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Cell Pathway And Malignancy

Małgorzata Dawidowska, Roman Jaksik, Monika Drobna, Bronisława Szarzyńska-Zawadzka, Maria Kosmalska, Łukasz Sędek, Ludomiła Machowska, Anna Lalik, Monika Lejman, Marek Ussowicz, Krzysztof Kałwak, Jerzy R Kowalczyk, Tomasz Szczepański, Michał Witt
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we characterized the miRNome of 34 pediatric T-ALL samples, including the expression of isomiRs and the identification of candidate novel miRNAs (not previously annotated in miRBase). For the first time, we show that immunophenotypic subtypes of T-ALL present different miRNA expression profiles...
February 11, 2019: Neoplasia: An International Journal for Oncology Research
Fan Meng, Ruifeng Li, Liyu Ma, Lifang Liu, Xiaorong Lai, Dongyang Yang, Junmin Wei, Dong Ma, Zijun Li
Esophageal carcinoma, with a increasing incidence, is one of the most aggressive carcinomas in gastrointestinal tract. Epidemiologic studies demonstrate an association of oral pathogens with multiple diseases, including rheumatoid arthritis, cardiovascular diseases, diabetes, and gastrointestinal malignancies. Nevertheless, a causal relationship between oral pathogens and esophageal squamous cell carcinoma (ESCC) has not been elucidated. Here, we found that Porphyromonas was significantly enriched in the saliva of patients with ESCC, compared with that in normal human...
February 11, 2019: Microbes and Infection
Yucheng Guo, Chen Bao, Dacheng Ma, Yubing Cao, Yanda Li, Zhen Xie, Shao Li
Tumorigenesis is a complex process that is driven by a combination of the networks of genes and environmental factors; however, efficient approaches for identifying functional networks that are perturbed by the process of tumorigenesis is poorly understood. Then, the identification of functional synergistic modules and pathways is often limited by computational method and experiment measures. Here, we propose an integrated network-based approach for the systematic discovery of functional synergistic modules that are causal determinants of inflammation-induced tumorigenesis, by prioritizing candidate genes of integrating clinical-based and network-based genome-wide gene prediction methods and identify functional synergistic modules based on combinatorial CRISPR-Cas9 screens...
February 14, 2019: ACS Synthetic Biology
Serdal Korkmaz, Selahattin Erdem, Ebru Akay, Erdem Arzu Taşdemir, Hatice Karaman, Muzaffer Keklik
Background/aim: PD-1 (programmed death-1) is an immune checkpoint receptor that modulates T-cell activity in peripheral tissues via interaction with its ligands, PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2). Tumor cells upregulate PD-L1 or PD-L2 to inhibit this T lymphocyte attack. Our goal was to determine the PD-1 and PD-L2 expression rates of various hematologic malignancies, and evaluate whether PD-1 and PD-L2 expressions have an impact on prognosis. Materials and methods: For this purpose, pretreatment bone marrow biopsy specimens of 83 patients [42 multiple myeloma (MM), 21 acute leukemia, and 20 chronic lymphocytic leukemia (CLL)] were stained with monoclonal antibody immunostains of PD-1 and PD-L2...
February 11, 2019: Turkish Journal of Medical Sciences
Jiange Qiu, Qianqian Li, Katherine A Bell, Xue Yao, Yifeng Du, Erik Zhang, Jane J Yu, Ying Yu, Zhi Shi, Jianxiong Jiang
BACKGROUND AND PURPOSE: Induced cyclooxygenase-2 (COX-2) in malignant gliomas causes excessive synthesis of prostaglandin E2 (PGE2 ) that is thought to facilitate the brain tumor growth and invasion. However, which downstream PGE2 receptor subtype (i.e., EP1-EP4) directly contributes to COX activity-promoted glioma growth remains largely unknown. EXPERIMENTAL APPROACH: Using a publicly available database from The Cancer Genome Atlas (TCGA) research network, we compared the expression of PGE2 signaling-associated genes in human lower-grade glioma (LGG) and glioblastoma multiforme (GBM) samples...
February 14, 2019: British Journal of Pharmacology
Chao Shang, Cheng N Ao, Chi C Cheong, Lirong Meng
Endometrial cancer (EC) is the most common malignancy of the female reproductive tract. In this study, we clarified the clinical significance of CDKN2B antisense RNA 1 (CDKN2B-AS) gene, and its effects on paclitaxel sensitivity in EC. Firstly, CDKN2B-AS gene was highly expressed in EC tissues and cell lines. The high-expression of CDKN2B-AS gene was associated with high pathological grade and low paclitaxel sensitivity of EC tissues. Knockdown of CDKN2B-AS gene sensitized Ishikawa/PA and HEC1A/PA cells to paclitaxel, and promoted paclitaxel-induced cytotoxicity...
2019: Frontiers in Oncology
Cong Wang, Ziying Liu, Yuepeng Ke, Fen Wang
Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions...
2019: Frontiers in Genetics
Tadeo Enrique Velazquez-Caldelas, Sergio Antonio Alcalá-Corona, Jesús Espinal-Enríquez, Enrique Hernandez-Lemus
Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer...
2019: Frontiers in Immunology
Vincenzo Carafa, Lucia Altucci, Angela Nebbioso
Sirtuins (SIRTs), class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context and experimental conditions. SIRTs are involved in many important biological processes and play a critical role in cancer initiation, promotion, and progression. A growing body of evidence indicates the involvement of SIRTs in regulating three important tumor processes: epithelial-to-mesenchymal transition (EMT), invasion, and metastasis...
2019: Frontiers in Pharmacology
Chenling Meng, Jinyue Liao, Danfeng Zhao, Huihui Huang, Jinzhong Qin, Tin-Lap Lee, Degui Chen, Wai-Yee Chan, Yin Xia
Lethal (3) malignant brain tumor like 2 (L3MBTL2) is a member of the MBT-domain proteins, which are involved in transcriptional repression and implicated in chromatin compaction. Our previous study has shown that L3MBTL2 is highly expressed in the testis, but its role in spermatogenesis remains unclear. In the present study, we found that L3MBTL2 was most highly expressed in pachytene spermatocytes within the testis. Germ cell-specific ablation of L3mbtl2 in the testis led to increased abnormal spermatozoa, progressive decrease of sperm counts and premature testicular failure in mice...
February 13, 2019: Cell Death and Differentiation
Dennis P O'Malley, Yuhang Yang, Saskia Boisot, Sucha Sudarsanam, Jian-Feng Wang, Vladislav Chizhevsky, Guohua Zhao, Shehla Arain, Lawrence M Weiss
Targeting of the PD1/PD-L1 immune checkpoint pathway has rapidly gained acceptance as a therapeutic strategy for a growing number of malignancies. Testing for expression of PD-L1 in tumor cells and immune cells has been used as a companion or complementary test for drugs targeting the PD1/PD-L1 pathway. We evaluated the results of PD-L1 testing in a large reference lab cohort. Using Food and Drug Administration-approved methods and interpretive instructions for each individual test, 62,896 cases were evaluated for PD-L1 using antibody clone 22C3, 28-8, SP142, or SP263...
February 13, 2019: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Shunsaku Takayanagi, Ryohei Otani, Takahide Nejo, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Mayu Omata, Fumi Higuchi, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Nobuhito Saito, Hiroyuki Aburatani, Akitake Mukasa
To elucidate the mechanisms of malignant progression of lower-grade glioma, molecular profiling using methylation array, whole-exome sequencing, and RNA sequencing was performed for 122, 36 and 31 gliomas, respectively. This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP)...
February 13, 2019: Scientific Reports
Zhi-Bo Xie, Yi-Fan Zhang, Chen Jin, Yi-Shen Mao, De-Liang Fu
BACKGROUND: The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined. METHODS: The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells...
February 13, 2019: Journal of Experimental & Clinical Cancer Research: CR
Joseph M Jacob, Elizabeth K Ferry, Laurie M Gay, Julia A Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Andrea Necchi, J Keith Killian, Siraj M Ali, Alexa B Schrock, Nick W Liu, J Chung, V A Miller, P J Stephens, A Welsh, Robert J Corona, Jeffrey S Ross, Gennady Bratslavsky
PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma...
March 2019: Journal of Urology
Johannes Jung, Sonja C Buisman, Ellen Weersing, Albertina Dethmers-Ausema, Erik Zwart, Hein Schepers, Mike R Dekker, Seka S Lazare, Franziska Hammerl, Yulia Skokova, Susanne M Kooistra, Karin Klauke, Raymond A Poot, Leonid V Bystrykh, Gerald de Haan
In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis. Gene expression and chromatin analyses revealed perturbations in genes involved in differentiation, DNA and chromatin maintenance, and cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and its genetic or pharmacological repression in AML cells inhibited proliferation and induced differentiation...
February 12, 2019: Cell Reports
Ahmet M Aydin, Nirmish Singla, Vandana Panwar, Solomon L Woldu, Yuval Freifeld, Christopher G Wood, Jose A Karam, Alon Z Weizer, Jay D Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Mary E Westerman, Arthur I Sagalowsky, Shahrokh F Shariat, Yair Lotan, Aditya Bagrodia, Payal Kapur, Vitaly Margulis, Laura-Maria Krabbe
PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1...
February 13, 2019: World Journal of Urology
Yang Liu, Yanxin Lu, Orieta Celiku, Aiguo Li, Qixin Wu, Yiqiang Zhou, Chunzhang Yang
Background: Neomorphic IDH1 mutations disrupt the redox balance by promoting reactive oxygen species (ROS) production. However, the mechanism by which IDH1-mutant cells maintain ROS homeostasis remains elusive. It is also not known whether reprogrammed ROS homeostasis establishes targetable vulnerability in IDH1-mutated cancers. Methods: We investigated ROS homeostasis in wild-type (GSC827, GSC923, GSC627, and GSC711) and IDH1-mutated cells (IDH1R132C- and IDH1R132H-transduced U87, U251; MGG152, and TS603 cells)...
February 12, 2019: Journal of the National Cancer Institute
Xiaoying Guan, Ying Fang, Jie Long, Yajie Zhang
BACKGROUND: Annexin 1 (ANXA1) expression is associated with the malignant tumor phenotype, making it an attractive therapeutic target. However, little is known about the regulation of ANXA1 in non-small cell lung cancer (NSCLC). METHODS: We investigated the biological roles of ANXA1 in tumor growth, migration, and invasion, and explored the possibility of ANXA1 as a potential therapeutic target for the treatment of NSCLC. RESULTS: Our findings revealed that ANXA1 enhanced nuclear factor (NF)-κB activation in NSCLC cells by interaction with inhibitor of NF-κB kinase complex subunit, IKKγ...
February 12, 2019: Thoracic Cancer
Maiya J Mao, Donna E Leonardi
Isocitrate dehydrogenases (IDHs) are enzymes involved in the production of α-ketoglutarate (αkg) in normal cellular metabolism. Cells with IDH mutations reduce αkg to 2-hydroxyglutarate (2HG), an oncometabolite, and 2HG directly transforms normal cells to malignant cells through histone demethylation and epigenetic dysregulation. However, whether IDH mutations affect cancer stromal cells is elusive, and little is known whether 2HG may impact the tumor microenvironment. We hypothesized that the IDH mutant cancer secretome and metabolites would stimulate primitive vascular-endothelial genesis...
2019: American Journal of Cancer Research
Jia Ren, Mengjie Yang, Fengyang Xu, Juwu Chen
microRNAs (miRNAs) are frequently aberrantly expressed in osteosarcoma (OS) and are implicated in its development. Dysregulation of miR-758 has been reported in various human malignancies. However, whether miR-758 is involved in the oncogenesis and progression of OS remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction was performed to detect miR-758 expression in OS tissues and cell lines. A series of functional experiments were employed to explore the regulatory effects of miR-758 on the malignant behaviors of OS cells both in vitro and in vivo...
2019: American Journal of Cancer Research
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