tbuckley/cabot-search huggingface dataset:
Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic Cooperative Oncology Group.
Authors: P A Kosmidis, N Tsavaris, D Skarlos, D Theocharis, E Samantas, N Pavlidis, E Briassoulis, G Fountzilas
Journal: Journal of Clinical Oncology (1996)

PURPOSE To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions. CONCLUSION Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.
Retreatment with pemetrexed-based chemotherapy (PBC) in patients with malignant pleural mesothelioma (MPM): An observational study.
Authors: F. De Vincenzo, P. Zucali, G. Ceresoli, L. Gianoncelli, E. Lorenzi, M. Simonelli, C. Ripa, L. Giordano, A. Santoro
Journal: Journal of Clinical Oncology (2010)

e18106 Background: The role of second-line therapy in MPM patients (pts) is currently undefined. Recent case series have suggested a possible role of re-treatment PBC. Aim of this study was to evaluate this therapeutic option in a consecutive series of pts previously treated with first-line PBC. Methods: Pts with partial response (PR) or stable disease (SD) for at least 3 months after first-line PBC were eligible for the study. Pts receiving retreatment with PBC either as second-line (2L) or further-line (> 2L) therapy were considered. Results: 34 pts were retrospectively evaluated (2L: 20 pts; > 2L: 14 pts). Median age was 65 (range 36-81). EORTC prognostic score was poor in 19 pts, good in 12, not available in 3. In 2L setting 1 RC, 5 PR, 9 SD were observed, whereas 1 SD was observed in > 2L, for an overall disease control rate (DCR) of 47%. 17 pts (50%) had progressive disease (2L: 4 pts; > 2L: 13 pts). Median progression free survival (mPFS) was 3.1 mo (1.1-24.3 mo). Pts receiving PBC as 2L therapy had a longer mPFS (4.8 vs 2.1 mo; p < 0.001). Pts with a good EORTC score had a longer mPFS (4.1 vs 2.8 mo; p.02). Median overall survival (OS) was 10,1 mo (1.8-49.2 mo). Overall survival (OS) and PFS after re-treatment with PBC were correlated to first-line progression time (FLPT) (FLPT < 6 mo, 6-12 mo, > 12 mo, OS was 2.6 vs 7.8 vs 14.8 mo; PFS was 1.4 vs 2.7 vs 4.8 mo; p < 0.01). A longer OS was observed in pts with a good EORTC score (p.02), in pts receiving PBC as 2L therapy (p.02) and achieving a DC (p < 0.002). Grade 3/4 haematological toxicity was observed in 5 pts (14.7%). Nonhematological toxicity was mild, with 1 case of grade 3 constipation. Conclusions: Re-treatment with PBC seems to be a possible option in the second-line setting in MPM pts achieving a durable DC with first-line treatment. Further evaluation in a prospective trial is warranted. No significant financial relationships to disclose.
Interleukin-2 therapy with or without lymphokine-activated killer-cell infusions for low-grade non-Hodgkin's lymphomas?
Authors: R Levy, J M Tourani, J M Andrieu
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.1992.10.8.1366 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1634929 Interleukin-2 therapy with or without lymphokine-activated killer-cell infusions for low-grade non-Hodgkin's lymphomas? R LevyxR LevySearch for articles by this author , J M TouranixJ M TouraniSearch for articles by this author , J M AndrieuxJ M AndrieuSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.8.1366 PDF "Interleukin-2 therapy with or without lymphokine-activated killer-cell infusions for low-grade non-Hodgkin's lymphomas?." Journal of Clinical Oncology, 10(8), p. 1366© 1992 by American Society of Clinical Oncology
On the Properties of the Lactic Dehydrogenase Agent&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Charles G. Crispens, Jr.
Journal: JNCI Journal of the National Cancer Institute (1965)

Results of studies on the properties of the lactic dehydrogenase (LDH) agent are described. Evidence is presented to suggest that this virus is heat labile, acid labile, and sensitive to treatment with sodium deoxycholate and diethyl ether. Exposure to ultraviolet irradiation resulted in complete inactivation after 90 minutes. No effect on virus titer was observed after incubation with papain or trypsin; hemagglutination tests against red blood cells from several species were negative. The possibility that lymphocytic choriomeningitis, pneumonia virus of mice, mouse hepatitis virus, and the LDH agent may belong in a single group is considered on the basis of similar properties shown by these viruses. The two particles reported in plasma of mice infected with the LDH agent might be differentiated by formalin treatment.
Population pharmacokinetic (PK)-pharmacodynamic (PD) model for gefitinib in cancer patients
Authors: J. Li, M. O. Karlsson, J. Brahmer, G. Cusatis, M. Hidalgo, S. D. Baker
Journal: Journal of Clinical Oncology (2005)

3083 Background: Gefitinib is highly bound to plasma proteins (≥97%), is metabolized by cytochrome P4503A (CYP3A), and exhibits wide interpatient variation in exposure (18-fold) (Li, Proc EORTC 2004). The objective was to develop a population PK (PPK) model for unbound and total gefitinib plasma concentrations and link exposure to toxicity and PD effects in 24 cancer patients with solid tumors receiving gefitinib 250 or 500mg orally once daily for 28d. Methods: Pre-treatment CYP3A activity was assessed by oral midazolam clearance (CL/FM). Serial plasma samples were obtained on d1 and 6 pre-treatment samples were obtained over 28d. Drug concentrations were measured in plasma using validated analytical Methods: Tumor biopsies were obtained pre-treatment and on d28, and changes in PD markers (↓pMAPK and ↑p27) were assessed by quantitative IHC. The PPK model was fitted to unbound and total concentrations simultaneously using NONMEMv5, and the association between drug exposure (AUC0–24h, Cpre-treatment), the probability of toxicity (skin rash and diarrhea) and PD effects was assessed using logistic regression analysis. Results: Midazolam and gefitinib PK studies are complete for 13 patients. CL/FM (mean, 42 L/h; range, 9.7–100) was a significant covariate for unbound gefitinib oral clearance (CL/FG), explaining 77% of variability in CL/FG. The population estimate for CL/FG was 6.77×e(-0.0291)×.21×CL/FM (L/h). AUC0–24h was correlated with Cpre-treatment (R2=0.84;P<0.01). Grade 1–2 diarrhea and grade 1 skin rash occurred in 54% and 46% of patients, respectively. Higher AUC was associated with development of diarrhea (P<0.05). PD data is available for 7 patients; preliminarily, unbound gefitninib exposure was positively associated with ↓pMAPK. Conclusions: A PPK model has been developed that describes gefitinib exposure during 28d. Gefitinib exposure was associated with both toxicity and PD effects. The described model has potential for optimization of gefitinib treatment. No significant financial relationships to disclose.
U.S. Trends in Inpatient Utilization of Fractional Flow Reserve and Percutaneous Coronary Intervention
Authors: Naga V. Pothineni, Nishi N. Shah, Yogita Rochlani, Ramez Nairooz, Sameer Raina, Massoud A. Leesar, Barry F. Uretsky, Abdul Hakeem
Journal: Journal of the American College of Cardiology (2016)
Long-Term Results Of Allogeneic Stem Cell Transplantation In 56 Adult Patients With Philadelphia-Positive Acute Lymphoblastic Leukemia: A 20-Year Single Center Experience
Authors: Adalberto Ibatici, Fabio Guolo, Federica Galaverna, Clara Delle Piane, Alida Dominietto, Anna Maria Raiola, Maria Teresa van Lint, Carmen Di Grazia, Angelo Michele Carella, Andrea Bacigalupo
Journal: Blood (2013)
Validation of markers for the intraoperative detection of metastasis in breast sentinel lymph nodes
Authors: J. Backus, T. Laughlin, C. J. Min, A. Mannie, L. Tafra, R. Belly, D. Atkins, K. M. Verbanac
Journal: Journal of Clinical Oncology (2004)

9547 Background: The presence of axillary lymph node (ALN) metastasis is the most important prognostic factor for breast cancer patients. Sentinel lymph node (SLN) status is highly predictive of overall ALN involvement. SLN-positive patients have historically undergone ALN dissection in a second surgery. Intraoperative SLN analysis methods have been implemented to reduce the cost and complications of second surgeries, but these methods suffer from poor and variable sensitivity and a lack of standardization. We are investigating the feasibility of RT-PCR as the basis for improving the intraoperative diagnosis of clinically relevant SLN metastasis. Methods: Eight molecular markers, including mammaglobin, were identified from a genome-wide gene expression analysis of breast and other tissues. Alternate serial sections of SLN from 254 breast cancer patients were analyzed by permanent section H&E or quick frozen for RNA extraction. Blinded SLN cDNAs were analyzed by quantitative RT-PCR. PCR signal was compared to H&E results on a patient basis. Using multivariate receiver operating curves (ROCs), PCR cut-offs were selected that optimally correlated with H&E results. Results: A two-gene assay (mammaglobin and VBM1) detected clinically actionable metastasis (> 0.2 mm) with 90% sensitivity and 94% specificity. The performance of this marker combination was validated by leave half out cross-validation. Addition of a third gene had minimal impact on overall performance. Conclusions: This is the first comprehensive study demonstrating the utility of RT-PCR as the basis of an intraoperative assay for detecting clinically actionable breast metastasis. Mammaglobin / VBM1 expression closely correlates with standard H&E detection of SLN metastasis, demonstrating that molecular analysis has the potential to significantly reduce second surgeries for patients undergoing SLN biopsies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Veridex, LLC, a Johnson & Johnson Co. Veridex, LLC, a Johnson & Johnson Co. Veridex, LLC, a Johnson & Johnson Co. Veridex, LLC
Correlation of apparent diffusion coefficients (ADCs) on diffusion-weighted (DW) magnetic resonance (MR) imaging with lesion size and prostate cancer risk.
Authors: Simpa Samuel Salami, Oksana Yaskiv, Baris Turkbey, Robert Villani, Eran Ben-Levi, Ardeshir Rastinehad
Journal: Journal of Clinical Oncology (2015)

48 Background: A negative correlation between ADC values and Gleason risk of prostate cancer (CaP) has been reported by the NIH. We correlate ADC values on DW MR imaging with lesion size and risk stratification of CaP. Methods: Men with abnormal DRE or PSA underwent a 3T MP-MRI (T2, DWI, and DCE) with an endorectal coil. ADC maps were calculated using b values of 0, 500, 1,000 and 1,500; additional b 2000 images were obtained separately. Three radiologists (EB, RV, AR) reviewed and graded all lesions using the 5-point Likert scale and PI-RADS score. A total of 268 men with suspicious lesion (s) on MRI were prospectively enrolled. The UroNav system (Invivo, Florida) was used to perform MR/TRUS fusion-guided prostate biopsies, obtaining one biopsy core in axial and sagittal planes from each lesion. Our institution’s pathologist reviewed all biopsies. Lowest ADC values of suspicious lesions were correlated against lesion size and Gleason risk stratification. Results: The median age and PSA were 65.0 years and 7.4 ng/mL respectively. An average of 1.5 (378/256) suspicious lesions per patient was identified on the MP-MRI. Median volume of MRI target lesions was 0.36 cm 3 . The cancer detection rate of fusion biopsy on lesion level analysis was 45.2 % (171/378). The mean ± SD ADC values (x 10 -6 mm 2 /sec) for lesions negative and positive for CaP were 1022 ± 260 and 724 ± 223 respectively (p &lt;0.0001). The mean ± SD ADC values (x 10 -6 mm 2 /sec) for lesion size &lt; 0.2 cm 3 , 0.2 – 0.5 cm 3 , 0.5 – 1.0 cm 3 , and &gt; 1 cm 3 were 771 ± 246, 677 ± 206, 629 ± 119, and 500 ± 86respectively. Higher risk CaP was associated with lower ADC values with AUC of 0.77 (p=0.0001). The mean ± SD ADC values (x 10 -6 mm 2 /sec) for low (≤6), intermediate (7), and high (8-10) Gleason grade CaP were 845 ± 285, 687± 195, and 628 ± 145 respectively. Conclusions: The ADC value of suspicious lesions on MRI has an inverse correlation with lesion size and prostate cancer risk. It may be a useful in predicting CaP and its clinical significance. Further studies are needed to determine its value in stratifying patients for prostate biopsy, active surveillance and/or treatment.
A molecule derived from mycobacterium tuberculosis Cpn60.1 (compound Y) inhibits lung inflammation induced by LPS in mice
Authors: Yanira Vasquez, Andrew Lightfoot, Clive Page
Journal: European Respiratory Journal (2014)

Introduction: We have previously shown that Cpn60.1 inhibits allergic pulmonary inflammation and bronchial hyperresponsiveness (BHR) in a murine model (Riffo-Vasquez, Y et al. AJRCMB,47(2):245, 2012). In this study we have investigated the effect of a shorter molecule derived from Cpn60.1 (compound Y) in a murine model of lung inflammation induced by LPS

Methods : Male BALB/c mice were pre-treated with compound Y (5-500 pg/mouse) intravenously minutes before intranasal instillation of LPS (25 µg). Controls received vehicle (saline) by the same route. Readouts were performed 4h later. Cytokines were measured in BAL using conventional ELISA, following instructions of the manufacturer. Results: Compound Y at 5, 50, but not 500 pg/mouse, significantly inhibited the number of neutrophils in the bronchoalveolar lavage (mean ± SEM x 104/ml) (LPS: 212.8 ± 12.1 vs LPS/compound Y: 113.2 ± 22; 101.6 ± 14.4 and 194.5 ± 50 for 5, 50 and 500 pg/mouse, respectively. p<0.05, n=8/group). Compound Y at 5, 50, but not 500 pg/mouse, reduced levels of IL-12 (mean ± SEM pg/ml) (LPS: 698 ± 55 vs LPS/compound Y: 533 ± 52, 289 ± 48, 833.4 ± 200 for 0.5, 5 and 500 pg/mouse respectively, n=4/group) and IL-6 (LPS: 1034 ± 55 vs LPS/compound Y: 492 ± 86, 525 ± 73 and 1044 ± 263 for 0.5, 5 and 500 pg/mouse respectively, n=4/group). Conclusion : Compound Y significantly reduces cell migration and the release of pro-inflammatory cytokines induced by LPS in the lung.
Value of Personalized Medicine
Authors: Henry M. Dunnenberger, Janardan D. Khandekar
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Influence of cellulose triacetate hemodialyzers on vancomycin pharmacokinetics.
Authors: L S Welage, N A Mason, E J Hoffman, R M Odeh, J Dombrouski, J A Patel, R D Swartz
Journal: Journal of the American Society of Nephrology (1995)

This study was designed to evaluate the pharmacokinetics of vancomycin during hemodialysis with cellulose triacetate (CT) high-flux dialyzers and to assess the influence of membrane surface area on intradialytic clearance. In a randomized crossover fashion, the pharmacokinetics of vancomycin were evaluated during dialysis with the CT 110 and CT 190 membranes. Six hemodialysis patients received 1 g of vancomycin immediately after the completion of a dialysis session, and subsequently, blood samples were obtained over a 5-day study period. On Day 3 subjects were dialyzed with CT 110 or CT 190 membranes. The mean intradialytic clearance of vancomycin was 56.7 +/- 7.5 and 100.70 +/- 10.7 mL/min with the CT 110 and CT 190 membranes, respectively (P < 0.05). Significant rebound in vancomycin serum concentrations occurred after dialysis; this rebound appeared to be complete 3 h postdialysis. On the basis of postrebound concentrations, the apparent percent removal of vancomycin was 23.6 +/- 1.2 and 25.2 +/- 8.6% for CT 110 and CT 190 membranes, respectively (not significant). Vancomycin is significantly cleared during dialysis with cellulose triacetate membranes, and its clearance is dependent on membrane surface area. Although a small supplemental dose of vancomycin could be administered after dialysis to replace drug lost during dialysis, it may be more efficient to give a larger dose of vancomycin after several dialysis periods. The determination of vancomycin removal can be used to estimate vancomycin serum concentrations as well as dosage requirements. This in conjunction with serum concentration monitoring can be used to optimize vancomycin dosing.
Phase II dose-ranging study of TLK286 a novel glutathione analog prodrug, in combination with cisplatin as first-line treatment in locally advanced or metastatic non-small cell lung cancer (NSCLC)
Authors: H. A. Burris, M. J. Edelman, D. Stewart, F. Fossella, S. Jones, N. Willcutt, J. G. Keck, G. L. Brown, V. Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2005)

7126 Background: TLK286, a novel glutathione analog prodrug, is activated by the enzyme GST P1–1 over-expressed in NSCLC, inducing apoptosis. TLK286 is not cross-resistant to cisplatin (C) and is synergistic with C in human A549 lung carcinoma cells. This synergy may be mediated by effects of TLK286 on glutathione/GST P1–1 resistance pathways. Since TLK286 has shown single agent activity in two phase II trials in platinum resistant NSCLC and has non overlapping toxicity, a phase II dose-ranging trial was conducted to study TLK286 in combination with C in patients (pts) with advanced NSCLC. Methods: The objectives were to determine maximum tolerated dose (MTD) of TLK286/C, the response rate (ORR) by RECIST and progression-free survival (PFS). Pts were treated at 3 escalating dose levels with TLK286 (750 or 1000 mg/m2) and C (75 or 100 mg/m2) q3 weeks until progression or unacceptable toxicity. At the MTD, an additional 35 pts are to be treated. Results: At interim analysis, 24 pts (19 M, 5 F), median age 65 (range 42–78), median ECOG PS 1, have received 70+ cycles (mean 2.9 cycles/patient, range 1–8+). TLK286 (1,000)/C (75) mg/m2, one level below the MTD of 1,000/100 mg/m2 of TLK286/C, showed Grade (G) 3 neutropenia in 2 of 5 pts, was chosen as the phase 2 dose. The most common adverse events: G 1–2 fatigue, nausea and vomiting. G 3 neutropenia occurred in 7 pts (28%) and G 3 thrombocytopenia in 1 (4%). No unexpected toxicities were reported. Conclusions: TLK286/C combination at 1,000/75 mg/m2 is well tolerated and is an active regimen in the first-line treatment of locally advanced or metastatic NSCLC. Enrollment in phase II continues to determine the final ORR, PFS and disease stabilization rate (DSR). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Telik Aventis, CTI, GlaxoSmithKline, Novartis Telik Aventis, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, SK, Lilly Oncology, Roche, Telik Aventis, Bristol-Myers Squibb, CTI, Genentech, GlaxoSmithKline, Lilly Oncology, Novartis, Roche Telik
Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Authors: Hertzel C. Gerstein, Guillaume Paré, Matthew J. McQueen, Heinz Haenel, Shun Fu Lee, Janice Pogue, Aldo P. Maggioni, Salim Yusuf, Sibylle Hess
Journal: Circulation (2015)

Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome or death when added to clinical measurements.A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 mL of stored frozen serum from every participant who provided biobanked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward-selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) all-cause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71 and 0.68 for the 2 CV composite outcomes, respectively, with the greatest increase to 0.75 for death (P<0.001 for the change).A systematic hypothesis-free approach identified combinations of up to 15 cardiometabolic biomarkers as independent determinants of CV outcomes or death in people with dysglycemia.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00069784.