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https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#1
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28431929/effects-of-naturally-occurring-charged-mutations-on-the-structure-stability-and-binding-of-the-pin1-ww-domain
#2
Xiaoya Qiao, Ying Liu, Liting Luo, Lei Chen, Caixian Zhao, Xuanjun Ai
Pin1 is a peptidyl-prolyl cis-trans isomerase, whose WW domain specifically recognizes the pSer/Thr-Pro motif. Pin1 is involved in multiple phosphorylation events that regulate the activities of various substrates, and Pin1 deregulation has been reported in various diseases, including cancer and Alzheimer's disease. The WW domain of Pin1 has been used as a small model protein to investigate the folding mechanisms of the β-sheet structure by studying the effect of mutations or its naturally occurring variants...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28426725/dynamic-regulation-of-pin1-expression-and-function-during-zebrafish-development
#3
Maria Solange Ibarra, Carla Borini Etichetti, Carolina Di Benedetto, Germán L Rosano, Ezequiel Margarit, Giannino Del Sal, Marina Mione, Javier Girardini
The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed phosphorylation signaling by inducing local conformational changes in phosphorylated protein substrates. Extensive studies showed different roles for Pin1 in physiological processes and pathological conditions such as cancer and neurodegenerative diseases. However, there are still several unanswered questions regarding its biological role. Notably, despite evidences from cultured cells showing that Pin1 expression and activity may be regulated by different mechanisms, little is known on their relevance in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28411196/correction-senp1-desumoylates-and-regulates-pin1-protein-activity-and-cellular-function
#4
(no author information available yet)
No abstract text is available yet for this article.
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#5
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383568/microrna-140-5p-inhibits-hepatocellular-carcinoma-by-directly-targeting-the-unique-isomerase-pin1-to-block-multiple-cancer-driving-pathways
#6
Xingxue Yan, Zhendong Zhu, Shenmin Xu, Li-Nan Yang, Xin-Hua Liao, Min Zheng, Dayun Yang, Jichuang Wang, Dongmei Chen, Long Wang, Xiaolong Liu, Jingfeng Liu, Ruey-Hwa Chen, Xiao Zhen Zhou, Kun Ping Lu, Hekun Liu
Hepatocellular carcinoma (HCC) is the second leading cause of cancer related-death. As a major common regulator of numerous cancer-driving pathways and a unique therapeutic target, the prolyl isomerase Pin1 is overexpressed in a majority of HCCs, whereas the mechanism underlying Pin1 overexpression remains elusive. Here we find that miR-140-5p inhibits HCC by directly targeting Pin1 to block multiple cancer-driving pathways. Bioinformatics analysis, miRNA binding and functional assays identify that miR-140-5p directly interacts with the 3'UTR of Pin1 and inhibits Pin1 translation...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365778/deficiency-of-cks1-leads-to-learning-and-long-term-memory-defects-and-p27-dependent-formation-of-neuronal-cofilin-aggregates
#7
Alexander Kukalev, Yiu-Ming Ng, Limei Ju, Amal Saidi, Sophie Lane, Angeles Mondragon, Dirk Dormann, Sophie E Walker, William Grey, Philip Wing-Lok Ho, David N Stephens, Antony M Carr, Karri Lamsa, Eric Tse, Veronica P C C Yu
In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in post-mitotic neurons of the adult hippocampus. Interestingly, Cks1 knockout (Cks1-/-) mice exhibited poor long-term memory, and diminished maintenance of long-term potentiation in the hippocampal circuits. Furthermore, there was neuronal accumulation of cofilin-actin rods or cofilin aggregates, which are associated with defective dendritic spine maturation and synaptic loss...
January 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28356516/efficacy-long-term-toxicity-and-mechanistic-studies-of-gold-nanorods-photothermal-therapy-of-cancer-in-xenograft-mice
#8
Moustafa R K Ali, Mohammad Aminur Rahman, Yue Wu, Tiegang Han, Xianghong Peng, Megan A Mackey, Dongsheng Wang, Hyung Ju Shin, Zhuo G Chen, Haopeng Xiao, Ronghu Wu, Yan Tang, Dong M Shin, Mostafa A El-Sayed
Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28350086/imazamethabenz-inhibits-human-breast-cancer-cell-proliferation-migration-and-invasion-via-combination-with-pin1
#9
Chen Liu, Chaoyu Mu, Zeng Li, Liang Xu
Overexpression of peptidyl-prolyl cis/trans isomerase, NIMA interacting‑1 (Pin1) is a significant marker of the occurrence and development of tumors. In the present study, the imidazoline ketone herbicide imazamethabenz was investigated as a potential antitumor drug by inhibiting Pin1. Molecular docking and enzyme activity tests verified, for the first time, that the imidazoline ketone compound imazamethabenz effectively inhibited Pin1 in vitro. MTT assays, western blotting, wound healing assay and Matrigel invasion assays revealed that imazamethabenz induced apoptosis and inhibited migration and invasion of the breast cancer cell line MCF‑7, which overexpresses Pin1, by inhibiting the Pin1‑mediated signaling pathway involving vascular endothelial growth factor and matrix metalloproteinase 9...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28340324/vps36-mediated-plasma-membrane-protein-turnover-is-critical-for-arabidopsis-root-gravitropism
#10
Ya-Wen Hsu, Guang-Yuh Jauh
The gravitropic response is an evolutionary adaptation for plants to cope with the altered gravitational field. It involves reestablishing the distribution of the phytohormone auxin by differential degradation of auxin influx and efflux carriers. This process includes the endosomal sorting complexes required for transport (ESCRT) machinery to recognize ubiquitinated proteins and deliver them to vacuoles for degradation, as evidenced by vps36-1 mutants. Here, we generated RNAi knockdown plants of Vacuolar Protein Sorting 36 (VPS36) that could survive to adulthood...
March 24, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28326089/dynamic-regulation-of-auxin-response-during-rice-development-revealed-by-newly-established-hormone-biosensor-markers
#11
Jing Yang, Zheng Yuan, Qingcai Meng, Guoqiang Huang, Christophe Périn, Charlotte Bureau, Anne-Cécile Meunier, Mathieu Ingouff, Malcolm J Bennett, Wanqi Liang, Dabing Zhang
The hormone auxin is critical for many plant developmental processes. Unlike the model eudicot plant Arabidopsis (Arabidopsis thaliana), auxin distribution and signaling in rice tissues has not been systematically investigated due to the absence of suitable auxin response reporters. In this study we observed the conservation of auxin signaling components between Arabidopsis and model monocot crop rice (Oryza sativa), and generated complementary types of auxin biosensor constructs, one derived from the Aux/IAA-based biosensor DII-VENUS but constitutively driven by maize ubiquitin-1 promoter, and the other termed DR5-VENUS in which a synthetic auxin-responsive promoter (DR5rev ) was used to drive expression of the yellow fluorescent protein (YFP)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28325828/the-prolyl-isomerase-pin1-is-a-novel-target-of-6-7-4-trihydroxyisoflavone-for-suppressing-esophageal-cancer-growth
#12
Tae Gyu Lim, Sung-Young Lee, Zhaoheng Duan, Mee-Hyun Lee, Hanyong Chen, Fangfang Liu, Kangdong Liu, Sung Keun Jung, Dong Joon Kim, Ann M Bode, Ki Won Lee, Zigang Dong
Intake of soy isoflavones is inversely associated with the risk of esophageal cancer. Numerous experimental results have supported the anti-cancer activity of soy isoflavones. The current study aimed to determine the anti-esophageal cancer activity of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, which is readily metabolized in the human body. Notably, 6,7,4'-THIF inhibited proliferation and increased apoptosis of esophageal cancer cells. Based on a virtual screening analysis, Pin1 was identified as a target protein of 6,7,4'-THIF...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28300760/the-essential-role-of-pin1-via-nf-%C3%AE%C2%BAb-signaling-in-vascular-inflammation-and-atherosclerosis-in-apoe-mice
#13
Ming Liu, Peng Yu, Hong Jiang, Xue Yang, Ji Zhao, Yunzeng Zou, Junbo Ge
Atherosclerosis, as a chronic inflammatory disease, is the major underlying cause of death worldwide. However, the mechanisms that underlie the inflammatory process are not completely understood. Prolyl-isomerase-1 (Pin1), as a unique peptidyl-prolyl isomerase, plays an important role in inflammation and endothelial dysfunction. Herein, we investigate whether Pin1 regulates vascular inflammation and atherosclerosis, and clarify its mechanisms in these processes. ApoE(-/-) mice were randomly given either juglone (0...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28300139/fine-tuning-the-extent-and-dynamics-of-binding-cleft-opening-as-a-potential-general-regulatory-mechanism-in-parvulin-type-peptidyl-prolyl-isomerases
#14
András Czajlik, Bertalan Kovács, Perttu Permi, Zoltán Gáspári
Parvulins or rotamases form a distinct group within peptidyl prolyl cis-trans isomerases. Their exact mode of action as well as the role of conserved residues in the family are still not unambiguously resolved. Using backbone S(2) order parameters and NOEs as restraints, we have generated dynamic structural ensembles of three distinct parvulins, SaPrsA, TbPin1 and CsPinA. The resulting ensembles are in good agreement with the experimental data but reveal important differences between the three enzymes. The largest difference can be attributed to the extent of the opening of the substrate binding cleft, along which motional mode the three molecules occupy distinct regions...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270611/coordination-of-auxin-triggered-leaf-initiation-by-tomato-leafless
#15
Yossi Capua, Yuval Eshed
Lateral plant organs, particularly leaves, initiate at the flanks of the shoot apical meristem (SAM) following auxin maxima signals; however, little is known about the underlying mechanisms. Here, we show that tomato leafless (lfs) mutants fail to produce cotyledons and leaves and grow a naked pin while maintaining an active SAM. A similar phenotype was observed among pin-like shoots induced by polar auxin transport inhibitors such as 2,3,5-triiodobenzoic acid (TIBA). Both types of pin-like shoots showed reduced expression of primordia markers as well as abnormal auxin distribution, as evidenced by expression of the auxin reporters pPIN1:PIN1:GFP and DR5:YFP Upon auxin microapplication, both lfs meristems and TIBA-pin apices activated DR5:YFP expression with similar kinetics; however, only lfs plants failed to concurrently initiate leaf primordia...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28262728/chemical-or-genetic-pin1-inhibition-exerts-potent-anticancer-activity-against-hepatocellular-carcinoma-by-blocking-multiple-cancer-driving-pathways
#16
Xin-Hua Liao, Arina Li Zhang, Min Zheng, Mei-Qing Li, Champ Peng Chen, Huijuan Xu, Qing-Song Chu, Dayun Yang, Wenxian Lu, Ting-Fen Tsai, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant cancers with high inter- and intra-tumor heterogeneity. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 is prevalently overexpressed in human cancers including ~70% of HCC, and promotes tumorigenesis by activating multiple cancer-driving pathways. However, it was challenging to evaluate the significance of targeting Pin1 in cancer treatment until the recent identification of all-trans retinoic acid (ATRA) as a Pin1 inhibitor...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239767/down-regulation-of-pin1-in-temporal-lobe-epilepsy-patients-and-mouse-model
#17
Lan Tang, Yanke Zhang, Guojun Chen, Yan Xiong, Xuefeng Wang, Binglin Zhu
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique PPIase belonging to the parvulin family, and it isomerizes peptide bond between phospho-(Ser/Thr) and Pro. Pin1 has been linked to the pathogenesis of various human diseases; however, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of Pin1 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic mouse model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that Pin1 protein was mainly distributed in neurons, demonstrated by colocalization with the dendritic marker, MAP2...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214206/involvement-of-prolyl-isomerase-pin1-in-the-cell-cycle-progression-and-proliferation-of-hepatic-oval-cells
#18
Prabodh Risal, Nirajan Shrestha, Lokendra Chand, Karl G Sylvester, Yeon Jun Jeong
Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation...
January 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28212614/transcriptomic-profiling-provides-molecular-insights-into-hydrogen-peroxide-induced-adventitious-rooting-in-mung-bean-seedlings
#19
Shi-Weng Li, Yan Leng, Rui-Fang Shi
BACKGROUND: Hydrogen peroxide (H2O2) has been known to function as a signalling molecule involved in the modulation of various physiological processes in plants. H2O2 has been shown to act as a promoter during adventitious root formation in hypocotyl cuttings. In this study, RNA-Seq was performed to reveal the molecular mechanisms underlying H2O2-induced adventitious rooting. RESULTS: RNA-Seq data revealed that H2O2 treatment greatly increased the numbers of clean reads and expressed genes and abundance of gene expression relative to the water treatment...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28203298/prolyl-isomerase-pin1-and-neurotrophins-a-loop-that-may-determine-the-fate-of-cells-in-cancer-and-neurodegeneration
#20
REVIEW
Francesco Angelucci, Jakub Hort
Increased survival, differentiation, and apoptotic death are common mechanisms relevant for both cancer and neurodegenerative diseases. Although these disorders are characterized by different manifestations, it appears that a common mechanism may be present which directs the fate of a cell to either degeneration or proliferation. There are two classes of proteins that have been extensively investigated in these diseases but their possible interaction during signal transduction has not been studied. Prolyl isomerase Pin1 is an enzyme which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates...
January 2017: Therapeutic Advances in Medical Oncology
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