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Upik Anderiani Miskad, Muhammad Husni Cangara, Syarifuddin Wahid
No abstract text is available yet for this article.
February 2016: Pathology
Min Thura, Abdul Qader Omer Al-Aidaroos, Wei Peng Yong, Koji Kono, Abhishek Gupta, You Bin Lin, Kousaku Mimura, Jean Paul Thiery, Boon Cher Goh, Patrick Tan, Ross Soo, Cheng William Hong, Lingzhi Wang, Suling Joyce Lin, Elya Chen, Sun Young Rha, Hyun Cheol Chung, Jie Li, Sayantani Nandi, Hiu Fung Yuen, Shu-Dong Zhang, Yeoh Khay Guan, Jimmy So, Qi Zeng
Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues...
June 16, 2016: JCI Insight
Pegah Abdollahi, Esten Nymoen Vandsemb, Magnus Aassved Hjort, Kristine Misund, Toril Holien, Anne-Marit Sponaas, Torstein B Ro, Tobias S Slordahl, Magne Borset
: Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual specificity phosphatase that is up-regulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several anti-apoptotic cytokines, including interleukin-6 (IL6), in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6...
October 3, 2016: Molecular Cancer Research: MCR
Shenyi Lian, Lin Meng, Xiaofang Xing, Yongyong Yang, Like Qu, Chengchao Shou
Phosphatase of regenerating liver-3 (PRL-3), also termed PTP4A3, is a metastasis-related protein tyrosine phosphatase. Its expression levels are significantly correlated with the progression and survival of a wide range of malignant tumors. However, the mechanism by which PRL-3 promotes tumor invasion and metastasis is not clear. In the present study, the functions of PRL-3 were systemically analyzed in the key events of metastasis including, motility and adhesion. A cell wounding assay, cell spread assay and cell-matrix adhesion assay were carried out to analyze the cell movement and cell adhesion ability of colon cancer, immunoprecipitation and immunofluorescence assay was confirmed the interaction of PRL-3 and JAM2...
September 2016: Oncology Letters
Jianbo Xiong, Zhengrong Li, Yang Zhang, Daojiang Li, Guoyang Zhang, Xianshi Luo, Zhigang Jie, Yi Liu, Yi Cao, Zhibiao Le, Shengxing Tan, Wenyu Zou, Peitao Gong, Lingyu Qiu, Yuanyuan Li, Huan Wang, Heping Chen
Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues...
October 2016: Oncology Reports
H H Gari, G D DeGala, M S Lucia, J R Lambert
Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis...
2016: Oncogenesis
Priyanka Soni, Nuzhat Husain, Anil Chandra, Bal Krishan Ojha, Madan Lal Brahma Bhatt, Rakesh Kumar Gupta
CONTEXT: Poor survival of the glioblastoma multiforme (GBM) has been attributed in part to the invasive nature of the lesion making complete surgical removal near impossible. Phosphatase of regenerating liver-3 (PRL-3), matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), and epidermal growth factor receptor (EGFR-1) play a role in invasive nature of tumor cells. AIMS: This study was conducted to evaluate PRL-3, MMP-2, MMP-9, and EGFR-1 (markers) expression in cases to GBM and to correlate their expression with therapy response and survival...
July 2016: Indian Journal of Pathology & Microbiology
Hamid H Gari, Gregory D DeGala, Rahul Ray, M Scott Lucia, James R Lambert
Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels...
October 1, 2016: Cancer Letters
Shifan Ren, Yefang Zhou, Xiaoling Fang, Xiaoling She, Yilin Wu, Xianqing Wu
OBJECTIVE: To investigate the role of phosphatase of regenerating liver-3 (PRL-3) in the 17β-estradiol (E2)- and interleukin 6 (IL-6)-induced migration of endometrial stromal cells (ESCs) from ectopic endometrium. METHODS: Ectopic endometrial tissues were collected from patients with endometriosis, and PRL-3 expression in ectopic and eutopic endometrium was examined by immunohistochemistry. Endometrial stromal cells isolated from ectopic endometrium were treated with E2, progesterone (P), IL-6, or sodium orthovanadate (Sov) to inhibit PRL-3...
May 24, 2016: Reproductive Sciences
Ilan Shimon, Ernesto Sosa, Victoria Mendoza, Yona Greenman, Amit Tirosh, Etual Espinosa, Vera Popovic, Andrea Glezer, Marcello D Bronstein, Moises Mercado
OBJECTIVES: Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized. METHODS: We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. RESULTS: Mean age was 36...
August 2016: Pituitary
Tobias S Slørdahl, Pegah Abdollahi, Esten N Vandsemb, Christoph Rampa, Kristine Misund, Katarzyna A Baranowska, Marita Westhrin, Anders Waage, Torstein B Rø, Magne Børset
Multiple myeloma (MM) is a neoplastic proliferation of bone marrow plasma cells. PRL-3 is a phosphatase induced by interleukin (IL)-6 and other growth factors in MM cells and promotes MM-cell migration. PRL-3 has also been identified as a marker gene for a subgroup of patients with MM. In this study we found that forced expression of PRL-3 in the MM cell line INA-6 led to increased survival of cells that were depleted of IL-6. It also caused redistribution of cells in cell cycle, with an increased number of cells in G2M-phase...
May 10, 2016: Oncotarget
Esten N Vandsemb, Helena Bertilsson, Pegah Abdollahi, Øystein Størkersen, Thea Kristin Våtsveen, Morten Beck Rye, Torstein Baade Rø, Magne Børset, Tobias S Slørdahl
BACKGROUND: PRL-3 is a phosphatase implicated in oncogenesis in multiple cancers. In some cancers, notably carcinomas, PRL-3 is also associated with inferior prognosis and increased metastatic potential. In this study we investigated the expression of PRL-3 mRNA in fresh-frozen samples from patients undergoing radical prostatectomy because of prostate cancer (PC) and the biological function of PRL-3 in prostate cancer cells. METHODS: Samples from 41 radical prostatectomy specimens (168 samples in total) divided into low (Gleason score ≤ 6), intermediate (Gleason score = 7) and high (Gleason score ≥ 8) risk were analyzed with gene expression profiling and compared to normal prostate tissue...
2016: Journal of Translational Medicine
Sheng-Yi Lin, Yue-Xun Lee, Sung-Liang Yu, Gee-Chen Chang, Jeremy J W Chen
Phosphatase of regenerating liver-3 (PRL-3) has been reported to be associated with colon and gastric cancer metastasis. However, the role and function of PRL-3 in human non-small cell lung cancer cells is unknown. Our studies showed that the expression of PRL-3mRNA and protein are higher in less invasive human lung adenocarcinoma cells than in highly invasive cell lines. Ectopic expression of PRL-3 reduced cell capacity for anchorage-dependent growth, anchorage-independent growth, migration, and invasion in vitro, as well as tumorigenesis in vivo...
April 19, 2016: Oncotarget
Petra den Hollander, Kathryn Rawls, Anna Tsimelzon, Jonathan Shepherd, Abhijit Mazumdar, Jamal Hill, Suzanne A W Fuqua, Jenny C Chang, C Kent Osborne, Susan G Hilsenbeck, Gordon B Mills, Powel H Brown
Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared with estrogen receptor (ER)-positive tumors...
April 1, 2016: Cancer Research
Hamid H Gari, Christy M Gearheart, Susan Fosmire, Gregory D DeGala, Zeying Fan, Kathleen C Torkko, Susan M Edgerton, M Scott Lucia, Rahul Ray, Ann D Thor, Christopher C Porter, James R Lambert
Triple-negative breast cancers (TNBC) are among the most aggressive and heterogeneous cancers with a high propensity to invade, metastasize and relapse. Here, we demonstrate that the anticancer compound, AMPI-109, is selectively efficacious in inhibiting proliferation and inducing apoptosis of multiple TNBC subtype cell lines as assessed by activation of pro-apoptotic caspases-3 and 7, PARP cleavage and nucleosomal DNA fragmentation. AMPI-109 had little to no effect on growth in the majority of non-TNBC cell lines examined...
March 29, 2016: Oncotarget
Hong Zhan, Junyan Ma, Fei Ruan, Mohamed A Bedaiwy, Bo Peng, Ruijin Wu, Jun Lin
STUDY QUESTION: Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma? SUMMARY ANSWER: Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma. WHAT IS KNOWN ALREADY: Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype. STUDY DESIGN, SIZE, DURATION: Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26)...
April 2016: Human Reproduction
Li Li, Hongshun Shi, Mingming Zhang, Xiaoling Guo, Fang Tong, Wenliang Zhang, Junyi Zhou, Haihe Wang, Shulan Yang
The metastasis-associated phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in progression of various human cancers; however, significance of its role during development has not been addressed. Here we cloned and characterized the expression pattern of zebrafish prl-3 transcript and showed that it is ubiquitiously expressed in the first 24 h of development with both maternal and zygotic expressions. The transcripts become progressively restricted to the notochord, vessels and the intestine by 96 h post-fertilization...
April 2016: International Journal of Oncology
Zu Ye, Abdul Qader Omer Al-Aidaroos, Jung Eun Park, Hiu Fung Yuen, Shu Dong Zhang, Abhishek Gupta, Youbin Lin, Han-Ming Shen, Qi Zeng
PRL-3, a metastasis-associated phosphatase, is known to exert its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1 (mTORC1), but a coherent link between PRL-3 and activation of mTOR has not yet been formally demonstrated. We report a positive correlation between PRL-3 expression and mTOR phospho-activation in clinical tumour samples and mouse models of cancer and demonstrate that PRL-3 increased downstream signalling to the mTOR substrates, p70S6K and 4E-BP1, by increasing PI3K/Akt-mediated activation of Rheb-GTP via TSC2 suppression...
2015: Scientific Reports
Cheng Zhang, Wei Tian, Lin Meng, Like Qu, Chengchao Shou
UNLABELLED: Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues...
April 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
D Aydin, A Bilici, S Kayahan, D Yavuzer, M Basar, M Aliustaoglu
BACKGROUND: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. METHODS: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. RESULTS: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression...
June 2016: Clinical & Translational Oncology
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