Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

Background

Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.

Materials and Methods

PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.

Results

PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.

Conclusions

Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.     

Fryns syndrome with atypical findings--with large midline cleft on forehead but normal cranial MRI findings

We report a newborn with Fryns syndrome and atypical findings like a large midline cleft on forehead. Abnormal findings included congenital left diaphragmatic hernia, prominent forehead, hypertelorism, broad nasal bridge, anteverted nostrils, cleft palate, low set ears, tapered fingers, macrocephaly, congenital heart defect, midline defects and renal anomalies. This is the first case that has a midline cleft on forehead with normal cranial MRI findings.     

A computational approach to motion perception

In this paper it is shown that the computation of the optical flow from a sequence of timevarying images is not, in general, an underconstrained problem. A local algorithm for the computation of the optical flow which uses second order derivatives of the image brightness pattern, and that avoids the aperture problem, is presented. The obtained optical flow is very similar to the true motion field — which is the vector field associated with moving features on the image plane — and can be used to recover 3D motion information. Experimental results on sequences of real images, together with estimates of relevant motion parameters, like time-to-crash for translation and angular velocity for rotation, are presented and discussed. Due to the remarkable accuracy which can be achieved in estimating motion parameters, the proposed method is likely to be very useful in a number of computer vision applications.     

Biosynthesis of silver nanoparticles using novel Bacillus sp. SBT8

Biosynthesis of silver nanoparticles (AgNPs) using microorganisms is an important application of nanobiotechnology and green chemistry because of interest by pharmaceutical and food manufacturers. In this study, biosynthesis of AgNPs by a novel Bacillus strain isolated from a soil sample from Sakarya district in Turkey was investigated. Biosynthesis was performed using cell-free supernatant of the bacterium following 24?h growth. Effects of varying AgNO₃ concentration (1–10?mM), pH (5–10), and temperature (30–40°C) on the synthesis of AgNPs were determined. Formation of AgNPs was monitored by UV–VIS spectroscopy. Field emission scanning electron microscopy was used to compare morphologies among the various culture conditions. The peaks created by surface plasmon resonance (SPR) of metals were obtained only at 4 and 6?mM AgNO₃ concentrations and the maximum concentration for the biosynthesis was observed at 6?mM. The highest yield was achieved at pH 10 and larger nanoparticles were obtained at this pH. The optimum temperatures for biosynthesis were 33 and 37°C. Fourier transform infrared spectroscopy analysis and transmission electron microcopy images confirmed that the proteins served as capping. Energy-dispersive spectroscopy analysis validated the formation of AgNPs. AgNPs exhibited antibacterial activity toward Gram-positive and Gram-negative pathogens.     

Pneumonia due to Enterobacter cancerogenus infection

Enterobacter cancerogenus (formerly known as CDC Enteric Group 19; synonym with Enterobacter taylorae) has rarely been associated with human infections, and little is known regarding the epidemiology and clinical significance of this organism. We describe a community-acquired pneumonia case in a 44-year-old female due to E. cancerogenus. Identification and antimicrobial susceptibility of the microorganism was performed by the automatized VITEK 2 Compact system (bioMerieux, France). The clinical case suggests that E. cancerogenus is a potentially pathogenic microorganism in determined circumstances; underlying diseases such as bronchial asthma, empiric antibiotic treatment, wounds, diagnostic, or therapeutic instruments.     

On the use of size functions for shape analysis

According to a recent mathematical theory a shape can be represented by size functions, which convey information on both the topological and metric properties of the viewed shape. In this paper the relevance of the theory of size functions to visual perception is investigated. An algorithm for the computation of the size functions is presented, and many theoretical properties of the theory are demonstrated on real images. It is shown that the representation of shape in terms of size functions (1) can be tailored to suit the invariance of the problem at hand and (2) is stable against small qualitative and quantitative changes of the viewed shape. A distance between size functions is used as a measure of similarity between the representations of two different shapes. The results obtained indicate that size functions are likely to be very useful for object recognition. In particular, they seem to be well suited for the recognition of natural and articulated objects.     

HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR–RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181—3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11—3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.     

Parazoanthus axinellae Extract Incorporated Hybrid Nanostructure and Its Potential Antimicrobial Activity**

This study, it was aimed to examine the change in the antimicrobial effect of sea anemone Parazoanthus axinellae extract by forming its nanoflowers. A scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were expended to observe the morphologies of the Cu NFs that had been produced. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) techniques were expended to analyze the managing assemblies in P. axinellae extract, which perform an effective part in the synthesis routine, as well as the crystal assembly of NFs. P. axinellae extract mediated the HNFs (Hybrid nanoflowers) are at high, pure crystalline nature, flower shape with a crystallographic system at the nanoscale with mean crystallite size 21.9 nm using XRD, and average particle size ~10 nm by SEM. The broad absorption band at 2981–2915 cm⁻¹ in the FT-IR spectra of anemone extract and Cu-anemone NFs represents the unique peak of hydroxy groups. In addition, Cu NFs were tested for their antibacterial properties. Cu NFs have been discovered to exhibit antibacterial properties. It is suggested that P. axinellae extract and various inorganic components be used to synthesize a variety of NFs and assess their suitability for usage in biomedical fields.