Refined immunoRNases for the efficient targeting and selective killing of tumour cells: A novel strategy.

In order to overcome limitations of conventional cancer therapy methods, immunotoxins with the capability of target-specific action have been designed and evaluated pre-clinically, and some of them are in clinical studies. Targeting cancer cells via antibodies specific for tumour-associated surface proteins is a new biomedical approach that could provide the selectivity that is lacking in conventional cancer therapy methods such as radiotherapy and chemotherapy. A successful example of an approved immunotoxin is represented by immunoRNases. ImmunoRNases are fusion proteins in which the toxin has been replaced by a ribonuclease. Conjugation of RNase molecule to monoclonal antibody or antibody fragment was shown to enhance specific cell-killing by several orders of magnitude, both in vitro and in animal models. There are several RNases obtained from different mammalian cells that are expected to be less immunogenic and systemically toxic. In fact, RNases are pro-toxins which become toxic only upon their internalization in target cells mediated by the antibody moiety. The structure and large size of the antibody molecules assembled with the immunoRNases have always been a challenge in the application of immunoRNases as an antitoxin. To overcome this obstacle, we have offered a new strategy for the application of immunoRNases as a promising approach for upgrading immunoRNAses with maximum affinity and high stability in the cell, which can ultimately act as an effective large-scale cancer treatment. In this review, we introduce the optimized antibody-like molecules with small size, approximately 10 kD, which are presumed to significantly enhance RNase activity and be a suitable agent with the potential for anti-cancer functionality. In addition, we also discuss new molecular entities such as monobody, anticalin, nonobody and affilin as refined versions in the development of immunoRNases. These small molecules express their functionality with the suitable small size as well as with low immunogenicity in the cell, as a part of immunoRNases.

Effects of feed form and xylanase supplementation on metabolizable energy partitioning in broiler chicken fed wheat-based diets.

An experiment was conducted to investigate the effects of feed form and xylanase supplementation on the growth performance, energetic efficiencies, energy partitioning, and nitrogen (N) balance of Ross 308 male broilers fed wheat-based diets. The experiment was conducted as a 2 × 2 × 5 factorial arrangement with 2 levels of feed forms (mash or pellets) and xylanase (0 or 500 mg/kg), and five feeding levels (ad libitum, 85%, 70%, 55%, and 40% of ad libitum intake). Each of the 20 dietary treatments was fed to 5 replicate pens (5 birds/pen) from 22 to 42 days of age. A significant interaction between feed form and xylanase on was observed for average daily feed intake and heat production (p < 0.01). Pelleting and dietary supplementation with xylanase increased average daily gain and feed conversion ratio but decreased (p < 0.05) average daily feed intake. Broilers fed xylanase-supplemented diet ingested and pelleted diet retained more than in those fed the mash form or the diet without xylanase. Xylanase and pellets decreased (p < 0.01) heat production and metabolizable energy intake (MEI), but increased retained energy (p < 0.05). The birds fed xylanase also needed less MEI per gram of N retained than those fed the diets without enzyme (p < 0.01). Estimation of both metabolizable and net energy requirements for maintenance as a function of BW0.75 showed that requirements for broilers fed pelleted diet and xylanase-supplemented diet were lower than in those fed mash form or the diet without xylanase (p < 0.01). The higher energetic efficiencies for retention were estimated in the birds offered pelleted and xylanase-supplemented diets compared with the values determined for those fed the diet with mash form or the diet without xylanase (p < 0.05). The efficiency of energy utilization for protein for birds fed xylanase-supplemented diets was higher (p < 0.01) than those fed diets without xylanase, and fat deposition for broilers fed the pelleted diet was greater than those fed the mash diet (p < 0.01). Because MEI for maintenance requirements represents a large portion of the MEI, the results from this experiment could be considered in calculation of energy requirements for finishing broilers fed wheat-based diets.

Effects of lysolecithin and xylanase supplementation on the growth performance, nutrient digestibility and lipogenic gene expression in broilers fed low-energy wheat-based diets.

This experiment was conducted to evaluate the effects of emulsifier (Lipidol, active ingredient: lysophospholipids; LPL) and xylanase (200 mg/kg of feed) supplementation in a lower energy diet on performance, nutrient retention, intestinal morphology, blood metabolites and meat quality in broilers. A total of 360 1-day-old male chicks (Ross 308) were assigned to five treatments, with six replications of 12 birds each per treatment in a completely randomized design. The five treatments were as follows: (a) higher energy diet (HE); (b) lower energy diet (LE; energy content reduced by 100 kcal/kg compared with the HE); (c) LE + 0.10% LPL (EM); (d) LE + 200 mg xylanase/kg (ENZ); and (e) LE + 0.10% LPL + 200 mg xylanase/kg (EM + ENZ). Broilers fed HE had a higher average daily gain (ADG, day 0-24) and lower average daily feed intake (ADFI) and feed conversion ratio (FCR) from day 11 to 24 and day 0 to 24 than those fed the LE diet. Broilers fed EM or ENZ diets also had lower FCR and ADFI (day 11-24 and day 0-24) than those fed reduced-energy diets. The inclusion of 0.10% LPL and/or xylanase to the LE diet increased the apparent digestibility of dry matter (DM), nitrogen (N), ether extract (EE) and gross energy (GE), as well as villous height and ratio of villous height to crypt depth in the duodenum and jejunum. Serum free fatty acid (FFA) concentration was lower in birds fed the HE diet, compared with those fed the LE diet. The low-density lipoprotein cholesterol, total cholesterol and triglyceride concentrations were decreased by LPL supplementation. The relative weight of abdominal fat was higher in birds fed the HE diet, but lower from LPL supplementation. It was concluded that a reduced-energy diet impaired bird performance, while dietary supplementation of LPL and xylanase to reduced-energy diets positively affected productive performance, nutrient utilization, intestinal morphology and abdominal fat percentage.