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singaling pathway

Jianming Tang, Yanxin Li, Youzhou Sang, Bo Yu, Deguan Lv, Weiwei Zhang, Haizhong Feng
Recent molecularly targeted approach gains advance in breast cancer treatment. However, the estimated 5-year survival rate has not met the desired expectation for improvement, especially for patients with triple-negative breast cancer (TNBC). Here we report that the lncRNA PVT1 promotes KLF5/beta-catenin signaling to drive TNBC tumorigenesis. PVT1 is upregulated in clinical TNBC tumors. Using genetic approaches targeting PVT1 in TNBC cells, we found that PVT1 depletion inhibited cell proliferation, colony formation, and orthotopic xenograft tumor growth...
May 15, 2018: Oncogene
Changliang Wang, Liang Chen, Yang Yang, Menglei Zhang, Garry Wong
Competitive endogenous RNAs (ceRNAs) are a newly proposed RNA interaction mechanism that has been associated with the initiation and progression of various cancers. In this study, we constructed an ageing gene related ceRNA network (AgeingCeNet) in bladder cancer. Network analysis revealed that ageing gene ceRNAs have a larger degree and closeness centrality than ageing genes themselves. Notably, the difference of betweenness centrality of ageing genes and their ceRNAs is not significant, suggesting that the ceRNAs of ageing genes and ageing genes themselves both play important communication roles in AgeingCeNet...
December 19, 2017: Oncotarget
Muskaan Belani, Abhilash Deo, Preeti Shah, Manish Banker, Pawan Singal, Sarita Gupta
Insulin resistance (IR) is one of the significant aberrations in polycystic ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and 20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin resistance (NIR). This could possibly be due to defects in the downstream signaling pathways. The study thus aims to unravel insulin and steroidogenic signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs matched controls...
April 2018: Journal of Steroid Biochemistry and Molecular Biology
Agostino Di Ciaula, David Q-H Wang, Emilio Molina-Molina, Raquel Lunardi Baccetto, Giuseppe Calamita, Vincenzo O Palmieri, Piero Portincasa
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i...
November 2017: Annals of Hepatology
Y Wang, W Deng, Y Zhang, S Sun, S Zhao, Y Chen, X Zhao, L Liu, J Du
AIM: MICAL2, a cytoskeleton dynamics regulator, is identified associated with survival and metastasis of several types of cancers recently. This study was designed to investigate the role of MICAL2 in breast cancer cell migration as well as its underlying mechanisms. METHODS: The relationship between MICAL2 and EGF/EGFR signalling was analysed by gene overexpression and knock-down techniques. Cell migration was measured by wound-healing assays. Activation of EGF/EGFR signalling pathways were evaluated by immunofluorescence, qPCR, Western blotting and zymography techniques...
July 18, 2017: Acta Physiologica
Ana Ludke, Gauri Akolkar, Prathapan Ayyappan, Anita K Sharma, Pawan K Singal
We previously reported that Vitamin C (Vit C) protects against doxorubicin (Dox)-induced cardiotoxicity by reducing oxidative stress, p38 mitogen-activated kinase (MAPK) and p53 activation and rescuing cell death in isolated adult cardiomyocytes. The pattern of activation and the role of oxidative stress as well as down-stream mechanisms for such protection remain elusive. Therefore the present study aims to analyze time-dependant generation of reactive oxygen species (ROS) and the activation of stress induced signalling pathways in cardiomyocytes treated with Dox and Vit C...
2017: PloS One
Junchao Duan, Hejing Hu, Lin Feng, Xiaozhe Yang, Zhiwei Sun
The safety evaluation of silica nanoparticles (SiNPs) are getting great attention due to its widely-used in food sciences, chemical industry and biomedicine. However, the adverse effect and underlying mechanisms of SiNPs on cardiovascular system, especially on angiogenesis is still unclear. This study was aimed to illuminate the possible mechanisms of SiNPs on angiogenesis in zebrafish transgenic lines, Tg(fli-1:EGFP) and Albino. SiNPs caused the cardiovascular malformations in a dose-dependent manner via intravenous microinjection...
September 2017: Chemosphere
Ali A Mokdad, Caitlin A Hester, Amit G Singal, Adam C Yopp
Hepatocellular carcinoma (HCC) is a major cause of cancer burden globally. In the United States, the incidence of HCC is forecast to continue to rise for the next 15 years. Patients with HCC vary markedly owing to heterogeneous tumor characteristics and concomitant liver dysfunction. In the United States and Europe, HCC is staged and managed according to the Barcelona Clinic Liver Cancer (BCLC) system. For very early and early stage HCC, or BCLC 0/A, liver transplant is the optimal treatment option. Liver resection and radiofrequency or microwave ablation are alternative treatment options...
April 2017: Chinese Clinical Oncology
Longjiang Xu, Hong Leng, Xin Shi, Jiang Ji, Jinxiang Fu, Hong Leng
MicroRNAs (miRNAs) have been demonstrated to contribute to malignant progression in psoriasis development. The purposes of the study was to evaluated the effects of miRNA-155 on cell proliferation, migration and apoptosis in psoriasis development via PTEN singaling pathway and identify its direct target protein. Quantitative real-time RT-PCR (qRT-PCR) was performed to examine the level of miR-155 in psoriasis cells, miR-155 was downregulated in a psoriasis cell line Hacat by transfected with small interfering RNA (siRNA), respectively...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sumant Arora, Steven Young, Sudha Kodali, Ashwani K Singal
Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT)...
November 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Ashwani K Singal, Vijay H Shah
Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline...
February 2016: Seminars in Liver Disease
Wenjie Deng, Luo Gu, Xiaojie Li, Jianchao Zheng, Yujie Zhang, Biao Duan, Jie Cui, Jing Dong, Jun Du
BACKGROUND: CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined. METHODS: The contents of CD24 and epidermal growth factor receptor (EGFR) in gastric cancer cells (SGC-7901 and BGC-823) and non-malignant gastric epithelial cells (GES-1) were evaluated by Western blotting assay. Cellular EGFR staining was examined by immunofluorescence assay. Cell migration rate was measured by wound healing assay...
February 1, 2016: Journal of Translational Medicine
Yanwei Liu, Sen Chen, Rui Xue, Juan Zhao, Maojun Di
Deregulation of PI3K/Akt/mTOR pathway has been recently identified to play a crucial role in the progress of human gastric cancer. In this study, we show that mefloquine, a FDA-approved anti-malarial drug, effectively targets human gastric cancer cells. Mefloquine potently inhibits proliferation and induces apoptosis of a panel of human gastric cancer cell lines, with EC50 ∼ 0.5-0.7 μM. In two independent gastric cancer xenograft mouse models, mefloquine significantly inhibits growth of both tumors. The combination of mefloquine with paclitaxel enhances the activity of either drug alone in in vitro and in vivo...
February 5, 2016: Biochemical and Biophysical Research Communications
Changbao Chen, Meng Zhao, Aixian Tian, Xiaolin Zhang, Zhi Yao, Xinlong Ma
Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors...
July 10, 2015: Oncotarget
Xiucai Xu, Liuyuan He, Aimei Zhang, Qing Li, Wen Hu, He Chen, Jian Du, Jilong Shen
Congenital toxoplasmosis may result in abortion, severe mental retardation and neurologic damage in the offspring. Placental damage is considered as the key event in this disease. Here we show that maternal infection with Toxoplasma gondii Wh3 isolate of genotype Chinese 1, which is predominantly prevalent in China, induced trophoblast apoptosis of pregnant mouse. PCR array analysis of 84 key genes in the biogenesis and functions of mouse mitochondrion revealed that ten genes were up-regulated at least 2-fold in the Wh3 infection group, compared with those in the control...
July 2015: Experimental Parasitology
Chang-min Lin, Yan-ping Yuan, Xian-cai Chen, Hai-hong Li, Bo-zhi Cai, Yang Liu, Huan Zhang, Yu Li, Keng Huang
The rat whisker hair follicle (HF) is a model for studying the reconstruction of the HF or dermal papilla (DP), and involves the Wnt/β-catenin signaling pathway, which is a key pathway in HF development and HF cycling after birth. It has been reported that Wnt/catenin signaling plays an indispensable role in human or rat pelages development and postnatal growth. However, the distribution of some Wnt/β-catenin signaling pathway factors and their relationship with the epithelial stem cell markers in whisker follicles has not been characterized...
June 2015: Journal of Molecular Histology
Rajalaxmi Natarajan, Vinamrata Singal, Richard Benes, Junling Gao, Hoi Chan, Haijun Chen, Yongjia Yu, Jia Zhou, Ping Wu
Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs...
2014: PloS One
Ashwani K Singal, Charles Parker, Christine Bowden, Manish Thapar, Lawrence Liu, Brendan M McGuire
UNLABELLED: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked...
September 2014: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Matthew Zeglinski, Sheena Premecz, Jordyn Lerner, Piotr Wtorek, Megan Dasilva, Devin Hasanally, Rakesh Chaudhary, Anita Sharma, James Thliveris, Amir Ravandi, Pawan K Singal, Davinder S Jassal
BACKGROUND: Doxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects. Among the potential mechanisms for this drug-induced cardiomyopathy, increased production of oxidative stress (OS) through a nitric oxide synthase 3 (NOS3)-dependent pathway has gained recent attention. The objective of the study was to determine the role of NOS3 and OS in a clinically relevant female murine model of DOX- and TRZ-induced heart failure...
March 2014: Canadian Journal of Cardiology
H B Singal, I S Sheoran, R Singh
Activities of key enzymes of Calvin cycle and C4 metabolism, rate of (14)CO2 fixation in light and dark and the initial products of photosynthetic (14)CO2 fixation were determined in flag leaf and different ear parts of wheat viz. pericarp, awn and glumes. Compared to the activities of RuBP carboxylase and other Calvin cycle enzymes viz. NADP-glyceraldehyde-3-phosphate dehydrogenase, NAD-glyceraldehyde-3-phosphate dehydrogenase and ribulose-5-phosphate kinase, the levels of PEP carboxylase and other enzymes of C4 metabolism viz...
January 1986: Photosynthesis Research
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