tbuckley/cabot-search huggingface dataset:
Platinum-Induced Ototoxicity in Children: A Consensus Review on Mechanisms, Predisposition, and Protection, Including a New International Society of Pediatric Oncology Boston Ototoxicity Scale
Authors: Penelope R. Brock, Kristin R. Knight, David R. Freyer, Kathleen C.M. Campbell, Peter S. Steyger, Brian W. Blakley, Shahrad R. Rassekh, Kay W. Chang, Brian J. Fligor, Kaukab Rajput, Michael Sullivan, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2012)

The platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important.This review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection.Platinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss.Collaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.
Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1-MMP activities
Authors: K. W. Lee, N. J. Kang, M.-H. Oak, M. K. Hwang, J. H. Kim, V. B. Schini-Kerth, H. J. Lee
Journal: Cardiovascular Research (2008)

Expression and activation of matrix metalloproteinase (MMP)-2 play pivotal roles in the migration and invasion of human aortic vascular smooth muscle cells (VSMC) originating from normal human tissue, which is strongly linked to atherosclerosis. The present study investigated the possible inhibitory effects of cocoa procyanidin on thrombin-induced expression and activation of MMP-2 in VSMC.Cocoa procyanidin fraction (CPF) and procyanidin B2, one of major procyanidins in cocoa (3 microg/mL and 5 microM, respectively), strongly inhibited thrombin-induced activation and expression of pro-MMP-2 in VSMC, as determined by zymography. The thrombin-induced invasion and migration of VSMC were inhibited by CPF or procyanidin B2 (P < 0.05), as assessed by a modified Boyden chamber and wound healing assays, respectively. An enzymatic assay data demonstrated that CPF and procyanidin B2 directly inhibited membrane type-1 (MT1)-MMP activity (P < 0.05), and this inhibition of CPF was greater than those of red wine polyphenols. Western blot data showed that CPF and procyanidin B2 inhibited thrombin-induced phosphorylation of extracellular signal-regulated protein kinase but not mitogen-activated protein kinase kinase (MEK) in VSMC. Kinase and pull-down data revealed that CPF and procyanidin B2 inhibited MEK1 activity and directly bound with glutathione-S-transferase-MEK1. In addition, the thrombin-induced invasion and migration and the activation and expression of pro-MMP-2 in VSMC were attenuated by U0126 (a well-known inhibitor of MEK1).Cocoa procyanidins are potent inhibitors of MEK and MT1-MMP, and subsequently inhibit the expression and activation of pro-MMP-2, and also the invasion and migration of VSMC, which may in part explain the molecular action of antiatherosclerotic effects of cocoa.
Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: A laser scanning confocal microscopic study
Authors: George Zahrebelski, Anna-Liisa Nieminen, Kristin Al-Ghoul, Ting Qian, Brian Herman, John J. Lemasters
Journal: Hepatology (1995)

The aim of this study was to evaluate changes in the subcellular organelles of cultured hepatocytes by laser scanning confocal microscopy during chemical hypoxia with cyanide and iodoacetate, inhibitors of mitochondrial respiration and glycolysis, respectively. Parameter-specific fluorophores used were calcein for cell topography and membrane permeability, rhodamine-dextran for lysosomes, rhodamine 123 and tetramethylrhodamine methylester (TMRM) for mitochondrial membrane potential (delta psi) and propidium iodide for loss of cell viability. During the first 30 to 40 minutes of chemical hypoxia to cultured hepatocytes, numerous surface blebs formed and cell volume increased, but delta psi decreased relatively little. Subsequently, the nonspecific permeability of mitochondrial membranes increased, and mitochondria depolarized. These events were followed a few minutes later by disintegration of individual lysosomes. After a few more minutes, viability was lost as indicated by bleb rupture, gross plasma membrane permeability to calcein, and nuclear labeling with propidium iodide. Thus, the following sequence of intracellular events occurred during chemical hypoxia: adenosine triphosphate (ATP) depletion, bleb formation with cellular swelling, onset of a mitochondrial permeability transition, disintegration of lysosomes, plasma membrane failure from bleb rupture, and cell death. Any explanation of the pathophysiology of hypoxic injury must take into account this unique sequence of events.
Fish-eye disease: Structural and in vivo metabolic abnormalities of high-density lipoproteins
Authors: Latifa Elkhalil, Zouher Majd, Redouane Bakir, Oscar Perez-Mendez, Graciela Castro, Philippe Poulain, Brigitte Lacroix, Nathalie Duhal, Jean-Charles Fruchart, Gérald Luc
Journal: Metabolism (1997)
Reply: Toward Primary Prevention of Asthma: Role of Corticosteroids for the First Rhinovirus Wheeze
Authors: Tina Hartert, Marc Hershenson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

design, showed that OCS had no overall effect in hospitalized firsttime wheezing children affected by RV (5).However, OCS was found effective in children with high RV genome load (.7,000 copies/mL) in terms of less recurrence in 2-month (HR, 0.2; 95% CI, 0.1-0.7)and 12-month (relative risk, 0.6; 95% CI, 0.4-0.98)follow-ups (5).Similarly, our new, yet unpublished, data from the 5-year follow-up strongly support this long-term effect of OCS in the hospitalized first-time wheezing children with high RV genome load (6).As Feldman and colleagues stated, the biologic mechanisms through which RV may cause asthma include its capacity to modify the epithelial barrier and induce acute and chronic asthma-like cytokine-dependent hyperreactivity and mucous metaplasia, as well as to up-regulate its own receptor, intercellular adhesion molecule-1, in airway mucosa (1).A plausible explanation for the effect of OCS is that it may effectively down-regulate this early and partly atopy-related inflammation in the airways.It is remarkable that we can expect long-term disease-modifying effects by a short course of OCS when it is targeted to high-risk children early.At this time, sensitive RV diagnostics have markedly improved the early identification of children at high risk for asthma.On the basis of these two studies, hospitalized first-time wheezing children affected by RV, especially those with high RV load, are likely to benefit from early OCS in terms of fewer relapses and asthma (2, 3,5).In other words, it seems possible to affect the natural course of asthma inception in the high-risk population by using early and effective intervention.This finding could also provide a novel approach to the mechanisms underlying childhood wheezing and asthma and will encourage us to find future therapeutic interventions to prevent asthma.
Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes: A Prospective Randomized Double-Blind Clinical Trial
Authors: Piero Ruggenenti, Annalisa Perna, Giuseppe Remuzzi
Journal: Diabetes Care (2010)

Sarigianni et al. (1) properly pointed out that in the Ezetimibe and Simvastatin in dyslipidemia of Diabetes (ESD) randomized clinical trial “the serum HDL cholesterol was significantly lower after adding ezetimibe compared with simvastatin monotherapy.” The concomitant reduction in LDL cholesterol observed during simvastatin and ezetimibe combination therapy, however, exceeded the decrease in HDL cholesterol (2). Consequently, the LDL-to-HDL cholesterol ratio decreased from (mean ± SD) 2.11 ± 0.64 at randomization …
SYNTHESIS, INTRACELLULAR DISTRIBUTION, AND SECRETION OF IMMUNOGLOBULIN AND H-2 ANTIGEN IN MURINE SPLENOCYTES
Authors: Dorothee Wernet, Ellen S. Vitetta, Jonathan W. Uhr, Edward A. Boyse
Journal: The Journal of Experimental Medicine (1973)

A/J spleen cells were labeled with [(3)H]leucine and at intervals thereafter were homogenized and separated into microsomes and cell sap. Ig and H-2 antigens were assayed in the cell fractions and cell supernatants using immunoprecipitation. In addition, cells labeled by enzymatic radioiodination were incubated to determine the rates of release of Ig and H-2 antigens from the surface. The results indicate that the majority of Ig and H-2 antigens remain membrane bound throughout their intracellular life. In contrast to Ig, H-2 antigens are neither secreted nor shed from the cell surface. It is suggested that Ig is a peripheral protein of the cell membrane, whereas H-2 antigens are integral ones. The release of Ig on a fragment of plasma membrane could occur at fixed cell surface areas that contain no H-2 antigens or from which they have migrated before release.
Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Marimastat After Response to First-Line Chemotherapy in Patients With Small-Cell Lung Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer
Authors: Frances A. Shepherd, Giuseppe Giaccone, Lesley Seymour, Channa Debruyne, Andrea Bezjak, Vera Hirsh, Michael Smylie, Sheldon Rubin, Heidi Martins, Alan Lamont, Maciej Krzakowski, Anna Sadura, Benny Zee
Journal: Journal of Clinical Oncology (2002)

Increased expression of metalloproteinases is associated with poor prognosis in small-cell lung cancer (SCLC). This trial was undertaken to determine whether adjuvant treatment with the metalloproteinase inhibitor marimastat could prolong survival in responding patients with SCLC after chemotherapy.SCLC patients in complete or partial remission were eligible. They were stratified by radiotherapy (early, late, or none), stage (extensive or limited), response (complete or partial), and cooperative group (National Cancer Institute of Canada-Clinical Trials Group or European Organization for Research and Treatment of Cancer). They were randomized to receive marimastat 10 mg or placebo orally bid for up to 2 years.There were 532 eligible patients (266 marimastat and 266 placebo). Stage was limited for 279 patients (52%) and extensive for 253 (48%). Best response to induction therapy was complete remission for 176 patients (33%), partial remission for 341 (64%), and 15 patients (3%) had undergone surgical resection. The median time to progression for marimastat patients was 4.3 months compared with 4.4 months for placebo patients (P =.81). Median survivals for marimastat and placebo patients were 9.3 months and 9.7 months, respectively (P =.90) Toxicity was generally limited to musculoskeletal symptoms (18% grade 3/4 for marimastat). Dose modifications for musculoskeletal toxicity were required in 90 patients (33%) on the marimastat arm, and 87 (32%) permanently stopped marimastat because of toxicity. Patients on marimastat had significantly poorer quality of life at 3 and 6 months.Treatment with marimastat after induction therapy for SCLC did not result in improved survival and had a negative impact on quality of life.
Radiopotassium Indicator-Dilution Studies During Angiocardiography
Authors: HADLEY L. CONN, CLAUDE R. JOYNER, DONALD F. HEIMAN, HARRY F. ZINSSER
Journal: Circulation Research (1957)

In an attempt to learn more about the physiologic changes in the cardiovascular system during angiocardiography and the nature of mixing of radio-opaque dyes with blood, radiopotassium and Diodrast I 131 dilution curves were obtained before and during angiocardiography. Studies in patients without vulvuar disease and with mitral valvular disease indicated an increased cardiac output during angiocardiography, but the increases were not statistically greater than those following control injections. No difference in indicator-dilution patterns of potassium and Diodrast was demonstrable, suggesting identical circulatory mixing pattterns.
Oncogenic Activation of the RAS/RAF Signaling Pathway Impairs the Response of Metastatic Colorectal Cancers to Anti–Epidermal Growth Factor Receptor Antibody Therapies
Authors: Silvia Benvenuti, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Carlo Zanon, Mauro Moroni, Silvio Veronese, Salvatore Siena, Alberto Bardelli
Journal: Cancer Research (2007)

Abstract Monoclonal antibodies (mAbs) against the extracellular domain of the epidermal growth factor receptor (EGFR) have been introduced for the treatment of metastatic colorectal cancer (mCRC). We have reported recently that increased copy number of the EGFR can predict response to anti-EGFR mAbs and that patients might be selected for treatment based on EGFR copy number. Here, we show that mutations activating the RAS/RAF signaling pathway are also predictive and prognostic indicators in mCRC patients, being inversely correlated with response to anti-EGFR mAbs. In cellular models of CRCs, activation of the RAS signaling pathway by introduction of an activated K-RAS allele (Gly12Val) impairs the therapeutic effect of anti-EGFR mAbs. In cancer cells carrying constitutively active RAS, the pharmacologic inhibition of the mitogen-activated protein kinase (MAPK) signaling cascade improves anti-EGFR treatment based on mAbs. These results have implications for the identification of patients who are likely to respond to anti-EGFR treatment. They also provide the rationale for combination therapies, targeted simultaneously to the EGFR and RAS/RAF/MAPK signaling pathways in CRC patients. [Cancer Res 2007;67(6):2643–8]
The Sarcoidosis Health Questionnaire
Authors: Christopher E. Cox, James F. Donohue, Cynthia D. Brown, Yash P. Kataria, Marc A. Judson
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The Sarcoidosis Health Questionnaire (SHQ) is a health-related quality-of-life (HRQL) instrument we designed in a two-part study to allow patients to describe their satisfaction with life as it is affected by sarcoidosis. In the Development Study, we created the SHQ from a 151-item pool generated from interviews with 107 patients, a search of the relevant literature, and discussion with sarcoidosis experts. Using clinical impact methodology and the questionnaire responses of a separate group of 149 patients, we reduced the total number of items to 29. The final SHQ has three domains: Daily Functioning, Physical Functioning, and Emotional Functioning. In the Validation Study, performed with a different group of 111 patients, we found that the SHQ had good internal consistency reliability, as well as evidence of content, criterion, and construct validity based on its comparison with other measures of HRQL (Medical Outcomes Study 36-Item short form and the St. George's Respiratory Questionnaire) and of mental health (the Center for Epidemiologic Study-Depression Scale), as well as with clinical variables including spirometry. The SHQ alone was sensitive to differences in HRQL based on the number of involved organ systems. In conclusion, we have developed a self-completed HRQL questionnaire for U.S. patients with sarcoidosis.
Paying attention to enthesitis in early untreated arthritis: MRI for the evaluation of enthesitis
Authors: Bo Zhou, Jian Zhu
Journal: Annals of the Rheumatic Diseases (2014)

We read with great interest the report by Paramarta et al 1 related to enthesitis in early untreated arthritis. We really appreciate the work done by the authors. However, there are some issues that need to be further discussed.

First, the author concluded that “the major findings are that the frequency as well as the extent and localisation of enthesitis are similar in SpA and RA”. However, the age of the patients may contribute …
Myc Down-Regulation Sensitizes Melanoma Cells to Radiotherapy by Inhibiting MLH1 and MSH2 Mismatch Repair Proteins
Authors: Barbara Bucci, Igea D'Agnano, Donatella Amendola, Arianna Citti, Giorgio H. Raza, Roberto Miceli, Ugo De Paula, Rodolfo Marchese, Sonia Albini, Armando Felsani, Ercole Brunetti, Aldo Vecchione
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Melanoma patients have a very poor prognosis with a response rate of &amp;lt;1% due to advanced diagnosis. This type of tumor is particularly resistant to conventional chemotherapy and radiotherapy, and the surgery remains the principal treatment for patients with localized melanoma. For this reason, there is particular interest in the melanoma biological therapy. Experimental Design: Using two p53 mutant melanoma models stably expressing an inducible c-myc antisense RNA, we have investigated whether Myc protein down-regulation could render melanoma cells more susceptible to radiotherapy, reestablishing apoptotic p53-independent pathway. In addition to address the role of p53 in the activation of apoptosis, we studied the effect of Myc down-regulation on radiotherapy sensitivity also in a p53 wild-type melanoma cell line. Results: Myc down-regulation is able per se to induce apoptosis in a fraction of the cell population (∼40% at 72 hours) and in combination with γ radiation efficiently enhances the death process. In fact, ∼80% of apoptotic cells are evident in Myc down-regulated cells exposed to γ radiation for 72 hours compared with ∼13% observed after only γ radiation treatment. Consistent with the enhanced apoptosis is the inhibition of the MLH1 and MSH2 mismatch repair proteins, which, preventing the correction of ionizing radiation mismatches occurring during DNA replication, renders the cells more prone to radiation-induced apoptosis. Conclusions: Data herein reported show that Myc down-regulation lowers the apoptotic threshold in melanoma cells by inhibiting MLH1 and MSH2 proteins, thus increasing cell sensitivity to γ radiation in a p53-independent fashion. Our results indicate the basis for developing new antitumoral therapeutic strategy, improving the management of melanoma patients.
Reply to the letter to the editor ‘Ablative therapies for lung metastases: a need to acknowledge the efficacy and toxicity of stereotactic ablative body radiotherapy’ by Siva et al.
Authors: T. de Baère, A. Aupérin, F. Deschamps, P. Chevallier, Y. Gaubert, V. Boige, M. Fonck, B. Escudier, J. Palussiére
Journal: Annals of Oncology (2015)
BAG-1 in Core Biopsies, Tissue Microarrays and Surgical Samples– Investigation of a Novel Apoptosis Biomarker in Two Independent Breast Cancer Cohorts
Authors: Q. Romero, O. Bjarnadottir, P. Bendahl, M. Klintman, M. Fernö, D. Grabau, S. Borgquist
Journal: Annals of Oncology (2013)
Persistence of Medical Change at Implementation of Clinical Guidelines on Medical Practice: A Controlled Study in a Cancer Network
Authors: Isabelle Ray-Coquard, Thierry Philip, Guy de Laroche, Xavier Froger, Jean-Philippe Suchaud, Alain Voloch, Hélène Mathieu-Daudé, Antoine Lurkin, Fadila Farsi, Pierre Bertrand, Franck Chauvin
Journal: Journal of Clinical Oncology (2005)

Purpose A cancer network of general or private hospitals of a French region was started in 1995 for improving quality of care and rationalizing medical prescriptions. The impact of implementing a clinical practice guidelines (CPG) project assessed conformity with guidelines in medical practice; significant changes were observed within the network, whereas no changes were observed in a control region without cancer network. In the present study, we evaluated the persistence of conformity to guidelines through a new medical audit. Patients and Methods In 1999, the hospitals of the previously compared experimental and control groups accepted to reassess the impact of CPG. A controlled transversal study was performed in the experimental group (cancer network) and in the control group (no regional cancer network). In 1996 (first audit) and in 1999 (present audit), all new patients with colon cancer (177 and 200 in experimental group and 118 and 100 in control group, respectively) and early breast cancer (444 and 381 in experimental group and 172 and 204 in control group, respectively) were selected. Results In the experimental group, the compliance of medical decisions with CPG was significantly higher in 1999 than in 1996 for colon cancer (73%; 95% CI, 67% to 79% v 56%; 95% CI, 49% to 63%, respectively; P = .003) and similar for the two periods for breast cancer (36%; 95% CI, 31% to 41% v 40%; 95% CI, 35% to 44%, respectively; P = .24). In the control group, compliance was significantly higher in 1999 than in 1996 for colon cancer (67%; 95% CI, 58% to 76% v 38%; 95% CI, 29% to 47%, respectively; P &lt; .001) and identical for the two periods for breast cancer (4%; 95% CI, 1% to 7% v 7%; 95% CI, 3% to 11%, respectively; P = .19). Conclusion The CPG program for cancer management produced persistent changes in medical practice in our cancer network in terms of conformity with CPG.