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Molecular Oncology

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https://www.readbyqxmd.com/read/28211215/zkscan1-gene-and-its-related-circular-rna-circzkscan1-both-inhibit-hepatocellular-carcinoma-cell-growth-migration-and-invasion-but-through-different-signaling-pathways
#1
Zhicheng Yao, Jingyan Luo, Kunpeng Hu, Jizong Lin, He Huang, Qiangliang Wang, Peng Zhang, Zhiyong Xiong, Zejian Huang, Chonghua He, Bo Liu, Yang Yang
There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development, but the regulation and function of human circRNAs remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P<0.05) in the HCC samples compared with that in matched adjacent non-tumorous tissues by reverse transcription PCR (RT-PCR)...
February 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28188704/cnot1-cooperates-with-lmna-to-aggravate-osteosarcoma-tumorigenesis-through-the-hedgehog-signaling-pathway
#2
Dong-Dong Cheng, Jing Li, Shi-Jie Li, Qing-Cheng Yang, Cun-Yi Fan
While treatments for childhood osteosarcoma have improved, the overall survival for this common type of bone cancer have not changed for three decades and thus new targets for therapeutic development are needed. To identify tumor-related proteins in osteosarcoma, we used isobaric tags in a relative and absolute quantitation (iTRAQ) proteomic approach to analyze the differentially expressed proteins between osteosarcoma cells and human osteoblastic cells. Through clinical screening and functional evaluation, CCR4-NOT transcription complex subunit 1 (CNOT1) correlated to the growth of osteosarcoma cells...
February 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28188683/functional-kras-mutations-and-a-potential-role-for-pi3k-akt-activation-in-wilms-tumors
#3
Dina Polosukhina, Harold D Love, Hernan Correa, Zengliu Su, Kimberly B Dahlman, William Pao, Harold L Moses, Carlos L Arteaga, Harold N Lovvorn, Roy Zent, Peter E Clark
Wilms tumor (WT) is the most common renal neoplasm of childhood and affects 1 in 10,000 children aged less than 15 years. These embryonal tumors are thought to arise from primitive nephrogenic rests that derive from the metanephric mesenchyme during kidney development and are characterized partly by increased Wnt/β-catenin signaling. We previously showed that coordinate activation of Ras and β-catenin accelerates the growth and metastatic progression of a murine WT model. Here, we show that activating KRAS mutations can be found in human WT...
February 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#4
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28182322/somatic-cancer-mutations-in-the-mll1-histone-methyltransferase-modulate-its-enzymatic-activity-and-dependence-on-the-wdr5-rbbp5-ash2l-complex
#5
Sara Weirich, Srikanth Kudithipudi, Albert Jeltsch
Somatic missense mutations in the MLL1 histone H3K4 methyltransferase are often observed in cancers. MLL1 forms a complex with WDR5, RBBP5 and ASH2L (WRA) which stimulates its activity. The MM-102 compound prevents the interaction between MLL1 and WDR5 and functions as an MLL1 inhibitor. We have studied the effects of four cancer mutations in the catalytic SET domain of MLL1 on the enzymatic activity of MLL1 and MLL1-WRA complexes. In addition, we studied the interaction of the MLL1 mutants with the WRA proteins and inhibition of MLL1-WRA complexes by MM-102...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28173629/enhanced-dependency-of-kras-mutant-colorectal-cancer-cells-on-rad51-dependent-homologous-recombination-repair-identified-from-genetic-interactions-in-saccharomyces-cerevisiae
#6
Murugan Kalimutho, Amanda L Bain, Bipasha Mukherjee, Purba Nag, Devathri M Nanayakkara, Sarah K Harten, Janelle L Harris, Goutham Narayanan Subramanian, Debottam Sinha, Senji Shirasawa, Sriganesh Srihari, Sandeep Burma, Kum Kum Khanna
Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti-EGFR targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS-mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling...
February 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28164434/dual-inhibition-of-akt-and-c-met-as-a-second-line-therapy-following-acquired-resistance-to-sorafenib-in-hepatocellular-carcinoma-cells
#7
Peng Han, Hali Li, Xian Jiang, Bo Zhai, Gang Tan, Dali Zhao, Haiquan Qiao, Bing Liu, Hongchi Jiang, Xueying Sun
Sorafenib displays a limited efficacy for advanced hepatocellular carcinoma (HCC). Some HCC patients initially respond to sorafenib but eventually succumb to the disease, indicating that the acquired resistance to sorafenib reduces its beneficial effects. No alternative drugs are available after the failure of sorafenib therapy. Therefore, investigation of the mechanisms underlying the acquired resistance and development of second-line treatments for sorafenib-resistant HCC are urgently required. In the present study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28164432/dysregulation-of-the-mir-194-cul4b-negative-feedback-loop-drives-tumorigenesis-in-non-small-cell-lung-carcinoma
#8
Jun Mi, Yongxin Zou, Xiaohua Lin, Juanjuan Lu, Xiaochen Liu, Hui Zhao, Xiang Ye, Huili Hu, Baichun Jiang, Bo Han, Changshun Shao, Yaoqin Gong
CUL4B, a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of cancers and represses many tumor suppressors through epigenetic mechanisms. However, the mechanisms by which CUL4B is upregulated remain to be elucidated. Here, we show that CUL4B was upregulated in non-small-cell lung carcinoma (NSCLC) tissues and was critically required for cell proliferation and migration in vitro and for xenograft tumor formation in vivo. We found that microRNA-194 (miR-194) and CUL4B protein were inversely correlated in cancer specimens and demonstrated that miR-194 could downregulate CUL4B by directly targeting its 3'UTR...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28164427/application-of-circulating-tumor-dna-in-prospective-clinical-oncology-trials-standardization-of-pre-analytical-conditions
#9
Lisanne F van Dessel, Nick Beije, Jean C A Helmijr, Silvia R Vitale, Jaco Kraan, Maxime P Look, Ronald de Wit, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens, Martijn P J K Lolkema
Circulating tumor DNA (ctDNA) has emerged as a potential new biomarker with diagnostic, predictive and prognostic applications for various solid tumor types. Before beginning large prospective clinical trials to prove the added value of utilizing ctDNA in clinical practice, it is essential to investigate the effects of various pre-analytical conditions on the quality of cell-free DNA (cfDNA) in general and of ctDNA in particular in order to optimize and standardize these conditions. Whole blood samples were collected from patients with metastatic cancer bearing a known somatic variant...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28156061/zinc-finger-protein-x-linked-zfx-promotes-expansion-of-epcam-cancer-stem-like-cells-in-hepatocellular-carcinoma
#10
Chao Wang, Si-Yuan Fu, Ming-da Wang, Wen-Bo Yu, Qin-Shu Cui, Hong-Ru Wang, Hai Huang, Wei Dong, Wei-Wei Zhang, Peng-Peng Li, Chuan Lin, Ze-Ya Pan, Yuan Yang, Meng-Chao Wu, Wei-Ping Zhou
Zinc finger protein X-linked (ZFX) is frequently upregulated in multiple human malignancies and also plays a critical role in the maintenance of self-renewal in embryonic stem cells (ESC). However, the role of ZFX in liver cancer stem cells (CSCs) remains obscure. We observed that the elevated expression of both ZFX and epithelial cell adhesion molecule (EpCAM) was associated with aggressive clinicopathological features and indicated poor prognosis in patients with HCC. ZFX was commonly enriched in liver EpCAM(+) CSCs...
February 3, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28156048/targeted-o-glycoproteomics-explored-increased-sialylation-and-identified-muc16-as-a-poor-prognosis-biomarker-in-advanced-stage-bladder-tumours
#11
Sofia Cotton, Rita Azevedo, Cristiana Gaiteiro, Dylan Ferreira, Luís Lima, Andreia Peixoto, Elisabete Fernandes, Manuel Neves, Diogo Neves, Teresina Amaro, Ricardo Cruz, Ana Tavares, Maria Rangel, André M N Silva, Lúcio Lara Santos, José Alexandre Ferreira
Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short-chain O-glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST), which are generally associated with poor prognosis...
February 3, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28100038/trim8-regulates-stemness-in-glioblastoma-through-pias3-stat3
#12
Changming Zhang, Subhas Mukherjee, Carol Tucker-Burden, James L Ross, Monica J Chau, Jun Kong, Daniel J Brat
Glioblastoma (GBM) is the most malignant form of primary brain tumor and GBM stem-like cells (GSCs) contribute to the rapid growth, therapeutic resistance and clinical recurrence of these fatal tumors. STAT3 signaling supports the maintenance and proliferation of GSCs, yet regulatory mechanisms are not completely understood. Here we report that tri-partite motif containing protein 8 (TRIM8) activates STAT3 signaling to maintain stemness and self-renewing capabilities of GSCs. TRIM8 (also known as "glioblastoma expressed ring finger protein") is expressed equally in GBM and normal brain tissues, despite its hemizygous deletion in the large majority of GBMs, and its expression is highly correlated with stem cell markers...
January 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28084011/sorafenib-analogue-sc-60-induces-apoptosis-through-the-shp-1-stat3-pathway-and-enhances-docetaxel-cytotoxicity-in-triple-negative-breast-cancer-cells
#13
Chun-Yu Liu, Jung-Chen Su, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Wan-Lun Wang, Chia-Han Lee, Ka-Yi Lau, Wen-Chun Tsai, Hsiu-Ping Yang, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
Recurrent triple-negative breast cancer (TNBC) needs new therapeutic targets. Src homology region 2 domain-containing phosphatase-1 (SHP-1) can act as a tumor suppressor by dephosphorylating oncogenic kinases. One major target of SHP-1 is STAT3, which is highly activated in TNBC. In this study, we tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity but acts as a SHP-1 agonist, in TNBC cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells (MDA-MB-231, MDA-MB-468, HCC1937)...
January 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#14
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28133913/the-role-of-epithelial-mesenchymal-transition-drivers-zeb1-and-zeb2-in-mediating-docetaxel-resistant-prostate-cancer
#15
Karen Hanrahan, Amanda O'Neill, Maria Prencipe, Jane Bugler, Lisa Murphy, Aurelie Fabre, Martin Puhr, Zoran Culig, Keefe Murphy, R William Watson
Docetaxel is the main treatment for advanced castration-resistant prostate cancer; however, resistance eventually occurs. The development of intratumoral drug-resistant subpopulations possessing a cancer stem cell (CSC) morphology is an emerging mechanism of docetaxel resistance, a process driven by epithelial-mesenchymal transition (EMT). This study characterised EMT in docetaxel-resistant sublines through increased invasion, MMP-1 production and ZEB1 and ZEB2 expression. We also present evidence for differential EMT across PC-3 and DU145 in vitro resistance models as characterised by differential migration, cell colony scattering and susceptibility to the CSC inhibitor salinomycin...
December 19, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28145100/profiling-of-micrornas-in-tumor-interstitial-fluid-of-breast-tumors-a-novel-resource-to-identify-biomarkers-for-prognostic-classification-and-detection-of-cancer
#16
Ann Rita Halvorsen, Åslaug Helland, Pavel Gromov, Vera Timmermans Wielenga, Maj-Lis Møller Talman, Nils Brunner, Vandana Sandhu, Anne-Lise Børresen-Dale, Irina Gromova, Vilde D Haakensen
It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer, and detectable microRNAs were analyzed and compared...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28145099/gene-expression-panel-predicts-metastatic-lethal-prostate-cancer-outcomes-in-men-diagnosed-with-clinically-localized-prostate-cancer
#17
Rohina Rubicz, Shanshan Zhao, Jonathan L Wright, Ilsa Coleman, Catherine Grasso, Milan S Geybels, Amy Leonardson, Suzanne Kolb, Craig April, Marina Bibikova, Dean Troyer, Raymond Lance, Daniel W Lin, Elaine A Ostrander, Peter S Nelson, Jian-Bing Fan, Ziding Feng, Janet L Stanford
Prognostic biomarkers are needed to distinguish patients with clinically localized prostate cancer (PCa) who are at high risk of metastatic progression. The tumor transcriptome may reveal its aggressiveness potential and have utility for predicting adverse patient outcomes. Genomewide gene expression levels were measured in primary tumor samples of 383 patients in a population-based discovery cohort, and from an independent clinical validation dataset of 78 patients. Patients were followed for ≥ 5 years after radical prostatectomy to ascertain outcomes...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28145098/mir-15b-modulates-multidrug-resistance-in-human-osteosarcoma-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Zhenfeng Duan, Yan Gao, Jacson Shen, Edwin Choy, Gregory Cote, David Harmon, Karen Bernstein, Santiago Lozano-Calderon, Henry Mankin, Francis J Hornicek
The development of multidrug resistance (MDR) in cancer cells to chemotherapy drugs continues to be a major clinical problem. MicroRNAs (miRNA, miR) play an important role in regulating tumour cell growth and survival; however, the role of miRs in the development of drug resistance in osteosarcoma cells is largely uncharacterized. We sought to identify and characterize human miRs that act as key regulators of MDR in osteosarcoma. We utilized a miR microarray to screen for differentially expressed miRs in osteosarcoma MDR cell lines...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28145097/multiregion-ultra-deep-sequencing-reveals-early-intermixing-and-variable-levels-of-intratumoral-heterogeneity-in-colorectal-cancer
#19
Yuka Suzuki, Sarah Boonhsi Ng, Clarinda Chua, Wei Qiang Leow, Jermain Chng, Shi Yang Liu, Kalpana Ramnarayanan, Anna Gan, Dan Liang Ho, Rachel Ten, Yan Su, Alexandar Lezhava, Jiunn Herng Lai, Dennis Koh, Kiat Hon Lim, Patrick Tan, Steven G Rozen, Iain Beehuat Tan
Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number, and transcriptomic alterations involving clinically and biologically relevant gene pathways in colorectal cancer (CRC). We performed multiregion, high-depth (384× on average) sequencing of 799 cancer-associated genes in 24 spatially separated primary tumor and nonmalignant tissues from four treatment-naïve CRC patients. We then used ultra-deep sequencing (17 075× on average) to accurately verify the presence or absence of identified somatic mutations in each sector...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28145096/molecular-oncology-journal-has-moved-to-open-access
#20
EDITORIAL
Julio E Celis, Jose Moreira
No abstract text is available yet for this article.
February 2017: Molecular Oncology
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