tbuckley/cabot-search huggingface dataset:
Erythropoietin Addition to Granulocyte Colony-Stimulating Factor Abrogates Life-Threatening Neutropenia and Increases Peripheral-Blood Progenitor-Cell Mobilization After Epirubicin, Paclitaxel, and Cisplatin Combination Chemotherapy: Results of a Randomized Comparison
Authors: Luca Pierelli, Alessandro Perillo, Stefano Greggi, Giovanna Salerno, Pierluigi Benedetti Panici, Giacomo Menichella, Andrea Fattorossi, Giuseppe Leone, Salvatore Mancuso, Giovanni Scambia
Journal: Journal of Clinical Oncology (1999)

PURPOSE AND METHODS: The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support. RESULTS: Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P &lt; .0001 and P &lt; .0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF–treated patients (P = .0009 and P = .0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO–treated patients (P = .0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF– and G-CSF + EPO–mobilized PBPCs have comparable in vitro functional properties. CONCLUSION: This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.
The value of intensive combination chemotherapy for juvenile chronic myelogenous leukemia.
Authors: H S Chan, Z Estrov, S S Weitzman, M H Freedman
Journal: Journal of Clinical Oncology (1987)

Nine children with juvenile chronic myelogenous leukemia (JCML) were diagnosed in an 8-year period from 1977 to 1984. The clinical courses and outcomes of five patients who received minimal or no chemotherapy were compared with that of four patients who were treated with intensive acute nonlymphoblastic leukemia (ANLL) combination chemotherapy. None of the five patients in the former group achieved clinical remission and their survivals were 1, 4, 4, 7, and 29 months, respectively. All four patients in the latter group achieved clinical remissions that lasted 11, 21, 21, and 27 + months, respectively. The durations of their survival (21, 26, 30, and 32 + months) were significantly better than the five patients who received minimal or no chemotherapy (P less than .05). Despite hospitalizations for chemotherapy and for treatment of chemotherapy-associated complications, the clinical status and quality of life of the children who achieved clinical remission were superior to those who remained in relapse. Although intensive chemotherapy induced lengthy remissions, three of the four patients have relapsed. Cytogenetic and cell culture data indicated that the monocytic-macrophage cells characteristic of JCML appeared to be suppressed during remission rather than totally eliminated. We recommend that ANLL-type combination chemotherapy be used as the initial treatment of JCML because of its promptness in effecting clinical remissions. Improved maintenance and consolidation protocols have to be developed to produce durable remissions and cures. Alternatively, bone marrow transplantation may be a useful option soon after remission is achieved with chemotherapy.
American Joint Committee on Cancer Classification for Melanoma.
Authors: G J Hill
Journal: Journal of Clinical Oncology (1992)

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.1992.10.2.345 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1732436 American Joint Committee on Cancer Classification for Melanoma. G J HillxG J HillSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.2.345 PDF "American Joint Committee on Cancer Classification for Melanoma.." Journal of Clinical Oncology, 10(2), pp. 345–346© 1992 by American Society of Clinical Oncology
Quality of life assessment of patients participating in phase I clinical trials during treatment (MC0115)
Authors: P. J. Atherton, D. W. Szydlo, C. E. Erlichman, J. A. Sloan
Journal: Journal of Clinical Oncology (2008)

9613 Background: There are psychological challenges associated with participation in Phase I clinical trials due to many consenting patients hoping for a cure despite assertions to dissuade such expectations. This study explored the impact of Phase I trial participation on patient quality of life (QOL). Methods: Patients enrolled onto Phase I studies between 9/10/2002 and 3/6/2007 were asked to complete the Control Preferences Scale (CPS) at baseline, the Linear Analogue Self Assessment (LASA) weekly during cycle 1, and the Trial Satisfaction (TS) survey at the end of cycle 1. All QOL was measured on a 0–10 point scale, 10 being best. The primary endpoint was the change in overall QOL at the end of cycle 1. Summary statistics were calculated for baseline covariates, QOL responses, treatment response and adverse events (AEs). Student’s t-test, Kruskall-Wallis and Pearson/Spearman correlation methodology were utilized. Results: 30 patients from 12 different Phase I trials participated. Overall QOL change from baseline was not significant (mean of -0.5, 95% CI [-0.92, 0.05], p=0.08). Four patients experienced a clinically meaningful deficiency by having an overall QOL decrease of at least 2 points. Significant decreases were seen in Physical Well-Being (WB), Emotional WB, and Mood (p=0.04, 0.04, 0.03, respectively). Correlations comparing QOL with the maximum AE grade were weak, the highest being for Emotional WB and Hopefulness (r=−0.41, −0.35). Gender and performance status were related to QOL domains of Fatigue, Anxiety and Hopefulness. CPS indicates concordance in preferred compared to played roles. CPS results and treatment response were unrelated to QOL scores. According to TS, patients seemed to feel participation in the treatment trial was worthwhile, they would do it again, and they would recommend the treatment trial to others (means of 8.7, 8.7 and 9.2, respectively), but they did not feel that their QOL improved as a result of the trial (mean of 4.0). Conclusions: Despite being satisfied with their participation in Phase I clinical trials, deficits in QOL appeared, independent of AEs or tumor response. Hence, it would seem advisable to include assessments in Phase I trials in order to identify and improve patient QOL. Supported in part by CA69912. No significant financial relationships to disclose.
Inhibition of Rat Natural Killer Cell Function by Carcinogenic Nickel Compounds: Preventive Action of Manganese&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J G Judde, F Breillout, C Clemenceau, M F Poupon, C Jasmin
Journal: JNCI Journal of the National Cancer Institute (1987)

The effects of carcinogenic nickel [(Ni) CAS: 7440-02-0] and Ni compounds on the natural killer (NK) cell activity of rat peripheral blood mononuclear cells (PBMCs) were studied. Rhabdomyosarcomas were locally induced by one im injection of Ni or Ni subsulfide [(Ni3S2) CAS: 12035-72-2] dust in the hind leg of WAG rats. A weakly tumorigenic dose of 5 mg Ni3S2 (tumor incidence, 2%) induced a transient decrease of PBMC NK activity against YAC-1 cells in vitro (from the 17th to the 23d wk after Ni3S2 inoculation), which could be restored by in vivo injections of partially purified rat fibroblastic interferon (IFN). Injection of 20 mg Ni (tumor incidence, 47.5%) produced a long-lasting depression of NK cell activity (from the 8th to the 23d wk). In vivo chronic IFN treatment of the Ni-injected rats neither restored NK cell activity nor affected the tumor incidence. However, NK cells of Ni-treated animals responded normally to IFN in vitro. Prospective analysis of individual NK cell responses showed that a persistent depression of basal NK cell activity was restricted to rats that subsequently developed a tumor. In these animals the time between carcinogen treatment and clinical detection of the primary tumor was positively correlated with the mean level of NK cell activity (3-4 determinations/rat). Admixture of manganese to Ni inhibited the development of tumors and also prevented the depression of NK cell activity produced by Ni alone. Noncarcinogenic Ni oxide stimulated NK cell activity. These results point out the possible involvement of NK cells in resistance to Ni-induced carcinogenesis.
Abstract 209: Different Reaction To Lactate Between The Atrial And The Ventricular Muscle In Excitation-contraction Coupling
Authors: Daisuke Shimura, Yoichiro Kusakari, Nobuhito Goda, Susumu Minamisawa
Journal: Circulation Research (2014)

Background: The effect of a metabolic change on excitation-contraction (EC) coupling is poorly understood in the atrial myocardium, while the previous studies have mainly focused on EC coupling in the ventricular myocardioum. Although the myocardium mostly uses fatty acid as an energy source, we have reported that metabolic substrate, includes lactate, can be used for energy production and that the metabolomic profile is different between the atria and the ventricles in mouse heart. In addition, it is still under discussion whether lactate can be an energy source for muscles. In the present study, we aimed to investigate the effect of lactate exposure on EC coupling in the atrial and the ventricular myocardium. Methods: We micro-injected aequorin (a Ca2+-sensitive photoprotein) into superficial cells of the left atrium and/or the left ventricular papillary muscle isolated from mice (C57/BL6, 12 - 17 weeks of age), and simultaneously measured intracellular Ca2+ concentration and tension (1 Hz at 36 °C). We added lactate (~10 mM) into HEPES-Tyrode solution (pH was adjusted at 7.4) and observed the changes in the peak tension and the peak Ca2+ concentration. Results and Conclusion: Lactate at a concentration of 10 mM significantly decreased the peak tension (61.7±6.0%; n = 3; P &lt; 0.05.) and the peak Ca2+ concentration (78.8±4.8%; n = 3; P &lt; 0.05.) in the atrial myocardium. Although we observed similar effect of lactate on the ventricular papillary muscle, it was modest compared with the atrial myocardium (72.8±5.6%, 91.6±13.5%, peak tension and Ca2+, respectively; n = 3; no significance). Our results suggest that the atrium has different characteristic of EC coupling from the ventricles in response to an increase in lactate, of which condition is often observed in myocardial ischemia. Moreover, lactate did not seem to contribute to make energy in terms of the tension in the heart. Simultaneous measurement of tension and intracellular Ca2+ concentration can be useful to analyze the atrial physiological property.
Phase-II trial of thalidomide for patients with metastatic renal cell carcinoma (RCC)
Authors: D. Green, J. Meza-Junco, C. Arce, M. Chavez-Macgregor, R. de la Peña, M. Sotomayor, F. Gabilondo
Journal: Journal of Clinical Oncology (2005)

4761 Background: Interferon-alfa and interleukin-2 are considered the standard treatment for patients with advanced RCC. However, most patients respond poorly to treatment with few long-term survivors and considerable toxicity. Clinical investigations of novel treatment strategies are needed. Thalidomide has been recognized as an antiangiogenic drug. Considering the overexpression of various angiogenic factors in RCC, we performed this phase-II trial of thalidomide in patients with metastatic RCC, in order to asses its efficacy and toxicity in this clinical scenario. Methods: Twenty patients were included, 12 (60%) had prior nephrectomy and none had received systemic therapy. Patients were treated with thalidomide at a starting dose of 100mg/day, duplicating the dose every two weeks until a maximum dose of 800mg/day or prohibitive toxicity was reached. Results: A maximum dose of 800mg, 600mg and ≤400mg was reached in 15 (75%), 1 (5%) and 4 (20%) patients, respectively. Two patients (10%) achieved a partial response, 11 (55%) had stable disease for at least 3 months and 7 (35%) progressed, none withdrew due to adverse effects. The median progression-free survival was 4.2 months (95% CI, 2.9–5.4) and overall survival 10 months (95% CI, 5.2–14.7); seven patients (35%) were alive after one year. Toxicity was common but mild, grade 1–2 constipation was observed in 12 patients, nausea in 6 and somnolence in 7; the only grade 3–4 toxicity was constipation (grade 3) in 2 patients (10%). In all cases toxicity was controlled with symptomatic treatment or after a dose-reduction. Conclusions: Our results, in terms of efficacy and toxicity, are in concordance with previous reports showing that thalidomide can be an alternative treatment in metastatic RCC, with the added advantage of being an orally administered drug with a favorable safety profile. Because stable disease is seen even without treatment in RCC, a phase-III trial is needed in order to confirm our results and clarify the role of thalidomide. No significant financial relationships to disclose.
APRICoT-P: A phase II randomized placebo controlled study of apricoxib, a potent COX-2 inhibitor in combination with erlotinib and gemcitabine in pancreatic cancer patients.
Authors: G. P. Keogh, R. M. Langdon, P. J. Stella, R. Manges, C. H. Chay, E. Looper, S. L. Zaknoen
Journal: Journal of Clinical Oncology (2010)

TPS224 Background: Apricoxib is a once-daily, oral, potent and selective inhibitor of COX-2. The COX-2 pathway plays a key role in tumor growth, angiogenesis, and resistance to therapy. COX-2 and EGFR signaling regulate the dominant ERK/MAPK, AKT and b-catenin pathways in this disease, so combinations of COX-2 and EGFR inhibitors are of particular interest in pancreatic cancer. In addition, b-catenin activity is implicated in gemcitabine resistance, so combination of standard chemotherapy with apricoxib and erlotinib could have synergistic effects. In a previous phase I study in NSCLC the combination of apricoxib and erlotinib was found to be safe and demonstrated a tumor control rate of 60% in recurrent patients. In an ongoing phase II study in NSCLC patients are being selected based on a decrease in PGE-M a urinary marker of COX-2 activity. Because pancreatic cancer overwhelmingly overexpresses COX-2 in tumor cells, patients were not selected on the basis of decreases in PGE-M. However, baseline and post-treatment urine are being collected will be evaluated in an exploratory analysis. Methods: Pts with recurrent, locally advanced, or metastatic pancreatic cancer were treated with erlotinib 100 mg PO daily and apricoxib/placebo 400mg PO daily and gemcitabine on the standard schedule for pancreatic cancer. The primary objective was a 60% improvement in time to progression over the placebo arm. Results: 57 (76%) patients of a planned accrual of 75 patients have been randomized in a 2:1 (active:placebo) fashion. Data are available for 43 patients. Characteristics: Sex: M/F: 13/30; Age range 47-86 yrs.; 12, ECOG PS 0, 23, PS 1, 2, PS 2 and NA, 6. Safety data is available for 40 patients. The most common adverse events included; rash (63%), diarrhea (50%) and nausea (35%). Drug-related serious adverse events included GI bleeding, MI and CVA. Conclusions: This study is the first randomized placebo controlled trial combining chemotherapy with COX-2 inhibition and EGFR kinase inhibition. Safety of this combination is acceptable in this patient population. Time to progression and overall survival data is expected in the 4th quarter of 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tragara Pharmaceuticals Tragara Pharmaceuticals
Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus
Authors: Louise H. Moncla, Gongxun Zhong, Chase W. Nelson, Jorge M. Dinis, James Mutschler, Austin L. Hughes, Tokiko Watanabe, Yoshihiro Kawaoka, Thomas C. Friedrich
Journal: Cell Host & Microbe (2016)
An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease
Authors: Sufeng Zhang, Joerg Ermann, Marc D. Succi, Allen Zhou, Matthew J. Hamilton, Bonnie Cao, Joshua R. Korzenik, Jonathan N. Glickman, Praveen K. Vemula, Laurie H. Glimcher, Giovanni Traverso, Robert Langer, Jeffrey M. Karp
Journal: Science Translational Medicine (2015)

A hydrogel binds to inflamed tissues, delivering therapeutics locally and reducing systemic drug exposure in mouse models of inflammatory bowel disease.
MarkPap test for cervical cancer screening
Authors: N. S. Markovic, O. Markovic, E. S. Henderson
Journal: Journal of Clinical Oncology (2005)

1021 Background: At ASCO 2001 we introduced a new biomarker driven technology MarkPap(r) for improving visualization of epithelial cell abnormalities on Pap smears. The biomarker is cervical acid phosphatase labeling dysplastic cells. At ASCO 2004, we presented data of two clinical trials. We are presenting results of comparison of the new test with the conventional Pap smear in general population. Material and Methods: MarkPap test is available as MarkPap Research Kit (www.markpap.com). The kit was given to cytopathology laboratories with instructions (2-level Screening Procedure and the Criteria for Reading and Interpretation of MarkPap slides) how to use it for cervical cancer screening. Cervical specimens were obtained from women coming for regular Pap test checkup after they signed an IRB approved informed consent. Doctors collected and split specimens into a control (Pap smear first) and a research sample (MarkPap smear). Demography, Pap test results, and disease progress were recorded on CRF up to two years. The study was conducted as a multicenter, recruitment in order of arrival, concurrent control clinical laboratory trial, split-sample, 2-group, assessor blinded study design. Performance measures (Pe, Ps) were the proportion of detected abnormal specimens, and the sensitivity and specificity of screening (standard for validation was the optimized cytologic truth). Statistical analyses were based upon alpha = 0.05, power 80%, 95% Confidence Interval, and minimal clinically meaningful difference of 10%. We compared proportions in paired groups. Results: One thousand twenty-three specimens were obtained. Nine hundred sixty-nine were received in pairs. Twenty-two were rejected as non-satisfactory. Among control slides (Ps) 21 were true positive-abnormal comparing to 38 in the new test group (Pe). Superiority of detection was confirmed because delta was below the lower level 95% CI. The equivalence was confirmed because both the upper and lower levels of 95%CI were between plus/minus delta. Conclusion: We concluded that the MarkPap test increases sensitivity of detection of abnormal cervical specimens while keeping the specificity equivalent with the conventional Pap test. Acknowledgment: Supported in part by NIH SBIR grant 2R44CA086767–02 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioSciCon BioSciCon BioSciCon BioSciCon
Clinical progress over time in children with primary ciliary dyskinesia
Authors: Wasim Qayum, Lee Tim, Blackburn Louise
Journal: European Respiratory Journal (2013)

Background 

Little is known regarding clinical progress over time in children with PCD, particularly once transferred to adult care.

 Aims 

The aim of this study was to look at clinical progress over a decade in a cohort of children with PCD first studied in 2002, measuring their lung function (% predicted FEV1), growth and chest exacerbations.

 Methods 

Ethical approval was obtained to approach subjects previously studied in 2002. Review of paper and electronic case notes of consenting subjects was conducted to determine hospital admission(s), lung function and nutritional parameters over time, and previous and current treatment.

 Results 

Eight out of 28 participants from the initial cohort were recruited into this study. Five participants in the initial study were not receiving any secondary care respiratory follow up and could not be contacted. There was a mean annual loss of 0.6% of % predicted FEV1, with % predicted FEV1 decreasing in 75% of participants. There was no statistical difference in the weight, height and BMI z scores at the two time points (current study period and initial study period in 2002) p>0.05. 37.5% of the participants had a gastrostomy in situ.

Significantly one of the eight participants had undergone a bilateral lung transplant, and another had died with respiratory failure secondary to a respiratory tract infection at the age of 11.

 Conclusions 

Children with PCD can have significant respiratory disease resulting in death and lung transplantation. Follow-up regimens in adult respiratory clinics appear variable.

There was no significant change in growth of individuals with PCD over time, however some participants were receiving nutritional support via a gastrostomy.