Proteomic investigations into resistance in colorectal cancer.

Introduction: Despite advances in screening and treatment options, colorectal cancer (CRC) remains one of the most prevalent and lethal cancer subtypes. Resistance to cytotoxic or targeted therapy has remained a constant challenge to the treatment and long-term management of patients, attracting intense worldwide investigation since the 1950s. Through extensive investigations into the proteomic mechanisms and functions that convey resistance to therapy/s, researchers have become able to implicate alterations in several signaling pathways that provide and sustain resistance to treatment.Areas covered: In this review, we summarize how protein alterations are associated with resistance to therapy, with particular emphasis on CRC. An overview of the mechanisms of therapeutic resistance is described, highlighting recent studies which endeavor to elucidate the proteomic changes that are associated with the acquisition and promulgation of therapeutic resistance.Expert opinion: While cancers such as CRC have been intensively studied for decades, unresponsiveness and the resistance to therapy remain critical obstacles in the treatment of patients. Due to the inherent biological and clinical heterogeneity of individual CRCs, proteomic methods stand to become powerful tools to provide biological insights that may guide therapeutic strategies with the ultimate goal of refining emergent immunotherapeutic treatments.

Recent findings from the Human Proteome Project: opening the mass spectrometry toolbox to advance cancer diagnosis, surveillance and treatment.

The Human Proteome Project stands to eclipse the Human Genome Project in terms of scope, content and interpretation. Its outputs, in conjunction with recent developments across the proteomics community, provide new tools for cancer research with the potential of providing clinically relevant insights into the disease. These collectively may guide the development of future diagnosis, surveillance and treatment strategies. Having established a robust organizational framework within the international community, the Human Proteome Organization and the proteomics community at large have made significant advances in biomarker discovery, detection, molecular imaging and in exploring tumor heterogeneity. Here, the authors discuss some developments in cancer proteomics and how they can be implemented to reduce the global burden of the disease.

Transgenic, high-protein sorghums display promise in poultry diets in an initial comparison.

This study aimed to compare the inclusion of transgenic sorghums against commercially available sorghums on growth performance in broiler chickens. Isonitrogenous and isoenergetic diets were offered to a total 288 male Ross 308 broiler chickens from 14 to 35 d posthatch. Three dietary treatments were diets based on transgenic sorghums with a mean protein content of 154.7 g/kg and 5 treatments were based on commercially available sorghum hybrids with a mean protein content of 90.6 g/kg. Soybean meal inclusions in the commercial sorghum diets averaged 215 g/kg, which was reduced to 171 g/kg in the transgenic sorghum diets because of the higher protein contents. Overall growth performance was highly satisfactory, and commercial sorghums supported 2.55% (2,330 vs. 2,272 g/bird; P = 0.010) more weight gains and 2.74% (2,929 vs. 2,851 g/bird; P = 0.012) higher feed intakes; however, the transgenic sorghums supported a fractionally better FCR (1.255 vs 1.257; P = 0.826). There were no statistical differences in apparent jejunal and ileal starch and protein (N) digestibility coefficients between treatments. The transgenic sorghum diets generated slightly, but significantly, higher AME:GE ratios and AMEn, but the commercial sorghum diets generated 6.33% (235 vs. 221 g/kg; P < 0.001) greater breast meat yields. Apparent ileal digestibility coefficients of 16 amino acids averaged 0.839 and 0.832 for transgenic and commercial sorghum-based diets, respectively, without any significant differences in individual amino acids. This outcome suggests amino acid digestibilities of the transgenic sorghums may be inherently higher than commercial hybrid sorghums as the 25.7% higher average soybean meal inclusions would have advantaged amino acid digestibilities in commercial sorghum diets. The possibility that the digestibilities of amino acids in the kafirin component of transgenic sorghums was enhanced by modifications to the structure of kafirin protein bodies is discussed. In conclusion, transgenic sorghums with higher protein concentrations led to 20.5% reduction of soybean meal inclusions in broiler diets, and this change did not compromise feed conversion efficiency compared to standard commercial hybrid sorghums.

Implications of excreta uric acid concentrations in broilers offered reduced-crude protein diets and dietary glycine requirements for uric acid synthesis.

In a previous experiment, male Ross 308 broiler chickens were offered dietary treatments with 3 levels of crude protein (222, 193, 165 g/kg) and 3 feed grains (ground maize, ground wheat, whole wheat) from 7 to 35 d post-hatch. Maize-based diets supported superior growth performance in comparison to wheat-based diets. Uric acid concentrations in excreta were retrospectively determined and related to total nitrogen (N) excreta concentrations. Uric acid concentrations ranged from 28.5 to 69.4 mg/g and proportions of uric acid-N to total excreta-N ranged from 27.4% to 42.6% in broiler chickens offered the 3 × 3 factorial array of dietary treatments. Proportions of uric acid-N to total N in excreta in birds offered the 165 g/kg CP, maize-based diet were significantly lower by 10.6 percentage units (27.4% versus 38.0%; P = 0.00057) than their wheat-based counterparts. Total excreta analysed had been collected from 35 to 37 d post-hatch when feed intakes and excreta outputs were monitored. There were linear relationships between proportions of uric acid-N to total N in excreta in birds offered the three 165 g/kg CP diets with weight gain (r = -0.587; P = 0.010), feed intake (r = -0.526; P = 0.025) and feed conversion ratios (r = 0.635; P = 0.005). The possibility that increasing uric acid-N proportions in excreta is indicative of excessive ammonia accumulations compromising growth performance is discussed. The mean proportion of dietary glycine involved in uric acid excretion was 49.2% across all dietary treatments but ranged from 25.0% to 80.9%. Thus, the appropriate amount of dietary glycine is variable and largely dependent on the volume of uric acid synthesised and excreted.

Tissue and plasma proteomics for early stage cancer detection.

The pursuit of novel and effective biomarkers is essential in the struggle against cancer, which is a leading cause of mortality worldwide. Biomarkers can be used as specific diagnostic tools, prognostic predictors, markers of the development of therapeutic resistance or even as therapeutic targets themselves. Through the application of sensitive and specific proteomic techniques, oncoproteomics investigates the proteins associated with cancer processes, to better understand their biological function/s and their associated pathways during tumorigenesis. Such studies seek to identify both potential biomarkers and drug targets in order to improve patient survival and quality of life whilst reducing the global health budget. Tissue and plasma are the most commonly utilised biological samples for such studies as they are readily available, non-invasive and generally acceptable. Here, we outline the relative advantages and disadvantages of the most frequently used techniques for cancer diagnosis, prognosis, treatment and surveillance, concentrating on the latest advances and application of tissue and plasma proteomics for novel cancer biomarker discovery and disease surveillance.