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Xiao-Wen Zhu, Hai-Zhen Zhu, You-Qing Zhu, Mao-Hui Feng, Jian Qi, Zhi-Fen Chen
The mechanism underlying CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4(+)CD25(+)Foxp3(+)Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Yuan Seng Wu, Ivy Chung, Won Fen Wong, Atsushi Masamune, Maw Shin Sim, Chung Yeng Looi
BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process...
October 14, 2016: Biochimica et Biophysica Acta
Ji Eun Park, Byoungduck Park, In Gyeong Chae, Do-Hee Kim, Juthika Kundu, Joydeb Kumar Kundu, Kyung-Soo Chun
After carefully checking the original data of ROS generation experiment, we found that in Fig. 3E the x-axis was incorrently labeled. ISL should be substituted with CA. The corrected version of Fig. 3E is shown below. We apologize for the error and appreciate the opportunity to correct the scientific record. All authors agree with this correction. [the original article was published in the Oncology Reports 35: 2723-2732, 2016; DOI: 10.3892/or.2016.4642].
September 29, 2016: Oncology Reports
Ying Li Gu, Guan Qun Gao, Ning Ma, Lin Lin Ye, Li Wei Zhang, Xu Gao, Zhuo Bo Zhang
The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system...
October 13, 2016: International Journal of Molecular Medicine
Li Lin, David Jou, Yina Wang, Haiyan Ma, Tianshu Liu, James Fuchs, Pui-Kai Li, Jiagao Lü, Chenglong Li, Jiayuh Lin
Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+)...
October 12, 2016: International Journal of Oncology
Jianheng Wu, Linfan Li, Guangyuan Jiang, Hui Zhan, Nannan Wang
Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues...
October 12, 2016: International Journal of Oncology
A Cacace, M Sboarina, T Vazeille, P Sonveaux
Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. Although both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione...
October 17, 2016: Oncogene
J Wu, W Liu, J P Williams, N Ratner
Neurofibromatosis type 1 (NF1) is an inherited disease in which affected patients are predisposed to develop benign Schwann cell (SC) tumours called neurofibromas. In the mouse, loss of Nf1 in the SC lineage causes neurofibroma formation. The tyrosine kinase receptor EGFR is expressed in Schwann cell precursors (SCP), which have been implicated in plexiform neurofibroma initiation. To test if EGFR activity affects neurofibroma initiation, size, and/or number, we studied mice expressing human EGFR in SCs and SCP in the context of mice that form neurofibromas...
October 17, 2016: Oncogene
M S Patton, D J Lodge, D A Morilak, M Girotti
Deficits in cognitive flexibility are prominent in stress-related psychiatric disorders, including depression. Ketamine has rapid antidepressant efficacy, but it is unknown if ketamine improves cognitive symptoms. In rats, 2 weeks chronic intermittent cold (CIC) stress impairs reversal learning, a form of cognitive flexibility mediated by the orbitofrontal cortex (OFC) that we have used previously to model cognitive dysfunction in depression. We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-induced reversal learning deficit...
October 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Franklin D Echevarria, Abigayle E Rickman, Rebecca M Sappington
OBJECTIVE: The interleukin-6 (IL-6) family of cytokines and their signal transducer glycoprotein (gp130) are implicated in inflammatory and cell survival functions in glaucoma. There are several avenues for interdependent modulation of IL-6 family members and gp130 signaling. Here we investigated whether IL-6 modulates gp130 and related neuroinflammatory, cell survival and regulatory signaling in both healthy and glaucomatous retina. METHODS: In naïve and glaucomatous (Microbead Occlusion Model), wildtype (WT) and IL-6 knockout (IL-6-/-) mice, we examined gp130 protein expression and localization, using western blot and immunohistochemistry...
August 2016: Journal of Clinical & Cellular Immunology
Toru Hosoi, Yuka Suyama, Takaaki Kayano, Koichiro Ozawa
Leptin resistance is one of the mechanisms involved in the pathophysiology of obesity. The present study showed that glucose deprivation inhibited leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) and signal transducer and activator of transcription 5 (STAT5) in neuronal cells. Flurbiprofen reversed glucose deprivation-mediated attenuation of STAT3, but not STAT5 activation, in leptin-treated cells. Glucose deprivation increased C/EBP-homologous protein and glucose regulated protein 78 induction, indicating the activation of unfolded protein responses (UPR)...
2016: Frontiers in Pharmacology
Kenichi Shinagawa, Souichi Yanamoto, Tomofumi Naruse, Akiko Kawakita, Kota Morishita, Yuki Sakamoto, Satoshi Rokutanda, Masahiro Umeda
The effect inflammation has on cancer prognosis is marked by the presence of cytokines and chemokines. Interleukin-6 (IL-6) is one a multifunctional cytokine that regulates inflammatory responses. We investigated the roles of IL-6 and STAT3 and examined the relationship between IL-6 signaling and clinicopathological factors in patients with oral squamous cell carcinoma (OSCC). We retrospectively examined 116 patients who underwent radical surgery for OSCC. IL-6 and STAT3 expression were detected by immunohistochemistry...
October 15, 2016: Pathology Oncology Research: POR
Dom-Gene Tu, Wei-Ting Lin, Cheng-Chia Yu, Shiuan-Shinn Lee, Chih-Yu Peng, Taichen Lin, Chuan-Hang Yu
BACKGROUND/PURPOSE: Previously, we successfully identified oral cancer stem cells (OCSC) displaying enhanced stemness and tumorigenic potentials. In the study, we investigated the chemotherapeutic effect of the flavonoid luteolin, commonly found in fruits and vegetables, on targeting OCSC. METHODS: Oralspheres was applied to isolate OCSC. aldehyde dehydrogenase 1 activity and CD44 positivity of OCSC with luteolin treatment were assessed by flow cytometry analysis...
October 11, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Yu Shi, Wenchao Zhou, Lin Cheng, Cong Chen, Zhi Huang, Xiaoguang Fang, Qiulian Wu, Zhicheng He, Senlin Xu, Justin D Lathia, Yifang Ping, Jeremy N Rich, Xiu-Wu Bian, Shideng Bao
Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the pro-survival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in GSCs...
October 14, 2016: Cell Death and Differentiation
Wen-Juan Lu, Scheffer C G Tseng, Shuangling Chen, Sean Tighe, Yuan Zhang, Xin Liu, Szu-Yu Chen, Chen-Wei Su, Ying-Ting Zhu
Human corneal endothelial cells (HCECs) have limited proliferative capacity due to "contact-inhibition" at G1 phase. Such contact-inhibition can be delayed from Day 21 to Day 42 by switching EGF-containing SHEM to LIF/bFGF-containing MESCM through transient activation of LIF-JAK1-STAT3 signaling that delays eventual nuclear translocation of p16(INK4a). Using the latter system, we have reported a novel tissue engineering technique by implementing 5 weekly knockdowns with p120 catenin (p120) and Kaiso siRNAs since Day 7 to achieve effective expansion of HCEC monolayers to a transplantable size with a normal HCEC density, through reprogramming of HCECs into neural crest progenitors by activating p120-Kaiso-RhoA-ROCK-canonical BMP signaling...
October 14, 2016: Scientific Reports
Qian Chen, Yonghong Gu, Shengwang Zhang, Hao Deng
This study aimed to characterize the role and mechanisms of action of suppressor of AP-1, regulated by IFN (SARI) in androgen-independent prostate cancer cells using the DU145 cell line. Prostate cancer cell lines were transfected to permit both the overexpression and inhibition of SARI. MTT assays and Transwell assays were performed to detect the effects of SARI overexpression and inhibition on the proliferation activity, invasiveness, and metastatic ability of DU145 cells. Expression of vascular endothelial growth factor (VEGF) and tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was monitored in the experimental groups using a qPCR assay and western blot analysis...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Dan Wang, Tong Xiang, Zhongquan Zhao, Kailong Lin, Pin Yin, Lupin Jiang, Zhiqing Liang, Bo Zhu
Cancer stem cells (CSCs) are a group of cells which possess the ability of self-renewing and unlimited proliferation. And these CSCs are thought to be the cause of metastasis, recurrence and resistance. Recent study has found that pro-inflammatory cytokine and chemotactic factor mediate the self-renewing and differentiation of most of CSCs. Thus we speculate that ovarian cancer stem cells (OCSCs) can also maintain the ability of self-renewing and differentiation by releasing inflammatory factor. This report we discuss the biological characteristics and the specific molecular mechanism mediated by interleukin-23 (IL-23) and its receptor on the self-renewing of OCSCs...
October 12, 2016: Oncotarget
Junxiong Wang, Shuo Yang, Xiqiang Cai, Jiaqiang Dong, Zhangqian Chen, Rui Wang, Song Zhang, Haichao Cao, Di Lu, Tong Jin, Yongzhan Nie, Jianyu Hao, Daiming Fan
Cetuximab plus chemotherapy for advanced gastric cancer (GC) shows an active result in phase 2 trials. Unfortunately, Combination of cetuximab does not provide enough benefit to chemotherapy alone in phase 3 trials. Studies have demonstrated that berberine can suppress the activation of EGFR in tumors. In this study, we evaluated whether berberine could enhance the effects of EGFR-TKIs in GC cell lines and xenograft models. Our data suggest that berberine could effectively enhance the activity of erlotinib and cetuximab in vitro and in vivo...
October 12, 2016: Oncotarget
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yun Mai, J Jessica Yu, Boris Bartholdy, Zijun Y Xu-Monette, Esther E Knapp, Fei Yuan, Hongshan Chen, B Belinda Ding, Zhihua Yao, Bhaskar Das, Yiyu Zou, Ken He Young, Samir Parekh, B Hilda Ye
Diffuse large B cell lymphomas (DLBCL) contain two major molecular subtypes, namely, the germinal center B cell-like (GCB) and the activated B cell-like (ABC) DLBCLs. It is well documented that ABC-DLBCL cases have a significantly poorer survival response than GCB-DLBCLs in both the CHOP and the R-CHOP eras. However, the underlying cause of this subtype disparity is poorly understood. Nevertheless, these clinical observations raise the possibility for an ABC-DLBCL-specific resistance mechanism that is directed towards one of the CHOP components and inadequately addressed by rituximab...
October 13, 2016: Blood
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