Breast cancer diagnosis using a hybrid genetic algorithm for feature selection based on mutual information

Feature Selection is the process of selecting a subset of relevant features (i.e. predictors) for use in the construction of predictive models. This paper proposes a hybrid feature selection approach to breast cancer diagnosis which combines a Genetic Algorithm (GA) with Mutual Information (MI) for selecting the best combination of cancer predictors, with maximal discriminative capability. The selected features are then input into a classifier to predict whether a patient has breast cancer. Using a publicly available breast cancer dataset, experiments were performed to evaluate the performance of the Genetic Algorithm based on the Mutual Information approach with two different machine learning classifiers, namely the k-Nearest Neighbor (KNN), and Support vector machine (SVM), each tuned using different distance measures and kernel functions, respectively. The results revealed that the proposed hybrid approach is highly accurate for predicting breast cancer, and it is very promising for predicting other cancers using clinical data

An investigation into the immunomodulatory activities of human placental protein 14 (PP14).

PP14 has been shown to suppress the incorporation of [3]H-Thymidine into both mitogenically and allogeneically stimulated lymphocytes in a dose dependent manner. The suppressive activity was shown to be specific, in that PP14 did not affect cellular viability, nor interact with the mitogen phytohaemagglutinin (PHA). Flow cytometric analysis indicated that PP14 had no effect on the expression of the Tac antigen, the transferrin receptor or HLA-DR molecules on the surface of stimulated lymphocytes. Neither did PP14 affect the interaction of interleukin-2 (IL-2) with its cell surface receptor. The suppressive activity was partially reversed by the addition of exogenous IL-2. PP14 inhibited the production of IL-2 from mitogenically stimulated lymphocytes and led to a small, but significant reduction in soluble IL-2 receptor release. Radiolabel binding studies and IL-2 dose response curves indicated that PP14 affected the affinity of the IL-2 receptor on PHA stimulated lymphocytes. This was supported by the observation that PP14 increased the level of cell surface-associated IL-2 on stimulated lymphocytes. There was a small inhibition of gamma interferon levels early in the culture period. PP14 had no effect on the CD4/CD8 ratio following stimulation and was not found to be associated with the cell surface, nor mask cell surface expression of the CD2 antigen.These data suggest that the immunosuppressive activity of PP14 may, in part, be mediated via a modulation of the functional, high affinity IL-2 receptor. It is not known as yet whether such an activity is effective at the level of induction of the receptors or whether the primary control is at another level of the response. PP14 may have implications in the study of implantation and fertility and prove of wider interest in the field of transplantation biology and the control of the immune response

PROCEE: a PROstate Cancer Evaluation and Education serious game for African Caribbean men

Purpose – Prostate cancer is the most common cancer diagnosed in men in the UK. Black men are in a higher prostate cancer risk group possibly due to inherent genetic factors. The purpose of this paper is to introduce PROstate Cancer Evaluation and Education (PROCEE), an innovative serious game aimed at providing prostate cancer information and risk evaluation to black African-Caribbean men. Design/methodology/approach – PROCEE has been carefully co-designed with prostate cancer experts, prostate cancer patients and members of the black African-Caribbean community in order to ensure that it meets the real needs and expectations of the target audience. Findings – During the co-design process, the users defined an easy to use and entertaining game which can effectively raise awareness, inform users about prostate cancer and their risk, and encourage symptomatic men to seek medical attention in a timely manner. Originality/value – During focus group evaluations, users embraced the game and emphasised that it can potentially have a positive impact on changing user behaviour among high risk men who are experiencing symptoms and who are reluctant to visit their doctor

Editorial: radioimmunotherapy—translational opportunities and challenges

It has become evident that radiotherapy has both, immune suppressive, and immune activating properties (1). This is why this important component of cancer treatment should be combined with immune therapies to shift the balance toward immune activation against tumor cells. During the last decade a manifold of pre-clinical work was put into investigation of combination of radiotherapy either with additional immune stimulants such as cytokines or vaccines or in combination with antibodies that target immune suppressive molecules such as immune checkpoint inhibitors. Luckily, some of these approaches are currently tested in clinical trials, high lightening the huge translational opportunities by examination of modes of action of radiotherapy in combination with immunotherapy; named in this special issue radioimmunotherapy. However, one has always to keep in mind that many challenges do still exist such as what is the best sequence and timing of joint applications, what are the best immunotherapy approaches, how to overcome tumor resistances, what about healthy tissue cytotoxicity, or which biomarkers or matrices of biomarkers are most beneficial for patients stratification, just to mention the most burning ones. The articles in this special issue grab many of these challenges

Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition

The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)—an essential element of the metastatic process—is frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the “capture” of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)—cmHsp70.1—can be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression

Novel combinatorial approaches to tackle the immunosuppressive microenvironment of prostate cancer

Prostate cancer (PCa) is the second-most common cancer in men worldwide and treatment options for patients with advanced or aggressive prostate cancer or recurrent disease continue to be of limited success and are rarely curative. Despite immune checkpoint blockade (ICB) efficacy in some melanoma, lung, kidney and breast cancers, immunotherapy efforts have been remarkably unsuccessful in PCa. One hypothesis behind this lack of efficacy is the generation of a distinctly immunosuppressive prostate tumor microenvironment (TME) by regulatory T cells, MDSCs, and type 2 macrophages which have been implicated in a variety of pathological conditions including solid cancers. In PCa, Tregs and MDSCs are attracted to TME by low-grade chronic inflammatory signals, while tissue-resident type 2 macrophages are induced by cytokines such as IL4, IL10, IL13, transforming growth factor beta (TGFβ) or prostaglandin E2 (PGE2) produced by Th2 cells. These then drive tumor progression, therapy resistance and the generation of castration resistance, ultimately conferring a poor prognosis. The biology of MDSC and Treg is highly complex and the development, proliferation, maturation or function can each be pharmacologically mediated to counteract the immunosuppressive effects of these cells. Herein, we present a critical review of Treg, MDSC and M2 involvement in PCa progression but also investigate a newly recognized type of immune suppression induced by the chronic stimulation of the sympathetic adrenergic signaling pathway and propose targeted strategies to be used in a combinatorial modality with immunotherapy interventions such as ICB, Sipuleucel-T or antitumor vaccines for an enhanced anti-PCa tumor immune response. We conclude that a strategic sequence of therapeutic interventions in combination with additional holistic measures will be necessary to achieve maximum benefit for PCa patients

Extracellular cell stress (heat shock) proteins - immune responses and disease: an overview

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory ‘danger signals’ for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease

Tumor-Specific Hsp70 Plasma Membrane Localization Is Enabled by the Glycosphingolipid Gb3

Human tumors differ from normal tissues in their capacity to present Hsp70, the major stress-inducible member of the HSP70 family, on their plasma membrane. Membrane Hsp70 has been found to serve as a prognostic indicator of overall patient survival in leukemia, lower rectal and non small cell lung carcinomas. Why tumors, but not normal cells, present Hsp70 on their cell surface and the impact of membrane Hsp70 on cancer progression remains to be elucidated.Although Hsp70 has been reported to be associated with cholesterol rich microdomains (CRMs), the partner in the plasma membrane with which Hsp70 interacts has yet to be identified. Herein, global lipid profiling demonstrates that Hsp70 membrane-positive tumors differ from their membrane-negative counterparts by containing significantly higher amounts of globotriaoslyceramide (Gb3), but not of other lipids such as lactosylceramide (LacCer), dodecasaccharideceramide (DoCer), galactosylceramide (GalCer), ceramide (Cer), or the ganglioside GM1. Apart from germinal center B cells, normal tissues are Gb3 membrane-negative. Co-localization of Hsp70 and Gb3 was selectively determined in Gb3 membrane-positive tumor cells, and these cells were also shown to bind soluble Hsp70-FITC protein from outside in a concentration-dependent manner. Given that the latter interaction can be blocked by a Gb3-specific antibody, and that the depletion of globotriaosides from tumors reduces the amount of membrane-bound Hsp70, we propose that Gb3 is a binding partner for Hsp70. The in vitro finding that Hsp70 predominantly binds to artificial liposomes containing Gb3 (PC/SM/Chol/Gb3, 17/45/33/5) confirms that Gb3 is an interaction partner for Hsp70.These data indicate that the presence of Gb3 enables anchorage of Hsp70 in the plasma membrane of tumors and thus they might explain tumor-specific membrane localization of Hsp70