tbuckley/cabot-search huggingface dataset:
Control of Melanogenesis in Mouse Melanoma Cells of Varying Metastatic Potential&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Richard M. Niles, Joseph S. Makarski
Journal: JNCI Journal of the National Cancer Institute (1978)

The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants. In B16-F1 cells (low metastatic potential), MSH or cAMP greatly elevated tyrosinase activity and melanin content while inhibiting cell replication. The same parameters in B16-F5 cells (intermediate metastatic potential) were altered to a much lesser degree, whereas B16-F10 cells (high metastatic potential) were not significantly affected by MSH or cAMP. Therefore, a correlation exists between loss of hormonal regulation and increased metastatic potential.
Ewing's family of tumors in adults: multivariate analysis of survival and long-term results of multimodality therapy in 182 patients.
Authors: K Fizazi, N Dohollou, J Y Blay, S Guérin, A Le Cesne, F André, P Pouillart, T Tursz, B B Nguyen
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the outcome and the prognosis of adults with a neoplasm related to the Ewing's sarcoma family of tumors. PATIENTS AND METHODS The outcomes of 182 consecutive patients older than 15 years with Ewing's sarcoma or related neoplasms managed from 1982 to 1992 were reviewed, without any selection according to primary tumor site or disease extension. RESULTS Of 182 patients, 53 had evidence of metastases at presentation (29%). Tumor size was greater than 10 cm in 70 patients (41%). With a median follow-up duration of 66 months, the 5-year overall survival (OS) rate was 41%. In patients with localized disease, 5-year OS rate was 54% and 5-year progression-free survival (PFS) rate, 43%. Late relapses after 5 years accounted for 9% of relapses. Metastasis at presentation (P = .00001), pelvic primary lesion (P = .0025), and tumor size greater than 10 cm (P = .004) were independent prognostic factors for survival. Five-year OS was 67% in patients with nonpelvic tumors &lt; or = 10 cm, 52% in those with pelvic tumors less than 10 cm or extrapelvic tumors &gt; or = 10 cm, 16% in those with pelvic tumors greater than 10 cm, and 9% in those with metastasis (P = .00001). CONCLUSION Based on our experience and a review of the literature, we concluded that the natural history and the prognosis of the Ewing's family of tumors in adults are not different from that found in children. A greater tumor bulk in adults may explain the less favorable prognosis previously reported by others. Outcome could be adequately monitored by a simple prognostic index.
Morphologic Studies of Lymphoid Tissues During the Growth of an lsotransplanted Mouse Tumor&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Gerhard Krüger
Journal: JNCI Journal of the National Cancer Institute (1967)

The morphologic changes in the regional lymph nodes and spleens of C3H/HeN mice were analyzed after transplantation of an isogeneic methylcholanthrene-induced sarcoma. This tumor has strong transplantation antigenicity. The results were compared with those obtained after transplantation of isogeneic and allogeneic spleen cells. The changes in the lymphoid organs of the mice receiving either tumor cells or allogeneic spleen cells corresponded with those described in the literature after administration of well-defined antigens. Consequently, the morphology of the lymphoid organs of the animals with tumors indicates that an antigenic substance stimulates these organs. However, this antigen may not be an integral part of the tumor itself, since a virus or other extraneous antigenic agent could have been present.
Abstract 273: Sildenafil and Beraprost Therapy Improve Arrhythmogenicity Through Connexin 43 Expression and Electrophysiological Property in Monocrotaline-Induced Rat Pulmonary Hypertension: Optical Mapping Analysis
Authors: Bonpei Takase, Yoshihiro Tanaka, Masayuki Ishihara
Journal: Circulation (2011)

Severe pulmonary hypertension (PH) is associated with sudden cardiac death (SCD). Optical mapping analysis (OMP) with electrophysiological study (EPS) and connexin-43 measures were performed weekly in Sprague-Dawley rat with monocrotaline (MCTi, 60 mg/kg) induced PH. Right ventricular pressure (RVP) and pulmonary vascular remodeling (PVR) were measured. EPS for ventricular fibrillation (VF) induction and RT-PCR for mRNA expression of connexin-43 (Conx-Ex) were performed. Daily administration of sildenafil (5 mg/kg) and beraprost (100 μg/kg) was initiated at 2 or 3 weeks after MCTi. OMP revealed abnormal RV conduction and action potential dispersion with high VF induction rate. Decreased Conx-Ex with high RVP at 3,4 and 5 weeks after MCTi were observed. Sildenafil with beraprost improved PVR, RV arrhythmogenicity, Conx-Ex, cardiac function (Table) and survival rates. Conclusions: Sildenafil with beraprost therapy improves prognosis by preventing SCD and heart failure. These results give us further insights for understanding PH-induced SCD and therapeutic option for PH.
Clinical Implications of JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) in a U.S. Population
Authors: Eric Y. Yang, Vijay Nambi, Zhengzheng Tang, Salim S. Virani, Eric Boerwinkle, Ron C. Hoogeveen, Brad C. Astor, Thomas H. Mosley, Josef Coresh, Lloyd Chambless, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2009)
Abstract 13031: Survival with PCI versus CABG in Multivessel Coronary Disease in the Moderan Era of Revascularization
Authors: Sawar H Orakzai, Craig W Langner, John F Robb, Lawrence J Dacey, Mirle A Kellett, Reed D Quinn, Peter N Ver Lee, Robert A Clough, Richard A Boss, William J Phillips, David Goldberg, Benjamin M Westbrook, Matthew D Watkins, Bruce J Leavitt, Donald S Likosky, David J Malenka
Journal: Circulation (2010)

Background: Although SYNTAX (n=1,800) reported equivalent 2 year survival for select patients with left main or 3VD randomized to PCI v CABG, a broader range of patients with multivessel CAD face the choice of PCI v CABG. We assessed 4.5 year survival rates from our regional registry of consecutive procedures for a cohort of BARI-like patients with multivessel CAD (n=7,180) who chose PCI or CABG. Methods: From our Northern New England relational registries of PCI and CABG procedures we identified patients with 2VD or 3VD (excluding left main disease) undergoing a first, non-emergent PCI (n-3,334, 88% DES) or CABG (n=3,846) from 10/2003–2007. Survival was obtained by linkage to SSA death index. Cox proportional-hazards models and propensity matching were used to adjust for differences in age, sex, comorbidities, CHF, recent MI, priority, EF, anatomy. Results: PCI patients were slightly older and more likely male. CABG patients had more diabetes, PVD, EFs <40%, and 3VD (57.5% CABG v 21.1% PCI). Completeness...
Evaluation of a Web-based cognitive rehabilitation program for cancer survivors with self-reported cognitive impairment.
Authors: V. J. Bray, H. M. Dhillon, J. L. Vardy
Journal: Journal of Clinical Oncology (2010)

TPS316 Background: Studies in cancer survivors have shown a 15-50% incidence of cognitive impairment following chemotherapy, with up to 70% self reporting cognitive impairment (Vardy J, et al. Ann Oncol 19:623-9, 2008). There are no proven treatments to manage this problem. Cognitive rehabilitation is effective in other patient groups and a single arm pilot study of cognitive behavior therapy in cancer survivors showed promise (Ferguson RJ, et al. Psycho-oncology 16:772-7, 2007). Our randomized controlled trial evaluates a cognitive rehabilitation program (CRP) in cancer survivors with solid tumors (excluding primary brain tumors), self-reporting cognitive impairment following curative chemotherapy. Our primary hypothesis is that a CRP will improve self reported cognitive function. Secondary hypotheses are that a CRP can improve objective neuropsychological performance and patient reported outcomes including: (i) quality of life; (ii) depression and anxiety; (iii) stress; (iv) fatigue. Methods: We are recruiting cancer survivors with self-reported cognitive impairment, as indicated by changes in concentration and memory on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Cognitive Functioning scale. Participants must have completed potentially curative chemotherapy within 6 to 60 months and have no cancer recurrence. The intervention arm perform a home-based, internet CRP for 4× 40 minute sessions per week for 15 weeks. Both intervention and control arms participate in a 30-minute scripted teleconference discussing strategies to manage cognitive impairment. Participants complete neuropsychological tests and questionnaires evaluating patient reported outcomes at baseline, post intervention and 6 months post intervention. Primary endpoint is self-reported cognitive function assessed by the Functional Assessment of Cancer Treatment–Cognition questionnaire. Sample size is 280, with 20 patients accrued to date. No significant financial relationships to disclose.
Real-Time Ultrawide Field Image Evaluation of Retinopathy in a Diabetes Telemedicine Program
Authors: Paolo S. Silva, Jerry D. Cavallerano, Ann M. Tolson, Jessica Rodriguez, Sashida Rodriguez, Radwan Ajlan, Dorothy Tolls, Bina Patel, Mina Sehizadeh, Komal Thakore, Jennifer K. Sun, Lloyd Paul Aiello
Journal: Diabetes Care (2015)

OBJECTIVE To evaluate the ability of trained nonphysician retinal imagers to perform diabetic retinopathy (DR) evaluation at the time of ultrawide field retinal (UWF) imaging in a teleophthalmology program. RESEARCH DESIGN AND METHODS Clinic patients with diabetes received Joslin Vision Network protocol retinal imaging as part of their standard medical care. Retinal imagers evaluated UWF images for referable DR at the time of image capture. Training of the imagers included 4 h of standardized didactic lectures and 12 h of guided image review. Real-time evaluations were compared with standard masked gradings performed at a centralized reading center. RESULTS A total of 3,978 eyes of 1,989 consecutive patients were imaged and evaluated. By reading center evaluation, 3,769 eyes (94.7%) were gradable for DR, 1,376 (36.5%) had DR, and 580 (15.3%) had referable DR. Compared with the reading center, real-time image evaluation had a sensitivity and specificity for identifying more than minimal DR of 0.95 (95% CI 0.94–0.97) and 0.84 (0.82–0.85), respectively, and 0.99 (0.97–1.00) and 0.76 (0.75–0.78), respectively, for detecting referable DR. Only three patients with referable DR were not identified by imager evaluation. CONCLUSIONS Point-of-care evaluation of UWF images by nonphysician imagers following standardized acquisition and evaluation protocols within an established teleophthalmology program had good sensitivity and specificity for detection of DR and for identification of referable retinal disease. With immediate image evaluation, &amp;lt;0.1% of patients with referable DR would be missed, reading center image grading burden would be reduced by 60%, and patient feedback would be expedited.
Interpreting the significance of changes in health-related quality-of-life scores.
Authors: D Osoba, G Rodrigues, J Myles, B Zee, J Pater
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). PATIENTS AND METHODS A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. RESULTS For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. CONCLUSION The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.
Dynamic hyperinflation in cystic fibrosis
Authors: François Tremblay, Julie Morisset, Claude Poirier
Journal: European Respiratory Journal (2012)

Introduction: Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease. CF affects the exocrine glands of lungs, pancreas, intestines and liver. Lungs are usually affected more critically. Exercise tolerance is reduced in patients with CF. It has been shown that pulmonary function weakly correlates with peak exercise capacity. Furthermore, it has been demonstrated that oxygen desaturation during exercise is present in severe lung involvement, but not in mild to moderate disease. Peripheral muscle dysfunction has been demonstrated to be to main factor limiting factor of exercise tolerance. Few studies have looked at dynamic hyperinflation as a limiting factor of exercise tolerance.

Objectives: The aim of this study is was to evaluate the relationship between dyspnea and dynamic hyperinflation in CF during exercise.

Results: Six patients with mild to moderate CF (FEV1 45 to 79%) were studied during incremental treadmill exercise and changes in inspiratory capacity (IC) were obtained to measure dynamic hyperinflation. During the exercise, dyspnea was assessed by Borg scale. Of the 6 CF patients, 5 patients showed a decrease in IC (dynamic hyperinflation). Furthermore, there was a direct relation between dyspnea assessed by Borg scale and change in IC (r = 0,38).

Conclusion: Our study is the first to demonstrate dynamic hyperinflation in mild to moderate CF and a direct relationship between dyspnea and IC in CF during exercise. This provides a better understanding on exercise limitations in CF.
Computer EEG and Auditory Evoked Potential Investigations in Children at High Risk for Schizophrenia
Authors: T. M. ITIL, W. HSU, B. SALETU, S. MEDNICK
Journal: American Journal of Psychiatry (1974)

Computerized EEG and evoked auditory potential investigations demonstrated that the patterns of a group of children at high risk for schizophrenia (children of schizophrenic parents) had statistically significant differences when compared with those of a matched control group of children. High-risk children were characterized by the presence of high-frequency beta activity, fewer fast alpha waves, and more very slow low-voltage delta activity in computerized EEG as well as by shorter latencies in auditory evoked potential. These neurophysiological characteristics of high-risk children showed striking similarities to computerized EEG and evoked potential findings in psychotic children and schizophrenic adults, suggesting that this pattern may be the neurophysiological measurement of schizophrenia. These findings support some of the most recent biochemical hypotheses in schizophrenia and, if confirmed by further work, suggest new means in the preventive treatment of this illness.
Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.
Authors: J L Murray, J E Cunningham, H Brewer, K Mujoo, A A Zukiwski, D A Podoloff, L P Kasi, V Bhadkamkar, H A Fritsche, R S Benjamin
Journal: Journal of Clinical Oncology (1994)

PURPOSE The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients. PATIENTS AND METHODS Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. CONCLUSION Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.
Prognostic factors associated with progression of myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) in patients (pts) treated with decitabine.
Authors: A. Fullmer, G. Borthakur, T. M. Kadia, G. Garcia-Manero, E. Jabbour
Journal: Journal of Clinical Oncology (2010)

6571 Background: About 50% of pts with MDS ultimately progress to AML with no clear pattern in underlying parameters leading to progression. This analysis sought to identify predictive factors in pts with MDS that are associated with progression to AML after treatment with either a 3-day or 5-day decitabine regimen. Methods: Pts from two separate studies of decitabine treatment regimens using 3 days (15 mg/m2 IV q8h/Dx3) or 5-days (20 mg/m2 IV/Dx5) of decitabine were stratified on the basis of those who progressed to AML (P) versus those who did not (NP). Logistic regression stepwise selection procedure with a cut-off p-value of 0.3 was utilized to determined the final selected logistic regression model with progression to AML or not as the response variable. The following predictor variables were selected: study effect (3-day or 5-day), prior treatment, time to diagnosis, baseline ANC (< 500, 500 - 1,000, or > 1,000 U/L), BM Blast (< 5%, 5%-10%, or 10%-20%), cytogenetic (good, intermediate, worse), and IPSS (low, int-1, int-2). Pts with blasts ≥ 20% were excluded. Results: A total of 163 pts were included; 37 in the P group (3-day n = 24; 5-day n = 13) versus 126 in the NP group (3-day n = 50; 5-day n = 76). In the 3-day group, the baseline characteristics in pts that progressed were significantly older with a lower baseline hemoglobin value and had significantly less prior treatment, growth factors and longer time from diagnosis. In the 5-day group pts that progressed had significantly higher risk IPSS score with a significantly lower hemoglobin value and a higher WBC baseline value. No significant differences were observed in objective response rate, objective improvement rate, overall survival, or transfusion independency. Logistic regression showed that study effect of 3-day decitabine and 10%-20% blast percent were significant predictors of progression (p = 0.0017, 0.0282). No significant differences were observed in the safety profiles between the two groups. Conclusions: Decitabine given at the dose of 20 mg/m2 IV daily for 5 days is effective in pts with MDS. Pts with more than 10% blasts are at high risk of progression into AML and therefore should be offered additional options. No significant financial relationships to disclose.
Cytoplasmic Inclusions in Spontaneous Hepatomas of CBA/H-T6T6 Mice. Histochemistry and Electron Microscopy2
Authors: Bryan J. Helyer, Mary Petrell
Journal: JNCI Journal of the National Cancer Institute (1978)

Spontaneous hepatomas were found in 80% of adult male CBA/H-T6T6 mice, and a high proportion of these tumors had cytoplasmic Inclusion bodies (CIB). Three types of CIB were distinguished morphologically. By electron microscopy, the commonest (type 1) were membrane-bound bodies, arising within the rough endoplasmic reticulum of neoplastic cells. They were composed of a reticulated electron-dense component associated with a more diffuse granulofibrillary material. When mature, they were 1–20 μ in diameter; some filled the cells. By light microscopy, they were globular, hyaline, and eosinophilic. Most showed internal substructures (some eccentrically placed), were multiple, and stained differently from the general inclusion matrix. Type 2 CIB were less common, larger, and composed predominantly of fine granular matrix; however, they seemed to be related to type 1. Type 3 CIB were rare and resembled Mallory's hyalin. Types 1 and 2 consisted largely of protein and phospholipid without detectable nucleic acids or virus particles. Type 1 CIB were present only in the most highly differentiated neoplasms. Immunologic assay of sera from hepatoma-bearing animals revealed that 18% contained α-fetoprotein (AFP). AFP was more frequent in sera from animals with less differentiated tumors. No AFP was detected in the CIB. Type 1 and type 2 CIB represented material that had aggregated within the rough endoplasmic reticulum; however, the specific roles of increased production, decreased utilization, or defective transportation were not elucidated.
The relative responsiveness to inhaled leukotriene E4, methacholine and histamine in normal and asthmatic subjects
Authors: SP O'Hickey, JP Arm, PJ Rees, BW Spur, TH Lee
Journal: European Respiratory Journal (1988)

The relative bronchoconstricting potencies of leukotriene E4 (LTE4) methacholine and histamine have been compared in asthmatic and normal subjects. LTE4 responsiveness in asthmatic subjects, as measured by the dose which produced a 35% fall in specific airways conductance (PD35), ranged from 0.06-24.4 nmol (geom mean 4.1 nmol, n = 20). This was significantly less than the PD35 in normal subjects (range 39.0-370 nmol, geom mean 105 nmol, n= 6; p less than 0.001). There was a correlation between LTE4 and methacholine responsiveness (r = 0.84, p less than 0.001) and between LTE4 and histamine responsiveness (r = 0.79, p less than 0.001). LTE4 was 73 times more potent than methacholine and 112 times more potent than histamine in asthmatic subjects. LTE4 was 20 times more potent than methacholine and 58 times more potent than histamine in normal subjects. LTE4 is a potent bronchoconstrictor agent, and LTE4 responsiveness correlates with both histamine and methacholine responsiveness.