Biomarkers characterization of circulating tumour cells in breast cancer patients

Introduction: Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease. Methods: Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics. Results: Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03). Conclusions: This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted

Treatment options for patients with triple-negative breast cancer

Breast cancer is a heterogeneous disease composed of different subtypes, characterized by their different clinicopathological characteristics, prognoses and responses to treatment. In the past decade, significant advances have been made in the treatment of breast cancer sensitive to hormonal treatments, as well as in patients whose malignant cells overexpress or amplify HER2. In contrast, mainly due to the lack of molecular targets, little progress has been made in the treatment of patients with triple-negative breast cancer. Recent improved understanding of the natural history, pathophysiology, and molecular features of triple-negative breast cancers have provided new insights into management and therapeutic strategies for women affected with this entity. Ongoing and planned translational clinical trials are likely to optimize and improve treatment of women with this disease

Nuclear Translocation of CAM-Associated Protein Activates Transcription for Long-Term Facilitation in Aplysia.

In this study we have identified a cell-adhesion-associated molecule (CAMAP) that translocates to the nucleus of the sensory neuron following application of 5-HT at the synapse and coactivates CREB-mediated gene transcription required for long-term facilitation

Spatial trends of dry spells over Peninsular Malaysia during monsoon seasons

This study aims to trace changes in the dry spells over Peninsular Malaysia based on the daily rainfall data from 36 selected rainfall stations which include four subregions, namely northwest, west, southwest, and east for the periods of 1975 to 2004. Six dry spell indices comprising of the main characteristics of dry spells, the persistency of dry events, and the frequency of the short and long duration of dry spells will be used to identify whether or not these indices have increased or decreased over Peninsular Malaysia during the monsoon seasons. The findings of this study indicate that the northwestern areas of the Peninsular could be considered as the driest area since almost all the indices of dry spells over these areas are higher than in the other regions during the northeast (NE) monsoon. Based on the individual and the field significant trends, the results of the Mann–Kendall test indicate that as the total number of dry days, the maximum duration, the mean, and the persistency of dry days are decreased, the trend of the frequency of long dry spells of at least 4 days is also found to decrease in almost all the stations over the Peninsula; however, an increasing trend is observed in the frequency of short spells in these stations during the NE monsoon season. On the other hand, during the southwest monsoon, a positive trend is observed in the characteristics of dry spells including the persistency of two dry days in many stations over the Peninsula. The frequency of longer dry periods exhibits a decreasing trend in most stations over the western areas during both monsoon seasons for the periods of 1975 to 2004