Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

STIR, SPIR and SPAIR techniques in magnetic resonance of the breast: a comparative study

The amount of fat is a component that complicates the clinical evaluation and the differential diagnostic between benign and malign lesions in the breast MRI examinations. To overcome this problem, an effective erasing of the fat signal over the images acquisition process, is essentials. This study aims to compare three fat suppression techniques (STIR, SPIR, SPAIR) in the MR images of the breast and to evaluate the best image quality regarding its clinical usefulness. To mimic breast women, a breast phantom was constructed. First the exterior contour and, in second time, its content which was selected based on 7 samples with different components. Finally it was undergone to a MRI breast protocol with the three different fat saturation techniques. The examinations were performed on a 1.5 T MRI system (Philips®). A group of 5 experts evaluated 9 sequences, 3 of each with fat suppression techniques, in which the frequency offset and TI (Inversion Time) were the variables changed. This qualitative image analysis was performed according 4 parameters (saturation uniformity, saturation efficacy, detail of the anatomical structures and differentiation between the fibroglandular and adipose tissue), using a five-point Likert scale. The statistics analysis showed that anyone of the fat suppression techniques demonstrated significant differences compared to the others with (p > 0.05) and regarding each parameter independently. By Fleiss’ kappa coefficient there was a good agreement among observers P(e) = 0.68. When comparing STIR, SPIR and SPAIR techniques it was confirmed that all of them have advantages in the study of the breast MRI. For the studied parameters, the results through the Friedman Test showed that there are similar advantages applying anyone of these techniques.

Learner’s satisfaction within a breast imaging eLearning course for radiographers

Background: An asynchronous eLearning system was developed for radiographers in order to promote a better knowledge about senology and mammography. Objectives: to assess the learners’ satisfaction. Methods: Target population included radiographers and radiogr aphy students, in order to assess eLearning satisfaction according to different experience levels in breast imaging. Satisfaction was measured through a questionnaire developed especially for eLearning systems, using a seven - point Likert scale. Main topics related are content, interface, personalization and learning community. Results: Overall, 85% of learners were satisfied with the course and 87,5% considered that the course is successful. Main areas that were evaluated by most learners in a positive way were interface and content (between six and seven - point); on the other hand, learning community presented a wider distribution of answers . Conclusions: The course provides an overall high degree of learner satisfaction, thus providing more effective knowle dge gain on breast imaging for radiographers.

Comparison of the pencil beam convolution algorithm and the analytical anisotropic algorithm in breast tumors

The calculation of the dose is one of the key steps in radiotherapy planning1-5. This calculation should be as accurate as possible, and over the years it became feasible through the implementation of new algorithms to calculate the dose on the treatment planning systems applied in radiotherapy. When a breast tumour is irradiated, it is fundamental a precise dose distribution to ensure the planning target volume (PTV) coverage and prevent skin complications. Some investigations, using breast cases, showed that the pencil beam convolution algorithm (PBC) overestimates the dose in the PTV and in the proximal region of the ipsilateral lung. However, underestimates the dose in the distal region of the ipsilateral lung, when compared with analytical anisotropic algorithm (AAA). With this study we aim to compare the performance in breast tumors of the PBC and AAA algorithms.

Radiographers practice concerning breast compression in mammography: gradual versus no gradual

Purpose: Evaluate the type of breast compression (gradual or no gradual) that provides less discomfort to the patient. Methods and Materials: The standard projections were simulated [craniocaudal/(CC) and mediolateral-oblique/(MLO)] with the two breast compressions in 90 volunteers women aged between 19 and 86. The women were organised in groups according to the breast density. The intensity of discomfort was evaluated using the scale that have represented several faces (0-10) proposed by Wong Baker in the end of each simulation. It was also applied an interview using focus group to debate the score that were attributed during pain evaluation and to identify the criteria that were considered to do the classification. Results: The women aged between 19-29y (with higher breast density) classified the pain during no gradual compression as 4 and the gradual compression as 2 for both projections. The MLO projection was considered the most uncomfortable. During the focus group interview applied to this group was highlighted that compression did not promoted pain but discomfort. They considered that the high expectations of pain did not correspond to the discomfort that they felt. Similar results were identified for the older women (30-50y; > 50y). Conclusion: The radiographers should considerer the technique for breast compression. The gradual compression was considered for the majority of the women as the most comfortable regardless of breast density. The MLO projection was considered as uncomfortable due to the positioning (axila and inclusion of pectoral muscle) and due to the higher breast compression compared to the CC projection.

Disparities in cervical and breast cancer mortality in Brazil

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. 

Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD

Human epidermal growth factor receptor 2 (HER2) is a breast cancer biomarker that plays a major role in promoting breast cancer cell proliferation and malignant growth. The extracellular domain (ECD) of HER2 can be shed into the blood stream and its concentration is measurable in the serum fraction of blood. In this work an electrochemical immunosensor for the analysis of HER2 ECD in human serum samples was developed. To achieve this goal a screen-printed carbon electrode, modified with gold nanoparticles, was used as transducer surface. A sandwich immunoassay, using two monoclonal antibodies, was employed and the detection of the antibody–antigen interaction was performed through the analysis of an enzymatic reaction product by linear sweep voltammetry. Using the optimized experimental conditions the calibration curve (ip vs. log[HER2 ECD]) was established between 15 and 100 ng/mL and a limit of detection (LOD) of 4.4 ng/mL was achieved. These results indicate that the developed immunosensor could be a promising tool in breast cancer diagnostics, patient follow-up and monitoring of metastatic breast cancer since it allows quantification in a useful concentration range and has an LOD below the established cut-off value (15 ng/mL).

Prognostic modelling of breast cancer patients: a benchmark of predictive models with external validation

Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Electrotécnica e de Computadores – Sistemas Digitais e Percepcionais pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Development and Assessment of an E-Learning Course on Breast Imaging for Radiographers: A Stratified Randomized Controlled Trial

Background: Mammography is considered the best imaging technique for breast cancer screening, and the radiographer plays an important role in its performance. Therefore, continuing education is critical to improving the performance of these professionals and thus providing better health care services. Objective: Our goal was to develop an e-learning course on breast imaging for radiographers, assessing its efficacy , effectiveness, and user satisfaction. Methods: A stratified randomized controlled trial was performed with radiographers and radiology students who already had mammography training, using pre- and post-knowledge tests, and satisfaction questionnaires. The primary outcome was the improvement in test results (percentage of correct answers), using intention-to-treat and per-protocol analysis. Results: A total of 54 participants were assigned to the intervention (20 students plus 34 radiographers) with 53 controls (19+34). The intervention was completed by 40 participants (11+29), with 4 (2+2) discontinued interventions, and 10 (7+3) lost to follow-up. Differences in the primary outcome were found between intervention and control: 21 versus 4 percentage points (pp), P<.001. Stratified analysis showed effect in radiographers (23 pp vs 4 pp; P=.004) but was unclear in students (18 pp vs 5 pp; P=.098). Nonetheless, differences in students’ posttest results were found (88% vs 63%; P=.003), which were absent in pretest (63% vs 63%; P=.106). The per-protocol analysis showed a higher effect (26 pp vs 2 pp; P<.001), both in students (25 pp vs 3 pp; P=.004) and radiographers (27 pp vs 2 pp; P<.001). Overall, 85% were satisfied with the course, and 88% considered it successful. Conclusions: This e-learning course is effective, especially for radiographers, which highlights the need for continuing education.

Using data mining techniques to support breast cancer diagnosis

More than ever, there is an increase of the number of decision support methods and computer aided diagnostic systems applied to various areas of medicine. In breast cancer research, many works have been done in order to reduce false-positives when used as a double reading method. In this study, we aimed to present a set of data mining techniques that were applied to approach a decision support system in the area of breast cancer diagnosis. This method is geared to assist clinical practice in identifying mammographic findings such as microcalcifications, masses and even normal tissues, in order to avoid misdiagnosis. In this work a reliable database was used, with 410 images from about 115 patients, containing previous reviews performed by radiologists as microcalcifications, masses and also normal tissue findings. Throughout this work, two feature extraction techniques were used: the gray level co-occurrence matrix and the gray level run length matrix. For classification purposes, we considered various scenarios according to different distinct patterns of injuries and several classifiers in order to distinguish the best performance in each case described. The many classifiers used were Naïve Bayes, Support Vector Machines, k-nearest Neighbors and Decision Trees (J48 and Random Forests). The results in distinguishing mammographic findings revealed great percentages of PPV and very good accuracy values. Furthermore, it also presented other related results of classification of breast density and BI-RADS® scale. The best predictive method found for all tested groups was the Random Forest classifier, and the best performance has been achieved through the distinction of microcalcifications. The conclusions based on the several tested scenarios represent a new perspective in breast cancer diagnosis using data mining techniques.

MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

Molecular aspects of hepatic carcinogenesis

Exogenous agents correlated with hepatocellular carcinoma (HCC) have been identified and well characterized. These agents, including the different viruses that cause chronic hepatitis and cirrhosis, can lead to regenerative nodules and dysplastic nodules/adenomatous hyperplasia. These conditions associated with several molecular alterations of hepatocyte ultimately culminate in hepatocellular carcinoma. Recently, there has been a great progress in the identification of somatic and germinative mutations that may be correlated with the development of HCC, justifying a review on the subject. Hence, the factors involved in the process of hepatic carcinogenesis, such as infection by the hepatitis B and C viruses, with a special focus in the molecular alterations described in recent years are discussed herein, pointing out areas potentially relevant for clinical development.

A novel antibody-like material for breast cancer antigen CA15-3, used to track breast cancer by potentiometric transduction

This work presents the development of a low cost sensor device for the diagnosis of breast cancer in point-of-care, made with new synthetic biomimetic materials inside plasticized poly(vinyl chloride), PVC, membranes, for subsequent potentiometric detection. This concept was applied to target a conventional biomarker in breast cancer: Breast Cancer Antigen (CA15-3). The new biomimetic material was obtained by molecularly-imprinted technology. In this, a plastic antibody was obtained by polymerizing around the biomarker that acted as an obstacle to the growth of the polymeric matrix. The imprinted polymer was specifically synthetized by electropolymerization on an FTO conductive glass, by using cyclic voltammetry, including 40 cycles within -0.2 and 1.0 V. The reaction used for the polymerization included monomer (pyrrol, 5.0×10-3 mol/L) and protein (CA15-3, 100U/mL), all prepared in phosphate buffer saline (PBS), with a pH of 7.2 and 1% of ethylene glycol. The biomarker was removed from the imprinted sites by proteolytic action of proteinase K. The biomimetic material was employed in the construction of potentiometric sensors and tested with regard to its affinity and selectivity for binding CA15-3, by checking the analytical performance of the obtained electrodes. For this purpose, the biomimetic material was dispersed in plasticized PVC membranes, including or not a lipophilic ionic additive, and applied on a solid conductive support of graphite. The analytical behaviour was evaluated in buffer and in synthetic serum, with regard to linear range, limit of detection, repeatability, and reproducibility. This antibody-like material was tested in synthetic serum, and good results were obtained. The best devices were able to detect 5 times less CA15-3 than that required in clinical use. Selectivity assays were also performed, showing that the various serum components did not interfere with this biomarker. Overall, the potentiometric-based methods showed several advantages compared to other methods reported in the literature. The analytical process was simple, providing fast responses for a reduced amount of analyte, with low cost and feasible miniaturization. It also allowed the detection of a wide range of concentrations, diminishing the required efforts in previous sample pre-treating stages.

Pulmonary thromboembolism in AIDS patient with chronic venous insufficiency, pulmonary tuberculosis and breast cancer: a case report and pathophysiology review

Recent literature reports thrombotic episodes occurring in patients with HIV infection associated with other abnormalities including neoplasms and infections predisposing to a hypercoagulable state. We report a 47-year-old woman who developed pulmonary thromboembolism in association with HIV infection, pulmonary tuberculosis and breast cancer. She was treated with rifampin, isoniazid, pyrazinamide; heparin, phenprocoumon, zidovudine, lamivudine and efavirenz. Acid fast bacilli were visualized in a sputum smear and three months after, Mycobacterium tuberculosis was isolated from lymph node biopsy during a episode of immune reconstitution. The isolated mycobacteria showed sensitivity to all first-line drugs. HIV infection, breast cancer and pulmonary tuberculosis have several mechanisms that induce hypercoagulable state and can lead to thromboembolic complications. Pulmonary thromboembolism in this patient was a diagnostic challenge because of all the other severe diseases that she experienced at the same time.

Longitudinal analysis of tumor marker CEA of breast cancer patients from Braga's hospital

Allied to an epidemiological study of population of the Senology Unit of Braga’s Hospital that have been diagnosed with malignant breast cancer, we describe the progression in time of repeated measurements of tumor marker Carcinoembryonic antigen (CEA). Our main purpose is to describe the progression of this tumor marker as a function of possible risk factors and, hence, to understand how these risk factors influences that progression. The response variable, values of CEA, was analyzed making use of longitudinal models, testing for different correlation structures. The same covariates used in a previous survival analysis were considered in the longitudinal model. The reference time used was time from diagnose until death from breast cancer. For diagnostic of the models fitted we have used empirical and theoretical variograms. To evaluate the fixed term of the longitudinal model we have tested for a changing point on the effect of time on the tumor marker progression. A longitudinal model was also fitted only to the subset of patients that died from breast cancer, using the reference time as time from date of death until blood test.