Fermentation products as feed additives mitigate some ill-effects of heat stress in pigs
JOURNAL OF ANIMAL SCIENCE
Authors: Kumar, S.; Bass, B. E.; Bandrick, M.; Loving, C. L.; Brockmeier, S. L.; Looft, T.; Trachsel, J.; Madson, D. M.; Thomas, M.; Casey, T. A.; Frank, J. W.; Stanton, T. B.; Allen, H. K.
Abstract
Heat stress (HS) may result in economic losses to pig producers across the USA and worldwide. Despite significant advancements in management practices, HS continues to be a challenge. In this study, an in-feed antibiotic (carbadox, CBX) and antibiotic alternatives (Saccharomyces cerevisiae [XPC], and Lactobacillus acidophilus [SGX] fermentation products) were evaluated in a standard pig starter diet as mitigations against the negative effects of HS in pigs. A total of 100 gilts were obtained at weaning (6.87 +/- 0.82 kg BW, 19.36 +/- 0.72 d of age) and randomly assigned to dietary treatments (2 rooms/treatment, 2 pens/room, 6 to 7 pigs/pen). After 4 wk of dietary acclimation, half of the pigs in each dietary group (1 room/dietary treatment) were exposed to repeated heat stress conditions (RHS; daily cycles of 19 h at 25 degrees C and 5 h at 40 degrees C, repeated for 9 d), and the remaining pigs were housed at constant thermal neutral temperature (25 degrees C, [NHS]). Pigs subjected to RHS had elevated skin surface temperature (P < 0.05; average 41.7 degrees C) and respiration rate (P < 0.05; 199 breaths per minute (bpm) during HS, and overall reduced (P < 0.05) BW, ADG, ADFI, and G: F regardless of dietary treatment. Independent of diet, RHS pigs had significantly shorter (P < 0.05) jejunum villi on d 3 and d 9 compared to NHS pigs. Heat stress resulted in decreased villus height to crypt depth ratio (V: C) in pigs fed with control diet with no added feed additive (NON) and CBX diets at d 3, whereas the pigs fed diets containing XPC or SGX showed no decrease. Transcriptional expression of genes involved in cellular stress (HSP27, HSP70, HSP90, HIF1A), tight junction integrity (OCLN, CLDN3, CLDN4), and immune response (TNFA, IFNG, and IL8) were measured in the ileum mucosa. Pigs in all dietary treatments subjected to RHS had significantly higher (P < 0.05) transcript levels of HSP27 and HSP90, and an upward trend (P < 0.07) of HSP70 mRNA expression. RHS pigs had higher (P < 0.05) transcript levels of IFNG and CLDN4 in NON diet, TNFA in XPC and CBX diets, and HSP70 in SGX diet compared to the respective diet-matched pigs in the NHS conditions. Neither RHS nor diet affected peripheral natural killer (NK) cell numbers or NK cell lytic activity. In conclusion, pigs subjected to RHS had decreased performance, and supplementation with fermentation products in the feed (XPC and SGX) protected pigs from injury to the jejunum mucosa.
IPH-926 lobular breast cancer cells are triple-negative but their microarray profile uncovers a luminal subtype
CANCER SCIENCE
Authors: Christgen, Matthias; Geffers, Robert; Kreipe, Hans; Lehmann, Ulrich
Abstract
Human primary breast cancers and breast cancer cell lines are classified by microarray-defined molecular subtypes, which reflect differentiation characteristics. Estrogen receptor (ER) expression is indicative of the luminal molecular subtype. We have previously established IPH-926, the first well-characterized cell line from infiltrating lobular breast cancer. IPH-926 displays an ER/PR/ErbB2 triple-negative immunophenotype, which is due to a loss of ER expression in its in vivo clonal ancestry. Loss of ER might indicate a fundamental change of cellular differentiation and it is unclear whether a luminal subtype is preserved beyond ER conversion. Using Affymetrix microarray analysis, seven different classifier gene lists (PAM305, DISC256, TN1288, PAM50, UNC1300, LAB704, INT500) and a background population of 50 common mammary carcinoma cell lines, we have now determined the molecular subtype of IPH-926. Strikingly, the IPH-926 expression profile is highly consistent with a luminal subtype. It is nearest to luminal/ER-positive breast cancer cell lines and far apart from basal breast cancer cell lines. Quantitative real-time RT-PCR confirmed enhanced expression of luminal marker genes (AGR2, CLU, CA12, EMP2, CLDN3) and low or absent expression of basal marker genes (KRT5, CD44, CAV1, VIM). Moreover, IPH-926 lacked androgen receptor (AR) expression, a transcription factor previously associated with luminal-like gene expression in a subset of triple-negative or molecular apocrine breast cancers. In conclusion, IPH-926 is triple-negative but belongs to the luminal subtype. Luminal differentiation characteristics can be preserved beyond ER conversion and might not require a compensatory expression of AR.