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https://www.readbyqxmd.com/read/28938749/the-testicular-transcriptome-associated-with-spermatogonia-differentiation-initiated-by-gonadotrophin-stimulation-in-the-juvenile-rhesus-monkey-macaca-mulatta
#1
Suresh Ramaswamy, William H Walker, Paula Aliberti, Rahil Sethi, Gary R Marshall, Alyxzandria Smith, Seyedmehdi Nourashrafeddin, Alicia Belgorosky, Uma R Chandran, Mark P Hedger, Tony M Plant
STUDY QUESTION: What is the genetic landscape within the testis of the juvenile rhesus monkey (Macaca mulatta) that underlies the decision of undifferentiated spermatogonia to commit to a pathway of differentiation when puberty is induced prematurely by exogenous LH and FSH stimulation? SUMMARY ANSWER: Forty-eight hours of gonadotrophin stimulation of the juvenile monkey testis resulted in the appearance of differentiating B spermatogonia and the emergence of 1362 up-regulated and 225 down-regulated testicular mRNAs encoding a complex network of proteins ranging from enzymes regulating Leydig cell steroidogenesis to membrane receptors, and from juxtacrine and paracrine factors to transcriptional factors governing spermatogonial stem cell fate...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#2
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938631/microrna-455-targets-cullin-3-to-activate-nrf2-signaling-and-protect-human-osteoblasts-from-hydrogen-peroxide
#3
Dawei Xu, Hao Zhu, Chengniu Wang, Xinhui Zhu, Genxiang Liu, Chu Chen, Zhiming Cui
Over-production of hydrogen peroxide (H2O2) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation. We demonstrate that microRNA-455 ("miR-455") is a putative Cul3-targeting microRNA. Forced-expression of miR-455 in both hFOB1. 19 osteoblast cell line and primary human osteoblasts induced Cul3 degradation and Nrf2 protein stabilization, which led to subsequent transcription of ARE (anti-oxidant response element)-dependent genes (NQO1, HO1 and GCLC)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938623/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#4
Ning Zheng, Jiahang Chen, Weiqun Liu, Jian Liu, Tao Li, Hongning Chen, Jichuang Wang, Lee Jia
SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938613/high-phlpp1-expression-levels-predicts-longer-time-of-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-in-patients-with-lung-adenocarcinoma
#5
Youyou Xie, Dongqing Lv, Wei Wang, Minhua Ye, Xiaofeng Chen, Haihua Yang
BACKGROUND: In spite of an initial good response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in lung adenocarcinoma patients, resistance to treatment eventually occurs. Epidermal growth factor receptor (EGFR) activation stimulates Ras/Raf/Erk/MAPK and influences PI3K/Akt pathways, respectively. PHLPP negatively regulates PI3K/Akt and the RAF/RAS/ERK signaling pathways. Our study aimed to investigate the association between PH domain leucine-rich-repeats protein phosphatase (PHLPP) expression levels and the acquired resistance to EGFR TKIs in lung adenocarcinoma...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938608/use-of-confocal-laser-endomicroscopy-with-a-fluorescently-labeled-fatty-acid-to-diagnose-colorectal-neoplasms
#6
Feihong Deng, Yuan Fang, Zhiyong Shen, Wei Gong, Tao Liu, Jing Wen, Wanling Zhang, Xianjun Zhu, Hui Zhong, Tong Wang, Fachao Zhi, Biao Nie
Endoscopic treatment for early colorectal cancer closely correlates with patient prognosis. However, endoscopic differentiation between carcinomas and non-neoplastic lesions remains difficult. Here, we topically stained colorectal neoplasms with a fatty acid analogue (BODIPY-FA) and quantified the fluorescent signals using confocal laser endomicroscopy (CLE) and fluorescence microscopy. We also analyzed protein expression in colorectal cancer tissues. We found that expression of fatty acid synthase was elevated, while the expression of fatty acid transporters was reduced in colorectal cancer...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938602/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#7
Ming Zhao, Erin W Howard, Amanda B Parris, Zhiying Guo, Qingxia Zhao, Zhikun Ma, Ying Xing, Bolin Liu, Susan M Edgerton, Ann D Thor, Xiaohe Yang
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938585/the-trophoblast-cell-surface-antigen-2-and-mir-125b-axis-in-urothelial-bladder-cancer
#8
Chiara Avellini, Caterina Licini, Raffaella Lazzarini, Rosaria Gesuita, Emanuela Guerra, Giovanni Tossetta, Clara Castellucci, Stefano Raffaele Giannubilo, Antonio Procopio, Saverio Alberti, Roberta Mazzucchelli, Fabiola Olivieri, Daniela Marzioni
Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938584/bmpr2-promotes-invasion-and-metastasis-via-the-rhoa-rock-limk2-pathway-in-human-osteosarcoma-cells
#9
Shidong Wang, Tingting Ren, Guangjun Jiao, Yi Huang, Xing Bao, Fan Zhang, Kuisheng Liu, Bingxin Zheng, Kunkun Sun, Wei Guo
Bone morphogenetic protein receptor 2 (BMPR2) has been identified in several types of cancer. However, its role in osteosarcoma is largely unknown. We systematically investigated the role of BMPR2 in osteosarcoma cell lines, human tissue samples and xenograft models. The relationship between BMPR2 expression and osteosarcoma patients' survival was investigated by bioinformatics and clinical data. Wound healing assay and transwell assay were used to detect the changes of cell migration and invasion ability after BMPR2 transfection...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938583/ppa1-regulates-tumor-malignant-potential-and-clinical-outcome-of-colon-adenocarcinoma-through-jnk-pathways
#10
Ping Wang, Yi Zhou, Qi Mei, Jing Zhao, Liu Huang, Qiang Fu
Colorectal cancer (CRC) represents one of the most prevalent malignancies and the third leading cause of cancer death worldwide. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, therefore participates in the energy metabolism. Proteomic studies have demonstrated the up-regulated expression of PPA1 in various tumors, however, its expression pattern in CRC hasn't been reported. In the current study, we used RT-qCR, Western Blot and immunohistochemical (IHC) staining to explore the expression of PPA1 in 113 paired colon cancer tissues and adjacent normal tissues, which revealed that PPA1 was correlated with lymph node metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938569/evaluation-of-autoantibody-signatures-in-meningioma-patients-using-human-proteome-arrays
#11
Shabarni Gupta, Shuvolina Mukherjee, Parvez Syed, Narendra Goud Pandala, Saket Choudhary, Vedita Anand Singh, Namrata Singh, Heng Zhu, Sridhar Epari, Santosh B Noronha, Aliasgar Moiyadi, Sanjeeva Srivastava
Meningiomas are one of the most common tumors of the Central nervous system (CNS). This study aims to identify the autoantibody biomarkers in meningiomas using high-density human proteome arrays (~17,000 full-length recombinant human proteins). Screening of sera from 15 unaffected healthy individuals, 10 individuals with meningioma grade I and 5 with meningioma grade II was performed. This comprehensive proteomics based investigation revealed the dysregulation of 489 and 104 proteins in grades I and II of meningioma, respectively, along with the enrichment of several signalling pathways, which might play a crucial role in the manifestation of the disease...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938568/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#12
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938560/inflammatory-factor-tnf-%C3%AE-promotes-the-growth-of-breast-cancer-via-the-positive-feedback-loop-of-tnfr1-nf-%C3%AE%C2%BAb-and-or-p38-p-stat3-hbxip-tnfr1
#13
Xiaoli Cai, Can Cao, Jiong Li, Fuquan Chen, Shuqin Zhang, Bowen Liu, Weiying Zhang, Xiaodong Zhang, Lihong Ye
In the connection between inflammation and cancer development, tumor necrosis factor-alpha (TNF-α) contributes to the tumorigenesis. However, the underlying mechanism remains poorly understood. In this study, we report that TNF-α enhances the growth of breast cancer through up-regulation of oncoprotein hepatitis B X-interacting protein (HBXIP). Our data showed that the levels of TNF-α were positively related to those of HBXIP in clinical breast cancer tissues. Moreover, TNF-α could up-regulate HBXIP in breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938523/hypothermia-induced-by-anesthesia-regulates-various-signals-expressions-in-the-hippocampus-of-animals
#14
Huimei Hao, Shanshan Wang
Though important for a variety of medical procedures, general anesthesia is not a problem free. Some anesthetics have been suggested to affect a number of signals, which are associated with memory consolidation and cognition. In the present study, we attempted to investigate the molecular mechanism of anesthesia-regulated processes. We found that under hypothermic condition, anesthetic of isoflurane enhances various signals expression in hippocampus, including Hspd1, Actb, Mgst1, THBS4, Syp, C1QC, Serpine, Plat, and Ngf, which were related to cellular stress, neural plasticity responses, and hippocampal injury...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938492/a-long-noncoding-rna-lncrna-amhr2-plays-a-role-in-amhr2-gene-activation-in-mouse-ovarian-granulosa-cells
#15
Atsushi P Kimura, Ryoma Yoneda, Misuzu Kurihara, Shota Mayama, Shin Matsubara
Anti-Müllerian hormone (AMH) is critical to the regression of Müllerian ducts during mammalian male differentiation and targets ovarian granulosa cells and testicular Sertoli and Leydig cells of adults. Specific effects of AMH are exerted via its receptor, AMH type II receptor (Amhr2), but the mechanism by which the Amhr2 gene is specifically activated is not fully understood. To see whether a proximal promoter was sufficient to Amhr2 gene activation, we generated transgenic mice that bore the enhanced green fluorescent protein (EGFP) gene driven by a 500-bp mouse Amhr2 gene promoter...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938491/inhibition-of-fgfr-signaling-partially-rescues-hypophosphatemic-rickets-in-hmwfgf2-tg-male-mice
#16
Liping Xiao, Erxia Du, Collin Homer-Bouthiette, Marja M Hurley
Transgenic mice harboring high molecular weight FGF2 isoforms (HMWTg) in osteoblast lineage cells phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets. Since HMWFGF2 was upregulated in bones of Hyp mice and abnormal FGF receptor (FGFR) signaling is important in XLH, HMWTg mice were used to examine the effect of the FGFR inhibitor NVP-BGJ398, now in clinical trials for cancer therapy, on hypophosphatemic rickets...
August 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938449/tsh-igf-1-receptor-cross-talk-rapidly-activates-extracellular-signal-regulated-kinases-in-multiple-cell-types
#17
Christine C Krieger, Joseph D Perry, Sarah J Morgan, George J Kahaly, Marvin C Gershengorn
We previously showed that TSH/IGF-1 receptor cross-talk appears to be involved in Graves' orbitopathy (GO) pathogenesis and up-regulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients (GOFs), co-administration of TSH and IGF-1 induces synergistic increases in hyaluronan secretion. In human thyrocytes, TSH plus IGF-1 synergistically increased expression of sodium-iodide symporter that appeared to involve ERK1/2 activation. However, the details of ERK1/2 activation were not known nor whether ERK1/2 was involved in this synergism in other cell types...
August 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938448/novel-autosomal-dominant-pth-gene-signal-sequence-mutation-in-a-family-with-familial-isolated-hypoparathyroidism
#18
Luigia Cinque, Angelo Sparaneo, Laura Penta, Amedea Mencarelli, Daniela Rogaia, Susanna Esposito, Federico Pio Fabrizio, Filomena Baorda, Alberto Verrotti, Alberto Falorni, Gabriela Stangoni, Geoffrey N Hendy, Vito Guarnieri, Paolo Prontera
Context: Familial isolated hypoparathyroidism (FIH) is a genetically heterogeneous disorder due to mutations of the calcium-sensing receptor (CASR), glial cells missing-2 (GCM2), guanine nucleotide binding protein alpha 11 (GNA11), or parathyroid hormone (PTH) genes. Thus far, only 4 cases with homozygous and 2 cases with heterozygous mutations in the PTH gene have been reported. Objective: To clinically describe an FIH family and identify and characterize the causal gene mutation...
August 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938438/targeted-disruption-of-yap-and-taz-impairs-the-maintenance-of-the-adrenal-cortex
#19
Adrien Levasseur, Guillaume St-Jean, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway. They act as major regulators of stem cell maintenance, cell growth and differentiation. To characterize their roles in the adrenal cortex, we generated a mouse model in which Yap and Taz were conditionally deleted in steroidogenic cells (Yapflox/flox;Tazflox/flox;Nr5a1cre/+). Male Yapflox/flox;Tazflox/flox;Nr5a1cre/+ mice were characterized by an age-dependent degeneration of the adrenal cortex associated with an increase in apoptosis and a progressive reduction in the expression levels of steroidogenic genes...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#20
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
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