tbuckley/cabot-search huggingface dataset:
Comparative effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor after high-dose cyclophosphamide cancer therapy.
Authors: M Bregni, S Siena, M Di Nicola, A Dodero, F Peccatori, F Ravagnani, G Danesini, A Laffranchi, G Bonadonna, A M Gianni
Journal: Journal of Clinical Oncology (1996)

We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting.Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX.Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group.GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.
Increased DNA methylation of Dnmt3b targets impairs leukemogenesis
Authors: Isabell Schulze, Christian Rohde, Marina Scheller-Wendorff, Nicole Bäumer, Annika Krause, Friederike Herbst, Pia Riemke, Katja Hebestreit, Petra Tschanter, Qiong Lin, Heinz Linhart, Lucy A. Godley, Hanno Glimm, Martin Dugas, Wolfgang Wagner, Wolfgang E. Berdel, Frank Rosenbauer, Carsten Müller-Tidow
Journal: Blood (2016)
Effects of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) on proliferation and cytokine secretion of immune cells in malignant pleural effusion
Authors: M. Sebastian, M. Jaeger, P. Kiewe, W. Schuette, R. Wiewrodt, H. Lindhofer, B. Mueller, H. Friccius-Quecke, H. Friccius- Quecke, A. Schmittel
Journal: Journal of Clinical Oncology (2007)

3046 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via FcγR I/III. Thus the antibody induces tumor specific cell mediated cytotoxicity in vitro and in vivo. Following last years’ ASCO presentation on a phase I/II trial showing safety and efficacy of repetitive intrapleural administration of catumaxomab in patients with EpCAM positive, malignant pleural effusion (MPE), we now present data on the responsiveness of immune cells from pleural fluid to catumaxomab. Methods: Pleural fluid of patients with EpCAM-positive MPE treated with i.pl. catumaxomab was collected before treatment. Cells were harvested from the fluid and cultured ± 100 ng/ml catumaxomab using an in vitro proliferation assay. After 72 h of culture, proliferation of T cells (CD4+ and CD8+) and monocytes (CD11c+) was determined. In addition, cell supernatants after 24h incubation ± catumaxomab were analysed for their T H1 /T H2 cytokine profile (IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF- a). Results: Incubation in presence of catumaxomab led to a pronounced increase of CD4+ CD8+ and CD11+ cell numbers indicating a proliferation of these cells, whereas cultures without catumaxomab showed no proliferation of immune cells. Analysis of supernatants after 24 h revealed levels of IL-2, IL-6, IFN-γ and TNF-a, from cells incubated with catumaxomab that were distinctly higher than in cultures without catumaxomab. Conclusions: The immunologic nature of catumaxomab-induced responses in patients with pleural effusion accompanied by a reduction of tumor cells, could be underlined impressively with in vitro data obtained from pleural cells showing catumaxomab-induced proliferation of T cells and accessory cells and T H1 -directed cytokine secretion. The data are equivalent to results observed in the peritoneal fluid of ascites patients. [Table: see text]
Liver Plaques: Portal Vein Deposition of Oxidized Low-density Lipoprotein in Non-alcoholic Fatty Liver Disease
Authors: Cheng-Maw Ho, Shu-Li Ho, Yu-Sheng Lai, Ya-Hui Chen, Shao-Chun Lu, Hui-Ling Chen, Po-Yuan Chang, Rey-Heng Hu, Po-Huang Lee
Journal: Clinical Gastroenterology and Hepatology (2015)
Preoperative pitfalls: Prediction of pathologic lymph node status in patients undergoing neoadjuvant chemotherapy and radical cystectomy.
Authors: Patrick Espiritu, Adam Luchey, Hui-Yi Lin, Binglin Yue, Jorge Lockhart, Julio Pow-Sang, Philippe E. Spiess, Wade Jeffers Sexton, Michael Adam Poch
Journal: Journal of Clinical Oncology (2014)

352 Background: Category 1 evidence supports neoadjuvant chemotherapy (NC) prior to radical cystectomy (RC) in patients with muscle invasive urothelial carcinoma of the bladder (UC). In addition, patients with clinical node (cN) positive disease may undergo RC after consolidative chemotherapy. Pathologic node (pN) positive disease at the time of radical cystectomy for UC portends a poor prognosis but is often challenging to predict. The purpose of this study was to investigate clinical predictors of pN positive disease in patients receiving NC followed by RC. Methods: After IRB approval, a retrospective analysis was performed on all patients who underwent neoadjuvant chemotherapy followed by RC from 2001-2013. Chi-square, Fisher’s exact, and logistic regression analyses were performed to analyze relationships between preoperative variables including clinical grade, stage, lymphovascular invasion, histologic variance, concomitant carcinoma in−situ, cycles of NC, smoking status with pN status. Overall survival (OS) and progression free survival (PFS) analysis was performed using Kaplan-Meier methodology. Results: 158 patients met inclusion criteria for the study. Fifty-five (35%) patients had pN positive disease at the time of RC. Of all of the preoperative variables assessed, cN positive disease was the only factor associated with pN positive disease (p &lt;0.001). Of the 129 patients with cN negative disease 36 (28%) patients had pN positive disease. Six patients (32%) who were cN positive were pN negative at RC. Overall survival for the cohort was 30 months. Compared to pN negative disease, patients with pN positive disease had a worse PFS (p &lt;0.01) and OS (p &lt;0.01). Compared to non−organ confined (≥ pT3) pN positive disease, patients with organ confined (≤pT2) pN positive tumors had an improved PFS (p&lt;0.01) and OS (p&lt;0.01). Conclusions: Clinical node status is the only preoperative variable associated with pN status at the time of RC for patients receiving NC. A large percentage of patients who are cN negative will be pN positive at RC. As expected, patients who are pN positive had poor PFS and OS compared to pN negative patients.
Abstract 17956: External Validation of a Prediction Model for the Development of Atrial Fibrillation in a Repository of Electronic Medical Records
Authors: Matthew J Kolek, Amy J Graves, Aihua Bian, Pedro L Teixeira, Moore B Shoemaker, Babar Parvez, Hua Xu, Susan R Heckbert, Patrick T Ellinor, Emelia J Benjamin, Alvaro Alonso, Joshua C Denny, Karel G Moons, Ayumi K Shintani, Dan M Roden, Dawood Darbar
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) contributes to substantial morbidity, mortality, and healthcare costs. Accurate prediction of incident AF might enhance patient care and improve outcomes. We aimed to externally validate the AF risk model developed by the CHARGE-AF investigators utilizing a large repository of electronic medical records (EMR). Methods: Using a database of de-identified EMRs, we conducted a retrospective cohort study of subjects serially followed in internal medicine clinics at our institution (minimum 3 visits in a 24 month window). Subjects were followed for incident AF from 2005 until 2010. We applied the published CHARGE-AF Cox proportional hazards model beta coefficients to our cohort. Predictors included age, race, height, weight, systolic and diastolic blood pressure, treatment for hypertension, smoking status, diabetes, heart failure, history of myocardial infarction, left ventricular hypertrophy, and PR interval. Calibration and discrimination were assessed by generating calibration plots and calculating C-statistics. Results: The study included 33,494 subjects with median age 57 years (25th to 75th percentile: 49 - 67), 57% women, 86% whites, and 14% African Americans. During the mean follow-up period of 4.8 ± 0.85 years, 2455 (7.3%) subjects developed AF. After correcting for baseline hazard, the CHARGE-AF model over-predicted AF at the highest risk deciles but was otherwise well-calibrated (Figure) and showed good discrimination, with a C-statistic of 0.746 (95% confidence interval: 0.738 to 0.754). Conclusion: From clinical factors readily accessible in a large de-identified EMR repository, we externally validated the CHARGE-AF risk prediction model to identify individuals at risk for developing AF in an ambulatory setting. These data not only provide strong validation for the CHARGE-AF risk prediction tool, but also indicate that the tool, and thus primary prevention strategies, can be implemented in an EMR context.
Biomarkers and obesity in surgically treated patients with prostate cancer
Authors: R. Shazer, A. Bharne, E. Nepomuceno, J. Mirocha, C. Ramirez, D. Luthringer, S. Holden, D. B. Agus, M. Gross
Journal: Journal of Clinical Oncology (2006)

14536 Background: Obesity is associated with poor outcomes in prostate cancer (PC). We explored if biomarkers for proliferation and estrogen signaling relate to obesity and surgical outcomes in PC patients (pts) treated by radical prostatectomy (RP). Methods: Pts with RP at a single institution between 1993 and 2002 were reviewed (1156 pts). The analysis subset included pts with full preoperative staging and anthropometric variables (541 pts). Clinical variables examined included: age, PSA, pre-operative hemoglobin (Hgb), ethnicity, and body mass index (BMI). Surgical outcomes included: estimated blood loss (EBL), Gleason score ≥ 7 (GS &gt;7), extra-capsular extension (ECE), positive margins (MR+), and pathologic stage (pT2 vs. pT3/T4). Biomarkers examined in a convenience subset (n = 61) included proliferation index (Ki67% in cancer cells) and ERα positivity (nuclei staining ≥5% in cancer or peri-tumoral stromal cells). Obesity was defined as BMI ≥ 30 kg/m 2 . A step-wise logistic regression analysis was used to determine odds ratio (OR) in relation to obesity. Results: Mean ± standard deviation for pre-operative data included: age 62.7 ± 7.5 yrs; PSA 8.4 ± 6.8 ng/dl; Hgb 13.6 ± 1.8 g/dl; and BMI 26.5 ± 3.8 kg/m 2 . Pt reported ethnicities included: white (432 pts), Black/African-American (69 pts), Asian/Pacific Islander (20 pts), Hispanic (16 pts). BMI correlated highly with race (Kruskal-Wallis p = 0.002) and weakly with EBL (Spearman 0.11, p = 0.009) and Hgb (Spearman 0.15, p = 0.002). No correlation was observed between obesity and Gleason score. Regression models showed obesity was independently associated with ECE (OR 2.5, 95% CI 1.2–5.3) and pT3/T4 (OR 1.9, 95% CI 1.0–3.3). Biomarker analysis showed Ki67% correlated with GS &gt;7, (Spearman 0.25, p = 0.048), but not BMI. No ERα positivity was noted in cancer cells. Stromal ERα positivity was noted in 21/30=70% of non-obese and 15/31=48% of obese pts (Fisher’s exact test p = 0.12). Conclusion: We confirm the association between obesity, ethnicity, and poor surgical outcomes. Biomarker analysis shows that obesity has no effect on proliferation index or tumor grade. However, we observe a trend towards down-regulation of stromal ERα expression in obese patients. No significant financial relationships to disclose.
A phase I trial of intraperitoneal (IP) chemohyperthermia (CH) with oxaliplatin (L-OHP) and irinotecan (CPT-11) in patients (pts) with peritoneal carcinomatosis (PC): Pharmacokinetic (PK),tissue distribution and tolerance
Authors: M. Ducreux, V. Boige, M. Pocard, P. Lasser, D. Malka, M. Bonnay, E. Magherini, C. Oprea, D. Elias
Journal: Journal of Clinical Oncology (2004)

3672 Background: The complete resection of macroscopic PC followed by intraoperative IPCH to treat residual microscopic disease enables curing some patients (pts). Methods: Pts with PC from gastrointestinal or other origin underwent complete cytoreductive surgery followed by intraoperative IPCH with a fixed dose of L-OHP (460 mg/m2) and one of the 7 increasing doses of CPT-11 (from 300 to 700 mg/m2). IPCH was performed using an open procedure for 30 min at an IP temperature of 43°C with 2l/m2 of 5% dextrose instillation in a closed continuous circuit. Just before IPCH, pts received systemic IV leucovorin (LV) 20mg/m2 and 5FU 400mg/m2 to maximize the effect of L-OHP and CPT-11. Results: From May 2002 to June 2003, 39 pts were included with: M/F: 13/26; median age: 46y[26–60]; primary tumor was: 20 colorectal,11 appendix pseudomyxoma,3 endocrine tumors,3 mesothelioma, 2 small bowel. The PK of IP L-OHP was not modified by increasing doses of IP CPT-11, and the drug concentration was 17.8 higher in bathed tumor tissue that in non-bathed tissue. The PK of IP CPT-11 showed an exponential decrease in the peritoneal perfusion and a peak of plasma concentration at 30 min. SN-38 was present in peritoneal instillation immediately after the beginning of IPCH. CPT concentration in tumor tissue increased until the step of 400 mg/m2, and then remained stable. It was 16 to 23 higher than in non-bathed tissues. Half of the L-OHP and CPT-11 was absorbed during the procedure. The hospital mortality rate was 2.5% and the non hematological grade 3 to 5 complication rate (abdominal and intraabdominal) was 25%. At the recommended dose of 400mg/m2, 5/6 pts had grade ½ hematological toxicity: 2 anemia, 5 neutropenia, 1 thrombopenia.The hematological toxicity was correlated to the extent of PC (p=0.017) and duration of surgery (p=0.046). Conclusions: This trial demonstrated a dose related exposure and efficient intratumoral penetration of the 2 drugs. The recommended dose of IP CPT-11 was 400 mg/m2, for phase 2. This phase 2 trial is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Aventis Pharmaceutical Co. Aventis Pharamceutical Co. Aventis Pharamceutical Co. Aventis; Sanofi-Synthelabo
Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis
Authors: Sander P. van Rijn, Richard van Altena, Onno W. Akkerman, Dick van Soolingen, Tridia van der Laan, Wiel C.M. de Lange, Jos G.W. Kosterink, Tjip S. van der Werf, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2016)

Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is becoming more challenging because of increased levels of drug resistance against second-line TB drugs. One promising group of antimicrobial drugs is carbapenems. Ertapenem is an attractive carbapenem for the treatment of MDR- and XDR-TB because its relatively long half-life enables once-daily dosing.A retrospective study was performed for all patients with suspected MDR-TB at the Tuberculosis Center Beatrixoord of the University Medical Center Groningen (Haren, the Netherlands) who received ertapenem as part of their treatment regimen between December 1, 2010 and March 1, 2013. Safety and pharmacokinetics were evaluated.18 patients were treated with 1000 mg ertapenem for a mean (range) of 77 (5-210) days. Sputum smear and culture were converted in all patients. Drug exposure was evaluated in 12 patients. The mean (range) area under the concentration-time curve up to 24 h was 544.9 (309-1130) h·mg·L(-1) The mean (range) maximum observed plasma concentration was 127.5 (73.9-277.9) mg·L(-1)In general, ertapenem treatment was well tolerated during MDR-TB treatment and showed a favourable pharmacokinetic/pharmacodynamic profile in MDR-TB patients. We conclude that ertapenem is a highly promising drug for the treatment of MDR-TB that warrants further investigation.
Outcome of patients with HER2+ advanced breast cancer (ABC) progressing during trastuzumab (T)-based treatment
Authors: F. Montemurro, M. Donadio, M. Clavarezza, S. Redana, G. Vietti Ramus, A. Durando, M. E. Iacomuzzi, R. Ponzone, G. Valabrega, M. Venturini, M. Aglietta
Journal: Journal of Clinical Oncology (2005)

593 Background: the optimal treatment for HER2+ ABC patients (pts) progressing during T-based treatment is undefined. Retrospective studies (Fountzilas Clin Breast Cancer 2003; Gelmon Clin Breast Cancer 2004; Tripathy J Clin Oncol 2004) suggest that continuing T beyond progression, in combination with further chemotherapy, is safe and yields encouraging results. We describe the clinical outcome of pts progressing while on T-based regimens and treated upon progression with different modalities +/− T. Methods: from a database of 165 pts with HER2+ (immunohistochemistry 2/3+ or FISH+) ABC we identified 120 pts progressing during or after an initial T-based regimen. Eleven of these pts had stopped T prematurely because of toxicity or patient’s decision (median T duration: 3 weeks, range 1–9). Of the remaining 109 pts, 19 could receive only supportive care (rapid progression and performance status decline), 31 continued T (T + radiotherapy: 7 pts with isolated CNS progression; T + chemotherapy: 19 pts; T + endocrine therapy: 5 pts), 59 stopped T and received chemotherapy (52 pts) or endocrine therapy (7 pts). At the time of this analysis 76 pts had died (median follow-up 17 months, range 1.2–60.8). Results: the response rate (RR, CR+PR) to the first post-progression treatment, the overall survival from the first administration of T (OS), the time to second progression (TT-SP) and the post progression survival (PP-OS) are summarized in the table. Conclusions: progressing pts who could receive additional therapy had similar clinical outcomes regardless of T continuation. These outcomes were in the range reported in papers focusing on continuing T beyond progression. Our results confirm the limit of retrospective analyses in addressing the optimal treatment in HER2+ ABC pts progressing during T-based treatments. Given the high cost and pts-burden of T treatment, the therapeutic strategy in this setting of pts needs urgent evaluation in randomized trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
James Joseph Cockburn
Authors: Ann Cockburn. Olga Bowey-Cockburn
Journal: BMJ (2015)

James Joseph Cockburn (“Jim”) was appointed consultant psychiatrist to Long Grove Hospital, Epsom, and to Kingston Hospital in 1964. He later specialised in the psychiatry of old age. He was instrumental in the development and organisation of local psychiatric services; seeing the catchment area of Long Grove Hospital switch from the East End of London to Kingston and Richmond, including a new psychiatric unit built in Kingston Hospital. He took an active role in management of the hospital and served for many years as …
Short IV infusion of oblimersen (OBL) in patients with solid tumors: safety and pharmacokinetics
Authors: T. Mays, C. H. Takimoto, A. Patnaik, K. P. Papadopoulos, T. N. Julian, A. Qureshi, E. M. Gilles, B. D. Brown, A. W. Tolcher
Journal: Journal of Clinical Oncology (2008)

14606 Background: OBL downregulates Bcl-2, enhancing the activity of cytotoxic anticancer drugs. In clinical studies, OBL is usually administered by continuous IV infusion to avoid high peak plasma concentrations. As intratumoral uptake of OBL is enhanced with short IV infusion preclinically, we initiated a Phase I study of OBL given by short (2-hour) IV infusion. Methods: Eligible pts have solid tumors for which no standard therapy is available and ECOG performance status of ≤2. In Part 1, Cohort 1 receives a once weekly short IV infusion for 3 weeks at a starting dose of 300 mg and increasing in increments of 100 mg to the MTD; Cohort 2 receives a corticosteroid prior to the once-weekly short IV infusion for 3 weeks. In Part 2, pts receive a twice weekly short IV infusion at the MTD determined in Cohort 1. All pts may receive up to 4 additional cycles. Blood samples are obtained for complement assay and PK (Parts 1 and 2) and pharmacodynamics (Part 2). Results: Fifteen pts were treated in Cohort 1. Single pts received doses of 300 to 800 mg. At 900 mg, 1 pt experienced syncope, but 2 additional pts had no dose-limiting toxicity. At 1000 mg, all 6 pts had fever, chills, and moderate decreases in blood pressure. Enrollment in Cohort 2 and Part 2 was initiated. Three pts premedicated with a corticosteroid received OBL 1100 mg in Cohort 2 and 3 pts in Part 2 received 900 mg twice weekly: no dose-limiting toxicity occurred in any pt. Dose-proportional PK was observed over the 300–900 mg dose range; metabolism and plasma clearance did not change with increasing dose. Conclusions: OBL can be safely administered by short IV infusion. Weekly doses up to 900 mg were well tolerated without corticosteroid pretreatment, and enrollment is ongoing in Cohort 2 and Part 2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genta Incorporated Genta Incorporated Genta Incorporated Genta Incorporated Genta Incorporated Genta Incorporated
The Expression of Bcl-x Is Downregulated During Differentiation of Human Hematopoietic Progenitor Cells Along the Granulocyte But Not the Monocyte/Macrophage Lineage
Authors: Cristina Sanz, Adalberto Benito, Maite Silva, Beatriz Albella, Carlos Richard, Jose Carlos Segovia, Andres Insunza, Juan Antonio Bueren, Jose Luis Fernández-Luna
Journal: Blood (1997)
Another look at the age-old question: Which came first, the elevated C-reactive protein or the atherothrombosis?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Marc S. Sabatine, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2005)