Molecular Prognostic and Predictive Markers in Triple - Negative Breast Cancer

Triple-negative breast cancer (TNBC) is defined as a molecular subtype of breast cancer that lacks expression of hormone receptors (oestrogen and progesterone receptor) and HER2/neu/ErbB2 protein. It accounts for 15–20% of all invasive breast cancers. The occurrence of TNBC is often associated with younger age at the time of diagnosis and pre-menopausal status, early onset of menarche, higher body mass index (BMI) in the pre-menopausal period, race and ethnicity (African, Hispanic) and the presence of germline mutation in the BRCA1/2 genes or somatic mutation in the TP53 or PTEN genes. TNBCs are specific in its aggressive biological behaviour, shorter interval to disease progression and more frequent relapse within five years (19 to 40 months). The most of TNBCs are represented by high-grade invasive carcinomas of no special type (NST) with high proliferation index measured by Ki-67 nuclear expression, followed by metaplastic carcinomas, secretory carcinomas, and adenoid cystic carcinomas. Genetical and morphological heterogeneity inside TNBC is responsible for the higher frequency of primary and secondary resistance to systemic therapy. The scope of this chapter is to summarise the potential therapeutic agents involved in regulation of cell proliferation, migration, angiogenesis, apoptosis, gene expression and DNA damage or immune response. The insight into this issue is essential for the setting of the optimal chemotherapy regimen and targeted therapeutic strategy

Measurement of colour coordinates of LEDs used in the automotive exterior lighting

Article deals with dichromatic white light-emitting diode (LED’s) color coordinates used in automotive exterior lighting. This article also describes basic white automotive LED functionality and basic physical processes that create white light of these LEDs. It focuses on measuring color coordinates of white automotive LEDs with different temperature of LED and how the LED’s color depends on LED’s temperature. The article is comparing very important datasheet information of LED producers and values measured in the laboratory at university. The article contains statistical results of measurements and graphical representation of measured values and declared color bins which are very important for producers of headlamps for automotive companies

Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

BACKGROUND: Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. METHODS: We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. RESULTS: Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. CONCLUSION: IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Deployment and Measurement of Quality of Service Parameters for Triple Play Services in Optical Access Networks

Broadband telecommunication networks are the future of communication and distribution of multimedia services. Thanks to the high transmission potential and capacity of optical fibres, the optical networks are predestined to be more widely used in telecommunications considering the higher data rates through Triple Play services. This paper describes the impact of selected quality parameters on multimedia services defined as Triple Play within an optical network based on the EPON standard. The Triple Play services are then evaluated with measuring instruments and software applications according to QoS requirements and using evaluation methods based on generally defined standards. These are mainly subjective (listening and conversational) and objective (MSE, PSNR, SSIM) methods, or parameters (MOS) and factors (bitrate, delay, packet loss rate, jitter, BER) that are defined for the respective service. The values measured during the experimental tests were related to the limiting parameters of optical topology based on EPON networks for individual services according to their QoS requirements and objective user evaluation

Implementation of a Thermally Loaded EDFA Amplifier into a WDM-PON Optical Network

With deployment and continuous development of optical routes, the issues concerning the thermal loading of erbium-doped optical fibres become more and more relevant. As we were able to see a significant expansion of optical communication systems in the recent years, it was also necessary to find ways for bridging longer distances between individual points of the optical route. Modern optical telecommunication routes mainly use the DWDM system and optical transmission in the C and L bands. For this purpose, optical amplifiers that are mainly based on erbium doping are used. The aim of this paper is to point out the issues associated with the implementation of erbium-doped amplifying fibres into optical transmission routes that are made using the WDM-PON technology, with regard to the thermal load of these amplifying fibres

The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy

The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5–10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of KLK3 (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., PCA3, AMACR, TRPM8, MSMB and PSGR). AMACR, PCA3, TRPM8 and EZH2 mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus PCA3 and AMACR) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of PCA3, % free PSA, EPCAM and PSGR. PCA3 mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy