Correlates of screening mammography for Italian and Anglo-Australian women

The first aim of the research was to determine the applicability of certain variables from the Health Belief Model (HBM), the Theory of Reasoned Action (TRA), the risk dimensions from the Psychometric Paradigm, the Common-Sense Model of Illness Representations and the Locus of Control to Italian women’s beliefs and behaviours in relation to screening mammography. These models have predominantly been derived and evaluated with English-speaking persons. The study used quantitative and qualitative methods to enable explanation of research-driven and participant-driven issues. The second aim was to include Italian women in health behaviour research and to contrast the Italian sample with the Anglo-Australian sample to determine if differences exist in relation to their beliefs. In Australia many studies in health behaviour research do not include women whose first language is not English. The third aim was to evaluate the Anti-Cancer Council of Victoria’s (ACCV) Community Language Program (CLP) by: (a) identifying the strengths and weaknesses of the program as seen by the participants; and (b) assessing the impact of the program on women’s knowledge and beliefs about breast cancer, early detection of breast cancer, self-reported and intended breast screening behaviours. The CLP is an information service that uses women’s first language to convey information to women whose first language is not English. The CLP was designed to increase knowledge about breast and cervical cancer. The research used a pre-test-intervention-post-test design with 174 Italian-born and 138 Anglo-Australian women aged 40 years and over. Interviews for the Italian sample were conducted in Italian. The intervention was an information session that related to breast health and screening mammography. Demographic variables were collected in the Pre-Test only. Qualitative open-ended questions that related specifically to the information session were collected in the Post-Test phase of the study. Direct logistic regression was used with the participants’ beliefs and behaviours to identify the relevant variables for language (Italian speaking and English-speaking), attendance to an information session, mammography screening and breast self-examination (BSE) behaviour. Pre- and Post-Test comparisons were conducted using chi-square tests for the non-parametric data and paired sample t-tests for the parametric data. Differences were found between the Italian and Anglo-Australian women in relation to their beliefs about breast cancer screening. The Italian women were: (1) more likely to state that medical experts understood the causes of breast cancer; (2) more likely to feel that they had less control over their personal risk of getting breast cancer; (3) more likely to be upset and frightened by thinking about breast cancer; (4) less likely to perceive breast cancer as serious; (4) more likely to only do what their doctor told them to do; and (5) less likely to agree that there were times when a person has cancer and they don’t know it. A pattern emerged for the Italian and Anglo-Australian women from the logistic regression analyses. The Italian women were much more likely to comply with medical authority and advice. The Anglo-Australian women were more likely to feel that they had some control over their health. Specifically, the risk variable ‘dread’ was more applicable to the Italian women’s behaviour and internal locus of control variable was more relevant to the Anglo-Australian women. The qualitative responses also differed for the two samples. The Italian women’s comments were more general, less specific, and more limited than that of the Anglo-Australian women. The Italian women talked about learning how to do BSE whereas the Anglo-Australian women said that attending the session had reminded them to do BSE more regularly. The key findings and contributions of the present research were numerous. The focus on one cultural group ensured comprehensive analyses, as did the inclusion of an adequate sample size to enable the use of multivariate statistics. Separating the Italian and Anglo-Australian samples in the analyses provided theoretical implications that would have been overlooked if the two groups were combined. The use of both qualitative and quantitative data capitalised on the strengths of both techniques. The inclusion of an Anglo-Australian group highlighted key theoretical findings, differences between the two groups and unique contributions made by both samples during the collection of the qualitative data. The use of a pre-test-intervention-post-test design emphasised the reticence of the Italian sample to participate and talk about breast cancer and confirmed and validated the consistency of the responses across the two interviews for both samples. The inclusion of non-cued responses allowed the researcher to identify the key salient issues relevant to the two groups. The limitations of the present research were the lack of many women who were not screening and reliance on self-report responses, although few differences were observed between the Pre- and Post-Test comparisons. The theoretical contribution of the HBM and the TRA variables was minimal in relation to screening mammography or attendance at the CLP. The applicability of these health behaviour theories may be less relevant for women today as they clearly knew the benefits of and the seriousness of breast cancer screening. The present research identified the applicability of the risk variables to the Italian women and the relevance of the locus of control variables to the Anglo-Australian women. Thus, clear cultural differences occurred between the two groups. The inclusion of the illness representations was advantageous as the responses highlighted ideas and personal theories salient to the women not identified by the HBM. The use of the illness representations and the qualitative responses further confirmed the relevance of the risk variables to the Italian women and the locus of control variables to the Anglo-Australian women. Attendance at the CLP did not influence the women to attend for mammography screening. Behavioural changes did not occur between the Pre- and Post-Test interviews. Small incremental changes as defined by the TTM and the stages of change may have occurred. Key practical implications for the CLP were identified. Improving the recruitment methods to gain a higher proportion of women who do not screen is imperative for the CLP promoters. The majority of the Italian and Anglo-Australian women who attended the information sessions were women who screen. The fact that Italian women do not like talking or thinking about cancer presents a challenge to promoters of the CLP. The key theoretical finding that Italian women dread breast cancer but comply with their doctor provides clear strategies to improve attendance at mammography screening. In addition, the inclusion of lay health advisors may be one way of increasing attendance to the CLP by including Italian women already attending screening and likely to have attended a CLP session. The present research identified the key finding that improving Anglo-Australian attendance at an information session is related to debunking the myth surrounding familial risk of breast cancer and encouraging the Anglo-Australian women to take more control of their health. Improving attendance for Italian women is related to reducing the fear and dread of breast cancer and building on the compliance pattern with medical authority. Therefore, providing an information session in the target language is insufficient to attract non-screeners to the session and then to screen for breast cancer. Suggestions for future research in relation to screening mammography were to include variables from more than one theory or model, namely the risk, locus of control and illness representations. The inclusion of non-cued responses to identify salient beliefs is advantageous. In addition, it is imperative to describe the profile of the cultural sample in detail, include detailed descriptions of the translation process and be aware of the tendency of Italian women to acquiesce with medical authority.

Microarray classification using statistical learning and decision tree algorithms

This considers the challenging task of cancer prediction based on microarray data for the medical community. The research was conducted on mostly common cancers (breast, colon, long, prostate and leukemia) microarray data analysis, and suggests the use of modern machine learning techniques to predict cancer.

Dimensionality reduction of protein mass spectrometry data using random projection

Protein mass spectrometry (MS) pattern recognition has recently emerged as a new method for cancer diagnosis. Unfortunately, classification performance may degrade owing to the enormously high dimensionality of the data. This paper investigates the use of Random Projection in protein MS data dimensionality reduction. The effectiveness of Random Projection (RP) is analyzed and compared against Principal Component Analysis (PCA) by using three classification algorithms, namely Support Vector Machine, Feed-forward Neural Networks and K-Nearest Neighbour. Three real-world cancer data sets are employed to evaluate the performances of RP and PCA. Through the investigations, RP method demonstrated better or at least comparable classification performance as PCA if the dimensionality of the projection matrix is sufficiently large. This paper also explores the use of RP as a pre-processing step prior to PCA. The results show that without sacrificing classification accuracy, performing RP prior to PCA significantly improves the computational time.

Synthesis and characterization of surface-enhanced Raman-scattered gold nanoparticles

In this paper, we report a simple, rapid, and robust method to synthesize surface-enhanced Raman-scattered gold nanoparticles (GNPs) based on green chemistry. Vitis vinifera L. extract was used to synthesize noncytotoxic Raman-active GNPs. These GNPs were characterized by ultraviolet-visible spectroscopy, dynamic light-scattering, Fourier-transform infrared (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy. The characteristic surface plasmon-resonance band at ~528 nm is indicative of spherical particles, and this was confirmed by TEM. The N–H and C–O stretches in FTIR spectroscopy indicated the presence of protein molecules. The predominant XRD plane at (111) and (200) indicated the crystalline nature and purity of GNPs. GNPs were stable in the buffers used for biological studies, and exhibited no cytotoxicity in noncancerous MIO-M1 (Müller glial) and MDA-MB-453 (breast cancer) cell lines. The GNPs exhibited Raman spectral peaks at 570, 788, and 1,102 cm-1. These new GNPs have potential applications in cancer diagnosis, therapy, and ultrasensitive biomarker detection.

PET imaging of tumours with a 64Cu labeled macrobicyclic cage amine ligand tethered to Tyr3-octreotate

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.

Locked nucleic acid aptamer based microfluidic devices for capturing tumor cells

Design and fabrication of novel microfluidic devices for sensitive and specific capture of circulating tumor cells using locked nucleic acid modified aptamers and antibodies targeting EpCAM/Nucleolin expression. These devices also allow re-usability, on-chip characterization of multiple markers and release of viable captured cells for further culture and in vitro characterization for cancer diagnosis, prognosis and therapeutic planning.

A novel aggregate gene selection method for microarray data classification

This paper introduces a novel method for gene selection based on a modification of analytic hierarchy process (AHP). The modified AHP (MAHP) is able to deal with quantitative factors that are statistics of five individual gene ranking methods: two-sample t-test, entropy test, receiver operating characteristic curve, Wilcoxon test, and signal to noise ratio. The most prominent discriminant genes serve as inputs to a range of classifiers including linear discriminant analysis, k-nearest neighbors, probabilistic neural network, support vector machine, and multilayer perceptron. Gene subsets selected by MAHP are compared with those of four competing approaches: information gain, symmetrical uncertainty, Bhattacharyya distance and ReliefF. Four benchmark microarray datasets: diffuse large B-cell lymphoma, leukemia cancer, prostate and colon are utilized for experiments. As the number of samples in microarray data datasets are limited, the leave one out cross validation strategy is applied rather than the traditional cross validation. Experimental results demonstrate the significant dominance of the proposed MAHP against the competing methods in terms of both accuracy and stability. With a benefit of inexpensive computational cost, MAHP is useful for cancer diagnosis using DNA gene expression profiles in the real clinical practice.

Genomics based biomarker discovery in oral squamous cell carcinoma

 The present thesis showed signaling mechanisms and pathways essential for oral cancer progression through genomics approach. It has identified markers that are of diagnostic, prognostic and therapeutic importance. It has also shown that aspirin is a potential drug in oral cancer treatment.

Quick chip assay using locked nucleic acid modified epithelial cell adhesion molecule and nucleolin aptamers for the capture of circulating tumor cells

The role of circulating tumor cells (CTCs) in disease diagnosis, prognosis, monitoring of the therapeutic efficacy, and clinical decision making is immense and has attracted tremendous focus in the last decade. We designed and fabricated simple, flat channel microfluidic devices polydimethylsiloxane (PDMS based) functionalized with locked nucleic acid (LNA) modified aptamers (targeting epithelial cell adhesion molecule (EpCAM) and nucleolin expression) for quick and efficient capture of CTCs and cancer cells. With optimized flow rates (10 μl/min), it was revealed that the aptamer modified devices offered reusability for up to six times while retaining optimal capture efficiency (>90%) and specificity. High capture sensitivity (92%) and specificity (100%) was observed in whole blood samples spiked with Caco-2 cells (10-100 cells/ml). Analysis of blood samples obtained from 25 head and neck cancer patients on the EpCAM LNA aptamer functionalized chip revealed that an average count of 5 ± 3 CTCs/ml of blood were captured from 22/25 samples (88%). EpCAM intracellular domain (EpICD) immunohistochemistry on 9 oral squamous cell carcinomas showed the EpICD positivity in the tumor cells, confirming the EpCAM expression in CTCs from head and neck cancers. These microfluidic devices also maintained viability for in vitro culture and characterization. Use of LNA modified aptamers provided added benefits in terms of cost effectiveness due to increased reusability and sustainability of the devices. Our results present a robust, quick, and efficient CTC capture platform with the use of simple PDMS based devices that are easy to fabricate at low cost and have an immense potential in cancer diagnosis, prognosis, and therapeutic planning.

Early breast cancer identification : Which way to go? Microarray or image based computer aided diagnosis!

The goal of this research is to develop a computer aided diagnostic (CAD) system that can detect breast cancer in the early stage by using microarray and image data. We verified the performance of six well known classification algorithms with various performance matrices. Although we do not suggest a unique classifier algorithm for a CAD system, we do identify a number of algorithms whose performance is very promising. The algorithms performance was validated by 3 images dataset; two have been used for the first time in this experiment. Multidimensional image filtering is adopted for the final data extraction. The image data classification performance is compared with microarray data. Results suggest the most effective means of breast cancer identification in the early stage is a hybrid approach.

The use of sensitive chemical antibodies for diagnosis: detection of low levels of Epcam in breast cancer

EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70–90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues.

Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non- specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.

A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol.

AIM: To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance. BACKGROUND: Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy. DESIGN: A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods. METHODS: Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012). DISCUSSION: Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.

How acceptable is a referral and telephone-based outcall programme for men diagnosed with cancer? A feasibility study

The objective of this study was to determine the feasibility and acceptability of a referral and outcall programme from a telephone-based information and support service, for men newly diagnosed with colorectal or prostate cancer. A block randomized controlled trial was performed involving 100 newly diagnosed colorectal and prostate cancer patients. Patients were referred to the Cancer Information Support Service (CISS) through clinicians at diagnosis. Clinicians were randomized into one of three conditions. Active referral 1: specialist referral with four CISS outcalls: (1) ≤1 week of diagnosis; (2) at 6 weeks; (3) 3 months; and (4) 6 months post diagnosis. Active referral 2: specialist referral with one CISS outcall ≤1 week of diagnosis. Passive referral: specialist recommended patient contacts CISS, but contact at the patient's initiative. Patients completed research questionnaires at study entry (before CISS contact), then 4 and 7 months post diagnosis. Overall, 96% of participants reported a positive experience with the referral process; 87% reported they were not concerned about receiving the calls; and 84% indicated the timing of the calls was helpful. In conclusion, the referral and outcall programme was achievable and acceptable for men newly diagnosed with colorectal or prostate cancer.