tbuckley/cabot-search huggingface dataset:
A phase II randomized trial of docetaxel weekly or every 3 weeks in elderly and/or poor performance status (PS) patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: R. Lilenbaum, M. Rubin, J. Samuel, L. Boros, T. Chidiac, L. Seigel, P. Graham
Journal: Journal of Clinical Oncology (2004)

7057 Background: Docetaxel has been used in elderly and PS 2 pts with advanced NSCLC with acceptable toxicity. However, myelosuppression can be severe on the every 3-week schedule. Docetaxel weekly appears to have similar efficacy and less hematologic toxicity. Practice varies widely and no comparative study has yet been completed in the US. Methods: Randomized phase II trial of docetaxel 75mg/m2 d1 q.3 wks (arm A) versus docetaxel 30 mg/m2 d1,8,15 q. 28 days (arm B) in chemo-naive, elderly (=70) and/or PS 2 patients with advanced NSCLC. Overall toxicity is the primary endpoint; response, survival, and quality of life are also evaluated. Results: 96 patients have been enrolled; 54 elderly and 42 PS 2; 30 pts are both elderly and PS 2; 22% are =80; M/F: 54/42; 85% stage IV. 65 pts are evaluable for toxicity and 55 for response and survival. Gr 3–4 ANC was 30% in arm A and 3% in arm B. One episode of febrile neutropenia was observed in arm A. Gr 3–4 non-heme toxicities (arm A vs. B): fatigue (12% vs 6%), N/V ( 3% vs. 12.5%), and diarrhea (6% vs. 0%). Pts = 80 had more toxicity in arm A. Four patients in each arm had documented responses (15%). Preliminary median TTP: 25 and 50.5 days, respectively. MST in arm A is 41 days and 91 days in arm B. Conclusions: Both schedules have acceptable toxicity in previously untreated elderly and/or PS 2 patients. Hematologic toxicity is lower in the weekly schedule. Octogenarians tolerate the weekly schedule better. Preliminary efficacy results appear comparable between the arms. Weekly docetaxel is an attractive option for advanced NSCLC patients treated with single-agent therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline Bristol-Myers Oncology Aventis
水肿-腹泻-低白蛋白血症
Authors: 曹玮, 舒慧君, 吴东, 朱峰
Journal: BMJ (2011)

患者，女，47岁，因“双下肢水肿7年，间断腹泻2年余”于2010年4月18日入住本院消化科。患者自2003年起出现双足踝处可凹性水肿，逐渐累及双侧小腿，伴颜面及眼睑轻度水肿，休息后减轻；体力较前下降，无发热、气短、血压升高、腹胀、纳差、尿色及尿量改变，未就诊。
Re: Endothelin antagonism and internal mammary artery endothelial function [Cardiovascular Research 2001;52:160–162]
Authors: S Verma
Journal: Cardiovascular Research (2001)

To the editor,

We thank Glodny and Barton for their interpretation of our paper and the accompanying editorial. A few important issues were raised which we would like to address. We agree with the authors regarding the resilience of the internal mammary artery (IMA) and its intrinsic resistance against atherosclerosis. This has been ascribed to greater endothelium-dependent nitric oxide (NO) production/availability of this conduit. Atherosclerotic vascular disease does occur in the IMA and, as you correctly point out, may be observed in the setting of cardiac transplant arteriopathy. Our data suggest that endothelin antagonists may improve endothelial function in the IMA; this effect may serve to retard atherosclerosis and/or vasospasm which, in some cases, may be an important perioperative problem. To our knowledge, this was the first report of improved endothelial function in response to endothelin antagonism in human segments …
Staging and the evaluation of prognosis for patients with small-cell carcinoma of the lung.
Authors: D E Bergsagel, R Feld
Journal: Journal of Clinical Oncology (1986)

AbstractSeptember 01, 1986 Share on Staging and the evaluation of prognosis for patients with small-cell carcinoma of the lung.Authors: D E Bergsagel and R FeldAuthors Info & AffiliationsPublication: Journal of Clinical OncologyVolume 4, Number 9https://doi.org/10.1200/JCO.1986.4.9.1291 Get Access
Sequential vinorelbine (V) and docetaxel (D) in advanced non-small cell lung cancer (NSCLC) patients age &gt; 70, or with performance status (PS) 2: A SWOG phase II trial (S0027)
Authors: P. J. Hesketh, K. Chansky, D. H. Lau, J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2004)

7056 Background: The value of V in elderly patients (pts) with advanced NSCLC was demonstrated in the ELVIS and MILES trials. (JNCI 1999,91:66; JNCI 2003,95:362) More limited evidence suggests value for V and D in PS 2 NSCLC pts. Toxicity concerns have hindered enrollment of PS 2 and elderly pts into trials of combination chemotherapy. No prospective trial targeting these pts has compared a single agent to a platinum-based doublet. Given the efficacy and tolerability of sequential chemotherapy in several settings, we conducted a phase II trial of sequential V and D. Methods: Eligibility: stage IIIB (pleural effusion)/stage IV NSCLC, age ≥ 70 and/or a PS of 2. Treatment: V 25 mg/m2 days 1,8 every 21 days for 3 cycles immediately followed by D 35 mg/m2 days 1,8,15 every 28 days for 3 cycles. Strata: age ≥ 70, PS 0,1; PS 2, any age. Comorbidities (CM) were noted at entry. Results: Patients: 125 from 42 institutions; 119 eligible; 118 assessable for toxicity; 99 for response. Stage IV: 83%. Response (RR), progression free survival (PFS), median survival (MST) and toxicity - see table. Treatment was generally well tolerated. There were 2 toxic deaths per stratum. A trend toward worse survival was noted with presence of CM. In ≥ 70, PS 0,1 group, survival by CM count(mo): 0 = 13;1 = 9; ≥ 2 = 6.Conclusions: Sequential V and D is well tolerated. Efficacy data confirm that good PS elderly pts do better than PS 2 pts. Survival of elderly good PS pts compares favorably to phase III trials with younger pts employing platinum regimens. Good PS elderly pts with no CM had encouraging survival (median = 13 mo; 1-yr 56%). Survival in the PS 2 group is comparable, with less toxicity, to the experience of PS 2 pts in ECOG 1594 (Cancer 2001,92:2639) a trial of 4 platinum doublets. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Aventis; GlaxoSmithKline
Prognostic role of plasma chromogranin A levels in prostate cancer patients with hormone refractory disease
Authors: A. Mosca, A. Berruti, M. Tucci, F. Vana, R. Bitossi, C. Cracco, M. Torta, M. Poggio, R. M. Scarpa, L. Dogliotti
Journal: Journal of Clinical Oncology (2004)

9563
Abstract 371: Mitochondrial Antiviral Signaling (MAVS) Protects Cardiomyocytes Under Oxidative Stress by Interfering with Bax-Mediated Cell Death
Authors: Toshitaka Yajima, Stanley Park, Hanbing Zhou, Michinari Nakamura, Mitsuyo Machida, Arthur Uyesugi, Vineel Pokala, Andrea Domenighetti
Journal: Circulation Research (2012)

MAVS is a mitochondrial outer membrane protein that activates innate antiviral signaling by recognizing cytosolic viral RNAs and DNAs. While the discovery of MAVS is the first molecular evidence that links mitochondria to innate immune mechanisms, it is still unclear whether MAVS affects mitochondrial cell death as a member of caspase activation and recruitment domain (CARD)-containing proteins. We found that MAVS interacts with Bax through CARD by Yeast two-hybrid and a series of immunoprecipitation (IP) assay, which led us to hypothesize that MAVS functions not only in the innate antiviral mechanisms but also in the mitochondrial cell death pathway. Methods: 1) We examined molecular interaction between MAVS and Bax under oxidative stress by IP using isolated myocytes with H2O2 stimulation and the heart post ischemia-reperfusion (I/R). 2) We evaluated the effect of MAVS on mitochondrial membrane potential and apoptosis under H2O2 stimulation using isolated myocytes with adenoviral MAVS knockdown. 3) We investigated the impact of MAVS on %myocardial infarction (%MI) post I/R using cardiac-specific MAVS knockout (cKO) and transgenic (cTg) mice which we have originally generated. 4) We examined the effect of MAVS on recombinant Bax (rBax)-mediated cytochrome c release using isolated mitochondria from wild type (WT) and MAVS KO mice. Results: 1) The amount of Bax pulled down with MAVS was significantly increased in isolated myocytes with 0.2 mM H2O2 compared to those without stimulation (mean±SD; 1.808±0.14, n=5, p&lt;0.001) and in the heart post I/R compared to sham (2.2±1.19, n=3, p=0.0081). 2) Myocytes with MAVS knockdown showed clear abnormalities in mitochondrial membrane potential and caspace-3 cleavage with 0.2 mM H2O2 compared to control cardiomyocytes. 3) MAVS cKO had significantly larger %MI than WT (81.9 ± 5.8% vs. 42.6 ± 13.6%, n=8, p=0.0008). In contrast, MAVS cTg had significantly smaller %MI that WT (30.0 ± 4.8% vs. 49.2 ± 4.8%, n=10, p=0.0113). 4) Mitochondria from MAVS KO exhibited cytochrome c release after incubation with 2.5 μ g of rBax while those from WT required 10 μ g of rBax. Conclusion: These results demonstrate that MAVS protects cardiomyocyte under oxidative stress by interfering with Bax-mediated cytochrome c release from mitochondria.
A Rationale for the Treatment of Metastatic Neuroblastoma12
Authors: Lawrence Helson, Christiane Helson, Robert F. Peterson, Susanta K. Das
Journal: JNCI Journal of the National Cancer Institute (1976)

In developing a chemotherapeutic program for children with disseminated neuroblastoma, we established three human neuroblastoma lines in cell culture to study the effects of dibutyryl cyclic AMP, papaverine, 5-trifluoromethyl-2′-deoxyuridine, and cyclophosphamide on cell growth, biochemical behavior, and morphology. Based upon our studies, a clinical treatment program was designed. We have treated 15 patients with disseminated neuroblastoma and have established the optimum dose range and sequence of these drugs. Early results were promising; plans for continuation of clinical and experimental studies were discussed.
Risk Factors and Incidence of Macular Edema after Cataract Surgery
Authors: Colin J. Chu, Robert L. Johnston, Charlotte Buscombe, Ahmed B. Sallam, Queresh Mohamed, Yit C. Yang
Journal: Ophthalmology (2015)

To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors.Retrospective database study of electronic medical records (EMRs).A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites.Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded.Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery.Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57-4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45-9.07), uveitis (RR, 2.88; 95% CI, 1.50-5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56-5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60-5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36-2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12-7.58) and rose proportionately with increasing severity of DR.Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs.
A proposal for an abbreviated onco-geriatric assessment in daily practice
Authors: V. Girre
Journal: Journal of Clinical Oncology (2006)

18565 Background: In order to describe the elderly population in Institut Curie and to determine if a brief multidimensional assessment may influence our decision to treat elderly patients with cancers we decided to realize a short assessment for each patient, 70 years and older. In a prospective study we evaluated such diverse areas as functional status, comorbidity, nutrition, polypharmacy and the presence or absence of geriatric syndromes. Methods: We studied 105 elderly cancer patients, median age 80 years with solid tumors. In addition to PS, their physical function was assessed by the activity of daily living (ADL) and instrumental activity of daily living (IADL) scales. During consultation comorbidities, Geriatric depression scale (GDS), the number of falls in the past year, concomitant medications, weight measurements and social environment were collected in a questionnaire. Cognitive functions were assesed if troubles were suspected. Blood tests were performed secondary. Results: To date 105 patients were evaluated : 10 % live in institution, 16% have no social environment, 35 % have a loss of autonomy in ADL and 7% were dependant. In the IADL: 30% presented a loss of autonomy and 24% were dependant. The median Body Mass Index (BMI) was 23.8 kg/m 2 , but the BMI was in 14% &lt; 19kg/m 2 ; 20% of the patients fall more than 2 times in the year and 53% have a suspicion of depression in the GDS in 4 items. 74% take more than 3 drugs per day. The median of comorbidities was 1.3. According to the results the decision of treatment was modified in 28% of patients. Conclusion: This questionnaire is not a replacement for the entire Comprehensive Geriatric assessment but is a reasonable prescreening instrument that may be performed in less than 15 minutes and be helpful to the clinician in his decision. No significant financial relationships to disclose.
A Transient Translaminar GABAergic Interneuron Circuit Connects Thalamocortical Recipient Layers in Neonatal Somatosensory Cortex
Authors: Andre Marques-Smith, Daniel Lyngholm, Anna-Kristin Kaufmann, Jacqueline A. Stacey, Anna Hoerder-Suabedissen, Esther B.E. Becker, Michael C. Wilson, Zoltán Molnár, Simon J.B. Butt
Journal: Neuron (2016)

GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex.
Potential transfer of endotoxin across high-flux polysulfone membranes.
Authors: J Bommer, K P Becker, R Urbaschek
Journal: Journal of the American Society of Nephrology (1996)

It has been postulated that synthetic membranes, such as polysulfone membranes, are rather impermeable for endotoxin or endotoxin fragments and can be used for sterile filtration of dialysate. It has never been investigated, however, whether endotoxin permeability may be different in commercially available polysulfone membranes. In vitro, we found a significantly different permeability for endotoxin in two standard dialyzers and one test dialyzer with high-flux polysulfone membranes. In contrast to the F-60 dialyzer with a very low permeability for endotoxin, a stepwise increasing load of endotoxin concentration in the dialysate compartment of the PN 1913 test dialyzer and Primus 1350 polysulfone dialyzer was followed by a stepwise increase of endotoxin in the blood compartment. A significant transfer across the membranes was found when the endotoxin concentration in the dialysate compartment was > 10 ng/mL in the PN 1913 and > 0.5 ng/mL in the Primus 1350. In the latter, about 0.5% of the endotoxin concentration of the dialysate compartment was found in the blood compartment. The data suggest that manufacturers have to evaluate the performance and other properties of their synthetic membranes in detail.
Phase 1 Study of the Parp Inhibitor E7449 As a Single Agent in Patients with Advanced Solid Tumors or B-Cell Lymphoma
Authors: R. Plummer, D. Dua, N. Cresti, A. Suder, Y. Drew, V. Prathapan, P. Stephens, J. Thornton, B.D.L. Heras, B. Ink, L. Lee, M. Matijevic, S. McGrath, D. Sarker
Journal: Annals of Oncology (2014)
Abstract 17585: Optical Coherence Tomography Findings of Macrophage Accumulation in Atherothrombotic Plaques
Authors: Takao Sato, Tomoki Kameyama, Takahisa Noto, Hiroshi Inoue
Journal: Circulation (2010)

Backgrounds:  Macrophage plays an important role in triggering plaque rupture and in the development of acute coronary syndrome (ACS). Optical coherence tomography (OCT) is a high resolution (about 10μm), intravascular imaging modality, capble of investigating detailed coronary plaque morphology. This study aimed to investigate the clinical significance of OCT for detecting macrophage accumulation in patients.   Methods and Results:  Ex-Vivo Study. OCT images of 30 atherothrombotic debris captured by filter based distal protection device (Filtrap, NIPRO, Japan) (Figure B) were compared with histology. Macrophage density was quantified by immunohistochemical staining with CD14 (proinflammatory surface marker of macrophage), and compared with the maximal normalized standard deviation of the OCT signal intensity (NSD) in each debris (Figure A). There were significant positive correlation between CD14-positive macrophage density and NSD (R=0.523, P=0.04).   In-Vivo Study:  OCT were performed to detect macrophage accumulation (MPA), characterized by high intensity signal with increased NSD within fibrous cap (Figure C), in patients with ACS and stable angina pectoris (SAP). MPA was detected in 23 of 24 ACS patients and in 22 of 42 SAP patients (P   Conclusions:  OCT can be used to estimate macrophage contents within atherothrombotic plaque and, therefore, to detect vulnerable plaque in patients.
Effect of inhibition of the PI3K/Akt/mTOR pathway on AR splicing and downstream targets.
Authors: XiaoMei Liu, Alejandro Gomez-Pinillos, Payal Shah, Carmencita Lavilla, Anna C. Ferrari
Journal: Journal of Clinical Oncology (2013)

101 Background: Increased androgen receptor (AR) and PI3K/Akt/mTOR signaling drive androgen-independent (AI) prostate cancer (PC) progression. AR splice variants (SV) lacking the ligand-binding domain activate ligand-independent transcriptional programs that support castration resistant proliferation and survival. Treatment of the androgen-dependent PTEN null LNCaP (AD-cells), its AI derivative (AI-cells) and wt PTEN RV1 cells with the dual PI3K/mTOR inhibitor BEZ235 (E) combined with the histone deacetylase inhibitor Panobinostat (PAN) induced synergistic growth inhibition and cell death in vitro and in vivo. The effect of these treatments on AR splicing is unknown. Methods: LNCaP AD, AI and RV1 cells were treated with PAN 20nM, E 350nM, rapamycin (Rapa) 20nM and PI3Ki BKM120 (K) 1.5µM for 24h. Total (t) AR, SV’s and AR targets mRNA were measured by qtPCR and western. RV1 xenografts received 3 weeks E 35mg/kg/d or PAN 10mg/kg/QOD or PAN+E. Results: Baseline levels of tAR mRNA in AI were higher than AD and RV1 cells while SV1, SV7 and SV5-7 were higher in RV1 than AD and AI cells. Treatment with E, Rapa and K increased both tAR and SV’s mRNA’s and AR and PSA proteins. In contrast, treatment with PAN reduced tAR and SV’s levels in AD and AI with no effect on RV1. PAN reduced the induction of tAR by Rapa or K in AD, AI and RV1 but did not abrogate induction of SV’s. PAN inhibition was sufficient to abrogate the effect of E and decrease tAR and SV’s levels as well as AR protein and AR canonical and non-canonical targets (PSA, TMPRSS2 and UBE2C) and PSA protein below baseline levels in all cells treated with PAN+E. Similarly, RV1 tumors treated with E had a 50% increase in tAR and 20% in SV5-7 but no induction of CDK1 or UBE2C and a 35% reduction in PSA while RV1 tumors treated with PAN+E showed 40% reduction in both SV’s 1 and 7 and downstream targets CDK1 and UBE2C. Conclusions: Inhibition of PI3K/mTOR with E increases overall levels of AR transcription that is more pronounced on SV’s and uncouples AR’s transcriptional activity on canonical downstream targets in vivo. PAN can abrogate the stimulation of E by decreasing both SV’s expression and AR transcriptional activity on non-canonical targets. These effects may underlie their synergistic growth inhibition.