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https://www.readbyqxmd.com/read/29775845/toward-innovative-combinational-immunotherapy-a-systems-biology-perspective
#1
REVIEW
Xue-Tao Li, Jin-Ji Yang, Yi-Long Wu, Jun Hou
The treatment of non-small-cell lung cancer (NSCLC) has advanced significantly in the last decades. Especially immune checkpoint inhibitors have shown inconceivable effect on enhancing host anti-tumor activity in NSCLC. However, the limitation of checkpoint blockade monotherapy seems unavoidable in most of the NSCLC patients and only ∼20% of them achieved response to monotherapy with immune checkpoint inhibitors. Thus combining immune checkpoint inhibitors with other agents with different action mechanisms holds a promise to revitalize NSCLC treatment, such as the combination of checkpoint inhibitors with angiogenesis inhibitors, or with chemotherapy, as well as the combination of two checkpoint inhibitors...
May 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29769144/contributions-of-the-rhoa-guanine-nucleotide-exchange-factor-net1-to-polyoma-middle-t-antigen-mediated-mammary-gland-tumorigenesis-and-metastasis
#2
Yan Zuo, Arzu Ulu, Jeffrey T Chang, Jeffrey A Frost
BACKGROUND: The RhoA activating protein Net1 contributes to breast cancer cell proliferation, motility, and invasion in vitro, yet little is known about its roles in mammary gland tumorigenesis and metastasis. METHODS: Net1 knockout (KO) mice were bred to mice with mammary gland specific expression of the polyoma middle T antigen (PyMT) oncogene. Mammary gland tumorigenesis and lung metastasis were monitored. Individual tumors were assessed for proliferation, apoptosis, angiogenesis, RhoA activation, and activation of PyMT-dependent signaling pathways...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29764837/il22-promotes-kras-mutant-lung-cancer-by-induction-of-a-pro-tumor-immune-response-and-protection-of-stemness-properties
#3
Nasim Khosravi, Mauricio S Caetano, Amber M Cumpian, Nese Unver, Cynthia De la Garza Ramos, Oscar Noble, Soudabeh Daliri, Belinda J Hernandez, Berenice A Gutierrez, Scott E Evans, Samir Hanash, Andrei M Alekseev, Yi Yang, Seon Hee Chang, Roza Nurieva, Humam Kadara, Jichao Chen, Edwin J Ostrin, Seyed Javad Moghaddam
Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-kB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on non-hematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29763721/new-insights-into-hypoxia-related-mechanisms-involved-in-different-microvascular-patterns-of-bronchopulmonary-carcinoids-and-poorly-differentiated-neuroendocrine-carcinomas-role-of-ribonuclease-t2-rnaset2-and-hif-1-alpha
#4
Silvia Uccella, Stefano La Rosa, Debora Scaldaferri, Laura Monti, Roberta Maragliano, Elisa Sorrenti, Marzia Gariboldi, Roberto Taramelli, Fausto Sessa, Francesco Acquati
Ribonuclease T2 (RNASET2) is a pleiotropic and polyfunctional protein, which exerts several different activities in neoplastic cells since the early steps of tumor development. Besides having an antitumorigenic activity, RNASET2 inhibits both bFGF-induced and VEGF-induced angiogenesis and has a role as a stress-response, alarmin-like, protein. In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior...
May 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/29763380/angiogenin-and-the-mmp9-timp2-axis-are-up-regulated-in-proangiogenic-decidual-nk-like-cells-from-patients-with-colorectal-cancer
#5
Antonino Bruno, Barbara Bassani, Davide Giuseppe D'Urso, Ilvana Pitaku, Elisa Cassinotti, Giuseppe Pelosi, Luigi Boni, Lorenzo Dominioni, Douglas M Noonan, Lorenzo Mortara, Adriana Albini
NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solid malignancies, NK cells have compromised functions. We have previously reported that lung tumor-associated NK cells (TANKs; peripheral blood) and tumor-infiltrating NK cells (TINKs) show proangiogenic, decidual NK-like (dNK) phenotype. In this study, we functionally and molecularly investigated TINKs and TANKs from blood and tissue samples of patients with colorectal cancer (CRC), a neoplasm in which inflammation and angiogenesis have clinical relevance, and compared them to NK cells from controls and patients with nononcologic inflammatory bowel disease...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29763371/normobaric-hyperoxia-inhibits-the-progression-of-lung-cancer-by-inducing-apoptosis
#6
Sei Won Kim, In Kyoung Kim, Jick Hwan Ha, Chang Dong Yeo, Hyeon Hui Kang, Jin Woo Kim, Sang Haak Lee
Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks...
May 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29749499/stable-silencing-of-dll4-gene-suppresses-the-growth-and-metastasis-of-esophagus-cancer-cells-by-attenuating-akt-phosphorylation
#7
Xianzhi Guo, Yingchun Duan, Xiaolei Ye, Lina Hu, Tong Xu, Li Tong, Minghua Yu
δ‑Like ligand 4 (DLL4) has recently been reported to be involved in the process of cancer angiogenesis and considered to play a vital role in vascular endothelial growth factor (VEGF) signaling, while the role of DLL4 in cancer metastasis and growth has not been systematically studied. In the present study, the esophagus cancer cell line Eca109 was infected in vitro with a lentiviral vector loaded with dll4‑shRNA to obtain a stable cell line of DLL4 expression which was downregulated through puromycin screening...
May 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29749480/morusin-suppresses-a549-cell-migration-and-induces-cell-apoptosis-by-downregulating-the-expression-of-cox%C3%A2-2-and-vegf-genes
#8
Xiao-Lu Yin, Yi Lv, Shu Wang, Yu-Qing Zhang
The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549. Various doses of morusin were applied to A549 cells and the effects were assessed by wound‑healing and MTT assays, flow cytometry analysis of apoptosis, a mitochondrial membrane potential assay and RT‑PCR. The results indicated that the concentrations of 10 and 30 µg/ml morusin significantly inhibited A549 cells and signs of apoptosis were observed. In addition, the wound‑healing assay results revealed that morusin inhibited cell migration...
May 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29747940/insights-into-the-role-of-il-32-in-cancer
#9
REVIEW
Yvette J E Sloot, Johannes W Smit, Leo A B Joosten, Romana T Netea-Maier
Interleukin 32 (IL-32) is a proinflammatory cytokine involved in the development of several diseases, including cancer. IL-32 is a rather peculiar cytokine because its protein structure does not show resemblance with any of the known cytokines, and an IL-32 receptor to facilitate extracellular signaling has not yet been identified. Thus far, 9 isoforms of IL-32 have been described, all of which show differences in terms of effects and in potency to elicit a specific effect. Since the first report of IL-32 in 2005, there is increasing evidence that IL-32 plays an important role in the pathophysiology of both hematologic malignancies and solid tumors...
May 7, 2018: Seminars in Immunology
https://www.readbyqxmd.com/read/29744876/flubendazole-elicits-anti-metastatic-effects-in-triple-negative-breast-cancer-via-stat3-inhibition
#10
Eunhye Oh, Yoon-Jae Kim, Hyunsook An, Daeil Sung, Tae-Min Cho, Lee Farrand, Seojin Jang, Jae Hong Seo, Ji Young Kim
Tumor metastasis remains the cause of 90% of cancer-related deaths. Cancer stem cells (CSC) are thought to be responsible for the aggressive and metastatic nature of triple-negative breast cancers (TNBC), and new therapeutic strategies are being devised to target them. Flubendazole (FLU) is a widely used anthelmintic agent that also exhibits anticancer activity in several cancer types. The aim of the present study was to characterize the mechanism of action of FLU on breast cancer stem cell (BCSC)-like properties and metastasis in TNBC...
May 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29743091/the-dysregulation-of-trnas-and-trna-derivatives-in-cancer
#11
REVIEW
Shi-Qiong Huang, Bao Sun, Zong-Ping Xiong, Yan Shu, Hong-Hao Zhou, Wei Zhang, Jing Xiong, Qing Li
Transfer RNAs (tRNAs), traditionally considered to participate in protein translation, were interspersed in the entire genome. Recent studies suggested that dysregulation was observed in not only tRNAs, but also tRNA derivatives generated by the specific cleavage of pre- and mature tRNAs in the progression of cancer. Accumulating evidence had identified that certain tRNAs and tRNA derivatives were involved in proliferation, metastasis and invasiveness of cancer cell, as well as tumor growth and angiogenesis in several malignant human tumors...
May 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29737958/increased-efficacy-of-stereotactic-ablative-radiation-therapy-after-bevacizumab-in-lung-oligometastases-from-colon-cancer
#12
Rosario Mazzola, Umberto Tebano, Dario Aiello, Gioacchino Di Paola, Niccolò Giaj-Levra, Francesco Ricchetti, Sergio Fersino, Alba Fiorentino, Ruggero Ruggieri, Filippo Alongi
Aim Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months' follow-up after SABR; presence of KRAS mutation...
December 1, 2017: Tumori
https://www.readbyqxmd.com/read/29731862/synergistic-anti-tumor-effects-of-dasatinib-and-dendritic-cell-vaccine-on-metastatic-breast-cancer-in-a-mouse-model
#13
Ningning Song, Hulin Guo, Jia Ren, Suhong Hao, Xinchao Wang
Immunotherapy is currently considered as one of the major anti-tumor modalities, but its efficacy is limited. Dasatinib could improve the expansion and recruitment of cluster of differentiation (CD) 8+ T cells and natural killer (NK) cells to the tumor microenvironment. The present study aimed to evaluate the synergistic anti-tumor effects of dasatinib with dendritic cell (DC) vaccine in metastatic breast cancer. Dasatinib with DC vaccine was administered to mice inoculated with 4T1 breast cancer cells. Thereafter, tumor volume was measured every other day...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29730225/pm2-5-exposure-significantly-improves-the-exacerbation-of-a549-tumor-bearing-cb17-scid-mice
#14
Biao Yang, Chunling Xiao
Here we investigate the effects and potential mechanisms of PM2.5 on tumor development in a lung cancer mouse model. Tumor-bearing mice (n = 32) were established and randomized into two groups: the PM2.5 or NS exposure group. Compared with the NS exposure group, mice in the PM2.5 exposure group showed an increased number of tumor nodules, increased BAL fluid protein levels, and elevated expressions of MMP1, IL1β and VEGF. Measurement of angiogenesis from blood serum using an angiogenesis antibody array revealed increased levels of 12 angiogenesis factors in mice after PM2...
May 1, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29722542/repolarization-of-tumor-associated-macrophages-in-a-genetically-engineered-non-small-cell-lung-cancer-model-by-intraperitoneal-administration-of-hyaluronic-acid-based-nanoparticles-encapsulating-microrna-125b
#15
Neha N Parayath, Avani Parikh, Mansoor M Amiji
Tumor-associated macrophages (TAMs) acquire a pro-tumor (M2) phenotype, which promotes tumor growth, angiogenesis, and metastasis. Certain microRNAs (miRs), such as miR-125b, can reprogram TAMs into an anti-tumor/pro-inflammatory (M1) phenotype. Using CD44 targeting hyaluronic acid-poly(ethyleneimine) (HA-PEI)-based nanoparticles encapsulating miR-125b, we have herein shown macrophage-specific delivery and transfection upon intraperitoneal (i.p.) administration. We have exploited the inherent ability of peritoneal macrophages to migrate towards the inflammation/injury and demonstrated that following intraperitoneal administration of HA-PEI nanoparticles, there is an accumulation of HA-PEI nanoparticles in the macrophage-ablated lung tissues of both naïve and KRAS/p53 double mutant genetically engineered (KP-GEM) non-small cell lung cancer (NSCLC) mouse model...
May 3, 2018: Nano Letters
https://www.readbyqxmd.com/read/29721204/comparison-and-evaluation-of-two-rgd-peptides-labelled-with-68-ga-or-18-f-for-pet-imaging-of-angiogenesis-in-animal-models-of-human-glioblastoma-or-lung-carcinoma
#16
Claire Provost, Aurélie Prignon, Laura Rozenblum-Beddok, Quentin Bruyer, Sylvie Dumont, Fatiha Merabtene, Valérie Nataf, Cédric Bouteiller, Jean-Noël Talbot
The aim of this study was to evaluate two RGD radiotracers radiolabelled with fluorine-18 or gallium-68, in detecting angiogenesis in grafted human tumours and monitoring their treatment with the anti-angiogenic agent bevacizumab. Sixteen mice bearing an U87MG tumour in one flank and a contralateral A549 tumour were treated with intravenous injections of bevacizumab twice a week for 3 weeks. PET images with 18 F-RGD-K5 and 68 Ga-RGD were acquired before treatment (baseline), after three bevacizumab injections (t1) and after seven bevacizumab injections (t2)...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721203/patient-derived-xenografts-pdx-predict-an-effective-heparanase-based-therapy-for-lung-cancer
#17
Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721065/development-of-a-novel-albumin-based-and-maleimidopropionic-acid-conjugated-peptide-with-prolonged-half-life-and-increased-in-vivo-anti-tumor-efficacy
#18
Junnan Feng, Chuanke Zhao, Lixin Wang, Like Qu, Hua Zhu, Zhi Yang, Guo An, Huifang Tian, Chengchao Shou
Angiogenesis plays a critical role in tumor aggressiveness, and a lot of anti-angiogenic agents have been used in clinical therapy. The therapeutic efficacy of peptides are generally restricted by the short in vivo life-time, thus, we were interested in developing a novel albumin-based and maleimidopropionic acid-conjugated peptide to prolong the half-life and improve the anti-tumor effect. Methods: We developed a peptide F56 with a maleimidopropionic acid (MPA) at the C-terminal (denoted as F56-CM), which allows immediate and irreversible conjugation with serum albumin...
2018: Theranostics
https://www.readbyqxmd.com/read/29719394/preparation-characterization-in-vitro-and-in-vivo-anti-tumor-effect-of-thalidomide-nanoparticles-on-lung-cancer
#19
Long Xia Chen, Xiao Ling Ni, Heng Zhang, Min Wu, Jing Liu, Shan Xu, Ling Lin Yang, Shao Zhi Fu, Jingbo Wu
Introduction: Thalidomide (THA) is an angiogenesis inhibitor and an efficient inhibitor of the tumor necrosis factor-α (TNF-α). However, the clinical application of THA has been limited due to hydrophobicity of the compound. Materials and methods: To increase the water solubility of THA and in order to evaluate the anticancer abilities of this material on human lung carcinoma, methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles loaded with THA (THA-NPs) were prepared...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29714636/extracellular-vesicles-released-in-response-to-respiratory-exposures-implications-for-chronic-disease
#20
Birke J Benedikter, Emiel F M Wouters, Paul H M Savelkoul, Gernot G U Rohde, Frank R M Stassen
Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. The aim of this review was to examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Publications were searched using PubMed and Google Scholar with the search terms (cigarette smoke OR tobacco smoke OR air pollution OR particulate matter) AND (extracellular vesicles OR exosomes OR microvesicles OR microparticles OR ectosomes)...
May 1, 2018: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
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