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

Immunotherapy in melanoma: Can we predict response to treatment with circulating biomarkers?

Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures

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

Cohabitation : the Pan-America View

In this concluding chapter we reflect on a series of issues of both a methodological and substantive nature encountered in this research project. Firstly, we must realize that the use of individual census records not only opened vast possibilities, but also entails a number of limitations. Secondly, the very large sample sizes allowed for the disaggregation of national trends into far more detailed spatial, ethnic and educational patterns. This, in its turn, allowed us to adopt a "geo-historical" view of the rise of cohabitation for almost the entire American continent, from Alaska to Tierra del Fuego. Furthermore, statistical analyses could be performed at the individual and contextual levels simultaneously. Results show that the effects of social stratification, religion and ethnicity are continuing to be of major importance. This not only holds at the individual level, but at the contextual level as well. Nevertheless, an entirely new wave of change started rolling over the pre-existing patterns from the 1970s onward. These trends are following a firm course, irrespective of the economic ups and downs. The Americas, as opposed to many Asian societies and Africa, are now following in the European footsteps, be it with their own distinct and path-dependent characteristics associated with regionally varying historical antecedents

Quantum non-demolition measurement of an electron spin qubit through its low-energy many-body spin environment

The measurement problem dates back to the dawn of quantum mechanics. Here, we measure a quantum dot electron spin qubit through off-resonant coupling with thousands of redundant nuclear spin ancillae. We show that the link from quantum to classical can be made without any "wavefunction collapse", in agreement with the Quantum Darwinism concept. Large ancilla redundancy allows for single-shot readout with high fidelity $\approx99.85\%$. Repeated measurements enable heralded initialization of the qubit and probing of the equilibrium electron spin dynamics. Quantum jumps are observed and attributed to burst-like fluctuations in a thermally populated phonon bath

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

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

Collective Excitation of Spatio-Spectrally Distinct Quantum Dots Enabled by Chirped Pulses

For a scalable photonic device producing entangled photons, it is desirable to have multiple quantum emitters in an ensemble that can be collectively excited, despite their spectral variability. For quantum dots, Rabi rotation, the most popular method for resonant excitation, cannot assure a universal, highly efficient excited state preparation, because of its sensitivity to the excitation parameters. In contrast, Adiabatic Rapid Passage (ARP), relying on chirped optical pulses, is immune to quantum dot spectral inhomogeneity. Here, we advocate the robustness of ARP for simultaneous excitation of the biexciton states of multiple quantum dots. For positive chirps, we find that there is also regime of phonon advantage that widens the tolerance range of spectral detunings. Using the same laser pulse we demonstrate the simultaneous excitation of energetically and spatially distinct quantum dots. Being able to generate spatially multiplexed entangled photon pairs is a big step towards the scalability of photonic devices