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https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#1
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445967/lactobacillus-casei-zhang-and-vitamin-k2-prevent-intestinal-tumorigenesis-in-mice-via-adiponectin-elevated-different-signaling-pathways
#2
Yong Zhang, Chen Ma, Jie Zhao, Haiyan Xu, Qiangchuan Hou, Heping Zhang
The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445944/angiotensin-converting-enzyme-2-overexpression-protects-against-doxorubicin-induced-cardiomyopathy-by-multiple-mechanisms-in-rats
#3
Hui Ma, Jing Kong, Yu-Lin Wang, Jun-Long Li, Nai-Hao Hei, Xin-Ran Cao, Jing-Jing Yang, Wen-Jiang Yan, Wen-Jing Liang, Hong-Yan Dai, Bo Dong
Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445620/smad4-inhibits-vegf-a-and-vegf-c-expressions-via-enhancing-smad3-phosphorylation-in-colon-cancer
#4
Xuemei Li, Xinlei Li, Xiaohong Lv, Jianbing Xiao, Baoquan Liu, Yafang Zhang
Smad4 is a critical factor in the TGF-β pathway and is involved in tumor progression and metastasis, but the role of Smad4 in colon cancer cells is unclear. The aim of this study is to explore the effect and the underlying mechanism of Smad4 on the growth, migration and apoptosis of colon cancer cells as well as vascular endothelial growth factor (VEGF)-A and VEGF-C secreted by these cells. In this study, we showed that Smad4, VEGF-A and VEGF-C are independent prognostic factors of colon cancer, and Smad4 expression was negatively correlated with VEGF-A and -C in samples...
April 26, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#5
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445259/the-role-of-stat3-and-ahr-in-the-differentiation-of-cd4-t-cells-into-th17-and-treg-cells
#6
Xingxing Liu, Hui Hu, Heng Fan, Dongmei Zuo, Zhexing Shou, Yi Liao, Zhen Nan, Qing Tang
BACKGROUND: This study aimed to investigate the role of aryl hydrocarbon receptor (AhR) and STAT3 gene during the differentiation of cluster of differentiation (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells. METHODS: First, CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one of the following treatments: Th17 group: antibodies against CD3 and CD28, 2...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28443643/faf1-phosphorylation-by-akt-accumulates-tgf-%C3%AE-type-ii-receptor-and-drives-breast-cancer-metastasis
#7
Feng Xie, Ke Jin, Li Shao, Yao Fan, Yifei Tu, Yihao Li, Bin Yang, Hans van Dam, Peter Ten Dijke, Honglei Weng, Steven Dooley, Shuai Wang, Junling Jia, Jin Jin, Fangfang Zhou, Long Zhang
TGF-β is pro-metastatic for the late-stage breast cancer cells. Despite recent progress, the regulation of TGF-β type II receptor remains uncertain. Here we report that FAF1 destabilizes TβRII on the cell surface by recruiting the VCP/E3 ligase complex, thereby limiting excessive TGF-β response. Importantly, activated AKT directly phosphorylates FAF1 at Ser 582, which disrupts the FAF1-VCP complex and reduces FAF1 at the plasma membrane. The latter results in an increase in TβRII at the cell surface that promotes both TGF-β-induced SMAD and non-SMAD signalling...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28442634/pharmacologic-targeting-erk1-2-attenuates-the-development-and-progression-of-hyperuricemic-nephropathy-in-rats
#8
Na Liu, Liuqing Xu, Yingfeng Shi, Lu Fang, Hongwei Gu, Hongrui Wang, Xiaoqiang Ding, Shougang Zhuang
The pathogenesis of hyperuricemia-induced chronic kidney disease is largely unknown. In this study, we investigated whether extracellular signal-regulated kinases1/2 (ERK1/2) would contribute to the development of hyperuricemic nephropathy (HN). In a rat model of HN induced by feeding mixture of adenine and potassium oxonate, increased ERK1/2 phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, in parallel with diminished levels of renal function and increased urine microalbumin excretion...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28441730/regulatory-mirnas-in-colorectal-carcinogenesis-and-metastasis
#9
REVIEW
Yongchen Guo, Yonghua Bao, Wancai Yang
Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441080/color-coded-intravital-imaging-demonstrates-a-transforming-growth-factor-beta-tgf-%C3%AE-antagonist-selectively-targets-stromal-cells-in-a-human-pancreatic-cancer-orthotopic-mouse-model
#10
Takashi Murakami, Yukihiko Hiroshima, Kentaro Miyake, Ho Kyoung Hwang, Tasuku Kiyuna, Jonathan C DeLong, Thinzar M Lwin, Ryusei Matsuyama, Ryutaro Mori, Takafumi Kumamoto, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M Hoffman
Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-beta (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP)...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28441069/low-doses-of-igg-from-atopic-individuals-can-modulate-in-vitro-ifn-%C3%AE-production-by-human-intra-thymic-tcd4-and-tcd8-cells-an-ivig-comparative-approach
#11
Fábio da Ressureição Sgnotto, Marília Garcia de Oliveira, Aline Aparecida de Lima Lira, Luciana Bento-de-Souza, Alberto José da Silva Duarte, Jefferson Russo Victor
The regulatory effect of allergic responses induced by IgG antibodies on human intra-thymic cells has not been reported in the literature. The aim of this study was to evaluate the possible differential effect of purified IgG from atopic and non-atopic individuals on human intra-thymic αβT cell cytokine production. Thymic tissues were obtained from 14 patients who were less than seven days old. Additionally, blood samples were collected from atopic and non-atopic volunteers. Thymocytes and peripheral blood mononuclear cells were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production was assessed...
April 25, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28441064/bacillus-calmette-guerin-alleviates-airway-inflammation-and-remodeling-by-preventing-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition
#12
Xinrui Tian, Xinli Tian, Rujie Huo, Qin Chang, Guoping Zheng, Yan Du, Yan Chen, Bo Niu
Bacillus Calmette-Guerin (BCG) is a potent agent for the prevention of tuberculosis. Current studies have regarded BCG as an immunomodulator. However, there is little information on whether it can be used to inhibit airway inflammation and airway remodeling caused by asthma. Therefore, in this study, we investigate the role of epithelial-mesenchymal transition (EMT) in airway inflammation and airway remodeling as well as the possible therapeutic mechanism of BCG for the treatment of asthma. Wistar rats were sensitized and challenged by ovalbumin for 2 weeks or 8 weeks...
April 25, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28440736/levistilide-a-inhibits-angiogenesis-in-liver-fibrosis-via-vascular-endothelial-growth-factor-signaling-pathway
#13
Zhi-Min Zhao, Hong-Liang Liu, Xin Sun, Tao Guo, Li Shen, Yan-Yan Tao, Cheng-Hai Liu
Levistilide A (C24H28O4, molecular weight = 380.48) derived from Angelica sinensis (Danggui) has been reported to inhibit hepatic stellate cell proliferation. This study investigated the effects of levistilide A on liver fibrosis relating to angiogenesis, particularly on the characteristic change in liver sinusoidal endothelial cells. LX-2 cells were activated by TGF-β1, and the human hepatic sinusoidal endothelial cells (HHSECs) were induced by endothelial cell growth supplement. Cell viability was detected using a methylthiazoldiphenyl-tetrazolium bromide assay; F-actin was visualized through the fluorescence probe method; cell proliferation was examined using the EdU kit; antiangiogenesis activity was assessed using the tube formation assay and transgenic zebrafish model...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28440536/selected-bone-morphogenetic-proteins-the-possibility-of-their-use-in-the-diagnostics-and-therapy-of-severe-asthma
#14
Marcelina Koćwin, Mateusz Jonakowski, Marcelina Przemęcka, Michał Panek, Piotr Kuna
Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates processes in embryonic and post-embryonic development...
2017: Advances in Respiratory Medicine
https://www.readbyqxmd.com/read/28440482/kmup-1-attenuates-high-glucose-and-transforming-growth-factor-%C3%AE-1-induced-pro-fibrotic-proteins-in-mesangial-cells
#15
Sheng-Hsuan Lin, Ing-Jun Chen, Chao-Tang Chuang, Wan-Ting Ho, Lea-Yea Chuang, Jinn-Yuh Guh
We have previously demonstrated that KMUP-1, a xanthine-based nitric oxide enhancer, attenuates diabetic glomerulosclerosis, while increasing renal endothelial nitric oxide synthase expression in rats. However, the anti‑fibrotic mechanisms of KMUP‑1 treatment in diabetic nephropathy in terms of cell biology and transforming growth factor-β1 (TGF‑β1) remain unclear. Therefore, the present study involved investigating the effects of KMUP‑1 on high glucose (HG) or TGF‑β1‑induced pro‑fibrotic proteins in mouse mesangial (MES13) cells, and the effects of KMUP‑1 on streptozotocin (STZ)‑induced diabetic rats...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440452/bambi-overexpression-together-with-%C3%AE-sitosterol-ameliorates-nsclc-via-inhibiting-autophagy-and-inactivating-tgf-%C3%AE-smad2-3-pathway
#16
Xingchun Wang, Minjie Li, Mengyao Hu, Ping Wei, Wei Zhu
Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA‑BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440420/wound-healing-effect-of-an-astragalus%C3%A2-membranaceus-polysaccharide-and-its-mechanism
#17
Bingjiang Zhao, Xuanfen Zhang, Wei Han, Ju Cheng, Yonghong Qin
In the present study, a novel polysaccharide, APS2-1, was isolated and purified from Astragalus membranaceus using DEAE-cellulose and Sephadex G-100 chromatography. The effect of APS2‑1 on the promotion of wound healing was evaluated and its preliminary mechanism was investigated. In vitro experiments showed that APS2‑1 was able to promote human skin fibroblast (HSF) propagation and accelerate cell cycle progression. For further examination, a scalded mice model was used to verify the effect of APS2‑1 and investigate its mechanism of action...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440409/microrna-145-regulates-the-differentiation-of-human-adipose-derived-stem-cells-to-smooth-muscle-cells-via-targeting-kr%C3%A3-ppel-like-factor-4
#18
Kaisaier Aji, Yun Zhang, Abudusaimi Aimaiti, Yujie Wang, Mulati Rexiati, Baihetiya Azhati, Hamulati Tusong, Lei Cui, Chen Wang
Understanding the molecular mechanisms underlying human adipose-derived stem cell (hASC) differentiation to smooth muscle may contribute to the development of effective therapies for relevant muscle defects, such as bladder wall and urethral defects. A previous study described the differentiation of hASCs to smooth muscle cells (SMCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein‑4 (BMP4) treatment. The present study investigated whether microRNA-145 (miR‑145) may be involved in the process of hASC differentiation...
April 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440392/suppressive-role-of-diallyl-trisul%C3%AF-de-in-the-activated-platelet-mediated-hematogenous-metastasis-of-mda-mb-231-human-breast-cancer-cells
#19
Yuping Liu, Yang Zhao, Yingyu Wang, Pingting Zhu, Zhonghong Wei, Siliang Wang, Li Tao, Zhaoguo Liu, Hongyan Wu, Xiaobo Sheng, Yin Lu
Accumulating evidence has indicated that garlic consumption may reduce the risk of developing several types of cancer, and extensive studies have revealed the effects of its bioactive component, diallyl trisulfide (DATS), on the proliferation and apoptosis of tumor cells. The present study was undertaken to examine whether DATS affects hematogenous metastasis. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we attempted to demonstrate the role of DATS in the metastatic behavior of MDA-MB-231 human breast cancer cells, which were co-incubated with activated platelets...
April 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440207/epithelial-mesenchymal-transition-in-cancer-progression-preventive-phytochemicals
#20
Soorya Parathodi Illam, Arunaksharan Narayanankutty, Shaji Edappilly Mathew, Remya Valsalakumari, Rosemol M Jacob, Achuthan Chathrattil Raghavamenon
BACKGROUND: Epithelial-Mesenchymal Transition (EMT) is the conversion of epithelial cells into mesenchymal phenotype generally observed during embryogenesis and wound healing as well as in malignant transformation. Several signaling pathways and transcription factors associated with EMT have been explored. Dietary phytochemicals are multi-targeted agents that interfere with these pathways, assume preventive potential against pathologic EMT. OBJECTIVE: Present review aims to provide a detailed description on the nature, characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention...
April 24, 2017: Recent Patents on Anti-cancer Drug Discovery
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