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https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#1
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#2
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862552/solution-structure-of-the-first-rna-recognition-motif-domain-of-human-spliceosomal-protein-sf3b49-and-its-mode-of-interaction-with-a-sf3b145-fragment
#3
Kanako Kuwasako, Nobukazu Nameki, Kengo Tsuda, Mari Takahashi, Atsuko Sato, Naoya Tochio, Makoto Inoue, Takaho Terada, Takanori Kigawa, Naohiro Kobayashi, Mikako Shirouzu, Takuhiro Ito, Taiichi Sakamoto, Kaori Wakamatsu, Peter Güntert, Seizo Takahashi, Shigeyuki Yokoyama, Yutaka Muto
The spliceosomal protein SF3b49, a component of the splicing factor 3b (SF3b) protein complex in the U2 small nuclear ribonucleoprotein, contains two RNA recognition motif (RRM) domains. In yeast, the first RRM domain (RRM1) of Hsh49 protein (yeast orthologue of human SF3b49) reportedly interacts with another component, Cus1 protein (orthologue of human SF3b145). Here, we solved the solution structure of the RRM1 of human SF3b49 and examined its mode of interaction with a fragment of human SF3b145 using NMR methods...
November 16, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27799531/recognition-of-the-3-splice-site-rna-by-the-u2af-heterodimer-involves-a-dynamic-population-shift
#4
Lena Voith von Voithenberg, Carolina Sánchez-Rico, Hyun-Seo Kang, Tobias Madl, Katia Zanier, Anders Barth, Lisa R Warner, Michael Sattler, Don C Lamb
An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27748721/precision-medicine-and-pancreatic-cancer-a-gemcitabine-pathway-approach
#5
James J Farrell, Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine...
November 2016: Pancreas
https://www.readbyqxmd.com/read/27587543/polymorphisms-in-cancer-related-pathway-genes-and-lung-cancer
#6
Shin Yup Lee, Hyo-Gyoung Kang, Jin Eun Choi, Deuk Kju Jung, Won Kee Lee, Hyun Chul Lee, So Yeon Lee, Seung Soo Yoo, Jaehee Lee, Yangki Seok, Eung Bae Lee, Seung Ick Cha, Sukki Cho, Chang Ho Kim, Myung Hoon Lee, Jae Yong Park
We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication...
October 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27579614/gbm-associated-mutations-and-altered-protein-expression-are-more-common-in-young-patients
#7
Sherise D Ferguson, Joanne Xiu, Shiao-Pei Weathers, Shouhao Zhou, Santosh Kesari, Stephanie E Weiss, Roeland G Verhaak, Raymond J Hohl, Geoffrey R Barger, Sandeep K Reddy, Amy B Heimberger
BACKGROUND: Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age ≥ 70) and younger (18 < = age < = 45) cohort to explore potential therapeutic opportunities. RESULTS: Alterations more prevalent in the young GBM cohort compared to the older cohort (P < 0.05) were: overexpression of ALK, RRM1, TUBB3 and mutation of ATRX, BRAF, IDH1, and TP53...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27576612/gene-expression-ratio-as-a-predictive-determinant-of-nelarabine-chemosensitivity-in-t-lymphoblastic-leukemia-lymphoma
#8
Pornpun Sripornsawan, Yasuhiro Okamoto, Takuro Nishikawa, Yuichi Kodama, Yuni Yamaki, Koichiro Kurauchi, Takayuki Tanabe, Shunsuke Nakagawa, Yuichi Shinkoda, Naoko Imuta, Yoshifumi Kawano
BACKGROUND: Nelarabine has been used for the treatment of T-cell malignancies including T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma. However, the mechanisms that underlie the susceptibility or resistance to nelarabine have not been fully elucidated. The aim of this study was to determine the significance of nelarabine transport and metabolism in the context of nelarabine cytotoxicity. PROCEDURE: The expression profiles of six genes in the nelarabine pathway were analyzed in blast cells from six patients with T-ALL as well as in three T-ALL cell lines...
August 31, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27566080/rrm1-rrm2-and-ercc2-gene-polymorphisms-in-coronary-artery-disease
#9
Emre Murat Altinkilic, Selim Isbir, Uzay Gormus, Seda Gulec Yilmaz, Altay Burak Dalan, Selvi Duman, Turgay Isbir
BACKGROUND/AIM: Coronary artery disease (CAD) is a chronic inflammatory disease seen as formation of atherosclerotic plaques (atheroma) in coronary arteries. Recent published papers show that DNA damage and repair mechanisms play a crucial role on the development and severity of atheromas. In this study, we investigated nucleotide excision repair (NER) pathway-related gene polymorphisms in atherosclerosis. XPD, encoded by ERCC2 gene, is an ATP-depended helicase enzyme involved in the NER pathway...
September 2016: In Vivo
https://www.readbyqxmd.com/read/27551518/repositioning-of-a-cyclin-dependent-kinase-inhibitor-gw8510-as-a-ribonucleotide-reductase-m2-inhibitor-to-treat-human-colorectal-cancer
#10
Y-Y Hsieh, C-J Chou, H-L Lo, P-M Yang
Colorectal cancer (CRC) is the second leading cause of cancer-related death in males and females in the world. It is of immediate importance to develop novel therapeutics. Human ribonucleotide reductase (RRM1/RRM2) has an essential role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools. RRM2 is a prognostic biomarker and predicts poor survival of CRC. In addition, increased RRM2 activity is associated with malignant transformation and tumor cell growth...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27502726/predictors-of-chemotherapy-efficacy-in-non-small-cell-lung-cancer-a-challenging-landscape
#11
K A Olaussen, S Postel-Vinay
BACKGROUND: Conventional cytotoxic chemotherapy (CCC) is the backbone of non-small-cell lung cancer (NSCLC) treatment since decades and still represents a key element of the therapeutic armamentarium. Contrary to molecularly targeted therapies and immune therapies, for which predictive biomarkers of activity have been actively looked for and developed in parallel to the drug development process ('companion biomarkers'), no patient selection biomarker is currently available for CCC, precluding customizing treatment...
August 8, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27483029/interaction-of-individual-structural-domains-of-hnrnp-ll-with-the-bcl2-promoter-i-motif-dna
#12
Basab Roy, Poulami Talukder, Hyun-Jin Kang, Shujian S Tsuen, Mohammad P Alam, Laurence H Hurley, Sidney M Hecht
The recently discovered role of the BCL2 (B-cell lymphoma 2 gene) promoter i-motif DNA in modulation of gene expression via interaction with the ribonucleoprotein hnRNP L-like (hnRNP LL) has prompted a more detailed study of the nature of this protein-DNA interaction. The RNA recognition motifs (RRMs) of hnRNP LL were expressed individually, and both RRM1 and RRM2 were found to bind efficiently to the BCL2 i-motif DNA, as well as being critical for transcriptional activation, whereas RRM3-4 bound only weakly to this DNA...
August 31, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27437398/crystal-structure-of-the-n-terminal-rna-recognition-motif-of-mrna-decay-regulator-auf1
#13
Young Jun Choi, Je-Hyun Yoon, Jeong Ho Chang
AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3'-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27335251/rrm1-151a-t-rrm1-756t-c-and-rrm1-585t-gis-associated-with-increased-susceptibility-of-lung-cancer-in-chinese-patients
#14
Xiao-Ling Xu, Ji Zheng, Wei-Min Mao, Zhi-Qiang Ling
Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine-based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age- and sex-matched population controls using SNaPshot detection technology...
August 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27301448/unraveling-the-conformational-determinants-of-larp7-and-7sk-small-nuclear-rna-by-theoretical-approaches
#15
Lei Xu, Ren Kong, Jingyu Zhu, Huiyong Sun, Shan Chang
LARP7, a member of the La-related proteins (LARPs), shares a conserved La module comprising the La-motif (LAM) and the RNA-recognition motif (RRM1), binding exclusively to the non-coding RNA 7SK. LARP7 is a component of the small nuclear ribonucleoprotein (7SKsnRNP) required for the stability and function of the RNA, and implicated in the transcription termination and regulation of translation. In the current work, molecular dynamics simulations were employed to investigate the recently determined crystal structures of the La module of LARP7 in complexs with a stretch of uridines at the 3'-end of 7SK in the presence and absence of RNA and two different mutants...
July 19, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27179014/association-of-the-genetic-polymorphisms-rrm1-756t-c-and-269c-a-with-cervical-neoplasia
#16
Ching-Wen Chang, Shun-Fa Yang, Po-Hui Wang, Hsiu-Ju Chang, Wen-Chi Liu, Hsiu-Ting Tsai
Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 -756T>C and -269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 -756T>C and -269 C>A in patients with cervical neoplasia and healthy controls...
October 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27173327/comparison-of-the-expression-of-human-equilibrative-nucleotide-transporter-1-hent1-and-ribonucleotide-reductase-subunit-m1-rrm1-genes-in-seven-non-hodgkin-lymphoma-cell-lines
#17
H B Zhao, X F Zhang, F Shi, M Z Zhang, W L Xue
We investigated the variability in the expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit M1 (RRM1) in non-Hodgkin lymphoma cell lines. hENT1 and RRM1 mRNA expression levels in natural killer (NK) cells and seven non-Hodgkin lymphoma cell lines (YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, and Jurket) were studied using reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) and the results were compared using the Student t-test. mRNA expression of hENT1 was detectable in YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, Jurket, and NK cells, which revealed variability in gene expression...
2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27117533/p21-activated-kinase-1-pak1-signaling-influences-therapeutic-outcome-in-pancreatic-cancer
#18
S Jagadeeshan, A Subramanian, S Tentu, S Beesetti, M Singhal, S Raghavan, R P Surabhi, J Mavuluri, H Bhoopalan, J Biswal, R S Pitani, S Chidambaram, S Sundaram, R Malathi, J Jeyaraman, A S Nair, G Venkatraman, S K Rayala
BACKGROUND: Therapeutic resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) is attributed to various cellular mechanisms and signaling molecules that influence as a single factor or in combination. DESIGN: In this study, utilizing in vitro p21-activated kinase 1 (Pak1) overexpression and knockdown cell line models along with in vivo athymic mouse tumor xenograft models and clinical samples, we demonstrate that Pak1 is a crucial signaling kinase in gemcitabine resistance...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27081844/tissue-micrornas-as-predictive-markers-for-gastric-cancer-patients-undergoing-palliative-chemotherapy
#19
David Smid, Vlastimil Kulda, Kristyna Srbecka, Dasa Kubackova, Jan Dolezal, Ondrej Daum, Radek Kucera, Ondrej Topolcan, Vladislav Treska, Tomas Skalicky, Martin Pesta
MicroRNAs have the potential to become valuable predictive markers for gastric cancer. Samples of biopsy tissue, routinely taken from gastric cancer patients undergoing palliative chemotherapy, constitute suitable material for microRNA profiling with the aim of predicting the effect of chemotherapy. Our study group consisted of 54 patients, all of whom underwent palliative chemotherapy based on 5-fluorouracil (5-FU) or 5-FU in combination with platinum derivatives between 2000 and 2013. The expression of 29 selected microRNAs and genes BRCA1, ERCC1, RRM1 and TS, in gastric cancer tissue macrodissected from FFPE tissue samples, was measured by quantitative RT-PCR...
June 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27064654/structure-dynamics-and-interaction-of-p54-nrb-nono-rrm1-with-5-splice-site-rna-sequence
#20
Jean-Baptiste Duvignaud, Mikaël Bédard, Takashi Nagata, Yutaka Muto, Shigeyuki Yokoyama, Stéphane M Gagné, Michel Vincent
p54(nrb)/NonO is a nuclear RNA-binding protein involved in many cellular events such as pre-mRNA processing, transcription, and nuclear retention of hyper-edited RNAs. In particular, it participates in the splicing process by directly binding the 5' splice site of pre-mRNAs. The protein also concentrates in a nuclear body called paraspeckle by binding a G-rich segment of the ncRNA NEAT1. The N-terminal section of p54(nrb)/NonO contains tandem RNA recognition motifs (RRMs) preceded by an HQ-rich region including a threonine residue (Thr15) whose phosphorylation inhibits its RNA binding ability, except for G-rich RNAs...
May 10, 2016: Biochemistry
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