tbuckley/cabot-search huggingface dataset:
Chemotherapy Response in East Asian Non-small Cell Lung Cancer Patients Harboring Wild-Type or Activating Mutation of Epidermal Growth Factor Receptors
Authors: Chia-Chi Lin, Hsin-Hsin Hsu, Chia-Tung Sun, Jin-Yuan Shih, Zhong-Zhe Lin, Chong-Jen Yu, George G. Chen, Michael Kuan Yew Hsin, Kwok Chi Lam, Linda Leung, Chih-Hsin Yang, Tony Mok
Journal: Journal of Thoracic Oncology (2010)
In vitro susceptibility of non-tuberculous mycobacterial strains against moxifloxacin
Authors: Timo Weiss, Nicolas Schönfeld, Thomas Bergmann, Harald Mauch, Torsten Blum, Holger Rüssmann, Torsten Thomas Bauer
Journal: European Respiratory Journal (2012)

Introduction  Pulmonary infections due to non-tuberculous mycobacteria (NTM) are a clinical challenge. There are to date no recommendations for the use of potential second line drugs, when first line treatment failures. For Moxifloxacin, in vitro susceptibility could be shown for M. avium-komplex (MAC), but almost no data available on its in vitro effectivity against various other NTM species.  Methods  From 100 NTM-positive cultures other than MAC isolated at our center during 2003-2010 (9 M. fortuitum, 2 M. chelonae, 6 M. gordonae, 5 M. marinum and 78 M. kansasii), we tested the minimal inhibitory concentrations (MIC) of moxifloxacin and thus the sensitivity(breakpoint ≤ 2 µg/ml). Culturing and resistance testing was performed on solid Middlebrook agar plates (7H11) by agar dilution.  Results  Out of 100 tested NTM-positive cultures, 98 (98%) showed sensitivity to moxifloxacin at. Only two strains (M. fortuitum and M. chelonae) showed higher MIC.  Conclusions  Our study revealed a high sensitivity rate of moxifloxacin against several NTM strains other than MAC in vitro. Despite the absence of clinical treatment studies, we see a potential use of moxifloxacin as a second line drug.
Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer
Authors: Ping Li, Ru Yang, Wei-Qiang Gao
Journal: Molecular Cancer (2014)

An important clinical challenge in prostate cancer therapy is the inevitable transition from androgen-sensitive to castration-resistant and metastatic prostate cancer. Albeit the androgen receptor (AR) signaling axis has been targeted, the biological mechanism underlying the lethal event of androgen independence remains unclear. New emerging evidences indicate that epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) play crucial roles during the development of castration-resistance and metastasis of prostate cancer. Notably, EMT may be a dynamic process. Castration can induce EMT that may enhance the stemness of CSCs, which in turn results in castration-resistance and metastasis. Reverse of EMT may attenuate the stemness of CSCs and inhibit castration-resistance and metastasis. These prospective approaches suggest that therapies target EMT and CSCs may cast a new light on the treatment of castration-resistant prostate cancer (CRPC) in the future. Here we review recent progress of EMT and CSCs in CRPC.
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Authors: Jedd D. Wolchok, Axel Hoos, Steven O'Day, Jeffrey S. Weber, Omid Hamid, Celeste Lebbé, Michele Maio, Michael Binder, Oliver Bohnsack, Geoffrey Nichol, Rachel Humphrey, F. Stephen Hodi
Journal: Clinical Cancer Research (2009)

Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes. Resulting clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions (progressive disease). Response Evaluation Criteria in Solid Tumors or WHO criteria, designed to detect early effects of cytotoxic agents, may not provide a complete assessment of immunotherapeutic agents. Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required.The phase II clinical trial program with ipilimumab, an antibody that blocks CTL antigen-4, represents the most comprehensive data set available to date for an immunotherapeutic agent. Novel immune therapy response criteria proposed, based on the shared experience from community workshops and several investigators, were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma.Ipilimumab monotherapy resulted in four distinct response patterns: (a) shrinkage in baseline lesions, without new lesions; (b) durable stable disease (in some patients followed by a slow, steady decline in total tumor burden); (c) response after an increase in total tumor burden; and (d) response in the presence of new lesions. All patterns were associated with favorable survival.Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria. Further prospective evaluations of the immune-related response criteria, particularly their association with overall survival, are warranted.
The acinar-ductal tango in the pathogenesis of acute pancreatitis
Authors: P. Hegyi, S. Pandol, V. Venglovecz, Z. Rakonczay
Journal: Gut (2010)

There is an unacceptably high mortality in acute pancreatitis, which is due to the lack of specific treatments for the disease. A major reason stated to account for the inability to develop effective treatments is that there are multiple pathobiologic pathways activated in the acinar cell mediating pancreatitis making it difficult to choose molecular targets for therapeutic strategies. However, this reasoning limits opportunities for therapeutic development because it does include another important participant in pancreatitis - the pancreatic duct cells. The most recent advance in pancreatitis research is that depletion of both glycolytic and oxidative ATP synthesis is a common event in both acinar and ductal cells. Although ATP has a very short half-life in the blood and is hydrolysed to ADP, there is clear evidence that encapsulating ATP into liposomes can effectively drive ATP into the cells which can be effective in protecting them from necrosis. In this review, we will examine the effects of different insults associated with pancreatitis on both the acinar and ductal components of the exocrine pancreas pointing out the role of the ductal epithelial responses in both attenuating and increasing the severity of pancreatitis. In addition, we propose that exogenous ATP administration may restore ductal and acinar function providing therapeutic benefit.
Breast Density as a Predictor of Mammographic Detection: Comparison of Interval- and Screen-Detected Cancers
Authors: M. T. Mandelson
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. Methods: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. Results: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95–19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78–32.3). Conclusion: Mammographic breast density appears to be a major risk factor for interval cancer.
11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice
Authors: Anne Hermanowski-Vosatka, James M. Balkovec, Kang Cheng, Howard Y. Chen, Melba Hernandez, Gloria C. Koo, Cheryl B. Le Grand, Zhihua Li, Joseph M. Metzger, Steven S. Mundt, Heather Noonan, Christian N. Nunes, Steven H. Olson, Bill Pikounis, Ning Ren, Nancy Robertson, James M. Schaeffer, Kashmira Shah, Martin S. Springer, Alison M. Strack, Matthias Strowski, Kenneth Wu, TsueiJu Wu, Jianying Xiao, Bei B. Zhang, Samuel D. Wright, Rolf Thieringer
Journal: The Journal of Experimental Medicine (2005)

The enzyme 11β–hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11β-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11β-HSD1 inhibitor lowered body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet-induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides, and free fatty acids, as well as improved glucose tolerance, in a mouse model of type 2 diabetes. Most importantly, inhibition of 11β-HSD1 slowed plaque progression in a murine model of atherosclerosis, the key clinical sequela of metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited 84% less accumulation of aortic total cholesterol, as well as lower serum cholesterol and triglycerides, when treated with an 11β-HSD1 inhibitor. These data provide the first evidence that pharmacologic inhibition of intracellular GC activation can effectively treat atherosclerosis, the key clinical consequence of metabolic syndrome, in addition to its salutary effect on multiple aspects of the metabolic syndrome itself.
Rate and pattern of epithelial cell proliferation in ulcerative colitis.
Authors: E P Serafini, A P Kirk, T J Chambers
Journal: Gut (1981)

We investigated the pattern of proliferation of epithelial cells in rectal mucosa taken from normal individuals and patients with ulcerative colitis by incubating mucosa with tritiated thymidine in vitro and processing for autoradiography. We found that patients with ulcerative colitis in remission showed a proliferative pattern similar to that seen in both regenerating and "precancerous9 mucosa. Patients with a short history were as likely to show this pattern as those with a long history, and this shows that the abnormal pattern does not signify impending malignant change. We also found that mucosa from patients with ulcerative colitis in remission showed an increased proportion of cells synthesising DNA, a proportion surprisingly close to that seen in an active phase; this suggests that the abnormal pattern seen in remission is the pattern of a regenerating mucosa. We feel that this high rate of mucosal turnover, sustained not just during clinically active disease but throughout remission, leads to the increased incidence of carcinoma and to the development of carcinoma in flat mucosa.
Effect of Childhood Obesity Prevention Programs on Blood Pressure
Authors: Li Cai, Yang Wu, Renee F. Wilson, Jodi B. Segal, Miyong T. Kim, Youfa Wang
Journal: Circulation (2014)

Childhood overweight and obesity are associated with elevated blood pressure (BP). However, little is known about how childhood obesity lifestyle prevention programs affect BP. We assessed the effects of childhood obesity prevention programs on BP in children in developed countries. We searched databases up to April 22, 2013, for relevant randomized, controlled trials, quasi-experimental studies, and natural experiments. Studies were included if they applied a diet or physical activity intervention(s) and were followed for ≥ 1 year (or ≥ 6 months for school-based intervention studies); they were excluded if they targeted only overweight/obese subjects or those with a medical condition. In our meta-analysis, intervention effects were calculated for systolic BP and diastolic BP with the use of weighted random-effects models. Of the 23 included intervention studies (involving 18 925 participants), 21 involved a school setting. Our meta-analysis included 19 studies reporting on systolic BP and 18 on diastolic BP. The pooled intervention effect was -1.64 mm Hg (95% confidence interval, -2.56 to -0.71; P=0.001) for systolic BP and -1.44 mm Hg (95% confidence interval, -2.28 to -0.60; P=0.001) for diastolic BP. The combined diet and physical activity interventions led to a significantly greater reduction in both systolic BP and diastolic BP than the diet-only or physical activity-only intervention. Thirteen interventions (46%) had a similar effect on both adiposity-related outcomes and BP, whereas 11 interventions (39%) showed a significant desirable effect on BP but not on adiposity-related outcomes. Obesity prevention programs have a moderate effect on reducing BP, and those targeting both diet and physical activity seem to be more effective.
Alymphoplasia (<i>aly</i>)-Type Nuclear Factor κB–Inducing Kinase (Nik) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-Associated Lymphatic Tissue System
Authors: Sidonia Fagarasan, Reiko Shinkura, Tadashi Kamata, Fumiaki Nogaki, Koichi Ikuta, Kei Tashiro, Tasuku Honjo
Journal: The Journal of Experimental Medicine (2000)

Alymphoplasia (aly) mice, which carry a point mutation in the nuclear factor κB–inducing kinase (NIK) gene, are characterized by the systemic absence of lymph nodes and Peyer's patches, disorganized splenic and thymic architectures, and immunodeficiency. Another unique feature of aly/aly mice is that their peritoneal cavity contains more B1 cells than normal and aly/+ mice. Transfer experiments of peritoneal lymphocytes from aly/aly mice into recombination activating gene (RAG)-2−/− mice revealed that B and T cells fail to migrate to other lymphoid tissues, particularly to the gut-associated lymphatic tissue system. In vivo homing defects of aly/aly peritoneal cells correlated with reduction of their in vitro chemotactic responses to secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC). The migration defect of aly/aly lymphocytes was not due to a lack of expression of chemokines and their receptors, but rather to impaired signal transduction downstream of the receptors for SLC, indicating that NIK is involved in the chemokine signaling pathway known to couple only with G proteins. The results showed that the reduced serum levels of immunoglobulins (Igs) and the absence of class switch to IgA in aly/aly mice are due, at least in part, to a migration defect of lymphocytes to the proper microenvironment where B cells proliferate and differentiate into Ig-producing cells.
Causal Links between RSV Infection and Asthma
Authors: Claudia E. Kuehni, Ben D. Spycher, Michael Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

This is the authors' final version of the paper published in Amercian Journal of Respiratory and Critical Care, 2009, 179(12), pp. 1079-1080. The definitive version is available at http://ajrccm.atsjournals.org/content/vol179/issue12/index.dtl. DOI: 10.1164/rccm.200904-0567ED
Using patients' and rheumatologists' opinions to specify a short form of the WOMAC function subscale
Authors: F Tubach
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> The WOMAC (Western Ontario and McMaster Universities) function subscale is widely used in clinical trials of hip and knee osteoarthritis. Reducing the number of items of the subscale would enhance efficiency and compliance, particularly for use in clinical practice applications. <b>Objective:</b> To develop a short form of the WOMAC function subscale based on patients' and experts' opinions (WOMAC function short form). <b>Methods:</b> WOMAC function subscale data (Likert version) were obtained from 1218 outpatients with painful hip or knee osteoarthritis. These patients and their rheumatologists selected the five items that they considered most in need of improvement. The rheumatologists were asked to select the five items for which patients in general are the most impaired. Items that were least important to patients and experts, those with a high proportion of missing data, and those with a response distribution showing a floor or ceiling response were excluded, along with one of a pair of items with a correlation coefficient &gt;0.75. <b>Results:</b> The WOMAC function short form included items 1, 2, 3, 6, 7, 8, 9, and 15 of the long form. The short form did not differ substantially from the long form in responsiveness (standardised response mean of 0.84 <i>v</i> 0.80). <b>Conclusions:</b> A short form of the WOMAC function subscale was developed according to the views of patients and rheumatologists, based on the responses of 1218 patients and 399 rheumatologists. The clinical relevance and applicability of this WOMAC function subscale short form require further evaluation.
DNA diagnosis for the detection of sickle hemoglobinopathies
Authors: Martin H. Steinberg
Journal: American Journal of Hematology (1993)

Abstract At this time, the sole generally accepted use for DNA diagnosis in the hemoglobinopathies is for the prenatal detection of disease, which can be identified by these means early in the first trimester of pregnancy. By ascertaining genotype rather than phenotype, the confusion that results from diagnostic errors should be diminished. DNA diagnostics are the future of all genetic disease detection and this future will soon be upon us.
Are 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors Renoprotective?
Authors: Vito M. Campese, Mitra K. Nadim, Murray Epstein
Journal: Journal of the American Society of Nephrology (2005)

Statins reduce serum cholesterol and cardiovascular morbidity and mortality. The mechanisms for these beneficial effects are reviewed. Altered inflammatory responses and improved endothelial function mediated by statins are thought to be partly responsible for the reduction of morbidity and mortality as a result of cardiovascular events. In analogy, whether statins confer similar benefits on the kidney has not been established. This review critically considers the available data whereby dyslipidemia mediates renal dysfunction by modulating the inflammatory response to diverse cytokines. Also reviewed is the emerging database indicating that statins may modulate renal function by altering the response of the kidney to dyslipidemia.
In Vitro Induction of Tumor Necrosis Factor , Tumor Cytolysis, and Blast Transformation by Spiroplasma Membranes
Authors: T. Sher, A. Yamin, S. Rottem, R. Gallily
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article In Vitro Induction of Tumor Necrosis Factor α, Tumor Cytolysis, and Blast Transformation by Spiroplasma Membranes Get access Talia Sher, Talia Sher * The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical SchoolJerusalem, Israel Present address: T. Sher, Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Md. * Correspondence to: Talia Sher, Ph.D., BWg. 37, Rm. 3D07, National Institutes of Health, Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar Aviva Yamin, Aviva Yamin The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical SchoolJerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Shlomo Rottem, Shlomo Rottem Department of Membrartes.and Ultra-structure Research, The Hebrew University-Hadassah Medical SchoolJerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth Gallily Ruth Gallily The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical SchoolJerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 13, 4 July 1990, Pages 1142–1145, https://doi.org/10.1093/jnci/82.13.1142 Published: 04 July 1990 Article history Received: 17 November 1989 Revision received: 11 April 1990 Accepted: 12 April 1990 Published: 04 July 1990
Combined Inhibition of Janus Kinase 1/2 for the Treatment of JAK2V617F-Driven Neoplasms: Selective Effects on Mutant Cells and Improvements in Measures of Disease Severity
Authors: Phillip C.C. Liu, Eian Caulder, Jun Li, Paul Waeltz, Alex Margulis, Richard Wynn, Mary Becker-Pasha, Yanlong Li, Erin Crowgey, Gregory Hollis, Patrick Haley, Richard B. Sparks, Andrew P. Combs, James D. Rodgers, Timothy C. Burn, Kris Vaddi, Jordan S. Fridman
Journal: Clinical Cancer Research (2009)

Deregulation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is a hallmark for the Philadelphia chromosome-negative myeloproliferative diseases polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We tested the efficacy of a selective JAK1/2 inhibitor in cellular and in vivo models of JAK2-driven malignancy.A novel inhibitor of JAK1/2 was characterized using kinase assays. Cellular effects of this compound were measured in cell lines bearing the JAK2V617F or JAK1V658F mutation, and its antiproliferative activity against primary polycythemiavera patient cells was determined using clonogenic assays. Antineoplastic activity in vivo was determined using a JAK2V617F-driven xenograft model, and effects of the compound on survival, organomegaly, body weight, and disease-associated inflammatory markers were measured.INCB16562 potently inhibited proliferation of cell lines and primary cells from PV patients carrying the JAK2V617F or JAK1V658F mutation by blocking JAK-STAT signaling and inducing apoptosis. In vivo, INCB16562 reduced malignant cell burden, reversed splenomegaly and normalized splenic architecture, improved body weight gains, and extended survival in a model of JAK2V617F-driven hematologic malignancy. Moreover, these mice suffered from markedly elevated levels of inflammatory cytokines, similar to advanced myeloproliferative disease patients, which was reversed upon treatment.These data showed that administration of the dual JAK1/2 inhibitor INCB16562 reduces malignant cell burden, normalizes spleen size and architecture, suppresses inflammatory cytokines, improves weight gain, and extends survival in a rodent model of JAK2V617F-driven hematologic malignancy. Thus, selective inhibitors of JAK1 and JAK2 represent a novel therapy for the patients with myeloproliferative diseases and other neoplasms associated with JAK dysregulation.