tbuckley/cabot-search huggingface dataset:
Phase I study of a multipeptide melanoma vaccine (MPV) (MAGE-10.A2, Melan-A ELA, NY-ESO-1b, tyrosinase leader) in patients with melanoma (M)
Authors: K. P. Papadopoulos, C. Visser, K. Chu, J. Ellis, P. Harris, C. Hesdorffer, E. Hoffman, M. L. Keohan
Journal: Journal of Clinical Oncology (2005)

7551 Background: Vaccination of melanoma (M) patients (pts) with a combination of cancer-testis and M associated peptides may circumvent tumor escape due to antigen loss. GM-CSF may promote T-cell mediated anti-tumor activity. This study was designed to determine, in pts with high-risk or metastatic M, the safety and tolerability of intradermal multipeptide melanoma vaccine MPV [MAGE-10.A2 (300 μg), Melan-A ELA (100 μg), NY-ESO-1b (100 μg) and tyrosinase leader (100 μg)] and to assess antigen-specific cellular and humoral immunologic efficacy with or without subcutaneous GM-CSF. Some peptides used in this trial have previously been used individually in trials involving pts with M. Study design: Twenty HLA-A2+ pts with Stage III or Stage IV M were randomized to receive either MPV alone or MPV plus GM-CSF (75μg for 5 days starting 2 days before each MPV administration) weekly x 6. DTH, peripheral blood CD8+ cells by tetramer and NY-ESO-1 specific antibodies by ELISA were measured. Results: Of twenty pts with stage III (15 pts) and IV (5 pts) M [12 male/8 female, median age 54 years, range (28–74)] enrolled, 1 pt failed to complete all six vaccinations due to disease progression. No treatment related adverse events ≥ grade 1 occurred except for 2 injection site reactions and 2 allergic reactions to GM-CSF. Antigen specific DTH reactions were detected for MAGE-10 (MPV+GMCSF=1pt), NY-ESO-1b (MPV=3pts/MPV+GMCSF=3pts) and tyrosinase leader (MPV=6pts/MPV+GMCSF=5pts). Tetramer analysis showed no detectable induction of peptide specific CD8+ T-cells. Pre-existing NY-ESO-1 specific antibodies were detected in 2 patients. Antigen specific DTH and tetramer responses showed no correlation to each other, nor was there correlation with the use of GM-CSF. 3 pts were evaluable for tumor response (2PD, 1SD). Conclusions: The multipeptide vaccine [MAGE-10, Melan-A, NY-ESO-1 tyrosinase leader] is safe and tolerable. It does not induce humoral or antigen specific CD8+ T-cells, either alone or with GM-CSF, at the schedule utilized in this study. Combination of MPV with a more effective adjuvant is required to achieve induction of immune response Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration LICR LICR
An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies
Authors: R. Rosso, M.R. Sertoli, P. Quierolo, O. Sanguineti, M.C. Barzacchi, G.L. Mariani, L. Miglio, M. Venturini, S. Toma
Journal: Annals of Oncology (1992)
Reply
Authors: Kai‐Henrik Peiffer, Lisa Sommer, Stefan Zeuzem, Christoph Sarrazin
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Peiffer received grants from Gilead and Bristol‐Myers Squibb. Dr. Zeuzem consults for, advises for, and is on the speakers' bureaus of AbbVie, Bristol‐Myers Squibb, Gilead, Janssen, and Roche. Dr. Sarrazin consults for and is on the speakers' bureaus of Gilead, Merck, Bristol‐Myers Squibb, and AbbVie. Author names in bold designate shared co‐first authorship. REPLY: Interesting data were presented by Pedergnana et al. to add to the picture of the association between the host interferon lambda 4 (IFNL4) genotype and the presence of the NS5A resistance‐associated variant (RAV), Y93H, in hepatitis C virus (HCV)‐infected patients. Recently, we and other groups observed a highly significant correlation between the presence of Y93H and the rs12979860 (IL28B) C/C genotype in HCV genotype (GT) 1b–infected patients.1 Whereas our analyzed cohort also contained a small number of GT3‐infected patients (n = 51), Pedergnana et al. examined this phenomenon in a large cohort including (n = 496) GT3a‐infected patients. Interestingly, the strong association observed in GT1b seems to be absent in GT3a, which indicates a HCV genotype‐depending underlying mechanism. However, from our perspective, a weak, but nonsignificant, trend for a higher prevalence of Y93H in rs12979860 C/C can also be observed in this analysis as well as at the consensus level as at any level of RAV detection slightly more C/C patients than non‐C/C patients were Y93H positive (6.5% in comparison to 3.5% and 13.5%‐9.6%, respectively). In the case of HCV GT1a, because of a low overall prevalence of Y93H in GT1a samples in our study (1.5%; n = 259), we could not observe a significant association between Y93H and rs12979860 C/C.2 In contrast, Zeuzem et al. described a highly significant correlation between Y93H and rs12979860 C/C also in GT1a‐infected patients when analyzing all patients who have been enrolled globally in sofosbuvir‐based clinical studies (n = 3,312; P < 0.0001).3 Thus, it seems well possible that a significant association of IFNL4 genotype and Y93H might be only detectable in larger patient cohorts. Furthermore, also the ethnic origin of the patient cohorts might be of importance. Finally, deep sequence analysis as well as sequencing of the entire HCV genome most likely will help to improve our understanding of HCV viral variants within different HCV genes associated with specific IFNL4 genotypes. It seems to be likely that Y93H will not be the only variant associated with IFNL4 genotypes, and functional studies to clarify the underlying molecular mechanisms of these observations are required.
CERA (Continuous Erythropoiesis Receptor Activator): Dose-response, pharmacokinetics and tolerability in phase I multiple ascending dose studies
Authors: F. C. Dougherty, B. Reigner, P. Jordan, A. Pannier
Journal: Journal of Clinical Oncology (2004)

6692 Background: Preclinical trials have shown that the innovative erythropoietic agent CERA stimulates erythropoiesis more potently than epoetin (in terms of magnitude and duration of response) and has a prolonged serum half-life. Its use may thus allow less frequent dosing (every 3 or 4 weeks) and more flexible treatment of anemia associated with cancer or renal disease. In phase I single ascending dose studies, CERA administered intravenously (IV) or subcutaneously (SC) produced potent dose-dependent erythropoietic activity (Reigner et al. Proc Am Soc Clin Oncol 2003; 22: 732). To examine the pharmacodynamic effect and tolerability of CERA with multiple ascending doses, additional phase I studies were performed. Methods: In two open-label, parallel-group, placebo-controlled studies, healthy volunteers were randomized to receive CERA (0.4, 0.8, 1.6, or 3.2 μg/kg) by IV injection on three occasions at 3-weekly intervals (n=61), or by SC injection on four occasions at 2-weekly intervals (n=48). Results: A rapid and dose-dependent erythropoietic response to CERA was observed; peak effects in reticulocyte counts were seen 7 and 10 days after IV and SC administration, respectively, with cumulative hematocrit, hemoglobin, and RBC responses. Mean (± SEM) elimination half-life was 133 ± 9.83 h for IV and 137 ± 21.9 h for SC CERA. Repeated dosing had no apparent clinically relevant effect on pharmacokinetics. Volume of distribution was small with IV CERA (3.0–5.4 L) and clearance was low with both IV and SC CERA (IV 27.6–44.6 mL/h, SC 97–347 mL/h). Accumulation did not occur with 3-weekly IV dosing and was small with 2-weekly SC dosing. Adverse events were generally mild and there were no serious adverse events. No antibodies were detected by ELISA in any subject. Conclusions: CERA administered either IV or SC demonstrated potent, prolonged dose-dependent erythropoietic activity and was generally well tolerated in phase I multiple ascending dose studies. Phase II studies administering CERA at various dosing intervals to cancer patients are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration F. Hoffmann-La Roche
Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema
Authors: John A. Wells, Adam R. Glassman, Allison R. Ayala, Lee M. Jampol, Neil M. Bressler, Susan B. Bressler, Alexander J. Brucker, Frederick L. Ferris, G. Robert Hampton, Chirag Jhaveri, Michele Melia, Roy W. Beck
Journal: Ophthalmology (2016)
Using Small Molecules To Identify Critical Signaling Pathways Of Mutant N-RAS In Acute Leukemia Cells
Authors: Atsushi Nonami, Martin Sattler, Ellen L. Weisberg, Jianming Zhang, Qingsong Liu, Matthew Patricell, Hojong Yoon, Amanda L. Christie, Amy M. Sauer, Nancy Kohl, Andrew L. Kung, Taebo Sim, Nathanael S. Gray, James D. Griffin
Journal: Blood (2013)
Transfer of Viable Putative Preneoplastic Hepatocytes to the Livers of Syngeneic Host Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Brian A. Laishes, Emmanuel Farber
Journal: JNCI Journal of the National Cancer Institute (1978)

A new approach was developed by which freshly isolated, chemical carcinogen-altered hepatocytes with the positive marker gamma-glutamyl transpeptidase (gamma-GT) could be transferred from adult donor F344 rats to the livers of syngeneic, adult host rats. Selective proliferation of gamma-GT-positive hepatocytes was induced in host rat livers, such that large, macroscopic colonies of altered hepatocytes could be generated within 10 days of the cell transfer operation. Quantitation of the number of gamma-GT-positive hepatocyte colonies (foci) appearing per square centimeter of host liver section area on day 10 following cell transfer revealed that prior treatment of host rats with a low dose of 2-acetylaminofluorene was essential for the appearance of large numbers of foci. In addition, the appearance of foci on day 10 depended on the presence of intact, gamma-GT-positive hepatocytes in the infused (transferred) cell suspensions.
Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer.
Authors: R T Chlebowski, L Bulcavage, M Grosvenor, E Oktay, J B Block, J S Chlebowski, I Ali, R Elashoff
Journal: Journal of Clinical Oncology (1990)

This randomized, prospective, placebo-controlled clinical trial compares the influence on nutritional status and survival of hydrazine sulfate with placebo addition to cisplatin-containing combination chemotherapy in patients with unresectable non-small-cell lung cancer (NSCLC). The trial consisted of 65 patients with advanced, unresectable NSCLC who had had no prior chemotherapy, were at least partially ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status [PS] level 0-2), and who had adequate hematologic, renal, and hepatic function. All patients received the same defined combination chemotherapy (cisplatin, vinblastine, and bleomycin) and the same defined dietary counseling with the addition of either three times daily oral hydrazine sulfate (60 mg) or placebo capsules. Hydrazine sulfate compared with placebo addition to chemotherapy resulted in significantly greater caloric intake and albumin maintenance (P less than .05). Considering all patients, survival was greater for the hydrazine sulfate compared with placebo group (median survival, 292 v 187 days), but the difference did not achieve statistical significance. In favorable PS patients (PS 0-1), survival was significantly prolonged (median survival, 328 days v 209 days; P less than .05) for hydrazine sulfate compared with placebo addition. In a multifactor analysis, PS, weight loss, and liver involvement were the final variables. Objective response frequency and toxicity were comparable on both arms. Hydrazine sulfate may favorably influence nutritional status and clinical outcome of patients with NSCLC. Further definitive studies of hydrazine sulfate addition to therapeutic regimens in NSCLC are warranted.
Indoor Allergens: Assessing and Controlling Adverse Health Effects
Journal: Thorax (1994)

The bowel habit of 350 preschool children from a single general practice was studied. Eighty five per cent of 1 to 4 year olds eating a predominantly low fibre diet opened their bowels once or twice a day and 96% of the children fell within the range of three times a day to every other day. At all ages most children produced soft stools of about 25 ml volume. Mean intestinal transit time of 35 (10%) randomly selected children was 33 hours. There is a significant correlation between infrequency of bowel action, longer transit time, hard stools, and the passage of blood.
LincRNA Expression Discriminates Cytogenetic Subtypes In B-Lymphoblastic Leukemia and Plays a Functional Role In Leukemia Cell Survival
Authors: Waters Ella, Thilini R Fernando, Norma Iris Rodriguez-Malave, Weihong Yan, Martina Pigazzi, Giuseppe Basso, Dinesh S. Rao
Journal: Blood (2013)
Cytokinetic Studies of the Effects of Activated Macrophages on Tumor Target Cells2
Authors: James L. Krahenbuhl, Lewis H. Lambert
Journal: JNCI Journal of the National Cancer Institute (1975)

The kinetics of the in vitro interaction between activated mouse macrophages and tumor target cells were studied in Swiss-Webster female mice with the use of the inhibition of uptake of tritiated thymidine by target cells as a quantitative measure of macrophage-effected cytostasis. Unlike the normal macrophage, the individual activated macrophage had an enhanced capacity to inhibit DNA synthesis in tumor target cells. Such cytostasis appeared to result from direct contact between activated macrophages and target cells. Culture conditions discouraging direct contact caused little or no cytostasis, regardless of the ratio of macrophages to target cells. When culture conditions favored direct contact between effector cells and target cells, cytostasis was markedly increased if the ratio of macrophages to target cells was raised.
A controlled study of self-help intervention for widows
Authors: M L Vachon, W A Lyall, J Rogers, K Freedman-Letofsky, S J Freeman
Journal: American Journal of Psychiatry (1980)

The authors conducted a 2-year study of postbereavement adaptation in 162 widows. Sixty-eight were paired with a widow contact who provided emotional support and practical assistance. The differences between the women receiving intervention and the controls at 6, 12, and 24 months after bereavement suggested that those receiving intervention followed the same general course of adaptation as control subjects but that the rate of achieving landmark stages was accelerated for the intervention group. The Goldberg General Health Questionnaire and two indices derived from the study questionnaire confirmed the hypothesized "pathway" of adaptation" through intra- and interpersonal adaptation to resolution of overall distress and the effectiveness of the intervention.
Group sequential design: Selecting appropriate bounds.
Authors: K. M. Anderson, J. Clark
Journal: Journal of Clinical Oncology (2010)

e13159 Background: Interim analysis is essential to protect the safety of patients in large trials as well as to focus research dollars and to get new therapies to patients in the quickest appropriate time frame. We start with the premise that trials should stop early when its results are overwhelming or when eventual demonstration of efficacy becomes futile. Methods: We will demonstrate how to select bounds on the basis of both clinical and statistical considerations, including a user-friendly open-source software tool. We apply the spending-function approach due to its flexibility and apply new families of spending functions to help make designs match desired properties. Results: The observed treatment effect required to stop, statistical evidence, and enrollment/endpoint dynamics are all considered in selecting interim analysis times and bounds. Conclusions: The approach reduces the need to work through technical statistical details and quickly compare multiple possible designs. No significant financial relationships to disclose.
Abstract 9139: Inspiratory and Expiratory Main Pulmonary Artery Dimensions on Chest CT Exclude Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Authors: Brett Fenster, Thomas Gethin-Jones, Samuel Lee, Alex Honeyman, Russell Bowler, Barry Make, J. Kern Buckner, Joyce Schroeder
Journal: Circulation (2012)

Background: Pulmonary hypertension (PH) is present in 30-70% of chronic obstructive pulmonary disease (COPD) and is a strong predictor of morbidity and mortality. Although previous studies have demonstrated that a chest CT-determined main pulmonary artery diameter (MPAD) of ≥ 29 mm during inspiration is associated with PH, these have utilized small groups of heterogenous pulmonary disease. Consequently, the predictive value of MPAD in a pure COPD population remains unknown. In addition, previous studies have not evaluated the diagnostic utility of expiratory phase MPAD. Since variable inspiratory effort and loading of the pulmonary vasculature may confound efforts to predict PH, expiratory phase MPAD measurement may be a reliable indicator of PH. COPDGene is multicenter prospective study that correlates genotype with chest CT COPD phenotype. Using a large subgroup of the COPDGene cohort, we hypothesized that inspiratory MPAD (iMPAD) and expiratory MPAD (eMPAD) on chest CT accurately predict PH when defined by echocardiographic estimation of RVSP in a cohort of COPD patients. Methods: COPDGene subjects who completed both high-resolution chest CT as well as echocardiography were included for analysis. Cross-sectional iMPAD and eMPAD were measured at the widest dimension at the level of the aorta using the VIDA Pulmonary Workstation 2 software by 3 blinded readers. Based upon the previous World Health Organization definition of mild PH as 40-50 mmHg, a right ventricular systolic pressure (RVSP) ≥ 45 mmHg was classified as PH. Results: Multivariate regression analysis of 182 COPD subjects revealed significant correlations between RVSP and iMPAD (r .45, p &lt; .0001) as well as eMPAD (r .41, p &lt; .0001). Optimal diagnostic performance of iMPAD occurred at ≥ 28 mm with an AUC of .69 and a NPV of 88% but a PPV of only 38%. In comparison, optimal performance of eMPAD occurred at ≥ 31 mm with an equal AUC (69%) and nearly equivalent NPV (85%) and PPV (42%). Conclusions: Both iMPAD and eMPAD perform with excellent NPV but poor PPV for prediction of PH in a COPD cohort. In contrast to previous studies indicating good PPV in heterogenous pulmonary disease populations, the diagnostic utility of pulmonary artery diameter measurement in the COPD population may reside in its NPV for PH.
Case Management for Depression by Health Care Assistants in Small Primary Care Practices
Authors: Jochen Gensichen, Michael von Korff, Monika Peitz, Christiane Muth, Martin Beyer, Marion Torge, Juliana J. Petersen, Thomas Rosemann, Ferdinand M. Gerlach
Journal: Annals of Internal Medicine (2009)

Gensichen and colleagues evaluated whether telephone case management facilitated by health care assistants can reduce depression symptoms and improve the process of care for patients with major dep...
Will There Be a Cure for Ebola?
Authors: Anthony P. Cardile, Travis K. Warren, Karen A. Martins, Ronald B. Reisler, Sina Bavari
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk–pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid–based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp). We review Ebola therapeutics progress in the aftermath of the West Africa Ebola virus outbreak and attempt to offer a glimpse of a path forward.
Correlation of immunological effects of anti-VEGF therapy with progression-free survival of advanced colorectal cancer patients
Authors: M. Manzoni, B. Rovati, S. Delfanti, K. Bencardino, S. Chatzileontiadou, S. Brugnatelli, F. Loupakis, E. Villa, A. Falcone, M. Danova
Journal: Journal of Clinical Oncology (2009)

e14559 Background: The clinical efficacy of Bevacizumab (BEV) in advanced colorectal cancer (mCRC) could be related not only to its well-established effect on tumor neoangiogenesis but also to a counteraction of VEGF-mediated dendritic cell (DC) abnormalities. The addition of BEV to chemotherapy (CT) may improve the number and function of blood DCs in cancer pts. We have focused on the correlation between this effect and the clinical efficacy of a BEV-based, 1 st -line treatment for mCRC. Methods: Starting from January 2007 we performed a flow cytometric analysis of PB lymphocytes and DC subsets in 53 mCRC pts who had not received prior CT for metastatic disease or for whom 6 months had elapsed since adjuvant CT (M/F: 31/22, median age: 59yrs; range 32–75; ECOG PS &lt;2), before and every 3 courses of a BEV+CT (5-FU± CPT11± Oxaliplatin) program. Biological data of the 42 evaluable pts that received all the planned treatment were correlated to both tumor response (OR) and progression free survival (PFS). Results: During treatment, DCs and their subsets showed a progressive, significant increase in absolute number, with respect to baseline, both in responder (CR,PR,SD) (67%) and in non responder pts. This effect on the DC profile was evidenced in responder pts up to 4 weeks since the last treatment course. After therapy completion, pts with PFS &gt; 15 months (58%) showed DC and DC1 absolute number significantly higher with respect to pts with shorter PFS (p&lt; .02). Conclusions: The recovery of blood DCs induced by 1 st - line, BEV-based therapy in mCRC pts indicates a potential additional anticancer mechanism of this drug. The improvement of DC number does not influence OR but correlates with longer PFS. This suggests that BEV can influence tumor regrowth by contributing to overcome the impairement of the host immune surveillance induced by VEGF. No significant financial relationships to disclose.
Dirty Dots as a Normal Trichoscopic Finding in the Elderly Scalp
Authors: Mariya Miteva, Mariana Lima, Antonella Tosti
Journal: JAMA Dermatology (2016)

Dirty Dots as a Normal Trichoscopic Finding in the Elderly ScalpTrichoscopy is a helpful tool in the diagnosis and management of hair and scalp disorders. 1Dirty dots have been described as a normal trichoscopic finding in the scalps of 10 of 19 healthy children (53%) between 5 months and 14 years of age. 2 None of the children had a preceding hair or scalp disorder.The dirty dots presented as clumped and haphazardly arrayed particulate debris and loose fibers of various colors.They are absent in adults 2 and, to our knowledge, have not been reported in people of other ages.
Metabolic Studies on the Mechanism of Urethan Action. II. Age and Tissue Specificity&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: C. P. Giri, S. V. Bhide
Journal: JNCI Journal of the National Cancer Institute (1967)

Immediate metabolic effects of intraperitoneal injection of urethan (1.0 mg/g body weight) were studied in lung, liver, and kidney tissues of young adult Swiss mice and compared with those of newborn mice of the same strain. Contents of ribonucleic and deoxyribonucleic acids of the three tissues as well as activities of aspartic and ornithine transcarbamylase were studied in both groups 6 hours after urethan injection. Urethan decreased the levels of ribonucleic and deoxyribonucleic acids of all the tissues as well as the activity of aspartic transcarbamylase in liver and lung tissues. Urethan exerted maximum effect on the lung tissue. The metabolic effects of urethan in the adult and newborn mice were comparable. Urethan did not exert any remarkable effect on the activity of liver ornithine transcarbamylase in the adult mice but decreased the activity of liver ornithine transcarbamylase in the newborn.