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Abstract Background: One of the main challenges in cancer prevention is the finding of tumor microenvironment factors that increase breast cancer susceptibility. The stromal matrix of the breast is largely composed of adipose and fibroblast tissue, and therefore it is critical to know how alterations in these constituents influence the onset of stromal fibrosis and cancer progression. In NeuT/ATTAC mice with SF, increased expression of the immune-related genes Cxcl1, Ly6d, and CD14 was found in mice with and without SF, as well as acute phase proteins Saa1 and S100a6. Conclusion: Induction of SF in an erbB2-dependent breast cancer model resulted in a tumor microenvironment more conducive to tumor formation and immune tolerance.
Source link: https://doi.org/10.1158/1538-7445.am2017-5892
We performed micro-computed tomographic analysis of femurs and vertebrae collected from a newly published report demonstrating that selenium supplementation reduced male mammary tumor formation in MMTV-PyMT mice to determine the effects of breast cancer on skeletal health. The presence of mammary tumors in bone density, trabecular thickness, and bone mineral density reduced bone volume fraction, trabecular thickness, and bone mineral density, as well as raising the structure model index in femoral trabecular bone relative to age-matched non-tumor-bearing mice. Except that vertebral trabeculae nor femoral and vertebral cortical bone were affected, mammary tumor formation did not influence vertebral trabeculae nor femoral and vertebral cortical bone, it did not influence vertebral trabeculae, but vertebral bone thickness decreased significantly. In this male MMTV-PyMT breast cancer model, mammary tumorigenesis causes bone loss and dietary selenium supplementation at 2. 5 mg Se/kg, which is antitumorigenic, does not influence mammary tumor-associated bone loss. Male MMTV-PyMT mice have bone loss, but dietary selenium supplementation does not have a role [abstract].
Source link: https://doi.org/10.1158/1538-7445.am2017-253
Abstract Male breast cancer makes up 1% of all breast cancers and less than 1% of all cancers in men in the United States. In MMTV-PyMT mice, the current research investigated the effects of selenium supplementation in male breast carcinogenesis. According to the control diet, Selenium supplementation reduced mammary tumor formation by 28% and tumor burden by 84%, respectively. Tumor progression was characterized as the change in tumor volume from the detection of the first palpable mammary tumor to its termination ten weeks later. When compared to the control group, selenium supplementation reduced the number of metastases by 83%. In conclusion, dietary supplementation with selenium in the form of methylseleninic acid reduces male breast carcinogenesis and mouse metastasis. Selenium, according to reports, can be helpful in male breast cancer prevention.
Source link: https://doi.org/10.1158/1538-7445.am2017-249
Abstract Lung cancer is the leading cause of cancer-related mortality worldwide, and 85 percent of lung cancer cases are due to tobacco use. In 25% of tobacco-associated lung cancers, triggering mutations in K-ras have been found in 25% of lung adenocarcinomas. We previously reported that deletion of the IGF-1 gene or reduction of systemic IGF-1 levels using the anti-antidiabetic drug metformin dramatically reduced tumor burden using mouse models of K-ras-driven lung tumorigenesis. For 12 weeks, 9 week old C57Bl/6J and A/J mice were fed standard cereal, high-carbohydrate, or high-fat diets. To determine the effect of diet on systemic IGF-1 levels, 9 week old C57Bl/6J and A/J mice were fed high-fat, high-carbohydrate, or high-fat diets for nine weeks. Plasma IGF-1 and insulin levels were elevated in both strains of mice fed a HFD, but not in mice fed a high carbohydrate diet. Using two mouse models, we then investigated the effects of HFD on lung tumorigenesis. In comparison to littermates on a cereal diet, the mice's HFD caused the Lung tumor burden in the mice fed HFD was up 2. 7 percent. There was no correlation between the weight of the mice and lung tumor burden in either model. Interestingly, both immunohistochemical analysis and flow cytometry showed a 50% decrease in the number of TIL in mice fed HFD relative to mice eating a cereal diet. These findings may indicate that a high fat diet raises lung tumorigenesis by raising systemic IGF-1 levels and creating an immune-permissive tumor microenvironment. [abstract]: Increased NSCLC tumorigenesis in mice fed a high fat diet is associated with elevated plasma IGF-1 levels and PD-1 expression in CD4+ tumor-infiltrating lymphocytes [abstract].
Source link: https://doi.org/10.1158/1538-7445.am2017-237
In several forms of tumorigenesis, Inflammatory signaling downstream of Toll-like receptor 4 is a trigger factor, but its role in solar UV-induced skin carcinogenesis remains unclear. Increased TLR4 expression was seen in association with tumorigenic transition from normal skin to actinic keratosis and cutaneous squamous cell carcinoma, according to our recently published study, based on immunohistochemical testing of NMSC tissue microarrays and proteomic analysis of reverse-phase protein microarrays from banked human tissue. Topical resatorvid antagonized UV-induced stress signaling in a new acute exposure model in SKH-1 mice, potentiating UV-induced epidermal apoptosis, thereby potentiating UV-induced epidermal apoptosis. For the first time in the current study, we show that pharmacological inhibition of TLR4 using the specific antagonist resatorvid blocks UV-induced tumor formation in SKH-1 mice. One hour before UV exposure, the control group had a topical vehicle on their backs 1 hour before. The u201cInterventionu201d company received a vehicle 1hr before each UV treatment, but a week after it was terminated, the u201cInterventionu201d group was switched to topical resatorvid. Both tumor area and tumor multiplicity were significantly reduced in both tumor size and tumor multiplicity in the Prevention model. As measured by IHC and RPPA results, suppression of UV-driven signaling in murine skin harvested at week 14 was also confirmed. These results, which were compiled using resatorvid in a murine photocarcinogenesis model, suggest that pharmacological TLR4 antagonism could be a novel molecular tactic for topical prevention of solar UV-induced NMSC. In SKH-1 mice, pharmacological TLR4 antagonism is triggered by topical resatorvid blocks solar UV-induced skin tumor formation [abstract].
Source link: https://doi.org/10.1158/1538-7445.am2017-2244
Tocotrienol, a natural vitamin E form abundant in annatto seeds, has been shown to reduce NF-u03baB in pancreatic cells, and has been shown to reduce NF-u03baB. However, the effect of u03b4TE on immune cell activation and the underlying mechanism has yet to be investigated. Using the fact that A20 construction intu2019s anti-NF-u03baB influence, Knockout of a partially reduced u03b4TE's anti-NF-u03baB effect, supports the belief that A20 installation in the wake of u03b4TE's anti-NF-u03baB demonstrations. We discovered that u03b4TE-rich mixed tocotrienols reduced colon tumorigenesis, as shown by a 36 percent decrease in multiplicity of large adenomatous polyps and reduced tumor surface area by 31%. We found that u03b4TE has potent anti-NF-u03baB activity, as well as this vitamin E form and its metabolite, which can prevent colitis-promoted colon tumor formation in mice. Vitamin E deb4-tocotrienol reduces NF-u03baB activation in mice by up-regulating A20 in macrophages and suppresses colitis-promoted colon tumor formation in mice [abstract].
Source link: https://doi.org/10.1158/1538-7445.am2017-2242
The direct effects of tofogliflozin on human HCC cell proliferation were also investigated. The growth of hepatic pre-neoplastic lesions was markedly reduced in mice treated with tofogliflozin, and hepatic steatosis and inflammation was markedly reduced, as indicated by the NAFLD activity score in comparison to those in the control mice. Tofogliflozin treatment reduced serum glucose and free fatty acid, and mRNA expression levels of pro-inflammatory markers in the liver. These results show that tofogliflozin delayed the early stages of obesity- and NAFLD-related liver carcinogenesis by attenuating chronic inflammation and steatosis in the liver, but that the drug had no effect on cell proliferation. [abstract]: Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on liver tumor formation in obese and diabetic mice [abstract].
Source link: https://doi.org/10.1158/1538-7445.am2017-2235
Social isolation, according to recent animal studies in our lab, may be able to mask the effects of a high fat diet on carcinogen-induced mammary cancer. We measured and compared metabolic endpoints in abdominal and mammary gland adipose cells in 7- and 23-week-old female mice kept in social isolation for either 4 or 20 weeks, respectively, to find out how these metabolic effects manifest. To investigate how these metabolic reactions manifest, we examined how these metabolic consequences manifested, we investigated how these metabolic pathways manifested. Four groups of C56BL/6 mice were tested: control diet fed group housed mice, HF diet fed group housed mice, control diet fed socially isolated mice, and HF diet fed socially isolated mice. abdominal adipocytes of HF diet-G mice were significantly larger than in C-G control mice at 7 weeks of age, indicating adipocyte hypertrophy, a hallmark of obesity. Both in C-ISO and HF-ISO reduced the presence of beige adipocytes in the mammary adipocytes of socially isolated mice's socially isolated mice, suggesting the presence of beige adipocytes in the mammary adipocytes. Beige adipocytes are white adipocytes with an appearance and function similar to brown adipocytes that dissipate energy. In HF-G, HF-ISO, and C-ISO, beige specific adipocyte markers in abdominal and mammary adipose tissue revealed increased staining for Uc1 and Pgc1 in abdominal and Mammary adipose tissue, in comparison to C-G controls. Our results show that social loneliness can influence the phenotype and function of abdominal and mammary adipocytes, and that these changes may play a role in breast cancer risk and mortality in socially isolated women and animal models.
Source link: https://doi.org/10.1158/1538-7445.am2016-lb-316
We developed the MMTV-driven polyoma middle T BC model mice with an inducible mammary epithelium-specific deletion of the insulin receptor. In the INSR knockout mice, the mammary gland's deletion of INSR in the mammary gland considerably reduced the mammary tumour burden relative to the INSR wildtype controls, but not affecting the tumour formation. The average weight of individual tumors was similar across the genotypes, indicating that deletion of INSR increased the tumor initiation potential of the epithelial cells rather than tumor formation. The INSR knockout mice had half the number of metastases compared to the INSR wildtype controls, which caused mammary tumour metastasis to the lung.
Source link: https://doi.org/10.1158/1538-7445.am2016-664
We also produced a doxycycline-inducible ES cell line and transgenic mouse in vivo, both of which overexpress a phosphomimic mutant of RXRu03b1. In the Mouse Embryonic Fibroblasts derived from the transgenic mice, the transcriptional functions of Retinoid X Receptor Response Element were significantly reduced, indicating that mouse retinoid signaling via RXRu03b1 were reduced. In addition, the production of liver tumors caused by liver carcinogen diethylnitrosamine in the transgenic mice that overexpress T82D/S260D protein in the liver was enhanced. The elevated liver tumors in the transgenic mice, not apoptosis, were triggered by cell cycle progression rather than the inhibition of apoptosis. These findings reveal that the phospho-modification of RXRu03b1 can aid in the formation of DEN-induced liver tumors in mice by the stimulation of u03b2-catenin signaling pathways.
Source link: https://doi.org/10.1158/1538-7445.am2016-4052
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