Biomedical students' satisfaction with and engagement in laboratory e-learning support are related to their self-regulation.

Laboratory e-learning support tools can assist students' learning while preparing for laboratory classes. To successfully work in such virtual experimental environments (VEEs) outside class, students require self-regulated learning (SRL) skills. A deeper understanding of the continuous reciprocal interactions between SRL, satisfaction, and online engagement is needed to develop more effective online learning experiences. This study therefore aimed to explore the interconnection between students' satisfaction with, effort/importance and engagement in an exemplary VEE, and to relate this to their perceived SRL and learning outcomes. Based on surveys in 79 university students, SRL was related to VEE engagement, effort/importance, and satisfaction. VEE engagement and satisfaction were not related to learning outcomes, while SRL and effort were. Students with different SRL also tended to interact differently with the VEE and experienced differing degrees of procedural and feedback support by the e-environment. We conclude that, for optimal learning experience and outcomes, students' effort regulation and SRL need to be supported while interacting with the VEE, preferably by interventions that integrate personalized and adaptive features. This study has implications for designing and optimizing VEEs and indicates that future research should focus on VEEs taking students' SRL and effort regulation into account to support individual learners effectively.

Genomic copy number alterations as biomarkers for triple negative pregnancy-associated breast cancer.

BACKGROUND: PABC, commonly defined as breast cancer diagnosed during or ≤ 1 year after pregnancy, accounts for 7% of all breast cancers in women ≤ 45 years. Compared to age-matched non-PABC patients, PABC is characterized by a particularly aggressive histopathologic profile with poorly differentiated and estrogen- and progesterone receptor negative tumors and associated high mortality rates. This study assessed the genomic background of triple-negative PABC tumors by detection of copy number alterations (CNAs). METHODS: MLPA was used to compare CNAs in breast cancer-associated chromosomal loci between triple-negative PABC- and subtype-matched non-PABC patients. Both CNA patterns were evaluated by cluster analysis; associations between individual gene CNAs, pathological characteristics and survival were explored. RESULTS: Triple-negative PABC tumors exhibited unique CNAs compared to non-PABC tumors, including enrichment for TOP2A copy number loss, an independent predictor of worse overall survival (HR 8.96, p = 0.020). Cluster analysis based on CNA profiles identified a triple-negative PABC-subgroup with a particularly poor prognosis, characterized by chromosome 8p copy number loss. Individual gene CNAs analysis revealed that FGFR1 copy number loss on chromosome 8p11.23 was an independent predictor of poor outcome in multivariate analysis (HR 3.59, p = 0.053) and predicted the development of distant metastases (p = 0.048). CONCLUSION: This study provides novel insights into the biology of triple-negative PABC tumors suggesting that CNAs, particularly 8p loss and TOP2A loss, are involved in the development of breast cancer during pregnancy. FGFR1 loss and TOP2A loss seem to be promising new biomarkers that independently identify subgroups of PABC patients with poor prognosis. These genomic biomarkers may provide clues for personalized therapy.

DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment.

OBJECTIVE: Epigenetic changes contribute to pancreatic neuroendocrine tumor (PanNET) development. Hypermethylation of promoter DNA as a cause of tumor suppressor gene silencing is a well-established oncogenic mechanism that is potentially reversible and therefore an interesting therapeutic target. Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of inherited PanNETs. The aim of this study was to determine promoter methylation profiles in MEN1-related PanNETs. DESIGN AND METHODS: Methylation-specific multiplex ligation-dependent probe amplification was used to assess promoter methylation of 56 tumor suppressor genes in MEN1-related (n = 61) and sporadic (n = 34) PanNETs. Differences in cumulative methylation index (CMI), individual methylation percentages and frequency of promoter hypermethylation between subgroups were analyzed. RESULTS: We found promoter methylation of a large number of potential tumor suppressor genes. CMI (median CMI: 912 vs 876, P = 0.207) was the same in MEN1-related and sporadic PanNETs. We found higher methylation percentages of CASP8 in MEN1-related PanNETs (median: 59% vs 16.5%, P = 0.002). In MEN1-related non-functioning PanNETs, the CMI was higher in larger PanNETs (>2 cm) (median: 969.5 vs 838.5; P = 0.021) and in PanNETs with liver metastases (median: 1036 vs 869; P = 0.013). Hypermethylation of MGMT2 was more frequent in non-functioning PanNETs compared to insulinomas (median: 44.7% vs 8.3%; P = 0.022). Hypermethylation of the Von Hippel-Lindau gene promoter was observed in one MEN1-related PanNET and was associated with loss of protein expression. CONCLUSION: Promoter hypermethylation is a frequent event in MEN1-related and sporadic PanNETs. Targeting DNA methylation could be of therapeutic value in MEN1 patients with advanced PanNETs.

Repeated nipple fluid aspiration: compliance and feasibility results from a prospective multicenter study.

BACKGROUND: Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method. METHODS: In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation. RESULTS: In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects. CONCLUSIONS: Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers.

Current technologies for HER2 testing in breast cancer.

BACKGROUND: Molecular techniques play an increasingly important role in breast cancer detection and help in the prediction of prognosis and treatment response. HER-2/neu predicts the sensitivity of breast tumors to trastuzumab and lapatinib. Presently there are several ways to assess HER2 status at the protein level (e.g. ELISA), at the RNA level (RT-PCR, microarray) and at the DNA level (fluorescence in situ hybridization, chromogenic in situ hybridization (ISH), silver in situ hybridization or multiplex ligation-dependent probe amplification). DESIGN: This paper provides an overview of new developments in HER2 testing. RESULTS: Although these techniques correlate well in comparative studies, discrepancies remain. Each technique has its own (dis)advantages and thus there is no real gold standard. Not surprisingly, there is no consensus at present on which of the protein- or gene-based techniques is superior, on the use of mono- or duo-probe ISH systems, nor on the use of manual or fully-automated staining- and scoring systems. CONCLUSION: Until large clinical trials clearly point out one strategy as the best predictive one for trastuzumab response, the choice for a testing strategy will probably be based on local preferences which consider both practical and economic issues. Standardization, proper internal and external quality control assessment, laboratory accreditation and automation of tissue processing (autostainers) and interpretation methods (image analysis) will play an increasingly important role in HER2 testing.