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https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#1
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156822/circular-rna-expression-profiles-reveal-that-hsa_circ_0018289-is-up-regulated-in-cervical-cancer-and-promotes-the-tumorigenesis
#2
Ya-Li Gao, Ming-Yun Zhang, Bo Xu, Li-Jie Han, Shou-Feng Lan, Ju Chen, Yu-Jin Dong, Li-Li Cao
Circular RNAs (circRNAs) are a type of non-coding RNAs that have been identified as critical regulators in various diseases, especially in cancers. However, the expression profiles and functions of circRNAs in cervical cancer are still unclear. In present study, human circRNAs microarray were performed to screen the circRNAs expression in cervical cancer tissue. Microarray analysis revealed 45 significantly expressed circRNAs with 4 fold change. Among these up-regulated circRNAs, hsa_circ_0018289 was validated to be significantly up-regulated in 35 pairs of cervical cancer tissue compared with adjacent normal tissue and cell lines...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156819/mir-29a-3p-suppresses-cell-proliferation-and-migration-by-downregulating-igf1r-in-hepatocellular-carcinoma
#3
Xiao Wang, Shasha Liu, Ling Cao, Tengfei Zhang, Dongli Yue, Liping Wang, Yu Ping, Qianyi He, Chaoqi Zhang, Meng Wang, Xinfeng Chen, Qun Gao, Dan Wang, Zhen Zhang, Fei Wang, Li Yang, Jieyao Li, Lan Huang, Bin Zhang, Yi Zhang
Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein that has been reported to promote transformation to malignancy and cancer cell proliferation and survival. In this study, we found that the expression of miR-29a-3p was downregulated in HCC patients, resulting in poor survival rates...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156743/hepatitis-c-virus-core-overcomes-all-trans-retinoic-acid-induced-apoptosis-in-human-hepatoma-cells-by-inhibiting-p14-expression-via-dna-methylation
#4
Juri Kwak, Jung-Hye Choi, Kyung Lib Jang
All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to induce p14 expression via promoter hypomethylation to activate the p14-MDM2-p53 pathway, which leads to activation of the p53-dependent apoptotic pathway and subsequent induction of apoptosis in human hepatoma cells. In the present study, we found that hepatitis C virus (HCV) Core derived from ectopic expression or HCV infection overcomes ATRA-induced apoptosis in p53-positive hepatoma cells. For this effect, HCV Core upregulated both protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b and thereby repressed p14 expression via promoter hypermethylation, resulting in inactivation of the pathway leading to p53 accumulation in the presence of ATRA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156726/adiponectin-receptor-agonists-inhibit-leptin-induced-pstat3-and-in-vivo-pancreatic-tumor-growth
#5
Fanuel Messaggio, Alisha M Mendonsa, Jason Castellanos, Nagaraj S Nagathihalli, Lee Gorden, Nipun B Merchant, Michael N VanSaun
Obesity is a significant risk factor for pancreatic cancer, harboring a chronic inflammatory condition characterized by dysregulation of the adipokines, leptin and adiponectin, that in turn alter oncogenic signaling pathways. We and others have shown that leptin promotes the proliferation and an invasive potential of pancreatic cancer cells through STAT3 mediated signaling. However, the role of adiponectin on the tumorigenicity of pancreatic cancer has not been elucidated. Adiponectin represents an important negative regulator of cytokines, which acts through two receptors, ADIPOR1 and ADIPOR2, to elicit pro-apoptotic, anti-inflammatory, and anti-angiogenic responses...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156725/methylation-of-cpg-sites-in-the-upstream-regulatory-region-physical-status-and-mrna-expression-of-hpv-6-in-adult-onset-laryngeal-papilloma
#6
Zeyi Deng, Taro Ikegami, Asanori Kiyuna, Chunlin Zhang, Tao Zhang, Sen Matayoshi, Takayuki Uehara, Hiroyuki Maeda, Mikio Suzuki, Akira Ganaha
The methylation status of HPV-6 upstream regulatory region (URR) in adult-onset laryngeal papillomatosis (AO-LP) remains unclear. The purpose of this study was to investigate the methylation status of URR and the physical status of HPV-6, as well as the dynamic variations of viral load and mRNA expression in AO-LP. We examined 18 specimens from 11 patients with AO-LP by real-time polymerase chain reaction (PCR), bisulfite-sequencing PCR, and amplification of papilloma oncogene transcripts. HPV-6 was identified in 9 of 11 patients (81...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156724/lncrna-pvt1-and-its-splicing-variant-function-as-competing-endogenous-rna-to-regulate-clear-cell-renal-cell-carcinoma-progression
#7
Tao Yang, Hui Zhou, Peijun Liu, Libin Yan, Weimin Yao, Ke Chen, Jin Zeng, Heng Li, Junhui Hu, Hua Xu, Zhangqun Ye
Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156705/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#8
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156698/combined-brd4-and-cdk9-inhibition-as-a-new-therapeutic-approach-in-malignant-rhabdoid-tumors
#9
Natalia Moreno, Till Holsten, Julius Mertins, Annabelle Zhogbi, Pascal Johann, Marcel Kool, Michael Meisterernst, Kornelius Kerl
Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156681/the-histone-demethylase-kdm3a-is-required-for-normal-epithelial-proliferation-ductal-elongation-and-tumor-growth-in-the-mouse-mammary-gland
#10
Li Qin, Yixiang Xu, Xiaobin Yu, Michael J Toneff, Dabing Li, Lan Liao, Jarrod D Martinez, Yi Li, Jianming Xu
Histone modification alters chromatin architecture to regulate gene transcription. KDM3A is a histone demethylase in the JmjC domain-containing protein family. It removes di- and mono- methyl residues from di- or mono-methylated lysine 9 of histone H3 (H3K9me2/me1). Recent studies have shown that Kdm3a plays an important role in self-renewal of embryonic stem cells, spermatogenesis, metabolism, sex determination and tumor angiogenesis. However, its role in mammary gland development and breast carcinogenesis remains unclear...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#11
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156578/pancreatic-cancer-molecular-characterization-clonal-evolution-and-cancer-stem-cells
#12
REVIEW
Elvira Pelosi, Germana Castelli, Ugo Testa
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development...
November 18, 2017: Biomedicines
https://www.readbyqxmd.com/read/29156535/hdacis-class-i-cancer-stem-cell-and-phytochemicals-cancer-therapy-and-prevention-implications
#13
REVIEW
Sahar Bayat, Mahmoud Shekari Khaniani, Jalal Choupani, Mohammad Reza Alivand, Sima Mansoori Derakhshan
Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy...
November 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156520/long-noncoding-rna-linc00961-inhibits-cell-invasion-and-metastasis-in-human-non-small-cell-lung-cancer
#14
Bin Jiang, Jing Liu, Yu-Hong Zhang, Dong Shen, Shaoping Liu, Feng Lin, Jun Su, Qing-Feng Lin, Shuai Yan, Yong Li, Wei-Dong Mao, Zhi-Li Liu
Long noncoding RNAs (LncRNAs) expression has been found to be misregulated in multiple human cancers, and a growing number of studies have revealed that lncRNAs can function as important oncogenes or tumor suppressors. In this study, we identified a lncRNA-LINC00961, which was significantly down-regulated in human non-small cell lung cancer tissues. Decreased LINC00961 was associated with NSCLC patients advanced clinical stage, lymph node metastasis, and shorter survival time. Further experiments demonstrated that LSD1 could directly bind to LINC00961 promoter regions and epigenetically repress its transcription in NSCLC cells...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156509/the-role-of-exosomes-on-colorectal-cancer-a-review
#15
REVIEW
Lidia Ruiz-López, Isabel Blancas, José M Garrido, Nuria Mut-Salud, Marta Moya-Jódar, Antonio Osuna, Fernando Rodríguez-Serrano
Exosomes are extracellular microvesicles released from cells, which are involved in many biological and pathological processes, mainly due to their role in intercellular communication. Exosomes derived from colorectal cancer (CRC) cells are related to oncogenesis, tumor cell survival, chemo-resistance and metastasis. The role of the exosomes in these processes involves the transfer of proteins, RNAs or mutant versions of proto-oncogenes to the target cells. In recent years, great efforts have been made to identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis and treatment response...
November 20, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29155772/preparation-of-primary-acute-lymphoblastic-leukemia-cells-in-different-cell-cycle-phases-by-centrifugal-elutriation
#16
Magdalena Delgado, Anisha Kothari, Walter N Hittelman, Timothy C Chambers
The ability to synchronize cells has been central to advancing our understanding of cell cycle regulation. Common techniques employed include serum deprivation; chemicals which arrest cells at different cell cycle phases; or the use of mitotic shake-off which exploits their reduced adherence. However, all of these have disadvantages. For example, serum starvation works well for normal cells but less well for tumor cells with compromised cell cycle checkpoints due to oncogene activation or tumor suppressor loss...
November 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155422/secretion-mediated-stat3-activation-promotes-self-renewal-of-glioma-stem-like-cells-during-hypoxia
#17
D A Almiron Bonnin, M C Havrda, M C Lee, H Liu, Z Zhang, L N Nguyen, L X Harrington, S Hassanpour, C Cheng, M A Israel
High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells...
November 20, 2017: Oncogene
https://www.readbyqxmd.com/read/29155348/progress-and-challenges-of-predictive-biomarkers-of-anti-pd-1-pd-l1-immunotherapy-a-systematic-review
#18
Feifei Teng, Xiangjiao Meng, Li Kong, Jinming Yu
Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies...
November 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29154989/targeting-bromodomain-and-extraterminal-proteins-in-breast-cancer
#19
REVIEW
Jennifer M Sahni, Ruth A Keri
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29154802/microrna-profiling-in-mda-mb-231-human-breast-cancer-cell-exposed-to-the-phaleria-macrocarpa-boerl-fruit-ethyl-acetate-fraction-pmeaf-through-iilumina-hi-seq-technologies-and-various-in-silico-bioinformatics-tools
#20
Nowroji Kavitha, Soundararajan Vijayarathna, Shanmugapriya, Chern Ein Oon, Yeng Chen, Jagat R Kanwar, Vasu Punj, Sreenivasan Sasidharan
ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. AIM OF THE STUDY: Recent studies have demonstrated a potent anticancer potential of P...
November 14, 2017: Journal of Ethnopharmacology
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