tbuckley/cabot-search huggingface dataset:
Alternative medicine: an attractive nuisance.
Authors: J R Durant
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9440714 Alternative medicine: an attractive nuisance. J R DurantxJ R DurantSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.1.1 PDF "Alternative medicine: an attractive nuisance.." Journal of Clinical Oncology, 16(1), pp. 1–2© 1998 by American Society of Clinical Oncology
Non-invasive bioluminescence imaging of caspase-3 activity in Breast Cancer
Authors: C. C. Olsen, F. Li, Z. He, W. Li, C. Li
Journal: Journal of Clinical Oncology (2009)

e14557 Background: Apoptosis is a major form of tumor cells death during cytotoxic therapy. Understanding the kinetics of apoptosis would greatly facilitate development of more effective therapeutic approaches. In order to monitor apoptosis activities in vivo, we developed a novel bioluminescence-based reporter gene to detect caspase 3 activities, which are elevated at the execution phase of apoptosis. Methods: A caspase-3 reporter system was constructed by combining two different reporter proteins; green fluorescent protein (GFP) and firefly luciferase (FL) linked through multiple polyubiquitin domains with a caspase-3 recognition site. Under normal circumstances, the reporter proteins are rapidly degraded by the proteasome system.. During apoptosis, activated caspse 3 cleaves off the multi-ubiquitin domain from the reporter protein. This enable the GFP and luciferase fusion reporter to be stabilized and achieve a significant gain in GFP protein and luciferase activities, which in turn could be monitored both in vitro and in vivo. 4T1 cells transduced with CMV-luc or Caspase-3 reporter xenografts were treated with both chemotherapy and radiation therapy and monitored for apoptosis activity. Results: In vitro experiments demonstrated increased luciferase with increasing radiation dose reflective of apoptosis with background levels nearly undetectable. Taxol was associated with a time-dependent increase from 24 to 72hrs after drug exposure, indicating that apoptosis is a gradual, heterogeneous process. EGFP signal increased from 1.85% in controls to 80.6% in cells treated with 1uM Taxol. Xenografts showed nearly undetectable luciferase background with Cytoxan therapy resulting in a 90-fold increase, 10 Gy a 24 fold increase and fractionated RT (5Gy x3) with a 46-fold increase. Conclusions: We developed a novel in vivo caspase reporter based on the ubiquitous proteosome system of protein degradation and bioluminsecence imaging. This allowed us to assess activation of apoptosis in response to chemoradiation therapy in tissue culture and breast cancer xenografts over the course of 2–3 weeks, which has not been possible with other technologies. No significant financial relationships to disclose.
Phase II trial of nonpegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer: A translational study.
Authors: M. Montanari, F. Fabbri, L. Frassineti, E. Rondini, R. Mattioli, S. Luzi Fedeli, D. Turci, S. Carloni, D. Amadori, G. Cruciani
Journal: Journal of Clinical Oncology (2010)

4683 Background: Nonpegylated liposomal doxorubicin(NPLD) (Myocet) has shown an important in vitro activity in hormone-refractory prostate cancer(HRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy after docetaxel failure in HRPC. Secondary objectives included treatment-related toxicity, time to-progression and overall survival. Methods: Fifty-eight patients were enrolled onto the study. Eligibility criteria were prostate cancer resistant to LHRH and antiandrogens, PSA > 20 ng/ml or measurable lesions according to RECIST criteria, previous docetaxel-based chemotherapy and adequate cardiac function with left ventricular ejection fraction (LVEF) > or = 50%. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. Objective responses were evaluated every nine weeks by PSA testing and imaging for measurable lesions. LVEF was also checked to monitor cardiac function. Results: Median patient age was 74 years (range 52-85) and median baseline PSA concentration was 102 ng/ml (range 5-3258). Twenty-two (37.9%) patients had measurable lesions. The first evaluation after 9 weeks showed objective or PSA responses (reduction > 50%) in 10 (17.2%) patients and stable PSA in 23 (39.6%) patients. Twenty-five (43.1%) patients had progressed (PSA increase > 25%). Toxicity was generally mild (grade 1/2) and infrequent with grade 3 leucopenia and neutropenia in 2 (3.4%) cases. No drug-related serious adverse events were reported and there were no cases of heart failure or decrease in LVEF > 10%. Conclusions: Our results show that weekly administration of NPLD is an active treatment with a good tolerability profile in older patients. The in vitro activity and mechanism of action of NPLD in docetaxel-resistant cells advocate further evaluation of this drug as second-line treatment for advanced HRPC. No significant financial relationships to disclose.
Roflumilast N-oxide, a PDE4 inhibitor, curbs bleomycin-induced lung fibroblast activation in vitro
Authors: Beatrice Arezzini, Daniela Vecchio, Piero A. Martorana, Hermann Tenor, Concetta Gardi
Journal: European Respiratory Journal (2011)

Objective:  Activated lung fibroblasts may foster small airway thickening in COPD. Roflumilast, an oral, selective PDE4 inhibitor approved in EU for severe COPD, mitigates bleomycin (BLM)-induced lung fibrosis  in vivo . This study addressed whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, modulates effects of BLM on human lung fibroblasts (HLF)  in vitro . RNO was used at 2nM, corresponding to therapeutic plasma levels.   Methods:  HLF pre-incubated with RNO (2nM) were exposed to BLM for 24 or 48h. Reactive oxygen species (ROS) were quantified by 29,79-dichlorofluorescein (DCF) accumulation from dichlorodihydrofluorescein diacetate. Total glutathione (GSH) was measured with the GSH reductase DTNB protocol. Proliferation and collagen synthesis was assessed as [ 3 H] thymidine and [ 3 H] proline incorporation (*p # p   Results:  BLM (24h) at 50 and 100μg ml -1  enhanced DCF accumulation by 1.9* and 1.4*-fold of control. RNO (2nM) reduced this increment by 50% #  and 85% # , respectively. In parallel, total GSH was reduced by BLM (100μg ml -1 ) yet rescued by RNO (2nM) (nmol mg protein -1 : Control 32.2±1.1, BLM 26.6±1.3*, BLM+2nM RNO 30±1.7 # ). BLM (50μg ml -1 ) increased [ 3 H] thymidine incorporation in HLF by 1.4*-fold that was abolished by RNO (2nM). Finally, RNO (2nM) reduced [ 3 H] proline incorporation that was increased to 179±35%* of control (100%) with BLM (50μg ml -1 ) to 83±13% #  of control. RNO (2nM) did not affect basal ROS, total GSH, [ 3 H] thymidine or [ 3 H] proline incorporation.   Conclusions:  BLM augmented ROS formation, reduced total GSH and increased proliferation and collagen synthesis of HLF  in vitro . RNO (2nM) prevented these effects.
QTc interval in advanced cancer patients
Authors: D. Trivanovic, R. Dobrila-Dintinjana, Z. Mavric, D. Stimac, M. Petkovic
Journal: Journal of Clinical Oncology (2009)

e20658 Background: The purpose is to identify prognostic factors that may have impact on survival in patients with advanced cancer. Methods: We retrospectively reviewed the data of patients who had biopsy proven advanced solid cancer disease in stage IV and no history or evidence of any prior cardiac disease. Univariate and multivariate stepwise Cox proportional hazard regression analysis were performed to identify independent predictors of one year survival. Results: Between 1/01 and 9/05, 143 patients (83 male and 60 female) with advanced cancers were evaluated in our institution. The primary site of disease was lung (28%), pancreas (19%), colon (15%), rectum (13%), breast (12%), and other (13%). The median follow-up was 12,5 months, median overall survival (OS) was 8.1 months, and 1-year OS rate was 62%. Median age was 65 years. OS was significantly related to the following pre-treatment prognostic factors: Age ≥65 (years), anaemia (hemoglobin level &lt;13.2 g/dl), Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and prolonged QTc interval in electrocardiogram (ECG). However, multivariate analysis revealed only prolonged QTc as independent prognostic parameter with 1-y survival status. Using 440 ms as the cut off value, the QTc interval was prolonged in 32 patients (22%) with median survival of 45 days and normal in 111 patients (78%) with median survival of 280 days. During the one-year 25 patients (78%) died in group with prolonged QTc interval while in group with normal QTc interval died 63 patients (57%). Conclusions: The results of our study indicate that a prolonged QTc interval (&gt; 440 ms) is an adverse prognostic sign in patients with advanced cancer and without cardiac disease which correlates with increased mortality rates within one year after the diagnosis. Our findings suggest that QTc prolongation may be a good adjunct in risk stratification of patients with advanced cancer who are being considered for aggressive treatment regimens. [Table: see text] No significant financial relationships to disclose.
Efficacy and safety of the vasopressin antagonist conivaptan in patients with euvolemic hyponatremia evaluated in a phase III clinical trial
Authors: J. G. Verbalis, J. K. Ghali, P. Gross, W. A. Long, N. Smith
Journal: Journal of Clinical Oncology (2006)

8550 Background: Hyponatremia, often caused by the inappropriate secretion of arginine vasopressin (AVP), is a common electrolyte disorder in patients with small-cell lung cancer (15%), head and neck cancer (3%), and non-small-cell lung cancer (0.7%). Conivaptan (CNV), a novel V 1A and V 2 AVP antagonist, produces aquaresis–the electrolyte-sparing excretion of water. CNV was recently approved for the treatment of euvolemic hyponatremia in hospitalized patients. The efficacy of CNV 40 mg/d was compared with that of placebo (PBO) on days 2 and 4 of a 4-day study in patients with euvolemic hyponatremia. Methods: This randomized, double-blind, multicenter, PBO-controlled trial enrolled 84 patients with euvolemic or hypervolemic hyponatremia (serum [Na + ] 115 to &lt;130 mEq/L). Patients were assigned to a PBO or a CNV 20-mg IV loading dose, followed by a continuous infusion of PBO or CNV 40 or 80 mg/d for 4 days. The primary efficacy measure was the change in serum [Na + ] from baseline during treatment, as measured by the area under the serum [Na + ]-time curve (AUC). Secondary efficacy measures included the change from baseline in serum [Na + ]; time from first dose to achieve a confirmed ≥4 mEq/L increase in serum [Na + ]; and the number of patients achieving a confirmed ≥6 mEq/L increase in serum [Na + ] or normal serum [Na + ] (≥135 mEq/L). Of the 84 patients enrolled, 56 (66.7%) had euvolemic hyponatremia; presented here are the results from 21 given PBO and 18 given CNV 40 mg/d. Results: The baseline serum [Na + ] was similar in both treatment groups (PBO: 124.3 mEq/L, CNV 40 mg/d: 123.6 mEq/L). CNV 40 mg/d improved serum [Na + ] and all secondary efficacy measures significantly more than PBO (Table). CNV was well tolerated; the most common adverse events associated with CNV at the end of the 4-day treatment were infusion-site reactions, postural hypotension, and thirst. Conclusion: CNV 40 mg/d increased serum [Na + ] significantly more than PBO on days 2 and 4 in patients with euvolemic hyponatremia. [Table: see text] [Table: see text]
G02 : Ledipasvir/sofosbuvir with ribavirin is safe and efficacious in decompensated and post liver transplantation patients with HCV infection: Preliminary results of the prospective solar 2 trial
Authors: M. Manns, X. Forns, D. Samuel, J. Denning, S. Arterburn, T. Brandt-Sarif, H. Dvory-Sobol, P.S. Pang, J.G. McHutchison, E. Gane, D. Mutimer
Journal: Journal of Hepatology (2015)
IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition
Authors: Zeliha Oruc, Christelle Oblet, Ahmed Boumediene, Anne Druilhe, Virginie Pascal, Elisabeth Le Rumeur, Armelle Cuvillier, Chahrazed El Hamel, Sandrine Lecardeur, Tomas Leanderson, Willy Morelle, Jocelyne Demengeot, Jean-Claude Aldigier, Michel Cogné
Journal: Journal of the American Society of Nephrology (2016)

IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch–Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α 1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen–free environment had less IgA deposition. However, serum IgA of specific pathogen–free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α 1KI, and even J chain–deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post–translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.
Canine Mastocytoma: Excess Risk as Related to Ancestry
Authors: James A. Peters
Journal: JNCI Journal of the National Cancer Institute (1969)

Common ancestral configuration may, in certain breeds of dogs (boxers, Boston terriers, bullterriers), explain their demonstrated increased relative risk to mastocytoma. Comparison of 230 study cases to a normal population sample indicated the relative risk (age-sex adjusted) to mastocytoma for the 3 breeds taken together was approximately 14, and no less than 8 for any breed within the group. Although available information indicates it would be impossible to identify specific breeds or genetic factors which contributed to an increased breed susceptibility to canine mastocytoma, evidence is presented indicating such susceptibility may be related to a strong relationship to the bulldog, English terrier, or both. These data provide statistical evidence of a positive correlation between genetic configuration and excess risk to canine mastocytoma and, hopefully, will stimulate further investigation into genetic susceptibility to neoplasia in comparative oncology and its extrapolation to studies of cancer causation in man.
DNA evolutionary rates in nine-primaried passerine birds.
Authors: A H Bledsoe
Journal: Molecular Biology and Evolution (1987)

Differences in single-copy nuclear-DNA sequences among 13 species of passerine birds were measured using DNA-DNA hybridization. A matrix of pairwise dissimilarity values (delta mode distances) was constructed from analysis of fitted thermal dissociation curves. A least-squares method of phylogenetic estimation was used to construct two topologies from the distance matrix, one constraining branch lengths of sister taxa to be equal and the other permitting such lengths to vary. These topologies were identical in the pattern of branching of taxa, and the difference in their sums of squares was not statistically significant, suggesting that rates of DNA evolution in sister groups of nine-primaried oscines are equal. A nonparametric test for nonrandom variation in distances of sister groups to outgroup taxa revealed no statistically significant deviation from random variation that would be expected as a result of measurement error. However, the level of measurement error was such that rates of DNA evolution in sister taxa could vary by as much as 10% without being detected with the statistical methods used here.
Patients with Hodgkin'S Lymphoma Have a Significantly Better Outcome If Treated Within a Clinical Trial
Authors: A.A. Moccia, G. Wiebke, A. Stathis, F. Cavalli, M. Ghielmini, K. Aprile von Hohenstaufen, B. Vannata, E. Zucca
Journal: Annals of Oncology (2014)
Cutaneous Cancer in Dakar
Authors: R. Camain, A. J. Tuyns, H. Sarrat, C. Quenum, I. Faye
Journal: JNCI Journal of the National Cancer Institute (1972)

The distribution pattern of skin cancer in West Africa was defined by the great frequency of squamous cell carcinoma, particularly on the lower limbs, frequency of melanoma and Kaposi's sarcoma, and rarity of basal cell carcinoma. The age, sex, and site distributions and histopathological features for each type were described for 972 cases in Dakar. The African pattern was compared to the Asian and European patterns. The significance of environmental factors (trauma and sunlight), the characteristics of pigmentation, and the pilary system of dark skin were discussed. The possible reticuloendothelial origin of Kaposi's sarcoma was suggested. Most skin tumors in Africa are potentially preventable.
Human T-lymphotropic virus type III infection in previously immunocompromised hosts.
Authors: J E Groopman, S M Hammer, S E Sallan, J D Allan
Journal: Journal of Clinical Oncology (1986)

The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection. Development of unusual infectious diseases in patients with neoplasms and other underlying immune deficiency disorders should lead to consideration of HTLV-III infection. Surveillance data should be obtained on these patients to accurately define the scope of HTLV-III infection.
Pain relief into practice: rhetoric without reform.
Authors: K M Foley
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.9.2149 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7545217 Pain relief into practice: rhetoric without reform. K M FoleyxK M FoleySearch for articles by this author https://doi.org/10.1200/JCO.1995.13.9.2149 First Page PDF © 1995 by American Society of Clinical Oncology
O-005 Ramucirumab (RAM) as second-Line treatment in patients with advanced hepatocellular carcinoma (HCC) following first-line therapy with sorafenib: comprehensive results from the randomized phase III REACH study
Authors: A. Zhu, M. Kudo, J.O. Park, B.-Y. Ryoo, C.-J. Yen, H.-C. Chung, A. Baron, T. Okusaka, R. Poon, D. Pastorelli, J.-F. Blanc, T. Flesch Pfiffer, K. Kubackova, J. Trojan, J. Sastre, P. Malfertheiner, M. Peck-Radosavljevic, S.-C. Chang, P. Abada, L. Yang, A. Girvan, I. Chau
Journal: Annals of Oncology (2015)
Generation of Cytotoxic Lymphocytes Against Human Tumor Cells In Vitro by Various Soluble Microbial Extracts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B Sharma, M J Brunda, P Minden
Journal: JNCI Journal of the National Cancer Institute (1979)

The abilities of soluble extracts of Salmonella typhimurium, Bordetella pertussis, Pseudomonas spp., Candida albicans, Mycobacterium tuberculosis (strain H37Rv), and Corynebacterium parvum to induce cytotoxic lymphocytes (CL) in vitro against human tumor cells were studied. Lymphocytes from most, but not all, normal persons became distinctly cytotoxic to malignant melanoma (RPMI-7932) and/or breast tumor (SH-3) but not to autologous phytohemagglutinin blast cells after stimulation with five of six microbial extracts tested. Variation in the cytotoxicity (CT) response by lymphocytes from different donors was considerable. In one case, microbial extracts rendered lymphocyte populations cytotoxic to one but not to the other tumor targets tested. Concentrations of 5–20 μg N/ml were more effective in the generation of CL than were concentrations of 37 mg N/ml or higher. In several cases, higher concentrations (37–80 ʼg N/ml) appeared to exert suppressive effects. The addition of extracts to mixed lymphocyte-tumor cell cultures (MLTC) had several different effects. In 7 of 19 experiments, neither tumor cells nor extracts generated significant CT. However, in five of these seven experiments, the combination of tumor cells and extracts did generate CT. In four other experiments, tumor cells alone did not induce CL, but microbial extracts alone did. The addition of extracts to MLTC significantly augmented CT in two of these cases and more than doubled the CT obtained with extracts alone in the other two. In two experiments, addition of extracts suppressed induction of CT.
Omission of Histologic Grading From Clinical Decision Making May Result in Overuse of Adjuvant Therapies in Breast Cancer: Results From a Nationwide Study
Authors: J. Lundin, M. Lundin, K. Holli, V. Kataja, L. Elomaa, L. Pylkkänen, T. Turpeenniemi-Hujanen, H. Joensuu
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.