413 research outputs found

    E03-02: Targeted therapy for non-small cell lung cancer: beyond EGFR and VEGF

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    Fiber spinning and rheology of liquid-crystalline polymers

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    Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1994.Includes bibliographical references (v. 2, leaves 365-374 ).by Suresh Ramalingam.Ph.D

    Hsp90 Inhibitors

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    ISOLATION, PURIFICATION AND CONFIRMATION OF METALLOTHIONEIN FROM THE LIVER TISSUE OF CADMIUM EXPOSED FRESHWATER FISH, CTENOPHARYNGODON IDELLA

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    Objective: Metallothioneins (MTs) are a group of low molecular mass, cysteine-rich proteins with a variety of functions including involvement in metal homeostasis, free radical scavenging, protection against heavy metal toxicity, and metabolic regulation. MT was obtained after purification from cadmium (Cd) exposed fish (Ctenopharyngodon idella) liver tissue using affinity chromatography. While various chromatographic separation methods are available, Affinity chromatography has been reported to be more suitable for separating low molecular weight metal bound proteins like MT. Affinity chromatography involves separating using biochemical mixture based on a highly specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligands. Methods: In the present study, in order to induce optimum MT concentrations in tissues, the experimental fishes were exposed to 5 ppm (which is about half the LC50 for this fish) of CdCl2 for 72 h. Results: The induced MT was isolated and purified by Affinity chromatography and desalting column (Sephadex G-25). Purified MT was evaluated by 15% SDS–PAGE and confirmed by western blot with specific antibodies. Conclusion: MT can be used in bio-monitoring programs as a biomarker of Cd exposure in aquatic environments

    Theory and Experiments towards Complete Generic Calibration

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    We consider the problem of calibrating a highly generic imaging model, that consists of a non-parametric association of a projection ray in 3D to every pixel in an image. Previous calibration approaches for this model do not seem to be directly applicable for cameras with large fields of view. In this paper, we describe a complete calibration approach that should in principle be able to handle any camera that can be described by the generic imaging model. Several contributions are provided. We show how to use the images of multiple calibration grids simultaneously, thus increasing the accuracy. This allows to calibrate an image region where these grids overlap. We then show how to calibrate the whole image, by iteratively estimating the pose of calibration grids and computing projection rays. A bundle adjustment procedure is also proposed, and several practical issues are discussed. The proposed approach has been applied on a wide variety of central and non-central cameras including fisheye lens, catadioptric cameras with spherical and hyperbolic mirrors, and multi-camera setups. We also consider the question if non-central models are more appropriate for certain cameras than central models

    A generic structure-from-motion algorithm for cross-camera scenarios

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    International audienceWe introduce a generic structure-from-motion approach based on a previously introduced, highly general imaging model, where cameras are modeled as possibly unconstrained sets of projection rays. This allows to describe most existing camera types (at least for those operating in the visible domain), including pinhole cameras, sensors with radial or more general distortions, catadioptric cameras (central or non-central), etc. We introduce a structure-from-motion approach for this general imaging model, that allows to reconstruct scenes from calibrated images, possibly taken by cameras of different types (cross-camera scenarios). Structure-from-motion is naturally handled via camera independent ray intersection problems, solved via linear or simple polynomial equations. We also propose two approaches for obtaining optimal solutions using bundle adjustment, where camera motion, calibration and 3D point coordinates are refined simultaneously. One is relatively straightforward, minimizing distances between 3D points and projection rays. The other minimizes reprojection error; the general imaging model does not provide analytical expressions for the reprojection error and its derivatives, which are desirable for efficient optimization. To achieve this, we propose to approximate the set of projection rays of a general non-central camera by several clusters of central rays, allowing us to formulate an analytical cost function. % that can be minimized using non-linear iteration. We present results for two cross-camera scenarios -- a pinhole used together with an omnidirectional camera and a stereo system used with an omnidirectional camera. Using ground-truth and 3D reconstruction results from classical techniques, we show that our generic algorithm is simple, general and accurate for extensions to various cross-camera and multi-camera scenarios

    Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design

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    BRAF V600 mutation; Binimetinib; EncorafenibMutació de BRAF V600; Binimetinib; EncorafenibMutación de BRAF V600; Binimetinib; EncorafenibBRAFV600 oncogenic driver mutations occur in 1–2% of non-small-cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic BRAFV600-mutant NSCLC, as first- or second-line treatment. The primary end point is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives evaluated additional efficacy end points and safety. Results from PHAROS will describe the antitumor activity/safety of encorafenib plus binimetinib in patients with metastatic BRAFV600-mutant NSCLC

    E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer.

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    PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC). METHODS: Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle. RESULTS: We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5 months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 % CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B. CONCLUSION: Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC

    Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study

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    PURPOSE Squamous non–small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546). PATIENTS AND METHODS Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52). RESULTS Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; P = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm. CONCLUSION In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy
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