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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/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#2
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156833/targeting-aggressive-prostate-cancer-associated-cd44v6-using-phage-display-selected-peptides
#3
Ying Peng, Austin R Prater, Susan L Deutscher
There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156828/the-%C3%AE-glucan-from-lentinus-edodes-suppresses-cell-proliferation-and-promotes-apoptosis-in-estrogen-receptor-positive-breast-cancers
#4
Hui Xu, Siwei Zou, Xiaojuan Xu
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156824/37-kda-lrp-flag-enhances-telomerase-activity-and-reduces-senescent-markers-in-vitro
#5
Tyrone C Otgaar, Eloise Ferreira, Sibusiso Malindisa, Martin Bernert, Boitelo T Letsolo, Stefan F T Weiss
One of the core regulators of cellular aging are telomeres, repetitive DNA sequences at the ends of chromosomes that are maintained by the ribonucleoprotein DNA polymerase complex, telomerase. Recently, we demonstrated that knockdown of the 37kDa/ 67kDa laminin receptor (LRP/LR), a protein that promotes cell viability in tumorigenic and normal cells, reduces telomerase activity. We therefore hypothesized that upregulating LRP/LR might increase telomerase activity and impede aging. Here we show that overexpression of LRP::FLAG resulted in significantly elevated hTERT levels, telomerase activity and telomere length, respectively, with concomitantly reduced levels of senescence markers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156820/a-water-soluble-polysaccharide-from-grifola-frondosa-induced-macrophages-activation-via-tlr4-myd88-ikk%C3%AE-nf-%C3%AE%C2%BAb-p65-pathways
#6
Lihua Hou, Meng Meng, Yuanyuan Chen, Chunling Wang
Here, the immunomodulatory effects of water-soluble polysaccharide from Grifola frondosa on RAW264.7 macrophages and its molecular mechanisms were investigated. G. frondosa polysaccharide could obviously enhance immunostimulatory activity such as the release of nitric oxide and cytokine production. Western blotting results showed that G. frondosa polysaccharide elevated the TLR4, which might act as an upstream regulator of MyD88 induced G. frondosa polysaccharide. MyD88 promoted IKKβ in endochylema and translocate NF-κB p65 subunit into the nucleus which increased the NO production and cytokine/chemokines level...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156818/a-plasmid-containing-cpg-odn-as-vaccine-adjuvant-against-grass-carp-reovirus-in-grass-carp-ctenopharyngodon-idella
#7
Hang Su, Zhiwei Liao, Gailing Yuan, Jianguo Su
CpG oligodeoxynucleotides (ODNs) are proved to have strong immune stimulatory activity. Plasmids containing CpG ODNs could be conveniently and low-costly used as vaccine adjuvant. However, they are different among various plasmids, motif repeats, species, etc. In the present study, plasmid pcDNA3.1 (+) containing five repetitions of CpG ODN 1670A named pcDNA3.1-1670A*5 with strong immunostimulation was screened out from twelve recombinant plasmids and three empty vectors by cell proliferation activity, interferon promoter activities and immune related gene expressions in CIK cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156815/the-effect-of-aspirin-on-circulating-netrin-1-levels-in-humans-is-dependent-on-the-inflammatory-status-of-the-vascular-endothelium
#8
Kerry Layne, Timothy Goodman, Albert Ferro, Gabriella Passacquale
In atherosclerotic animal models, the cyclo-oxygenase (COX)-inhibitor aspirin counteracts downregulation of endothelial-derived netrin-1, thus reducing arterial inflammation. We here explored the effect of aspirin on netrin-1 in healthy subjects undergoing influenza immunisation, which is an established experimental model of inflammation-related endothelial dysfunction. Our data showed that netrin-1 undergoes reduction (-29.25% from baseline; p=0.0017) in the presence of endothelial activation (VCAM-1 rose by 9...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156809/adipose-derived-stem-cells-seeded-bladder-acellular-matrix-graft-silk-fibroin-enhances-bladder-reconstruction-in-a-rat-model
#9
Dongdong Xiao, Qiong Wang, Hao Yan, Xiangguo Lv, Yang Zhao, Zhe Zhou, Ming Zhang, Qian Sun, Kang Sun, Wei Li, Mujun Lu
The unfavourable clinical outcomes of host cell-seeded scaffolds for bladder augmentation warrant improved bioactive biomaterials. This study aimed to examine the feasibility of adipose-derived stem cells (ASCs)-seeded bilayer bladder acellular matrix graft (BAMG)-silk fibroin (SF) scaffold in enhancing bladder reconstruction. Sprague Dawley rats were randomly divided into three groups: the BAMG-SF-ASCs group, the acellular BAMG-SF group and the cystotomy group. The BAMG-SF-ASCs group was sampled at 2, 4 and 12 weeks, and compared with the other groups at 12 weeks...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156807/halofuginone-inhibits-tgf-%C3%AE-bmp-signaling-and-in-combination-with-zoledronic-acid-enhances-inhibition-of-breast-cancer-bone-metastasis
#10
Patricia Juárez, Pierrick G J Fournier, Khalid S Mohammad, Ryan C McKenna, Holly W Davis, Xiang H Peng, Maria Niewolna, Alain Mauviel, John M Chirgwin, Theresa A Guise
More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFβ and BMP-signaling. Halofuginone blocked TGF-β-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-β-induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-β-regulated metastatic genes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156787/natural-compound-bavachalcone-promotes-the-differentiation-of-endothelial-progenitor-cells-and-neovascularization-through-the-ror%C3%AE-erythropoietin-ampk-axis
#11
Shuang Ling, Rong-Zhen Ni, Yunyun Yuan, Yan-Qi Dang, Qian-Mei Zhou, Shuang Liang, Fujiang Guo, Wei Feng, Yuanyuan Chen, Katsumi Ikeda, Yukio Yamori, Jin-Wen Xu
In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156785/in-silico-and-in-vitro-identification-of-inhibitory-activities-of-sorafenib-on-histone-deacetylases-in-hepatocellular-carcinoma-cells
#12
Tsang-Pai Liu, Yi-Han Hong, Pei-Ming Yang
Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156767/enhancing-conventional-chemotherapy-drug-cisplatin-induced-anti-tumor-effects-on-human-gastric-cancer-cells-both-in-vitro-and-in-vivo-by-thymoquinone-targeting-pten-gene
#13
Jingjing Ma, Xue Hu, Jiao Li, Dandan Wu, Qingzhi Lan, Qian Wang, Shan Tian, Weiguo Dong
Combination chemotherapy regimen with several anti-tumor drugs is a strategy to improve outcome. Thymoquinone (TQ) has been reported to exert biological activity on various types of human cancers without obvious toxicity. However, only few studies showed the anti-tumor effects of TQ combination with cisplatin on gastric cancer (GC). Here, we showed pretreatment with 5μM TQ significantly increased the apoptotic effects induced by cisplatin on GC cell lines. Combined treatment of cisplatin with TQ represented a significantly superior tumor suppression effect than either agent alone in a xenograft tumor mouse model...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156763/elas1-induces-apoptotic-death-in-adenocarcinoma-du145-and-squamous-cell-carcinoma-sas-cancer-cells-but-not-in-normal-kd-cells
#14
Toshihiro Uchihashi, Kaori Ota, Yusuke Yabuno, Shouichi Ohno, Kohshiro Fukushima, Yoko Naito, Mikihiko Kogo, Norikazu Yabuta, Hiroshi Nojima
We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells. Because the effect of ELAS1 is dependent on increased stability of p53 and enhanced phosphorylation of p53-S46, we exogenously expressed wild-type p53 protein to fully promote ELAS1-mediated induction of apoptosis in SAS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156754/functional-characterization-of-a-novel-transcript-of-ercc1-in-chemotherapy-resistance-of-ovarian-cancer
#15
Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu, Weiling Li
Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156740/improvement-of-therapeutic-effects-of-mesenchymal-stem-cells-in-myocardial-infarction-through-genetic-suppression-of-microrna-142
#16
Liu-Xue Yang, Chun-Ling Wei, Man-Li Guo, Yong Zhang, Feng Bai, Shao-Gang Ma
Transplanted mesenchymal stem cells (MSCs) have been shown to contribute to myocardial repair after myocardial infarction (MI), primarily through production and secretion some growth factors and cytokines related to cell survival and regeneration. Further improvement of the therapeutic potential of MSCs appears to be an attractive strategy for MI treatment. CXC chemokine receptor (CXCR) 7 is the receptor for stromal cell-derived factor-1 (SDF-1), an important chemokine that is essential for tissue repair and angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156739/electroacupuncture-alleviates-neuromuscular-dysfunction-in-an-experimental-rat-model-of-immobilization
#17
Jun Yang, Su Min, Fei Xie, Jingyuan Chen, Xuechao Hao, Li Ren
Immobilization-related skeletal muscle atrophy is a major concern to patients in Intensive Care Units and it has a profound effect on the quality of life. However, the underlying molecular events for the therapeutic effect of electroacupuncture to treat muscle atrophy have not been fully elucidated. Here we developed an immobilization mouse model and tested the hypothesis that skeletal muscle weakness may be caused by the increased expression of γ and α7 nicotinic acetylcholine receptors (nAChRs) on muscle cell membranes, while electroacupuncture could decrease the expression of γ and α7 nicotinic acetylcholine receptors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156737/combination-treatment-with-recombinant-methioninase-enables-temozolomide-to-arrest-a-braf-v600e-melanoma-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#18
Kei Kawaguchi, Kentaro Igarashi, Shukuan Li, Qinghong Han, Yuying Tan, Tasuku Kiyuna, Kentaro Miyake, Takashi Murakami, Bartosz Chmielowski, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
An excessive requirement for methionine termed methionine dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by methionine deprivation such as with recombinant methioninase (rMETase). The present study used a previously-established patient-derived orthotopic xenograft (PDOX) nude mouse model of BRAF V600E-mutant melanoma to determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156731/mir-21-modulates-the-effect-of-ezh2-on-the-biological-behavior-of-human-lung-cancer-stem-cells-in-vitro
#19
Hui Xia, Wen Zhang, Baoshi Zhang, Yingnan Zhao, Yunlong Zhao, Shaojun Li, Yang Liu
Non-small-cell lung cancer has a high mortality rate and poor prognosis. Therefore, novel therapeutic approaches are urgently needed to enhance patient survival rates. In this study, we investigated the effects of miR-21 and EZH2 on the biological behavior of human lung cancer stem cells in vitro. We found increased expression of EZH2 and miR-21 in LCSCs, and miR-21 overexpression increased EZH2 levels in LCSCs. In addition, EZH2 and miR-21 knockdown increased the sensitivity of LCSCs to chemo- and radiation therapy, and exogenous EZH2 expression rescued the effects of anti-miR-21...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156720/novel-strategies-of-raman-imaging-for-brain-tumor-research
#20
Imiela Anna, Polis Bartosz, Polis Lech, Abramczyk Halina
Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls...
October 17, 2017: Oncotarget
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