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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/28938737/complex-catsper-dependent-and-independent-ca2-i-signalling-in-human-spermatozoa-induced-by-follicular-fluid
#2
Sean G Brown, Sarah Costello, Mark C Kelly, Mythili Ramalingam, Ellen Drew, Stephen J Publicover, Christopher L R Barratt, Sarah Martins Da Silva
STUDY QUESTION: Does progesterone in human follicular fluid (hFF) activate CatSper and do other components of hFF modulate this effect and/or contribute separately to hFF-induced Ca2+ signaling? SUMMARY ANSWER: hFF potently stimulates CatSper and increases [Ca2+]i, primarily due to high concentrations of progesterone, however, other components of hFF also contribute to [Ca2+]i signaling, including modulation of CatSper channel activity and inhibition of [Ca2+]i oscillations...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938736/deep-sequencing-shows-that-oocytes-are-not-prone-to-accumulate-mtdna-heteroplasmic-mutations-during-ovarian-ageing
#3
L Boucret, C Bris, V Seegers, D Goudenège, V Desquiret-Dumas, M Domin-Bernhard, V Ferré-L'Hotellier, P E Bouet, P Descamps, P Reynier, V Procaccio, P May-Panloup
STUDY QUESTION: Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? SUMMARY ANSWER: Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. WHAT IS KNOWN ALREADY: Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#4
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/28938632/the-%C3%AE-secretase-inhibitors-enhance-the-anti-leukemic-activity-of-ibrutinib-in-b-cll-cells
#5
Paola Secchiero, Rebecca Voltan, Erika Rimondi, Elisabetta Melloni, Emmanouil Athanasakis, Veronica Tisato, Stefania Gallo, Gian Matteo Rigolin, Giorgio Zauli
Ibrutinib blocks B-cell receptor signaling and interferes with leukemic cell-to-microenvironment interactions. Ibrutinib plays a key role in the management of B-CLL and is recommended for first line treatment of high-risk CLL patients with 17p deletion. Therefore, elucidating the factors governing sensitivity/resistance to Ibrutinib represents a relevant issue. For this purpose, in 3 B-CLL patient samples harboring functional TP53 mutations, the frequency of the mutated clones was monitored during in vivo Ibrutinib therapy, revealing a progressive decline of the frequency of TP53(mut) clones during 12 months of treatment...
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
#6
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/28938626/infiltrating-mast-cells-enhance-benign-prostatic-hyperplasia-through-il-6-stat3-cyclin-d1-signals
#7
Zhenyu Ou, Yao He, Lin Qi, Xiongbin Zu, Longxiang Wu, Zhenzhen Cao, Yuan Li, Longfei Liu, Daud Athanasius Dube, Zhi Wang, Long Wang
Early evidences have showed that mast cells could infiltrate into benign prostatic hyperplasia (BPH) tissues, but the exact role of mast cells in BPH development remains unclear. In this study, we identified more mast cells existing in human BPH tissues compared with that in the normal prostate. In the in vitro co-culture system, BPH-1 prostate cells promoted activation and migration of mast cells, and mast cells conversely stimulated BPH-1 cells proliferation significantly. Molecular analysis demonstrated that mast cell-derived interleukin 6 (IL-6) could activate STAT3/Cyclin D1 signals in BPH-1 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938623/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#8
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/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#9
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#10
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938612/magnetic-resonance-imaging-tracking-and-assessing-repair-function-of-the-bone-marrow-mesenchymal-stem-cells-transplantation-in-a-rat-model-of-spinal-cord-injury
#11
Hongwu Zhang, Liqin Wang, Shihong Wen, Qingfeng Xiang, Xianhong Xiang, Caixia Xu, Yong Wan, Jingnan Wang, Bin Li, Yiqian Wan, Zhiyun Yang, David Y B Deng
The transplantation of bone marrow mesenchymal stem cells (BMSCs) to repair spinal cord injury (SCI) has become a promising therapy. However, there is still a lack of visual evidence directly implicating the transplanted cells as the source of the improvement of spinal cord function. In this study, BMSCs were labeled with NF-200 promoter and lipase-activated gadolinium-containing nanoparticles (Gd-DTPA-FA). Double labeled BMSCs were implanted into spinal cord transaction injury in rat models in situ, the function recovery was evaluated on 1st, 7th, 14th, 28 th days by MRI, Diffusion Tensor Imaing, CT imaging and post-processing, and histological observations...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938611/dickkopf-1-induces-angiogenesis-via-vegf-receptor-2-regulation-independent-of-the-wnt-signaling-pathway
#12
Sung Hoon Choi, Hyemi Kim, Hyun Gyu Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
Tumor angiogenesis is essential for invasive tumor growth and metastasis. Dickkopf-1 (DKK-1), an antagonist of Wnt signaling, participates in tumor development and progression. We evaluated whether DKK-1 stimulation induces angiogenesis and the endothelial-mesenchymal transition (EnMT). Human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant DKK-1 (rDDK-1) or conditioned medium from a culture of DKK-1-transfected 293 cells. Following stimulation, the expression levels of angiogenesis-related factors and EnMT related markers were determined by immunoblot assays...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938607/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#13
Sasha J Ruiz-Torres, Nancy M Benight, Rebekah A Karns, Elyse E Lower, Jun-Lin Guan, Susan E Waltz
Breast cancer stem cells (BCSCs), which drive tumor progression, recurrence, and metastasis, are considered a major challenge for breast cancer treatments, thus the discovery of novel pathways regulating BCSC maintenance remains essential to develop new strategies to effectively target this population and combat disease mortality. The HGFL-RON signaling is overexpressed in human breast cancers and is associated with increased breast cancer progression, metastasis, and poor prognosis. Here, we report that overexpression of RON/MST1R and HGFL/MST1 in cell lines and primary tumors increases BCSC self-renewal, numbers, and tumorigenic potential after syngeneic transplantation...
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
#14
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/28938599/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#15
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938597/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#16
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#17
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938587/transcriptomic-profiles-of-human-foreskin-fibroblast-cells-in-response-to-orf-virus
#18
Daxiang Chen, Mingjian Long, Bin Xiao, Yufeng Xiong, Huiqin Chen, Yu Chen, Zhenzhan Kuang, Ming Li, Yingsong Wu, Daniel L Rock, Daoyuan Gong, Yong Wang, Haijian He, Fang Liu, Shuhong Luo, Wenbo Hao
Orf virus has been utilized as a safe and efficient viral vector against not only diverse infectious diseases, but also against tumors. However, the nature of the genes triggered by the vector in human cells is poorly characterized. Using RNA sequencing technology, we compared specific changes in the transcriptomic profiles in human foreskin fibroblast cells following infection by the orf virus. The results indicated that orf virus upregulates or downregulates expression of a variety of genes, including genes involved in antiviral immune response, apoptosis, cell cycle and a series of signaling pathways, such as the IFN and p53-signaling pathways...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938585/the-trophoblast-cell-surface-antigen-2-and-mir-125b-axis-in-urothelial-bladder-cancer
#19
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
#20
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
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