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https://www.readbyqxmd.com/read/29456722/fucosterol-exhibits-selective-antitumor-anticancer-activity-against-hela-human-cervical-cell-line-by-inducing-mitochondrial-mediated-apoptosis-cell-cycle-migration-inhibition-and-downregulation-of-m-tor-pi3k-akt-signalling-pathway
#1
Hongye Jiang, Jie Li, Aiyue Chen, Yinguang Li, Meng Xia, Peng Guo, Shuzhong Yao, Shuqin Chen
Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456672/roles-of-autophagy-in-androgen-induced-benign-prostatic-hyperplasia-in-castrated-rats
#2
Rong-Fu Liu, Guo Fu, Jian Li, Yu-Feng Yang, Xue-Gang Wang, Pei-De Bai, Yue-Dong Chen
The present study investigated the role of androgen in the process of androgen-induced prostate hyperplasia in castrated rats and assessed the role of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway in this process. Furthermore, the extent to which autophagy may affect the level of androgen-induced benign prostatic hyperplasia was also explored. A total of 40 Sprague Dawley rats were randomly divided into four groups: Testosterone group, rapamycin group, 3-methyladenine (3-MA) group, and control group...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456661/anticancer-activity-of-23-24-dihydrocucurbitacin-b-against-the-hela-human-cervical-cell-line-is-due-to-apoptosis-and-g-2-m-cell-cycle-arrest
#3
Jun-Xiao Zhang, Hong Wei-Tan, Chun-Yan Hu, Wei-Qiang Wang, Guang-Hua Chu, Li-Hui Wei, Liu Chen
Cervical cancer is one of the primary causes of cancer-associated mortality worldwide. Due to the increasing incidence of cervical cancer, multiple treatment options are required. Initial responses to chemotherapy and surgical interventions are generally positive, however patients often experience relapse and tumor recurrence. Currently, the effects of cucurbitacins on different types of cancer are being investigated, as they exhibit a wide variety of bioactivities. The anticancer activity of the cucurbitacin 23,24-dihydrocucurbitacin B against a panel of human cervical cancer cell lines was investigated in the current study...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29455662/the-role-of-rictor-downstream-of-receptor-tyrosine-kinase-in-cancers
#4
REVIEW
Ahlem Jebali, Nicolas Dumaz
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454321/safety-and-efficacy-of-temsirolimus-as-second-line-treatment-for-patients-with-recurrent-bladder-cancer
#5
Marina Pulido, Guilhem Roubaud, Anne-Laure Cazeau, Hakim Mahammedi, Lionel Vedrine, Florence Joly, Loic Mourey, Christian Pfister, Alejandro Goberna, Barbara Lortal, Carine Bellera, Philippe Pourquier, Nadine Houédé
BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#6
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29453775/effect-of-pparg-on-ages-induced-akt-mtor-signaling-associated-human-chondrocytes-autophagy
#7
Zhao-Jun Wang, Hai-Bin Zhang, Cheng Chen, Hao Huang, Jian-Xia Liang
Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone...
February 17, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#8
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#9
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29451218/pten-knockdown-with-the-y444f-mutant-aav2-vector-promotes-axonal-regeneration-in-the-adult-optic-nerve
#10
Zheng-Ru Huang, Hai-Ying Chen, Zi-Zhong Hu, Ping Xie, Qing-Huai Liu
The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449346/shikonin-suppresses-proliferation-and-induces-apoptosis-in-endometrioid-endometrial-cancer-cells-via-modulating-mir-106b-pten-akt-mtor-signaling-pathway
#11
Caimei Huang, Guohua Hu
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, which exerts anti-cancer effects in various cancers. However, the molecular mechanisms underlying the therapeutic effects of shikonin against endometrioid endometrial cancer (EEC) have not yet been fully elucidated. Herein, we investigated anti-cancer effects of shikonin on EEC cells and explored the underlying molecular mechanism. We observed that shikonin inhibits proliferation in human EEC cell lines with in a dose-dependent manner...
February 15, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29447541/jtc-801-exerts-anti-proliferative-effects-in-human-osteosarcoma-cells-by-inducing-apoptosis
#12
Chang-Jun Zheng, Li-Li Yang, Jun Liu, Lei Zhong
BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro...
February 15, 2018: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29443546/akt1-deficiency-diminishes-skeletal-muscle-hypertrophy-by-reducing-satellite-cell-proliferation
#13
Nobuki Moriya, Mitsunori Miyazaki
Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29443392/spatial-aspects-of-oncogenic-signaling-determine-response-to-combination-therapy-in-slice-explants-from-kras-driven-lung-tumors
#14
Katja Närhi, Ashwini S Nagaraj, Elina Parri, Riku Turkki, Petra W van Duijn, Annabrita Hemmes, Jenni Lahtela, Virva Uotinen, Mikko I Mäyränpää, Kaisa Salmenkivi, Jari Räsänen, Nina Linder, Jan Trapman, Antti Rannikko, Olli Kallioniemi, Taija Af Hällström, Johan Lundin, Wolfgang Sommergruber, Simon Anders, Emmy W Verschuren
A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision-cut slices from Kras-driven non-small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates that signaling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma (ASC), and MAPK activity in adenocarcinoma (AC)...
February 14, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29439710/semet-attenuates-ota-induced-pcv2-replication-promotion-by-inhibiting-autophagy-by-activating-the-akt-mtor-signaling-pathway
#15
Gang Qian, Dandan Liu, Junfa Hu, Fang Gan, Lili Hou, Nianhui Zhai, Xingxiang Chen, Kehe Huang
Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells...
February 13, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29439667/impact-of-pkc%C3%AE%C2%B5-downregulation-on-autophagy-in-glioblastoma-cells
#16
Ewa Toton, Aleksandra Romaniuk, Natalia Konieczna, Johann Hofmann, Jan Barciszewski, Maria Rybczynska
BACKGROUND: Several efforts have been focused on identification of pathways involved in malignancy, progression, and response to treatment in Glioblastoma (GB). Overexpression of PKCε was detected in histological samples from GB, anaplastic astrocytoma, and gliosarcoma and is considered an important marker of negative disease outcome. In multiple studies on GB, autophagy has been shown as a survival mechanism during cellular stress, contributing to resistance against anti-cancer agents...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29438034/c1qtnf3-in-the-murine-ovary-and-its-function-in-folliculogenesis
#17
Zhoufei Mao, Liuhong Yang, Xiaosheng Lu, Anni Tan, Yuxia Wang, Fei Ding, Luanjuan Xiao, Xufeng Qi, Yanhong Yu
C1q/tumor necrosis factor-related protein 3 (C1QTNF3) is a novel adipokine with modulating effects on metabolism, inflammation, and the cardiovascular system. C1QTNF3 expression levels in the sera and omental adipose tissues of women with PCOS are low compared to control subjects. However, the expression and function of C1QTNF3 in the ovary has not previously been examined. Here, we assessed the expression patterns of C1qtnf3 in the ovary and explored its role in folliculogenesis. The C1qtnf3 transcript abundance was higher in large follicles than in small follicles and was under the influence of gonadotropin...
February 1, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29436654/tetrahydrocurcumin%C3%A2-induced-autophagy-via-suppression-of-pi3k-akt-mtor-in-non%C3%A2-small-cell-lung-carcinoma-cells
#18
Guoqiang Song, Honghui Lu, Fei Chen, Youmei Wang, Weibin Fan, Weifang Shao, Huoquan Lu, Bin Lin
Lung carcinoma is the leading cause of mortality due to cancer worldwide. Autophagy has a significant role in the development and progression of non‑small cell lung carcinoma (NSCLC). A previous study has revealed that tetrahydrocurcumin (THC), a traditional Chinese medicine isolated from Curcuma wenyujin (Chen & Ling, 1981), induces autophagy in human A549 NSCLC cells. The present study evaluated THC‑induced autophagy in A549 cells using various assays, including the Cell Counting Kit‑8, acridine orange staining, flow cytometry, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and western blot analysis of the markers of autophagy...
February 13, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436648/mir%C3%A2-539-suppresses-proliferation-and-induces-apoptosis-in-renal-cell-carcinoma-by-targeting-high-mobility-group-a2
#19
Zhi-Hua Ye, Ding-Wen Gui
Renal cell carcinoma (RCC) is one of the most common urinary malignancies with a high rate of morbidity. MicroRNAs (miRNAs) have been shown to be critical post‑transcriptional regulators in tumorigenesis. The present study aimed to investigate the effect of miRNA (miR)‑539 on the proliferation and apoptosis of RCC. The expression of miR‑539 and high mobility group AT‑hook 2(HMGA2) were examined in clinical RCC specimens. The 786‑O RCC cell line was also used and was transfected with miR‑539 mimics or inhibitors...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436645/ouabain-suppresses-the-growth-and-migration-abilities-of-glioma-u%C3%A2-87mg-cells-through-inhibiting-the-akt-mtor-signaling-pathway-and-downregulating-the-expression-of-hif%C3%A2-1%C3%AE
#20
Xiao-Sa Yang, Zhong-Wei Xu, Tai-Long Yi, Rui-Cheng Xu, Jie Li, Wen-Bin Zhang, Sai Zhang, Hong-Tao Sun, Ze-Qi Yu, Hao-Xiang Xu, Yue Tu, Shi-Xiang Cheng
Glioma is one of the most malignant forms of brain tumor, and has been of persistent concern due to its high recurrence and mortality rates, and limited therapeutic options. As a cardiac glycoside, ouabain has widespread applications in congestive heart diseases due to its positive cardiac inotropic effect by inhibiting Na+/K+‑ATPase. Previous studies have demonstrated that ouabain has antitumor activity in several types of human tumor, including glioma. However, the exact underlying mechanism remains to be elucidated...
February 12, 2018: Molecular Medicine Reports
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