tbuckley/cabot-search huggingface dataset:
Rituximab and progressive multifocal leukoencephalopathy: A report of 35 cases
Authors: K. R. Carson, A. M. Evens, L. I. Gordon, J. F. Seymour, S. T. Rosen, N. Gottardi-Littell, K. Muro, E. Richey, C. L. Bennett
Journal: Journal of Clinical Oncology (2008)

8531 Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the brain caused by the reactivation of latent JC polyoma virus. PML is associated with profound immunosuppression such as: HIV, stem cell transplantation (SCT), purine analog therapy, organ transplantation, or lymphoma. Rituximab (R) is a B-cell depleting, monoclonal antibody, linked to the reactivation of hepatitis B and other viruses. We evaluated the characteristics of patients who developed PML after exposure to R, including T-cell and immunoglobulin studies, when available. Methods: Data sources included clinical observations of the authors, reports from the FDA MedWatch database, medical literature cases, and reports from the manufacturer, Genentech, that were submitted to the FDA. Reports that did not confirm PML diagnosis or were associated with known HIV were excluded. Results: Of 51 unique cases identified, 2 were excluded for HIV, and 14 for inadequate confirmation of PML. In the 35 remaining cases, survival for 1 year after PML diagnosis was reported in just three patients (9%). Diagnosis was made by brain biopsy (n=10), autopsy (n=6), or MRI of brain AND positive JC virus PCR (n=19). Indications for R were lymphoproliferative disorder (n=33) and systemic lupus erythematosus (n=2). Median age was 63 years (range 30–89), with 19 female and 16 male patients. Seven cases were seen after SCT, 5 autologous and 2 allogeneic. In the 28 remaining patients, 10 received purine analog therapy and 24 received an alkylating agent. T-cell studies were obtained on 9 patients (Table). Conclusions: Eight of 9 patients with complete T-cell studies had abnormal CD4/CD8 ratios or severe T-cell lymphopenia with CD4 count <100. This suggests that dysregulation of the cellular immune system may contribute to the development of PML after treatment with R and chemotherapy. Prospective study of T-cell changes following R administration would allow better understanding of the potential contribution of R to T-cell dysregulation and viral reactivation. T-cell and immunoglobulin studies Case Transplant Indication CD4+ (cells/μl) CD8+ (cells/μl) CD4/CD8 Ratio IgG (mg/dl) IgA (mg/dl) IgM (mg/dl) 1 Allo ALL 1059 3453 0.31 69 151 96 2 Auto Follicular NHL 234 1015 0.23 501 62 N/A 3 Auto NHL 89 41 2.17 627 58 19 4 Auto NHL 551 2596 0.21 163 17 2 5 None CLL 287 311 0.92 448 213 316 6 None DLBCL 94 243 0.39 603 41 355 7 None Mantle cell NHL 110 310 0.35 770 195 91 8 None Waldenstrom 2100 6200 0.34 N/A N/A N/A 9 None SLE 71 57 1.25 N/A N/A N/A N/A denotes not available Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech
DUOX1-mediated hydrogen peroxide release regulates sodium transport in bronchiolar epithelial cells
Authors: Vadim Shlyonsky, Myrna Virreira, Frédérique Mies, Arnaud Goolaerts, Robert Naeije, Renaud Beauwens, Alain Boom
Journal: European Respiratory Journal (2011)

Clara-like H441 cells grown on non porous support form epithelial domes in the presence of dexamethasone. This reflects an increase in expression and activity of amiloride inhibitable epithelial sodium channels, ENaC. Dexamethasone has been also shown to facilitate the expression of NADPH oxidase DUOX1 in lung fetal cells. We assessed the role of DUOX1 and submillimolar ( 2 O 2  on both ENaC expression and activity in H441 cells. Cells forming epithelial domes induced by dexamethasone (0.1 μM, 24h) and by another differentiation agent 5-aza-29-deoxytidine (5AZA, 1 μM, 48h) expressed higher amounts of DUOX1 as evidenced by RT-PCR and immunocytochemistry. Dome induction by dexamethasone and 5AZA can be inhibited by exogenous catalase in concentration-dependent manner (5-10 kU/ml) and by the NADPH oxidase inhibitor diphenyl iodonium (2.5 μM), thus suggesting the involvement of H 2 O 2 . Single application of 0.2 mM H 2 O 2  induced transient dome formation. Dexamethasone stimulated mRNA expression of all the subunits of ENaC, however this expression was not inhibited by catalase, thus suggesting that H 2 O 2  increased only the channel activity. In patch-clamp experiments, H 2 O 2  (0.1 mM) activated amiloride-sensitive whole-cell currents from 3.91±0.79 pA/pF to 4.76±0.98 pA/pF (p=0.01) as well as ENaC single-channel activity in cell-attached patches. These observations suggest that tonic production of H 2 O 2  by DUOX1 maintains the level of vectoral sodium transport by lung alveolar cells. They also suggest that the upregulation of DUOX-mediated H 2 O 2  release observed in cystic fibrosis (CF) may contribute to the hyperabsorptive epithelial cell phenotype observed in CF lung disease.
Abstract 12375: Inhibition of ERS Leads to Cardioprotection against Ischemia Reperfusion Injury by Preventing the mPTP Opening
Authors: Jinkun Xi, Yonggui He, Yidong Zhang, Huan Zheng, Yuxi Xie, Wangfang Li, Zhelong Xu
Journal: Circulation (2012)

While it is well known that endoplasmic reticulum stress (ERS) plays an important role in myocardial ischemia/reperfusion (I/R) injury and inhibition of ERS leads to cardioprotection against I/R in...
Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma—results from the DIRECTOR trial
Authors: Bogdana Suchorska, Michael Weller, Ghazaleh Tabatabai, Christian Senft, Peter Hau, Michael C Sabel, Ulrich Herrlinger, Ralf Ketter, Uwe Schlegel, Christine Marosi, Guido Reifenberger, Wolfgang Wick, Jörg C Tonn, Hans-Georg Wirsching
Journal: Neuro-Oncology (2016)

The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM.We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast-enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS2) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals.Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS2 (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5-18.2] vs 6.5 mo [95% CI: 3.6-9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups.Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved.
Predictive value for engraftment and survival of total nucleated cell dose (TNC) as compared to CD34+ cell dose after autologous and allogeneic bone marrow transplant (BMT) for hematologic malignancies
Authors: C. A. Brown, S. Mineishi, M. Jagasia, J. P. Greer, K. Ruffner, D. S. Morgan, R. S. Stein, F. G. Schuening, A. A. Kassim
Journal: Journal of Clinical Oncology (2005)

6706 Background: An adequate dose of CD34+ cells is necessary for autologous (auto) or allogeneic (allo) transplants of peripheral blood stem cells (PBSC), to ensure engraftment. CD34+ cell dose is predictive of survival, morbidity and rate of engraftment following allo BMT. High TNC doses have been found to influence the outcome of auto and allo BMT favorably. A low CD34+ cell dose results in higher mortality and poor survival after PBSC and marrow stem cell transplantation from an HLA-identical sibling. There are no comparative data on the relationship of TNC dose and CD34+ cell dose of unmanipulated marrow on transplant outcome. Methods: 54 patients received BMT from HLA-identical sibling donors between January 1999 and June 2004. 29 (51%) patients had CML, 13(24%) AML, five (9%) NHL, four (7%) MDS, three (5%) ALL, one (2%) CLL, one (2%) Myelofibrosis, one (2%) MM, one (2%) HD and one (2%) Aplastic Anemia. Nine patients received auto, G-CSF mobilized marrow, after failing PBSC collection (7 NHL, 1 HD and 1 MM). TNC and CD34+ cell doses of each graft were analyzed. Results: There was no correlation between the TNC and the CD34+ cell content of the grafts in either allo or auto BMT. The median TNC and CD34+ cell doses were 3.16 x 108/kg and 3.67 x 106/kg respectively for allo patients and 3.62 x 108/kg and 1.61 x 106/kg for auto patients. In allo patients, TNC dose above 3.16 x 108/kg correlated with better neutrophil (p=0.0130) and platelet engraftment (p=0.0002), while CD34+ cell dose above 3.67 x 106/kg correlated with better platelet engraftment (p= 0.0221). TNC and CD34+ cell doses were not predictive of overall survival in allo patients. CD34+ cell dose correlated with platelet engraftment (p= 0.0448) in auto patients. Average neutrophil recovery time was 20 days in both auto and allo patients, while platelet recovery time was 29 days for allo and 48 days for auto. Conclusions: For patients undergoing allo BMT, CD34+ count in the allograft may not add valuable information, while in patients who failed auto PBSC mobilization and undergoing BMT, CD34+ counts may add useful information, particularly for platelet engraftment. No significant financial relationships to disclose.
DSM-5® Handbook on the Cultural Formulation Interviewedited by Roberto Lewis-Fernández, M.D., M.T.S., Neil Krishan Aggarwal, M.D., M.B.A., M.A., Ladson Hinton, M.D., Devon E. Hinton, M.D., Ph.D., and Laurence J. Kirmayer, M.D., F.R.C.P.C. Washington, D.C., American Psychiatric Association Publishing, 2016, 364 pp., $65.00 (paperback).
Authors: Rajiv Radhakrishnan
Journal: American Journal of Psychiatry (2016)
Tumor-Associated Antigens in Cervical Cancer Tissues and in Sera From Patients With Cervical Cancer or With Head and Neck Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A N Ibrahim, R A Robinson, L Marr, A T Abdelal, A J Nahmias
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Tumor-Associated Antigens in Cervical Cancer Tissues and in Sera From Patients With Cervical Cancer or With Head and Neck Cancer Get access Adly N. Ibrahim, Adly N. Ibrahim Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth Ann Robinson, Ruth Ann Robinson Search for other works by this author on: Oxford Academic PubMed Google Scholar Lee Marr, Lee Marr Search for other works by this author on: Oxford Academic PubMed Google Scholar Ahmed T. H. Abdelal, Ahmed T. H. Abdelal Search for other works by this author on: Oxford Academic PubMed Google Scholar Andre J. Nahmias Andre J. Nahmias Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 2, August 1979, Pages 319–323, https://doi.org/10.1093/jnci/63.2.319 Published: 01 August 1979 Article history Received: 15 August 1978 Accepted: 04 January 1979 Published: 01 August 1979
Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre-Clinical Diastolic Dysfunction (Stage B Heart Failure)
Authors: Siu-Hin Wan, Paul M. McKie, John A. Schirger, Joshua P. Slusser, David O. Hodge, Margaret M. Redfield, John C. Burnett, Horng H. Chen
Journal: JACC Heart Failure (2016)
Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment
Authors: Elizabeth O. Hexner, Selina M. Luger, Ran Reshef, Grace R. Jeschke, James K. Mangan, Noelle V. Frey, Dale M. Frank, Lee P. Richman, Robert H. Vonderheide, Nicole A. Aqui, Misha Rosenbach, Yi Zhang, Anne Chew, Alison W. Loren, Edward A. Stadtmauer, Bruce L. Levine, Carl H. June, Stephen G. Emerson, David L. Porter
Journal: American Journal of Hematology (2016)

Limited cell numbers in umbilical cord blood (UCB) grafts present a major impediment to favorable outcomes in adult transplantation, largely related to delayed or failed engraftment. The advent of UCB transplantation (UCBT) using two grafts successfully circumvents this obstacle, despite the engraftment of only one unit. Preclinical models suggested that the addition of UCB T cells at the time of transplant can enhance engraftment. We tested whether ex vivo activation by CD3/CD28 costimulation and expansion of T cells from a single UCB graft would be safe and feasible in adults with advanced hematologic malignancies, with an overall objective of optimizing engraftment in single unit UCBT. In this phase 1 study, recipients of single UCB units were eligible if the unit was stored in two adequate fractions. Dose limiting toxicity was defined as grade 3 or grade 4 GVHD within 90 days of UCBT. Four patients underwent UCBT; all were treated at the first dose level (10(5) cells/kg). At the 10(5) cells/kg dose level two subjects experienced grade 3 intestinal GVHD, thus meeting stopping criteria. For three subjects, neutrophil engraftment was early (12, 17, and 20 days), while one subject experienced primary graft failure. We observed early donor T cell trafficking and found that expanded T cells produced supraphysiologic levels of cytokines relevant to engraftment and to lymphoid differentiation and function. Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD.
Measurement of alveolar nitric oxide in patients with lung cancer
Authors: Anastasios Kallianos, Sotirios Tsimpoukis, Harpidou Andriani, Rapti Aggeliki, Syrigos Konstantinos
Journal: European Respiratory Journal (2012)

Introduction:  The presence of NO as a marker of airway inflammation and indirectly as a general indicator of inflammation and oxidative stress-incrimination as incriminating factor in lung cancer at an early stage and then the treatment of disease after chemotherapy.  Purpose:  We studied whether exhaled NO levels altered by 3 cycles of chemotherapy the levels at diagnosis and whether directly or indirectly related to the course of disease. Also, correlation levels of NO with other markers of inflammation.  Method:  We studied 28 patients early diagnosed -18 men and 10 women with lung cancer.We analyse.blood tests for control of inflammatory markers, functional pulmonary tests and alveolar exhaled nitric oxide.  Results:  Recorded decrease in exhaled NO after 3 cycles of chemotherapy in all patients regardless of histological type and stage.  28 patients with a mean 6.8 NO occurs after 3 cycles average 4.9, a value which is normal.  Also appears strong correlation between NO before and after chemotherapy and CRP (p   It is a further breakdown of data by the statistical program SPSS, with subgroups for analysis based histological types.  Conclusions:  NO alveolar as an indicator of airway inflammation, indicates response to chemotherapy in lung cancer. Also the inflammatory process in lung cancer confirmed and indicates response to chemotherapy through an index which is sensitive to inflammatory diseases of the airways and not reused in lung cancer before and after chemotherapy.
Iron deficiency in patients with systemic sclerosis-associated pulmonary arterial hypertension
Authors: Gerrina Ruiter, Alexandre Voskuyl, Irene Lanser, Frances de Man, Pieter Postmus, John Wharton, Nico Westerhof, Willem van der Laarse, Luke Howard, Martin Wilkins, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2012)

Background  Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) has a poor clinical outcome compared to other types of PAH. Recent data has shown that iron deficiency (ID) is associated with poor survival in idiopathic PAH. Inflammatory cytokines and increased hepcidin levels play a role. We hypothesise that a high prevalence of ID in SSc-PAH is linked to poor clinical outcome.  Methods  Measures of body iron status were performed retrospectively in serum from SSc-PAH patients (n=49) and systemic sclerosis patients without PAH (SSc, n=131). Six minute walking distance (6MWD) was also compared between the groups.  Results  Circulating soluble transferrin receptor (sTfR) levels in SSc-PAH patients were higher than in SSc (p 28.1 nmol/L, was 47% in SSc-PAH compared to 20% in SSc (p  Conclusions  Iron deficiency is more prevalent in SSc-PAH than in SSc patients and is associated with lower exercise capacity. The role of hepcidin in this process remains to be elucidated.
Differential response to primary chemotherapy and long-term survival in patients with triple-negative breast cancer
Authors: C. Liedtke, C. Mazouni, K. R. Hess, A. Tordai, F. André, W. F. Symmans, A. M. Gonzalez-Angulo, M. Green, G. N. Hortobagyi, L. Pusztai
Journal: Journal of Clinical Oncology (2007)

10519 Objective. Triple-negative breast cancer is defined as a subtype of invasive breast cancer which lacks estrogen and progesterone receptor expression as well as HER2/neu expression and is highly similar to the basal-like subtype defined by gene expression profiling. Method. 1,143 patients treated at MD Anderson Cancer Center in neoadjuvant trials were included in a retrospective comparative analysis between triple-negative tumors and non-triple-negative tumors for response to neoadjuvant chemotherapy as well as long- term survival. Results. 827/1,143 (72%) patients had received taxanes, either as a single-agent (n=60) or in combination with anthracycline (n=767), whereas the remainder patients received an anthracycline-only chemotherapy. Overall 258/1,143 (23%) tumors were triple- negative. Complete pathological response (pCR) was achieved in 63/257 (25%) patients with triple-negative tumors compared to 99/888 (11%) in patients with non-triple-negative tumors (odds ratio [OR] 1.14, 95%CI: 1.09–1.20, p=.0082). Triple-negative status correlated significantly with high nuclear grade (p&lt;.0001), whereas no significant correlation with any established clinicopathologic parameter was observed. However, 5-year overall survival (5yrOS) was 66% in the triple-negative group compared to 83% in the non-triple-negative control group (OR 2.1, 95%CI: 1.6–2.8, p&lt;.0001). In multivariate analyses, triple-negative status (hazard ratio [HR] 2.0, 95%CI: 1.4–2.8, p&lt;.0001), high nuclear grade, increased tumor size (HR 1.5, 95%CI: 1.3–1.8, p&lt;.0001), positive nodal status (HR 1.4, 95%CI: 1.2–1.7, p=.0002) and high nuclear grade (HR 1.7, 95%CI: 1.1- 2.4, p=.0089) were significantly associated with decreased 5yrOS. When survival was analyzed according to both response rate and triple negative status, achievement of pCR was a stronger predictor of survival compared to triple-negative status. Conclusion. Triple- negative expression status among patients with breast cancer constitutes an independent unfavorable prognostic factor with regards to overall survival unless achieving pCR after neoadjuvant chemotherapy. No significant financial relationships to disclose.
Gene expression determinants of ovarian cancer platinum-response in older women
Authors: J. M. Cragun, T. Boren, Y. Xiong, M. Indermaur, S. Kamath, H. Cottrill, L. Balducci, R. Sayer, H. K. Dressman, A. Berchuck, J. Lancaster
Journal: Journal of Clinical Oncology (2008)

22059 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and more than half of new ovarian cancer cases arise in women over age 65. Although older women with EOC have poorer overall prognosis compared to younger women, the exact molecular basis to this difference remains unclear. The goal of this study is to improve our understanding of the molecular underpinnings of advanced stage EOC in older women and identify genes associated with chemo-response in older women such that therapy may be tailored to individual patients. Methods: We performed Affymetrix microarray gene expression analysis on 122 primary advanced stage epithelial ovarian cancers resected from 73 younger (<65 years) and 49 older (>65 years) women. For each age group, gene expression data was compared using Significance Analysis of Microarrays (SAM), between patients who demonstrated a complete-response (>65 years, n=38; <65 years, n=48) and incomplete-response (>65 years, n=11; <65 years, n=25) to primary platinum-based chemotherapy. Differential expression was determined by two class unpaired t-tests (false discovery rate, 0%), and results ranked according to d score. Results: We identified 317 genes associated with platinum-response in cancers from younger women, and 264 genes associated with platinum-response in cancers from older women. Six genes (JRKL, LRP8, OVOL2, PKP4, SRD5A1, TMEM1) demonstrated differential expression associated with platinum-response in cancers from both age groups. Genes associated with platinum-response in older, but not younger, women have functional links to apoptosis regulation, programmed cell death, and cell growth. In contrast, genes associated with platinum-response in younger women have functional links to DNA repair. Conclusions: We have identified genes associated with response to platinum-based therapy in younger and older women with EOC. Our data provides insights into biologic functions that may underlie differences in chemo-responsiveness in older versus younger women with EOC. Identifying the molecular underpinnings that drive response to chemotherapy in older women may enable clinicians to tailor therapy and identify potential novel therapeutic targets. No significant financial relationships to disclose.