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https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#1
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#2
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394354/oncogenic-mct-1-activation-promotes-yy1-egfr-mnsod-signaling-and-tumor-progression
#3
H-Y Tseng, Y-A Chen, J Jen, P-C Shen, L-M Chen, T-D Lin, Y-C Wang, H-L Hsu
Tumor cells often produce high levels of reactive oxygen species (ROS) and display an increased ROS scavenging system. However, the molecular mechanism that balances antioxidative and oxidative stress in cancer cells is unclear. Here, we determined that oncogenic multiple copies in T-cell malignancy 1 (MCT-1) activity promotes the generation of intracellular ROS and mitochondrial superoxide. Overexpression of MCT-1 suppresses p53 accumulation but elevates the manganese-dependent superoxide dismutase (MnSOD) level via the YY1-EGFR signaling cascade, which protects cells against oxidative damage...
April 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28376190/effects-of-ctgf-blockade-on-attenuation-and-reversal-of-radiation-induced-pulmonary-fibrosis
#4
Sebastian Bickelhaupt, Christian Erbel, Carmen Timke, Ute Wirkner, Monika Dadrich, Paul Flechsig, Alexandra Tietz, Johanna Pföhler, Wolfgang Gross, Peter Peschke, Line Hoeltgen, Hugo A Katus, Hermann-Josef Gröne, Nils H Nicolay, Rainer Saffrich, Jürgen Debus, Mark D Sternlicht, Todd W Seeley, Kenneth E Lipson, Peter E Huber
Background: Radiotherapy is a mainstay for the treatment of lung cancer that can induce pneumonitis or pulmonary fibrosis. The matricellular protein connective tissue growth factor (CTGF) is a central mediator of tissue remodeling. Methods: A radiation-induced mouse model of pulmonary fibrosis was used to determine if transient administration of a human antibody to CTGF (FG-3019) started at different times before or after 20 Gy thoracic irradiation reduced acute and chronic radiation toxicity...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28365931/the-effect-of-granulocyte-and-granulocyte-macrophage-colony-stimulating-factors-on-tumor-promotion
#5
Qiqi Liu, Lili Qiao, Pingping Hu, Guodong Deng, Jingxin Zhang, Ning Liang, Jian Xie, Jiandong Zhang
GM-CSF and G-CSF are capable to regulate the maturation of undifferentiated multipotent stem cells into mature granulocytes, macrophages and T cells in the bone marrow. Thereby, clinicians correct neutropenia induced by chemotherapy or radiation routinely with recombinant G- or GM-CSFs in clinical practice. However, relevant studies found that treatment for cancer patients with adjuvant G-/GM-CSF would occasionally enhance the progression of tumors. Besides, constitutive production of G-CSF or GM-CSF by lung cancer cells could stimulate the growth or the invasion of tumor and result in protecting the tumor against unfavorable environment...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28351890/targeting-cd47-and-autophagy-elicited-enhanced-antitumor-effects-in-non-small-cell-lung-cancer
#6
Xuyao Zhang, Jiajun Fan, Shaofei Wang, Yubin Li, Yichen Wang, Song Li, Jingyun Luan, Ziyu Wang, Ping Song, Qicheng Chen, Wenzhi Tian, Dianwen Ju
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in NSCLC. SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28346430/il-17c-mediates-the-recruitment-of-tumor-associated-neutrophils-and-lung-tumor-growth
#7
C Jungnickel, L H Schmidt, L Bittigkoffer, L Wolf, A Wolf, F Ritzmann, A Kamyschnikow, C Herr, M D Menger, T Spieker, R Wiewrodt, R Bals, C Beisswenger
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and is the major pathogen triggering exacerbations. The epithelial cytokine interleukin-17C (IL-17C) promotes the recruitment of neutrophils into inflamed tissues. The purpose of this study was to investigate the function of IL-17C in the pulmonary tumor microenvironment...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345958/macrophage-elastase-induces-trail-mediated-tumor-cell-death-through-its-carboxyterminal-domain
#8
Nadine Dandachi, Neil J Kelly, John P Wood, Christine L Burton, Josiah E Radder, Adriana S Leme, Alyssa D Gregory, Steven D Shapiro
RATIONALE: Macrophage elastase (MMP12) is a potent protease that contributes to the lung destruction that accompanies cigarette smoking while it simultaneously inhibits lung tumor angiogenesis and metastasis by catalyzing the formation of anti-angiogenic peptides. Recent studies have revealed novel non-proteolytic functions of MMP12, including antimicrobial activity through a peptide within its C-terminal domain (CTD). OBJECTIVES: Our objective was to determine whether the MMP12 CTD contributes to its anti-tumor activity in lung cancer...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28285690/the-cell-cell-interaction-between-tumor-associated-macrophages-and-small-cell-lung-cancer-cells-is-involved-in-tumor-progression-via-stat3-activation
#9
Toyohisa Iriki, Koji Ohnishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Cheng Pan, Koei Ikeda, Takeshi Mori, Makoto Suzuki, Hidenori Ichiyasu, Hirotsugu Kohrogi, Motohiro Takeya, Yoshihiro Komohara
OBJECTIVES: Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. It is well known that various stromal cells, including macrophages, play a role in tumor progression in several types of malignant tumors; however, the significance of tumor-associated macrophages (TAMs) in SCLC has not been fully elucidated. Signal transducer and activator of transcription 3 (STAT3) is a molecule well-known to be related to tumor progression. In the present study, we investigated the relationship of TAMs and SCLC cells to test the hypothesis that TAMs induce tumor progression in SCLC via STAT3 activation...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#10
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28256196/afatinib-ameliorates-osteoclast-differentiation-and-function-through-downregulation-of-rank-signaling-pathways
#11
Hye Jung Ihn, Ju Ang Kim, Yong Chul Bae, Hong-In Shin, Moon-Chang Baek, Eui Kyun Park
Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor κB (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs)...
March 2017: BMB Reports
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#12
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John V Heymach, Stephen G Swisher, Chantale Bernatchez, Gheath Alatrash, Samir Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these reinvigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28245875/severe-nivolumab-induced-pneumonitis-preceding-durable-clinical-remission-in-a-patient-with-refractory-metastatic-lung-squamous-cell-cancer-a-case-report
#13
Hong Li, Weijie Ma, Ken Y Yoneda, Elizabeth H Moore, Yanhong Zhang, Lee L Q Pu, Garrett M Frampton, Michael Molmen, Philip J Stephens, Tianhong Li
BACKGROUND: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28228217/-t-peptide-enhances-the-killing-effects-of-cisplatinum-on-lung-cancer
#14
Hongyi Zhang, Minghui Liu, Ying Li, Yongwen Li, Song Xu, Zhenhua Pan, Mingbiao Li, Haiyang Fan, Hongyu Liu, Jun Chen
BACKGROUND: T peptide is extensively used in anti-tumor treatment. The aims of this study were to investigate whether T peptide enhances cisplatinum efficiency while reducing its side effects and to identify its effective mechanisms. METHODS: (1) Human macrophage U937 cells were treated with T peptide and/or cisplatinum. The levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) of each group were detected by enzyme-linked immunosorbent assay (ELISA); (2) Xenograft mouse models of human lung cancer were treated with T peptide and/or cisplatinum once every five days for three times...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#15
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g., graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery, and biomolecular detection. GO recently emerged as a chemosensitizer; however, the detailed molecular basis underlying GO-conducted sensitization and corresponding biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state, including disorders of plasma membrane and cytoskeleton construction, we aimed here to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
March 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/28202524/scavenger-receptor-a1-prevents-metastasis-of-non-small-cell-lung-cancer-via-suppression-of-macrophage-serum-amyloid-a1
#16
Yan Zhang, Yongyue Wei, Bin Jiang, Lili Chen, Hui Bai, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, David C Christiani, Qi Chen
Mechanisms of cross-talk between tumor cells and tumor-associated macrophages (TAM), which drive metastasis, are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics, and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced stage NSCLC patients in the Harvard Lung Cancer Study cohort...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#17
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28173772/potential-importance-of-protease-activated-receptor-par-1-expression-in-the-tumor-stroma-of-non-small-cell-lung-cancer
#18
Cong Lin, Christof J Majoor, Joris J T H Roelofs, Martijn D de Kruif, Hugo M Horlings, Keren Borensztajn, C Arnold Spek
BACKGROUND: Protease activated receptor (PAR)-1 expression is increased in a variety of tumor cells. In preclinical models, tumor cell PAR-1 appeared to be involved in the regulation of lung tumor growth and metastasis; however the role of PAR-1 in the lung tumor microenvironment, which is emerging as a key compartment in driving cancer progression, remained to be explored. METHODS: In the present study, PAR-1 gene expression was determined in lung tissue from patients with non-small-cell lung cancer (NSCLC) using a combination of publicly available RNA microarray datasets and in house-made tissue microarrays including tumor biopsies of 94 patients with NSCLC (40 cases of adenocarcinoma, 42 cases of squamous cell carcinoma and 12 cases of other type of NSCLC at different stages)...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28166195/detecting-intratumoral-heterogeneity-of-egfr-activity-by-liposome-based-in-vivo-transfection-of-a-fluorescent-biosensor
#19
G Weitsman, N J Mitchell, R Evans, A Cheung, T L Kalber, R Bofinger, G O Fruhwirth, M Keppler, Z V F Wright, P R Barber, P Gordon, T de Koning, W Wulaningsih, K Sander, B Vojnovic, S Ameer-Beg, M Lythgoe, J N Arnold, E Årstad, F Festy, H C Hailes, A B Tabor, T Ng
Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28160492/a-prognostic-4-gene-expression-signature-for-squamous-cell-lung-carcinoma
#20
Jun Li, Jing Wang, Yanbin Chen, Lijie Yang, Sheng Chen
Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression...
February 4, 2017: Journal of Cellular Physiology
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