BW-Sp3 is a BW-5147-derived T cell lymphoma with limited immunogenicity since, despite regression of the majority of subcutaneous tumors, an important fraction of the animals will die from metastases. In the present study, the BW-Sp3 cells were transfected with genes encoding B7-1 or B7-2, known to be involved in the induction of T cell responses. The resulting transfectants exhibited a reduced tumorigenicity and did not cause mortality in the syngeneic recipients. Furthermore, immunization with the B7-1 or B7-2 transfectants resulted in an increased generation of cytotoxic T lymphocytes (CTL) that lysed both the transfectants and the wild-type BW-Sp3 cells. Since the B7 transfectants were completely rejected in syngeneic recipients and induced potent CTL recognizing the wild-type BW-Sp3 cells, these engineered cells were considered as candidates for immunotherapy. Vaccinations with the B7-1 or B7-2 transfectants could completely protect the animals from metastatic disease when subsequently challenged with wild-type BW-Sp3 cells. Furthermore, immunization with the B7 transfectants could prolong the survival time of mice that had been challenged intravenously with BW-Sp3 cells. Surprisingly, however, when these transfectants, as well as the wild-type BW-Sp3 cells, were used for vaccination of tumor-bearing animals, the presence of the subcutaneous BW-Sp3 tumors clearly interfered with the outcome of immunotherapy, resulting in increased malignancy, as reflected by a higher incidence of progressing tumors and a reduced survival rate. Possible implications for immunotherapy in humans are discussed.
According to the cancer immunoediting concept, inflammatory mediators play not only a critical role in promoting host protection against cancer but also contribute to cancer cell growth and survival. TNF-α is a critical factor in this network. However, the mechanisms underlying the tumor-promoting effect of TNF-α have not been fully elucidated yet. We previously reported that in vitro culture of Lewis lung carcinoma 3LL cells with TNF-α-producing macrophages resulted in enhanced resistance toward TNF-α-mediated lysis and increased malignancy of the 3LL cells. In this study, we analyzed the effects of endogenous TNF-α on TNF-α resistance and malignant behavior in vivo of low-malignant/TNF-α-sensitive 3LL-S cells and cancer cells derived from 3LL-S tumors that developed in wild-type or TNF-α−/− mice. Interestingly, 3LL-S cells acquired a malignant phenotype in vivo depending on the presence of host TNF-α, whereas acquisition of TNF-α resistance was TNF-α-independent. This result suggested that malignancy-promoting characteristics of 3LL-S cells other than TNF-α resistance are influenced in vivo by TNF-α. We previously identified the malignancy-promoting genes, secretory leukocyte protease inhibitor (SLPI) and S100A4, as being up-regulated in 3LL-S cells upon their s.c. growth in wild-type mice. In this study, we show that SLPI, but not S100A4, was induced in 3LL-S cells both in vitro and in vivo by TNF-α, and that silencing of in vivo induced 3LL-S SLPI expression using RNA interference abrogated in vivo progression but did not influence TNF-α resistance. These data indicate that SLPI induction may be one mechanism whereby TNF-α acts as an endogenous tumor promoter.
Yucca contains high a content of saponin that has a glucocorticord-like effect in animals, e.g., anti-inflammation and anti-microbiota. The objective of the present study was to test the hypothesis that dietary supplementation of yucca powder may alleviate heat stress and improve growth performance of growing broilers subjected to cycling high ambient temperature. A total of 240 male broiler chicks (yellow feathered chicken) aged 28 days, with body weight (BW) of 792 ± 43.7 g, were randomly allocated to one of four treatments (6 replicates per treatment): control (normal temperature, 24 ± 2°C, 24 h), fed diets supplemented with 100 mg/kg yucca under normal temperature (Y), high ambient temperature exposure (HT, 34 ± 2°C, 11 h), fed diets supplemented with 100 mg/kg yucca (HT+Y) under high ambient temperature. After 7 days of adaption, the experiment was conducted for 4 weeks (aged 28–56 days). HT significantly reduced feed intake, BW, and average daily gain (ADG) of broiler, but yucca improved the feed intake under HT condition. Yucca supplementation reduced (P < 0.05) the HT-induced increase in temperature of rectum and leg skin. Supplementation of yucca increased the hypothalamic mRNA expression of TRPV2, TRPV4, and TRPM8 (P < 0.05). Yucca reduced (P < 0.05) the plasma lipid oxidation product malondialdehyde (MDA), but did not affect the activities of antioxidant enzyme superoxide oxidase (SOD) and glutathione peroxidase (Gpx). Yucca did not affect the plasma neuro peptide Y (NPY), which was reduced by HT, yucca reduced circulation cholecystokinin (CCK) and hypothalamic mRNA expression of CCK. Supplementation of yucca increased the mRNA expression of both heat and cool sensing receptors. The results of the present study indicate that yucca could improve antioxidant status and attenuate the heat stress response by regulating hypothalamic temperature-sensing genes in growing chickens. Besides, yucca supplementation improved feed intake probably through modulating CCK in growing broilers under high ambient temperature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.