed. These results suggest that type II-b HLP may be associated with sarcoidosis with systemic sarcoid infiltration (stage II or III).
Effects of PEEP-like cyclic stretch on the IL-6 protein production in normal human pulmonary artery endothelial cells in vitro
Authors: Kozue Kobayashi, Hidenori Inaoka, Satoru Nebuya, Yutaka Fukuoka, Kenichi Kokubo, Hirosuke Kobayashi, Makoto Noshiro
Journal: European Respiratory Journal (2012)

Background and Aim: Excessive cyclic stretch is one of the main causes of ventilator-induced lung injury. However, the molecular mechanisms of the injury by cyclic stretch have not yet been fully understood. The aim of the present study was to examine the effects of PEEP-like cyclic stretch on the IL-6 protein production in human pulmonary artery endothelial cells (HPAECs) in vitro .

Methods: Normal HPAECs were stretched by a FlexcellR FX-4000T™ Tension System (Flexcell International). The stretching rate was 15 cycles/minute, and the cells were cyclicly stretched from 0 to 5%, 0 to 10%, 0 to 20%, 3 to 20% and 5 to 20%. Stretch from 3 to 20% and from 5 to 20% simulated excessive stretch during mechanical ventilation with PEEP. The cells were stretched for various durations (0, 1, 3, 6 and 12 hours). During the experiments, culture medium was sampled 0, 3, 6 and 12 hours after stretch started. The IL-6 concentration of the samples was determined by ELISA.

Results : Excessive stretch (0 to 20%) significantly increased the IL-6 production of the cells stretched for more than 3 hours compared to the unstretched cells (n=5, P <0.05), but moderate stretch (0 to 5% and 0 to 10%) did not. PEEP-like stretch (3 to 20% and 5 to 20%) produced no significant changes in the IL-6 protein production of the cells at any sampling points.

Conclusions: The IL-6 protein was produced by excessive cyclic stretch (0 to 20%). However, the IL-6 production was significantly suppressed by PEEP-like cyclic stretch (3 to 20% and 5 to 20%). This result suggests that HPAECs would be protected by PEEP during mechanical ventilation even if the cells are excessively stretched.
Right ventricular (RV) remodelling in PAH: Impact of RV mass/volume ratio on survival
Authors: Carmine Dario Vizza, Roberto Badagliacca, Roberto Poscia, Marco Francone, Serena Marcon, Cristina Gambardella, Silvia Papa, Ilaria Iacucci, Beatrice Pezzuto, Alfred Nona, Francesco Fedele
Journal: European Respiratory Journal (2011)

Pulmonary arterial hypertension (PAH) is characterized by an impressive increase in pulmonary vascular resistances (PVR) that causes severe right ventricular (RV) dysfunction. Because the pathophysiologic model is an afterload mismatch we hypotisize that the best RV adaptation is a concentric hypertrophy (high RV mass/volume ratio (RV M/V)).   Methods:  63 consecutive patients with PAH (50 idiopathic, 13 associated to SSc) who underwent clinical (NYHA class) effort capacity (6MWT, six-minute walk-test) hemodynamic and heart magnetic resonance evaluation as routine work-up at the time of diagnosis. Population was divided in two groups on the basis of median value of RV M/V (cut-off 0,6) and followed-up for deaths (average 2.3 years).   Results:  Patients with RV M/V>0.6 have lower RV systolic and diastolic volumes but similar RV mass compared to patients with RV M/V 0,6 have a lower mortality compared to patients with RV M/V   Conclusion:  In PAH it is possible to identify a subgroup of patients with RV hypertrophy and moderate diastolic volume increase (i.e. high RV mass/volume ratio) which has a low rate of deaths, suggesting a better RV adaptation to the increased afterload.
Physiological Functions of Cyclic ADP-Ribose and NAADP as Calcium Messengers
Authors: Hon Cheung Lee
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The crystal structure of the cyclase has been solved and its active site identified. These two novel nucleotides have now been shown to be involved in a wide range of cellular functions including: cell cycle regulation in Euglena, a protist; gene expression in plants; and in animal systems, from fertilization to neurotransmitter release and long-term depression in brain. A battery of pharmacological reagents have been developed, providing valuable tools for elucidating the physiological functions of these two novel Ca(2+) messengers. This article reviews these recent results and explores the implications of the existence of multiple Ca(2+) messengers and Ca(2+) stores in cells.
Efficacy and safety of perilesional/intralesional triamcinolone injections in oral mucous membrane pemphigoid
Authors: A. Kalinska-Bienias, M. Kalowska, B. Kwiek, B. Jakubowska, N. Ishii, T. Hashimoto, C. Kowalewski, K. Wozniak
Journal: British Journal of Dermatology (2015)

Journal Article Efficacy and safety of perilesional/intralesional triamcinolone injections in oral mucous membrane pemphigoid Get access A. Kalinska‐Bienias, A. Kalinska‐Bienias Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar M. Kalowska, M. Kalowska Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar B. Kwiek, B. Kwiek Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar B. Jakubowska, B. Jakubowska Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar N. Ishii, N. Ishii Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Kurume Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto, T. Hashimoto Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Kurume Japan Search for other works by this author on: Oxford Academic Google Scholar C. Kowalewski, C. Kowalewski Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar K. Wozniak K. Wozniak Department of Dermatology and Immunodermatology Medical University of Warsaw Str. Koszykowa 82a 02‐008 Warsaw Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 436–438, https://doi.org/10.1111/bjd.14043 Published: 01 February 2016
Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma
Authors: L.P. Madhubhani P. Hemachandra, Dong-Hui Shin, Usawadee Dier, James N. Iuliano, Sarah A. Engelberth, Larissa M. Uusitalo, Susan K. Murphy, Nadine Hempel
Journal: Cancer Research (2015)

Epithelial ovarian cancer (EOC) is the fourth leading cause of death due to cancer in women and comprises distinct histologic subtypes, which vary widely in their genetic profiles and tissues of origin. It is therefore imperative to understand the etiology of these distinct diseases. Ovarian clear cell carcinoma (OCCC), a very aggressive subtype, comprises >10% of EOCs. In the present study, we show that mitochondrial superoxide dismutase (Sod2) is highly expressed in OCCC compared with other EOC subtypes. Sod2 is an antioxidant enzyme that converts highly reactive superoxide (O2 (•-)) to hydrogen peroxide (H2O2) and oxygen (O2), and our data demonstrate that Sod2 is protumorigenic and prometastatic in OCCC. Inhibiting Sod2 expression reduces OCCC ES-2 cell tumor growth and metastasis in a chorioallantoic membrane (CAM) model. Similarly, cell proliferation, migration, spheroid attachment and outgrowth on collagen, and Akt phosphorylation are significantly decreased with reduced expression of Sod2. Mechanistically, we show that Sod2 has a dual function in supporting OCCC tumorigenicity and metastatic spread. First, Sod2 maintains highly functional mitochondria, by scavenging O2 (•-), to support the high metabolic activity of OCCC. Second, Sod2 alters the steady-state ROS balance to drive H2O2-mediated migration. While this higher steady-state H2O2 drives prometastatic behavior, it also presents a doubled-edged sword for OCCC, as it pushed the intracellular H2O2 threshold to enable more rapid killing by exogenous sources of H2O2. Understanding the complex interaction of antioxidants and ROS may provide novel therapeutic strategies to pursue for the treatment of this histologic EOC subtype.
When the Oncologist Calls
Authors: Bonnie Salomon
Journal: Annals of Internal Medicine (2015)

Ad Libitum15 September 2015When the Oncologist CallsBonnie Salomon, MDBonnie Salomon, MDFrom Northwestern Lake Forest Hospital, Deerfield, Illinois.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1201 Audio Reading - “When the Oncologist Calls” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "When the Oncologist Calls," by B. Salomon. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail You pick up the phone and hold your breathEven though your breath is what the call is aboutHis voice comes thru fluttering wordsMingling with air, tiny currents of windThat rise, then fall, angelic on your ear.The nodes are smaller, there's less fluid.Then the words float upwards again, taking wingReady to land on snow covered groundTo push life into roots taken holdIn the hard frozen ground.Bonnie Salomon, MDNorthwestern Lake Forest HospitalDeerfield, Illinois Author, Article, and Disclosure InformationAffiliations: From Northwestern Lake Forest Hospital, Deerfield, Illinois.Current Author Address: Bonnie Salomon, MD, Northwestern Lake Forest Hospital, 139 Riverside Drive, Deerfield, IL 60015; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “When the Oncologist Calls” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "When the Oncologist Calls," by B. Salomon. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 15 September 2015Volume 163, Issue 6Page: 488KeywordsFallsHematology and oncologyInterleukins ePublished: 15 September 2015 Issue Published: 15 September 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Activity of Allergenic Proteins from <i>Dermatophagoides pteronyssinus</i>
Authors: U. Wahn, B. Müuller‐Krampe, P. Lind
Journal: Allergy (1985)

Two purified allergens from Dermatophagoides pteronyssinus , Dp 42 (identical to P 1 ) and Dp X were studied for their ability to induce histamine release from washed leukocytes and to bind to IgE antibodies from the serum of 27 mite‐sensitive children. Almost all patients were demonstrated to be sensitive to both proteins by both assays. Dp 42 was found to have the highest allergenic activity, releasing histamine from leukocytes at a median concentration 10 times lower than for Dp X. There was a positive correlation between basophil sensitivity to both proteins and allergen specific serum IgE concentrations.
Behavior of Cervical Epithelium During Carcinogenesis: Autoradiography of Tritiated Cytidine in the C57BL Mouse2
Authors: C. A. Rubio
Journal: JNCI Journal of the National Cancer Institute (1979)

The autoradiographic patterns of the cervical epithelia of 39 virgin C57BL mice after in vivo injection of [3H]cytidine was investigated. Of the 22 animals painted with benzo[a]pyrene for 5 months, 8 developed intraepithelial atypias and 2 had invasive carcinoma. The mean number of silver grains in individual cells increased from histologically normal cervical epithelium through atypical epithelium to invasive carcinoma. It is apparent that the autoradiographic patterns in normal, atypical, and invasive carcinoma cells reflected quantitative differences in cytidine incorporation. These differences may denote increased demand for RNA precursors in the cervical epithelium during carcinogenesis.
Fibrinogen and all-cause mortality in a nationally representative US cohort
Authors: Deepa Valvi, Hana Muellerova, Ruth Tal-Singer, David Mannino
Journal: European Respiratory Journal (2011)

Background:  We aimed to study the association of lung function, fibrinogen and mortality.   Methods:  We analyzed data from 8201 adults aged =>25 years from the National Health and Nutritional Examination Survey (NHANES III). Hazard ratios were calculated to determine the risk of dying (all cause mortality) due to elevated fibrinogen values defined > 400 mg/dL (the top decile) and the interaction with lung function (determined using modified GOLD staging) and adjusted for age, sex, race-ethnicity, smoking, cardiac disease and diabetes.   Results:  3198 subjects (weighted%, 28) died during the follow-up of up to 18 years. The predictors of mortality are shown in the table (normal lung function with a fibrinogen level    Conclusion:  Elevated fibrinogen values are important predictors of death and add to the predictive ability of impaired lung function to predict mortality.
Detecting transcriptionally active regions using genomic tiling arrays.
Authors: Gabor Halasz, Marinus F van Batenburg, Joelle Perusse, Sujun Hua, Xiang-Jun Lu, Kevin P White, Harmen J Bussemaker
Journal: Genome biology (2006)

We have developed a method for interpreting genomic tiling array data, implemented as the program TranscriptionDetector. Probed loci expressed above background are identified by combining replicates in a way that makes minimal assumptions about the data. We performed medium-resolution Anopheles gambiae tiling array experiments and found extensive transcription of both coding and non-coding regions. Our method also showed improved detection of transcriptional units when applied to high-density tiling array data for ten human chromosomes.
Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group.
Authors: C A Sklar, L L Robison, M E Nesbit, H N Sather, A T Meadows, J A Ortega, T H Kim, G D Hammond
Journal: Journal of Clinical Oncology (1990)

Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.