tbuckley/cabot-search huggingface dataset:
Quality of life and patient (pt) preference for oral chemotherapy in metastatic colorectal carcinoma (MCRC): Comparison of XELOX and FOLFOX regimens
Authors: Z. Spurna, D. Brancikova, T. Urbanek
Journal: Journal of Clinical Oncology (2008)

20697 Background: We evaluated the quality of life of pts with MCRC and their preferences for oral versus intravenous chemotherapy following treatment with either capecitabine + oxaliplatin (XELOX - capecitabine 1000mg/m2 bid for 14 days plus oxaliplatin 130mg/m2 on day 1 every 3 weeks) or 5-FU/FA + oxaliplatin (FOLFOX4). Methods: Pts with MCRC (PS 0–1) who had received first-line treatment with either XELOX or FOLFOX were eligible. Each pt completed the Life Quality Questionnaire within 3 weeks after the completion of chemotherapy. This Life Quality Questionnaire was created for scientific reasons in co-operation between oncologists and the Institute of Psychology in order to assess MCRC pts. The Life Quality Questionnaire included several functional scales including physical, emotional, social, ability to perform every day tasks and leisure time activities. Respondents were also asked, given their experiences with chemotherapy, if they would prefer oral chemotherapy or continuous intravenous infusional chemotherapy assuming that the efficacy and toxicity of both chemotherapy schedules were similar. Results: A total of 80 pts were involved of whom 38 had received XELOX and 42 had received FOLFOX. In the FOLFOX group, 35 (83%) pts stated that they would mostly prefer oral therapy. According to the Life Quality Questionnaire, 26 (60%) pts who had received FOLFOX selected “neither contented nor discontented”, “rather discontented” and/or “discontented” in their responses to individual categories. In the XELOX group, 35 (92%) pts stated that they would prefer oral therapy. According to the Life Quality Questionnaire, 34 (90%) of XELOX pts selected “rather contented”, “contented” and/or “very contented” as their response to individual categories. Only 4 (10%) pts selected neutral or negative responses. Conclusions: Most pts prefer oral chemotherapy. Our results further suggest that the quality of life of most pts treated with an oral fluoropyrimidine-based chemotherapy regimen is good and better than that of pts treated with a regimen based on continuous intravenous infusional 5-FU/FA. No significant financial relationships to disclose.
Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer.
Authors: N Kemeny, K Israel, D Niedzwiecki, D Chapman, J Botet, B Minsky, V Vinciguerra, R Rosenbluth, B Bosselli, C Cochran
Journal: Journal of Clinical Oncology (1990)

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.
Karnofsky Memorial Lecture. Marrow transplantation for malignant diseases.
Authors: E D Thomas
Journal: Journal of Clinical Oncology (1983)

Marrow grafting, once undertaken only after failure of all other forms of therapy, is now the preferred therapy for some malignant diseases. Chemoradiotherapy and marrow grafting for patients with acute leukemia who have failed chemotherapy results in cure rates of 10%-30%. For patients under the age of 50 with acute nonlymphoblastic leukemia transplanted in first remission, the cure rate is approximately 50% with better results in younger patients. Marrow grafting is now being explored in a variety of types of malignant diseases having in common a steep dose-response curve to therapy, therapy limited by marrow toxicity, and the availability of a suitable marrow donor. Current research in the field of marrow transplantation is reviewed and provides a basis for a reasonable expectation that results of marrow transplantation will continue to improve. The use of partially matched family members or phenotypically histocompatibility leukocyte antigen-identical unrelated donors will make marrow grafting available to a larger fraction of patients. Marrow grafting, developed for the treatment of malignant disease, has found an important application to nonmalignant diseases, including immunodeficiency syndromes, aplastic anemia, and thalassemia and other genetic disorders of hematopoiesis.
Abstract 13432: Noninvasive Cardiac Activation Imaging of Premature Ventricular Contractions in Human Patients
Authors: Long Yu, Dakun Lai, Jian Sun, Zhaoye Zhou, Chengzong Han, Yigang Li, Bin He
Journal: Circulation (2012)

Introduction Noninvasive imaging of cardiac electrical activity is important to aid in ablation therapy of cardiac arrhythmia and cardiovascular research. We present our clinical investigation of a novel three dimensional (3D) cardiac electrical imaging (3DCEI) technique to image premature ventricular contractions (PVCs) in patients undergoing catheter ablation. Methods Up to 208-channel body surface electrocardiograms (ECGs) were recorded in 5 patients (averaged age 53±22) with symptomatic PVCs. CT scans were performed to build subject-specific heart-torso geometry models. Data analysis was performed on PVCs recorded during body surface potential mapping. The noninvasively-imaged results were compared with the surgical outcome and the activation map obtained from CARTO system during electrophysiological (EP) study. Results Frequent PVCs (averaged ∼20,000 beats/day) were observed in each patient during Holter monitoring. Ventricular tachycardia was induced during an EP study with the same ECG morphology a...
Abstract 239: p53 Protects Cardiac Stem Cells From the Toxic Effects of Chemotherapy and Controls their Fate
Authors: Ramaswamy Kannappan, Giorgia Palano, Polina Goichberg, Fumihiro Sanada, Sergio Signore, Junghyun Kim, Marcello Rota, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2013)

Doxorubicin (DOXO) causes dilated cardiomyopathy and heart failure. We have documented previously that DOXO-mediated cardiotoxicity is dictated by functional alterations of cardiac stem cells (CSCs). DOXO-induced myopathy was coupled with a reduction in CSC number due to increased death, inhibition of proliferation, and senescence. We raised the possibility that survival and growth of CSCs following DOXO treatment may be enhanced by modulating the intracellular level of p53, which plays a critical role in the determination of stem cell fate. For this purpose, transgenic mice carrying an additional p53 allele (Sp53) were studied. With respect to wild-type mice (WT), CSCs isolated from Sp53 mice (Sp53-CSCs) showed increased apoptosis with accumulation of the pro-apoptotic p53 targets BAX, PUMA and Pidd. Conversely, the expression of p21Cip1, a cell cycle inhibitor and inducer of cell senescence, was lower in Sp53-CSCs than WT cells. Upon DOXO treatment, Sp53-CSCs exhibited accelerated onset of apoptosis. However, viable Sp53-CSCs showed enhanced formation of DNA damage response foci, indicative of a very efficient DNA repair mechanism. Following removal of DOXO, Sp53-CSCs re-entered the cell cycle and divided, while WT cells continued to die by apoptosis or became senescent. The response of WT-CSCs to DOXO involved the pro-apoptotic Bcl2 family member Noxa and the senescence-associated protein p16INK4a. In contrast, exposure of Sp53-CSCs to DOXO provoked pulses of p53 expression, which favored sustained upregulation of Mdm2. Mdm2 antagonized the inhibitory effect of p53 on cell growth and prevented apoptosis. Ultimately, Sp53-CSCs showed accumulation of PCNA, which is required for DNA repair and synthesis. Importantly, IGF-1 release was higher in Sp53-CSCs, promoting their replication through an autocrine-paracrine mechanism. Collectively, our data demonstrate that changes in the pattern of p53 expression have beneficial effects on CSCs by amplifying the DNA repair response, facilitating the clearance of cells with non-repairable DNA damage, and enabling the proliferation of cells in which DNA lesions are effectively removed. Thus, targeting p53 expression in CSCs may protect the heart from the toxic effects of chemotherapy.
Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis
Authors: Wei Dong, Hans Goost, Xiang-Bo Lin, Christof Burger, Christian Paul, Zeng-Li Wang, Fan-Lin Kong, Kristian Welle, Zhi-Chao Jiang, Koroush Kabir
Journal: British Journal of Sports Medicine (2015)

Background There are many injection therapies for lateral epicondylalgia but there has been no previous comprehensive comparison, based on the Bayesian method. Methods The MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for appropriate literature. The outcome measurement was the pain score. Direct comparisons were performed using the pairwise meta-analysis, and network meta-analysis, based on a Bayesian model, was used to calculate the results of all of the potentially possible comparisons and rank probabilities. A sensitivity analysis was performed by excluding low-quality studies. The inconsistency of the model was assessed by means of the node-splitting method. Metaregression was used to assess the relationship between the sample size and the treatment effect. Results All of the injection treatments showed a trend towards better effects than placebo. Additionally, the peppering technique did not add additional benefits when combined with other treatments. No significant changes were observed by excluding low-quality studies in the sensitivity analysis. No significant inconsistencies were found according to the inconsistency analysis, and metaregression revealed that the sample size was not associated with the treatment effects. Conclusions Some commonly used injection therapies can be considered treatment candidates for lateral epicondylalgia, such as botulinum toxin, platelet-rich plasma and autologous blood injection, but corticosteroid is not recommended. Hyaluronate injection and prolotherapy might be more effective, but their superiority must be confirmed by more research. The peppering technique is not helpful in injection therapies.
Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making
Authors: Elisabet Berggren, Patric Amcoff, Romualdo Benigni, Karen Blackburn, Edward Carney, Mark Cronin, Hubert Deluyker, Francoise Gautier, Richard S. Judson, Georges E.N. Kass, Detlef Keller, Derek Knight, Werner Lilienblum, Catherine Mahony, Ivan Rusyn, Terry Schultz, Michael Schwarz, Gerrit Schüürmann, Andrew White, Julien Burton, Alfonso M. Lostia, Sharon Munn, Andrew Worth
Journal: Environmental Health Perspectives (2015)

BackgroundSafety assessment for repeated dose toxicity is one of the largest challenges in the process to replace animal testing. This is also one of the proof of concept ambitions of SEURAT-1, the largest ever European Union research initiative on alternative testing, co-funded by the European Commission and Cosmetics Europe. This review is based on the discussion and outcome of a workshop organized on initiative of the SEURAT-1 consortium joined by a group of international experts with complementary knowledge to further develop traditional read-across and include new approach data.ObjectivesThe aim of the suggested strategy for chemical read-across is to show how a traditional read-across based on structural similarities between source and target substance can be strengthened with additional evidence from new approach data—for example, information from in vitro molecular screening, "-omics" assays and computational models—to reach regulatory acceptance.MethodsWe identified four read-across scenarios that cover typical human health assessment situations. For each such decision context, we suggested several chemical groups as examples to prove when read-across between group members is possible, considering both chemical and biological similarities.ConclusionsWe agreed to carry out the complete read-across exercise for at least one chemical category per read-across scenario in the context of SEURAT-1, and the results of this exercise will be completed and presented by the end of the research initiative in December 2015.CitationBerggren E, Amcoff P, Benigni R, Blackburn K, Carney E, Cronin M, Deluyker H, Gautier F, Judson RS, Kass GE, Keller D, Knight D, Lilienblum W, Mahony C, Rusyn I, Schultz T, Schwarz M, Schüürmann G, White A, Burton J, Lostia AM, Munn S, Worth A. 2015. Chemical safety assessment using read-across: assessing the use of novel testing methods to strengthen the evidence base for decision making. Environ Health Perspect 123:1232–1240; http://dx.doi.org/10.1289/ehp.1409342
Characterization of Tumor-Specific Transplantation Antigen Induced in Cells Infected or Transformed by Polyomavirus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Y Barra, Y Ito, D Depétris, G Meyer
Journal: JNCI Journal of the National Cancer Institute (1983)

Tumor-specific transplantation antigen (TSTA) activity was investigated (with the use of inbred BALB/c and C3H mice and inbred Fisher and Wistar rats) in various early polyomavirus (Py)-coded proteins by three methodologies: 1) immunoprecipitation by anti-T-antigen sera, gel slicing, and immunization; 2) affinity chromatography with the use of anti-tumor-associated antigen serum; and 3) use of a Py mutant, NG18. The results obtained by all three techniques allowed refutation of the hypothesis that the three major species of T-antigen possess the main TSTA activity, particularly middle-sized T-antigen which is a plasma membrane protein. TSTA activity was found to be associated with proteins having a molecular weight of approximately 37,000. The exact origin of this protein is discussed.
Recombinant arginase as a novel anti-melanoma agent
Authors: E. C. Hsueh, S. Knebel, I. Collier, M. Kadze, C. Hsueh, T. Lo, P. Cheng, T. Leung
Journal: Journal of Clinical Oncology (2006)

12032 Background: BCT-100 is a recombinant arginase comprised of 329 amino acid residues. Arginase converts arginine to urea and ornithine. Previous studies suggested that melanoma cells were auxotrophic for arginine due to absence of argininosuccinate synthetase (ASS) expression. Thus, we hypothesized that recombinant arginase, BCT-100, is cytotoxic to human melanoma cells and its cytotoxicity correlates with absence of ASS expression. Methods: BCT-100 pegylated recombinant human arginase was manufactured by large scale fermentation of a recombinant B. subtilis strain LLC101 encoded with a human arginase gene. Following fermentation, the recombinant protein was extracted, purified, pegylated, and ultra-dialyzed. Ten established human melanoma cell lines were used. Cells were grown to 90% confluence, harvested, and plated at 10 4 cells per well in a 96-well plate and co-cultured with increasing concentrations of pegylated BCT-100 for 72 hours. CellTiter 96 Aqueous Non-radioactive Cell Proliferation Assay (Promega, Madison, WI) was used to measure percent viability, with absorbances measured at 490 nm. Total cellular RNA was isolated from established melanoma cell lines converted to cDNA at a concentration of 5 ng/ul. Quantitative real time polymerase chain reaction was performed on a 7300 Real Time PCR System, using Gene Expression Assays for ASS and GAPDH (Applied Biosystems). 10,000 fold standard curves were generated for all samples using GAPDH expression. Results: All ten cell lines demonstrated decreased viability as concentrations of BCT-100 increased. Average IC 50 value was 0.11 IU/ml. Eight of the 10 cells lines have IC 50 values &lt; 0.1 IU/ml. Of the 8 cell lines with IC 50 &lt; 0.1 IU/ml, all of them have low or undetectable ASS expression using quantitative RT-PCR. Of the 2cell lines with IC 50 &gt; 0.1 IU/ml, ASS expression was detected in 1 of 2. Conclusions: Arginine depletion with recombinant arginase, BCT-100, was cytotoxic to melanoma cells in vitro. The cytotoxic effect of BCT-100 on melanoma cells correlated with expression of argininosuccinate synthetase. BCT-100 is a promising novel agent for treatment of melanoma. Further in vivo experiment with BCT-100 is ongoing. [Table: see text]
Relationship of Leukocyte Numbers, Immunoregulatory Cell Function, and Phytohemagglutinin Responsiveness in Cancer Patients&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D P Braun, J E Harris
Journal: JNCI Journal of the National Cancer Institute (1981)

Leukocytes were quantitated in peripheral blood from 35 solid-tumor cancer patients and related to levels of phytohemagglutinin (PHA)-induced DNA synthesis. Levels of glass-adherent, indomethacin-sensitive, or 24-hour preculture-sensitive immunoregulatory activity were evaluated in PHA-stimulated peripheral blood mononuclear cells (PBMC). Cancer patients and patients with depressed PHA responses had significantly greater monocyte percentages in their PBMC than did healthy subjects; patients with normal PHA responses did not. Patients with disseminated disease had significantly greater monocyte percentages and depressed T-cell percentages than did controls; patients with at most minimum residual disease did not. When monocyte and lymphocyte percentages were correlated by linear regression analysis to PHA responsiveness, no significant correlation was found. A highly significant negative correlation was noted between PHA responsiveness and levels of immunoregulatory cell function. Abnormal immunoregulatory function, apart from alterations in peripheral blood leukocyte percentages and numbers contributes to impaired T-cell function in cancer patients.
Activity and Pharmacodynamics of 21-Day Topotecan Infusion in Patients With Ovarian Cancer Previously Treated With Platinum-Based Chemotherapy
Authors: Howard Hochster, Scott Wadler, Carolyn Runowicz, Leonard Liebes, Henry Cohen, Robert Wallach, Joan Sorich, Beth Taubes, James Speyer
Journal: Journal of Clinical Oncology (1999)

Twenty-one-day topotecan infusion was administered as second-line therapy in patients with previously treated ovarian cancer (based on our prior favorable phase I experience) to determine its activity, time to progression, and pharmacodynamics.Ovarian cancer patients with measurable lesions and one prior platinum-containing regimen were eligible. Topotecan 0.4 mg/m(2)/d 21-day continuous ambulatory intravenous infusion, with appropriate dose modifications for toxicity, was administered every 28 days. Weekly blood levels of topotecan and topoisomerase-1 (topo-1) levels in peripheral-blood mononuclear cells (PBMCs) were determined for pharmacodynamic correlation.Twenty-four patients were entered onto the study (six cisplatin-refractory, five relapsing within < 6 months and 13 relapsing > 6 months after platinum-based therapy). A total of 128 cycles of topotecan (median, four cycles per patient; range, one to 12 cycles) were administered. The major toxicity was neutropenia (29% grade 3 in all cycles and 4% grade 4). One episode of grade 4 thrombocytopenia (4%) occurred. Fifty-two percent of the patients had anemia that required transfusions. Eight of 23 patients with measurable disease (35%; 95% confidence interval [CI], 15% to 54%) had partial responses (PRs) lasting longer than 1 month. Two of these patients had minor residual computed tomographic changes but had clinical complete remissions that lasted up to 53 weeks while they were not undergoing further therapy. One patient with nonmeasurable disease had a PR (by CA-125 criteria) that lasted 6 months, for an overall response rate of 38% in nine of 24 patients (95% CI, 18% to 57%). The median time to progression was 26 weeks. Pharmacodynamic analysis demonstrated a statistically significant decrease in free PBMC topo-1 level at weeks 2 and 3 of drug administration. There was a strong statistical correlation between the decrease in free topo-1 levels and increasing area under the curve (AUC) for topotecan. This was confirmed in a pharmacodynamic model.Twenty-one-day infusion is a well-tolerated method of administering topotecan. Pharmacodynamic studies demonstrate correlations between (1) the week of infusion and the PBMC topo-1 level, (2) the AUC of topotecan and the decrease in topo-1 levels, and (3) the change in topo-1 level and the neutrophil nadir. The objective response rate of 35% to 38% (95% CI, 15% to 57%) in this small multicenter study is at the upper level for topotecan therapy in previously treated ovarian cancer. Prolonged topotecan administration therefore warrants further investigation in larger, randomized studies comparing this 21-day schedule with the once-daily-for-5-days schedule.
Authors' response
Authors: D. Jimenez
Journal: Thorax (2011)

In an attempt to identify patients who can be appropriately managed in a semioutpatient (after day 2) ambulatory manner and, at the other extreme, patients for active thrombolysis, we have used the enclosed protocol (figure 1) where individual components are based on published evidence but not necessarily guidelines.More specifically it incorporates the pulmonary embolism severity index (PESI) 5 in the two-test approach and gives more confidence, particularly when thrombolysis becomes an option in those with high severity (class IV and V) scores.Using the initial troponin, as a sensitive but not specific triage tool addressing right heart strain, reduces the overuse of ECHO and adds to the value of the pathway as there will still be patients who can be discharged diagnosed with a small PTE and low PESI score (class I and II) and therefore low risk of mortality.The future may see further validated use of highly sensitive cardiac troponin (hsTnT) and CT assessment of the right heart, but it is likely that a two-test approach will be maintained in risk stratification.