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https://www.readbyqxmd.com/read/29348559/plk1-protects-against-sepsis-induced-intestinal-barrier-dysfunction
#1
Yingya Cao, Qun Chen, Zhen Wang, Tao Yu, Jingyi Wu, Xiaogan Jiang, Xiaoju Jin, Weihua Lu
Sepsis and sepsis-associated intestinal barrier dysfunction are common in intensive care units, with high mortality. The aim of this study is to investigate whether Polo-like kinase 1 (PLK1) ameliorates sepsis-induced intestinal barrier dysfunction in the intestinal epithelium. The mouse intestinal barrier was disrupted after Lipopolysaccharide (LPS) injection due to intestinal epithelial cell apoptosis and proliferation inhibition, accompanied by decreased PLK1. In HT-29 intestinal epithelial cells, LPS stimulation induced cell apoptosis and inhibited cell proliferation...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339720/plumbagin-inhibits-the-proliferation-and-survival-of-esophageal-cancer-cells-by-blocking-stat3-plk1-akt-signaling
#2
Ying-Ya Cao, Jing Yu, Ting-Ting Liu, Kai-Xia Yang, Li-Yan Yang, Qun Chen, Feng Shi, Jia-Jie Hao, Yan Cai, Ming-Rong Wang, Wei-Hua Lu, Yu Zhang
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent manner in vitro. The drug also effectively inhibited the viability of primary ESCC cells from fresh biopsy specimens. Furthermore, plumbagin-induced mitotic arrest and massive apoptosis in ESCC cells...
January 16, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29331044/journey-of-oocyte-from-metaphase-i-to-metaphase-ii-stage-in-mammals
#3
Alka Sharma, Meenakshi Tiwari, Anumegha Gupta, Ashutosh N Pandey, Pramod K Yadav, Shail K Chaube
In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage...
January 13, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29329658/novel-compounds-with-potent-cdk9-inhibitory-activity-for-the-treatment-of-myeloma
#4
Zsófia Czudor, Mária Balogh, Péter Bánhegyi, Sándor Boros, Nóra Breza, Judit Dobos, Márk Fábián, Zoltán Horváth, Eszter Illyés, Péter Markó, Anna Sipos, Csaba Szántai-Kis, Bálint Szokol, László Őrfi
Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226)...
January 2, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29295989/amphiphilic-nanocarrier-induced-modulation-of-plk1-and-mir-34a-leads-to-improved-therapeutic-response-in-pancreatic-cancer
#5
Hadas Gibori, Shay Eliyahu, Adva Krivitsky, Dikla Ben-Shushan, Yana Epshtein, Galia Tiram, Rachel Blau, Paula Ofek, Joo Sang Lee, Eytan Ruppin, Limor Landsman, Iris Barshack, Talia Golan, Emmanuelle Merquiol, Galia Blum, Ronit Satchi-Fainaro
The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29288948/design-synthesis-and-biological-evaluation-of-polo-like-kinase-1-eukaryotic-elongation-factor-2-kinase-plk1-eef2k-dual-inhibitors-for-regulating-breast-cancer-cells-apoptosis-and-autophagy
#6
Zhaoping Pan, Yujuan Chen, Jingyan Liu, Qinglin Jiang, Shengyong Yang, Li Guo, Gu He
Both PLK1 and EEF2K are serine⁄threonine kinases that play important roles in the proliferation and programmed cell death of various types of cancer. They are highly expressed in breast cancer tissues. Based on the multiple-complexes generated pharmacophore models of PLK1 and homology models of EEF2K, the integrated virtual screening is performed to discover novel PLK1/EEF2K dual inhibitors. The top ten hit compounds are selected and tested in vitro, and five of them display PLK1 and EEF2K inhibition in vitro...
December 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29284501/nucleoli-cytomorphology-in-cutaneous-melanoma-cells-a-new-prognostic-approach-to-an-old-concept
#7
Piotr Donizy, Przemyslaw Biecek, Agnieszka Halon, Adam Maciejczyk, Rafal Matkowski
BACKGROUND: The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients. Moreover, we analyzed the correlation between cytomorphological parameters of nucleoli and immunoreactivity of selected proteins responsible for, among others, regulation of epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and motility (ALCAM, ADAM-10), mitotic divisions (PLK1), cellular survival (FOXP1) and the functioning of Golgi apparatus (GOLPH3, GP73)...
December 29, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29282278/gravin-regulates-centrosome-function-through-plk1
#8
Erica G Colicino, Alice M Garrastegui, Judy Freshour, Peu Santra, Dawn E Post, Leszek Kotula, Heidi Hehnly
Here we propose to understand how the mitotic kinase PLK1 drives chromosome segregation errors, with a specific focus on Gravin, a PLK1 scaffold. In both 3-D primary prostate cancer cell cultures that are prone to Gravin-depletion and Gravin shRNA treated cells, an increase in cells containing micronuclei was noted when compared to controls. To examine whether the loss of Gravin affected PLK1 distribution and activity we utilized photokinetics and a PLK1 activity-biosensor. Gravin-depletion resulted in an increased PLK1 mobile fraction, causing the redistribution of active-PLK1 that leads to increased defocusing and phosphorylation of the mitotic centrosome protein CEP215 at serine-613...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29246203/comprehensive-analysis-of-differentially-expressed-genes-associated-with-plk1-in-bladder-cancer
#9
Zhe Zhang, Guojun Zhang, Zhipeng Gao, Shiguang Li, Zeliang Li, Jianbin Bi, Xiankui Liu, Zhenhua Li, Chuize Kong
BACKGROUND: The significance of PLK1 (polo-like kinase 1) has become increasingly essential as both a biomarker and a target for cancer treatment. Here, we aimed to determine the downstream genes of PLK1 and their effects on the carcinogenesis and progression of bladder cancer. METHODS: Specific siRNA was utilized to silence the target gene expression. The cell proliferation, invasion and migration of bladder cancer cells by MTT assay, BrdU assay and transwell assay...
December 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29233929/single-cell-rna-seq-reveals-a-subpopulation-of-prostate-cancer-cells-with-enhanced-cell-cycle-related-transcription-and-attenuated-androgen-response
#10
Aaron M Horning, Yao Wang, Che-Kuang Lin, Anna D Louie, Rohit R Jadhav, Chia-Nung Hung, Chiou-Miin Wang, Chun-Lin Lin, Nameer B Kirma, Michael A Liss, Addanki P Kumar, LuZhe Sun, Zhijie Liu, Wei-Ting Chao, Qianben Wang, Victor X Jin, Chun-Liang Chen, Tim H-M Huang
Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen-deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228663/targeting-plk1-as-a-novel-chemopreventive-approach-to-eradicate-preneoplastic-mucosal-changes-in-the-head-and-neck
#11
D Vicky de Boer, Sanne R Martens-de Kemp, Marijke Buijze, Marijke Stigter-van Walsum, Elisabeth Bloemena, Ralf Dietrich, C René Leemans, Victor W van Beusechem, Boudewijn J M Braakhuis, Ruud H Brakenhoff
Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified Polo-like kinase 1 (PLK1) as essential for survival of preneoplastic cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228610/targeting-polo-like-kinase-1-in-smarcb1-deleted-atypical-teratoid-rhabdoid-tumor
#12
Irina Alimova, Angela M Pierce, Peter Harris, Andrew Donson, Diane K Birks, Eric Prince, Ilango Balakrishnan, Nicholas K Foreman, Marcel Kool, Lindsey Hoffman, Sujatha Venkataraman, Rajeev Vibhakar
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive and malignant pediatric brain tumor. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and essential for mitosis. Overexpression of PLK1 promotes chromosome instability and aneuploidy by overriding the G2-M DNA damage and spindle checkpoints. Recent studies suggest that targeting PLK1 by small molecule inhibitors is a promising approach to tumor therapy. We investigated the effect of PLK1 inhibition in ATRT. Gene expression analysis showed that PLK1 was overexpressed in ATRT patient samples and tumor cell lines...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220793/design-synthesis-and-biological-evaluation-of-novel-highly-selective-polo-like-kinase-2-inhibitors-based-on-the-tetrahydropteridin-chemical-scaffold
#13
Mei-Miao Zhan, Yang Yang, Jinfeng Luo, Xing-Xing Zhang, Xuan Xiao, Shiyu Li, Kai Cheng, Zhouling Xie, Zhengchao Tu, Chenzhong Liao
Polo-like kinase 2 (Plk2) is a potential target for the treatment of cancer, which displays an important role in tumor cell proliferation and survival. In this report, according to the analysis of critical amino acid residue differences among Plk1, Plk2 and Plk3, and structure-based drug design strategies, two novel series of selective Plk2 inhibitors based on tetrahydropteridin chemical scaffold were designed and synthesized to target two specific residues, Lys86 and Tyr161 of Plk2. All compounds were evaluated for their inhibitory activity against Plk1-Plk3 and the cellular inhibition activity on six different human cancer cell lines...
November 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#14
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29209646/re-investigating-plk1-inhibitors-as-antimitotic-agents
#15
Quentin Delacour, Olivier Gavet
Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the development of PLK1 inhibitors for anticancer therapy. We recently determined that PLK1 is crucially required for entry into mitosis. Hence, we discuss the potential and limitations of PLK1 inhibition strategies to promote mitotic arrest and death of cancer cells.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29201613/genome-editing-for-cancer-therapy-delivery-of-cas9-protein-sgrna-plasmid-via-a-gold-nanocluster-lipid-core-shell-nanocarrier
#16
Peng Wang, Lingmin Zhang, Yangzhouyun Xie, Nuoxin Wang, Rongbing Tang, Wenfu Zheng, Xingyu Jiang
The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 (CRISPR-associated protein) system (CRISPR-Cas9) is a powerful toolbox for gene-editing, however, the nonviral delivery of CRISPR-Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV-1-transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei...
November 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29191835/phosphorylation-of-human-enhancer-filamentation-1-hef1-stimulates-interaction-with-polo-like-kinase-1-leading-to-hef1-localization-to-focal-adhesions
#17
Kyung Ho Lee, Jeong-Ah Hwang, Sun-Ok Kim, Jung Hee Kim, Sang Chul Shin, Eunice EunKyeong Kim, Kyung S Lee, Kunsoo Rhee, Byeong Hwa Jeon, Jeong Kyu Bang, Hyunjoo Cha-Molstad, Nak-Kyun Soung, Jae-Hyuk Jang, Sung-Kyun Ko, Hee Gu Lee, Jong Seog Ahn, Yong Tae Kwon, Bo Yeon Kim
Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, upregulation of polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29191522/cyclodextrin-sirna-conjugates-as-versatile-gene-silencing-agents
#18
Meenakshi Malhotra, Matt Gooding, James C Evans, Daniel O'Driscoll, Raphael Darcy, Caitriona O'Driscoll
Functional siRNAs (luciferase and PLK1) have been conjugated to β-cyclodextrin and the ability of the conjugates to retain gene knockdown activity has been assessed by delivery to cancer cell lines using various formulations. Initially two formulations used complexation with polycations, namely Lipofectamine 2000 and an amphiphilic polycationic cyclodextrin. Gene knockdown results for human glioblastoma cells (U87) and prostate cancer cells (PC3, DU145) showed that conjugation to the cyclodextrin did not reduce gene silencing by the RNA...
November 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29190933/the-anticipating-value-of-plk1-for-diagnosis-progress-and-prognosis-and-its-prospective-mechanism-in-gastric-cancer-a-comprehensive-investigation-based-on-high-throughput-data-and-immunohistochemical-validation
#19
Peng Lin, Dan-Dan Xiong, Yi-Wu Dang, Hong Yang, Yun He, Dong-Yue Wen, Xin-Gan Qin, Gang Chen
Polo-like kinase 1 (PLK1) is a multi-functional protein and its aberrant expression is a driver of cancerous transformation and progression. To increase our understanding of the clinical value and potential molecular mechanism of PLK1 in gastric cancer (GC), we performed this comprehensive investigation. A total of 25 datasets and 12 publications were finally incorporated. Additional immunohistochemistry was conducted to validate the expression pattern of PLK1 in GC. The pooled standard mean deviation (SMD) indicated that PLK1 mRNA was up-regulated in GC (SMD=1...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187890/decreased-kpnb1-expression-is-induced-by-plk1-inhibition-and-leads-to-apoptosis-in-lung-adenocarcinoma
#20
Noboru Sekimoto, Yutaka Suzuki, Sumio Sugano
Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being the most frequently diagnosed subtype in Japan. Finding the target of an anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of PLK1 inhibitors have been identified for cancer treatments. In this study, we looked for the target gene of the anticancer drug that has synergy with PLK1 inhibitors...
2017: Journal of Cancer
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