PD-0283: 4D dose accumulation for dose painting by numbers for lung cancer

In conventional radiotherapy of locally advanced lung cancer (LALC) doses levels are homogeneously delivered to the entire PTV, whereat dose escalation is restricted by normal tissue toxicity. Several studies have shown the geometrical correlation between high FDG uptake in a PET scan and tumour recurrence. This is the rationale for FDG-based local dose escalation, e.g. by dose prescription on the voxel values of a PET scan – dose painting by numbers (DPBN). The aim of this study is to investigate the robustness of the DPBN plans against tumour motio

Synthesis of Positron Emission Tomography (PET) Images via Multi-channel Generative Adversarial Networks (GANs)

Positron emission tomography (PET) image synthesis plays an important role, which can be used to boost the training data for computer aided diagnosis systems. However, existing image synthesis methods have problems in synthesizing the low resolution PET images. To address these limitations, we propose multi-channel generative adversarial networks (M-GAN) based PET image synthesis method. Different to the existing methods which rely on using low-level features, the proposed M-GAN is capable to represent the features in a high-level of semantic based on the adversarial learning concept. In addition, M-GAN enables to take the input from the annotation (label) to synthesize the high uptake regions e.g., tumors and from the computed tomography (CT) images to constrain the appearance consistency and output the synthetic PET images directly. Our results on 50 lung cancer PET-CT studies indicate that our method was much closer to the real PET images when compared with the existing methods.Comment: 9 pages, 2 figure

Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Looking into the future, what do we see?

This series of short communications introduces and celebrates the occasion of World Nutrition Rio2012, and looks ahead. There will be another series published next month in our May issue, which will be on-line early, at 0001 GMT on Thursday 26 April, the day before Rio2012 begins. The questions and answers: Our contributors, this month and next month, have been asked to write within a standard framework, based on their knowledge and experience, in a style comparable with those of the news and comment sections of journals concerned with public health. Their contributions are judgements, as any policy statements are and must be. The first question is about Rio2012 itself. The second question is addressed to young colleagues. All the questions are designed to look forward and to advise, warn and encourage. What do I hope Rio2012 will achieve? My advice to a young public health nutritionist When I am optimistic, what is my vision? When I am pessimistic, what do I foresee? My most highly recommended writer One choice of my own publication

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

User Interaction in Semi-Automatic Segmentation of Organs at Risk: a Case Study in Radiotherapy

Accurate segmentation of organs at risk is an important step in radiotherapy planning. Manual segmentation being a tedious procedure and prone to inter- and intra-observer variability, there is a growing interest in automated segmentation methods. However, automatic methods frequently fail to provide satisfactory result, and post-processing corrections are often needed. Semi-automatic segmentation methods are designed to overcome these problems by combining physicians’ expertise and computers’ potential. This study evaluates two semi-automatic segmentation methods with different types of user interactions, named the “strokes” and the “contour”, to provide insights into the role and impact of human-computer interaction. Two physicians participated in the experiment. In total, 42 case studies were carried out on five different types of organs at risk. For each case study, both the human-computer interaction process and quality of the segmentation results were measured subjectively and objectively. Furthermore, different measures of the process and the results were correlated. A total of 36 quantifiable and ten non-quantifiable correlations were identified for each type of interaction. Among those pairs of measures, 20 of the contour method and 22 of the strokes method were strongly or moderately correlated, either directly or inversely. Based on those correlated measures, it is concluded that: (1) in the design of semi-automatic segmentation methods, user interactions need to be less cognitively challenging; (2) based on the observed workflows and preferences of physicians, there is a need for flexibility in the interface design; (3) the correlated measures provide insights that can be used in improving user interaction design

Combined Treatment of an Intratumoral Injection of Dendritic Cells and Systemic Chemotherapy (Paclitaxel) for Murine Fibrosarcoma

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma

Type I Interferon: Potential Therapeutic Target for Psoriasis?

Background: Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors. Methodology/Principal Findings: We observed robust overexpression of type I interferon (IFN)–inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs for IFN-a subtypes was observed in lesional skin compared with nonlesional skin. Enrichment of mature dendritic cells and 2 type I IFN–inducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-c and TNF-a–inducible gene signatures occurred at the same disease sites. Conclusions/Significance: Up-regulation of TNF-a and elevation of the TNF-a–inducible gene signature in lesional skin underscore the importance of this cytokine in psoriasis; these data describe a molecular basis for the therapeutic activity of anti–TNF-a agents. Furthermore, these findings implicate type I IFNs in the pathogenesis of psoriasis. Consistent and significant up-regulation of type I IFNs and their associated gene signatures in psoriatic skin suggest that type I IFNs may b