tbuckley/cabot-search huggingface dataset:
Interferon-Induced Nuclear DNA Alterations in Malignant Carcinoid Tumors In Vivo&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Wilander, A Bengtsson, I Norheim, K Oberg
Journal: JNCI Journal of the National Cancer Institute (1986)

Tumor cell specimens were obtained by ultrasonically guided percutaneous needle liver biopsy from 23 patients with metastatic small intestinal carcinoid tumors. The patients were admitted to the hospital for antitumor therapy (streptozocin, 5-fluorouracil, and leukocyte interferon). The tumor cell samples were used for DNA cytofluorometry. All tumors (12 cases) from untreated patients exhibited diploid DNA stem lines with low proliferative activity. The mean number of tetraploid cells was 8%. Altered nuclear DNA records were obtained in tumors of 8 patients, all of which were treated with leukocyte interferon at 3-6 X 10(6) IU/day for 4-32 months. The DNA records in these tumors varied, but they were mainly in the range between diploid and tetraploid values. In some cases several nuclear DNA peaks were observed within the limits for the cell cycle. It is assumed that the interferon treatment was responsible for the development of altered DNA cell lines because: 1) all untreated tumors yielded regular diploid DNA histograms, 2) interferon was the only drug administered to all patients with tumors displaying altered DNA records, and 3) modal diploid DNA values were observed prior to the interferon treatment in some patients. It is suggested that interferon in vivo blocked carcinoid tumor cell populations in different phases of the cell cycle. This result might explain the nuclear DNA profiles registered in the treated patients as well as the therapeutic effect obtained by interferon.
Occurence of venothromboembolism (VTE) in patients (pts) with acute lymphocytic leukemia (ALL), Burkitt's leukemia/lymphoma (BL), or lymphoblastic leukemia (LL)
Authors: N. V. Luong, H. M. Kantarjian, S. H. Faderl, D. A. Thomas, K. D. Vu
Journal: Journal of Clinical Oncology (2009)

7059 Background: Venous thromboembolism (VTE) is a significant public health issue. Although neoplastic diseases are known risk factors for the development of VTE, little is known about the incidence and predisposing factors of VTE among leukemia patients (pts). Methods: We performed a retrospective study to determine the incidence and risk factors associated with development of VTE among pts with ALL, BL, LL at M. D. Anderson Cancer Center between 1999 and 2005. Medical records of 299 ALL pts were reviewed and analyzed. All computations were conducted using Stata 10. Results: Of the 299 pts with a male/female ratio of 182/117 and a median age of 43 yrs (range 15–83 yrs), 18% had VTE. Recurrent VTE occurred in 10 pts. VTE were identified in upper extremities (59%), lower extremities (30%), pulmonary vasculature (7%), and within venous catheters (4%). In a univariate model, pts with baseline platelet (plt) count 50–99 x 10 9 /L were 2.2 times (95% CI: 1.05–4.55) more likely to develop VTE than pts who had plt &gt;100 x 10 9 /L. Pts aged 40–59 yrs were 2.3 times (95% CI: 1.15–4.59) more likely to develop VTE than pts aged 15–39 yrs. Women were 1.8 times (95%CI: 1.04–3.4) more likely than men to have a VTE. Pts with a history of VTE were 15.2 times (95% CI: 2.97–77.51) more likely to develop a VTE than pts who had no prior VTE history. Pts with &gt; 3 comorbidities were 2.6 times (95% CI: 1.19–5.48) more likely to develop VTE than pts without comorbidities. Pts who used oral contraception or hormone replacement therapy (OCP/HRT) were 2 times (95% CI: 1.07–3.92) more likely to develop VTE than non-users. Pts with Philadelphia chromosome (Ph)-positive ALL were 3 times (95%CI: 1.41–6.17) more likely to develop VTE than pts with Ph-negative ALL. In a multivariate model, significant predictors of VTE were age 40–59 yrs, plt count 50–99 x 10 9 /L, diagnosis of Ph-positive ALL, history of VTE, and OCP/HRT use. Conclusions: Pts with ALL have a high VTE rate. In addition to traditional risk factors, disease-specific features may also predispose pts to higher VTE risk. Further studies should be done in other leukemias to establish guidelines in the prevention and management of VTE in pts with leukemia. [Table: see text]
Diet and Trend in Prostate-Specific Antigen: Inferences for Prostate Cancer Risk
Authors: Alan R. Kristal
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.17.3570 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12202653 Diet and Trend in Prostate-Specific Antigen: Inferences for Prostate Cancer Risk Alan R. KristalxAlan R. KristalSearch for articles by this author Show More Fred Hutchinson Cancer Research Center, Seattle, WA https://doi.org/10.1200/JCO.2002.20.17.3570 Full Text PDF Figures and Tables "Diet and Trend in Prostate-Specific Antigen: Inferences for Prostate Cancer Risk." Journal of Clinical Oncology, 20(17), pp. 3570–3571© 2002 by American Society of Clinical Oncology
F-18-labeled fluorodeoxyglucose positron emission tomography for evaluation of disease extent, response to treatment and follow-up in primary CNS lymphoma
Authors: P. M. Kiewe, S. Maza, D. Munz, A. Korfel, E. Thiel
Journal: Journal of Clinical Oncology (2007)

2015 Background: Fluorine-18-labeled ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has demonstrated remarkable sensitivity in the detection and follow-up of malignant lymphoma. The aim of this study was the prospective evaluation of potential benefits of FDG-PET including whole-body PET for evaluation of disease extent, response to treatment and follow-up of patients with primary CNS lymphoma (PCNSL). Methods: Extent of disease and response to therapy were evaluated using homologous scans of MR imaging and a total number of 36 18 F-FDG-PET examinations in 10 immunocompetent patients with newly diagnosed or recurrent PCNSL before and repeatedly during treatment and follow-up. Results: In 4 of 10 patients before treatment, MRI findings lacked a PET correlative, and in two patients each one additional lesion not visualized by MRI was detected by PET. Additional systemic spots of activity in whole-body PET were found in two patients and confirmed as asymptomatic lymphoma manifestations by computed tomography (CT) in one patient. Under treatment, tumor response was congruent on PET and MRI in 4 of 6 patients. In two patients, however, PET indicated complete disappearance of vital tumor while findings persisted on MRI. During follow-up in a series of 5 patients, pathologic FDG-uptake had been found in one patient on PET 34 weeks after therapy and 9 weeks before relapse was diagnosed on MRI. In another patient, relapse was suspected on PET 76 weeks after therapy without a correlative on MRI performed 2 and 6 weeks thereafter. Conclusions: In PCNSL, FDG-PET may contribute additional information regarding the extent of disease and response to treatment. Relapse can probably be detected earlier than with MRI. No significant financial relationships to disclose.
Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: the effect of index date selection?
Authors: Johannes TH Nielen, Olorunfemi Oshagbemi, Frank de Vries, Andrea M Burden
Journal: Annals of the Rheumatic Diseases (2016)

Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: the effect of index date selection?We read with great interest the study by Solomon et al 1 regarding the effect of colchicine on risk of cardiovascular (CV) events and all-cause mortality.In their study, they report a marked reduction in the number of CV events and all-cause mortality with the use of colchicine when compared with a reference group not using this drug.Sensitivity analyses mimicking an intention to treat approach showed similar results.Interestingly, no clear gradient of effect according to duration of use was found.The striking protective effect and the limited evidence for a causal relationship raised some questions regarding methodological aspects of this study that we feel warrants further discussion.We agree with the authors that the non-users may have been sicker despite similar baseline characteristics, and therefore did not receive colchicine.We would like to propose an extension to this theory.As described in the methods section, non-users were matched by age, gender and index date.In order to minimise selection bias, a non-user is usually assigned the index date of his matched exposed patient. 2 3 While this was the case in this study, an additional condition for the non-user (control) index date was required.In order to be eligible for matching, non-users had to have a Medicare visit, which could include hospitalisations or physician visits, on the same day as the colchicine user index date.This would entail that patients who were eligible to be matched were not average patients, but those who had a reason to visit a physician.Inherently, the non-users were then likely to have an illness (ie, reason to visit the physician) on or close to the index date.Moreover, if the visit was for, or associated with, one of the CV outcomes, this could have led to the selection of a high-risk reference group.If this were true we would expect higher rates of CV outcomes among the control patients immediately following the index date, with a waning of risk during follow-up.Indeed this is what is suggested by the results in this study, and particularly in the sensitivity analysis, where control patients with a physician visit, which was interpreted as the index date, are more likely to experience the outcome shortly after the index date rather than later.Perhaps excluding patients with visits related to the outcomes, or assigning control patients a random index date (ie, incident density sampling), would help mediate concerns of a sicker control group.
Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.
Authors: Renata D'Alpino Peixoto, Aalok Kumar, Sharlene Gill, Howard John Lim
Journal: Journal of Clinical Oncology (2015)

753 Background: Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods: We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results: 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. 176 pts recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first line in 3 pts (13.6%), as second line in 14 (63.6%), and third line in 5 (22.7%). Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and OS were 3.3 (95% CI 1.4-5.1) and 10.0 months (95% CI 5.3-14.6), respectively. There was no difference in PFS for patients who were re-exposed to oxaliplatin in less than 36 months or later than that (3.6 versus 3.1 months, p=0.793, HR=0.88). Conclusions: In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.
&lt;italic&gt;Brief Communication:&lt;/italic&gt;Type-C Virus Particles in a Feline Angioma: A Case Report
Authors: D G Feldman, T Ehrenreich, L Gross
Journal: JNCI Journal of the National Cancer Institute (1974)

Examination of a spontaneous, subcutaneous angioma of a cat revealed type-C virus particles budding from the cell membrane of histiocytes and fibroblasts. Many mature and immature type-C particles were present in intercellular spaces. A few intracytoplasmic type-A particles were also observed. The causal relationship between the virus particles and the tumor has not been determined.
Medium Pollution Rates in Cell Cultures
Authors: Gio Batta Gori, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1970)

Growth of cell cultures represents a balance between available nutrients and catabolic pollutants. Experimental evidence indicates that pollution rate values depend on the individual ceil type, growth condition, and the relative mass of cells (density) rather than on the number of cells in a culture. Medium pollutants were found to be dialyzable and nondialyzable factors. Lactic acid was used to monitor the degree and rate of pollution when correlated with cloning efficiency tests. The biological significance of the pollution rate ω as a quantitative indicator of catabolic activity is proposed. This rate can be utilized as a new index of cell response to physiological and environmental stimulation, as a marker of cellular specificity, in the accurate prediction of medium-turnover rates, and, when optimization and characterization of growth conditions are required, for the accurate design and interpretation of experiments.
Respiratory pathogens, immunodeficiency or systemic response - What comes first in the etiology of severe community-acquired pneumonia (sCAP)
Authors: Kseniia Bielosludtseva, Tetyana Kireeva
Journal: European Respiratory Journal (2013)

Aim: to study the diagnostic value of CD4 marker and procalcitonin (PCT) at patients with sCAP in connection with the respiratory pathogen.

Materials and methods: we studied 32 patients (pts) with sCAP and identified respiratory pathogen: physical examination, identification of agent, HIV-test, CD4 counting, the study of PCT level on 1st day before antibiotic therapy.

Results: depending on the etiology of sCAP patients were retrospectively divided into 2 groups: group 1 - 24 HIV-negative pts, who were divided into 2 subgroups: 1A - 15 pts with Gr+bacteria, 1B - 9 patients with Gr-bacteria, group 2 - 8 HIV-positive pts with Pneumocystis pneumonia.

View this table:

Levels of CD4 and PCT in groups and subgroups





Pts of group 1 had strong inverse correlation between CD4 and PCT (r =-0,73, p < 0,05) in contrast with group 2.

Conclusions: 1)decreasing of CD4 at HIV-negative patients less than 500 ml-1 significantly increases the risk of sCAP causing Gr- agents, which, in turn, is accompanied with severe systemic inflammatory response; 2) for Pneumocystis pneumonia at HIV-positive patients do not observe correlation between CD4 and system response.
Ramucirumab (Ram) As Second-Line Treatment in Patients (Pts) with Advanced Hepatocellular Carcinoma (Hcc) Following First-Line Therapy with Sorafenib: Results from the Randomized Phase III Reach Study
Authors: A.X. Zhu, B.Y. Ryoo, C.J. Yen, M. Kudo, R. Poon, D. Pastorelli, J-F. Blanc, H.C. Chung, A.D. Baron, T.E.F. Pfiffer, T. Okusaka, K. Kubackova, J. Trojan, J. Sastre, I. Chau, S-C. Chang, P.B. Abada, L. Yang, J.D. Schwartz, J.O. Park
Journal: Annals of Oncology (2014)
Only By Products From Many Adjuvant Breast Cancer Studies
Authors: Christian Sauter
Journal: Journal of Clinical Oncology (1984)

To the Editor: The paper by Lippman et al prompts me to send you the following letter that might induce chairpersons of cooperative studies to reflect on the possibility that they may lose years of study time due to inadequate study designs. The report of Lippman et al shows a typical adjuvant breast cancer study where, on the grounds of the study design, only by-products can be expected as results. Surgery-only control subjects were omitted from the study design based on the hypothetical but until today never-proven efficacy of doxorubicincyclophosphamide combination chemotherapy in the adjuvant situation. The main aim of any adjuvant study, if treatment is better than nothing, can not be answered by such a study design. Thus, secondary problems such as the tolerance of cytotoxic drugs after irradiation are studied. In another recently published study, by 1974 surgery-only control subjects were already omitted in an adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) trial. The three treatment arms (CMF, CMF plus tamoxifen, and CMF plus tamoxifen plus BCG) showed no difference in time to relapse. To extract at least some useful information the prognostic value of progesterone receptors were analyzed. However, the hundreds of CMF cycles were unnecessary for this information. The similarly designed 1976 Swiss study (chlorambucil, methotrexate, and fluorouracil [LMF] for six months v LMF for 24 months) will only demonstrate the known fact of the oncogenicity of chlorambucil. The lessons from such insufficient study designs unfortunately have not been learned in the eighties: The Ludwig Institute V trial on perioperative and adjuvant treatment lacks adequate surgery-only groups for an important prognostic subset (node-positive postmenopausal patients). For this subset the recent publication of the side effects will probably be the only useful information; however, this type of result never justifies the chemotherapy-induced suffering of these women. The new Swiss trial implemented in 1982 that compares CMF v LMF without surgery-only control subjects in one to three node-positive patients is an example of unnecessary chemotherapy (CMF in node-positive postmenopausal women.) From all the studies without adequate control subjects, the best results we can expect are the type of results presented by Lippman et al. With respect to advances in therapeutic decision making, the years spent on these studies are lost.
Abstract 17088: Permanence of Pulmonary Vein Isolation Using Cryoballoon Observed in Repeat Left Atrial Ablation
Authors: Albert Chiu, Muhanad Al-Zubaidi, Wilber Su
Journal: Circulation (2014)

Background: Cryoballoon ablation using Arctic Front Advance (AFA) (Medtronic, Minneapolis, MN) has been used for the treatment of atrial fibrillation (AF). Permanence of pulmonary vein isolation (PVI) has not been established, particularly correlating to reduced dosing strategies and to time-to-isolation during PVI. Methods: A single center retrospective chart review of 644 patients who had undergone prior AF ablation using AFA was examined (195 paroxysmal, 335 persistent, and 114 long-standing persistent). Dosing of 3 minutes and repeat ablation at 2 minutes were utilized. In addition, termination with temperature <-55 C were utilized to minimize collateral injury. 73 of 644 patients underwent repeat ablation, where previous procedural characteristics and the status of PVI at the time of repeat ablation were analyzed. Results: 73 of 644 patients (11.3%) underwent repeat ablation for left atrial arrhythmias (6 paroxysmal, 28 persistent, 39 long-standing persistent) with time to repeat ablation 1.5 month t...
Abstract 18852: Adenylate Kinase Phosphotransfer and AMP Signaling Regulate Cardiomyocyte Cell Cycle and Heart Regenerative Capacity
Authors: Song Zhang, Emirhan Nemutlu, Andre Terzic, Petras Dzeja
Journal: Circulation (2012)

The mammalian heart loses its regenerative potential within a week after birth. Although under certain circumstances adult cardiomyocytes can re-enter the cell cycle, initiate DNA synthesis and progress towards mitosis, however, they do not complete a conventional mitosis cycle and proceed towards endomitosis resulting in polyploidy. This suggests that high-energy dependent steps in cell cycle and myofibrillar disassembly are malfunctioning in adult cardiomyocytes. It is known that nucleotide-based energetic signaling and metabolic environment are critical for initiation of tissue regeneration after injury. The regulatory mechanisms and energetic-metabolic signaling circuits that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. Using mouse neonatal (2 and 10 days) hearts, with high and low regenerative capacity, respectively, we have determined metabolomic profiles and dynamics of phosphotransfer circuits and AMP-signaling using 18O-phosphoryl labeling mass-spectrometric and 18O-assisted 31P NMR techniques. The results demonstrate that loss of heart regenerative capacity 10 days after birth is associated with marked changes in heart metabolome and adenylate kinase (AK)-catalyzed phosphotransfer flux. Among most altered metabolites were putrescine and myo-inositol, involved in tissue regeneration, Krebs cycle and amino acid metabolites, creatinine, glucose-6-phosphate and lactate indicating rearrangements in energy and substrate metabolic systems. AK flux was the only phosphotransfer flux significantly upregulated in hearts at 10 days of age along with increased in mitochondrial and glycolytic capacities and mitochondrial AK2 expression. Increased AK2 expression was associated with augmented AMP phosphorylation, measured by generation of β-ATP[18O], and reduction of AMPK activity. Thus, increased channeling of AMP into mitochondria and reduction of AK-AMP-AMPK signaling axis could contribute to the withdrawal from completion of cell cycle in terminally differentiated adult cardiomyocytes. The uncovered metabolic signaling mechanism opens new avenues for targeted regulation of heart regenerative potential critical for repair of injured hearts.
Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer.
Authors: J Crawford, M O'Rourke, J H Schiller, C H Spiridonidis, S Yanovich, H Ozer, A Langleben, L Hutchins, A Koletsky, G Clamon, S Burman, R White, J Hohneker, C H Spiridonitis
Journal: Journal of Clinical Oncology (1996)

PURPOSE This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study. PATIENTS AND METHODS Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy. RESULTS The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions. CONCLUSION This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.