tbuckley/cabot-search huggingface dataset:
Abstract 8892: Manganese Deficiency May Play a Role in Coronary Spasm, and Selenium Deficiency May Induce Cardiac Dysfunction Through the Microcirculatory Disturbance
Authors: Yuji Hiraoka, Akihiro Nakayama, Yutaka Iida, Taketoshi Yamazaki, Masato Tanabe, Masatoshi Fujita
Journal: Circulation (2012)

Background: Although manganese, zinc and copper are essential cofactors for superoxide dismutase (SOD) activation, and selenium is an essential cofactor required for activation of glutathione peroxidase (GSHPx), their roles in cardiac diseases remain unclear. We therefore investigated the relationship between levels of these trace elements and cardiac diseases using sera from patients with vasospastic angina(VSA), DCM and AMI. Methods: We compared serum concentrations of 19 elements (Li, B, Al, Ti, V, Cr, Mn, Co, Ni, As, Se, Sr, Mo, Cd, Sn, Sb, Ba, Pt and Pb) by high resolution inductively coupled plasma (ICP) mass spectrometry and of 6 other elements (Ca, Mg, P, Fe, Cu and Zn) by ICP atomic emission spectroscopy, among patients with VSA(n =12), DCM(n=41), AMI(n=18) and control subjects with normal cardiac function(n=29). We also determined serum GSHPx and free radical-generating activities and measured perivascular fibrosis ratio (PVFR) in histological preparations of autopsied hearts in DCM patients. Results: Compared to the control subjects, manganese concentrations were lower in VSA patients (0.60±0.12 vs. 0.40±0.14 ng/ml, p&lt;0.001), while selenium and manganese concentrations were markedly lower in DCM patients (146.0±23.3 vs. 95.1±21.5 ng/ml, p&lt;0.00001 ; 0.60±0.12 vs. 0.37±0.16 ng/ml, p&lt;0.0001, respectively). A significant correlation was found between serum selenium concentrations and left ventricular ejection fraction (p=0.0012). The GSHPx activity was significantly lower in DCM patients than in the control subjects (221±34 vs. 328±44 μ mol/min/L, p&lt;0.001). Furthermore, the DCM patients enhanced radical generation in the serum, and the PVFR was also increased in this group(p&lt;0.001). Conclusions: The present study indicates that manganese deficiency may play a significant role in coronary spasm via reduction in SOD activity, resulting in increased superoxide levels which in turn inactivate NO, leading to coronary spasm. The study also suggests the possibility that selenium deficiency may play an important role in cardiac dysfunction via reduction in GSHPx activity; the resultant increase in oxidative stress induces microcirculatory disturbance, which in turn induces cardiac dysfunction.
Association of immune-regulatory (FoxP3+)-T-cell tumor infiltration status with benefit from chemoimmunotherapy with gemcitabine, oxaliplatin, 5-FU/FA plus GM-CSF and aldesleukine (GOLFIG) in metastatic colon cancer patients
Authors: P. Correale, P. Tagliaferri, M. T. Del Vecchio, C. Remondo, C. Migali, K. Y. Tsang, M. S. Rotundo, F. Fulfaro, P. Tassone, G. Francini
Journal: Journal of Clinical Oncology (2009)

3045 Background: GOLFIG is a novel chemoimmunotherapy regimen, combining gemcitabine, oxaliplatin, 5-FU/FA with immunoadjuvant GM-CSF and aldesleukine, which resulted safe and very active in colon cancer patients. Antitumor activity and immunity feedback to the treatment resulted strictly correlated. The best outcome was observed in patients showing autoimmunity signs, rise in central-memory-T cells, and decline in peripheral and tumor infiltrating immuno-regulatory T (Treg) cells. On these bases, we investigated a possible correlation between Treg tumor infiltration at diagnosis and clinical outcome of these patients. Methods: An immunohistochemistry study was carried out to quantify the infiltration of Treg (FoxP3+) lymphocytes in tumor samples of 41 colon cancer patients who received FOLFOX-4 chemotherapy or GOLFIG chemo-immunotherapy as enrolled in the ongoing phase III GOLFIG-2 trial. Treg tumor infiltration score (range 0 to 5) was then correlated with survival (OS) and time to progression (TTP). Results: A higher Treg tumor infiltration score (score 3–5) was associated to a longer OS and TTP in the whole patient population (high vs low score; TTP=18 vs 9.4 months; p=0.002; OS=55.7 vs 28.9 months; p=0.001); however, those patients with high tumor infiltration of FoxP3+-T cells who received GOLFIG regimen showed the most favorable outcome (high vs low score; TTP=20.8 vs 11.6 months; p=0.04; OS=68.1 vs 41 months; p=0.04). A Cox regression model demonstrated in these patients that a high Treg tumor infiltration score is an independent variable of long survival and prolonged TTP. Conclusions: Our results suggest that GOLFIG chemoimmunotherapy is highly effective in colon carcinoma patients with high FoxP3+ infiltration score and that Treg-tumor infiltration score may be a favorable prognostic marker in colon cancer patients. No significant financial relationships to disclose.
Quality of Life Analysis of Esogia-Gfpc-Gecp Trial- a Phase Iii, Randomized, Multicenter Study Comparing in Elderly Patients (≥70 Years) with Stage Iv Nsclc a Treatment Allocation Based on Ps and Age with an Experimental Strategy According to a Comprehensive Geriatric Assessment (Cga)
Authors: R. Corre, C. Chouaid, L. Greillier, H. Le Caer, C. Audigier Valette, N. Baize, H. Berard, L. Falchero, R. Descourt, E. Dansin, A. Vergnenegre, L. Bigay-Gamé, R. Schott, G. Le Garff, J. Le Treut, B. Massuti Sureda, J. Daures, C. Plassot, H. Lena
Journal: Annals of Oncology (2014)
Early readmission after hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality
Authors: R.T.M. Sprooten, R.H.J. Slenter, D. Kotz, G. Wesselig, E.F.M. Wouters, G.G.U. Rohde
Journal: European Respiratory Journal (2013)

BACKGROUND:   Patients who survive acute hospitalized exacerbations of chronic obstructive pulmonary disease (AECOPD) are at high risk of readmission for COPD and death. Half of these readmissions occur within the first seven weeks after discharge.   OBJECTIVES:   To assess the clinical difference between patients with early (within 7 weeks) and late readmissions for AECOPD after hospitalization for AECOPD and identify determinants associated with early readmissions for AECOPD.   METHODS:   In a retrospective, observational cohort study including all consecutive patients admitted between January 1, 2009, and April 1, 2010, for AECOPD we identified 91 patients who had at least 1 readmission for AECOPD during 1 year follow-up. Readmission within 49 days was defined as an early readmission based on Kaplan-Meier analysis. Uni- and multivariate analysis was used to analyse differences between early and late readmissions and to identify predictors for early admission.   RESULTS:   47 patients were “early re-admitters”. Mortality was significantly higher (n=19, 40% vs. n=10, 23%, p 45 u/l and signs of heart failure on chest X ray were significantly associated with early readmissions. Base excess > 2.5 mmol/l at discharge was associated with a prolonged readmission free interval. Living not at home was the only independent factor for early readmisisons [HR =2.146; 95% CI=1.065-4.323].   CONCLUSIONS:   The “early re-admitters” for AECOPD have a significantly increased mortality rate. Living at own house is associated with reduced risk to be an “early re-admitter”.
PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non–Small-Cell Lung Cancer
Authors: Suresh Senan, Anthony Brade, Lu-hua Wang, Johan Vansteenkiste, Shaker Dakhil, Bonne Biesma, Maite Martinez Aguillo, Joachim Aerts, Ramaswamy Govindan, Belén Rubio-Viqueira, Conrad Lewanski, David Gandara, Hak Choy, Tony Mok, Anwar Hossain, Neill Iscoe, Joseph Treat, Andrew Koustenis, Bélen San Antonio, Nadia Chouaki, Everett Vokes
Journal: Journal of Clinical Oncology (2016)

Purpose The phase III PROCLAIM study evaluated overall survival (OS) of concurrent pemetrexed-cisplatin and thoracic radiation therapy (TRT) followed by consolidation pemetrexed, versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy. Patients and Methods Patients with stage IIIA/B unresectable nonsquamous non–small-cell lung cancer randomly received (1:1) pemetrexed 500 mg/m 2 and cisplatin 75 mg/m 2 intravenously every 3 weeks for three cycles plus concurrent TRT (60 to 66 Gy) followed by pemetrexed consolidation every 3 weeks for four cycles (arm A), or standard therapy with etoposide 50 mg/m 2 and cisplatin 50 mg/m 2 intravenously, every 4 weeks for two cycles plus concurrent TRT (60 to 66 Gy) followed by two cycles of consolidation platinum-based doublet chemotherapy (arm B). The primary objective was OS. The study was designed as a superiority trial with 80% power to detect an OS hazard ratio of 0.74 with a type 1 error of .05. Results Enrollment was stopped early because of futility. Five hundred ninety-eight patients were randomly assigned (301 to arm A, 297 to arm B) and 555 patients (283 in arm A, 272 in arm B) were treated. Arm A was not superior to arm B in terms of OS (hazard ratio, 0.98; 95% CI, 0.79 to 1.20; median, 26.8 v 25.0 months; P = .831). Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events (64.0% v 76.8%; P = .001), including neutropenia (24.4% v 44.5%; P &lt; .001), during the overall treatment period. Conclusion Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non–small-cell lung cancer.
A retrospective analysis of intramural NCI prostate cancer trials: Progress made and insights gleaned.
Authors: J. L. Gulley, W. D. Stein, J. Schlom, R. A. Madan, W. L. Dahut, W. D. Figg, Y. M. Ning, D. Price, S. E. Bates, A. T. Fojo
Journal: Journal of Clinical Oncology (2010)

4657 Background: In solid tumors such as prostate cancer, novel paradigms are needed to assess therapeutic efficacy. We describe a method for estimating PSA growth and regression rate constants from serial PSA measurements. We assessed the method's potential in patients with metastatic castration resistant prostate cancer (CRPC). Methods: Patients with CRPC enrolled in five phase II studies conducted over more than a decade were evaluated. The studies represent the evolution of CRPC therapy, and include a vaccine trial. PSA measurements obtained prior to, and during, therapy were used. Data analysis using a two-phase mathematical equation yielded concomitant PSA growth and regression rate constants Results: Incremental reductions in growth rate constants were recorded in successive chemotherapy trials enrolling similar patients. Growth rate constants correlated with survival, except in patients receiving a vaccine-based therapy where the evidence demonstrates prolonged survival presumably due to immunity developing subsequent to vaccine administration. In combination chemotherapy trials the analysis suggests prolonging drug exposure could have increased survival Conclusions: Incremental reductions in tumor growth rate constants suggest increased efficacy in successive trials. Because the derived growth rate constant correlates with survival, it may be useful in clinical trials to assess differences in efficacy. The PSA-TRICOM vaccine appears to have provided marked benefit not apparent during vaccination, but consistent with development of a growth-retarding immune response. If validated as a surrogate for survival the growth rate constant would offer an important new efficacy endpoint for clinical trials. Finally, pursuit of what appear to be very promising results with a PSA-TRICOM vaccine is warranted. No significant financial relationships to disclose.
Orientation of human respiratory cilia
Authors: ME Rautiainen
Journal: European Respiratory Journal (1988)

Ciliary orientation was studied on the respiratory epithelium of the nasal cavity or the sphenoidal sinus of ten adult nonsmokers without respiratory disease. The ciliary orientation was evaluated from micrographs by measuring the angle between the plane defined by the central tubules and reference line (with a semiautomatic image analyser (IBAS I]. The standard deviation of the angles of cilia population was counted in every field. The standard deviation of the measurements described the ciliary alignment. It varied from 12.1-41.2 degrees. The mean standard deviation was 27.3 +/- 7.4 degrees. 58% of all measured cilia were within +/- 0-20 degrees of the mean and 85% of cilia were within +/- degrees. However, a few cilia or small groups of cilia were found in most fields which differed dramatically from the main orientation. The size of these groups was always less than ten cilia. On the normal respiratory epithelium the standard deviation of ciliary orientation varies between +/- 10-40 degrees (at about 97% probability). For diagnostic conclusions more than 60 cilia should be measured.
Abstract 18112: Low-Energy Shock Wave Treatment Induces Angiogenesis in Ischemic Muscle by Stimulation of Toll-Like Receptor 3 Signaling
Authors: Johannes Holfeld, Can Tepeköylü, Radoslaw Kozaryn, Karin Albrecht-Schgoer, Christoph Krapf, Rudolf Kirchmair, David Bernhard, Kai Zacharowski, Anja Urbschat, Michael Grimm, Patrick Paulus
Journal: Circulation (2013)

Introduction: Low energy shock waves (SW) have been shown to induce angiogenesis in ischemic myocardium. The mechanism translating the physical stimulus to a biological signal is unknown. Toll-like receptor (TLR)-3 is activated by RNA binding. It plays a key role in inflammation and angiogenesis. Hypothesis: SW cause cellular cavitation, thus liberating cytoplasmic mRNA that activates TLR-3 as does the specific agonist Poly I:C. Effects are suppressed in TLR-3 silenced cells and in TLR-3 knock out mice. Methods: The effect of SW was tested in human umbilical vein endothelial cells (HUVECs): untreated (control) vs. SW treated (SW group) vs. treated with 200 μg/ml Poly I:C (agonist). TLR-3 gene silencing was done with siRNA. Hind limb ischemia was performed in wild type and TLR-3 kock-out mice. Expression of mRNA and proteins of the TLR-3 signaling pathway as well as typical angiogenic genes and proteins were measured. Laser doppler perfusion imaging and necrosis score were assessed for clinical outcome evaluation (n=6). Results: Shock wave treatment of HUVECs shows increase of mRNA expression (% of control) as does Poly I:C after 2 hours: TLR-3 (SW group 123.8 ± 8.0 and agonist group 237.7 ± 14.1, p&lt;0.0001), Tie-2 (SW group 154.3 ± 20.0 and agonist 125.7 ± 12.3, p&lt;0.008). TLR-3 gene silencing in SW treated HUVECs causes loss of response for TLR-3 mRNA (107.0 ± 13.3) as compared to SW group (378.3 ± 14.2) or agonist (1261 ± 72.1), both p&lt;0.0001. SW treated TLR-3 knock-out mice showed no improvement of perfusion ratio 4 weeks after hind limb ischemia (0.52 ± 0.07 vs. 0.53 ± 0.02 controls, p&gt;0.05), whereas SW treated wild type animals improved significantly (0.78 ± 0.03 vs. 0.48 ± 0.08 controls, p=0.015). Pro-angiogenic genes and proteins were up-regulated significantly. All known TLR-3 signaling pathways were involved as shown by significant increase of key proteins Trif, TRAF6 and IRF3. Conclusion: Low energy shock waves induce angiogenesis in ischemic muscle by stimulation of Toll-like receptor 3 signaling in endothelial cells. Effects are suppressed in TLR-3 silenced cells and in TLR-3 knock-out mice.
Topoisomerase II alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated with single-agent doxorubicin or single-agent docetaxel
Authors: Christine Desmedt, Virginie Durbecq, Marianne Paesmans, Christos Sotiriou, Jean-Yves Leroy, Ghizlane Rouas, S Chan, Kay Friedrichs, Tamas Pinter, S. Van Belle, Elizabeth Murray, Thimothy J. Perren, S. Olsen, Angelo Di Leo, Fatima Cardoso, Martine Piccart-Gebhart, Denis Larsimont
Journal: Cancer Research (2004)

1152  In order to identify molecules involved in pulmonary carcinogenesis and those to be useful as diagnostic markers as well as for development of novel drugs and immunotherapy, we established a screening system by a combination of the cDNA microarray analysis and experiments using antisense S-oligonucleotide, RNA interference (RNAi) technique, and tumor tissue microarray. We performed a cDNA microarray representing 27,648 genes for 37 non-small cell lung cancer cells (NSCLCs) purified by laser-capture microdissection and selected 428 candidate genes as tumor markers or therapeutic targets, which are specifically expressed in NSCLCs, but not in vital tissues. We then determined the full-length sequences of the 328 genes by EST screening and confirmed their gene expression pattern using semi-quantitative RT-PCR and/or northern-blot analyses. To assess whether each of these genes plays a role in the growth or survival of lung-cancer cells, we applied the antisense S-oligonucleotide and RNAi technique, and identified several genes that could be good candidates for the development of novel therapeutic drugs or immunotherapy. These genes encode proteins that enhanced cell growth, some in an autocrine manner. In addition to them, we also identified cytoplasmic membrane proteins that are likely to be candidate tumor markers for NSCLC. Subsequent analysis detected high levels of individual proteins in serum from NSCLC patients using ELISA. We also correlated their expression patterns with clinicopathological data, including prognosis by immunohistochemistry of tumor tissue microarrays in 400 archived NSCLCs. Our results, obtained by the combined analyses of the high throughput approaches to determine gene expression profiles, their oncogenic functions, and their correlation with the clinical phenotype, could provide valuable information that will help us to eventually identify novel therapeutic target molecules and predictive markers for this type of cancer.
Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas.
Authors: W H Wilson, R Little, D Pearson, E S Jaffe, S M Steinberg, B D Cheson, R Humphrey, D R Kohler, P Elwood
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the efficacy and maximum dose-intensity of a new topoisomerase I (topo I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. PATIENTS AND METHODS Eligible patients had measurable disease and were considered incurable. 9-AC was infused over 72 hours at an initial dose rate of 40 microg/m2/h every 3 weeks with subsequent intrapatient escalations or reductions in 10-microg/m2/h increments based on toxicity. To assess the impact of granulocyte-colony stimulating factor (G-CSF) on dose-intensity, the first 16 patients received no G-CSF and the subsequent 29 patients received G-CSF on all cycles. RESULTS Forty-five patients received a total of 142 cycles of 9-AC. The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggressive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respectively, and Hodgkin's lymphoma in 9%. Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy-sensitive disease. Of 40 assessable patients, 10 (25%) achieved a partial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a median follow-up duration of 35 months, the median event-free survival (EFS) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response was 5 months (range, 1 to 10). G-CSF significantly reduced the incidence of neutropenia and diarrhea, but did not permit a significant increase in dose-intensity. CONCLUSION 9-AC had a reasonable response rate of 25% in heavily pretreated patients. The low response rate in patients with chemotherapy-resistant disease suggests that there is cross-resistance between 9-AC and standard chemotherapy. However, there was no association between 9-AC response and the number of prior regimens. Due to dose-limiting thrombocytopenia, G-CSF support did not increase dose-intensity, although individual patients benefited from the use of G-CSF.
Hypothyroidism after interleukin-2 therapy.
Authors: L C Hartmann, W J Urba, R G Steis, J W Smith, L VanderMolen, S P Creekmore, D L Longo
Journal: Journal of Clinical Oncology (1989)

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.1989.7.5.686 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2785167 Hypothyroidism after interleukin-2 therapy. L C HartmannxL C HartmannSearch for articles by this author , W J UrbaxW J UrbaSearch for articles by this author , R G SteisxR G SteisSearch for articles by this author , J W Smith 2ndxJ W Smith 2ndSearch for articles by this author , L VanderMolenxL VanderMolenSearch for articles by this author , S P CreekmorexS P CreekmoreSearch for articles by this author , D L LongoxD L LongoSearch for articles by this author Show More https://doi.org/10.1200/JCO.1989.7.5.686 PDF "Hypothyroidism after interleukin-2 therapy.." Journal of Clinical Oncology, 7(5), pp. 686–687© 1989 by American Society of Clinical Oncology
Skunk-like cannabis may damage white matter in the brain, study shows
Authors: Jacqui Wise
Journal: BMJ (2015)

Frequent use of high potency, “skunk-like” cannabis can damage the white matter fibres in the brain, researchers report in the journal Psychological Medicine .1

Researchers from King’s College, London, UK, and from Sapienza University of Rome, Italy, examined the brains of 56 patients who had reported a first episode of psychosis, 37 of whom …
Minimal hepatic toxicity following infusion of adenoviral vector: Spatial restriction of CAR receptor in normal liver
Authors: D. Sze, T. Au, S. Thorne, D. Sze, D. Kirn, M. Korn, T. Reid
Journal: Journal of Clinical Oncology (2005)

3129 Background: We administered an adenoviral vector, Onyx-015, into the hepatic artery of patients with metastatic colorectal cancer involving the liver. Flu-like symptoms were observed in >90% of the patients, but no dose-limiting toxicity occurred during this study. However, in preclinical models, hepatic toxicity and metabolic abnormalities were the primary dose-limiting toxicity identified. Therefore, we undertook this analysis to determine the impact of repeated adenoviral exposure on hepatic function. Methods: Thirty-five patients enrolled in this multi-institutional phase I/II trial received up to 8 arterial infusions of up to 2 x 10e12 viral particles. 17 patients were treated at our institution, providing a detailed dataset on the changes in hepatic function following treatment. Results: No change in hepatic function occurred with the first treatment of Onyx-015 among these 17 patients. Transient increases (grade I-III) in transaminase levels occurred in one patient starting with the second infusion and transient increases in bilirubin was observed in 2 patients starting with the fifth treatment. When observed, the changes were mild and transient and occurred too early to be explained by viral mediated lysis of hepatocytes. To further understand the basis for potential hepatic toxicity of adenoviral vectors, we evaluated the infection of primary hepatocytes in vitro and the expression of the primary receptor, the coxsackie-adenoviral receptor (CAR) in normal liver. We found that primary hepatocytes, but not malignant hepatocytes or primary lung epithelial cells, are refractory to infection and that CAR is localized at junctions between hepatocytes and so is inaccessible to hepatic blood flow. Conclusions: 1) Changes in hepatic functions following repeated hepatic artery infusions of an adenoviral vector were mild and transient, and are probably due to immune factors rather than viral infection. 2) There is limited access of adenovirus in the circulation to CAR on hepatocytes, limiting hepatic toxicity. No significant financial relationships to disclose.