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https://www.readbyqxmd.com/read/28346427/mir-21-is-required-for-anti-tumor-immune-response-in-mice-an-implication-for-its-bi-directional-roles
#1
W He, C Wang, R Mu, P Liang, Z Huang, J Zhang, L Dong
Here we show that miR-21, a microRNA known for its oncogenic activity, is also essential for mediating immune responses against tumor. Knockout of miR-21 in mice slowed the proliferation of both CD4(+) and CD8(+) cells, reduced their cytokine production and accelerated the grafted tumor growth. Further investigations indicated that miR-21 could activate CD4(+) and CD8(+) T cells via the PTEN/Akt pathway in response to stimulations. Taken together, these data suggest the key functions of miR-21 in mediating anti-tumor immune response and thereby uncover a bi-directional role of this traditionally known 'oncomiR' in tumorigenesis...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345588/macrophages-induce-akt-%C3%AE-catenin-dependent-lgr5-stem-cell-activation-and-hair-follicle-regeneration-through-tnf
#2
Xusheng Wang, Haiyan Chen, Ruiyun Tian, Yiling Zhang, Marina S Drutskaya, Chengmei Wang, Jianfeng Ge, Zhimeng Fan, Deqiang Kong, Xiaoxiao Wang, Ting Cai, Ying Zhou, Jingwen Wang, Jinmei Wang, Shan Wang, Zhihai Qin, Huanhuan Jia, Yue Wu, Jia Liu, Sergei A Nedospasov, Edward E Tredget, Mei Lin, Jianjun Liu, Yuyang Jiang, Yaojiong Wu
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28342452/contribution-of-genetic-factors-to-platinum-based-chemotherapy-sensitivity-and-prognosis-of-non-small-cell-lung-cancer
#3
REVIEW
Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Miguel Ángel Molina, Ana I Robles, María José Faus-Dáder, Miguel Ángel Calleja-Hernández
Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28341640/impaired-b-cell-function-during-viral-infections-due-to-pten-mediated-inhibition-of-the-pi3k-pathway
#4
Andrew Getahun, Scott M Wemlinger, Pratyaydipta Rudra, Mario L Santiago, Linda F van Dyk, John C Cambier
Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression...
March 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28340593/erratum-to-aryl-hydrocarbon-receptor-cytochrome-p450-1a1-pathway-mediates-breast-cancer-stem-cells-expansion-through-pten-inhibition-and-%C3%AE-catenin-and-akt-activation
#5
Abdullah Al-Dhfyan, Ali Alhoshani, Hesham M Korashy
No abstract text is available yet for this article.
March 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28340209/a-novel-pten-mutation-associated-with-colonic-ganglioneuromatous-polyps
#6
Umair Masood, Natalie Pavelock, Anuj Sharma, Robert Roger Lebel, Anand Gupta, Uma Murthy
No abstract text is available yet for this article.
March 17, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28339086/identification-of-novel-mutations-in-endometrial-cancer-patients-by-whole-exome-sequencing
#7
Ya-Sian Chang, Hsien-Da Huang, Kun-Tu Yeh, Jan-Gowth Chang
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339072/hepatitis-b-virus-x-protein-increases-microrna%C3%A2-21-expression-and-accelerates-the-development-of-hepatoma-via-the-phosphatase-and-tensin-homolog-phosphoinositide-3%C3%A2-kinase-protein-kinase-b-signaling-pathway
#8
Zhouhua Hou, Jun Quan
Hepatitis B virus (HBV) X protein (HBx) is a key regulatory protein that is involved in HBV infection, replication and carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of HBx in the progression and metastasis of liver cancer cells and to determine the underlying molecular mechanism of HBx in metastatic liver cancer cells. HBx protein expression was detected by western blot analysis, and microRNA (miR)‑21 levels were determined by reverse transcription‑quantitative polymerase chain reaction in the highly metastatic MHCC‑97H low metastatic MHCC‑97L and SMMC‑7721 liver cancer cell lines...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339069/transglutaminase-2-is-upregulated-in-primary-hepatocellular-carcinoma-with-early-recurrence-as-determined-by-proteomic-profiles
#9
Hiromi Yamaguchi, Kazumichi Kuroda, Masahiko Sugitani, Tadatoshi Takayama, Kiyoshi Hasegawa, Mariko Esumi
The mechanism of early recurrence of hepato-cellular carcinoma (HCC) is not well understood. To examine whether early intrahepatic metastasis of HCC can be determined by the reliable molecular characteristics of the primary HCC, we focused on early-stage tumors of primary and solitary HCC cases. Proteomic differences were investigated between two groups, 11 early (recurrence within 12 months) and 10 late (no recurrence within 48 months) HCC cases, using two-dimensional fluorescence difference gel electrophoresis...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339030/increased-phosphorylation-of-4e%C3%A2-binding-protein-1-predicts-poor-prognosis-for-patients-with-colorectal-cancer
#10
Yufeng Miao, Lige Chen, Cuifen Shi, Rengen Fan, Ping Chen, Hongqi Liu, Aihua Xia, Haixin Qian
As demonstrated in previous studies, the phosphorylated form of 4E‑binding protein 1 (p‑4E‑BP1) may be a suitable tumor biomarker. The aim of the current study was to examine the expression status of p‑4E‑BP1 in colorectal cancer (CRC), in order to determine its clinical significance. The present study enrolled 89 patients with CRC that had undergone radical resection. Paired tumor and adjacent normal tissues were evaluated using immunohistochemistry to detect the protein expression of p‑4E‑BP1 and phosphatase and tensin homolog (PTEN)...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28337377/the-e3-ubiquitin-ligase-chip-mir-92b-pten-regulatory-network-contributes-to-tumorigenesis-of-glioblastoma
#11
Tao Xu, Hongxiang Wang, Mei Jiang, Yong Yan, Weiqing Li, Hanchong Xu, Qilin Huang, Yicheng Lu, Juxiang Chen
Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337018/rheumatoid-arthritis-fibroblast-like-synoviocyte-suppression-mediated-by-pten-involves-survivin-gene-silencing
#12
Danna Chen, Dongdong Liu, Dan Liu, Min He, Anping Peng, Jiarui Xu, Li Lin, Fudong Luo, Lin Chen, Xianzhang Huang, Junhua Zhuang, Jianhua Xu
Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332494/pten%C3%AE-is-an-alternatively-translated-isoform-of-pten-that-regulates-rdna-transcription
#13
Hui Liang, Xi Chen, Qi Yin, Danhui Ruan, Xuyang Zhao, Cong Zhang, Michael A McNutt, Yuxin Yin
PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTENβ. PTENβ translation is initiated from an AUU codon upstream of and in-frame with the AUG initiation sequence for canonical PTEN. We show that the Kozak context and a downstream hairpin structure are critical for this alternative initiation...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28330462/prospective-phase-ii-trial-of-everolimus-in-pik3ca-amplification-mutation-and-or-pten-loss-patients-with-advanced-solid-tumors-refractory-to-standard-therapy
#14
Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Won Ki Kang, Ho Yeong Lim
BACKGROUND: We designed a single-arm, open-label phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy (#NCT02449538). METHODS: Everolimus was administered orally at a daily dose of 10 mg continuously (28-day cycles). Treatment was continued until progression of the disease or intolerable toxicity was observed. Based on Simon's two-stage optimal design, 10 patients were treated with everolimus during the first stage...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28329541/cowden-syndrome-presenting-with-trichilemmomas
#15
Elise Ng, Vitaly Terushkin, Shane A Meehan, Roger Ho, Miriam Keltz Pomeranz
Cowden syndrome (CS) is a genetic cancerpredisposition syndrome that is associated withgermline mutations in the phosphate and tensinhomologue deleted on chromosome ten (PTEN)tumor suppressor gene. It is characterizedby the formation of benign and malignanttumors. Characteristic benign tumors includetrichilemmommas, acral keratoses, mucocutaneousneuromas, and oral papillomas. The most commonmalignant condition include breast, thyroid, andendometrial cancers. We present a case of a30-year-old woman with CS, who initially presentedwith trichilemmomas that were misdiagnosed ascomedonal acne...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28327666/hypoxia-induces-h19-expression-through-direct-and-indirect-hif-1%C3%AE-activity-promoting-oncogenic-effects-in-glioblastoma
#16
Weining Wu, Qi Hu, Er Nie, Tianfu Yu, Youzhi Wu, Tongle Zhi, Kuan Jiang, Feng Shen, Yingyi Wang, Junxia Zhang, Yongping You
H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325755/loss-of-pink1-leads-to-metabolic-deficits-in-adult-neural-stem-cells-and-impedes-differentiation-of-newborn-neurons-in-the-mouse-hippocampus
#17
Sandeep Kumar Agnihotri, Ruifang Shen, Jihong Li, Xu Gao, Hansruedi Büeler
Emerging evidence suggests that mitochondrial dynamics regulates adult hippocampal neurogenesis (AHN). Although abnormal AHN has been linked to depression, anxiety, and cognitive dysfunction, which are features of neurodegenerative conditions, including Parkinson's disease (PD), the impact of mitochondrial deficits on AHN have not been explored previously in a model of neurodegeneration. Here, we used PTEN-induced kinase 1-deficient (PINK1(-/-) ) mice that lacked a mitochondrial kinase mutated in recessive familial PD...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28323888/lzts2-and-pten-collaboratively-regulate-%C3%A3-catenin-in-prostatic-tumorigenesis
#18
Eun-Jeong Yu, Erika Hooker, Daniel T Johnson, Mi Kyung Kwak, Kang Zou, Richard Luong, Yongfeng He, Zijie Sun
The leucine zipper tumor suppressor 2 (LZTS2) was identified as a tumor susceptibility gene within the 10q24.3 chromosomal region, and is approximately 15Mb from the PTEN locus. This region containing the both loci is frequently deleted in a variety of human malignancies, including prostate cancer. LZTS2 is a ß-catenin-binding protein and a negative regulator of Wnt signaling. Overexpression of PTEN in prostate cancer cell lines reduces ß-catenin-mediated transcriptional activity. In this study, we examined the collaborative effect of PTEN and LZTS2 using multiple in vitro and in vivo approaches...
2017: PloS One
https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#19
ZhengRu Huang, ZiZhong Hu, Ping Xie, QingHuai Liu
Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm...
2017: PloS One
https://www.readbyqxmd.com/read/28323427/kinetin-riboside-and-its-protides-activate-the-parkinson-s-disease-associated-pten-induced-putative-kinase-1-pink1-independent-of-mitochondrial-depolarisation
#20
Laura Osgerby, Yu-Chiang Lai, Peter J Thornton, Joseph Amalfitano, Cécile S Le Duff, Iqra Jabeen, Hachemi Kadri, Ageo Miccoli, James H R Tucker, Miratul M K Muqit, Youcef Mehellou
Since loss of function mutations of PINK1 lead to early-onset Parkinson's disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases...
March 21, 2017: Journal of Medicinal Chemistry
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