tbuckley/cabot-search huggingface dataset:
Abstract 1309: Fitness of T cells for use in cellular therapy of pediatric malignancies
Authors: Nathan Singh, Jessica Hulitt, Stephan A. Grupp, David M. Barrett
Journal: Cancer Research (2015)

Abstract Despite promising clinical trial results, many patients are ineligible to receive cellular therapy, either due to an inability to harvest sufficient lymphocytes, or that the harvested cells fail to yield a clinically viable product. The ideal time to harvest these cells remains unclear, and is of significant clinical relevance. We collected blood from pediatric patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphomas (NHL) at time of diagnosis and after each cycle of chemotherapy. We plated these samples overnight to deplete adherent cells, quantified the CD3+ T cell population by flow cytometry, combined these T cells with CD3/CD28 stimulatory beads at a ratio of 3 beads/cell, and measured expansion over time. These studies (Table 1) revealed that ALL samples harvested earlier in therapeutic course demonstrated enhanced ex vivo expansion. We stratified our samples into standard (SR) and high-risk (HR+VHR) disease and found that SR patients have even more robust early expansion and that this expansion ability is maintained, while high-risk samples lose ex vivo expansion ability after consolidation. Broadening this analysis to lymphoma revealed that only a fraction of NHL diagnosis samples expand ex vivo, and nearly no expansion is observed after initiation of chemotherapy. We also examined T cell phenotype from our ALL samples, and found a correlation between expansion capability and presence of naïve T cells, and that larger terminal effector pools correlate with poor expansion. These data represent the most detailed analysis of T cell number, function and phenotype during chemotherapy for pediatric B cell malignancies to date. They suggest that T cell fitness is considerably affected by type of chemotherapy as well as underlying malignancy, and that fitness may correlate with phenotype. These findings have direct clinical relevance, suggesting that T cells should be harvested as early as possible after diagnosis. This practice has the potential to significantly expand the pool of patients eligible for cellular therapy. Table 1. Percentage of samples with &amp;gt;5-fold ex vivo expansion ALL (total)ALL (SR)ALL (HR+VHR)NHLDiagnosis80907025*Post induction82768412*Post consolidation668052*0*Post interim maintenance647846*0*Post delayed intensification618534*0*Maintenance37500*0**p&amp;lt;0.01 compared to ALL (SR) Citation Format: Nathan Singh, Jessica Hulitt, Stephan A. Grupp, David M. Barrett. Fitness of T cells for use in cellular therapy of pediatric malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1309. doi:10.1158/1538-7445.AM2015-1309
Minimal invasive perineal radical prostatectomy
Authors: P. Albers, S. Schaefers, H. Löhmer, P. De Geeter
Journal: Journal of Clinical Oncology (2007)

15566 Background: Radical perineal prostatectomy (RPP) has experienced a reappraisal as excellent surgical treatment option for patients with localized prostate cancer which is competing well with the retropubic (RRP), endoscopic and robotic approaches. Herein we report a new and improved minimal invasive technique of an intrafascial, nerve-sparing and seminal vesical sparing RPP. Methods: From July 2003 to July 2006, 507 radical prostatectomies (317 RPP, 190 RRP) have been performed by 3 surgeons. RPP selection criteria: PSA ≤ 10 ng/ml, Gleason sum ≤ 7, volume ≤ 50 ml. A minimal invasive technique (MI-RPP) was used in 146 of 317 RPP (46%) in order to potentially improve on the results of classical RPP. “Minimal invasive” was defined as an approach with reduced mobilisation of the rectum, intended bilateral nerve-sparing with intrafascial preparation and leaving the seminal vesicals in situ. This approach was compared to classical RPP and to RRP. Perioperative and follow-up data using validated questionnaires were centrally registered using an on-line internet-based prostate cancer data bank provided by the Tumorzentrum Berlin. Results: With a median follow-up of 12 months (0–24), the oncological outcome of patients with MI-RPP was not different to RPP or RRP (comparable T-stages). PSA relapse in MI-RPP, RPP, and RRP in pT2R0 was seen in 10.2%, 14.7%, and 9.7% respectively (n.s.). Continence rates (0–1 pad/d) at 4 weeks were 61.7%, 45.0%, and 43.8%, respectively. This improved at 12 months to 96.3%, 85.7%, and 85.6%, respectively (p &lt; 0,023; p &lt; 0,005). MI-RPP, RPP, and RRP showed pT2 in 70.5, 69.6, and 57.3% with R1pT2 in 1.9, 6.7, and 9.2%, resp. Nerve-sparing was performed in 90.4, 62.0, and 57.4% with median OR times of 90, 141, and 163 min. Catheter removal after more than 13 d was seen in 6.6, 13.6, and 33.3%, resp. Conclusions: MI-RPP represents an improved perineal technique regarding intraoperative and postoperative complications maintaining comparable oncological outcome to RPP and RRP. Leaving seminal vesicals in place did not increase PSA relapse rates. Since OR time is significantly less and early recovery is superior, MI-RPP should be the recommended first-line perineal approach to patients with low risk prostate cancer. At the time of the meeting, data of more than 600 patients will be presented. No significant financial relationships to disclose.
Efficacy Comparison of 16 Interventions for Myopia Control in Children
Authors: Jinhai Huang, Daizong Wen, Qinmei Wang, Colm McAlinden, Ian Flitcroft, Haisi Chen, Seang Mei Saw, Hao Chen, Fangjun Bao, Yune Zhao, Liang Hu, Xuexi Li, Rongrong Gao, Weicong Lu, Yaoqiang Du, Zhengxuan Jinag, Ayong Yu, Hengli Lian, Qiuruo Jiang, Ye Yu, Jia Qu
Journal: Ophthalmology (2016)

PurposeTo determine the effectiveness of different interventions to slow down the progression of myopia in children.MethodsWe searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to August 2014. We selected randomized controlled trials (RCTs) involving interventions for controlling the progression of myopia in children with a treatment duration of at least 1 year for analysis.Main Outcome MeasuresThe primary outcomes were mean annual change in refraction (diopters/year) and mean annual change in axial length (millimeters/year).ResultsThirty RCTs (involving 5422 eyes) were identified. Network meta-analysis showed that in comparison with placebo or single vision spectacle lenses, high-dose atropine (refraction change: 0.68 [0.52–0.84]; axial length change: −0.21 [−0.28 to −0.16]), moderate-dose atropine (refraction change: 0.53 [0.28–0.77]; axial length change: −0.21 [−0.32 to −0.12]), and low-dose atropine (refraction change: 0.53 [0.21–0.85]; axial length change: −0.15 [−0.25 to −0.05]) markedly slowed myopia progression. Pirenzepine (refraction change: 0.29 [0.05–0.52]; axial length change: −0.09 [−0.17 to −0.01]), orthokeratology (axial length change: −0.15 [−0.22 to −0.08]), and peripheral defocus modifying contact lenses (axial length change: −0.11 [−0.20 to −0.03]) showed moderate effects. Progressive addition spectacle lenses (refraction change: 0.14 [0.02–0.26]; axial length change: −0.04 [−0.09 to −0.01]) showed slight effects.ConclusionsThis network analysis indicates that a range of interventions can significantly reduce myopia progression when compared with single vision spectacle lenses or placebo. In terms of refraction, atropine, pirenzepine, and progressive addition spectacle lenses were effective. In terms of axial length, atropine, orthokeratology, peripheral defocus modifying contact lenses, pirenzepine, and progressive addition spectacle lenses were effective. The most effective interventions were pharmacologic, that is, muscarinic antagonists such as atropine and pirenzepine. Certain specially designed contact lenses, including orthokeratology and peripheral defocus modifying contact lenses, had moderate effects, whereas specially designed spectacle lenses showed minimal effect.
Accuracies of the Simple Methods for Estimating the Bootstrap Probability of a Maximum-Likelihood Tree
Authors: M Hasegawa, H Kishino
Journal: Molecular Biology and Evolution (1994)

Two simple methods have been proposed by Kishino et al. for estimating bootstrap probabilities of alternative trees from a maximum-likelihood analysis without performing maximum-likelihood estimation for each resampled data set; i.e., a resampling estimated log-likelihood method and a multivariate normal distribution method. To examine the extent to which these two methods provide good approximations, bootstrap probabilities estimated by these methods from real data were compared with those estimated by repeated bootstrap resampling and maximum-likelihood estimation. It turned out that both of these simple methods are good approximations to the computationally intensive bootstrap method. This finding should motivate people in this field to use the maximumlikelihood method when inferring molecular evolutionary trees.
Temporal integration of light flashes by the human circadian system
Authors: Raymond P. Najjar, Jamie M. Zeitzer
Journal: Journal of Clinical Investigation (2016)

BACKGROUND. Beyond image formation, the light that is detected by retinal photoreceptors influences subcortical functions, including circadian timing, sleep, and arousal. The physiology of nonimage-forming (NIF) photoresponses in humans is not well understood; therefore, the development of therapeutic interventions based on this physiology, such as bright light therapy to treat chronobiological disorders, remains challenging.
Discrimination of protein and peptide composition of exhaled breath condensate in patients with pulmonary disease by mass spectrometry
Authors: Anna Ryabokon, Viktoria Kurova, Eldar Anaev, Aleksey Kononikhin, Kristina Fedorchenko, Eugenie Nikolaev, Sergey Varfolomeev
Journal: European Respiratory Journal (2011)

Exhaled breath condensate (EBC) reflects the composition of the airway-lining fluid and may contain biomarkers of diseases of respiratory system.

The aim of this study is to identify proteins in EBC of patients with chronic obstructive pulmonary disease (COPD) and pneumonia using two techniques of proteome identification.

Seventeen COPD and thirteen pneumonia samples were collected using the Jaeger ECoScreen (VIASYS Healthcare, Germany), freeze dried, treated with trypsin and analyzed by nanoflow LC-MS/MS with a 7-Tesla Finnigan LTQ-FT mass spectrometer (Thermo Electron, Germany). Six COPD samples were mixed and applied to 2D-PAAGE by Mini-PROTEAN system (Bio-RAD, USA). Silver stained spots were analyzed by MALDI-TOF-MS using a Microflex device (Bruker Daltonics, Germany).

Using 2D-PAAGE and MALDI-TOF-MS we were able to show that EBC samples from patients with COPD contain whole “normal” keratins that were detected also in EBC of healthy donors.

Using LC-MS/MS, a method of comparable sensitivity, specific peptides of “abnormal” keratins 3, 4, 8 were identified in COPD samples. Keratin set identified in samples from patients with acute pneumonia was more varied.

Peptides of Plakoglobin, Desmoplakin, Alpha-1-acid glycoprotein, Filaggrin, Dynein, Collagen, Hornerin were discovered in COPD and pneumonia EBC samples. They are uncharacteristic of healthy EBC samples. None of these proteins was identified as a whole in 2D-PAA gels. These peptides seem to appear in airway-lining fluid due to proteolysis in respiratory tract tissue.

In conclusion, each of “abnormal” peptides, as well as their combinations, may have diagnostic value.
Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes
Authors: Yoonsang Park, Yuri Cho, Eun Ju Cho, Yoon Jun Kim
Journal: Clinical and Molecular Hepatology (2015)

Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone.This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes.The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups.The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.
Comparison of complications of total thyroidectomy in malignant vs. benign thyroid tumors
Authors: D. Iddings, S. Saha, E. Walsh, M. Raiji, M. Ghanem, V. Rao, D. Wiese, J. Hammoud, M. Bakleh, J. Nelson
Journal: Journal of Clinical Oncology (2008)

17012 Background: Total thyroidectomy (TT) is the procedure of choice for many benign and malignant thyroid diseases. There is still controversy regarding the use of total vs. sub TT for benign disease because many surgeons fear it is associated with a high complication (comp) rate. Few studies have investigated the safety of TT in benign vs. malignant thyroid disease. Methods: A chart review of 411 consecutive patients (pts) undergoing TT performed by a single oncologic surgeon was analyzed to compare the comp rates in benign vs. malignant disease. Serum iCa and intact-PTH levels were measured within 1week postoperatively, and 6 months afterwards. Permanent (perm) hypocalcemia (hypo Ca) and hypoparathyroidism (hypo PTH) were defined as an iCa level below 1.10 mmol/L or an intact PTH of less than 14 pg/mL respectively, persisting longer than 6 months. Results: Of the 411 pts who underwent TT, 278 (68%) had benign pathology (gp A) while the remaining 133 (32%) had malignant disease (gp B). Benign pathologies included bilateral goiter (71%), Hashimoto’s thyroiditis (30%), follicular adenoma (10%), and benign (1%). There was considerable overlap among benign pathologies as pts often presented with more than one type. Malignant pathologies included papillary (64%), follicular (30%), medullary (4%), and anaplastic (2%) cancers as well as lymphoma (2%). The comp rates for gp A vs. B respectively were as follows: perm hypo Ca 0.4% vs. 1.7% (p=0.57), perm hypo PTH 1.0% vs. 5.2% (p=0.21), bleeding 0.7% vs. 0.0% (p=0.83), and RLN injury 0.4% vs. 0.0% (p=0.71). There were no significant differences noted (p<0.05) between the two gps. Among gp B, 4 pts were noted to have perm hypo PTH, but two of these pts did not receive parathyroid reimplantation because of advanced malignant disease in the neck. The RLN was intentionally sacrificed in 5 pts with direct nerve involvement. There was no mortality in either gp. Conclusions: The comp rates of TT appear to be equal between benign and malignant diseases, and in both cases, perm comps are rare when performed by an experienced surgeon. Thereby, when performing TT in malignant and bilateral benign disease, one can avoid secondary completion thyroidectomy and/or avoid recurrent disease in the remaining lobe. This can be done safely and without any increase in morbidity. No significant financial relationships to disclose.
Intravenous MST-997 (TL- 909) formulated in intralipid 20% administered weekly in subjects with advanced malignant solid tumors: A phase I dose-escalation study
Authors: A. C. Lockhart, H. Hochster, K. Wang, V. Paty, J. Grover, C. Leister, M. Shapiro, M. L. Rothenberg, R. Bukowski
Journal: Journal of Clinical Oncology (2005)

2106 Background: MST-997 is a novel taxane with greater apparent potency in preclinical models than paclitaxel, and antitumor activity in cells that express low to moderate MDR1 levels. Pharmacokinetic (PK) and toxicity profiles also appear improved relative to conventional taxanes. Methods: This phase 1 dose-escalation study is designed to determine the safety and tolerability of IV MST-997 (in Intralipid) given weekly, and define the dose for phase 2 studies. Key eligibility criteria include adult subjects with refractory solid tumors; ECOG of 0 - 2; adequate hematologic, hepatic, and renal function. Dose escalation proceeded using accelerated dose titration with 1 or 2 subjects treated at initial dose levels. Cohorts were expanded to 3 subjects when related adverse events (AEs) ≥ grade 2 were observed. Planned dose levels are 5, 10, 20, 30, and 40 mg/m2 with PK analysis performed following the first drug dose. No premedications are given prior to MST-997 administration. Results: To date, 9 subjects (ECOG 0 -1) have been treated at dose levels of 5 to 30 mg/m2. Tumor types have included NSCLC, bladder, ovarian, pancreas, carcinoid, biliary, sarcoma and thyroid. One (1) patient developed a dose limiting toxicity (DLT) at the 30 mg/m2 dose level (grade 3 fatigue). Other grade 3 and 4 AEs that did not meet the criteria for a DLT have included: neutropenia (1) and pain (1). No complete or partial responses have been observed. Disease stabilization (per modified RECIST criteria) was seen in 3 subjects: pancreatic (with decreased Ca 19–9; unconfirmed), carcinoid, and ovarian cancers. Plasma concentrations from 4 patients receiving doses ranging from 5 to 30 mg/m2 suggest that MST-997 has a moderate clearance, ranging from 18 to 51 L/h; a high Vss, with values ranging from 940 to 2160 L; and a long t1/2, with values ranging from 13 to 71 h. Cmax and AUC values appeared to increase with dose level. Conclusions: MST-997 administered in an intralipid formulation appears well tolerated when given weekly in doses up to 30 mg/m2. Dose escalation is ongoing with a maximum tolerated dose confirmatory cohort planned. Additional phase 1 studies with MST-997 are also planned. No significant financial relationships to disclose.
Abstract 14134: Racial Disparities in Warfarin Time in INR Therapeutic Range in Patients With Atrial Fibrillation: Findings From the TREAT-AF Study
Authors: Celina Yong, Xiangyan Xu, Claire Than, Aditya Ullal, Susan Schmitt, Farnaz Azarbal, Paul Heidenreich, Mintu Turakhia
Journal: Circulation (2013)

Background: The influence of race on quality of anticoagulation control is not known. We examined the association between race, time in INR therapeutic range (TTR), and INR monitoring intensity (IN...
Persistence of circulating tumour cells after treatment predicts clinical outcome in breast cancer patients
Authors: M. Serrano, P. Sánchez-Rovira, M. Campos, F. Warleta, J. Ruiz-Mora, I. Algarra, M. Delgado-Rodríguez, M. Fernández, C. de la Torre, A. Peiró, J. J. Gaforio
Journal: Journal of Clinical Oncology (2007)

21080 Background: The hematogenous distant metastasis is the leading cause of cancer death. This process involves the passage through the blood and lymphatic circulation of circulating tumor cells (CTC) with metastatic properties. Thus, the early detection of such cells has important implication for cancer prognosis, monitoring of treatment and to predict clinical outcome. We present the results that showed that CTC are prognostic factor after chemotherapy independently of treatment. Methods: A total of 59 patients with breast cancer were enrolled in this study between April 2000 and December 2002. The median follow-up was 50 months. All patients received chemotherapy as first line treatment. Results of this work included CTC detection one month after of the end of chemotherapy. After informed consent, 10ml of heparinized peripheral blood was collected from patients. For enrichment of CTC we use the Carcinoma Cell Enrichment and Detection kit using MACS technology (Miltenyi Biotec). After enrichment of epithelial tumor cells immunomagnetic labeled with a multi- cytokeratin-specific antibody, the positive cells were detected by immunocytochemical staining with alkaline phosphatase substrate. Results: Analysis of CTC after chemotherapy: Circulating tumor cells were detected in 32 patients (54.23%). A mean number of cells were detected 3.7 (SD 13.9; range 1–105).The number of CTC was correlationed with progression free of disease (PFS) and overall survival (OS). In the univariate Cox proportional hazard regression analysis number cells were significantly associated with OS (p = 0.020) and PFS (p = 0.008). In the multivariate Cox proportional hazard regression analysis, number cells admit borderline statically significance with PFS (p = 0.052) and OS (p = 0.071). Conclusions: Our results suggest that the persistence of CTC after the treatment predicts clinical outcome and therefore the detection of CTC in breast cancer patients might allow monitoring of chemotherapy response. No significant financial relationships to disclose.
The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer.
Authors: R. C. Leonard, D. Adamson, R. Anderson, R. Ballinger, G. Bertelli, R. E. Coleman, L. Fallowfield, M. McLinden, J. Mansi, G. Thomas
Journal: Journal of Clinical Oncology (2010)

590 Background: Nonrandomised studies suggest that goserelin may protect the ovaries against chemotherapy induced premature menopause. The primary objective of the open, randomised multicentre OPTION trial was to determine the impact of goserelin on the incidence of premature ovarian failure following chemotherapy for operable breast cancer. Secondary objectives were to record menstruation (diary) and pregnancies, assess quality of life (FACT-ES) and menopausal symptoms, and measure changes in bone mineral density (BMD) and bone turnover markers, hormone levels (including AMH and inhibin B). Methods: All premenopausal ER negative women (or ER positive women for whom ovarian suppression was not considered necessary) planned for adjuvant or neoadjuvant chemotherapy, were considered for inclusion. Women were stratified by age >/ = 40 or < 40 years at randomisation, and by centre. Chemotherapy regimens comprised any 6-8 cycles of chemotherapy containing cyclophosphamide and/or anthracycline. Regimens could include taxanes. Goserelin was randomly allocated to start before or at first chemotherapy cycle and continued 3-4 weekly to final cycle. For the purposes of the sample size calculation, the rates of premature menopause were assumed to be 40% in the under 40 age group and 80% in the over 40 age group (Bines et al, J Clin Oncol 14(5):1718-29 1996). Reported rates of preservation of ovarian function using goserelin with chemotherapy in uncontrolled studies are around 80%, (possibly higher in the under 40's): i.e. rates of premature menopause with goserelin of around 20% or less. Based on a one sided test with 5% false positive rate, the groups required approximately 140 and 70 patients respectively to have a 80% chance of detecting an absolute reduction in premature menopause rate of 20% and 25% respectively, that is from 40% to 20% in the under 40 age group and from 80% to 55% in the over 40 age group. A total of 210 patients were therefore required. Results: At trial closure, 31/12/09, 227 patients had been randomised. Conclusions: The primary accrual endpoint of more than 210 patients has been achieved and so we expect the statistical requirements to be met. Primary and selected secondary endpoints will be presented. No significant financial relationships to disclose.