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Lung cancer AND anti-vegf

E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
Hidenori Fujita, Akira Gomori, Yayoi Fujioka, Yuki Kataoka, Kenji Tanaka, Akihiro Hashimoto, Takamasa Suzuki, Kenjiro Ito, Tomonori Haruma, Hiromi Yamamoto-Yokoi, Naomoto Harada, Motomu Sakuragi, Nobuyuki Oda, Kenichi Matsuo, Masaki Inada, Kazuhiko Yonekura
Approximately 25-40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice...
2016: PloS One
Qingxin Zhou, Yuekun Zhu, Xiaoli Wei, Jianhua Zhou, Liang Chang, Hong Sui, Yu Han, Daxun Piao, Ruihua Sha, Yuxian Bai
Altered expression of microRNA-590-5p (miR-590-5p) is involved in tumorigenesis, however, its role in colorectal cancer (CRC) remains to be determined. In this study, we focused on examining the effects of different expression levels of miR-590-5p in cancer cells and normal cells. Results showed that there are lower expression levels of miR-590-5p in human CRC cells and tissues than in normal control cells and tissues. Similarly, in our xenograft mouse model, knockdown of miR-590-5p promoted the progression of CRC...
October 13, 2016: Cell Death & Disease
Jie Xiao, Xiaobo Xu, Xiao Li, Yanli Li, Guobing Liu, Hui Tan, Hua Shen, Hongcheng Shi, Dengfeng Cheng
The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model...
September 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Valérie Paulus, Virginie Avrillon, Maurice Pérol
Angiogenesis is critical for tumor growth, proliferation and metastasis with the crucial role of Vascular Endothelial Growth factor (VEGF) pathway. Ramucirumab is a monoclonal antibody that specifically targets the extracellular domain of Vascular Endothelial Growth Factor Receptor 2. Areas covered: We performed a search on Medline to browse the current literature on Ramucirumab and anti-angiogenic agents, for the treatment of NSCLC. The REVEL study demonstrated a significant improvement of response rate, progression-free survival and overall survival by adding ramucirumab to docetaxel compared to docetaxel plus a placebo in second-line treatment of advanced non-small cell lung cancer, irrespective of histology, with an acceptable safety profile...
October 8, 2016: Expert Review of Anticancer Therapy
Florence T H Wu, Shan Man, Ping Xu, Annabelle Chow, Marta Paez-Ribes, Christina R Lee, Steven R Pirie-Shepherd, Urban Emmenegger, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) that target VEGF receptor-2 (VEGFR2) have not been effective as adjuvant treatments for micrometastatic disease in phase III trials. Angiopoietin-2 (Ang2) is a pro-angiogenic and pro-inflammatory vascular destabilizer that cooperates with VEGF. The purpose of this study was to test whether CVX-060 (an Ang2-specific CovX-body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat postsurgical metastatic disease in multiple orthotopically implanted human tumor xenograft and syngeneic murine tumor models...
September 20, 2016: Cancer Research
Dongdong Han, Chengjie Cao, Ya Su, Jun Wang, Jian Sun, Huasheng Chen, Aihua Xu
ETHNOPHARMACOLOGICAL RELEVANCE: A fruit of Ginkgo biloba L. also known as Ginkgo biloba, can be used for the treatment of cancer in Chinese traditional medicine. The scientific name of succulent skin, which is the episperm of Ginkgo nuts, is exocarp. Experiment shows that Ginkgo biloba exocarp extracts (GBEE) has the effects of immune promotion, cancer inhibition and etc. AIM OF STUDY: Study on the activity of GBEE against Lewis lung cancer (LLC) angiogenesis and its partial molecular mechanism...
November 4, 2016: Journal of Ethnopharmacology
Lukas Goertz, Stefan Werner Schneider, Anna Desch, Frank Thomas Mayer, Julian Koett, Kai Nowak, Ioannis Karampinis, Michael K Bohlmann, Viktor Umansky, Alexander Thomas Bauer
Von Willebrand factor (VWF) serves as a nidus for platelet aggregation and thrombosis. We hypothesize that VWF fibers contribute to the development of venous thromboembolism (VTE) and to metastasis formation. Here, we show that vascular and lymphatic endothelial cells (ECs) express VWF in vitro and release VWF fibers after activation by tumor cell supernatants. In contrast, an ex vivo analysis of primary mouse tumors revealed the presence of VWF fibers in the blood microvasculature but not in lymphatic vessels...
September 2, 2016: Oncotarget
Mary-Clare Cathcart, Zivile Useckaite, Clive Drakeford, Vikki Semik, Joanne Lysaght, Kathy Gately, Kenneth J O'Byrne, Graham P Pidgeon
BACKGROUND: Baicalein is a widely used Chinese herbal medicine derived from Scutellaria baicalenesis, which has been traditionally used as anti-inflammatory and anti-cancer therapy. In this study we examined the anti-tumour pathways activated following baicalein treatment in non-small cell lung cancer (NSCLC), both in-vitro and in-vivo. METHODS: The effect of baicalein treatment on H-460 cells in-vitro was assessed using both BrdU assay (cell proliferation) and High Content Screening (multi-parameter apoptosis assay)...
2016: BMC Cancer
Huanjun Chen, Qifei Cong, Zhenyun Du, Wenfeng Liao, Lei Zhang, Yanli Yao, Kan Ding
Fucoidan may inhibit angiogenesis. However, its functional target molecule and the underlying mechanism are still vague. In the present study, we showed that sulfated fucoidan FP08S2 from Sargassum fusiforme inhibited tube formation as well as migration and invasion of human microvascular endothelial cells (HMEC-1). In addition, FP08S2 was confirmed to disrupt VEGF-induced angiogenesis both in vitro and in vivo. Further study indicated that FP08S2 could bind to both VEGF and VEGFR2 to interfere with VEGF-VEGFR2 interaction...
August 26, 2016: Cancer Letters
Hua Shen, Xiaobo Yu, Fengming Yang, Zhihua Zhang, Jianxin Shen, Jin Sun, Swati Choksi, Siriporn Jitkaew, Yongqian Shu
Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa...
August 2016: PLoS Genetics
Sofie Frandsen, Sascha Kopp, Markus Wehland, Jessica Pietsch, Manfred Infanger, Daniela Grimm
BACKGROUND: Angiogenesis is a mechanism, which tumors use to recruit oxygen and nutrients in order to maintain growth. The vascular endothelial growth factor family is the primary mediator of this process. For the last couple of decades, inhibition of angiogenesis has been the subject of extensive research, but so far anti-angiogenic drugs have only shown a modest effect. METHODS: This paper reviews four relevant anti-angiogenic drugs: bevacizumab, ramucirumab, nintedanib and sunitinib...
July 15, 2016: Current Pharmaceutical Design
Dianbao Zhang, Xianfen Zhang, Chunling Zhao
AIMS: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis...
2016: OncoTargets and Therapy
Benjamin F Chu, Gregory A Otterson
Although molecular targeted agents have improved the treatment of lung cancer, their use has largely been restricted to limited subsets of the overall population that carry specific mutations. Angiogenesis, the formation of new blood vessels from existing networks, is an attractive, more general process for the development of targeted anticancer therapies, because it is critical for the growth of solid tumors, including non-small-cell lung cancer. Growing tissues require a vascular supply within a few millimeters...
June 8, 2016: Clinical Lung Cancer
Jianwei Tian, Liping Hu, Xiao Li, Jian Geng, Meng Dai, Xiaoyan Bai
BACKGROUND: The prognosis of non-small-cell lung cancer (NSCLC) is poor yet mechanistic understanding and therapeutic options remain limited. We investigated the biological and clinical significance of microRNA-130b and its relationship with apoptosis in NSCLC. METHODS: The level of microRNA-130b in relationship with the expression of PPARγ, VEGF-A, BCL-2 and apoptosis were analyzed in 91 lung cancer patient samples using immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on tissue microarrays...
2016: Journal of Experimental & Clinical Cancer Research: CR
Roni T Falk, Annetine Cathrine Staff, Gary Bradwin, S Ananth Karumanchi, Rebecca Troisi
PURPOSE: Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. METHODS: We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment...
August 2016: Cancer Causes & Control: CCC
Timothy R Holzer, Angie D Fulford, Leslie O'Neill Reising, Drew M Nedderman, Xuekui Zhang, Laura E Benjamin, Andrew E Schade, Aejaz Nasir
BACKGROUND: the vascular endothelial growth factor (VEGF) pathway plays a prominent role in the growth and progression of human cancer, including non-small cell lung carcinoma (NSCLC). The key mediators of VEGF signaling are a family of related receptor tyrosine kinases that include VEGFR1, VEGFR2, and VEGFR3. The relative expression levels, activity, and cross-talk among these receptors may contribute to response of NSCLC to anti-angiogenic therapies, and a better systematic, translatable approach to categorizing tumors is needed...
July 2016: Anticancer Research
L Geng, J Fan, Q L Gao, J Yu, B J Hua
OBJECTIVE: To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo. METHODS: Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group: PEG-PLGA-Rg3 nanoparticles group(Rg3-N), PEG-PLGA group (PEG), Rg3 group (Rg3), normal control group(C), saline control group(NS), and received intragastric administration for 14 days...
June 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
So Young Park, Soo Jin Kwon, Soon Sung Lim, Jin-Kyu Kim, Ki Won Lee, Jung Han Yoon Park
Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis...
2016: International Journal of Molecular Sciences
Yi Zhao, Wei Wang, Shutao Guo, Yuhua Wang, Lei Miao, Yang Xiong, Leaf Huang
Metformin, a widely implemented anti-diabetic drug, exhibits potent anticancer efficacies. Herein a polymeric construction of Metformin, PolyMetformin (PolyMet) is successfully synthesized through conjugation of linear polyethylenimine (PEI) with dicyandiamide. The delocalization of cationic charges in the biguanide groups of PolyMet reduces the toxicity of PEI both in vitro and in vivo. Furthermore, the polycationic properties of PolyMet permits capture of siRNA into a core-membrane structured lipid-polycation-hyaluronic acid (LPH) nanoparticle for systemic gene delivery...
2016: Nature Communications
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