Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours

Endoglin/CD105 is well acknowledged as being the most reliable marker of proliferation of endothelial cells, and it is overexpressed on tumour neovasculature. Our current knowledge of its structure, physiological role, and tissue distribution suggests that targeting of endoglin/CD105 is a novel and powerful diagnostic and therapeutic strategy in human malignancies, through the imaging of tumour-associated angiogenesis and the inhibition of endothelial cell functions related to tumour angiogenesis. Among biotherapeutic agents, monoclonal antibodies have shown a major impact on the clinical course of human malignancies of different histotypes. Along this line, the potential efficacy of anti-endoglin/CD105 antibodies and their derivatives for clinical purposes in cancer is supported by a large body of available pre-clinical in vitro and in vivo data. In this review, the main findings supporting the translation of antibody-based endoglin/CD105 targeting from pre-clinical studies to clinical applications in human cancer are summarized and discussed

Avaliação da ação anti-oxidante de coberturas a base da proteína Z19 do milho BR451 em noz Macadâmia.

bitstream/CNPDIA-2009-09/11887/1/CiT45_2008.pd

Monte Carlo-based 3D surface point cloud volume estimation by exploding local cubes faces

This article proposes a state-of-the-art algorithm for estimating the 3D volume enclosed in a surface point cloud via a modified extension of the Monte Carlo integration approach. The algorithm consists of a pre-processing of the surface point cloud, a sequential generation of points managed by an affiliation criterion, and the final computation of the volume. The pre-processing phase allows a spatial reorientation of the original point cloud, the evaluation of the homogeneity of its points distribution, and its enclosure inside a rectangular parallelepiped of known volume. The affiliation criterion using the explosion of cube faces is the core of the algorithm, handles the sequential generation of points, and proposes the effective extension of the traditional Monte Carlo method by introducing its applicability to the discrete domains. Finally, the final computation estimates the volume as a function of the total amount of generated points, the portion enclosed within the surface point cloud, and the parallelepiped volume. The developed method proves to be accurate with surface point clouds of both convex and concave solids reporting an average percentage error of less than 7 %. It also shows considerable versatility in handling clouds with sparse, homogeneous, and sometimes even missing points distributions. A performance analysis is presented by testing the algorithm on both surface point clouds obtained from meshes of virtual objects as well as from real objects reconstructed using reverse engineering techniques

Normas foliares para café conilon em pré-florada no sul da Bahia.

Objetivou-se estabelecer faixas de suficiências e normas DRIS para lavouras de cafeeiro Conilon em pré-florada, para região sul da Bahia (Atlântico)

Immunotherapy of brain metastases: breaking a "dogma"

Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases. Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events. Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting

A phase Ib study combining the second-generation DNA hypomethylating agent (DHA) guadecitabine (SGI-110) and ipilimumab in patients with metastatic melanoma: The NIBIT-M4 Study

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Whole genome methylation profiles as independent markers of survival in stage IIIc melanoma patients

Background: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.Methods: Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.Results: Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a " favorable" methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a " favorable" vs. " unfavorable" methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a " favorable" methylation profile was 41.2% as compared to 0% for patients with an " unfavorable" methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for " unfavorable" methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.Conclusions: A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients. © 2012 Sigalotti et al.; licensee BioMed Central Ltd

Resolving the temporal evolution of line broadening in single quantum emitters

Light emission from solid-state quantum emitters is inherently prone to environmental decoherence, which results in a line broadening and in the deterioration of photon indistinguishability. Here we employ photon correlation Fourier spectroscopy (PCFS) to study the temporal evolution of such a broadening in two prominent systems: GaAs and In(Ga)As quantum dots. Differently from previous experiments, the emitters are driven with short laser pulses as required for the generation of high-purity single photons, the time scales we probe range from a few nanoseconds to milliseconds and, simultaneously, the spectral resolution we achieve can be as small as ∼ 2µeV. We find pronounced differences in the temporal evolution of different optical transition lines, which we attribute to differences in their homogeneous linewidth and sensitivity to charge noise. We analyze the effect of irradiation with additional white light, which reduces blinking at the cost of enhanced charge noise. Due to its robustness against experimental imperfections and its high temporal resolution and bandwidth, PCFS outperforms established spectroscopy techniques, such as Michelson interferometry. We discuss its practical implementation and the possibility to use it to estimate the indistinguishability of consecutively emitted single photons for applications in quantum communication and photonic-based quantum information processing

Normas foliares para o café conilon no período de granação para o sul da Bahia.

Objetivou-se estabelecer faixas de suficiências e normas DRIS em fase de granação, para lavouras de cafeeiro Conilon, cultivadas na região Sul do Estado da Bahia (Atlântico)