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Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Laura M Divine, Mai R Nguyen, Eric Meller, Riva A Desai, Batool Arif, Erinn B Rankin, Katherine H Bligard, Cherise Meyerson, Ian S Hagemann, Maria Massad, Premal H Thaker, Andrea R Hagemann, Carolyn K McCourt, Matt A Powell, David G Mutch, Katherine C Fuh
The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9...
October 13, 2016: Oncotarget
Annu Makker, Madhu Mati Goel, Abbas Ali Mahdi, Vikram Bhatia, Vinita Das, Anjoo Agarwal, Amita Pandey
BACKGROUND & OBJECTIVES: Despite their high occurrence and associated significant level of morbidity manifesting as spectrum of clinical symptoms, the pathogenesis of uterine leiomyomas (ULs) remains unclear. We investigated expression profile of tumour suppressor genes PTEN (phosphatase and tensin homolog deleted on chromosome ten) and LKB1 (liver kinase B1), and key signaling components of P13K (phosphatidylinositol 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in leiomyomas and adjacent normal myometrium in women of reproductive age, to explore the possibility of targeting this pathway for future therapeutic implications...
May 2016: Indian Journal of Medical Research
So Min Lyu, Ju Yeon Wu, Ji Yeon Byun, Hae Young Choi, Sang Hee Park, You Won Choi
BACKGROUND: The role of the phosphatidylinositol-3 kinase signaling pathway in the development of acral melanoma has recently gained evidence. Phosphatase and tensin homologue (PTEN), one of the key molecules in the pathway, acts as a tumor suppressor through either an Akt-dependent or Akt-independent pathway. Akt accelerates degradation of p53. OBJECTIVE: We assessed the expression of PTEN, phospho-Akt (p-Akt), and p53 by immunohistochemistry in benign acral nevi, acral dysplastic nevi, and acral melanomas in the radial growth phase and with a vertical growth component...
October 2016: Annals of Dermatology
Hongyu Shen, Dandan Wang, Liangpeng Li, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
BACKGROUND AND PURPOSE: Acquisition of resistance to adriamycin (ADR) is one of the most important clinical obstacles in the treatment of breast cancer, but the molecular mechanisms underlying sensitivity to ADR remain elusive. In our previous study, through miRNA microarray and experiments, we have emphasized that miR-222 could promote the ADR-resistance in breast cancer cells. The aim of this study was to explore the possible mechanism by which miR-222 affects sensitivity to ADR. METHODS: Through pathway enrichment analyses for miR-222, we found that PTEN/Akt/FOXO1 signaling pathway may be of importance...
October 13, 2016: Gene
Pamela T Soliman, Qian Zhang, Russell R Broaddus, Shannon N Westin, David Iglesias, Mark F Munsell, Rosemarie Schmandt, Melinda Yates, Lois Ramondetta, Karen H Lu
OBJECTIVE: Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. METHODS: In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery...
October 13, 2016: Gynecologic Oncology
Mincione Gabriella, Di Marcantonio Maria Carmela, Tarantelli Chiara, Savino Luca, Ponti Donatella, Marchisio Marco, Lanuti Paola, Sancilio Silvia, Calogero Antonella, Di Pietro Roberta, Muraro Raffaella
Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas...
October 6, 2016: Oncotarget
Weiqing Liu, Dong Wang, Wenjuan Hong, Yi Yu, Jinsong Tang, Jicai Wang, Fang Liu, Xiufeng Xu, Liwen Tan, Xiaogang Chen
Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test...
October 7, 2016: Behavioural Brain Research
Dan-Dan Wang, Su-Jin Yang, Xiu Chen, Hong-Yu Shen, Long-Ji Luo, Xiao-Hui Zhang, Shan-Liang Zhong, Jian-Hua Zhao, Jin-Hai Tang
The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27 (kip1) pathway. Firstly, in vivo, we verified that miR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S)...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Aditya Shetty, Subramanyam Dasari, Souresh Banerjee, Taher Gheewala, Guoxing Zheng, Aoshuang Chen, Andre Kajdacsy-Balla, Maarten C Bosland, Gnanasekar Munirathinam
Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells...
September 27, 2016: Urologic Oncology
Jen-Chung Ko, Hao-Yu Zheng, Wen-Ching Chen, Yi-Shuan Peng, Chia-Hung Wu, Chia-Li Wei, Jyh-Cheng Chen, Yun-Wei Lin
Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells...
September 22, 2016: Biochemical Pharmacology
Purnima Gupta, Supriya Srivastav, Shriya Saha, Pijush K Das, Anindita Ukil
In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival...
November 1, 2016: Cell Death and Differentiation
Akhilendra Kumar Maurya, Manjula Vinayak
Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110α of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level...
September 23, 2016: Leukemia & Lymphoma
Luocheng Li, Zhiwei Wang, Xiaoping Hu, Ting Wan, Hongbing Wu, Wanli Jiang, Rui Hu
Dysregulation of autophagy in endothelial cells plays a vital role in cardiovascular dysfunction and atherosclerosis. Accumulating evidence shows that miRNAs regulate autophagy in various cell types by targeting autophagy-related genes. In the present study, we found that a co-culture of human umbilical vein endothelial cells (HUVECs) with human aortic smooth muscle cells (HAoSMCs) inhibited autophagy activity in HUVECs. Furthermore, we isolated exosomes secreted by HAoSMCs, and confirmed that the exosomes contain miR-221/222...
October 14, 2016: Biochemical and Biophysical Research Communications
Xue Liu, Ershun Liang, Xiuhui Song, Zhanhui Du, Yun Zhang, Yuxia Zhao
Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl-prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone...
October 7, 2016: Biochemical and Biophysical Research Communications
S R Ladyman, D R Grattan
Despite increased leptin concentrations during pregnancy, fat mass and food intake are increased. The satiety response to central leptin is suppressed indicating a state of leptin insensitivity in the hypothalamus. While the regulation of food intake is a major function of leptin, this hormone also influences a while range of functions within the body. These actions include regulation of glucose homeostasis, which undergoes major adaptation in the maternal body to generate optimal conditions for fetal development and growth...
September 13, 2016: Journal of Neuroendocrinology
Yu Zhang, Suning Huang, Yuhua Leng, Xin Chen, Tiantian Liu, Hanlin Wang, Fanglin Wei, Dianzhong Luo, Gang Chen, Zhuxin Wei
BACKGROUND: Previously, we found that the expression of decoy receptor 3 (DcR3) in gliomas was significantly upregulated compared to normal brain tissues. However, the effect of DcR3-specific small interfering RNA (siRNA) on cell biological function of glioma cells remains incompletely understood. OBJECTIVE: The aim of this study was to explore the effect of DcR3 siRNA on cell growth and apoptosis of glioma cells and to investigate the potential downstream pathways affected by DcR3...
2016: OncoTargets and Therapy
JiaXin Zong, YunTian Li, DaYong Du, Yang Liu, YongJun Yin
Intraplaque angiogenesis has been recognized as an important risk factor for the rupture of advanced atherosclerotic plaques in recent years. CD147, also called Extracellular Matrix Metalloproteinase Inducer, has been found the ability to promote angiogenesis in many pathological conditions such as cancer diseases and rheumatoid arthritis via the up-regulation of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis. We investigated whether CD147 would also induce the up-regulation of VEGF in the foam cells formation process and explored the probable signaling pathway...
November 1, 2016: Archives of Biochemistry and Biophysics
Takeshi Kaneko, Hironari Dehari, Takanori Sasaki, Tomohiro Igarashi, Kazuhiro Ogi, Jun-Ya Okamoto, Mayumi Kawata, Jun-Ichi Kobayashi, Akihiro Miyazaki, Kenji Nakamori, Hiroyoshi Hiratsuka
OBJECTIVE: Epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis induced by hypoxia. Here, we examined whether phosphorylation of GSK3-β via phosphoinositide 3-kinase (PI3 K)/Akt signaling is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma (OSCC). STUDY DESIGN: Experiments were performed in OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was assessed by Matrigel invasion assays and wound healing assays...
June 22, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Xue Zhao, Jun Hao, Huijun Duan, Zanhua Rong, Fan Li
In the present study, the effect and mechanism of periostin on renal proliferation and extracellular matrix accumulation of lupus mice were investigated. MRL/lpr mice, known as lupus mice, were revealed to show enhanced periostin, proliferating cell nuclear antigen (PCNA), and extracellular matrix accumulation in the kidney accompanied by increased serum platelet-derived growth factor (PDGF). Again, cultured mouse mesangial cells (MMCs) were treated with PDGF, then periostin, and PCNA and secreted fibronectin were detected...
September 2, 2016: Experimental Biology and Medicine
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