tbuckley/cabot-search huggingface dataset:
Early mobilization in a single ICU from a public hospital in São Paulo – Brazil
Authors: Ruy Pires-Neto, Nathalia Lima, Gregorio Cardim, Linda Denehy
Journal: European Respiratory Journal (2014)

INTRODUCTION: Mobilization therapy in mechanically ventilated critical care patients is feasible, safe and is associated with better functional improvement at ICU and hospital discharge. Physiotherapy (PT) treatment in ICU is not standardized worldwide and currently, there is a paucity of data from centers outside USA and Australia. AIM: Characterize mobilization therapy in a 6-bed medical ICU from a public hospital in Sao Paulo-Brazil. METHODS: Using a retrospective design we collected ICU and physiotherapy data from 120 mechanically ventilated patients: age (mean±SD) 49±17 years (SAPS3 = 46±19) using a specifically designed case report sheet introduced earlier for physiotherapists. RESULTS: Median (interquartile range) time of mechanical ventilation and ICU length of stay were 3 [4] and 8 [10] days respectively. ICU and one year mortality were 30% and 31%. Mobilization therapy was performed in 63% of the total of 1428 PT sessions. Frequency of activities were: Passive exercises (33%), in bed active exercises (24%), sit at the edge of bed (18%), standing-up (13%); ambulation away from bed (8%). Walking away from bed was associated with a lower ICU mortality (odds ratio (OR) =0.09; 95% confidence interval (CI) 0.02–0.43; p=0.0002), ICU discharge location (home) (OR=3.33, 95%CI = 1.14 - 9.6; p=0.02) and lower one year mortality (OR=0.33, 95%CI = 0.10 – 1.04; p=0.045). CONCLUSION: In our Brazilian ICU, mobilization therapy in mechanically ventilated critical care patients was safe and feasible, however only a small percentage were stood or mobilized away from the bed. For these patients this was a promising trend of improved outcome.
A randomized double-blind trial of carboplatin plus paclitaxel (CP) with daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo (PLA) in patients (pts) with previously untreated advanced non-small cell lung cancer (NSCLC): NCIC Clinical Trials Group study BR29.
Authors: Scott Andrew Laurie, Benjamin J. Solomon, Lesley Seymour, Peter Michael Ellis, Glenwood D. Goss, Frances A. Shepherd, Michael J. Boyer, Andrew Michael Arnold, Philip Clingan, Francis Laberge, Dave Fenton, Vera Hirsh, Mauro Zukin, Martin R. Stockler, Christopher W. Lee, Eric Xueyu Chen, Alexander Montenegro, Keyue Ding, Penelope Ann Bradbury
Journal: Journal of Clinical Oncology (2012)

7511 Background: In NCIC CTG study BR24, CED 30 mg/d + CP increased objective response rate (RR) and progression-free survival (PFS), but there were concerns regarding toxicity in some pts. BR29 tested a lower dose of CED 20 mg/d limiting accrual to pts without significant weight loss/hypoalbuminemia. Methods: Consenting, eligible adult pts with advanced incurable NSCLC of any histology were randomized to receive CED 20 mg/d or PLA with up to 6 cycles of C (AUC = 6) P (200 mg/m 2 ); non-progressing pts continued CED/PLA after CP until progression, unacceptable toxicity or pt request. The primary endpoint was overall survival (OS). An interim analysis (IA) for PFS was planned after 170 events in the first 260 pts; the study would continue if the hazard ratio (HR) for PFS was &lt; 0.7. Accrual continued until the required number of events was reached then held pending IA. Results: The trial was halted when the IA (n=260) revealed a HR for PFS of 0.89 (95% CI 0.66-1.20). A final analysis including all 306 randomized pts (median age 62, male 55%, PS 0 26%, PS 1 74%, adenocarcinoma 64%, squamous 13%, other histology 23%. RR was significantly higher with CED (52% vs 34 %, p = 0.001). For CED/PLA, respectively, median OS and PFS were 12.2/12.1 [HR: 0.95 (0.69-1.30, p=0.74)] and 5.5/5.5 months [HR: 0.91 (0.71-1.18, p=0.5)]. Grade &gt;3 hypertension (15% vs 3%, p=0.0002), anorexia (7% vs 1%, p=0.02) and diarrhea (16% vs 1%, p&lt;0.0001) were all significantly increased with CED; there were 2 deaths possibly-related to CED [1 each hemorrhage, leukoencephalopathy (prior radiation)]. Conclusions: Adding a lower dose of CED to CP increased RR and toxicity, but not PFS or OS.
Abstract 13789: Potential Role of PDGF-Activated JAK/STAT Pathway in CHF-Related Atrial-Selective Fibrotic Remodeling
Authors: Yu Chen, Sirirat Surinkaew, Chia-Tung Wu, XiaoYan Qi, Hai Huang, Doromir Dobrev, Stanley Nattel
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and its mechanisms are poorly understood. Platelet derived growth factor (PDGF) contributes to myofibroblast differentiati...
Interleukin-10 Inhibits Spontaneous Colony-Forming Unit–Granulocyte-Macrophage Growth From Human Peripheral Blood Mononuclear Cells by Suppression of Endogenous Granulocyte-Macrophage Colony-Stimulating Factor Release
Authors: Leopold Oehler, Manuela Foedinger, Markus Koeller, Marietta Kollars, Elisabeth Reiter, Barbara Bohle, Sonja Skoupy, Gerhard Fritsch, Klaus Lechner, Klaus Geissler
Journal: Blood (1997)
Observational study to evaluate the possible association between serum levels of C-reactive protein and response to the treatment of chemotherapy-induced anemia in solid tumors (Pronost Study).
Authors: G. Esquerdo, J. Cervera, E. Barrajon, A. Juarez, C. Llorca, N. Diaz, A. Lopez, R. Peiro
Journal: Journal of Clinical Oncology (2010)

e19546 Background: The EORTC (European Organisation for Research and Treatment of Cancer) recommends in cancer patients receiving chemotherapy and/or radiotherapy, that treatment with erythropoietic proteins should be initiated at a hemoglobin (Hb) level of 9-11 g/dL based on anemia-related symptoms. Likewise, EORTC recommends further studies on prognostic factors that could anticipate response to treatment. Between possible predictors of response, C-reactive protein (CRP) is mentioned. Primary study objective was to determine the association between CRP level and response to treatment of chemotherapy-induced anemia in cancer patients. Methods: This is a prospective observational study of patients ≥ 18 years with solid tumors who developed anemia induced by chemotherapy. Response to anemia therapy and CRP levels at baseline, and weeks 6, 9, 12 and 16 of treatment were registered. Tests for normality, bivariate tests and appropriate multivariate analysis, were performed. Results: 61 patients were included. Median age was 67 years, 64% male. 48% had mild anemia (10 g/dL ≤ Hb < 11 g/dL) and 35% had moderate anemia (8 g/dL ≤ Hb < 10 g/dL). CRP level was > 3 mg/L in 80% of patients. At weeks 6, 9, 12 and 16 after treatment initiation, response to anemia-therapy defined as increase of 1g/dL of Hb was observed in 36% (17/47), 29% (10/34), 23% (6/26) and 18% (3/17) of patients. CRP level registered at same time-endpoints was over 3 mg/L in 59% (10/17), 75% (9/12), 82% (9/11) and 87% (7/8) of patients. After anemia- therapy in each chemotherapy cycle, a significant difference was observed (p = 0.013) between registered Hb data associated with CRP ≤ 3 mg/L or > 3 mg/L. Hb data associated with CRP ≤ 3 mg/L value showed more often higher level than 11 g/dL than data associated with CRP > 3 mg/L value (75% (15/20) vs. 43% (34/79)). However, response to anemia-therapy defined as increase of 1 g/dL of Hb showed no significant differences in relation to CRP level. Conclusions: No association between CRP levels and response to treatment of chemotherapy-induced anemia and/or radiotherapy in cancer patients is demonstrated in this study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Breast Tumor Cell Lines From Pleural Effusions2
Authors: R. Cailleau, R. Young, M. Olivé, W. J. Reeves
Journal: JNCI Journal of the National Cancer Institute (1974)

Summary During 1973, 4 new epithelial tumor cell lines were isolated from pleural effusions from breast cancer patients. We describe 3 of these lines: MDA-MB-134, with a mean chromosome number of 43; MDA-MB-175, with a mean chromosome number of 49; and MDA-MB-231, with a mean chromosome number between 65 and 69. We isolated the same cell type from 4 of 10 effusions from MDA-MB-134 and from 6 of 8 effusions from MDA-MB-175. We found that pleural effusions as a source of breast tumor cells to be cultured and studied in vitro have the following advantages: 1) large amounts of material and the possibility of obtaining sequential samples from the same patient; 2) high viability of tumor cells; 3) scarcity or absence of fibroblasts; and 4) the possibility of separating the tumor cells from other “contaminating” cell types by differences in their speed or degree of attachment to the flask. All lines from different patients differed, as seen grossly and microscopically. All lines from sequential pleural effusions from the same patient were apparently alike. No viruses or mycoplasmas were detected in any line.
NADPH Oxidase 1 Activity and ROS Generation Are Regulated by Grb2/Cbl-Mediated Proteasomal Degradation of NoxO1 in Colon Cancer Cells
Authors: Jung Hee Joo, Hyunjin Oh, Myungjin Kim, Eun Jung An, Rae-Kwon Kim, So-Young Lee, Dong Hoon Kang, Sang Won Kang, Cheol Keun Park, Hoguen Kim, Su-Jae Lee, Daekee Lee, Jae Hong Seol, Yun Soo Bae
Journal: Cancer Research (2016)

Abstract The generation of reactive oxygen species (ROS) is required for proper cell signaling, but must be tightly regulated to minimize deleterious oxidizing effects. Activation of the NADPH oxidases (Nox) triggers ROS production and, thus, regulatory mechanisms exist to properly control Nox activity. In this study, we report a novel mechanism in which Nox1 activity is regulated through the proteasomal degradation of Nox organizer 1 (NoxO1). We found that through the interaction between NoxO1 and growth receptor–bound protein 2 (Grb2), the Casitas B–lineage lymphoma (Cbl) E3 ligase was recruited, leading to decreased NoxO1 stability and a subsequent reduction in ROS generation upon epidermal growth factor (EGF) stimulation. Additionally, we show that EGF-mediated phosphorylation of NoxO1 induced its release from Grb2 and facilitated its association with Nox activator 1 (NoxA1) to stimulate ROS production. Consistently, overexpression of Grb2 resulted in decreased Nox1 activity, whereas knockdown of Grb2 led to increased Nox1 activity in response to EGF. CRISPR/Cas9-mediated NoxO1 knockout in human colon cancer cells abrogated anchorage-independent growth on soft agar and tumor-forming ability in athymic nude mice. Moreover, the expression and stability of NoxO1 were significantly increased in human colon cancer tissues compared with normal colon. Taken together, these results support a model whereby Nox1 activity and ROS generation are regulated by Grb2/Cbl-mediated proteolysis of NoxO1 in response to EGF, providing new insight into the processes by which excessive ROS production may promote oncogenic signaling to drive colorectal tumorigenesis. Cancer Res; 76(4); 855–65. ©2016 AACR.
Imatinib (I) compared to I + cytarabine (Ara-C) for the frontline treatment of chronic phase (CP) chronic myeloid leukemia (CML)
Authors: R. Hurtado-Monroy, P. Vargas, A. Martinez, J. Cruz, V. Enriquez, O. Gutierrez, M. Candelaria, A. Aguayo, E. Cervera
Journal: Journal of Clinical Oncology (2007)

7048 Background: Imatinib is now worldwide accepted as the standard frontline therapy of CP CML. Regardless of their impressive clinical results and low toxicity profile, a small proportion of CP CML patients could develop primary or secondary resistance. Main objective of present trial was to increase the hematological (HR) and major cytogenetical responses (MCR) with the addition of Ara-C to standard doses of I as a frontline therapy of CP CML. Methods: on September, 2003 we began this multicentric, phase III randomized, clinical trial, comparing I (400 mg/day) vs I (400 mg/day) plus subcutaneous Ara-C (10 mg/m2/day, for 10 days/monthly cycles), doses could be adjusted due to tolerance and toxicity. Inclusion criteria: newly diagnosed CP CML, not elective to allogeneic transplant. Primary endpoint was the acquisition and time to acquisition of HR, MCR by conventional criteria. Secondary endpoints were main toxicities, dead to progression and overall survival. Results: 61 patients were randomized with median follow-up of 850 days (range 85–1151) for entire group. Table 1 shows results for both treatment arms. Table 1 Both treatment arms were well tolerated and the toxicity profile was low and manageable. Statistical analysis (chi- square, paired T-student, Log-rank survival analysis) did not show significant differences among treatment arms. Conclusions: The addition of cytarabine to conventional I doses on frontline therapy CP CML does not produce significant benefit on HR or MHR. Larger I doses or other therapeutic options should be explored. [Table: see text] [Table: see text]
Comparative Carcinogenesis by Hydroxylated Nitrosopropylamines in Syrian Hamsters&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: W Lijinsky, G L Knutsen, R M Kovatch
Journal: JNCI Journal of the National Cancer Institute (1985)

The relationship between the chemical structure of nitrosamines and their carcinogenic activity has been examined in Syrian golden hamsters in parallel with similar studies in rats to aid in explaining the sharp interspecies differences in response to these compounds. The relationship between the beta-oxidized N-propyl-nitrosamine structure and the induction of tumors of the pancreatic duct in Syrian golden hamsters was investigated by administration of a number of asymmetric acyclic nitrosamines containing that structure to female hamsters for 29-50 weeks. N-Nitroso-2-oxopropyl-2-hydroxyethylamine (OPE), N-nitroso-2-hydroxypropyl-2-hydroxyethylamine (NIEA), and N-nitroso-2,3-dihydroxypropyl-2-oxopropylamine (DHPOP) induced pancreatic tumors. OPE also induced a high incidence of liver neoplasms, and a number of animals given NIEA and N-nitrosoallyl-2-oxopropylamine (NAOP) also had liver neoplasms. N-Nitroso-2,3-dihydroxypropyl-2-hydroxyethylamine was very weakly carcinogenic. N-Nitroso-2,3-dihydroxypropyl-2-hydroxypropylamine and DHPOP induced a high incidence of neoplasms of the forestomach (mainly papillomas). N-Nitrosoallyl-2,3-dihydroxypropylamine, N-nitrosoallyl-2-hydroxypropylamine, and NAOP induced primarily neoplasms of the nasal mucosa but no neoplasms of the pancreatic ducts in hamsters.
Prediction of fluoropyrimidine toxicities by screening DPYD genetic variants.
Authors: M. Del Re, F. Loupakis, A. Michelucci, A. Di Paolo, A. Falcone, P. Simi, G. Bocci, M. Cantore, R. Bordonaro, A. Di Leo, C. Barbara, F. Cappuzzo, F. G. De Braud, R. Danesi
Journal: Journal of Clinical Oncology (2011)

10524 Background: Fluoropyrimidines are associated with gastrointestinal and hematologic adverse reactions which may be severe and, in sporadic cases, lethal. 5‐FU undergoes multi-step catabolism, the deficiency of which may be a reason for toxicity. The rate-limiting enzyme of drug detoxyfication is dihydropyrimidine dehydrogenase (DPD), which displays a substantial variability of activity in the population. Several genetic variants have been identified thus far within DPD, the majority of them having no functional consequences on enzyme activity. However, a systematic analysis of their occurrence in patients with toxicity is lacking. The aim of this study is the identification of deficient variants of DPD associated with severe toxicity to screen subjects before or after drug administration and to develop a clinical algorithm for prevention of fluoropyrimidine-related toxicity. Methods: This exploratory pharmacogenetic study enrolled 200 patients with breast and colorectal cancers treated with standard fluoropyrimidine-based regimens and suffering from grade ≥3 gastrointestinal and hematological toxicities. Blood samples for DNA analysis were collected and used to screen patients for DPD single nucleotide polymorphisms (SNPs) by PCR and automatic sequencing of the entire coding region of the DPD gene. Results: Seven SNPs were strongly associated to 5-FU toxicity, including 496A>G, 1601G>A, 1627A>G, 1896T>C, IVS14+1G>A, 2194G>A, and 2846T>C. The frequency of genotypes is reported in the table. A total of 87% patients with toxicity were found to have at least one genetic variant associated with enzyme deficiency. Conclusions: This study demonstrate that screening of DPD variants is clinically feasible and may help the clinician in preventing severe fluoropyrimidine-associated toxicity and adjust the drug dose based on the DPD polymorphism detected. Funded in part by Italian Association for Cancer Research (AIRC, Italy). Supported in part by AIRC, Milan, Italy. RD is national representative of EPMA, Brussels, Belgium. DPD polymorphisms in patients with fluoropyrimidine-associated toxicity. Heterozygous Homozygous variant 496A>G AG 20.2% GG 0.8% 1601G>A GA 8.5% AA 0% 1627A>G AG 28% GG 3.35% 1896T>C TC 2.5% CC 0% IVS14+1G>A GA 3.4% AA 0.8% 2194G>A GA 15.25% AA 3.4% 2846A>T AT 0.84% TT 0%
A novel therapeutic strategy for ER-negative human breast cancers, targeting AP-1 activity
Authors: K. Sakaguchi, H. Nakajima, I. Fujiwara, N. Mizuta, J. Magae
Journal: Journal of Clinical Oncology (2007)

14129 Background: While agents targeting estrogen receptors are the most effective in adjuvant therapy for human breast cancers expressing estrogen receptor(ER), breast cancers lacking ER are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Although a transcription factor, AP-1, is known to be related to tumor malignancy including metastasis, invasion and drug-resistance, it remains to be elucidated how AP-1 plays in development and expression of malignant characters of human breast cancers. Methods and Results: Here, we used MX-1, a human breast cancer cell line lacking ER and several ER positive cell lines, to clarify the roles of AP-1 and the therapeutic efficacy of ascochlorin, a newly developed prenylphenol antibiotic on ER-negative breast cancer. We found that MX-1 exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos and Fra-1 when compared with conventional ER-positive human breast cancer cell lines. Consistent with this study in vitro, histological study on human breast cancer tissues suggests that ER-negative cancers express high Fra-1 protein, and that paclitaxel- sensitive cancers express low Fra-1 protein. The ascochlorin, which inhibits AP-1 through the Erk signaling pathway, suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Moreover, administration of ascochlorin elongated life span of mice intraperitoneally implanted with murine mammary carcinoma cells. Conclusions: Our results suggest that AP-1 is an effective clinical target molecule for the treatment of ER-negative human breast cancer, and that ascochlorin is promising therapeutic agent for these refractory breast cancers. No significant financial relationships to disclose.
Oxygen Uptake Efficiency Slope and Breathing Reserve, Not Anaerobic Threshold, Discriminate Between Patients With Cardiovascular Disease Over Chronic Obstructive Pulmonary Disease
Authors: Anthony Barron, Darrel P. Francis, Jamil Mayet, Ralf Ewert, Anne Obst, Mark Mason, Sarah Elkin, Alun D. Hughes, Roland Wensel
Journal: JACC Heart Failure (2016)

The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease.CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared.A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after ∼10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC).Peak VO2 was similar between the 2 principal groups (COPD 17.1 ± 4.6 ml/min/kg; HFrEF 16.4 ± 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide.Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083).
Effects of cancer cachexia on the alveolar morphology of the mouse lung
Authors: Tilman Graulich, Suman Kumar Das, Gabriela Krasteva, Lars Wessels, Gerald Höfler, Christian Mühlfeld
Journal: European Respiratory Journal (2011)

Cancer cachexia is a complex syndrome with a significant reduction of body weight and a variety of systemic symptoms including respiratory dysfunction. In rodents, calorie restriction causes loss of alveolar surface area, the so-called nutritional emphysema. We hypothesized that alveolar alterations and loss of gas exchange surface area are present in the cancer-cachectic mouse.

C57Bl6 mice were randomly assigned to subcutaneous injection of Lewis lung carcinoma cells (tumor group, TG) or saline injection (control group, CG). Mice were sacrificed 21 days later and lungs were processed for light and electron microscopic design-based stereology (n=6 in each group) or for quantitative RT-PCR (n=5 each).

Body weight was reduced in TG vs. CG (TG: 17.4±0.4 g; CG: 22.1±1.0; p<0.01). Lung volume did not differ between TG (518.3±28.2 mm3) and CG (468.3±50.5 mm3). The alveolar surface area was similar in both groups (TG: 602.3±77.7 cm2; CG: 496.2±58.2 cm2). Although the total volume of lamellar bodies did not differ between the groups the volume of lamellar bodies per unit alveolar surface area was significantly reduced in TG (TG: 26.53±3.74 mm3/m2; CG: 40.25±13.05 mm3/m2; p<0.05). Quantitative expression of surfactant proteins A, B, C and D was not different between CG and TG as shown by RT-PCR.

In summary, despite a reduced ratio between the volume of the intracellular surfactant pool and the alveolar surface area in TG, there was no evidence for a significant disturbance of the gas exchange region due to cancer cachexia. In particular, weight loss was not associated with loss of alveolar surface area.