Proteomics advances for precision therapy in ovarian cancer.

Introduction: Due to the relatively low mutation rate and high frequency of copy number variation, finding actionable genetic drivers of high-grade serous carcinoma (HGSC) is a challenging task. Furthermore, emerging studies show that genetic alterations are frequently poorly represented at the protein level adding a layer of complexity. With improvements in large-scale proteomic technologies, proteomics studies have the potential to provide robust analysis of the pathways driving high HGSC behavior. Areas covered: This review summarizes recent large-scale proteomics findings across adequately sized ovarian cancer sample sets. Key words combined with 'ovarian cancer' including 'proteomics', 'proteogenomic', 'reverse-phase protein array', 'mass spectrometry', and 'adaptive response', were used to search PubMed. Expert opinion: Proteomics analysis of HGSC as well as their adaptive responses to therapy can uncover new therapeutic liabilities, which can reduce the emergence of drug resistance and potentially improve patient outcomes. There is a pressing need to better understand how the genomic and epigenomic heterogeneity intrinsic to ovarian cancer is reflected at the protein level and how this information could be used to improve patient outcomes.

Competitive adsorption of dihydroxy and trihydroxy bile salts with whey protein and casein in oil-in-water emulsions.

The competitive adsorption between whey protein concentrate (WPC) or sodium caseinate (SCN) and four bile salts, sodium cholate (NaC), dexocycholate (NaDC), taurocholate (NaTC), and glycodeoxycholate (NaGDC), has been studied in protein stabilized oil-in-water emulsions. The bile salts that contain a conjugated amino acid (NaTC and NaGDC) were considerably more efficient at displacing both WPC and SCN proteins from the emulsion droplet interface, even though they are known to have a hydrophobicity lower than that of NaC and NaDC. This is explained in terms of a steric resistance to adsorption from the conjugated amino acids in NaTC and NaGDC. This leads to their adopting an adsorbed conformation at the oil-water interface that penetrates less into the oil phase, causing greater disruption of the adsorbed layer, and hence leads to greater displacement of protein from the interface. Complementary computer simulations of the adsorption of the four bile salts at the decane-water interface support the hypothesis that the NaTC and NaGDC adopt flatter conformations that stick out further into the aqueous phase, which arises from a lower free energy of adsorption. The surface coverage as a function of bulk concentration for the four bile salts has also been measured. These have been found to have a form that fits closely the Langmuir-Freundlich isotherm. The results for NaC suggest that it adsorbs as individual molecules and forms a saturated monolayer over much of the concentration range used in the displacement experiments, since it is below its critical micelle concentration in this range. For the other three bile salts, on the other hand, the primary adsorbing species appears to be the micelle form, since the surface coverage is above that of a saturated monolayer for much of the concentration range studied.

Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity.

The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role in driving disease phenotypes is poorly understood. Here, we investigate the role of MYC in HER2+ disease, examining the relationship between HER2 expression and MYC phosphorylation in HER2+ patient tumors and characterizing the functional effects of deregulating MYC expression in the murine NeuNT model of amplified-HER2 breast cancer. Deregulated MYC alone was not tumorigenic, but coexpression with NeuNT resulted in increased MYC Ser62 phosphorylation and accelerated tumorigenesis. The resulting tumors were metastatic and associated with decreased survival compared with NeuNT alone. MYC;NeuNT tumors had increased intertumoral heterogeneity including a subtype of tumors not observed in NeuNT tumors, which showed distinct metaplastic histology and worse survival. The distinct subtypes of MYC;NeuNT tumors match existing subtypes of amplified-HER2, estrogen receptor-negative human tumors by molecular expression, identifying the preclinical utility of this murine model to interrogate subtype-specific differences in amplified-HER2 breast cancer. We show that these subtypes have differential sensitivity to clinical HER2/EGFR-targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYC breast cancers.

The major proteins of the seed of the fruit of the date palm (Phoenix dactylifera L.): Characterisation and emulsifying properties.

Proteins were extracted from the seeds of the fruit of the date palm. Proteomic analysis and SDS-PAGE electrophoresis of the extracted proteome suggested it is composed predominantly of the storage proteins glycinin and ß-conglycinin, although over 300 proteins were detected, 91 of which were identified with confidence. In terms of protein type, the largest numbers of proteins were associated, not unexpectedly, with metabolism and energy functions, which reflected the requirements of the germinating and growing embryonic plant. The emulsifying properties of the extracted proteins were determined. Date seed protein exhibited a lower emulsifying activity than either whey protein concentrate or soy protein isolate, at each of the pH values tested. However, the stability of the emulsions produced with all three proteins was very similar at the different pH values. This combination of large emulsion droplet size and high emulsion stability properties suggested that the date proteins may adsorb as large protein oligomers.

Effect of addition of thermally modified cowpea protein on sensory acceptability and textural properties of wheat bread and sponge cake.

This paper investigates the sensory acceptability and textural properties of leavened wheat bread and sponge cake fortified with cow protein isolates that had been denatured and glycated by thermal treatment. Defatted cowpea flour was prepared from cow pea beans and the protein isolate was prepared (CPI) and thermally denatured (DCPI). To prepare glycated cowpea protein isolate (GCPI) the cowpea flour slurry was heat treated before isolation of the protein. CPI was more susceptible to thermal denaturation than GCPI as determined by turbidity and sulphydryl groups resulting in greater loss of solubility. This is attributed to the higher glycation degree and higher carbohydrate content of GCPI as demonstrated by glycoprotein staining of SDS PAGE gels. Water absorption of bread dough was significantly enhanced by DCPI and to a larger extent GCPI compared to the control, resulting in softer texture. CPI resulted in significantly increased crumb hardness in baked bread than the control whereas DCPI or GCPI resulted in significantly softer crumb. Bread fortified with 4% DCPI or GCPI was similar to control as regards sensory and textural properties whereas 4% CPI was significantly different, limiting its inclusion level to 2%. There was a trend for higher sensory acceptability scores for GCPI containing bread compared DCPI. Whole egg was replaced by 20% by GCPI (3.5%) in sponge cake without affecting the sensory acceptability, whereas CPI and DCPI supplemented cakes were significantly different than the control.

Modification of functional properties of egg-white proteins.

Egg-white proteins are extensively utilised as food ingredients due to their unique functional properties. Several attempts have been made in order to improve the functional properties of egg-white proteins and to identify the optimal formulations for unique food products. Experimental data proves that controlled denaturation of egg-white proteins can have a beneficial impact on various functional applications in the food industry such as emulsifying ability, heat stability, and gelation. This review describes the effect of heat-induced denaturation on protein structure and functionality. Studies on the impact of Maillard reaction, which aim to elucidate the structure-function relationship of egg-white proteins, are presented. A novel approach which could be the basis for the development of new methods aiming to improve the functional properties of egg-white proteins is also discussed.