tbuckley/cabot-search huggingface dataset:
Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.
Authors: C L Vogel, R V Smalley, M Raney, S Krauss, J Carpenter, E Velez-Garcia, E Fishkin, S Raab, M R Moore, M Stagg
Journal: Journal of Clinical Oncology (1984)

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.
Calcite Single Crystals as Hosts for Atomic‐Scale Entrapment and Slow Release of Drugs
Authors: Giulia Magnabosco, Matteo Di Giosia, Iryna Polishchuk, Eva Weber, Simona Fermani, Andrea Bottoni, Francesco Zerbetto, Pier Giuseppe Pelicci, Boaz Pokroy, Stefania Rapino, Giuseppe Falini, Matteo Calvaresi
Journal: Advanced Healthcare Materials (2015)

Doxorubicin (DOX)/CaCO3 single crystals act as pH responsive drug carrier. A biomimetic approach demonstrates that calcite single crystals are able, during their growth in the presence of doxorubicin, to entrap drug molecules inside their lattice along specific crystallographic directions. Alterations in lattice dimensions and microstructural parameters are determined by means of high-resolution synchrotron powder diffraction measurements. Confocal microscopy confirms that doxorubicin is uniformly embedded in the crystal and is not simply adsorbed on the crystal surface. A slow release of DOX was obtained preferentially in the proximity of the crystals, targeting cancer cells.
Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma
Authors: Masafumi Ikeda, Takuji Okusaka, Shuichi Mitsunaga, Hideki Ueno, Toshiyuki Tamai, Takuya Suzuki, Seiichi Hayato, Tadashi Kadowaki, Kiwamu Okita, Hiromitsu Kumada
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To determine the maximum tolerable dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of lenvatinib in patients with advanced hepatocellular carcinoma (HCC). Experimental Design: This multicenter, open-label, phase I, dose-escalation study included patients aged 20 to 80 years, refractory to standard therapy, and stratified by hepatic function measured using Child–Pugh (CP) scores: CP-A (score, 5–6) and CP-B (score, 7–8). Lenvatinib was administered continually once daily for 4-week cycles. MTD was defined as the maximum dose associated with ≤ 1 dose-limiting toxicity (DLT) occurring in cycle 1 among 6 patients. Results: In total, 20 patients (9 in CP-A and 11 in CP-B) were enrolled. The MTD was 12 and 8 mg once daily in CP-A and CP-B, respectively; DLTs included proteinuria, hepatic encephalopathy, and hyperbilirubinemia. The most common grade 3 toxicities included hypertension in CP-A and hyperbilirubinemia in CP-B. Lenvatinib plasma concentration at 24 hours after administration (C24 h) for 12 mg once daily was higher in patients with HCC than in patients with other solid tumors shown in a previous phase I study, but C24 h for 25 mg once daily lenvatinib was comparable. After lenvatinib treatment, the number of circulating endothelial and c-Kit+ cells decreased and the levels of interleukin (IL)-6, IL10, granulocyte-colony stimulating factor, and vascular endothelial growth factor increased (P &amp;lt; 0.05). Partial responses were observed in 3 patients and tumor shrinkage occurred in 14 patients. Conclusions: Lenvatinib (12 mg once daily) demonstrated preliminary efficacy with manageable toxicity and is the recommended dose for phase II studies in patients with HCC and CP-A. Clin Cancer Res; 22(6); 1385–94. ©2015 AACR.
NITROGEN INHALATION THERAPY FOR SCHIZOPHRENIA
Authors: F. A. D. ALEXANDER, H. E. HIMWICH
Journal: American Journal of Psychiatry (1939)

Encouraging results from a year's experience in the treatment of schizophrenia in a small group of patients by nitrogen inhalation therapy have been noted. The methods and technique employed have been described. The landmarks of treatment and the signs and symptoms of acute anoxia observed during these treatments have been discussed. As a result of our experience with this form of therapy we believe that it can offer most promising and safest results if it is conducted by physicians well trained in the use of gas anesthesia apparatus, cognizant of the signs and symptoms of acute oxygen want, and capable of instituting efficient resuscitating measures in the event of untoward reaction. It appears that the most satisfactory results will obtain if the anoxia produced is severe and the time of the treatment limited to six minutes. The use of nitrous oxide as a substitute for nitrogen or the employment of depressant drug sedation in conjunction with nitrogen inhalation therapy are contraindicated.
Surgery for Early-Stage Small Cell Lung Cancer
Authors: Bryan J. Schneider, Ashish Saxena, Robert J. Downey
Journal: Journal of the National Comprehensive Cancer Network (2011)

Limited-stage small cell lung cancer remains one of the more frustrating malignancies to treat. Current standard of care typically includes platinum-based chemotherapy with thoracic radiation, and although response to therapy is high, most patients will ultimately experience relapse and die of recurrent disease. No high-level data exist supporting surgical resection of early-stage disease; however, several retrospective reviews and small single-arm studies suggest surgery may benefit patients with very limited extent of disease. This article reviews the available literature, and proposes guidelines for including potentially curative resection in the management of patients with limited-stage small cell lung cancer.
p53-dependent, replicative cell senescence suppresses chronic hypoxia-Induced pulmonary hypertension in mice
Authors: Christophe Guignabert, Ly Tu, Irena Drascovic, Charlene François, Philippe Dartevelle, Gérald Simonneau, Elie Fadel, Marc Humbert, Arturo Londoño-Vallejo, Saadia Eddahibi
Journal: European Respiratory Journal (2011)

Introduction: Excessive telomere shortening limits both cell proliferation and tissue regenerative capacity by inducing senescence, a permanent growth arrest mediated by the p53 pathway. The purpose of this study was to evaluate the susceptibility of mice with defective telomerase (TERC-/-) to develop hypoxia-associated pulmonary hypertension (PH).  Methods: TERC-/-, p53+/- TERC-/-, and wild-type (WT) mice at 12 weeks of age were randomly divided into two groups, one of which was maintained in room air (normoxia) and the other exposed to normobaric hypoxia (10% oxygen, 90% nitrogen) for 3 weeks. We evaluated pulmonary hemodynamics, vascular remodeling, and the p53-mediated response in the lung.  Results: The TERC-/- mice were efficiently protected against chronic hypoxia-induced PH as compared to WT mice. Interestingly, TERC-/- mice exhibited marked increase in p53 protein levels under normoxia and lacked all signs of tissue remodeling associated to vascular cell proliferation seen in WT mice upon hypoxia treatment. Remarkably, p53 heterozygous TERC-/- mice were fully susceptible to hypoxia-induced PH and developed all cell proliferation-related histopathological manifestations.  Conclusions: Taken together, these results show that a telomere-mediated, p53-dependent, senescence in vascular tissues confers a strong protective effect on chronic hypoxia-induced PH in mice.
Nosocomial hepatitis C virus infection in a renal transplantation center
Authors: A. Zeytinoğlu, S. Erensoy, H. Abacioğlu, A.A. Sayiner, T. Özacar, A. Baßçi, H. Kaplan, P. Simmonds, A. Bilgiç
Journal: Clinical Microbiology and Infection (2002)
Estrogen receptor-beta (ER-beta) expression and non-small cell lung cancer (NSCLC) outcome.
Authors: S. Navaratnam, L. Murphy, G. Qing, A. Demers, G. Skliris, K. Badiani, J. Nowatzki
Journal: Journal of Clinical Oncology (2010)

e21092 Background: Although women have an increased susceptibility to lung cancer, they also have a favorable clinical outcome. This is likely in part due to female specific genetic and hormonal factors. Methods: In the present study, expression of ER-beta, EGFR and HER2 was studied by immuno-histo chemistry using tissue samples from two cohorts: NSCLC diagnosed in 1999 in Manitoba and stage IV NSCLC patients from the NCIC-CTG BR 18 trial. Results: Tissue samples were available in 79 patients (32 females and 47 males) and the majority (75%) had resectable early stage disease in the Manitoba cohort. Forty- eight percent of patients expressed high levels of ER- beta (defined by > = 60, the median H-score) and its expression was comparable in males and females. The three-year overall survival of the group was 53% and females had significantly better survival compared to males. Three separate regression analysis were performed to test each biomarker in gender and stage adjusted model. A higher ER-beta level was associated with better survival in univariate (HR = 0.41, p = 0.009, 95%CI 0.21-0.80) and in multivariate (HR = 0.37, p = 0.008, 95%CI 0.18-0.77) analysis. Expression of EGFR and HER2 did not have significant impact on survival. In the 48 cases of stage IV NSCLC coming from the NCIC-CTG cohort, HER2 expression correlated with better outcome (HR = 0.39, p = 0.013) while higher ER-beta expression correlated with poorer survival (HR = 1.94, p = 0.047). Conclusions: These results suggest a differential impact of ER-beta expression on clinical outcome by stage of the disease, which needs to be explored further and may explain contradictory observations reported in the literature. No significant financial relationships to disclose.
Abstract 6: Formation of Human Heart Muscle Directly from Embryonic and Induced Pluripotent Stem Cells
Authors: James E Hudson, Malte Tiburcy, Wolfram-Hubertus Zimmermann
Journal: Circulation Research (2014)

Tissue engineering enables the simulation of human heart physiology and pathology. It typically requires a mixture of cardiomyocytes, stromal cells, and extracellular matrix for fabrication. Here, we hypothesised that bioengineered heart muscle (BHM) can be formed directly from undifferentiated pluripotent stem cells by triggering processes of embryonic cardiogenesis. Methods and Results: We tested our hypothesis by applying an optimized serum-free cardiac differentiation protocol to undifferentiated pluripotent stem cells in a collagen type 1 hydrogel. During this process BHMs traversed through distinct developmental stages: early mesoderm (3 days), cardiac specification (10 days), and cardiac maturation (up to 50 days). Flow cytometry demonstrated that BHMs are comprised of primarily cardiomyocytes (α-actinin positive cells, 51 ± 5%, n = 6) and stromal cells (CD90 positive cells, 41 ± 5%, n = 6), with low yields of contaminating cells. By 22 days the BHMs exhibited measurable contractile force (207 ± 19 μN) and contained elongated cross-striated cardiomyocytes. We next sought to optimize the force of contraction and also the maturity of the BHM, by investigating the effect of mechanical stimuli and growth factors. Mechanical stimulation was essential for BHM formation. Additionally, we found that 2 developmentally important growth factors, FGF2 and TGFβ1, induced pathological and physiological hypertrophy, respectively. This was characterized by an increase in cell size in both conditions coupled with reduced force and higher ANP expression in FGF2 treated BHM, and a higher force with reduced ANP expression and elevated β-MHC/α-MHC ratio TGFβ1 treated BHM. Using our optimized protocol, 28 day old BHM responded to electrical pacing, preloading, and inotropic stimuli similarly as bona fide myocardium. Conclusion: BHM can be formed directly with undifferentiated pluripotent stem cells by recapitulating normal cardiac development. The serum-free protocol with developmentally defined stimuli provides us with a useful in vitro model to study cardiac biology and potentially provides a method of producing cardiac tissue for regenerative applications.
Nonspecific T-Cell Reactivity in Mice Bearing Autochthonous Tumors or Early-Generation Transplanted Spontaneous Mammary Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Elaine Parthenais, Stephen Haskill
Journal: JNCI Journal of the National Cancer Institute (1979)

The mitogenic response to phytohemagglutinin (PHA) by spleen cells from C3H/HeJ mice bearing either autochthonous tumors or early-generation transplanted spontaneous mammary tumors was depressed in some, but not all, tumor-bearing animals. T-cell hyporesponsiveness in both groups was associated with the larger (more rapidly growing) tumor burdens. The growth patterns of the transplanted tumors and the associated PHA-induced responses were not affected by the initial tumor cell dose or by the number of in vivo passages of the tumor cell lines. Suppressor cell activity was detected in the hyporesponsive spleens of mice bearing transplanted tumors. Depletion of phagocytic macrophages, rayon wool-adherent cells, or theta-positive lymphocytes did not remove the suppressor cell activity. The mitogenic response of some but not all hyporesponsive spleens from autochthonous tumor bearers was restored after removal of phagocytic macrophages. The results demonstrated the heterogeneity of the factor(s) influencing non-specific T-cell reactivity in animals bearing spontaneous mammary tumors. Furthermore, our data suggest that nonspecific immunosuppression does not precede spontaneous tumor appearance but is probably a late result of rapid, extensive tumor growth.
Assessing bronchodilator response (BDR) in preschool children using spirometry
Authors: Luciano Enrique Busi, Peter Sly, Ricardo Daniel Tourres
Journal: European Respiratory Journal (2014)

Measuring bronchodilator response (BDR) can be a useful aid in the diagnosis and management of asthma in children; however information about the within-occasion (repeatability) and between-occasion (reproducibility) variability is necessary to interpret the results. In the present study we sought to determine the BDR repeatability and reproducibility in healthy preschoolers and in those with asthma. We recruited 519 healthy children from 7 randomly selected kindergartens and 201 asthmatics from the pulmonology clinic in Trelew, Argentina and performed spirometry according to ATS standards before and after salbutamol 400mcg or placebo (random allocation). The entire procedure was repeated within 8 weeks. The intra-occasion and inter-occasion coefficients of repeatability were calculated. All analyses were performed in SPSS 20.0. There were no significant differences between groups with respect to demographic and anthropometric data and exposition to environmental tobacco smoke. Asthmatic children showed greater BDR than healthy children in FEV 0.75  (13.2% v 4.6%), FEV 1  (10.3% v 4.3%) and FEF 25-75  (33% v 10.2%) (all p 0.75 , 16.9% for FEV 1  and 48.2% for FEF 25-75 . The area under the ROC curve for BDR-FEV 0.75  was 0.698. We conclude that BDR assessed by spirometry is a reliable test to discriminate asthma in preschool children, taking into account the high variability of this test.
Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.
Authors: H M Kantarjian, R S Walters, M J Keating, T L Smith, S O'Brien, E H Estey, Y O Huh, J Spinolo, K Dicke, B Barlogie
Journal: Journal of Clinical Oncology (1990)

One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.
Abstract 3742: Strain Echocardiography Suggests Plakophilin-2 Mutation is Associated With a Milder Functional Phenotype in Arrhythmogenic Right Ventricular Dysplasia
Authors: Kalpana R Prakasa, Darshan Dalal, Hugh Calkins, Daniel Judge, Theodore Abraham
Journal: Circulation (2006)

Background: Arrhythmogenic Right Ventricular Dysplasia (ARVD) is an inherited cardiomyop-athy characterized by fibro-fatty myocardial replacement in the right ventricle (RV) and presents with heart...
Air pollution and asthma hospitalizations in children
Authors: Amne Iskandar, Zorana J. Andersen, Klaus Bønnelykke, Klaus Andersen, Hans Bisgaard
Journal: European Respiratory Journal (2011)

Introduction:  Short-term exposure to air pollution can trigger asthma hospitalizations in children, but it is not known which components of air pollution are most important. There is no available evidence on the particular effect of ultrafine particles (UFPs) on admissions for asthma.   Aim:  To study whether short-term exposure to increased air pollution levels is associated with hospitalizations for asthma in children.   Hypotheses:  1) The association between asthma admissions and air pollution is stronger with UFPs than PM10, PM2.5, NOx. 2) Infants are more susceptible to the effects of exposure air pollution than older children.   Method:  Daily count of hospital admissions for asthma in children aged 0-18 years were extracted from Danish National Patient Registry between 2001 and 2008, from hospitals located within a 15 km radius from the central fixed urban air pollution monitor in Copenhagen. Time-stratified case-crossover design was applied and data analyzed using conditional logistic regression to estimate the effect of air pollution on asthma admissions.   Results:  We detected a significant association between asthma hospitalizations in children aged 0-18 years and NOx (Odds ratio: 1.11; 95% CI: 1.05-1.17), PM10 (1.07; 1.03-1.12), and PM2.5 (1.09; 1.04-1.13), and none with UFPs. Infants had higher risk of being hospitalized for asthma than older children, for all pollutants, but were not statistically significantly more susceptible.   Conclusion:  We find a significant association between air pollution and asthma hospitalization in children, with infants possibly most susceptible. Gases (NOx and NO2) originating from traffic showed strongest associations, while UFPs showed no effect.
Assessment of ultraviolet-radiation-induced DNA damage within melanocytes in skin of different constitutive pigmentation
Authors: S. Del Bino, J. Sok, F. Bernerd
Journal: British Journal of Dermatology (2013)

Journal Article Assessment of ultraviolet‐radiation‐induced DNA damage within melanocytes in skin of different constitutive pigmentation Get access S. Del Bino, S. Del Bino L'Oréal Research & Innovation, Centre Charles Zviak, 90 Rue du Général Roguet, 92583 Clichy CEDEX, France Sandra Del Bino. E‐mail: sdelbino@rd.loreal.com Search for other works by this author on: Oxford Academic Google Scholar J. Sok, J. Sok L'Oréal Research & Innovation, Centre Charles Zviak, 90 Rue du Général Roguet, 92583 Clichy CEDEX, France Search for other works by this author on: Oxford Academic Google Scholar F. Bernerd F. Bernerd L'Oréal Research & Innovation, Centre Charles Zviak, 90 Rue du Général Roguet, 92583 Clichy CEDEX, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 5, 1 May 2013, Pages 1120–1123, https://doi.org/10.1111/bjd.12201 Published: 01 May 2013 Article history Accepted: 19 December 2012 Published: 01 May 2013