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https://www.readbyqxmd.com/read/29227681/%C3%AE-hydroxy-%C3%AE-methyl-butyrate-is-more-potent-than-leucine-in-inhibiting-starvation-induced-protein-degradation-in-c2c12-myotubes
#1
Yehui Duan, Fengna Li, Qiuping Guo, Wenlong Wang, Lingyu Zhang, Chaoyue Wen, Xiao'an Chen, Yulong Yin
Leucine (Leu) and its metabolites α-ketoisocaproate (KIC) and β-hydroxy-β-methyl butyrate (HMB) are potent regulators of protein turnover. The aim of this study was to compare the inhibitory effects of Leu, KIC, and HMB on protein degradation and to investigate the mechanisms involved. The results showed that the inhibitory effect of HMB (0.38 ± 0.04) was more potent than that of Leu (0.76 ± 0.04) and KIC (0.56 ± 0.04, P < 0.01), and was significantly abolished in the presence of LY294002 (1.48 ± 0...
December 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29227548/resistance-of-oral-cancer-cells-to-5-ala-mediated-photodynamic-therapy
#2
Flávia Cristina Perillo Rosin, Marina Gabriela Teixeira, Cibele Pelissari, Luciana Corrêa
Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio-resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti-apoptotic proteins and those related to Akt/mTOR pathway. Sub-lethal doses of PDT were applied, consisting of a constant concentration of 5-aminolevulinic acid (5-ALA) (1 mM, 4-hour incubation) and increasing irradiation dose with LED (from 5...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29227203/therapeutic-charm-of-quercetin-and-its-derivatives-a-review-of-research-and-patents
#3
Ajay Sharma, Dharambir Kashyap, Katrin Sak, Hardeep Singh Tuli, Anil K Sharma
Bioactive polyphenolic compounds derived from plants are being utilized for prevention of various chronic diseases including cancer and cardiovascular disorders. Quercetin, a potential poly-phenolic flavonol, found in onions, apples and berries, has been implicated against cancer proliferation, chronic inflammation and various other oxidative manifestations. Evidences suggested that quercetin negatively regulates the numerous crucial signaling pathways associated with life-threatening diseases. Major signaling pathways including NF-κB, MAPK, PI3K-AKT and mTOR are found to be regulated by quercetin...
December 11, 2017: Pharmaceutical Patent Analyst
https://www.readbyqxmd.com/read/29223809/cadmium-induces-bnip3-dependent-autophagy-in-chicken-spleen-by-modulating-mir-33-ampk-axis
#4
Menghao Chen, Xiaojing Li, Ruifeng Fan, Jie Yang, Xi Jin, Sattar Hamid, Shiwen Xu
Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed...
December 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29223745/buparlisib-plus-fulvestrant-in-postmenopausal-women-with-hormone-receptor-positive-her2-negative-advanced-breast-cancer-progressing-on-or-after-mtor-inhibition-belle-3-a-randomised-double-blind-placebo-controlled-phase-3-trial
#5
Angelo Di Leo, Stephen Johnston, Keun Seok Lee, Eva Ciruelos, Per E Lønning, Wolfgang Janni, Ruth O'Regan, Marie-Ange Mouret-Reynier, Dimitar Kalev, Daniel Egle, Tibor Csőszi, Roberto Bordonaro, Thomas Decker, Vivianne C G Tjan-Heijnen, Sibel Blau, Alessio Schirone, Denis Weber, Mona El-Hashimy, Bharani Dharan, Dalila Sellami, Thomas Bachelot
BACKGROUND: Activation of the PI3K/AKT/mTOR pathway occurs frequently in breast cancer that is resistant to endocrine therapy. Approved mTOR inhibitors effectively inhibit cell growth and proliferation but elicit AKT phosphorylation via a feedback activation pathway, potentially leading to resistance to mTOR inhibitors. We evaluated the efficacy and safety of buparlisib plus fulvestrant in patients with advanced breast cancer who were pretreated with endocrine therapy and mTOR inhibitors...
December 6, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29222553/ghrelin-attenuates-retinal-neuronal-autophagy-and-apoptosis-in-an-experimental-rat-glaucoma-model
#6
Ke Zhu, Meng-Lu Zhang, Shu-Ting Liu, Xue-Yan Li, Shu-Min Zhong, Fang Li, Ge-Zhi Xu, Zhongfeng Wang, Yanying Miao
Purpose: Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model. Methods: The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29222171/tankyrase-inhibition-enhances-the-anti-proliferative-effect-of-pi3k-and-egfr-inhibition-mutually-affecting-%C3%AE-catenin-and-akt-signaling-in-colorectal-cancer
#7
Nina T Solberg, Jo Waaler, Kaja Lund, Line Mygland, Petter A Olsen, Stefan Krauss
Over-activation of the WNT/β-catenin signaling axis is a common denominator in colorectal cancer (CRC). Currently there is no available WNT inhibitor in clinical practice. Although tankyrase inhibitors have been proposed as promising candidates there are many CRC models that do not respond positively to tankyrase inhibition in vitro and in vivo. Therefore, a combinatorial therapeutic approach combining a tankyrase inhibitor (G007-LK) with PI3K (BKM120) and EGFR (Erlotinib) inhibitors in CRC was investigated...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29221790/fam3-gene-family-a-promising-therapeutical-target-for-nafld-and-type-2-diabetes
#8
REVIEW
Zhang Xiaoyan, Weili Yang, Junpei Wang, Yuhong Meng, Youfei Guan, Jichun Yang
Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health issues worldwide. The Family with sequence similarity 3 (FAM3) gene family consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D, respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate steatosis and hyperglycemia in obese diabetic mice...
December 5, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29221726/mirna-495-suppresses-proliferation-and-migration-of-colorectal-cancer-cells-by-targeting-fam83d
#9
Likun Yan, Jianfeng Yao, Jian Qiu
microRNAs (miRNAs) have been reported to play crucial roles in malignant tumor progression, including cell development, proliferation, and progression. Increasing evidence suggests that miR-495 functions as either an oncogene or tumor suppressor in several tumor types. However, its biological role in the development of colorectal cancer (CRC) still remains unclear. In this study, we found that miR-495 expression level was remarkably down-regulated in CRC tissues samples and cell lines when compared to adjacent normal tissues and cell line by using qRT-PCR detection...
December 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29221190/the-m6a-methyltransferase-mettl3-acting-as-a-tumor-suppressor-in-renal-cell-carcinoma
#10
Xiao Li, Jingyuan Tang, Wen Huang, Feng Wang, Pu Li, Chao Qin, Zhiqiang Qin, Qing Zou, Jifu Wei, Lixin Hua, Haiwei Yang, Zengjun Wang
We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis and development. Immunohistochemistry was performed in clinical tissue microarray. Expression level of METTL3 in RCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the effects of METTL3 on proliferation, migration, invasion and cell cycle were studied in RCC cells. Additionally, in vivo study was carried out in nude mice. Negative METTL3 expression was associated with larger tumor size (P=0...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220539/significance-and-mechanism-of-androgen-receptor-ar-overexpression-and-ar-mtor-crosstalk-in-hepatocellular-carcinoma
#11
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29217770/protein-c-receptor-stimulates-multiple-signaling-pathways-in-breast-cancer-cells
#12
Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and trans-activation of insulin-like growth factor 1 receptor (IGF-1R)...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217681/the-protein-tyrosine-phosphatase-shp2-regulates-oligodendrocyte-differentiation-and-early-myelination-and-contributes-to-timely-remyelination
#13
Jared T Ahrendsen, Danielle E Harlow, Lisbet T Finseth, Jennifer N Bourne, Sean P Hickey, Elizabeth A Gould, Cecilia M Culp, Wendy B Macklin
Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mTOR and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance...
December 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217266/auriculasin-induced-ros-causes-prostate-cancer-cell-death-via-induction-of-apoptosis
#14
Hyun-Dong Cho, Ju-Hye Lee, Kwang-Deog Moon, Ki-Hun Park, Mi-Kyung Lee, Kwon-Il Seo
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model...
December 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29217185/selenizing-astragalus-polysaccharide-attenuates-pcv2-replication-promotion-caused-by-oxidative-stress-through-autophagy-inhibition-via-pi3k-akt-activation
#15
Dandan Liu, Jing Xu, Gang Qian, Mohammed Hamid, Fang Gan, Xingxiang Chen, Kehe Huang
Our previous studies have shown that oxidative stress could promote the porcine circovirus type 2 (PCV2) replication, and astragalus polysaccharide (APS)/selenium could suppress PCV2 replication. However, whether selenizing astragalus polysaccharide (sAPS) provides protection against oxidative stress-induced PCV2 replication promotion and the mechanism involved remain unclear. The present study aimed to explore the mechanism of the PCV2 replication promotion induced by oxidative stress and a novel pharmacotherapeutic approach involving the regulation of autophagy of sAPS...
December 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29217067/etiology-and-genetics-of-congenital-vascular-lesions
#16
REVIEW
Angela Queisser, Laurence M Boon, Miikka Vikkula
The detection of somatic, activating genetic mutations to underlie development of vascular tumors and malformations led to a better understanding of their pathophysiology. Proteins encoded by the detected mutated genes activate the two major signaling pathways, also involved in cancer: the RAS/MAPK/ERK pathway and/or the PI3K/AKT/mTOR pathway. This gives a strong basis for studies to repurpose cancer therapeutics to patients with vascular tumors and malformations.
February 2018: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/29215373/mangiferin-prevents-the-growth-of-gastric-carcinoma-by-blocking-the-pi3k-akt-signalling-pathway
#17
Min Du, Gang Wen, Juan Jin, Yuanguang Chen, Jun Cao, Aman Xu
The aim of the present study was to investigate the effects of mangiferin on gastric carcinoma cells and to determine the possible mechanisms underlying such effects. The MTT assay was performed to evaluate the antiproliferative effect of mangiferin. Following treatment, apoptosis rates of SGC-7901 were established by flow cytometry and laser confocal microscopy, and western blot analysis was used to detect the expression of apoptosis-related proteins. The MTT assay showed that mangiferin inhibited the proliferation of SGC-7901 and BCG-823 cells in a dose-dependent and time-dependent manner...
December 5, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29214525/treatment-of-melanoma-with-selected-inhibitors-of-signaling-kinases-effectively-reduces-proliferation-and-induces-expression-of-cell-cycle-inhibitors
#18
Dorota Ciołczyk-Wierzbicka, Dorota Gil, Piotr Laidler
Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin (mTOR), everolimus (mTOR), GDC-0879 (B-RAF), and CHIR-99021 (GSK3beta) in cell proliferation and expression of crucial regulatory cell cycle proteins in human melanoma cells: WM793 (VGP) and Lu1205 (metastatic)...
December 6, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29212252/c-c-motif-chemokine-receptor-1-ccr1-is-a-target-of-the-egf-akt-mtor-stat3-signaling-axis-in-breast-cancer-cells
#19
Soon Young Shin, Da Hyun Lee, Jishin Lee, Chan Choi, Ji-Young Kim, Jeong-Seok Nam, Yoongho Lim, Young Han Lee
The CC motif chemokine receptor 1 (CCR1) has been implicated in tumor invasion and metastasis in numerous cancers. However, the detailed mechanism of CCR1 upregulation in metastatic tumor cells is poorly understood. The aim of this study was to clarify the regulatory mechanism underlying transcriptional activation of the CCR1 gene in response to epidermal growth factor (EGF) stimulation in breast cancer cells. CCR1 was highly expressed in human breast invasive ductal carcinoma (IDC) compared to adjacent normal tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212166/dysregulated-lncrna-uca1-contributes-to-the-progression-of-gastric-cancer-through-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#20
Chengyun Li, Geyu Liang, Sheng Yang, Jing Sui, Wenzhuo Yao, Xian Shen, Yanqiu Zhang, Hui Peng, Weiwei Hong, Siyi Xu, Wenjuan Wu, Yancheng Ye, Zhiyi Zhang, Wenhua Zhang, Lihong Yin, Yuepu Pu
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis...
November 7, 2017: Oncotarget
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