Each lane depicts a representative tumor lysate from a different mouse of either vehicle or Reishi treatment.
Reishi downregulates the expression of key IBC proteins in vivo. Genetic aberrations such as loss of PTEN as in SUM cells used herein make this pathway one of the most commonly disrupted in human breast cancer. The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the downstream effector, mTOR. The influences of other oncogenic pathways such as MAPK on the PI3K pathway and the known feedback mechanisms of activation have prompted the testing and development of compounds with broader effect at multiple levels to obtain a more potent antitumor activity and possibly a meaningful clinical effect.
However, these transcription factors are regulated at various levels including transcriptionally, via mRNA stability, post-translational modifications such as phosphorylation and by protein turnover.
Contrary to Jiang et al. Our in vivo studies show that Reishi treated mice have statistically significantly reduced tumor growth and tumor weight. Previous studies have shown that individual components from Reishi, such as specific polysaccharides or triterpenes inhibit invasion and metastasis in various xenograft models  , . However, our study is the first to show that an extract containing a combination of polysaccharides and triterpenes derived from the Reishi mushroom has anti-tumor growth effects in a very aggressive type of cancer.
Even though the concentration of Reishi extract that was required to demonstrate a significant difference in tumor growth is higher than the current concentration suggested for humans, the concentration used was not toxic to the mice. The lag time in tumor growth observed for the first eight weeks was seen in both vehicle and Reishi treated animals. This phenomenon was reported in a similar study where caliper measurements could not be initiated until 30 days following SUM cell inoculation at the mammary fat pad of SCID mice .
This tumorigenic effect also resembles IBC tumor formation in women, where most present without a palpable mass at the time of diagnosis and then proliferates at high rates . Necrotic centers were observed equally in some vehicle and Reshi treated mice data not shown.
Reishi treated SUM tumors showed a decrease in the levels of the Ki cell proliferation and Vimentin mesenchymal markers compared with those from the control treatment. The anti-tumor effects of Reishi at the molecular level depicted here may be the result of different compounds within the Reishi extract that are affecting and targeting various signaling pathways simultaneously.
Specifically, Reishi affects mTOR levels and therefore, activity. This result is in contrast to that seen in vitro. However, our in vitro studies presented here show Reishi treatment at early timepoints, thus it will be interesting to study the effects of Reishi on mTOR activation at the cellular level at longer exposure times to determine if it mimics the in vivo effects. Herein we demonstrated that Reishi downregulates the expression of molecules involved in this pathway, effectively circumventing the PTEN null effect.
Moreover, there seems to be an impact of convergent signaling on cell cycle progression as evidenced by a decrease in the Ki proliferation marker. In this study we also show that in vivo E-cadherin and pcatenin downregulation occur together with reduced levels of eIF4G, confirming and extending our previous findings .
Here we show that downregulation of these proteins contribute to reduced tumor growth. Similar results were found by Silvera and collaborators where eIF4G silencing results in less pcatenin mRNA translation and subsequent E-cadherin cytoplasmic re-localization, disrupting tumor spheroid formation that is necessary for IBC invasion . Based on our findings, we conclude that Reishi is an anti-cancer agent that selectively affects gene and protein expression and therefore, activity of molecules involved on cancer cells and shows tumor inhibitory effects.
This action can be correlated with reduced levels of key signaling pathways that ultimately increase cancer cell growth, proliferation and survival. To date, effects of Reishi extract have not been tested on IBC in vivo models or patients. Studies are being conducted in vivo to test the efficacy of Reishi in IBC using this SCID mouse model in combination with conventional therapy and in vitro at longer exposure times. Therefore, our findings suggest that Reishi extract could be used as a novel anticancer therapeutic for IBC patients.
Effect of Reishi in the expression of cell cycle regulatory genes. Down-regulated genes are below the horizontal black line while up-regulated genes are above. Columns show means.inspirarte-qa-fabercastell.gingaone.com/the-mindful-english-teacher-a-toolkit-for.php
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Effect of Reishi in the expression of Akt in vitro. Equal protein concentration from each sample was used for Western blot analysis with antibodies against total and phosphorylated Akt. Reishi does not affect eIF4F complex assembly at 6 h of treatment. Effect of Reishi in the expression of Akt in vivo. Equal amount of protein from each sample was used for western blot analysis with antibodies against total and phosphorylated Akt. This table includes all genes that show tendency to be significantly up- or down- regulated with 0.
Cell viability assays
We thank Dr. Suranganie F. Dharmawardhane, for help in editing this manuscript. The technical assistance of Natalia Skachkova and Dr. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Introduction Inflammatory breast cancer IBC is a rare, aggressive and lethal type of breast cancer that particularly involves hyper-activation of protein synthesis pathways.
Download: PPT. Table 1. Metabolic Labeling Protein synthesis assays were conducted as described in . Immunohistochemistry Ki expression was analyzed in paraffin-embedded sections obtained from IBC mouse tumors. Figure 1.
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Table 2. In vitro effects of 0. Figure 2. Figure 3. Reishi reduces tumor growth, tumor weight, and proliferative and mesenchymal marker expression. Figure 4. Table 3. Supporting Information. Figure S1. Figure S2. Figure S3. Figure S4. Table S1. Table S2. Acknowledgments We thank Dr.
References 1. CA: Cancer J Clin — View Article Google Scholar 2. Int immunopharmacol 6: — View Article Google Scholar 3. Life Sci — View Article Google Scholar 4. Lin ZB Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci — View Article Google Scholar 5. J Ethnopharmacol — View Article Google Scholar 6.
Sliva D Cellular and physiological effects of Ganoderma lucidum Reishi. Mini Rev Med Chem 4: — View Article Google Scholar 7.
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It makes recording wine entries simple and fun. There is a place to paste-or draw and colour if you like-the label, post comments from friends and guests, and includes easy to us A fun book to take with you to wine tastings, tours, parties, or just chilling at home alone or with friends. There is a place to paste-or draw and colour if you like-the label, post comments from friends and guests, and includes easy to use index pages. It includes a simple scoring system as well.
The page layout is simple and straightforward, with plenty of room for creating your fondest wine memories. Keep track of what you bought, where and when, and whether or not you liked it! Get A Copy. Paperback , pages. More Details Original Title. Friend Reviews. To see what your friends thought of this book, please sign up. To ask other readers questions about Wine Journal , please sign up.
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Sort order. Oct 03, Becca Misuraca rated it really liked it Shelves: first-reads , i-own. I really like the set-up of the book! One wish I do have is that it wasn't a paperback. It's something we'd like to take with us to each local winery so a hard cover would help it hold up from one winery tour to the next.
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