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https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#1
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29786649/kudzu-leaf-extract-suppresses-the-production-of-inducible-nitric-oxide-synthase-cyclooxygenase-2-tumor-necrosis-factor-alpha-and-interleukin-6-via-inhibition-of-jnk-tbk1-and-stat1-in-inflammatory-macrophages
#2
Seok Hyun Eom, So-Jung Jin, Hee-Yeong Jeong, Youngju Song, You Jin Lim, Jong-In Kim, Youn-Hyung Lee, Hee Kang
Kudzu ( Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) is a perennial leguminous vine, and its root and flower have been used for herbal medicine in Asia for a long time. Most dietary flavonoids are reported to be concentrated in its root, not in its aerial parts including leaves. In this study, we investigated whether kudzu leaf and its major constituent, robinin (kaempferol-3- O -robinoside-7- O -rhanmoside) possessed anti-inflammatory activity. To test this hypothesis, we used peritoneal macrophages isolated from BALB/c mice and stimulated the cells with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786107/e3-ubiquitin-ligase-hakai-regulates-cell-growth-and-invasion-and-increases-the-chemosensitivity-to-cisplatin-in-non%C3%A2-small%C3%A2-cell-lung-cancer-cells
#3
Zi Liu, Yuqing Wu, Zijian Tao, Liang Ma
Hakai was originally identified as an E3 ubiquitin ligase of the E‑cadherin complex implicated in cell adhesion and invasion. Recently, emerging evidence has strongly suggested that Hakai serves a pivotal role in the tumorigenesis of certain tumors. However, the role of Hakai in non‑small‑cell lung cancer (NSCLC) and its underlying molecular mechanism have not been clarified. In the present study, it was observed that Hakai was highly expressed in NSCLC cell lines compared with human normal bronchial epithelial cells, and transfection with Hakai small interfering RNA significantly inhibited the growth of A549 and NCI‑H460 NSCLC cells...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786078/targeting-the-upstream-transcriptional-activator-of-pd-l1-as-an-alternative-strategy-in-melanoma-therapy
#4
Bo Zhu, Liming Tang, Shuyang Chen, Chengqian Yin, Shiguang Peng, Xin Li, Tongzheng Liu, Wei Liu, Changpeng Han, Lukasz Stawski, Zhi-Xiang Xu, Guangbiao Zhou, Xiang Chen, Xiumei Gao, Colin R Goding, Nan Xu, Rutao Cui, Peng Cao
Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2)...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29785781/schisantherin-a-protects-renal-tubular-epithelial-cells-from-hypoxia-reoxygenation-injury-through-the-activation-of-pi3k-akt-signaling-pathway
#5
Jiachuan Gong, Xuezhen Wang
Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, was reported to possess anti-inflammatory and antioxidant activities. However, its protective effect against renal ischemia-reperfusion (I/R) injury in human renal tubular epithelial cells subjected to hypoxia/reoxygenation (H/R) has never been studied. Thus, herein, we investigated the effect of SchA on renal I/R injury in vitro. Our results demonstrated that SchA pretreatment significantly improved HK-2 cell viability exposed to H/R...
May 22, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29785726/t2-hypointense-rim-of-breast-mass-lesions-on-magnetic-resonance-images-radiologic-pathologic-correlation
#6
Kazuaki Nakashima, Takayoshi Uematsu, Takashi Sugino, Kaoru Takahashi, Seiichirou Nishimura, Yukiko Tadokoro, Tomomi Hayashi
We investigated the radiologic-pathologic correlation of a strong hypointense rim on T2-weighted images (T2-hypo-rim) surrounding breast mass lesions and evaluated its clinical significance. We retrospectively reviewed 3503 consecutive breast magnetic resonance imaging (MRI) examinations. The T2-hypo-rim was defined as a border of strong hypointensity compared with the fat signal on fat-suppressed T2-weighted images. Detected lesions with T2-hypo-rim were classified as a solid or cystic mass with MRI and correlated with histopathologic findings...
May 21, 2018: Breast Journal
https://www.readbyqxmd.com/read/29785588/sam68-promotes-invasion-migration-and-proliferation-of-fibroblast-like-synoviocytes-by-enhancing-the-nf-%C3%AE%C2%BAb-p65-pathway-in-rheumatoid-arthritis
#7
Weiwei Sun, Rongqin Qin, Rui Wang, Dazhi Ding, Zhaohui Yu, Yuxi Liu, Ruilong Hong, Zhen Cheng, Youhua Wang
Src-associated substrate during mitosis of 68 KDa (Sam68), also known as KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1), is the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Previous studies have indicated that Sam68 regulates nuclear transcription factor kappa B (NF-κB) to mediate inflammation. In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the control group...
May 21, 2018: Inflammation
https://www.readbyqxmd.com/read/29785434/integration-of-phospholipid-hyaluronic-acid-methotrexate-nanocarrier-assembly-and-amphiphilic-drug-drug-conjugate-for-synergistic-targeted-delivery-and-combinational-tumor-therapy
#8
Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29785404/enhanced-suppressive-activity-of-regulatory-t-cells-in-the-microenvironment-of-malignant-pleural-effusions
#9
Joanna Budna, Mariusz Kaczmarek, Agata Kolecka-Bednarczyk, Łukasz Spychalski, Piotr Zawierucha, Joanna Goździk-Spychalska, Michał Nowicki, Halina Batura-Gabryel, Jan Sikora
Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs), indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF- β and IL-10 concentrations and measured expression of FOXP3 , CTLA-4 , CD28 , and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#10
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785139/blockage-of-store-operated-ca-2-entry-antagonizes-epstein-barr-virus-promoted-angiogenesis-by-inhibiting-ca-2-signaling-regulated-vegf-production-in-nasopharyngeal-carcinoma
#11
Jiaxiang Ye, Junqi Huang, Qian He, Weilin Zhao, Xiaoying Zhou, Zhe Zhang, Yongqiang Li, Jiazhang Wei, Jinyan Zhang
Background: Epstein-Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29785122/aloperine-executes-antitumor-effects-through-the-induction-of-apoptosis-and-cell-cycle-arrest-in-prostate-cancer-in-vitro-and-in-vivo
#12
Zhixin Ling, Han Guan, Zonghao You, Can Wang, Ling Hu, Lei Zhang, Yiduo Wang, Shuqiu Chen, Bin Xu, Ming Chen
Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785121/association-between-angiogenesis-and-cytotoxic-signatures-in-the-tumor-microenvironment-of-gastric-cancer
#13
Yi Feng, Ying Dai, Zhihua Gong, Jia-Nan Cheng, Longhui Zhang, Chengdu Sun, Xianghua Zeng, Qingzhu Jia, Bo Zhu
Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785050/the-tumor-suppressor-dlc1-inhibits-cancer-progression-and-oncogenic-autophagy-in-hepatocellular-carcinoma
#14
Hui-Ta Wu, Cheng-Rong Xie, Jie Lv, He-Qiang Qi, Fei Wang, Sheng Zhang, Qin-Liang Fang, Fu-Qiang Wang, Yu-Yan Lu, Zhen-Yu Yin
Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29785022/novel-peptide-gx1-inhibits-angiogenesis-by-specifically-binding-to-transglutaminase-2-in-the-tumorous-endothelial-cells-of-gastric-cancer
#15
Zhijie Lei, Na Chai, Miaomiao Tian, Ying Zhang, Guodong Wang, Jian Liu, Zuhong Tian, Xiaofang Yi, Di Chen, Xiaowei Li, Pengfei Yu, Hao Hu, Bing Xu, Chao Jian, Zhenyuan Bian, Hao Guo, Jinpeng Wang, Shiming Peng, Yongzhan Nie, Niu Huang, Sijun Hu, Kaichun Wu
The clinical application of GX1, an optimal gastric cancer (GC) targeting peptide, is greatly limited because its receptor in the GC vasculature is unknown. In this study, we screened the candidate receptor of GX1, transglutaminase-2(TGM2), by co-immunoprecipitation (co-IP) combined with mass spectrometry. We found that TGM2 was up-regulated in GC vascular endothelial cells and that GX1 receptor expression was suppressed correspondingly after TGM2 downregulation. A highly consistent co-localization of GX1 receptor and TGM2 was detected at both the cellular and tissue levels...
May 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784731/transformed-follicular-lymphoma-tfl-predicts-outcome-in-advanced-endometrial-cancer
#16
Senn Wakahashi, Fumi Kawakami, Kanako Wakahashi, Kentaro Minagawa, Keitaro Matsuo, Yoshio Katayama, Hideto Yamada, Toshimitsu Matsui, Tamotsu Sudo
BACKGROUND: Transformed follicular lymphoma (TFL, ZC3H12D) was identified, as a candidate tumor suppressor gene that contributes to cell-cycle arrest through regulation of Rb phosphorylation, but the clinical impact of TFL is unknown. The goal of this study was to evaluate the prognostic significance of TFL expression in advanced endometrial cancer. METHODS: Tissue samples were obtained from 103 patients with FIGO stage III-IV endometrial cancer. Associations between TFL expression and outcomes were evaluated using the Kaplan-Meier method and multivariate Cox proportional-hazards regression models...
May 21, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#17
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784669/autophagy-cell-viability-and-chemo-resistance-are-regulated-by-mir-489-in-breast-cancer
#18
Hexin Chen, Mithil Soni, Yogin Patel, Eleni Markoutsa, Chunfa Jie, Shou Liu, Peisheng Xu
It is postulated that the complexity and heterogeneity in cancer may hinder most efforts that target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as microRNAs (miRs), holds promise for future cancer therapy. One such miR, miR-489, is downregulated in majority of breast cancer cells and several drug-resistant breast cancer cell lines, but its role and underlying mechanism for tumor suppression and drug resistance needs further investigation. The current study identifies autophagy as a novel pathway targeted by miR-489 and reports Unc-51 like autophagy activating kinase 1 (ULK1) and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489...
May 21, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29784643/the-presence-of-large-focal-lesions-is-a-strong-independent-prognostic-factor-in-multiple-myeloma
#19
Leo Rasche, Edgardo J Angtuaco, Terri L Alpe, Grant H Gershner, James E McDonald, Rohan S Samant, Manoj Kumar, Rudy Van Hemert, Joshua Epstein, Shayu Deshpande, Ruslana Tytarenko, Shmuel Yaccoby, Jens Hillengass, Sharmilan Thanendrarajan, Carolina Schinke, Frits van Rhee, Maurizio Zangari, Brian A Walker, Bart Barlogie, Gareth J Morgan, Faith E Davies, Niels Weinhold
Spatial intra-tumor heterogeneity is frequently seen in Multiple Myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. As biopsy based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FL) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784636/adaptive-nk-cells-resist-regulatory-t-cell-suppression-driven-by-il-37
#20
Dhifaf Sarhan, Keli L Hippen, Amanda Lemire, Skyler Hying, Xianghua Luo, Todd Lenvik, Julie Curtsinger, Zachary Davis, Bin Zhang, Sarah Cooley, Frank Cichocki, Bruce R Blazar, Jeffrey S Miller
Natural Killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Tregs), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FcεRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus (CMV)-exposed individuals...
May 21, 2018: Cancer Immunology Research
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