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https://www.readbyqxmd.com/read/29667771/long-non-coding-rna-snhg14-contributes-to-gastric-cancer-development-through-targeting-mir-145-sox9-axis
#1
Zhao Liu, Yan Yan, Sizhe Cao, Yi Chen
This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time...
April 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29667769/targeting-the-phosphatidylinositol-3-kinase-akt-mechanistic-target-of-rapamycin-signaling-pathway-in-b-lineage-acute-lymphoblastic-leukemia-an-update
#2
REVIEW
Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Marco Vitale, James A McCubrey, Silvano Capitani, Luca M Neri
Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease...
April 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29666061/deptor-is-a-novel-target-of-wnt-%C3%AE-catenin-c-myc-and-contributes-to-colorectal-cancer-cell-growth
#3
Qingding Wang, Yuning Zhou, Piotr Rychahou, Jennifer W Harris, Yekaterina Y Zaytseva, Jinpeng Liu, Chi Wang, Heidi L Weiss, Chunming Liu, Eun Y Lee, B Mark Evers
Activation of the Wnt/β-catenin signaling pathway drives colorectal cancer (CRC) growth by deregulating expression of downstream target genes including the c-Myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in CRC have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to CRC growth and metastasis. Here we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/β-catenin/c-Myc signaling in CRC cells. Inhibition of Wnt/β-catenin or knockdown of c-Myc decreased, while activation of Wnt/β-catenin or overexpression of c-Myc increased, the expression of Deptor...
April 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29665365/dehydroeffusol-inhibits-viability-and-epithelial-mesenchymal-transition-through-the-hedgehog-and-akt-mtor-signaling-pathways-in-neuroblastoma-cells
#4
Kang He, Guoqing Duan, Yanyang Li
Neuroblastoma (NB) is the most predominant extracranial solid tumor of infancy in the world. However, current chemotherapy has limited efficacy for more advanced stages of NB due to acquired chemoresistance or acute toxicity in NB patients. Therefore, effective novel anti-NB drugs are desperately needed. The present study aimed to investigate the effects of dehydroeffusol (DHE), a phenanthrene isolated from J. effuses, on NB cells and its underlying mechanism. The results showed that DHE treatment effectively inhibited NB cell viability in a dose-dependent manner...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29662627/analysis-of-the-pi3k-akt-mtor-pathway-in-penile-cancer-evaluation-of-a-therapeutically-targetable-pathway
#5
Anthony Adimonye, Elzbieta Stankiewicz, Sakunthala Kudahetti, Giorgia Trevisan, Brendan Tinwell, Cathy Corbishley, Yong-Jie Lu, Nick Watkin, Daniel Berney
Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). Methods: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662193/spag5-promotes-proliferation-and-suppresses-apoptosis-in-bladder-urothelial-carcinoma-by-upregulating-wnt3-via-activating-the-akt-mtor-pathway-and-predicts-poorer-survival
#6
J Y Liu, Q H Zeng, P G Cao, D Xie, F Yang, L Y He, Y B Dai, J J Li, X M Liu, H L Zeng, X J Fan, L Liu, Y X Zhu, L Gong, Y Cheng, J D Zhou, J Hu, H Bo, Z Z Xu, K Cao
Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29658590/cucurbitacin-d-impedes-gastric-cancer-cell-survival-via-activation-of-the-inos-no-and-inhibition-of-the-akt-signalling-pathway
#7
Yan Zhen Zhang, Chun Feng Wang, Lian Feng Zhang
Cucurbitacin D (CuD), isolated from plants from the Cucurbitaceae family, is a potential antitumour agent since it inhibits proliferation, migration and metastasis of cancer cells. Despite CuD antitumour activity in cancer cells, the effects of CuD on gastric cancer cell lines remain unclear. The present study aimed to investigate the effects of CuD on gastric cancer cell growth and death. Human gastric cancer cell lines (AGS, SNU1 and Hs746T) were cultured and treated with different concentrations of CuD (0, 0...
April 10, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29656208/akt-mtor-and-nf-%C3%AE%C2%BAb-pathway-activation-in-treponema-pallidum-stimulates-m1-macrophages
#8
Li-Rong Lin, Zheng-Xiang Gao, Yong Lin, Xiao-Zhen Zhu, Wei Liu, Dan Liu, Kun Gao, Man-Li Tong, Hui-Lin Zhang, Li-Li Liu, Yao Xiao, Jian-Jun Niu, Fan Liu, Tian-Ci Yang
The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1β and TNF-α) expression in a dose- and time-dependent manner...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29655701/apoptosis-and-pro-death-autophagy-induced-by-a-spirostanol-saponin-isolated-from-rohdea-chinensis-baker-n-tanaka-synonym-tupistra-chinensis-baker-on-hl-60-cells
#9
Xiaomin Yi, Limin Xiang, Yuying Huang, Yihai Wang, Xiangjiu He
BACKGROUND: Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655686/physakengose-g-induces-apoptosis-via-egfr-mtor-signaling-and-inhibits-autophagic-flux-in-human-osteosarcoma-cells
#10
Hua Lin, Chao Zhang, Hao Zhang, Yuan-Zheng Xia, Chuan-Yang Zhang, Jie Luo, Lei Yang, Ling-Yi Kong
BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. PURPOSE: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29652546/ataxia-telangiectasia-mutated-kinase-deficiency-impairs-autophagic-response-early-during-myocardial-infarction
#11
Patsy R Thrasher, Stephanie L C Scofield, Suman Dalal, Claire C Crawford, Mahipal Singh, Krishna Singh
Ataxia-telangiectasia mutated kinase (ATM) is activated in response to DNA damage. We have previously shown that ATM plays a critical role in myocyte apoptosis and cardiac remodeling following myocardial infarction (MI). Here, we tested the hypothesis that ATM deficiency results in autophagic impairment in the heart early during MI. MI was induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery (LAD). Structural and biochemical parameters of the heart were measured 4 hours following LAD ligation...
April 13, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29651246/lactone-component-from-ligusticum-chuanxiong-alleviates-myocardial-ischemia-injury-through-inhibiting-autophagy
#12
Gang Wang, Guoliang Dai, Jie Song, Maomao Zhu, Ying Liu, Xuefeng Hou, Zhongcheng Ke, Yuanli Zhou, Huihui Qiu, Fujing Wang, Nan Jiang, Xiaobin Jia, Liang Feng
The dysregulation of autophagy is associated with a series of cardiovascular diseases, such as myocardial ischemia injury. Lactone component from Ligusticum chuanxiong (LLC) is the major constituent of the traditional Chinese herb L. chuanxiong Hort., which has been reported to hold potential cardioprotective effects. In this study, to determine whether LLC protects the heart through regulation of autophagy, we explored the effects of LLC on cardioprotection and autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29649487/expression-patterns-and-role-of-pten-in-rat-peripheral-nerve-development-and-injury
#13
Hui Chen, Jianping Xiang, Junxia Wu, Bo He, Tao Lin, Qingtang Zhu, Xiaolin Liu, Canbin Zheng
Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons...
April 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29642553/genomic-profiling-on-an-unselected-solid-tumor-population-reveals-a-highly-mutated-wnt-%C3%AE-catenin-pathway-associated-with-oncogenic-egfr-mutations
#14
Jingrui Jiang, Alexei Protopopov, Ruobai Sun, Stephen Lyle, Meaghan Russell
Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples...
April 9, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29642462/new-challenges-in-targeting-signaling-pathways-in-acute-lymphoblastic-leukemia-by-ngs-approaches-an-update
#15
REVIEW
Adrián Montaño, Maribel Forero-Castro, Darnel Marchena-Mendoza, Rocío Benito, Jesús María Hernández-Rivas
The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures...
April 7, 2018: Cancers
https://www.readbyqxmd.com/read/29627363/nesfatin-1-functions-as-a-switch-for-phenotype-transformation-and-proliferation-of-vsmcs-in-hypertensive-vascular-remodeling
#16
Qing-Bo Lu, Hui-Ping Wang, Zi-Han Tang, Han Cheng, Qiong Du, Yuan-Ben Wang, Wu-Bing Feng, Ke-Xue Li, Wei-Wei Cai, Li-Ying Qiu, Hai-Jian Sun
The phenotypic transformation from differentiated to dedifferentiated vascular smooth muscle cells (VSMCs) plays a crucial role in VSMC proliferation and vascular remodeling in many cardiovascular diseases including hypertension. Nesfatin-1, a multifunctional adipocytokine, is critically involved in the regulation of blood pressure. However, it is still largely unexplored whether nesfatin-1 is a potential candidate in VSMC phenotypic switch and proliferation in hypertension. Experiments were carried out in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), human VSMCs and primary rat aortic VSMCs...
April 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29627129/-new-nosological-and-therapeutic-perspectives-in-syndromic-vascular-malformations-with-a-vein-lymphatic-component
#17
P Henneton, S Mestre, M Nou, I Quere
Vascular malformations are poorly recognized constitutional anomalies which arises during early childhood. Several classifications tried to draw a distinction across the different entities. Recent advances in molecular biology have contributed to the update of their nosology. Syndromic vascular malformations are an example: while Klippel-Trenaunay syndrome, Proteus or CLOVES syndrome share many common features, understanding of pathological mechanism and specially the role of the PIK3/AKT/mTOR pathway enables us to rethink their classification...
April 4, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29625858/m2-polarization-of-macrophages-by-oncostatin-m-in-hypoxic-tumor-microenvironment-is-mediated-by-mtorc2-and-promotes-tumor-growth-and-metastasis
#18
Richa Shrivastava, Mohammad Asif, Varsha Singh, Parul Dubey, Showkat Ahmad Malik, Mehraj-U-Din Lone, Brij Nath Tewari, Khemraj Singh Baghel, Subhashis Pal, Geet Kumar Nagar, Naibedya Chattopadhyay, Smrati Bhadauria
Oncostatin M (OSM), an inflammatory cytokine belonging to the interleukin-6 (IL-6) superfamily, plays a vital role in multitude of physiological and pathological processes. Its role in breast tumor progression and metastasis to distant organs is well documented. Recent reports implicate OSM in macrophage M2 polarization, a key pro-tumoral phenomenon. M2 polarization of macrophages is believed to promote tumor progression by potentiating metastasis and angiogenesis. In the current study, we delineated the mechanism underlying OSM induced macrophage M2 polarization...
April 3, 2018: Cytokine
https://www.readbyqxmd.com/read/29625382/phthalimide-conjugations-for-the-degradation-of-oncogenic-pi3k
#19
Wenlu Li, Chunmei Gao, Lei Zhao, Zigao Yuan, Yuzong Chen, Yuyang Jiang
PI3K/Akt/mTOR pathway is crucial for carcinogenesis and its inhibitors have made a great progress in cancer treatment. However, there is still a great developing space for PI3K inhibitors as the acquired drug resistance hindered their application in clinical. Proteolysis-targeting chimeras (PROTACs) with the potential to handle the challenges faced in drug development could be an alternative therapeutic strategy. Moreover, the past two years have witnessed remarkable advances in the development of phthalimide conjugation as a strategy for the degradation instead of inhibition of the targets, including BET family proteins, Sirtuin 2, CDK 9, Smad 3, and BCR-ABL proteins...
March 26, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29625193/icaritin-induces-ovarian-cancer-cell-apoptosis-through-activation-of-p53-and-inhibition-of-akt-mtor-pathway
#20
Lvfen Gao, Ming Chen, Yuan Ouyang, Ruobin Li, Xian Zhang, Xuesong Gao, Xiaoyu Wang, Shaoqiang Lin
AIMS: Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. Currently, the first-line OC treatment consists of cytoreductive surgery and platinum-based chemotherapy. However, most patients develop chemoresistance after the first-line treatment limits the success of treatment. Therefore, there is an urgent need to identify effective therapeutic agents. MAIN METHODS: Cell viabilities were detected by MTS assay; Annexin V-FITC/PI assay and western blotting assay were performed to analyze the apoptotic cells in vitro; An immunofluorescence assay was performed to analyze the TUNEL+ apoptotic cells in vivo; Patient-derived xenografts were established to test the in vivo antitumor effects; The key proteins of p53, caspase-mediated apoptotic pathway and Akt/mTOR pathway were detected by Western blotting...
April 3, 2018: Life Sciences
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